The benefit of HH during the CPAP titration in the cool sleeping environment.

PubMed

Li, Yayong; Wang, Yina

2016-12-01

Upper airway symptom associated with continuous positive airway pressure (CPAP) treatment is an important factor influencing CPAP adherence. There are conflicting data on the effect of a heated humidifier (HH) during CPAP titration for patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study investigated the effects of HH during CPAP titration in the cool sleeping environment. Forty newly diagnosed OSAHS patients who received CPAP titration in the cool sleeping environment were randomly assigned to HH and non-HH groups. A questionnaire was used to evaluate upper airway symptoms, satisfaction with initial CPAP treatment, and willingness to further use CPAP. Some therapy parameters including leak, apnea hypopnea index (AHI) reduction, and optimal CPAP pressure level were analyzed. We compared these subjective and objective data between the two groups. In subjective sensation, the use of HH can alleviate upper airway symptoms associated with CPAP titration (P < 0.001). The HH group has benefit in satisfaction with initial CPAP treatment (P < 0.001) and further willingness to use CPAP (P < 0.01), although there were no significant differences in leak, AHI reduction, and optimal CPAP pressure between the two groups. The use of HH is recommended during CPAP titration in the cool sleeping environment because of its benefit in the treatment of upper airway symptoms associated with CPAP therapy and improvement of the CPAP acceptance.

A Comparison of the Radio and Optical Time-Evolution of HH 1 and 2

NASA Astrophysics Data System (ADS)

Rodríguez, L. F.; Raga, A. C.; Rodríguez-Kamenetzky, A.; Carrasco-González, C.

2018-04-01

We present a comparison between the time-evolution over the past ≍20 years of the radio continuum and Hα emission of HH 1 and 2. We find that the radio continuum and the Hα emission of both objects show very similar trends, with HH 1 becoming fainter and HH 2 brightening quite considerably (by about a factor of 2). We also find that the FHα /Fff (Hα to freefree continuum) ratio of HH 1 and 2 has higher values than the ones typically found in planetary nebulae (PNe), which we interpret as an indication that the Hα and free-free emission of HH 1/2 is produced in emitting regions with lower temperatures (≍2000 K) than the emission of PNe (with ≍104 K).

Deuterated formaldehyde in the low-mass protostar HH212

NASA Astrophysics Data System (ADS)

Sahu, Dipen; Minh, Y. C.; Lee, Chin-Fei; Liu, Sheng-Yuan; Das, Ankan; Chakrabarti, S. K.; Sivaraman, Bhala

2018-04-01

HH212, a nearby (400 pc) object in Orion, is a class 0 protostellar system with a Keplerian disc and collimated bipolar SiO jets. Deuterated water, HDO, and a deuterated complex molecule, methanol (CH2DOH), have been reported in the source. Here, we report the HDCO (deuterated formaldehyde) line observation from Atacama Large Millimeter Array data to probe the inner region of HH212. We compare HDCO line with other molecular lines to understand the possible chemistry and physics of the source. The distribution of HDCO emission suggests that it may be associated with the base of the outflow. The emission also shows a rotation but it is not associated with the Keplerian rotation of disc or the rotating infalling envelope, rather it is associated with the outflow as previously seen in C34S. From the possible deuterium fractionation, we speculate that the gas phase formation of deuterated formaldehyde is active in the central hot region of the low-mass protostar system, HH212.

The Late-Time Evolution of SN 2002hh

NASA Astrophysics Data System (ADS)

Clayton, G. C.; Welch, D. L.

2005-12-01

We present new spectroscopic and photometric observations of the interesting Type II-P supernova, SN 2002hh, in NGC 6946. Gemini/GMOS-N has been used to acquire visible spectra and also g'r'i' photometry covering 5 epochs between August 2004 and October 2005, following the evolution of the supernova from 650 to 1050 d since its initial explosion. Supernova spectra obtained 3 years after outburst are rare. In addition, data have been obtained at several epochs in the JHK bands using the Steward 90" with the 256x256 imager and with Gemini/NIRI. Dust emission from SN 2002hh has been detected at mid-infrared wavelengths by SST/IRAC and confirmed by higher angular resolution Gemini/Michelle observations (Barlow et al. 2005, ApJ, 627, L113). There is a pre-existing optically thick dust shell having a mass of ˜0.1 Msun, suggesting a massive M supergiant or luminous blue variable precursor. However, the formation of new dust in the ejecta of SN 2002hh has not been ruled out. The IR emission from any such new dust would be swamped by the emission from the existing circumstellar dust. The new data, presented here, are being used to investigate the late-time evolution of SN 2002hh and whether new dust has been formed in its ejecta. In particular, we are looking for changes in the H-alpha emission line profiles and for variations in brightness due to changes in the extinction and emission due to dust. This study is partially supported by the Natural Sciences and Engineering Research Council of Canada (NSERC).

Luminous Herbig-Haro objects from a massive protostar: The unique case of HH 80/81

NASA Astrophysics Data System (ADS)

Reipurth, Bo

2017-08-01

Herbig-Haro (HH) objects are the optical manifestations of shock waves excited by outflows from young stars. They represent one of the few classes of spatially extended astronomical objects where both structural changes and proper motions can be measured on time scales of years to decades. HH 80/81 is a pair of HH objects in Sagittarius which are the intrinsically most luminous HH objects known. The driving source of HH 80/81 is the embedded star IRAS 18162-2048, which has a luminosity of 20,000 Lsun and excites a compact HII region, suggesting that it is a newborn massive star. HH objects associated with massive young stars are very rare, only a handful of cases are known, but what makes the HH 80/81 source unique among massive protostars is that it produces a finely collimated bipolar radio jet with extremely high velocity and pointing straight to HH 80/81. We propose to observe the HH 80/81 complex with WFC3 and the following four filters: Halpha 6563, Hbeta 4861, [SII] 6717/31, and [OIII] 5007. First epoch HST images were obtained 22 years ago, which now allows a very precise determination of proper motions. Groundbased optical and radio proper motions are not only uncertain, but actually contradict each other, a controversy that will be resolved by HST. The fine resolution of WFC3 allows a study of both fine structural details and structural changes of the shocks. Finally we will use a sophisticated adaptive grid code to interpret the (de-reddened) line ratios across the shocks.

Structure and Biological Roles of Sinorhizobium fredii HH103 Exopolysaccharide

PubMed Central

Acosta-Jurado, Sebastián; Soto, María J.; Margaret, Isabel; Crespo-Rivas, Juan C.; Sanjuan, Juan; Temprano, Francisco; Gil-Serrano, Antonio; Ruiz-Sainz, José E.; Vinardell, José M.

2014-01-01

Here we report that the structure of the Sinorhizobium fredii HH103 exopolysaccharide (EPS) is composed of glucose, galactose, glucuronic acid, pyruvic acid, in the ratios 5∶2∶2∶1 and is partially acetylated. A S. fredii HH103 exoA mutant (SVQ530), unable to produce EPS, not only forms nitrogen fixing nodules with soybean but also shows increased competitive capacity for nodule occupancy. Mutant SVQ530 is, however, less competitive to nodulate Vigna unguiculata. Biofilm formation was reduced in mutant SVQ530 but increased in an EPS overproducing mutant. Mutant SVQ530 was impaired in surface motility and showed higher osmosensitivity compared to its wild type strain in media containing 50 mM NaCl or 5% (w/v) sucrose. Neither S. fredii HH103 nor 41 other S. fredii strains were recognized by soybean lectin (SBL). S. fredii HH103 mutants affected in exopolysaccharides (EPS), lipopolysaccharides (LPS), cyclic glucans (CG) or capsular polysaccharides (KPS) were not significantly impaired in their soybean-root attachment capacity, suggesting that these surface polysaccharides might not be relevant in early attachment to soybean roots. These results also indicate that the molecular mechanisms involved in S. fredii attachment to soybean roots might be different to those operating in Bradyrhizobium japonicum. PMID:25521500

Physical structure and dust reprocessing in a sample of HH jets

NASA Astrophysics Data System (ADS)

Podio, L.; Medves, S.; Bacciotti, F.; Eislöffel, J.; Ray, T.

2009-11-01

Context: Stellar jets are an essential ingredient of the star formation process and a wealth of information can be derived from their characteristic emission-line spectra. Aims: We investigate the physical structure and dust reprocessing in the shocks along the beam of a number of classical Herbig-Haro (HH) jets in the Orion and Lupus molecular clouds (HH 111, HH 1/2, HH 83, HH 24 M/A/E/C, and Sz68). Parameters describing plasma conditions, as well as dust content, are derived as a function of distance from the source and, for HH 111, of gas velocity. Methods: Spectral diagnostic techniques are applied to obtain the jet physical conditions (the electron and total density, ne and n_H, the ionisation fraction, x_e, and the temperature, T_e) from the ratios of selected forbidden lines. The presence of dust grains is investigated by estimating the gas-phase abundance of calcium with respect to its solar value. Results: We find the electron density varies between 0.05-4×103 cm-3, the ionisation fraction xe from 0.01-0.7, the temperature ranges between 0.6-3×104 K, and the hydrogen density between 0.01-6×104 cm-3. Interestingly, in the HH 111 jet, n_e, x_e, and Te peak in the high velocity interval (HVI) of the strongest working surfaces, confirming a prediction from shocks models. Calcium turns out to be depleted with respect to its solar value, but its gas-phase abundance is higher than estimates for the interstellar medium in Orion. The depletion is high (up to 80%) along the low-excited jets, while low or no depletion is measured in those jets which show higher excitation conditions. Moreover, for HH 111 the depletion is lower in the HVI of the fastest shock. Conclusions: Our results confirm the shock structure predicted by models and indicate that shocks occurring along jets, and presumably those present in the launch zone, only partially destroy dust grains and that the efficiency of dust reprocessing strongly depends on shock velocity. However, the high Ca gas

Ab Initio Potential Energy Surface for H-H2

NASA Technical Reports Server (NTRS)

Patridge, Harry; Bauschlicher, Charles W., Jr.; Stallcop, James R.; Levin, Eugene

1993-01-01

Ab initio calculations employing large basis sets are performed to determine an accurate potential energy surface for H-H2 interactions for a broad range of separation distances. At large distances, the spherically averaged potential determined from the calculated energies agrees well with the corresponding results determined from dispersion coefficients; the van der Waals well depth is predicted to be 75 +/- 3 micro E(h). Large basis sets have also been applied to reexamine the accuracy of theoretical repulsive potential energy surfaces (25-70 kcal/mol above the H-H2 asymptote) at small interatomic separations; the Boothroyd, Keogh, Martin, and Peterson (BKMP) potential energy surface is found to agree with results of the present calculations within the expected uncertainty (+/- 1 kcal/mol) of the fit. Multipolar expansions of the computed H-H2 potential energy surface are reported for four internuclear separation distances (1.2, 1.401, 1.449, and 1.7a(0)) of the hydrogen molecule. The differential elastic scattering cross section calculated from the present results is compared with the measurements from a crossed beam experiment.

31 CFR 353.31 - Series HH bonds.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the owner or coowner's account at a financial institution. Checks will be mailed to the delivery...) (c) Delivery of interest. Notices affecting the delivery of interest payments. To ensure appropriate action, notices affecting the delivery of interest payments on Series HH bonds must be received by the...

Nuclear Decay Data Evaluations at IFIN-HH, Romania

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

Luca, A., E-mail: aluca@nipne.ro

2014-06-15

An IAEA Coordinated Research Project (CRP) on Updated Decay Data Library for Actinides was implemented during the period 2005-2012. The author participated in the CRP, as a representative of the Horia Hulubei National Institute of Physics and Nuclear Engineering (IFIN-HH), the Radionuclide Metrology Laboratory. Decay data for five actinide nuclides were evaluated by the author, according to the procedures and rules of the international cooperation Decay Data Evaluation Project (DDEP): {sup 236}U, {sup 234}Th, {sup 228}Ra, {sup 211}Bi and {sup 211}Po. The most important results, conclusions and some recommendations of the evaluator are presented. The IFIN-HH involvement in several newmore » international and national research projects in the field is briefly mentioned; new evaluations and experimental determination of some nuclear decay data (photon absolute emission probability, half-life) for nuclear medicine applications are foreseen.« less

An Analysis of Coast Guard HH-65 Engine Reliability: A Comparison of Malfunctions to Component Removals

DTIC Science & Technology

2004-03-01

developed while the HH-65 was still in the developmental phase and a Full Authority Digital Engine Control ( FADEC ) system (Chisom, 1984:189). In 1982...Lucas Aerospace developed a FADEC system for the HH-65. While test flights of this system were successful in demonstrating the feasibility of the...Lucas FADEC for the HH-65, there were problems associated with a lack of redundancy of the Engine Control Computer software and lack of cockpit

Ab initio Potential Energy Surface for H-H2

NASA Technical Reports Server (NTRS)

Partridge, Harry; Bauschlicher, Charles W., Jr.; Stallcop, James R.; Levin, Eugene

1993-01-01

Ab initio calculations employing large basis sets are performed to determine an accurate potential energy surface for H-H2 interactions for a broad range of separation distances. At large distances, the spherically averaged potential determined from the calculated energies agrees well with the corresponding results determined from dispersion coefficients; the van der Waals well depth is predicted to be 75 +/- (mu)E(sub h). Large basis sets have also been applied to reexamine the accuracy of theoretical repulsive potential energy surfaces. Multipolar expansions of the computed H-H2 potential energy surface are reported for four internuclear separation distances (1.2, 1.401, 1.449, and 1.7a(sub 0) of the hydrogen molecule. The differential elastic scattering cross section calculated from the present results is compared with the measurements from a crossed beam experiment.

A New Look at Stellar Outflows: Spitzer Observations of the HH 46/47 System

NASA Technical Reports Server (NTRS)

Noriega-Crespo, Alberto; Morris, Patrick; Marleau, Francine R.; Carey, Sean; Boogert, Adwin; van Dishoeck, Ewine; Evans, Neal J., II; Keene, Jocelyn; Muzerolle, James; Stapelfeldt, Karl;

High resolution simulations of a variable HH jet

NASA Astrophysics Data System (ADS)

Raga, A. C.; de Colle, F.; Kajdič, P.; Esquivel, A.; Cantó, J.

2007-04-01

Context: In many papers, the flows in Herbig-Haro (HH) jets have been modeled as collimated outflows with a time-dependent ejection. In particular, a supersonic variability of the ejection velocity leads to the production of "internal working surfaces" which (for appropriate forms of the time-variability) can produce emitting knots that resemble the chains of knots observed along HH jets. Aims: In this paper, we present axisymmetric simulations of an "internal working surface" in a radiative jet (produced by an ejection velocity variability). We concentrate on a given parameter set (i.e., on a jet with a constante ejection density, and a sinusoidal velocity variability with a 20 yr period and a 40 km s-1 half-amplitude), and carry out a study of the behaviour of the solution for increasing numerical resolutions. Methods: In our simulations, we solve the gasdynamic equations together with a 17-species atomic/ionic network, and we are therefore able to compute emission coefficients for different emission lines. Results: We compute 3 adaptive grid simulations, with 20, 163 and 1310 grid points (at the highest grid resolution) across the initial jet radius. From these simulations we see that successively more complex structures are obtained for increasing numerical resolutions. Such an effect is seen in the stratifications of the flow variables as well as in the predicted emission line intensity maps. Conclusions: .We find that while the detailed structure of an internal working surface depends on resolution, the predicted emission line luminosities (integrated over the volume of the working surface) are surprisingly stable. This is definitely good news for the future computation of predictions from radiative jet models for carrying out comparisons with observations of HH objects.

Metabolism of hydroxydibenzofurans, methoxydibenzofurans, acetoxydibenzofurans, and nitrodibenzofurans by Sphingomonas sp. strain HH69

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

Harms, H.; Wittich, R.M.; Fortnagel, P.

The metabolism of 11 substituted dibenzofurans by the dibenzofuran-degrading Sphingomonas sp. strain HH69 was investigated. Strain HH69 utilizes 2-, 3-, and 4-acetoxydibenzofuran as well as 2-, 3-, and 4-hydroxydibenzofuran as sole sources of carbon and energy. The degradation of acetoxydibenzofurans is initiated by hydrolysis of the ester bonds, yielding the corresponding hydroxydibenzofurans and acetate. Strain HH69 grew on 2-methoxydibenzofuran only after it was adapted to the utilization of 5-methoxysalicylic acid, whereas 3- and 4-methoxydibenzofuran as well as 2- and 3-nitrodibenzofuran were only cooxidized. During the breakdown of all eight hydroxy-, methoxy-, and nitrodibenzofurans studied here, the corresponding substituted salicylic acidsmore » accumulated in the culture broth. In the cases of 2- and 3-hydroxydibenzofuran as well as 2- and 3-nitrodibenzofuran, salicylic acid was also formed. Those four dibenzofurans which did not serve as carbon sources for strain HH69 were converted to a nonutilizable salicylic acid derivative. From turnover experiments with the mutant HH69/II, which is deficient in meta-cleavage, 2,2{prime}, 3,4{prime}-tetrahydroxybiphenyl, 2,2{prime},3-trihydroxy-5{prime}-methoxybiphenyl, 2,2{prime},3-trihydroxy-5{prime}-nitrobiphenyl, and 2,2{prime},3-trihydroxy-4{prime}-nitrobiphenyl were isolated as the main products formed from 3-hydroxydibenzofuran, 2-methoxydibenzofuran, and 2- and 3-nitrodibenzo-furan, respectively. These results indicate significant regioselectivity for the dioxygenolytic cleavage of the ether bond of these monosubstituted dibenzofurans, with a preference for the nonsubstituted aromatic nucleus. Substituted trihydroxybiphenyls are converted further by meta-cleavage followed by the removal of the side chain of the resulting product. A stepwise degradation of this side chain was found to be involved in the metabolism of 2-hydroxydibenzofuran. 34 refs., 5 figs., 2 tabs.« less

The Time-Dependent Wavelet Spectrum of HH 1 and 2

NASA Astrophysics Data System (ADS)

Raga, A. C.; Reipurth, B.; Esquivel, A.; González-Gómez, D.; Riera, A.

2018-04-01

We have calculated the wavelet spectra of four epochs (spanning ≍20 yr) of Hα and [S II] HST images of HH 1 and 2. From these spectra we calculated the distribution functions of the (angular) radii of the emission structures. We found that the size distributions have maxima (corresponding to the characteristic sizes of the observed structures) with radii that are logarithmically spaced with factors of ≍2→3 between the successive peaks. The positions of these peaks generally showed small shifts towards larger sizes as a function of time. This result indicates that the structures of HH 1 and 2 have a general expansion (seen at all scales), and/or are the result of a sequence of merging events resulting in the formation of knots with larger characteristic sizes.

The Three-Dimensional Structure of HH 32 from GMOS IFU Spectroscopy

NASA Astrophysics Data System (ADS)

Beck, Tracy L.; Riera, A.; Raga, A. C.; Aspin, C.

2004-01-01

We present new high-resolution spectroscopic observations of the Herbig-Haro object HH 32 from system verification observations made with the GMOS IFU at Gemini North Observatory. The three-dimensional spectral data cover a 8.7"×5.85" spatial field and 4820-7040 Å spectral region centered on the HH 32 A knot complex. We show the position-dependent line profiles and radial velocity channel maps of the Hα line, as well as line ratio velocity channel maps of [O III] λ5007/Hα, [O I] λ6300/Hα, [N II] λ6583/Hα, [S II] λλ(6716+6730)/Hα, and [S II] λ6716/λ6730. We find that the line emission and the line ratios vary significantly on spatial scales of ~1" and over velocities of ~50 km s-1. A ``3/2-dimensional'' bow shock model is qualitatively successful at reproducing the general features of the radial velocity channel maps, but it does not show the same complexity as the data, and it fails to reproduce the line ratios in our high spatial resolution maps. The observations of HH 32 A show two or three superposed bow shocks with separations of ~3", which we interpret as evidence of a line-of-sight superposition of two or three working surfaces located along the redshifted body of the HH 32 outflow. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the National Science Foundation on behalf of the Gemini partnership: the NSF, the Particle Physics and Astronomy Research Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), CNPq (Brazil), and CONICET (Argentina).

CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.

PubMed

Kang, Yu; Zheng, Bo; Shen, Bin; Chen, Yongchang; Wang, Lei; Wang, Jianying; Niu, Yuyu; Cui, Yiqiang; Zhou, Jiankui; Wang, Hong; Guo, Xuejiang; Hu, Bian; Zhou, Qi; Sha, Jiahao; Ji, Weizhi; Huang, Xingxu

2015-12-20

Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in testicular development, including disorganized and incompletely formed testis cords with decreased number of peritubular myoid cells and male-to-female sex reversal. We previously reported successful clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome targeting in cynomolgus monkeys. Here, we describe a male fetal monkey in which targeted genome editing using CRISPR/Cas9 produced Dax1-null mutations in most somatic tissues and in the gonads. This DAX1-deficient monkey displayed defects in adrenal gland development and abnormal testis architecture with small cords, expanded blood vessels and extensive fibrosis. Sertoli cell formation was not affected. This phenotype strongly resembles findings in human patients with AHC-HH caused by mutations in DAX1. We further detected upregulation of Wnt/β-catenin-VEGF signaling in the fetal Dax1-deficient testis, suggesting abnormal activation of signaling pathways in the absence of DAX1 as one mechanism of AHC-HH. Our study reveals novel insight into the role of DAX1 in HH and provides proof-of-principle for the generation of monkey models of human disease via CRISPR/Cas9-mediated gene targeting. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Efficient heterologous expression and secretion in Aspergillus oryzae of a llama variable heavy-chain antibody fragment V(HH) against EGFR.

PubMed

Okazaki, Fumiyoshi; Aoki, Jun-ichi; Tabuchi, Soichiro; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko

2012-10-01

We have constructed a filamentous fungus Aspergillus oryzae that secretes a llama variable heavy-chain antibody fragment (V(HH)) that binds specifically to epidermal growth factor receptor (EGFR) in a culture medium. A major improvement in yield was achieved by fusing the V(HH) with a Taka-amylase A signal sequence (sTAA) and a segment of 28 amino acids from the N-terminal region of Rhizopus oryzae lipase (N28). The yields of secreted, immunologically active anti-EGFR V(HH) reached 73.8 mg/1 in a Sakaguchi flask. The V(HH) fragments were released from the sTAA or N28 proteins by an indigenous A. oryzae protease during cultivation. The purified recombinant V(HH) fragment was specifically recognized and could bind to the EGFR with a high affinity.

Warm Molecular Hydrogen and Ionized Neon in the HH 2 Outflow

NASA Astrophysics Data System (ADS)

Lefloch, B.; Cernicharo, J.; Cabrit, S.; Noriega-Crespo, A.; Moro-Martín, A.; Cesarsky, D.

2003-06-01

We report on spectro-imaging observations of the Herbig-Haro 2 outflow with the ISOCAM camera on board the Infrared Space Observatory. The [Ne II] 12.81 μm and [Ne III] 15.55 μm lines are detected only toward the jet working surface (HH 2H), consistent with the high excitation of this knot in the optical range, while H2 pure rotational emission is found all over the shocked region HH 2. The low-energy transition S(2) traces warm gas (T~400 K) peaked toward knots E and F and extended ejecta (T~250-380 K) with masses of a few times 10-3 Msolar in the high-velocity CO outflow extending between the powering source and HH 2. Such emission could arise from low-velocity C-type shocks (v~=10-15 km s-1). The higher transitions S(3)-S(7) trace the emission of hot shocked gas (T=1000-1400 K) from individual optical knots in the HH 2 region. The ortho-to-para (OTP) ratio exhibits large spatial variations between 1.2 (knot E) and 2.5 (knot H), well below its value at LTE. The emission of the S(3)-S(7) lines is well accounted for by planar C-shock models with a typical velocity Vs=20-30 km s-1 propagating into a medium of density ni=104-105 cm-3 with an initial OTP ratio close to 1 in the preshock gas. In the leading edge of the jet, where the geometry of the emission allows a simple modeling, a good agreement is found with velocities derived from the optical proper motions measured in the ionized gas. Based on observations with the Infrared Space Observatory, an ESA project with instruments funded by ESA member states (especially the PI countries: France, Germany, the Netherlands, and the United Kingdom) and with the participation of ISAS and NASA.

Progress towards next generation hadron colliders: FCC-hh, HE-LHC, and SPPC

NASA Astrophysics Data System (ADS)

Zimmermann, Frank; EuCARD-2 Extreme Beams Collaboration; Future Circular Collider (FCC) Study Collaboration

2017-01-01

A higher-energy circular proton collider is generally considered to be the only path available in this century for exploring energy scales well beyond the reach of the Large Hadron Collider (LHC) presently in operation at CERN. In response to the 2013 Update of the European Strategy for Particle Physics and aligned with the 2014 US ``P5'' recommendations, the international Future Circular Collider (FCC) study, hosted by CERN, is designing such future frontier hadron collider. This so-called FCC-hh will provide proton-proton collisions at a centre-of-mass energy of 100 TeV, with unprecedented luminosity. The FCC-hh energy goal is reached by combining higher-field, 16 T magnets, based on Nb3Sn superconductor, and a new 100 km tunnel connected to the LHC complex. In addition to the FCC-hh proper, the FCC study is also exploring the possibility of a High-Energy LHC (HE-LHC), with a centre-of-mass energy of 25-27 TeV, as could be achieved in the existing 27 km LHC tunnel using the FCC-hh magnet technology. A separate design effort centred at IHEP Beijing aims at developing and constructing a similar collider in China, with a smaller circumference of about 54 km, called SPPC. Assuming even higher-field 20 T magnets, by relying on high-temperature superconductor, the SPPC could reach a c.m. energy of about 70 TeV. This presentation will report the motivation and the present status of the R&D for future hadron colliders, a comparison of the three designs under consideration, the major challenges, R&D topics, the international technology programs, and the emerging global collaboration. Work supported by the European Commission under Capacities 7th Framework Programme project EuCARD-2, Grant Agreement 312453, and the HORIZON 2020 project EuroCirCol, Grant Agreement 654305.

Binary energy source of the HH 250 outflow and its circumstellar environment

NASA Astrophysics Data System (ADS)

Comerón, Fernando; Reipurth, Bo; Yen, Hsi-Wei; Connelley, Michael S.

2018-04-01

Aims: Herbig-Haro flows are signposts of recent major accretion and outflow episodes. We aim to determine the nature and properties of the little-known outflow source HH 250-IRS, which is embedded in the Aquila clouds. Methods: We have obtained adaptive optics-assisted L-band images with the NACO instrument on the Very Large Telescope (VLT), together with N- and Q-band imaging with VISIR also on the VLT. Using the SINFONI instrument on the VLT we carried out H- and K-band integral field spectroscopy of HH 250-IRS, complemented with spectra obtained with the SpeX instrument at the InfraRed Telescope Facility (IRTF) in the JHKL bands. Finally, the SubMillimeter Array (SMA) interferometer was used to study the circumstellar environment of HH 250-IRS at 225 and 351 GHz with CO (2-1) and CO (3-2) maps and 0.9 mm and 1.3 mm continuum images. Results: The HH 250-IRS source is resolved into a binary with 0.''53 separation, corresponding to 120 AU at the adopted distance of 225 pc. The individual components show heavily veiled spectra with weak CO absorption indicative of late-type stars. Both are Class I sources, but their spectral energy distributions between 1.5 μm and 19 μm differ markedly and suggest the existence of a large cavity around one of the components. The millimeter interferometric observations indicate that the gas mainly traces a circumbinary envelope or disk, while the dust emission is dominated by one of the circumstellar envelopes. Conclusions: HH 250-IRS is a new addition to the handful of multiple systems where the individual stellar components, the circumstellar disks and a circumbinary disk can be studied in detail, and a rare case among those systems in which a Herbig-Haro flow is present. Based on observations obtained with the VLT (Cerro Paranal, Chile) in programs 089.C-0196(A), 095.C-0488(A), and 095.C-0488(B), as well as with IRTF (Mauna Kea, Hawaii), SMA (Mauna Kea, Hawaii), and the Nordic Optical Telescope (La Palma, Canary Islands, Spain

20 years of cosmic muons research performed in IFIN-HH

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

Mitrica, Bogdan

2012-11-20

During the last two decades a modern direction in particle physics research has been developed in IFIN-HH Bucharest, Romania. The history started with the WILLI detector built in IFIN-HH Bucharest in collaboration with KIT Karlsruhe (formerly Forschungszentrum Karlsruhe). The detector was designed for measurements of the low energy muon charge ratio (< 1GeV) based on a delayed coincidence method, measuring the decay time of the muons stopped in the detector: the positive muons decay freely, but the negative muons are captured in the atom thus creating muonic atoms and decay depending on the nature of the host atom. In amore » first configuration, the WILLI detector was placed in a fixed position for measuring vertical muons. Further WILLI has been transformed in a rotatable device which allows directional measurements of muon charge ratio and muon flux. The results exhibit a pronounced azimuthal asymmetry (East-West effect) due to the different in fluence of the geomagnetic field on the trajectories of positive and negative muons in air. In parallel, flux measurement, taking into account muon events with nergies > 0.4GeV, show a diurnal modulation of the muon flux. The analysis of the muon events for energies < 0.6GeV reveals an aperiodic variation of the muon flux. A new detection system performing coincidence measurements between the WILLI calorimeter and a small array of 12 scintillators plates has been installed in IFIN-HH starting from the autumn of 2010. The aim of the system is to investigate muon charge ratio from individual EAS by using the mini-array as trigger for the WILLI calorimeter. Such experimental studies could provide detailed information on hadronic interaction models and primary cosmic ray composition at energies around 10{sup 15}eV. Simulation studies and preliminary experimental tests, regarding the performances of the mini-array, have been performed using H and Fe primaries, with energies in a range 10{sup 13}eV - 10{sup 15}eV. The results

CENTIMETER CONTINUUM OBSERVATIONS OF THE NORTHERN HEAD OF THE HH 80/81/80N JET: REVISING THE ACTUAL DIMENSIONS OF A PARSEC-SCALE JET

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

Masque, Josep M.; Estalella, Robert; Girart, Josep M.

2012-10-10

We present 6 and 20 cm Jansky Very Large Array/Very Large Array observations of the northern head of the HH 80/81/80N jet, one of the largest collimated jet systems known so far, aimed to look for knots farther than HH 80N, the northern head of the jet. Aligned with the jet and 10' northeast of HH 80N, we found a radio source not reported before, with a negative spectral index similar to that of HH 80, HH 81, and HH 80N. The fit of a precessing jet model to the knots of the HH 80/81/80N jet, including the new source,more » shows that the position of this source is close to the jet path resulting from the modeling. If the new source belongs to the HH 80/81/80N jet, its derived size and dynamical age are 18.4 pc and >9 Multiplication-Sign 10{sup 3} yr, respectively. If the jet is symmetric, its southern lobe would expand beyond the cloud edge resulting in an asymmetric appearance of the jet. Based on the updated dynamical age, we speculate on the possibility that the HH 80/81/80N jet triggered the star formation observed in a dense core found ahead of HH 80N, which shows signposts of interaction with the jet. These results indicate that parsec-scale radio jets can play a role in the stability of dense clumps and the regulation of star formation in the molecular cloud.« less

The Sinorhizobium fredii HH103 Lipopolysaccharide Is Not Only Relevant at Early Soybean Nodulation Stages but Also for Symbiosome Stability in Mature Nodules

PubMed Central

Margaret, Isabel; Lucas, M. Mercedes; Acosta-Jurado, Sebastián; Buendía-Clavería, Ana M.; Fedorova, Elena; Hidalgo, Ángeles; Rodríguez-Carvajal, Miguel A.; Rodriguez-Navarro, Dulce N.; Ruiz-Sainz, José E.; Vinardell, José M.

2013-01-01

In this work we have characterised the Sinorhizobium fredii HH103 greA lpsB lpsCDE genetic region and analysed for the first time the symbiotic performance of Sinorhizobium fredii lps mutants on soybean. The organization of the S. fredii HH103 greA, lpsB, and lpsCDE genes was equal to that of Sinorhizobium meliloti 1021. S. fredii HH103 greA, lpsB, and lpsE mutant derivatives produced altered LPS profiles that were characteristic of the gene mutated. In addition, S. fredii HH103 greA mutants showed a reduction in bacterial mobility and an increase of auto-agglutination in liquid cultures. RT-PCR and qPCR experiments demonstrated that the HH103 greA gene has a positive effect on the transcription of lpsB. Soybean plants inoculated with HH103 greA, lpsB or lpsE mutants formed numerous ineffective pseudonodules and showed severe symptoms of nitrogen starvation. However, HH103 greA and lps mutants were also able to induce the formation of a reduced number of soybean nodules of normal external morphology, allowing the possibility of studying the importance of bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis. The infected cells of these nodules showed signs of early termination of symbiosis and lytical clearance of bacteroids. These cells also had very thick walls and accumulation of phenolic-like compounds, pointing to induced defense reactions. Our results show the importance of bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis and their role in preventing host cell defense reactions. S. fredii HH103 lpsB mutants also showed reduced nodulation with Vigna unguiculata, although the symbiotic impairment was less pronounced than in soybean. PMID:24098345

Design and performance studies of a hadronic calorimeter for a FCC-hh experiment

NASA Astrophysics Data System (ADS)

Faltova, J.

2018-03-01

The hadron-hadron Future Circular Collider (FCC-hh) project studies the physics reach of a proton-proton machine with a centre-of-mass-energy of 100 TeV and five times greater peak luminosities than at the High-Luminosity LHC (HL-LHC). The high-energy regime of the FCC-hh opens new opportunities for the discovery of physics beyond the standard model. At 100 TeV a large fraction of the W, Z, H bosons and top quarks are produced with a significant boost. It implies an efficient reconstruction of very high energetic objects decaying hadronically. The reconstruction of those boosted objects sets the calorimeter performance requirements in terms of energy resolution, containment of highly energetic hadron showers, and high transverse granularity. We present the current baseline technologies for the calorimeter system in the barrel region of the FCC-hh reference detector: a liquid argon electromagnetic and a scintillator-steel hadronic calorimeters. The focus of this paper is on the hadronic calorimeter and the performance studies for hadrons. The reconstruction of single particles and the achieved energy resolution for the combined system of the electromagnetic and hadronic calorimeters are discussed.

40 CFR Appendix to Subpart Hh of... - Tables

Code of Federal Regulations, 2011 CFR

2011-07-01

... specified in § 63.760(h). § 63.1(c)(3) and (c)(4) No Section reserved. § 63.1(c)(5) Yes. § 63.1(d) No... category and there are additional definitions in subpart HH. § 63.3(a) through (c) Yes. § 63.4(a)(1) through (a)(2) Yes. § 63.4(a)(3) through (a)(5) No Section reserved. § 63.4(b) Yes. § 63.4(c) Yes. § 63.5...

Infrasound Generation from the HH Seismic Hammer.

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

Jones, Kyle Richard

2014-10-01

The HH Seismic hammer is a large, "weight-drop" source for active source seismic experiments. This system provides a repetitive source that can be stacked for subsurface imaging and exploration studies. Although the seismic hammer was designed for seismological studies it was surmised that it might produce energy in the infrasonic frequency range due to the ground motion generated by the 13 metric ton drop mass. This study demonstrates that the seismic hammer generates a consistent acoustic source that could be used for in-situ sensor characterization, array evaluation and surface-air coupling studies for source characterization.

Optimizing laboratory animal stress paradigms: The H-H* experimental design.

PubMed

McCarty, Richard

2017-01-01

Major advances in behavioral neuroscience have been facilitated by the development of consistent and highly reproducible experimental paradigms that have been widely adopted. In contrast, many different experimental approaches have been employed to expose laboratory mice and rats to acute versus chronic intermittent stress. An argument is advanced in this review that more consistent approaches to the design of chronic intermittent stress experiments would provide greater reproducibility of results across laboratories and greater reliability relating to various neural, endocrine, immune, genetic, and behavioral adaptations. As an example, the H-H* experimental design incorporates control, homotypic (H), and heterotypic (H*) groups and allows for comparisons across groups, where each animal is exposed to the same stressor, but that stressor has vastly different biological and behavioral effects depending upon each animal's prior stress history. Implementation of the H-H* experimental paradigm makes possible a delineation of transcriptional changes and neural, endocrine, and immune pathways that are activated in precisely defined stressor contexts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sequential Application of Ligand and Structure Based Modeling Approaches to Index Chemicals for Their hH4R Antagonism

PubMed Central

Basile, Livia; Milardi, Danilo; Zeidan, Mouhammed; Raiyn, Jamal; Guccione, Salvatore; Rayan, Anwar

2014-01-01

The human histamine H4 receptor (hH4R), a member of the G-protein coupled receptors (GPCR) family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE) and Iterative Stochastic Elimination (ISE) approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and increase the

Sequential application of ligand and structure based modeling approaches to index chemicals for their hH4R antagonism.

PubMed

Pappalardo, Matteo; Shachaf, Nir; Basile, Livia; Milardi, Danilo; Zeidan, Mouhammed; Raiyn, Jamal; Guccione, Salvatore; Rayan, Anwar

2014-01-01

The human histamine H4 receptor (hH4R), a member of the G-protein coupled receptors (GPCR) family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE) and Iterative Stochastic Elimination (ISE) approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼ 4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and increase the

Atomic hydrogen surrounded by water molecules, H(H2O)m, modulates basal and UV-induced gene expressions in human skin in vivo.

PubMed

Shin, Mi Hee; Park, Raeeun; Nojima, Hideo; Kim, Hyung-Chel; Kim, Yeon Kyung; Chung, Jin Ho

2013-01-01

Recently, there has been much effort to find effective ingredients which can prevent or retard cutaneous skin aging after topical or systemic use. Here, we investigated the effects of the atomic hydrogen surrounded by water molecules, H(H2O)m, on acute UV-induced responses and as well as skin aging. Interestingly, we observed that H(H2O)m application to human skin prevented UV-induced erythema and DNA damage. And H(H2O)m significantly prevented UV-induced MMP-1, COX-2, IL-6 and IL-1β mRNA expressions in human skin in vivo. We found that H(H2O)m prevented UV-induced ROS generation and inhibited UV-induced MMP-1, COX-2 and IL-6 expressions, and UV-induced JNK and c-Jun phosphorylation in HaCaT cells. Next, we investigated the effects of H(H2O)m on intrinsically aged or photoaged skin of elderly subjects. In intrinsically aged skin, H(H2O)m application significantly reduced constitutive expressions of MMP-1, IL-6, and IL-1β mRNA. Additionally, H(H2O)m significantly increased procollagen mRNA and also decreased MMP-1 and IL-6 mRNA expressions in photoaged facial skin. These results demonstrated that local application of H(H2O)m may prevent UV-induced skin inflammation and can modulate intrinsic skin aging and photoaging processes. Therefore, we suggest that modifying the atmospheric gas environment within a room may be a new way to regulate skin functions or skin aging.

Atomic Hydrogen Surrounded by Water Molecules, H(H2O)m, Modulates Basal and UV-Induced Gene Expressions in Human Skin In Vivo

PubMed Central

Shin, Mi Hee; Park, Raeeun; Nojima, Hideo; Kim, Hyung-Chel; Kim, Yeon Kyung; Chung, Jin Ho

2013-01-01

Recently, there has been much effort to find effective ingredients which can prevent or retard cutaneous skin aging after topical or systemic use. Here, we investigated the effects of the atomic hydrogen surrounded by water molecules, H(H2O)m, on acute UV-induced responses and as well as skin aging. Interestingly, we observed that H(H2O)m application to human skin prevented UV-induced erythema and DNA damage. And H(H2O)m significantly prevented UV-induced MMP-1, COX-2, IL-6 and IL-1β mRNA expressions in human skin in vivo. We found that H(H2O)m prevented UV-induced ROS generation and inhibited UV-induced MMP-1, COX-2 and IL-6 expressions, and UV-induced JNK and c-Jun phosphorylation in HaCaT cells. Next, we investigated the effects of H(H2O)m on intrinsically aged or photoaged skin of elderly subjects. In intrinsically aged skin, H(H2O)m application significantly reduced constitutive expressions of MMP-1, IL-6, and IL-1β mRNA. Additionally, H(H2O)m significantly increased procollagen mRNA and also decreased MMP-1 and IL-6 mRNA expressions in photoaged facial skin. These results demonstrated that local application of H(H2O)m may prevent UV-induced skin inflammation and can modulate intrinsic skin aging and photoaging processes. Therefore, we suggest that modifying the atmospheric gas environment within a room may be a new way to regulate skin functions or skin aging. PMID:23637886

Perspective view, northeast. Billings Memorial Library was designed by H.H. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Perspective view, northeast. Billings Memorial Library was designed by H.H. Richardson in 1883-85 in his characteristic Romanesque Revival mode. Located on the University of Vermont campus, it is now a student center. - University of Vermont, Billings Memorial Library, 48 University Place, Burlington, Chittenden County, VT

Hubble Space Telescope Images of the HH 34 Jet and Bow Shock: Structure and Proper Motions

NASA Astrophysics Data System (ADS)

Reipurth, Bo; Heathcote, Steve; Morse, Jon; Hartigan, Pat; Bally, John

2002-01-01

We present new, deep Hα and [S II] images of the HH 34 jet and bow shock obtained with the Wide Field Planetary Camera 2 on board the Hubble Space Telescope (HST), which reveal the structure of this fine HH flow with unprecedented detail. Many of the knots in the jet appear to form small working surfaces with bright [S II] cores and thin Hα filaments where the mini-bow shocks extend into the surrounding medium. In combination with earlier, short-exposure HST images we have determined very precise proper-motion vectors for the various shock structures in the outflow. The jet becomes visible within about an arcsecond of the source, where a new knot has emerged between our two epoch images; it has a space velocity of at least 300 km s-1, as derived from the proper motions and correcting for the 30° angle of the flow to the line of sight. The jet rapidly slows down to a mean space velocity of about 220 km s-1, with a standard deviation of 20 km s-1 among the jet knots. Such low internal velocities lead to weak shocks, consistent with the high [S II]/Hα ratio along the jet body and in accordance with the internal working surface model for jets. The jet motion appears to be ballistic, with no evidence for a turbulent boundary layer. The jet is well resolved and steadily expands with a half-opening angle of 0.4d. The large HH 34 working surface shows a multitude of knots, all of which are enveloped by a series of very thin, limb-brightened Hα-emitting filaments immediately behind the shock front where the flow faces into the preshock medium. One of these filaments developed four regularly spaced tiny knots between the two epochs, possibly due to a Rayleigh-Taylor instability along the filament or caused by the presence of small, dense clumps in the ambient medium. Proper motions of the HH 34 working surface show an obvious expansion due to material being squirted sideways. In addition to the large-scale S-shaped symmetry of the giant HH 34 flow, the jet shows a

Diagnostic value of progesterone receptor, p16, p53 and pHH3 expression in uterine atypical leiomyoma.

PubMed

Liang, Yun; Zhang, Xiaofei; Chen, Xiaoduan; Lü, Weiguo

2015-01-01

The differential diagnosis between atypical leiomyoma and leiomyosarcoma may be hard based on morphological criterion at times. It would be helpful to find out biomarkers that can be used to distinguish them. The aim of the study was to investigate the diagnostic value of progesterone receptor (PR), p16, p53 and pHH3 expression in a series of uterine smooth muscle tumors. Immunohistochemical expression of PR, p16, p53 and pHH3 was investigated on 32 atypical leiomyomas, 15 leiomyosarcomas and 15 usual leomyomas. The difference in expression was compared between atypical leiomyoma and other groups. The expression of PR, p16, and pHH3 was found significantly different between atypical leiomyomas and leiomyosarcomas, but lack of significant difference between atypical leiomyomas and usual leiomyomas. There was no significant difference with regard to p53 distribution among these uterine smooth muscle tumors. High p16, pHH3 expression and low PR expression preferred the diagnosis of leiomyosarcoma. The panel of antibodies used in this study is a useful complementary analysis in the assessment of problematic uterine smooth muscle tumors.

Diagnostic value of progesterone receptor, p16, p53 and pHH3 expression in uterine atypical leiomyoma

PubMed Central

Liang, Yun; Zhang, Xiaofei; Chen, Xiaoduan; Lü, Weiguo

2015-01-01

The differential diagnosis between atypical leiomyoma and leiomyosarcoma may be hard based on morphological criterion at times. It would be helpful to find out biomarkers that can be used to distinguish them. The aim of the study was to investigate the diagnostic value of progesterone receptor (PR), p16, p53 and pHH3 expression in a series of uterine smooth muscle tumors. Immunohistochemical expression of PR, p16, p53 and pHH3 was investigated on 32 atypical leiomyomas, 15 leiomyosarcomas and 15 usual leomyomas. The difference in expression was compared between atypical leiomyoma and other groups. The expression of PR, p16, and pHH3 was found significantly different between atypical leiomyomas and leiomyosarcomas, but lack of significant difference between atypical leiomyomas and usual leiomyomas. There was no significant difference with regard to p53 distribution among these uterine smooth muscle tumors. High p16, pHH3 expression and low PR expression preferred the diagnosis of leiomyosarcoma. The panel of antibodies used in this study is a useful complementary analysis in the assessment of problematic uterine smooth muscle tumors. PMID:26261614

4D display of the outflow track of embryonic-chick hearts (HH 14-19) using a high speed streak mode OCT

NASA Astrophysics Data System (ADS)

Ma, Siyu; Wang, Rui; Goodwin, Richard L.; Markwald, Roger R.; Borg, Thomas K.; Runyan, Raymond B.; Gao, Zhi

2013-02-01

Congenital Heart Disease (CHD) is the most common congenital malformation in newborns in the US. Although knowledge of CHD is limited, altered hemodynamic conditions are suspected as the factor that stimulates cardiovascular cell response, resulting in the heart morphology remodeling that ultimately causes CHDs. Therefore, one of recent efforts in CHD study is to develop high-speed imaging tools to correlate the rapidly changing hemodynamic condition and the morphological adaptations of an embryonic heart in vivo. We have developed a high-speed streak mode OCT that works at the center wavelength of 830 nm and is capable of providing images (292x220 μm2) of the outflow tract of an embryonic chick heart at the rate of 1000 Hz. The modality can provide a voxel resolution in the range of 10 μm3, and the spectral resolution allows a depth range of 1.63 mm. In the study reported here, each of the 4D images of an outflow tract was recorded for 2 seconds. The recording was conducted every 2 hours (HH17 to HH18), 3 hours (HH14 to HH17), and 4 hours (HH18 to HH19). Because of the fast scan speed, there is no need for postacquisition processing such as use of gating techniques to provide a fine 3D structure. In addition, more details of the outflow tract are preserved in the recorded images. The 4D images can be used in the future to determine the role of blood flow in CHD development.

Transformation of Dibenzo-p-Dioxin by Pseudomonas sp. Strain HH69

PubMed Central

Harms, Hauke; Wittich, Rolf-Michael; Sinnwell, Volker; Meyer, Holger; Fortnagel, Peter; Francke, Wittko

1990-01-01

Dibenzo-p-dioxin was oxidatively cleaved by the dibenzofuran-degrading bacterium Pseudomonas sp. strain HH69 to produce minor amounts of 1-hydroxydibenzo-p-dioxin and catechol, while a 2-phenoxy derivative of muconic acid was formed as the major product. Upon acidic methylation, the latter yielded the dimethylester of cis, trans-2-(2-hydroxyphenoxy)-muconic acid. PMID:16348160

The HhH(2)/NDD Domain of the Drosophila Nod Chromokinesin-like Protein Is Required for Binding to Chromosomes in the Oocyte Nucleus

PubMed Central

Cui, Wei; Hawley, R. Scott

2005-01-01

Nod is a chromokinesin-like protein that plays a critical role in segregating achiasmate chromosomes during female meiosis. The C-terminal half of the Nod protein contains two putative DNA-binding domains. The first of these domains, known as the HMGN domain, consists of three tandemly repeated high-mobility group N motifs. This domain was previously shown to be both necessary and sufficient for binding of the C-terminal half of Nod to mitotic chromosomes in embryos. The second putative DNA-binding domain, denoted HhH(2)/NDD, is a helix-hairpin-helix(2)/Nod-like DNA-binding domain. Although the HhH(2)/NDD domain is not required or sufficient for chromosome binding in embryos, several well-characterized nod mutations have been mapped in this domain. To characterize the role of the HhH(2)/NDD domain in mediating Nod function, we created a series of UAS-driven transgene constructs capable of expressing either a wild-type Nod-GFP fusion protein or proteins in which the HhH(2)/NDD domain had been altered by site-directed mutagenesis. Although wild-type Nod-GFP localizes to the oocyte chromosomes and rescues the segregation defect in nod mutant oocytes, two of three proteins carrying mutants in the HhH(2)/NDD domain fail to either rescue the nod mutant phenotype or bind to oocyte chromosomes. However, these mutant proteins do bind to the polytene chromosomes in nurse-cell nuclei and enter the oocyte nucleus. Thus, even though the HhH(2)/NDD domain is not essential for chromosome binding in other cell types, it is required for chromosome binding in the oocyte. These HhH(2)/NDD mutants also block the localization of Nod to the posterior pole of stage 9–10A oocytes, a process that is thought to facilitate the interaction of Nod with the plus ends of microtubules (Cui et al. 2005). This observation suggests that the Nod HhH2/NDD domain may play other roles in addition to binding Nod to meiotic chromosomes. PMID:16143607

Structure-guided mutational analysis of the OB, HhH, and BRCT domains of Escherichia coli DNA ligase.

PubMed

Wang, Li Kai; Nair, Pravin A; Shuman, Stewart

2008-08-22

NAD(+)-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains is linked via a tetracysteine zinc finger to distal helix-hairpin-helix (HhH) and BRCT (BRCA1-like C-terminal) domains. The OB and HhH domains contribute prominently to the protein clamp formed by LigA around nicked duplex DNA. Here we conducted a structure-function analysis of the OB and HhH domains of Escherichia coli LigA by alanine scanning and conservative substitutions, entailing 43 mutations at 22 amino acids. We thereby identified essential functional groups in the OB domain that engage the DNA phosphodiester backbone flanking the nick (Arg(333)); penetrate the minor grove and distort the nick (Val(383) and Ile(384)); or stabilize the OB fold (Arg(379)). The essential constituents of the HhH domain include: four glycines (Gly(455), Gly(489), Gly(521), Gly(553)), which bind the phosphate backbone across the minor groove at the outer margins of the LigA-DNA interface; Arg(487), which penetrates the minor groove at the outer margin on the 3 (R)-OH side of the nick; and Arg(446), which promotes protein clamp formation via contacts to the nucleotidyltransferase domain. We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation.

A conceptual solution for a beam halo collimation system for the Future Circular hadron-hadron Collider (FCC-hh)

NASA Astrophysics Data System (ADS)

Fiascaris, M.; Bruce, R.; Redaelli, S.

2018-06-01

We present the first conceptual solution for a collimation system for the hadron-hadron option of the Future Circular Collider (FCC-hh). The collimation layout is based on the scaling of the present Large Hadron Collider collimation system to the FCC-hh energy and it includes betatron and momentum cleaning, as well as dump protection collimators and collimators in the experimental insertions for protection of the final focus triplet magnets. An aperture model for the FCC-hh is defined and the geometrical acceptance is calculated at injection and collision energy taking into account mechanical and optics imperfections. The performance of the system is then assessed through the analysis of normalized halo distributions and complete loss maps for an ideal lattice. The performance limitations are discussed and a solution to improve the system performance with the addition of dispersion suppression collimators around the betatron cleaning insertion is presented.

HH-65A Dolphin digital integrated avionics

NASA Technical Reports Server (NTRS)

Huntoon, R. B.

1984-01-01

Communication, navigation, flight control, and search sensor management are avionics functions which constitute every Search and Rescue (SAR) operation. Routine cockpit duties monopolize crew attention during SAR operations and thus impair crew effectiveness. The United States Coast Guard challenged industry to build an avionics system that automates routine tasks and frees the crew to focus on the mission tasks. The HH-64A SAR avionics systems of communication, navigation, search sensors, and flight control have existed independently. On the SRR helicopter, the flight management system (FMS) was introduced. H coordinates or integrates these functions. The pilot interacts with the FMS rather than the individual subsystems, using simple, straightforward procedures to address distinct mission tasks and the flight management system, in turn, orchestrates integrated system response.

Analysis of Rare Earth Elements in Uranium Using Handheld Laser-Induced Breakdown Spectroscopy (HH LIBS)

DOE PAGES

Manard, Benjamin T.; Wylie, E. Miller; Willson, Stephen P.

2018-05-22

In this paper, a portable handheld laser-induced breakdown spectroscopy (HH LIBS) instrument was evaluated as a rapid method to qualitatively analyze rare earth elements in a uranium oxide matrix. This research is motivated by the need for development of a method to perform rapid, at-line chemical analysis in a nuclear facility, particularly to provide a rapid first pass analysis to determine if additional actions or measurements are warranted. This will result in the minimization of handling and transport of radiological and nuclear material and subsequent exposure to their associated hazards. In this work, rare earth elements (Eu, Nd, and Yb)more » were quantitatively spiked into a uranium oxide powder and analyzed by the HH LIBS instrumentation. This method demonstrates the ability to rapidly identify elemental constituents in sub-percent levels in a uranium matrix. Preliminary limits of detection (LODs) were determined with values on the order of hundredths of a percent. Validity of this methodology was explored by employing a National Institute of Standards and Technology (NIST) standard reference materials (SRM) 610 and 612 (Trace Elements in Glass). Finally, it was determined that the HH LIBS method was able to clearly discern the rare earths elements of interest in the glass or uranium matrices.« less

Analysis of Rare Earth Elements in Uranium Using Handheld Laser-Induced Breakdown Spectroscopy (HH LIBS)

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

Manard, Benjamin T.; Wylie, E. Miller; Willson, Stephen P.

In this paper, a portable handheld laser-induced breakdown spectroscopy (HH LIBS) instrument was evaluated as a rapid method to qualitatively analyze rare earth elements in a uranium oxide matrix. This research is motivated by the need for development of a method to perform rapid, at-line chemical analysis in a nuclear facility, particularly to provide a rapid first pass analysis to determine if additional actions or measurements are warranted. This will result in the minimization of handling and transport of radiological and nuclear material and subsequent exposure to their associated hazards. In this work, rare earth elements (Eu, Nd, and Yb)more » were quantitatively spiked into a uranium oxide powder and analyzed by the HH LIBS instrumentation. This method demonstrates the ability to rapidly identify elemental constituents in sub-percent levels in a uranium matrix. Preliminary limits of detection (LODs) were determined with values on the order of hundredths of a percent. Validity of this methodology was explored by employing a National Institute of Standards and Technology (NIST) standard reference materials (SRM) 610 and 612 (Trace Elements in Glass). Finally, it was determined that the HH LIBS method was able to clearly discern the rare earths elements of interest in the glass or uranium matrices.« less

Analysis of Rare Earth Elements in Uranium Using Handheld Laser-Induced Breakdown Spectroscopy (HH LIBS).

PubMed

Manard, Benjamin T; Wylie, E Miller; Willson, Stephen P

2018-01-01

A portable handheld laser-induced breakdown spectroscopy (HH LIBS) instrument was evaluated as a rapid method to qualitatively analyze rare earth elements in a uranium oxide matrix. This research is motivated by the need for development of a method to perform rapid, at-line chemical analysis in a nuclear facility, particularly to provide a rapid first pass analysis to determine if additional actions or measurements are warranted. This will result in the minimization of handling and transport of radiological and nuclear material and subsequent exposure to their associated hazards. In this work, rare earth elements (Eu, Nd, and Yb) were quantitatively spiked into a uranium oxide powder and analyzed by the HH LIBS instrumentation. This method demonstrates the ability to rapidly identify elemental constituents in sub-percent levels in a uranium matrix. Preliminary limits of detection (LODs) were determined with values on the order of hundredths of a percent. Validity of this methodology was explored by employing a National Institute of Standards and Technology (NIST) standard reference materials (SRM) 610 and 612 (Trace Elements in Glass). It was determined that the HH LIBS method was able to clearly discern the rare earths elements of interest in the glass or uranium matrices.

Structure-guided Mutational Analysis of the OB, HhH, and BRCT Domains of Escherichia coli DNA Ligase*S⃞

PubMed Central

Wang, Li Kai; Nair, Pravin A.; Shuman, Stewart

2008-01-01

NAD+-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains is linked via a tetracysteine zinc finger to distal helix-hairpin-helix (HhH) and BRCT (BRCA1-like C-terminal) domains. The OB and HhH domains contribute prominently to the protein clamp formed by LigA around nicked duplex DNA. Here we conducted a structure-function analysis of the OB and HhH domains of Escherichia coli LigA by alanine scanning and conservative substitutions, entailing 43 mutations at 22 amino acids. We thereby identified essential functional groups in the OB domain that engage the DNA phosphodiester backbone flanking the nick (Arg333); penetrate the minor grove and distort the nick (Val383 and Ile384); or stabilize the OB fold (Arg379). The essential constituents of the HhH domain include: four glycines (Gly455, Gly489, Gly521, Gly553), which bind the phosphate backbone across the minor groove at the outer margins of the LigA-DNA interface; Arg487, which penetrates the minor groove at the outer margin on the 3 ®-OH side of the nick; and Arg446, which promotes protein clamp formation via contacts to the nucleotidyltransferase domain. We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation. PMID:18515356

The Janthinobacterium sp. HH01 Genome Encodes a Homologue of the V. cholerae CqsA and L. pneumophila LqsA Autoinducer Synthases

PubMed Central

Hornung, Claudia; Poehlein, Anja; Haack, Frederike S.; Schmidt, Martina; Dierking, Katja; Pohlen, Andrea; Schulenburg, Hinrich; Blokesch, Melanie; Plener, Laure; Jung, Kirsten; Bonge, Andreas; Krohn-Molt, Ines; Utpatel, Christian; Timmermann, Gabriele; Spieck, Eva; Pommerening-Röser, Andreas; Bode, Edna; Bode, Helge B.; Daniel, Rolf; Schmeisser, Christel; Streit, Wolfgang R.

2013-01-01

Janthinobacteria commonly form biofilms on eukaryotic hosts and are known to synthesize antibacterial and antifungal compounds. Janthinobacterium sp. HH01 was recently isolated from an aquatic environment and its genome sequence was established. The genome consists of a single chromosome and reveals a size of 7.10 Mb, being the largest janthinobacterial genome so far known. Approximately 80% of the 5,980 coding sequences (CDSs) present in the HH01 genome could be assigned putative functions. The genome encodes a wealth of secretory functions and several large clusters for polyketide biosynthesis. HH01 also encodes a remarkable number of proteins involved in resistance to drugs or heavy metals. Interestingly, the genome of HH01 apparently lacks the N-acylhomoserine lactone (AHL)-dependent signaling system and the AI-2-dependent quorum sensing regulatory circuit. Instead it encodes a homologue of the Legionella- and Vibrio-like autoinducer (lqsA/cqsA) synthase gene which we designated jqsA. The jqsA gene is linked to a cognate sensor kinase (jqsS) which is flanked by the response regulator jqsR. Here we show that a jqsA deletion has strong impact on the violacein biosynthesis in Janthinobacterium sp. HH01 and that a jqsA deletion mutant can be functionally complemented with the V. cholerae cqsA and the L. pneumophila lqsA genes. PMID:23405110

Structure and spectral features of H+(H2O)7: Eigen versus Zundel forms.

PubMed

Shin, Ilgyou; Park, Mina; Min, Seung Kyu; Lee, Eun Cheol; Suh, Seung Bum; Kim, Kwang S

2006-12-21

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H(+)(H(2)O)(7). For H(+)(H(2)O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H(+)(H(2)O)(7) [though nearly isoenergetic to the 3D structure for D(+)(D(2)O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments.

Structure and spectral features of H+(H2O)7: Eigen versus Zundel forms

NASA Astrophysics Data System (ADS)

Shin, Ilgyou; Park, Mina; Min, Seung Kyu; Lee, Eun Cheol; Suh, Seung Bum; Kim, Kwang S.

2006-12-01

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)7. For H+(H2O)7 the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Møller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)7 [though nearly isoenergetic to the 3D structure for D+(D2O)7]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments.

Physical Properties of Pyridinium Fluorohydrogenate, [pyridine · H+][H2F3]-

NASA Astrophysics Data System (ADS)

Hulse, Ryan; Singh, Rajiv

2008-12-01

Ionic liquids (ILs), also referred to as molten salts, have found application as electrolytes for batteries and super-capacitors, in electroplating baths, as designer solvents, and as reaction media. A few of the desired properties of a super-capacitor electrolyte are nonflammability, thermal stability, and electrochemical stability. ILs containing aromatic cations have been shown to have low viscosity which results in a high electrochemical conductivity. There is a delicate balance between increasing the thermal stability, or decreasing the melting point, and increasing the electrochemical conductivity of the IL. This study focuses on pyridinium fluorohydrogenate, [pyridine · H+][H2F3]-. Pyridinium fluorohydrogenate has been synthesized by the reaction of pyridine and anhydrous hydrofluoric acid. This IL has a relatively high electrical conductivity (~98 mS · cm-1 at 23 °C), a wide electrochemical window, and a boiling point of 186 °C. A stable gel can also be formed by combining [pyridine · H+][H2F3]- and a super absorbent polymer such as polyacrylic acid. The gel adds mechanical stability to the matrix while not greatly affecting the conductivity of the IL.

Testing electronic structure methods for describing intermolecular H...H interactions in supramolecular chemistry.

PubMed

Casadesús, Ricard; Moreno, Miquel; González-Lafont, Angels; Lluch, José M; Repasky, Matthew P

2004-01-15

In this article a wide variety of computational approaches (molecular mechanics force fields, semiempirical formalisms, and hybrid methods, namely ONIOM calculations) have been used to calculate the energy and geometry of the supramolecular system 2-(2'-hydroxyphenyl)-4-methyloxazole (HPMO) encapsulated in beta-cyclodextrin (beta-CD). The main objective of the present study has been to examine the performance of these computational methods when describing the short range H. H intermolecular interactions between guest (HPMO) and host (beta-CD) molecules. The analyzed molecular mechanics methods do not provide unphysical short H...H contacts, but it is obvious that their applicability to the study of supramolecular systems is rather limited. For the semiempirical methods, MNDO is found to generate more reliable geometries than AM1, PM3 and the two recently developed schemes PDDG/MNDO and PDDG/PM3. MNDO results only give one slightly short H...H distance, whereas the NDDO formalisms with modifications of the Core Repulsion Function (CRF) via Gaussians exhibit a large number of short to very short and unphysical H...H intermolecular distances. In contrast, the PM5 method, which is the successor to PM3, gives very promising results. Our ONIOM calculations indicate that the unphysical optimized geometries from PM3 are retained when this semiempirical method is used as the low level layer in a QM:QM formulation. On the other hand, ab initio methods involving good enough basis sets, at least for the high level layer in a hybrid ONIOM calculation, behave well, but they may be too expensive in practice for most supramolecular chemistry applications. Finally, the performance of the evaluated computational methods has also been tested by evaluating the energetic difference between the two most stable conformations of the host(beta-CD)-guest(HPMO) system. Copyright 2003 Wiley Periodicals, Inc. J Comput Chem 25: 99-105, 2004

A survey of ab initio conical intersections for the H+H2 system

NASA Astrophysics Data System (ADS)

Halász, Gábor; Vibók, Ágnes; Mebel, Alexander M.; Baer, Michael

2003-02-01

In this article we present a survey of the various conical intersections which govern potential transitions between the three lower electronic states for the title molecular system. It was revealed that these three states, for a given fixed HH distance, RHH, usually form four conical intersections: two, between the two lower states and two, between the two upper states. One of the four is the well known equilateral D3h ci and the others are, essentially, C2v cis: One of them is located on the symmetry line perpendicular to the HH axis (just like the D3h ci) and the other two are located on both sides of this symmetry line and in this way form the ci-twins. The study was carried out for four RHH-values, namely, RHH=0.74, 0.5417, 0.52, and 0.4777 Å. It was also established that there exists one single RHH-value designated as R˜HH, located in the interval {0.52, 0.53 Å}, for which all four cis coalesce to become one kind of "super" ci which couples the three states. The numerical study was carried out employing the line integral approach for groups of two and three states. As for the two-state calculations we found that all D3h-cis, at close proximity, are circular (ordinary) Jahn-Teller-type cis, whereas all C2v-cis, at close proximity, are elliptic Jahn-Teller cis [Chem. Phys. Lett 354, 243 (2002)]. Particular attention is given to the 3-state quantization of the nonadiabatic coupling matrix. The quantization is found to be fulfilled in all situations as long as the regions in configuration space are not too far from the relevant cis. In the Discussion and Conclusion we discuss, among other subjects, the possibility to diabatize the adiabatic potential matrix.

A new AMS facility based on a Cockcroft-Walton type 1 MV tandetron at IFIN-HH Magurele, Romania

NASA Astrophysics Data System (ADS)

Stan-Sion, C.; Enachescu, M.; Ghita, D. G.; Calinescu, C. I.; Petre, A.; Mosu, D. V.; Klein, M.

2014-01-01

A 1 MV AMS machine was recently installed in the National Institute for Physics and Nuclear Engineering IFIN-HH, Bucharest Romania. It is the second AMS facility at IFIN-HH having the goal not only to continue but mainly to enlarge the research area of this highly sensitive analyzing method. The multi-element AMS was developed by HVEE to measure 14C, 10Be, and 26Al, and 129I. The results of an acceptance test are presented and demonstrate that this machine is capable of routine 14C age dating and of measurements of other radioisotopes in terms of accuracy and precision as well as a low background level.

Toward understanding the roaming mechanism in H + MgH → Mg + HH reaction

DOE PAGES

Mauguiere, Frederic A. L.; Collins, Peter; Stamatiadis, Stamatis; ...

2016-02-26

The roaming mechanism in the reaction H + MgH →Mg + HH is investigated by classical and quantum dynamics employing an accurate ab initio threedimensional ground electronic state potential energy surface. The reaction dynamics are explored by running trajectories initialized on a four-dimensional dividing surface anchored on three-dimensional normally hyperbolic invariant manifold associated with a family of unstable orbiting periodic orbits in the entrance channel of the reaction (H + MgH). By locating periodic orbits localized in the HMgH well or involving H orbiting around the MgH diatom, and following their continuation with the total energy, regions in phase spacemore » where reactive or nonreactive trajectories may be trapped are found. In this way roaming reaction pathways are deduced in phase space. Patterns similar to periodic orbits projected into configuration space are found for the quantum bound and resonance eigenstates. Roaming is attributed to the capture of the trajectories in the neighborhood of certain periodic orbits. As a result, the complex forming trajectories in the HMgH well can either return to the radical channel or “roam” to the MgHH minimum from where the molecule may react.« less

Simulation of L-band and HH microwave backscattering from coniferous forest stands - A comparison with SIR-B data

NASA Technical Reports Server (NTRS)

Sun, Guo-Qing; Simonett, David S.

1988-01-01

SIR-B images of the Mt. Shasta region of northern California are used to evaluate a composite L-band HH backscattering model of coniferous forest stands. It is found that both SIR-B and simulated backscattering coefficients for eight stands studied have similar trends and relations to average tree height and average number of trees per pixel. Also, the dispersion and distribution of simulated backscattering coefficients from each stand broadly match SIR-B data from the same stand. Although the limited quality and quantity of experimental data makes it difficult to draw any strong conclusions, the comparisons indicate that a stand-based L-band HH composite model seems promising for explaining backscattering features.

Itinerant Deaf Educator and General Educator Perceptions of the D/HH Push-in Model

ERIC Educational Resources Information Center

Rabinsky, Rebecca J.

2013-01-01

A qualitative case study using the deaf and hard of hearing (D/HH) push-in model was conducted on the perceptions of 3 itinerant deaf educators and 3 general educators working in 1 school district. Participants worked in pairs of 1 deaf educator and 1 general educator at 3 elementary schools. Open-ended research questions guided the study, which…

ERDA at the 9 MV Tandem and at the 3 MV Tandetron of IFIN-HH

NASA Astrophysics Data System (ADS)

Petrascu, H.; Petrascu, M.; Pantelica, D.; Negoita, F.; Ionescu, P.; Mihai, M. D.; Acsente, T.; Statescu, M.; Scafes, A. C.

2017-09-01

Recoil spectrometry using heavy ions proposed in 1976 by L'Ecuyer has evolved into a universal IBA technique. Few years later an experimental setup for simultaneous light and medium heavy element detection including a compact ΔE(gas)-Er(solid) telescope, was developed at the Tandem accelerator of IFIN-HH. To increase the resolution, an integrated preamplifier was mounted close to the ionization chamber. The calibration procedure for the telescope and the software for the quantitative evaluation of the data are briefly presented. Recently, a 3 MV Tandetron accelerator has been installed and commissioned at the IFIN-HH. Among several ion-beam techniques for detection and depth profiling of hydrogen isotopes, Elastic Recoil Detection Analysis (ERDA) technique using a low energy 4He beam, proposed by Doyle and Peercy, is particularly advantageous. By measuring simultaneously both the H or D recoiling at a forward angle and backscattered 4He ions, a rather complete characterization of the sample can be achieved. Selected results from our investigations, obtained using these facilities, are presented.

Molecular and enzymatic characterization of a subfamily I.4 lipase from an edible oil-degrader Bacillus sp. HH-01.

PubMed

Kamijo, Takashi; Saito, Akihiro; Ema, Sadaharu; Yoh, Inchi; Hayashi, Hiroko; Nagata, Ryo; Nagata, Yoshiho; Ando, Akikazu

2011-02-01

An edible-oil degrading bacterial strain HH-01 was isolated from oil plant gummy matter and was classified as a member of the genus Bacillus on the basis of the nucleotide sequence of the 16S rRNA gene. A putative lipase gene and its flanking regions were cloned from the strain based on its similarity to lipase genes from other Bacillus spp. The deduced product was composed of 214 amino acids and the putative mature protein, consisting of 182 amino acids, exhibited 82% amino acid sequence identity with the subfamily I.4 lipase LipA of Bacillus subtilis 168. The recombinant product was successfully overproduced as a soluble form in Escherichia coli and showed lipase activity. The gene was, therefore, designated as lipA of HH-01. HH-01 LipA was stable at pH 4-11 and up to 30°C, and its optimum pH and temperature were 8-9 and 30°C, respectively. The enzyme showed preferential hydrolysis of the 1(3)-position ester bond in trilinolein. The activity was, interestingly, enhanced by supplementing with 1 mM CoCl(2), in contrast to other Bacillus lipases. The lipA gene seemed to be constitutively transcribed during the exponential growth phase, regardless of the presence of edible oil.

40 CFR Table Nn-2 to Subpart Hh of... - Lookup Default Values for Calculation Methodology 2 of This Subpart

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Municipal Solid Waste Landfills Pt. 98, Subpt. NN, Table NN-2 Table NN-2 to Subpart HH of Part 98—Lookup Default Values...

State-of-the-art cockpit design for the HH-65A helicopters

NASA Technical Reports Server (NTRS)

Castleberry, D. E.; Mcelreath, M. Y.

1982-01-01

In the design of a HH-65A helicopter cockpit, advanced integrated electronics systems technology was employed to achieve several important goals for this multimission aircraft. They were: (1) integrated systems operation with consistent and simplified cockpit procedures; (2) mission-task-related cockpit displays and controls, and (3) reduced pilot instrument scan effort with excellent outside visibility. The integrated avionics system was implemented to depend heavily upon distributed but complementary processing, multiplex digital bus technology, and multifunction CRT controls and displays. This avionics system was completely flight tested and will soon enter operational service with the Coast Guard.

Radical-molecule reaction C3H+H2O: a mechanistic study.

PubMed

Dong, Hao; Ding, Yi-Hong; Sun, Chia-Chung

2005-02-08

Despite the importance of the C(3)H radical in both combustion and interstellar space, the reactions of C(3)H toward stable molecules have never been studied. In this paper, we report our detailed mechanistic study on the radical-molecule reaction C(3)H+H(2)O at the Becke's three parameter Lee-Yang-Parr-B3LYP6-311G(d,p) and coupled cluster with single, double, and triple excitations-CCSD(T)6-311G(2d,p) (single-point) levels. It is shown that the C(3)H+H(2)O reaction initially favors formation of the carbene-insertion intermediates HCCCHOH (1a,1b) rather than the direct H- or OH-abstraction process. Subsequently, the isomers (1a,1b) can undergo a direct H- extrusion to form the well-known product propynal HCCCHO (P(5)). Highly competitively, (1a,1b) can take the successive 1,4- and 1,2-H-shift interconversion to isomer H(2)CCCHO(2a,2b) and then to isomer H(2)CCHCO(3a,3b), which can finally take a direct C-C bond cleavage to give product C(2)H(3) and CO (P(1)). The other products are kinetically much less feasible. With the overall entrance barrier 10.6 kcal/mol, the title reaction can be important in postburning processes. Particularly, our calculations suggest that the title reaction may play a role in the formation of the intriguing interstellar molecule, propynal HCCCHO. The calculated results will also be useful for the analogous C(3)H reactions such as with ammonia and alkanes.

Revisit the landscape of protonated water clusters H+(H2O)n with n = 10-17: An ab initio global search

NASA Astrophysics Data System (ADS)

Shi, Ruili; Li, Keyao; Su, Yan; Tang, Lingli; Huang, Xiaoming; Sai, Linwei; Zhao, Jijun

2018-05-01

Using a genetic algorithm incorporated with density functional theory, we explore the ground state structures of protonated water clusters H+(H2O)n with n = 10-17. Then we re-optimize the isomers at B97-D/aug-cc-pVDZ level of theory. The extra proton connects with a H2O molecule to form a H3O+ ion in all H+(H2O)10-17 clusters. The lowest-energy structures adopt a monocage form at n = 10-16 and core-shell structure at n = 17 based on the MP2/aug-cc-pVTZ//B97-D/aug-cc-pVDZ+ZPE single-point-energy calculation. Using second-order vibrational perturbation theory, we further calculate the infrared spectra with anharmonic correction for the ground state structures of H+(H2O)10-17 clusters at the PBE0/aug-cc-pVDZ level. The anharmonic correction to the spectra is crucial since it reproduces the experimental results quite well. The extra proton weakens the O-H bond strength in the H3O+ ion since the Wiberg bond order of the O-H bond in the H3O+ ion is smaller than that in H2O molecules, which causes a red shift of the O-H stretching mode in the H3O+ ion.

Search and Rescue Aircrewman/HH3F Avionics, 2-11. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This self-paced, individualized course, adapted from military curriculum materials for use in vocational and technical education, teaches students the skills needed to become a qualified avionics worker and aircrew rescuer on the HH-3F helicopter. The course materials consist of four pamphlets: two student workbooks and two student syllabuses. The…

Infrared Space Observatory Observations of Molecular Hydrogen in HH 54: Measurement of a Nonequilibrium Ratio of Ortho- to Para-H2

NASA Technical Reports Server (NTRS)

Neufeld, David A.; Melnick, Gary J.; Harwit, Martin

1998-01-01

We have detected the S(1), S(2), S(3), S(4), and S(5) pure rotational lines of molecular hydrogen toward the outflow source HH 54 using the Short Wavelength Spectrometer on board the Infrared Space Observatory. The observed H2 line ratios indicate the presence of warm molecular gas with an H2 density of at least 10(sup 5) /cc and a temperature approximately 650 K in which the ratio of ortho- to para-H2 is only 1.2 -+ 0.4, significantly smaller than the equilibrium ratio of 3 expected in gas at that temperature. These observations imply that the measured ratio of ortho- to para-H2 is the legacy of an earlier stage in the thermal history of the gas when the gas had reached equilibrium at a temperature approximately 90 K. Based upon the expected timescale for equilibration, we argue that the nonequilibrium ratio of ortho- to para-H2 observed in HH 54 serves as a chronometer that places a conservative upper limit of approximately 5000 yr on the period for which the emitting gas has been warm. The S(2)/,S(l) and S(3)/S(1) H2 line ratios measured toward HH 54 are consistent with recent theoretical models of Timmermann for the conversion of para- to ortho-H2 behind slow, C-type shocks, but only if the preshock ratio of ortho- to para-H2 was approximately < 0.2.

Search and Rescue Aircrewman/HH3F Flight Mechanic, 2-10. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This self-paced, individualized course, adapted from military curriculum materials for use in vocational and technical education, teaches students the skills needed to become a qualified avionics worker on the HH-3F helicopter. The course materials consist of three pamphlets: two student workbooks and a composite ground/flight syllabus. Each…

Clinicians' perceptions of usefulness of the PubMed4Hh mobile device application for clinical decision making at the point of care: a pilot study.

PubMed

Gartrell, Kyungsook; Brennan, Caitlin W; Wallen, Gwenyth R; Liu, Fang; Smith, Karen G; Fontelo, Paul

2018-05-08

Although evidence-based practice in healthcare has been facilitated by Internet access through wireless mobile devices, research on the effectiveness of clinical decision support for clinicians at the point of care is lacking. This study examined how evidence as abstracts and the bottom-line summaries, accessed with PubMed4Hh mobile devices, affected clinicians' decision making at the point of care. Three iterative steps were taken to evaluate the usefulness of PubMed4Hh tools at the NIH Clinical Center. First, feasibility testing was conducted using data collected from a librarian. Next, usability testing was carried out by a postdoctoral research fellow shadowing clinicians during rounds for one month in the inpatient setting. Then, a pilot study was conducted from February, 2016 to January, 2017, with clinicians using a mobile version of PubMed4Hh. Invitations were sent via e-mail lists to clinicians (physicians, physician assistants and nurse practitioners) along with periodic reminders. Participants rated the usefulness of retrieved bottom-line summaries and abstracts and indicated their usefulness on a 7-point Likert scale. They also indicated location of use (office, rounds, etc.). Of the 166 responses collected in the feasibility phase, more than half of questions (57%, n = 94) were answerable by both the librarian using various resources and by the postdoctoral research fellow using PubMed4Hh. Sixty-six questions were collected during usability testing. More than half of questions (60.6%) were related to information about medication or treatment, while 21% were questions regarding diagnosis, and 12% were specific to disease entities. During the pilot study, participants reviewed 34 abstracts and 40 bottom-line summaries. The abstracts' usefulness mean scores were higher (95% CI [6.12, 6.64) than the scores of the bottom-line summaries (95% CI [5.25, 6.10]). The most frequent reason given was that it confirmed current or tentative diagnostic or

Whole-Genome Sequence of the Anaerobic Isosaccharinic Acid Degrading Isolate, Macellibacteroides fermentans Strain HH-ZS

PubMed Central

Rout, Simon P.; Salah, Zohier B.; Charles, Christopher J.

2017-01-01

Abstract The ability of micro-organisms to degrade isosaccharinic acids (ISAs) while tolerating hyperalkaline conditions is pivotal to our understanding of the biogeochemistry associated within these environs, but also in scenarios pertaining to the cementitious disposal of radioactive wastes. An alkalitolerant, ISA degrading micro-organism was isolated from the hyperalkaline soils resulting from lime depositions. Here, we report the first whole-genome sequence, ISA degradation profile and carbohydrate preoteome of a Macellibacteroides fermentans strain HH-ZS, 4.08 Mb in size, coding 3,241 proteins, 64 tRNA, and 1 rRNA. PMID:28859355

Infrared Space Observatory Observations of Molecular Hydrogen in HH 54: Measurement of a Nonequilibrium Ratio of Ortho- to Para-H2

NASA Technical Reports Server (NTRS)

Neufeld, David A.; Melnick, Gary J.; Harwit, Martin

1998-01-01

We have detected the S(1), S(2), S(3), S(4), and S(5) pure rotational lines of molecular hydrogen toward the outflow source HH 54 using the Short Wavelength Spectrometer on board the Infrared Space Observatory. The observed H2 line ratios indicate the presence of warm molecular gas with an H2 density of at least 10(exp 5) cm(exp -3) and a temperature approximately 650 K in which the ratio of ortho- to para-H2 is only 1.2 +/- 0.4, significantly smaller than the equilibrium ratio of 3 expected in gas at that temperature. These observations imply that the measured ratio of ortho- to para-H2 is the legacy of an earlier stage in the thermal history of the gas when the gas had reached equilibrium at a temperature approximately less than 90 K. Based upon the expected timescale for equilibration, we argue that the nonequilibrium ratio of ortho- to para-H2 observed in HH 54 serves as a chronometer that places a conservative upper limit of approximately 5000 yr on the period for which the emitting gas has been warm. The S(2)/S(1) and S(3)/S(1) H2 line ratios measured toward HH 54 are consistent with recent theoretical models of Timmermann for the conversion of para- to ortho-H2 behind slow, C-type shocks, but only if the preshock ratio of ortho- to para-H2 was approximately less than 0.2.

Elemental classification of the tusks of dugong (Dugong dugong) by HH-XRF analysis and comparison with other species

NASA Astrophysics Data System (ADS)

Nganvongpanit, Korakot; Buddhachat, Kittisak; Piboon, Promporn; Euppayo, Thippaporn; Kaewmong, Patcharaporn; Cherdsukjai, Phaothep; Kittiwatanawong, Kongkiat; Thitaram, Chatchote

2017-04-01

The elemental composition was investigated and applied for identifying the sex and habitat of dugongs, in addition to distinguishing dugong tusks and teeth from other animal wildlife materials such as Asian elephant (Elephas maximus) tusks and tiger (Panthera tigris tigris) canine teeth. A total of 43 dugong tusks, 60 dugong teeth, 40 dolphin teeth, 1 whale tooth, 40 Asian elephant tusks and 20 tiger canine teeth were included in the study. Elemental analyses were conducted using a handheld X-ray fluorescence analyzer (HH-XRF). There was no significant difference in the elemental composition of male and female dugong tusks, whereas the overall accuracy for identifying habitat (the Andaman Sea and the Gulf of Thailand) was high (88.1%). Dolphin teeth were able to be correctly predicted 100% of the time. Furthermore, we demonstrated a discrepancy in elemental composition among dugong tusks, Asian elephant tusks and tiger canine teeth, and provided a high correct prediction rate among these species of 98.2%. Here, we demonstrate the feasible use of HH-XRF for preliminary species classification and habitat determination prior to using more advanced techniques such as molecular biology.

Dust destruction and thermal inhomogeneities in the Orion Nebula. Results of HH 202.

NASA Astrophysics Data System (ADS)

Espíritu, J.; Peimbert, A.; Delgado-Inglada, G.; Ruiz, M. T.

2017-11-01

We present a long-slit spectroscopic analysis of Herbig-Haro 202 and the surrounding gas of the Orion Nebula using data from the Very Large Telescope. We determined the spatial variation of its physical conditions and chemical abundances. Special attention was paid to the iron (Fe) and oxygen (O) abundances, which show a peak at the brightest part of HH 202, allowing us to estimate that 57% of the dust is the destroyed; we also calculate the amount of depletion of oxygen in dust grains. Finally we show that O abundances determined from collisionally excited lines and recombination lines are irreconcilable at the center of the shock unless thermal inhomogeneities are considered.

Adapting National Water Model Forecast Data to Local Hyper-Resolution H&H Models During Hurricane Irma

NASA Astrophysics Data System (ADS)

Singhofen, P.

2017-12-01

The National Water Model (NWM) is a remarkable undertaking. The foundation of the NWM is a 1 square kilometer grid which is used for near real-time modeling and flood forecasting of most rivers and streams in the contiguous United States. However, the NWM falls short in highly urbanized areas with complex drainage infrastructure. To overcome these shortcomings, the presenter proposes to leverage existing local hyper-resolution H&H models and adapt the NWM forcing data to them. Gridded near real-time rainfall, short range forecasts (18-hour) and medium range forecasts (10-day) during Hurricane Irma are applied to numerous detailed H&H models in highly urbanized areas of the State of Florida. Coastal and inland models are evaluated. Comparisons of near real-time rainfall data are made with observed gaged data and the ability to predict flooding in advance based on forecast data is evaluated. Preliminary findings indicate that the near real-time rainfall data is consistently and significantly lower than observed data. The forecast data is more promising. For example, the medium range forecast data provides 2 - 3 days advanced notice of peak flood conditions to a reasonable level of accuracy in most cases relative to both timing and magnitude. Short range forecast data provides about 12 - 14 hours advanced notice. Since these are hyper-resolution models, flood forecasts can be made at the street level, providing emergency response teams with valuable information for coordinating and dispatching limited resources.

[Ultrastructural observation of tendonization of artificial tendon 109HH in rabbit].

PubMed

Liu, L; Cao, Q; Xiao, H

1995-09-01

Ten New Zealand rabbits were divided into 5 groups at random. Calcaneal tendons were cut bilaterally, then atificial tendon 109HH was used to connect the two ends of the cut tendon. Ultrastructural changes of control group and experimental groups at 2, 6, 12, 28 weeks after section were observed. The results showed that fibroblast proliferated and a lot of ribosome and RER appeared in plasm during 2 approximately 6 weeks, indicating artificial tendon caused fibroblast proliferation. During this period, fibroblast over synthesized collagenous protein and the synthesis of collagenous fibers peaked. During 12-28 weeks, the number of fibroblasts and the synthesis of collagenous protein decreased. Finally, fibroblasts became inactive tendon cells. With the formation of new tendons, the artificial tendens were degradated and absorbed, and disappeared after 12 weeks. The new tendon fibers became thicker and had the correct direction through reconstruction. The structure and function of new tendons could be restored to be consistent with normal values.

Infrared photodissociation spectroscopy of H(+)(H2O)6·M(m) (M = Ne, Ar, Kr, Xe, H2, N2, and CH4): messenger-dependent balance between H3O(+) and H5O2(+) core isomers.

PubMed

Mizuse, Kenta; Fujii, Asuka

2011-04-21

Although messenger mediated spectroscopy is a widely-used technique to study gas phase ionic species, effects of messengers themselves are not necessarily clear. In this study, we report infrared photodissociation spectroscopy of H(+)(H(2)O)(6)·M(m) (M = Ne, Ar, Kr, Xe, H(2), N(2), and CH(4)) in the OH stretch region to investigate messenger(M)-dependent cluster structures of the H(+)(H(2)O)(6) moiety. The H(+)(H(2)O)(6), the protonated water hexamer, is the smallest system in which both the H(3)O(+) (Eigen) and H(5)O(2)(+) (Zundel) hydrated proton motifs coexist. All the spectra show narrower band widths reflecting reduced internal energy (lower vibrational temperature) in comparison with bare H(+)(H(2)O)(6). The Xe-, CH(4)-, and N(2)-mediated spectra show additional band features due to the relatively strong perturbation of the messenger. The observed band patterns in the Ar-, Kr-, Xe-, N(2)-, and CH(4)-mediated spectra are attributed mainly to the "Zundel" type isomer, which is more stable. On the other hand, the Ne- and H(2)-mediated spectra are accounted for by a mixture of the "Eigen" and "Zundel" types, like that of bare H(+)(H(2)O)(6). These results suggest that a messenger sometimes imposes unexpected isomer-selectivity even though it has been thought to be inert. Plausible origins of the isomer-selectivity are also discussed.

Influence of nuclear exchange on nonadiabatic electron processes in H(+)+H2 collisions.

PubMed

Errea, L F; Illescas, Clara; Macías, A; Méndez, L; Pons, B; Rabadán, I; Riera, A

2010-12-28

H(+)+H(2) collisions are studied by means of a semiclassical approach that explicitly accounts for nuclear rearrangement channels in nonadiabatic electron processes. A set of classical trajectories is used to describe the nuclear motion, while the electronic degrees of freedom are treated quantum mechanically in terms of a three-state expansion of the collision wavefunction. We describe electron capture and vibrational excitation, which can also involve nuclear exchange and dissociation, in the E = 2-1000 eV impact energy range. We compare dynamical results obtained with two parametrizations of the potential energy surface of H(3)(+) ground electronic state. Total cross sections for E > 10 eV agree with previous results using a vibronic close-coupling expansion, and with experimental data for E < 10 eV. Additionally, some prototypical features of both nuclear and electron dynamics at low E are discussed.

Kinetic fractionation processes recorded in the stalagmites of some limestone caves in Korea

NASA Astrophysics Data System (ADS)

Woo, K. S.; Jo, K.; Edwards, L. R.; Cheng, H.; Wang, Y.; Yoon, H.

2006-12-01

Stable isotope data (oxygen and carbon) of carbonate minerals (mostly calcite, but sometimes aragonite) in stalagmites have been the most commonly and widely used proxies for paleoclimatic research. This is based upon the assumption that carbonate minerals precipitated in isotopic equilibrium with dripping waters from stalactites, thus should reflect paleoclimatic variations. The state of equilibrium, so called "Hendy Test", has been commonly used. Hendy (1971) showed that during kinetic fractionation both oxygen and carbon isotopes behaves in a similar way due to faster degassing rate of cabon dioxide, resulting in the enrichment of both isotopes. The stalagmites from three limestone caves (Gwaneum, Eden and Daeya Caves) in Korea were investigated to understand the effects of kinetic fractionation during their growth. The stalagmites are mostly composed of columnar calcites, but contains the layers of cave coral that is composed of fibrous calcite. The cave coral layers should have grown when the supply rate of dripping water decreased significantly. Stable isotope pattern in three stalagmites do not show the same pattern of disequilibrium process. The cave corals in the Eden stalagmite show the enriched carbon and oxygen isotope values (15 and 5 per mil, respectively) that has the same bimodal pattern as suggested by Hendy (1971). However, the cave corals in the Gwaneum stalagmites show the enriched carbon, but depleted oxygen isotope values (3 and 1 per mil, respectively). Also, the calcite layer precipitated in disequilibrium in the Daeya stalagmite show more enriched carbon isotope values by up to 6 per mil, but show more or less the same oxygen isotopic values, compared to the columnar calcite which was precipitated in equilibrium. Therefore, caution should be made to determine the state of equilibrium precipitation of carbonate minerals in stalagmites. The "Hendy Test" may not be the only solution because other types of speleothems can be formed in

LineageSpecificSeqgen: generating sequence data with lineage-specific variation in the proportion of variable sites

PubMed Central

Grievink, Liat Shavit; Penny, David; Hendy, Mike D; Holland, Barbara R

2009-01-01

Correction to Shavit Grievink L, Penny D, Hendy MD, Holland BR: LineageSpecificSeqgen: generating sequence data with lineage-specific variation in the proportion of variable sites. BMC Evol Biol 2008, 8(1):317.

USAF Bioenvironmental Noise Data Handbook. Volume 156. HH-1N In-flight Crew Noise

NASA Astrophysics Data System (ADS)

Hille, H. K.

1982-11-01

The HH-IN is a USAF multi-purpose utility helicopter providing support for various USAF missions. This report provides measured data defining the bioacoustic environments at flight crew locations inside this helicopter during normal flight operations. Data are reported for two locations in a wide variety of physical and psychoacoustic measures: overall and band sound pressure levels, C-weighted and A-weighted sound levels, preferred speech interference level, perceived noise level, and limiting times for total daily exposure of personnel with and without standard Air Force ear protectors. Refer to Volume 1 of this handbook, USAF Bioenvironmental Noise Data Handbook, Vol. 1: Organization, Content and Application, AMRL-TR-75-50(1) 1975, for discussion of the objective and design of the handbook, the types of data presented, measurement procedures, instrumentation, data processing, definitions of quantities, symbols, equations, applications, limitations, etc.

MULTI-COMPONENT ANALYSIS OF POSITION-VELOCITY CUBES OF THE HH 34 JET

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

Rodriguez-Gonzalez, A.; Esquivel, A.; Raga, A. C.

We present an analysis of H{alpha} spectra of the HH 34 jet with two-dimensional spectral resolution. We carry out multi-Gaussian fits to the spatially resolved line profiles and derive maps of the intensity, radial velocity, and velocity width of each of the components. We find that close to the outflow source we have three components: a high (negative) radial velocity component with a well-collimated, jet-like morphology; an intermediate velocity component with a broader morphology; and a positive radial velocity component with a non-collimated morphology and large linewidth. We suggest that this positive velocity component is associated with jet emission scatteredmore » in stationary dust present in the circumstellar environment. Farther away from the outflow source, we find only two components (a high, negative radial velocity component, which has a narrower spatial distribution than an intermediate velocity component). The fitting procedure was carried out with the new AGA-V1 code, which is available online and is described in detail in this paper.« less

Biomechanics of the Chick Embryonic Heart Outflow Tract at HH18 Using 4D Optical Coherence Tomography Imaging and Computational Modeling

PubMed Central

Liu, Aiping; Yin, Xin; Shi, Liang; Li, Peng; Thornburg, Kent L.; Wang, Ruikang; Rugonyi, Sandra

2012-01-01

During developmental stages, biomechanical stimuli on cardiac cells modulate genetic programs, and deviations from normal stimuli can lead to cardiac defects. Therefore, it is important to characterize normal cardiac biomechanical stimuli during early developmental stages. Using the chicken embryo model of cardiac development, we focused on characterizing biomechanical stimuli on the Hamburger–Hamilton (HH) 18 chick cardiac outflow tract (OFT), the distal portion of the heart from which a large portion of defects observed in humans originate. To characterize biomechanical stimuli in the OFT, we used a combination of in vivo optical coherence tomography (OCT) imaging, physiological measurements and computational fluid dynamics (CFD) modeling. We found that, at HH18, the proximal portion of the OFT wall undergoes larger circumferential strains than its distal portion, while the distal portion of the OFT wall undergoes larger wall stresses. Maximal wall shear stresses were generally found on the surface of endocardial cushions, which are protrusions of extracellular matrix onto the OFT lumen that later during development give rise to cardiac septa and valves. The non-uniform spatial and temporal distributions of stresses and strains in the OFT walls provide biomechanical cues to cardiac cells that likely aid in the extensive differential growth and remodeling patterns observed during normal development. PMID:22844414

Itinerant deaf educator and general educator perceptions of the D/HH push-in model.

PubMed

Rabinsky, Rebecca J

2013-01-01

A qualitative case study using the deaf and hard of hearing (D/HH) push-in model was conducted on the perceptions of 3 itinerant deaf educators and 3 general educators working in 1 school district. Participants worked in pairs of 1 deaf educator and 1 general educator at 3 elementary schools. Open-ended research questions guided the study, which was concerned with teachers' perceptions of the model in general and with the model's advantages, disadvantages, and effectiveness. Data collected from observations, one-to-one interviews, and a focus group interview enabled the investigator to uncover 4 themes: Participants (a) had an overall positive experience, (b) viewed general education immersion as an advantage, (c) considered high noise levels a disadvantage, and (d) believed the effectiveness of the push-in model was dependent on several factors, in particular, the needs of the student and the nature of the general education classroom environment.

Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models.

PubMed

Rivas-Santiago, Bruno; Castañeda-Delgado, Julio E; Rivas Santiago, Cesar E; Waldbrook, Matt; González-Curiel, Irma; León-Contreras, Juan C; Enciso-Moreno, Jose Antonio; del Villar, Victor; Mendez-Ramos, Jazmin; Hancock, Robert E W; Hernandez-Pando, Rogelio

2013-01-01

Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15-30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB.

Ability of Innate Defence Regulator Peptides IDR-1002, IDR-HH2 and IDR-1018 to Protect against Mycobacterium tuberculosis Infections in Animal Models

PubMed Central

Rivas-Santiago, Bruno; Castañeda-Delgado, Julio E.; Rivas Santiago, Cesar E.; Waldbrook, Matt; González-Curiel, Irma; León–Contreras, Juan C.; Enciso-Moreno, Jose Antonio; del Villar, Victor; Mendez-Ramos, Jazmin; Hancock, Robert E. W.; Hernandez-Pando, Rogelio

2013-01-01

Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15–30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB. PMID:23555622

High resolution HH-XRF scanning and XRD modelling as a tool in sedimentological analysis - A case study from the Enreca-3 core, Bach Long Vi Island, Vietnam

NASA Astrophysics Data System (ADS)

Rizzi, Malgorzata; Hemmingsen Schovsbo, Niels; Korte, Christoph; Bryld Wessel Fyhn, Michael

2017-04-01

To improve the understanding and interpretation of the depositional environment of a late Oligocene lacustrine organic rich oil-prone source rock succession, 2464 hand held (HH)-XRF measurements were made systematically on the 500 m long, continuous core from the fully cored Enreca-3 well. This core, drilled on the remote Bach Long Vi Island, northern Gulf of Tonkin, offshore Vietnam, represents a deep lake succession alternating between lacustrine pelagic dominated sediments interrupted by hyperpycnal turbidites, high density turbidites and debris flows [1, 2]. From a combined HH-XRF-XRD data set, multivariate data analysis and regression models are used to type the rock and to predict the XRD mineral composition based on HH-XRF composition. The rock types and the modelled mineral composition highlight the geochemical variations of the sediment and allows for direct comparison with sedimentological processes and facies changes. The modeling also depicts the cyclic alteration of rock types that are present on many different scales ranging from centimeters to hundreds of meters [1, 2]. The sedimentological and geochemical variations observed throughout the cored section reflects fluctuating paleoclimate, tectonism and hinterland condition controlling the depositional setting, which may provide a deeper understanding of the deposition of this and similar Paleogene syn-rift succession in the South China Sea region. It allows furthermore the development of a more generalized depositional model relevant for other deep-lacustrine syn-rift basins. [1] Petersen et al. (2014) Journal of Petroleum Geology, 37: 373-389. [2] Hovikoski et al. (2016) Journal of Sedimentary Research, 86(8): 982-1007.

Design and performance of an electromagnetic calorimeter for a FCC-hh experiment

NASA Astrophysics Data System (ADS)

Zaborowska, A.

2018-03-01

The physics reach and feasibility of the Future Circular Collider are currently under investigation. The goal is to collide protons with centre-of-mass energies up to 100 TeV, extending the research carried out at the current HEP facilities. The detectors designed for the FCC experiments need to tackle harsh conditions of the unprecedented collision energy and luminosity. The baseline technology for the calorimeter system of the FCC-hh detector is described. The electromagnetic calorimeter in the barrel, as well as the electromagnetic and hadronic calorimeters in the endcaps and the forward regions, are based on the liquid argon as active material. The detector layout in the barrel region combines the concept of a high granularity calorimeter with precise energy measurements. The calorimeters have to meet the requirements of high radiation hardness and must be able to deal with a very high number of collisions per bunch crossings (pile-up). A very good energy and angular resolution for a wide range of electrons' and photons' momentum is needed in order to meet the demands based on the physics benchmarks. First results of the performance studies with the new liquid argon calorimeter are presented, meeting the energy resolution goal.

Photometric study and absolute parameters of the short-period eclipsing binary HH Bootis

NASA Astrophysics Data System (ADS)

Gürol, B.; Bradstreet, D. H.; Demircan, Y.; Gürsoytrak, S. H.

2015-11-01

We present the results of our investigation on the geometrical and physical parameters of the W UMa type binary system HH Bootis from new CCD (BVRI) light curves and published radial velocity data. The photometric data were obtained in 2011 and 2012 at Ankara University Observatory (AUO). Light and radial velocity observations were analyzed simultaneously using the Wilson-Devinney (2013 revision) code to obtain absolute and geometrical parameters. The system was determined to be a W-type W UMa system of a type different from that suggested by Dal and Sipahi (2013). An interesting cyclic period variation in the time intervals between primary and secondary eclipses ("half-period variation") was discovered and analyzed and its possible cause is discussed. Combining our photometric solution with the spectroscopic data we derived masses and radii of the eclipsing system to be M1 = 0.627M⊙ , M2 = 1.068M⊙ , R1 = 0.782R⊙ and R2 = 0.997R⊙ . New light elements were derived and finally the evolutionary status of the system is discussed.

New cosmic rays experiments in the underground laboratory of IFIN-HH from Slanic Prahova, Romania

NASA Astrophysics Data System (ADS)

Mitrica, Bogdan; Stanca, Denis; Brancus, Iliana; Margineanu, Romul; Blebea-Apostu, Ana-Maria; Gomoiu, Claudia; Saftoiu, Alexandra; Toma, Gabriel; Rebel, Heinigerd; Haungs, Andreas; Sima, Octavian; Gherghel-Lascu, Alexandru; Niculescu-Oglinzanu, Mihai

2015-02-01

Since 2006 a modern laboratory has been developed by IFIN-HH in the underground of Slanic Prahova salt ore. This work presents a short review of previous scientific activities performed in the underground laboratory, in parallel with some plans for the future. A mobile detector for cosmic muon flux measurements has been set up at IFIN-HH, Romania. The device is used to measure the muon flux on different locations at the surface and underground and it consists of two detection layers, each one including four large scintillator plates. A new rotatable detector for measurements of the directional variation of the muon flux has been designed and it is presently under preliminary tests. Built from four layers of sensitive material and using for collecting the signals and directing them to the micro PMTs a new technique, through optical fibers instead wave length shifters, it allows an easy discrimination of the moun flux on the arrival directions of muons. Combining the possibility to rotate and the directionality properties, the underground muon detector is acting like a muon tomography device, being able to scan, using cosmic muons, the rock material above the detector. In parallel new detection system based on SiPM will be also installed in the following weeks. It should be composed by four layers, each layer consisting in 4 scintillator plates what we consider in the following as a module of detection. For this purpose, first two scintillator layers, with the optical fibers positioned on perpendicular directions are put in coincidence with other two layers, 1 m distance from the first two, with similar optical fiber arrangement, thus allowing reconstructing muon trajectory. It is intended also to design and construct an experimental device for the investigation of such radio antennas and the behavior of the signal in rock salt at the Slanic salt mine in Romania. Another method to detect high energy neutrinos is based on the detection of secondary particles resulting

Cellulose-dependent expression and antibacterial characteristics of surfactin from Bacillus subtilis HH2 isolated from the giant panda

PubMed Central

Zhong, Zhijun; Su, Huaiyi; Li, Jin; Li, Haozhou; Feng, Fan; Lan, Jingchao; Zhang, Zhihe; Fu, Hualin; Hu, Yanchun; Cao, Suizhong; Chen, Weigang; Deng, Jiabo; Yu, Jianqiu; Zhang, Wenping

2018-01-01

Surfactin secreted by Bacillus subtilis can confer strong, diverse antipathogenic effects, thereby benefitting the host. Carbon source is an important factor for surfactin production. However, the mechanism that bacteria utilize cellulose, the most abundant substance in the intestines of herbivores, to produce surfactin remains unclear. Here, we used B. subtilis HH2, isolated from the feces of a giant panda, as a model to determine changes in surfactin expression in the presence of different concentrations of cellulose by quantitative polymerase chain reaction and high-performance liquid chromatography. We further investigated the antimicrobial effects of surfactin against three common intestinal pathogens (Escherichia coli, Staphylococcus aureus, and Salmonella enterica) and its resistance to high temperature (60–121°C), pH (1–12), trypsin (100–300 μg/mL, pH 8), and pepsin (100–300 μg/mL, pH 2). The results showed that the surfactin expressed lowest in bacteria cultured in the presence of 1% glucose medium as the carbon source, whereas increased in an appropriate cellulose concentration (0.67% glucose and 0.33% cellulose). The surfactin could inhibit E. coli and Staphylococcus aureus, but did not affect efficiently for Salmonella enterica. The antibacterial ability of surfactin did not differ according to temperature (60–100°C), pH (2–11), trypsin (100–300 μg/mL), and pepsin (100–300 μg/mL; P > 0.05), but decreased significantly at extreme environments (121°C, pH 1 or 12; P < 0.05) compared with that in the control group (37°C, pH = 7, without any protease). In conclusion, our findings indicated that B. subtilis HH2 could increase surfactin expression in an appropriate cellulose environment and thus provide benefits to improve the intestinal health of herbivores. PMID:29385201

Cellulose-dependent expression and antibacterial characteristics of surfactin from Bacillus subtilis HH2 isolated from the giant panda.

PubMed

Zhou, Ziyao; Liu, Furui; Zhang, Xinyue; Zhou, Xiaoxiao; Zhong, Zhijun; Su, Huaiyi; Li, Jin; Li, Haozhou; Feng, Fan; Lan, Jingchao; Zhang, Zhihe; Fu, Hualin; Hu, Yanchun; Cao, Suizhong; Chen, Weigang; Deng, Jiabo; Yu, Jianqiu; Zhang, Wenping; Peng, Guangneng

2018-01-01

Surfactin secreted by Bacillus subtilis can confer strong, diverse antipathogenic effects, thereby benefitting the host. Carbon source is an important factor for surfactin production. However, the mechanism that bacteria utilize cellulose, the most abundant substance in the intestines of herbivores, to produce surfactin remains unclear. Here, we used B. subtilis HH2, isolated from the feces of a giant panda, as a model to determine changes in surfactin expression in the presence of different concentrations of cellulose by quantitative polymerase chain reaction and high-performance liquid chromatography. We further investigated the antimicrobial effects of surfactin against three common intestinal pathogens (Escherichia coli, Staphylococcus aureus, and Salmonella enterica) and its resistance to high temperature (60-121°C), pH (1-12), trypsin (100-300 μg/mL, pH 8), and pepsin (100-300 μg/mL, pH 2). The results showed that the surfactin expressed lowest in bacteria cultured in the presence of 1% glucose medium as the carbon source, whereas increased in an appropriate cellulose concentration (0.67% glucose and 0.33% cellulose). The surfactin could inhibit E. coli and Staphylococcus aureus, but did not affect efficiently for Salmonella enterica. The antibacterial ability of surfactin did not differ according to temperature (60-100°C), pH (2-11), trypsin (100-300 μg/mL), and pepsin (100-300 μg/mL; P > 0.05), but decreased significantly at extreme environments (121°C, pH 1 or 12; P < 0.05) compared with that in the control group (37°C, pH = 7, without any protease). In conclusion, our findings indicated that B. subtilis HH2 could increase surfactin expression in an appropriate cellulose environment and thus provide benefits to improve the intestinal health of herbivores.

Do nonbonded H--H interactions in phenanthrene stabilize it relative to anthracene? A possible resolution to this question and its implications for ligands such as 2,2'-bipyridyl.

PubMed

Hancock, Robert D; Nikolayenko, Igor V

2012-08-23

The problem of whether interactions between the hydrogen atoms at the 1,10-positions in the "cleft" of the "bent" phenanthrene stabilize the latter molecule thermodynamically relative to "linear" anthracene, or whether the higher stability of phenanthrene is due to a more energetically favorable π-system, is considered. DFT calculations at the X3LYP/cc-pVTZ(-f)++ level of the ground state energies (E) of anthracene, phenanthrene, and the set of five benzoquinolines are reported. In the gas phase, "bent" phenanthrene was computed to be thermodynamically more stable than "linear" anthracene by -28.5 kJ mol(-1). This fact was attributed predominantly to the phenomenon of higher aromatic stabilization of the π-system of phenanthrene relative to anthracene, and not to the stabilizing influence of the nonbonding H--H interactions in its cleft. In fact, these interactions in phenanthrene were shown to be destabilizing. Similar calculations for five benzoquinolines (bzq) indicate that ΔE values vary as: 6,7-bzq (linear) ≤ 2,3-bzq (linear) < 5,6-bzq (bent) ≤ 3,4-bzq (bent) < 7,8-bzq (bent, no H--H nonbonding interactions in cleft), supporting the idea that it is a more stable π-system that favors 7,8-bzq over 2,3-bzq and 6,7-bzq, and that the H--H interactions in the clefts of 3,4-bzq and 5,6-bzq are destabilizing. Intramolecular hydrogen bonding in the cleft of 7,8-bzq plays a secondary role in its stabilization relative 6,7-bzq. The question of whether H--H nonbonded interactions between H atoms at the 3 and 3' positions of 2,2'-bipyridyl (bpy) coordinated to metal ions are stabilizing or destabilizing is then considered. The energy of bpy is scanned as a function of N-C-C-N torsion angle (χ) in the gas-phase, and it is found that the trans form is 32.8 kJ mol(-1) more stable than the cis conformer. A relaxed coordinate scan of energy of bpy in aqueous solution as a function of χ is modeled using the PBF approach, and it is found that the trans conformer is

SEARCH FOR THE RADION DECAY ϕ → HH WITH γ γ +B barB , τ τ +B barB AND B barB +B barB FINAL STATES IN CMS

NASA Astrophysics Data System (ADS)

Dominici, D.; Dewhirst, G.; Gennai, S.; Fanò, L.; Nikitenko, A.

2005-04-01

The Randall Sundrum model (RS) 1,2 has recently received much attention because it could provide a solution to the hierarchy problem by means of an exponential factor in a five dimensional non-factorizable metric. In the simplest version the RS model is based on a five dimensional universe3,4,5,6,7,8. This scalar sector of the RS model is parametrized in terms of a dimensionless parameter ξ, of the Higgs and radion masses mh, mϕ and the vacuum expectation value of the radion field Λϕ. The presence in the Higgs radion sector of trilinear terms opens up the important possibility of ϕ → hh decay and h → ϕϕ. In this study we estimate the CMS discovery potential for the radion (ϕ) in two Higgs decay mode (ϕ → hh) with γ γ + bbarb , τ τ + bbarb and bbarb +bbarb final states.

Structural determination of a 5-acetamido-3,5,7, 9-tetradeoxy-7-(3-hydroxybutyramido)-L-glycero-L-manno-nonulos onic acid-containing homopolysaccharide isolated from Sinorhizobium fredii HH103.

PubMed Central

Gil-Serrano, A M; Rodríguez-Carvajal, M A; Tejero-Mateo, P; Espartero, J L; Menendez, M; Corzo, J; Ruiz-Sainz, J E; BuendíA-Clavería, A M

1999-01-01

The structure of a polysaccharide from Sinorhizobium fredii HH103 has been determined. This polysaccharide was isolated by following the protocol for lipopolysaccharide extraction. On the basis of monosaccharide analysis, methylation analysis, fast atom bombardment MS, matrix-assisted laser desorption ionization MS, electron-impact high-resolution MS, one-dimensional (1)H-NMR and (13)C-NMR and two-dimensional NMR experiments, the structure was shown to consist of a homopolymer of a 3:1 mixture of 5-acetamido-3,5,7, 9-tetradeoxy-7-[(R)- and (S)-3-hydroxybutyramido]-l-glycero-l-manno-nonulosonic acid. The sugar residues are attached via a glycosidic linkage to the OH group of the 3-hydroxybutyramido substituent and thus the monomers are linked via both glycosidic and amidic linkages. In contrast with the Sinorhizobium K-antigens previously reported, which are composed of a disaccharide repeating unit, the K-antigen polysacharide of S. fredii HH103 is a homopolysaccharide. PMID:10477263

Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo.

PubMed

Amoyel, Marc; Simons, Benjamin D; Bach, Erika A

2014-10-16

Neutral competition, an emerging feature of stem cell homeostasis, posits that individual stem cells can be lost and replaced by their neighbors stochastically, resulting in chance dominance of a clone at the niche. A single stem cell with an oncogenic mutation could bias this process and clonally spread the mutation throughout the stem cell pool. The Drosophila testis provides an ideal system for testing this model. The niche supports two stem cell populations that compete for niche occupancy. Here, we show that cyst stem cells (CySCs) conform to the paradigm of neutral competition and that clonal deregulation of either the Hedgehog (Hh) or Hippo (Hpo) pathway allows a single CySC to colonize the niche. We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process. © 2014 The Authors.

Vibrational inelastic and charge transfer processes in H++H2 system: An ab initio study

NASA Astrophysics Data System (ADS)

Amaran, Saieswari; Kumar, Sanjay

2007-12-01

State-resolved differential cross sections, total and integral cross sections, average vibrational energy transfer, and the relative probabilities are computed for the H++H2 system using the newly obtained ab initio potential energy surfaces at the full CI/cc-pVQZ level of accuracy which allow for both the direct vibrational inelastic and the charge transfer processes. The quantum dynamics is treated within the vibrational close-coupling infinite-order-sudden approximation approach using the two ab initio quasidiabatic potential energy surfaces. The computed collision attributes for both the processes are compared with the available state-to-state scattering experiments at Ec.m.=20eV. The results are in overall good agreement with most of the observed scattering features such as rainbow positions, integral cross sections, and relative vibrational energy transfers. A comparison with the earlier theoretical study carried out on the semiempirical surfaces (diatomics in molecules) is also made to illustrate the reliability of the potential energy surfaces used in the present work.

ALMA discovery of a rotating SO/SO2 flow in HH212. A possible MHD disk wind?

NASA Astrophysics Data System (ADS)

Tabone, B.; Cabrit, S.; Bianchi, E.; Ferreira, J.; Pineau des Forêts, G.; Codella, C.; Gusdorf, A.; Gueth, F.; Podio, L.; Chapillon, E.

2017-11-01

We wish to constrain the possible contribution of a magnetohydrodynamic disk wind (DW) to the HH212 molecular jet. We mapped the flow base with ALMA Cycle 4 at 0.̋13 60 au resolution and compared these observations with synthetic DW predictions. We identified, in SO/SO2, a rotating flow that is wider and slower than the axial SiO jet. The broad outflow cavity seen in C34S is not carved by a fast wide-angle wind but by this slower agent. Rotation signatures may be fitted by a DW of a moderate lever arm launched out to 40 au with SiO tracing dust-free streamlines from 0.05-0.3 au. Such a DW could limit the core-to-star efficiency to ≤50%.

The nearest X-ray emitting protostellar jet (HH 154) observed with Hubble

NASA Astrophysics Data System (ADS)

Bonito, R.; Fridlund, C. V. M.; Favata, F.; Micela, G.; Peres, G.; Djupvik, A. A.; Liseau, R.

2008-06-01

Context: The jet coming from the YSO binary L1551 IRS5 is the closest astrophysical jet known. It is therefore a unique laboratory for studies of outflow mechanisms and of the shocks occurring when expanding material hits the ambient medium as well as of how the related processes influence the star- (and planet-) forming process. Aims: The optical data are related to other data covering the spectrum from the optical band to X-rays with goal of understanding the energetics of low-mass star jets, in general, and of this jet in particular. We study the time evolution of the jet, by measuring the proper motions of knots as they progress outwards from the originating source. Methods: The nebulosities associated with the jet(s) from the protostellar binary L1551 IRS5 were imaged in a number of spectral bands using the Hubble Space Telescope. This allows the proper motion to be measured and permits a simple characterization of the physical conditions in different structures. To this end we developed a reproducible method of data analysis, which allows us to define the position and shape of each substructure observed within the protostellar jet. Using this approach, we derive the proper motion of the knots in the jet, as well as their flux variability and shock emission. Results: The time base over which HST observations were carried out is now about ten years. The sub-structures within the jet undergo significant morphological variations: some knots seem to disappear in a few years and collision between different knots, ejected at different epochs and maybe with different speed, may occur. The velocities along the jet vary between ~100 km s-1 and over 400 km s-1, with the highest speed corresponding to the knots at the base of the jet. Conclusions: There are indications that the HH 154 jet has been active relatively recently. Our results suggest the presence of a new shock front at the base of the jet identified with an internal working surface. From the analysis of the

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

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OT2_pbjerkel_1: Herschel observations of the shocked gas in HH54

NASA Astrophysics Data System (ADS)

Bjerkeli, P.

2011-09-01

A shock that can be studied in detail, using a very limited amount of Herschel time, is the Herbig-Haro object HH54 located in the nearby Chamaeleon II cloud at a distance of 180 pc. The shocked region has an angular extent of roughly 30'' and is not contaminated with emission from other nearby objects. The gas, traced by H2O and CO, emits radiation predominantly in the far-infrared regime. For that reason, this program can only be executed using the instruments aboard the Herschel Space Observatory. We propose spectroscopy of rotational H2O and CO transitions, falling in the wavelength range covered by SPIRE and PACS. These observations will allow us to stratify the shocked region in different physical/kinematical components. We will also improve our understanding of the mechanisms responsible for water production and destruction. Given the relatively large angular extent of the region, we will determine the types of shock responsible for the emission in different positions along the shocked surface. We also propose HIFI observations of selected CO and H2O transitions. A bullet feature has previously been observed in several CO line profiles. Using HIFI, we will constrain the origin and physical properties of the region responsible for this emission.

The Anatomy of the Young Protostellar Outflow HH 211

NASA Astrophysics Data System (ADS)

Tappe, A.; Forbrich, J.; Martín, S.; Yuan, Y.; Lada, C. J.

2012-05-01

We present Spitzer Space Telescope 5-36 μm mapping observations toward the southeastern lobe of the young protostellar outflow HH 211. The southeastern terminal shock of the outflow shows a rich mid-infrared spectrum including molecular emission lines from OH, H2O, HCO+, CO2, H2, and HD. The spectrum also shows a rising infrared continuum toward 5 μm, which we interpret as unresolved emission lines from highly excited rotational levels of the CO v = 1-0 fundamental band. This interpretation is supported by a strong excess flux observed in the Spitzer/IRAC 4-5 μm channel 2 image compared to the other IRAC channels. The extremely high critical densities of the CO v = 1-0 ro-vibrational lines and a comparison to H2 and CO excitation models suggest jet densities larger than 106 cm-3 in the terminal shock. We also observed the southeastern terminal outflow shock with the Submillimeter Array and detected pure rotational emission from CO 2-1, HCO+ 3-2, and HCN 3-2. The rotationally excited CO traces the collimated outflow backbone as well as the terminal shock. HCN traces individual dense knots along the outflow and in the terminal shock, whereas HCO+ solely appears in the terminal shock. The unique combination of our mid-infrared and submillimeter observations with previously published near-infrared observations allow us to study the interaction of one of the youngest known protostellar outflows with its surrounding molecular cloud. Our results help us to understand the nature of some of the so-called green fuzzies (Extended Green Objects), and elucidate the physical conditions that cause high OH excitation and affect the chemical OH/H2O balance in protostellar outflows and young stellar objects. In an appendix to this paper, we summarize our Spitzer follow-up survey of protostellar outflow shocks to find further examples of highly excited OH occurring together with H2O and H2.

Synthesis, biological evaluation, and computational studies of Tri- and tetracyclic nitrogen-bridgehead compounds as potent dual-acting AChE inhibitors and hH3 receptor antagonists.

PubMed

Darras, Fouad H; Pockes, Steffen; Huang, Guozheng; Wehle, Sarah; Strasser, Andrea; Wittmann, Hans-Joachim; Nimczick, Martin; Sotriffer, Christoph A; Decker, Michael

2014-03-19

Combination of AChE inhibiting and histamine H3 receptor antagonizing properties in a single molecule might show synergistic effects to improve cognitive deficits in Alzheimer's disease, since both pharmacological actions are able to enhance cholinergic neurotransmission in the cortex. However, whereas AChE inhibitors prevent hydrolysis of acetylcholine also peripherally, histamine H3 antagonists will raise acetylcholine levels mostly in the brain due to predominant occurrence of the receptor in the central nervous system. In this work, we designed and synthesized two novel classes of tri- and tetracyclic nitrogen-bridgehead compounds acting as dual AChE inhibitors and histamine H3 antagonists by combining the nitrogen-bridgehead moiety of novel AChE inhibitors with a second N-basic fragment based on the piperidinylpropoxy pharmacophore with different spacer lengths. Intensive structure-activity relationships (SARs) with regard to both biological targets led to compound 41 which showed balanced affinities as hAChE inhibitor with IC50 = 33.9 nM, and hH3R antagonism with Ki = 76.2 nM with greater than 200-fold selectivity over the other histamine receptor subtypes. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds and molecular dynamics studies to explain high affinity at the hH3R.

A Call to Lead

ERIC Educational Resources Information Center

Hamilton, Kendra

2006-01-01

Imam Yahya Hendi came from afar--the occupied Palestinian Territories--to become, in 1999, the first full-time Muslim chaplain serving at a university in the United States. He is now the chaplain at Georgetown University. Rumee Ahmed, appointed earlier this year as Brown University's first Muslim chaplain, had a significantly shorter trip, moving…

Disentangling the outflow and protostars in HH 900 in the Carina Nebula

NASA Astrophysics Data System (ADS)

Reiter, Megan; Smith, Nathan; Kiminki, Megan M.; Bally, John; Anderson, Jay

2015-04-01

HH 900 is a peculiar protostellar outflow emerging from a small, tadpole-shaped globule in the Carina Nebula. Previous Hα imaging with Hubble Space Telescope (HST)/Advanced Camera for Surveys showed an ionized outflow with a wide opening angle that is distinct from the highly collimated structures typically seen in protostellar jets. We present new narrowband near-IR [Fe II] images taken with the Wide Field Camera 3 on the HST that reveal a remarkably different structure than Hα. In contrast to the unusual broad Hα outflow, the [Fe II] emission traces a symmetric, collimated bipolar jet with the morphology and kinematics that are more typical of protostellar jets. In addition, new Gemini adaptive optics images reveal near-IR H2 emission coincident with the Hα emission, but not the [Fe II]. Spectra of these three components trace three separate and distinct velocity components: (1) H2 from the slow, entrained molecular gas, (2) Hα from the ionized skin of the accelerating outflow sheath, and (3) [Fe II] from the fast, dense, and collimated protostellar jet itself. Together, these data require a driving source inside the dark globule that remains undetected behind a large column density of material. In contrast, Hα and H2 emission trace the broad outflow of material entrained by the jet, which is irradiated outside the globule. As it get dissociated and ionized, it remains visible for only a short time after it is dragged into the H II region.

Semiclassical analysis of angular differential cross sections for single-electron capture in 250-eV H++H collisions

NASA Astrophysics Data System (ADS)

Frémont, F.

2015-05-01

A classical model based on the resolution of Hamilton equations of motion is used to determine the angular distribution of H projectiles following single-electron capture in H++H collisions at an incident projectile energy of 250 eV. At such low energies, the experimental charge-exchange probability and angular differential cross sections exhibit oscillatory structures that are classically related to the number of swaps the electron experiences between the target and the projectile during the collision. These oscillations are well reproduced by models based on quantum mechanics. In the present paper, the angular distribution of H projectiles is determined classically, at angles varying from 0.1° up to 7°. The variation in intensity due to interferences caused by the indiscernibility between different trajectories is calculated, and the role of these interferences is discussed.

NMR studies of double proton transfer in hydrogen bonded cyclic N,N'-diarylformamidine dimers: conformational control, kinetic HH/HD/DD isotope effects and tunneling.

PubMed

Lopez, Juan Miguel; Männle, Ferdinand; Wawer, Iwona; Buntkowsky, Gerd; Limbach, Hans-Heinrich

2007-08-28

Using dynamic NMR spectroscopy, the kinetics of the degenerate double proton transfer in cyclic dimers of polycrystalline (15)N,(15)N'-di-(4-bromophenyl)-formamidine (DBrFA) have been studied including the kinetic HH/HD/DD isotope effects in a wide temperature range. This transfer is controlled by intermolecular interactions, which in turn are controlled by the molecular conformation and hence the molecular structure. At low temperatures, rate constants were determined by line shape analysis of (15)N NMR spectra obtained using cross-polarization (CP) and magic angle spinning (MAS). At higher temperatures, in the microsecond time scale, rate constants and kinetic isotope effects were obtained by a combination of longitudinal (15)N and (2)H relaxation measurements. (15)N CPMAS line shape analysis was also employed to study the non-degenerate double proton transfer of polycrystalline (15)N,(15)N'-diphenyl-formamidine (DPFA). The kinetic results are in excellent agreement with the kinetics of DPFA and (15)N,(15)N'-di-(4-fluorophenyl)-formamidine (DFFA) studied previously for solutions in tetrahydrofuran. Two large HH/HD and HD/DD isotope effects are observed in the whole temperature range which indicates a concerted double proton transfer mechanism in the domain of the reaction energy surface. The Arrhenius curves are non-linear indicating a tunneling mechanism. Arrhenius curve simulations were performed using the Bell-Limbach tunneling model. The role of the phenyl group conformation and hydrogen bond compression on the barrier of the proton transfer is discussed.

Quality assurance for measurements of the radioactivity in the area of the"Horia Hulubei" National Institute for Physics and Nuclear Engineering, IFIN-HH.

PubMed

Stochioiu, Ana; Luca, Aurelian; Sahagia, Maria; Margineanu, Romul Mircea; Tudor, Ion

2012-10-01

This paper presents one part of the activities deployed by the Laboratory for Environment and Personnel Dosimetry (LDPM) of IFIN-HH, namely the radiological monitoring of the environment within the Institute's area and its surrounding influence zone, according to the program approved by the National Regulatory Body for Nuclear Activities, CNCAN. The representative reports regard the radioactive content of soil, surface and underground water, cultivated and spontaneous vegetation, aerosols and atmospheric fallout, sediments. The common requirement is that the measured quantities be precise and the reported values be reliable and credible. This goal is achieved by maintaining a Quality System, verified within the obtaining and maintaining of the laboratory accreditation, according to the international standard ISO/IEC 17025:2005.The LDPM is accredited by the Romanian accreditation body, RENAR, member of the European Accreditation, EA and is designed by CNCAN as a notified testing laboratory. Many measurements were performed in collaboration with the Radionuclide Metrology Laboratory (RML) from IFIN-HH, RENAR accredited and CNCAN notified for calibration and for testing in the field of radioactivity measurement. This paper proposes a short presentation of the important aspects in our activity: i. description of equipment, samplingmethods, processing and measurement of environmental samples; ii. validation of equipment and methods by participation in international and national proficiency tests; iii. a five year follow chart, containing the results in measurement of samples; iv. a recent application, with a wide impact in Romanian mass media: the credible daily report on the possible influence of Fukushima accident over the Romanian environmental radioactivity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transcriptional regulation and adaptation to a high-fiber environment in Bacillus subtilis HH2 isolated from feces of the giant panda.

PubMed

Zhou, Ziyao; Zhou, Xiaoxiao; Li, Jin; Zhong, Zhijun; Li, Wei; Liu, Xuehan; Liu, Furui; Su, Huaiyi; Luo, Yongjiu; Gu, Wuyang; Wang, Chengdong; Zhang, Hemin; Li, Desheng; He, Tingmei; Fu, Hualin; Cao, Suizhong; Shi, Jinjiang; Peng, Guangneng

2015-01-01

In the giant panda, adaptation to a high-fiber environment is a first step for the adequate functioning of intestinal bacteria, as the high cellulose content of the gut due to the panda's vegetarian appetite results in a harsh environment. As an excellent producer of several enzymes and vitamins, Bacillus subtilis imparts various advantages to animals. In our previous study, we determined that several strains of B. subtilis isolated from pandas exhibited good cellulose decomposition ability, and we hypothesized that this bacterial species can survive in and adapt well to a high-fiber environment. To evaluate this hypothesis, we employed RNA-Seq technology to analyze the differentially expressed genes of the selected strain B. subtilis HH2, which demonstrates significant cellulose hydrolysis of different carbon sources (cellulose and glucose). In addition, we used bioinformatics software and resources to analyze the functions and pathways of differentially expressed genes. Interestingly, comparison of the cellulose and glucose groups revealed that the up-regulated genes were involved in amino acid and lipid metabolism or transmembrane transport, both of which are involved in cellulose utilization. Conversely, the down-regulated genes were involved in non-essential functions for bacterial life, such as toxin and bacteriocin secretion, possibly to conserve energy for environmental adaptation. The results indicate that B. subtilis HH2 triggered a series of adaptive mechanisms at the transcriptional level, which suggests that this bacterium could act as a probiotic for pandas fed a high-fiber diet, despite the fact that cellulose is not a very suitable carbon source for this bacterial species. In this study, we present a model to understand the dynamic organization of and interactions between various functional and regulatory networks for unicellular organisms in a high-fiber environment.

Transcriptional Regulation and Adaptation to a High-Fiber Environment in Bacillus subtilis HH2 Isolated from Feces of the Giant Panda

PubMed Central

Zhou, Ziyao; Zhou, Xiaoxiao; Li, Jin; Zhong, Zhijun; Li, Wei; Liu, Xuehan; Liu, Furui; Su, Huaiyi; Luo, Yongjiu; Gu, Wuyang; Wang, Chengdong; Zhang, Hemin; Li, Desheng; He, Tingmei; Fu, Hualin; Cao, Suizhong; Shi, Jinjiang; Peng, Guangneng

2015-01-01

In the giant panda, adaptation to a high-fiber environment is a first step for the adequate functioning of intestinal bacteria, as the high cellulose content of the gut due to the panda's vegetarian appetite results in a harsh environment. As an excellent producer of several enzymes and vitamins, Bacillus subtilis imparts various advantages to animals. In our previous study, we determined that several strains of B. subtilis isolated from pandas exhibited good cellulose decomposition ability, and we hypothesized that this bacterial species can survive in and adapt well to a high-fiber environment. To evaluate this hypothesis, we employed RNA-Seq technology to analyze the differentially expressed genes of the selected strain B. subtilis HH2, which demonstrates significant cellulose hydrolysis of different carbon sources (cellulose and glucose). In addition, we used bioinformatics software and resources to analyze the functions and pathways of differentially expressed genes. Interestingly, comparison of the cellulose and glucose groups revealed that the up-regulated genes were involved in amino acid and lipid metabolism or transmembrane transport, both of which are involved in cellulose utilization. Conversely, the down-regulated genes were involved in non-essential functions for bacterial life, such as toxin and bacteriocin secretion, possibly to conserve energy for environmental adaptation. The results indicate that B. subtilis HH2 triggered a series of adaptive mechanisms at the transcriptional level, which suggests that this bacterium could act as a probiotic for pandas fed a high-fiber diet, despite the fact that cellulose is not a very suitable carbon source for this bacterial species. In this study, we present a model to understand the dynamic organization of and interactions between various functional and regulatory networks for unicellular organisms in a high-fiber environment. PMID:25658435

A new ion beam facility based on a 3 MV Tandetron™ at IFIN-HH, Romania

NASA Astrophysics Data System (ADS)

Burducea, I.; Straticiuc, M.; Ghiță, D. G.; Moșu, D. V.; Călinescu, C. I.; Podaru, N. C.; Mous, D. J. W.; Ursu, I.; Zamfir, N. V.

2015-09-01

A 3 MV Tandetron™ accelerator system has been installed and commissioned at the "Horia Hulubei" National Institute for Physics and Nuclear Engineering - IFIN-HH, Măgurele, Romania. The main purpose of this machine is to strengthen applied nuclear physics research ongoing in our institute for more than four decades. The accelerator system was developed by High Voltage Engineering Europa B.V. (HVE) and comprises three high energy beam lines. The first beam line is dedicated to ion beam analysis (IBA) techniques: Rutherford Backscattering Spectrometry - RBS, Nuclear Reaction Analysis - NRA, Particle Induced X-ray and γ-ray Emission - PIXE and PIGE and micro-beam experiments - μ-PIXE. The second beam line is dedicated to high energy ion implantation experiments and the third beam line was designed mainly for nuclear cross-sections measurements used in nuclear astrophysics. A unique feature, the first time in operation at an accelerator facility is the Na charge exchange canal (CEC), which is used to obtain high intensity beams of He- of at least 3 μA. The results of the acceptance tests demonstrate the huge potential of this new facility in various fields, from IBA to radiation hardness studies and from medical or environmental applications to astrophysics. The main features of the accelerator are presented in this paper.

Mo-Mo Quintuple Bond is Highly Reactive in H-H, C-H, and O-H σ-Bond Cleavages Because of the Polarized Electronic Structure in Transition State.

PubMed

Chen, Yue; Sakaki, Shigeyoshi

2017-04-03

The recently reported high reactivity of the Mo-Mo quintuple bond of Mo 2 (N ∧ N) 2 (1) {N ∧ N = μ-κ 2 -CH[N(2,6-iPr 2 C 6 H 3 )] 2 } in the H-H σ-bond cleavage was investigated. DFT calculations disclosed that the H-H σ-bond cleavage by 1 occurs with nearly no barrier to afford the cis-dihydride species followed by cis-trans isomerization to form the trans-dihydride product, which is consistent with the experimental result. The O-H and C-H bond cleavages by 1 were computationally predicted to occur with moderate (ΔG° ⧧ = 9.0 kcal/mol) and acceptable activation energies (ΔG° ⧧ = 22.5 kcal/mol), respectively, suggesting that the Mo-Mo quintuple bond can be applied to various σ-bond cleavages. In these σ-bond cleavage reactions, the charge-transfer (CT Mo→XH ) from the Mo-Mo quintuple bond to the X-H (X = H, C, or O) bond and that (CT XH→Mo ) from the X-H bond to the Mo-Mo bond play crucial roles. Though the HOMO (dδ-MO) of 1 is at lower energy and the LUMO + 2 (dδ*-MO) of 1 is at higher energy than those of RhCl(PMe 3 ) 2 (LUMO and LUMO + 1 of 1 are not frontier MO), the H-H σ-bond cleavage by 1 more easily occurs than that by the Rh complex. Hence, the frontier MO energies are not the reason for the high reactivity of 1. The high reactivity of 1 arises from the polarization of dδ-type MOs of the Mo-Mo quintuple bond in the transition state. Such a polarized electronic structure enhances the bonding overlap between the dδ-MO of the Mo-Mo bond and the σ*-antibonding MO of the X-H bond to facilitate the CT Mo→XH and reduce the exchange repulsion between the Mo-Mo bond and the X-H bond. This polarized electronic structure of the transition state is similar to that of a frustrated Lewis pair. The easy polarization of the dδ-type MOs is one of the advantages of the metal-metal multiple bond, because such polarization is impossible in the mononuclear metal complex.

Preparation for Testing, Safe Packing and Shipping of Spent Nuclear Fuel from IFIN-HH, Bucharest-Magurele to Russian Federation

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

Dragolici, C.A.; Zorliu, A.; Popa, V.

2007-07-01

The Russian Research Reactor Fuel Return (RRRFR) program is promoted by IAEA and DOE in order to repatriate of irradiated research reactor fuel originally supplied by Russia to facilities outside the country. Developed under the framework of the Global Threat Reduction Initiative (GTRI) the take-back program [1] common goal is to reduce both proliferation and security risks by eliminating or consolidating inventories of high-risk material. The main objective of this program is to support the return to Russian Federation of fresh or irradiated HEU and LEU fuel. Being part of this project, Romania is fulfilling its tasks by examining transportmore » and transfer cask options, assessment of transport routes, and providing cost estimates for required equipment and facility modifications. Spent Nuclear Fuel (SNF) testing, handling, packing and shipping are the most common interests on which the National Institute of Research and Development for Physics and Nuclear Engineering 'Horia Hulubei' (IFIN-HH) is focusing at the moment. (authors)« less

Osteoblast-Derived PTHRP and Breast Cancer Bone Metastasis

DTIC Science & Technology

2004-11-01

short arm of chromosome 11 using aniridia - Wilms ’ tumor -associated deletions. Hum Genet 75:180-187 28. Yasuda T, Banville D, Hendy GN, Goltzman D...survival. It is, however, still unknown whether PTHrP overexpression is simply a consequence of tumor progression, or whether it is mechanistically...mammary epithelial cells and determined the consequences of this ablation on tumor initiation, growth and metastasis ( 1) (Appendix 1) . Toward this

Formation and Atmosphere of Complex Organic Molecules of the HH 212 Protostellar Disk

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

Lee, Chin-Fei; Ho, Paul T. P.; Hirano, Naomi

HH 212 is a nearby (400 pc) Class 0 protostellar system recently found to host a “hamburger”-shaped dusty disk with a radius of ∼60 au, deeply embedded in an infalling-rotating flattened envelope. We have spatially resolved this envelope-disk system with the Atacama Large Millimeter/submillimeter Array at up to ∼16 au (0.″04) resolution. The envelope is detected in HCO{sup +} J = 4–3 down to the dusty disk. Complex organic molecules (COMs) and doubly deuterated formaldehyde (D{sub 2}CO) are detected above and below the dusty disk within ∼40 au of the central protostar. The COMs are methanol (CH{sub 3}OH), deuterated methanolmore » (CH{sub 2}DOH), methyl mercaptan (CH{sub 3}SH), and formamide (NH{sub 2}CHO, a prebiotic precursor). We have modeled the gas kinematics in HCO{sup +} and COMs and found a centrifugal barrier (CB) at a radius of ∼44 au, within which a Keplerian rotating disk is formed. This indicates that HCO{sup +} traces the infalling-rotating envelope down to the CB and COMs trace the atmosphere of a Keplerian rotating disk within the CB. The COMs are spatially resolved for the first time, both radially and vertically, in the atmosphere of a disk in the earliest, Class 0 phase of star formation. Our spatially resolved observations of COMs favor their formation in the disk rather than a rapidly infalling (warm) inner envelope. The abundances and spatial distributions of the COMs provide strong constraints on models of their formation and transport in low-mass star formation.« less

The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TBF1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB

PubMed Central

Schütz, Ekkehard; Wehrhahn, Christin; Wanjek, Marius; Bortfeld, Ralf; Wemheuer, Wilhelm E.; Beck, Julia; Brenig, Bertram

2016-01-01

Background With the availability of massive SNP data for several economically important cattle breeds, haplotype tests have been performed to identify unknown recessive disorders. A number of so-called lethal haplotypes, have been uncovered in Holstein Friesian cattle and, for at least seven of these, the causative mutations have been identified in candidate genes. However, several lethal haplotypes still remain elusive. Here we report the molecular genetic causes of lethal haplotype 5 (HH5) and cholesterol deficiency (CDH). A targeted enrichment for the known genomic regions, followed by massive parallel sequencing was used to interrogate for causative mutations in a case/control approach. Methods Targeted enrichment for the known genomic regions, followed by massive parallel sequencing was used in a case/control approach. PCRs for the causing mutations were developed and compared to routine imputing in 2,100 (HH5) and 3,100 (CDH) cattle. Results HH5 is caused by a deletion of 138kbp, spanning position 93,233kb to 93,371kb on chromosome 9 (BTA9), harboring only dimethyl-adenosine transferase 1 (TFB1M). The deletion breakpoints are flanked by bovine long interspersed nuclear elements Bov-B (upstream) and L1ME3 (downstream), suggesting a homologous recombination/deletion event. TFB1M di-methylates adenine residues in the hairpin loop at the 3’-end of mitochondrial 12S rRNA, being essential for synthesis and function of the small ribosomal subunit of mitochondria. Homozygous TFB1M-/- mice reportedly exhibit embryonal lethality with developmental defects. A 2.8% allelic frequency was determined for the German HF population. CDH results from a 1.3kbp insertion of an endogenous retrovirus (ERV2-1-LTR_BT) into exon 5 of the APOB gene at BTA11:77,959kb. The insertion is flanked by 6bp target site duplications as described for insertions mediated by retroviral integrases. A premature stop codon in the open reading frame of APOB is generated, resulting in a truncation of

Solving the Excitation and Chemical Abundances in Shocks: The Case of HH 1

NASA Astrophysics Data System (ADS)

Giannini, T.; Antoniucci, S.; Nisini, B.; Bacciotti, F.; Podio, L.

2015-11-01

We present deep spectroscopic (3600-24700 Å ) X-shooter observations of the bright Herbig-Haro object HH 1, one of the best laboratories to study the chemical and physical modifications caused by protostellar shocks on the natal cloud. We observe atomic fine structure lines, H i and He i recombination lines and H2 ro-vibrational lines (more than 500 detections in total). Line emission was analyzed by means of Non-local Thermal Equilibiurm codes to derive the electron temperature and density, and for the first time we are able to accurately probe different physical regimes behind a dissociative shock. We find a temperature stratification in the range 4000 K \\div 80,000 K, and a significant correlation between temperature and ionization energy. Two density regimes are identified for the ionized gas, a more tenuous, spatially broad component (density ˜103 cm-3), and a more compact component (density ≥slant 105 cm-3) likely associated with the hottest gas. A further neutral component is also evidenced, having a temperature ≲10,000 K and a density >104 cm-3. The gas fractional ionization was estimated by solving the ionization equilibrium equations of atoms detected in different ionization stages. We find that neutral and fully ionized regions co-exist inside the shock. Also, indications in favor of at least partially dissociative shock as the main mechanism for molecular excitation are derived. Chemical abundances are estimated for the majority of the detected species. On average, abundances of non-refractory/refractory elements are lower than solar of about 0.15/0.5 dex. This indicates the presence of dust inside the medium, with a depletion factor of iron of ˜40%. Based on observations collected at the European Southern Observatory, (92.C-0058).

Deuterated methanol on a solar system scale around the HH212 protostar

NASA Astrophysics Data System (ADS)

Bianchi, E.; Codella, C.; Ceccarelli, C.; Taquet, V.; Cabrit, S.; Bacciotti, F.; Bachiller, R.; Chapillon, E.; Gueth, F.; Gusdorf, A.; Lefloch, B.; Leurini, S.; Podio, L.; Rygl, K. L. J.; Tabone, B.; Tafalla, M.

2017-10-01

Context. Deuterium fractionation is a valuable tool for understanding the chemical evolution during the process that leads to the formation of a Sun-like planetary system. Aims: Methanol is thought to be mainly formed during the prestellar phase, and its deuterated form keeps a memory of the conditions at that epoch. The unique combination of high angular resolution and sensitivity provided by ALMA enables us to measure methanol deuteration in the planet formation region around a Class 0 protostar and to understand its origin. Methods: We mapped both the 13CH3OH and CH2DOH distribution in the inner regions ( 100 au) of the HH212 system in Orion B. To this end, we used ALMA Cycle 1 and Cycle 4 observations in Band 7 with angular resolution down to 0.̋15. Results: We detected 6 lines of 13CH3OH and 13 lines of CH2DOH with upper level energies of up to 438 K in temperature units. We derived a rotational temperature of (171 ± 52) K and column densities of 7 × 1016 cm-2 (13CH3OH) and 1 × 1017 cm-2 (CH2DOH), respectively. This yields a D/H ratio of (2.4 ± 0.4) × 10-2, which is lower by an order of magnitude than previously measured values using single-dish telescopes toward protostars located in Perseus. Our findings are consistent with the higher dust temperatures in Orion B with respect to the temperature derived for the Perseus cloud. The emission traces a rotating structure extending up to 45 au from the jet axis, which is elongated by 90 au along the jet axis. So far, the origin of the observed emission appears to be related with the accretion disc. Only higher spatial resolution measurements will be able to distinguish between different possible scenarios, however: disc wind, disc atmosphere, or accretion shocks.

Structure, stability, thermodynamic properties, and IR spectra of the protonated water decamer H+(H2O)10.

PubMed

Karthikeyan, S; Kim, Kwang S

2009-08-13

Protonated water clusters H+(H2O)n favor two-dimensional (2D) structures for n < or = 7 at low temperatures. At 0 K, the 2D and three-dimensional (3D) structures for n = 8 are almost isoenergetic, and the 3D structures for n > 9 tend to be more stable. However, for n = 9, the netlike structures are likely to be more stable above 150 K. In this regard, we investigate the case of n = 10 to find which structure is more stable between the 3D structure and the netlike structure around 150 and 250 K. We use density functional theory, Møller-Plesset second-order perturbation theory, and coupled cluster theory with single, double, and perturbative triple excitations (CCSD(T)). At the complete basis set limit for the CCSD(T) level of theory, three isomers of 3D cage structure are much more stable in zero point energy corrected binding energy and in free binding energies at 150 K than the lowest energy netlike structures, while the netlike structure would be more stable around approximately 250 K. The predicted vibrational spectra are in good agreement with the experiment. One of the three isomers explains the experimental IR observation of an acceptor (A) type peak of a dangling hydrogen atom.

The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

PubMed

Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

2015-07-01

Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

A 100 au Wide Bipolar Rotating Shell Emanating from the HH 212 Protostellar Disk: A Disk Wind?

NASA Astrophysics Data System (ADS)

Lee, Chin-Fei; Li, Zhi-Yun; Codella, Claudio; Ho, Paul T. P.; Podio, Linda; Hirano, Naomi; Shang, Hsien; Turner, Neal J.; Zhang, Qizhou

2018-03-01

HH 212 is a Class 0 protostellar system found to host a “hamburger”-shaped dusty disk with a rotating disk atmosphere and a collimated SiO jet at a distance of ∼400 pc. Recently, a compact rotating outflow has been detected in SO and SO2 toward the center along the jet axis at ∼52 au (0.″13) resolution. Here we resolve the compact outflow into a small-scale wide-opening rotating outflow shell and a collimated jet, with the observations in the same S-bearing molecules at ∼16 au (0.″04) resolution. The collimated jet is aligned with the SiO jet, tracing the shock interactions in the jet. The wide-opening outflow shell is seen extending out from the inner disk around the SiO jet and has a width of ∼100 au. It is not only expanding away from the center, but also rotating around the jet axis. The specific angular momentum of the outflow shell is ∼40 au km s‑1. Simple modeling of the observed kinematics suggests that the rotating outflow shell can trace either a disk wind or disk material pushed away by an unseen wind from the inner disk or protostar. We also resolve the disk atmosphere in the same S-bearing molecules, confirming the Keplerian rotation there.

Status and Perspectives for a Slow Positron Beam Facility at the HH-NIPNE Bucharest

NASA Astrophysics Data System (ADS)

Straticiuc, Mihai; Craciun, Liviu Stefan; Constantinescu, Olimpiu; Ghita, Ionica Alina; Ionescu, Cristina; Racolta, Petru Mihai; Vasilescu, Angela; Braic, Viorel; Zoita, Catalin; Kiss, Adrian; Bojin, Dionezie

2009-03-01

The development of a positron annihilation spectroscopy laboratory at the HH-NIPNE Bucharest-to be used for material studies and applications was started in the last 10 years. In the framework of a national research project extended over the last 3 years, was designed a low energy positron accelerator, as a high-vacuum dedicated beam line with two options: a 25 mCi 22NaCl source and in line with the NIPNE-cyclotron or a new intense compact cyclotron. The construction of the beam line was planned as a sequence of modules: source- moderator system; magnetical filter for fast positrons in order to select the positrons energies in the range 0.8-1 keV; a modular system for focusing, transport and acceleration of monoenergetic positrons in the energy range 0.8-50 keV and a CDBS analysis chamber. The moderator proposed-is tungsten as a foil of about 3 μm prepared at the Optoelectronics Institute were put into a thermal treatment vacuum chamber and bombarded with electrons from a 100 W electron gun After the treatment, they were tested for changes of elemental composition of the surface and structure at the Polytechnic University. The structure tests were performed on a DRON 3 M diffractometer, with a Co tube (λKα = 1.7903 A)-the angular regions studied were around 34° (1 0 0) and 69° (2 0 0). In the present time, the trajectories of the positron are going to be simulated with dedicated software (an ion and electron optics simulator). For the coincidence measurements (CDBS) set-up we used a home-made 22NaCl source, by separation without carrier from a metallic Mg target irradiated with 12 MeV protons and separated by columnar cation exchange. A home- made biparametric system for CDBS measurements will be reported, also.

Australian Tri-Service Anthropometric Survey, 1977. Part 1. Survey Planning, Conduct, Data Handling and Methods of Analysis,

DTIC Science & Technology

1979-07-01

information on this page): No Limitation 14. Descriptors: 15. Cosati Codes: Anthropometry Australia 0614 Surveys 0505 Biomedical data Military personnel... AUSTRALIA ) K C HENDY JUL 79 ARL/SYS-15 UNCASSFIE ) m.2 | 2 1 Lm MICROCOPY RESOLUTION TEST "ART N ATIONAL O € F ST" OANDOS1963A i0 __ 9 ,’ ARLjS¥S -R BW...was known about the anthropometry of Australian military personnel. For example, there have been no previously published attempts to compare the

Highly Collimated Jets and Wide-angle Outflows in HH 46/47: New Evidence from Spitzer Infrared Images

NASA Technical Reports Server (NTRS)

Velusamy, T.; Langer, William D.; Marsh, Kenneth. A.

2007-01-01

We present new details of the structure and morphology of the jets and outflows in HH 46/47 as seen in Spitzer infrared images from IRAC and MIPS, reprocessed using the 'HiRes' deconvolution technique. HiRes improves the visualization of spatial morphology by enhancing resolution (to subarcsecond levels in IRAC bands) and removing the contaminating side lobes from bright sources. In addition to sharper views of previously reported bow shocks, we have detected (1) the sharply delineated cavity walls of the wide-angle biconical outflow, seen in scattered light on both sides of the protostar, (2) several very narrow jet features at distances approximately 400 AU to approximately 0.1 pc from the star, and (3) compact emissions at MIPS 24 m with the jet heads, tracing the hottest atomic/ionic gas in the bow shocks. Together the IRAC and MIPS images provide a more complete picture of the bow shocks, tracing both the molecular and atomic/ionic gases, respectively. The narrow width and alignment of all jet-related features indicate a high degree of jet collimation and low divergence (width of approximately 400 AU increasing by only a factor of 2.3 over 0.2 pc). The morphology of this jet, bow shocks, wide-angle outflows, and the fact that the jet is nonprecessing and episodic, constrain the mechanisms for producing the jet's entrained molecular gas, and origins of the fast jet, and slower wide-angle outflow.

MicroHH 1.0: a computational fluid dynamics code for direct numerical simulation and large-eddy simulation of atmospheric boundary layer flows

NASA Astrophysics Data System (ADS)

van Heerwaarden, Chiel C.; van Stratum, Bart J. H.; Heus, Thijs; Gibbs, Jeremy A.; Fedorovich, Evgeni; Mellado, Juan Pedro

2017-08-01

This paper describes MicroHH 1.0, a new and open-source (www.microhh.org) computational fluid dynamics code for the simulation of turbulent flows in the atmosphere. It is primarily made for direct numerical simulation but also supports large-eddy simulation (LES). The paper covers the description of the governing equations, their numerical implementation, and the parameterizations included in the code. Furthermore, the paper presents the validation of the dynamical core in the form of convergence and conservation tests, and comparison of simulations of channel flows and slope flows against well-established test cases. The full numerical model, including the associated parameterizations for LES, has been tested for a set of cases under stable and unstable conditions, under the Boussinesq and anelastic approximations, and with dry and moist convection under stationary and time-varying boundary conditions. The paper presents performance tests showing good scaling from 256 to 32 768 processes. The graphical processing unit (GPU)-enabled version of the code can reach a speedup of more than an order of magnitude for simulations that fit in the memory of a single GPU.

A Case Study On Pile Relaxation In Dilative Silts

DTIC Science & Technology

2011-12-20

HHH +~H+~~++~~ r losr-~~~~~~~~~~~~H 21~~~~~~~~~~~~~ ~HH~~~~++~~~~44~ ~110~~~~~~~~~~~~~~ 22HHHH~--HHHH44~44444444~ r-H4+++H...i ne gravel, trace of clay, medium dense , wet. SILT, grey, and fine sand, medium stiff, non plastic, wet. -HH++ HHH +~H4~~++HH4 f- 45 1 01-H-HH-1...rHH++HH4~HH4 8HH+rH+.rH++HH+~H++H -HH++ HHH ++HH+~HH++HH4 --40~++HH~+HH+~HH++HH~ 9H+~H++HH++HH+rHH+~ --HH++~~rHH++HH4++HH4 _ srq-+H~~H++H4+HH4

Hubble Space Telescope Observations of the Disk and Jet of HH 30

NASA Astrophysics Data System (ADS)

Burrows, Christopher J.; Stapelfeldt, Karl R.; Watson, Alan M.; Krist, John E.; Ballester, Gilda E.; Clarke, John T.; Crisp, David; Gallagher, John S., III; Griffiths, Richard E.; Hester, J. Jeff; Hoessel, John G.; Holtzman, Jon A.; Mould, Jeremy R.; Scowen, Paul A.; Trauger, John T.; Westphal, James A.

1996-12-01

HH 30 in Taurus has been imaged with the Hubble Space Telescope WFPC2. The images show in reflected light a flared disk with a radius of about 250 AU that obscures the protostar. The disk resembles detailed accretion disk models that constrain its density distribution and show that its inclination is less than 100. There are bipolar emission-line jets perpendicular to the disk, a very clear demonstration of the standard paradigm for accretion disk and jet systems. However, asymmetries in the light distribution show that the disk has not completely settled into a quasi-equilibrium accretion state, or that some of the observed scattering is from an asymmetric envelope. The emission-line jet itself is resolved into a number of knots with typical lengths and separations of 0".4, much smaller and more numerous than indicated by lower resolution ground-based studies. There are indications of still finer structures in the jet all the way to the resolution limit of 0".1. The knots have proper motions ranging from 100 to 300 km s-1 and are therefore generated at the surprisingly high rate of about 0.4 knots per jet per year. The jet appears to be collimated within a cone of opening angle 3° and can be seen to within 30 AU of the star. Both single- and multiple-scattering disk models have a range of possible solutions, but by requiring pressure support and temperature equilibrium, a self-consistent model emerges. There is evidence for pressure support because the disk appears to have a Gaussian height profile. The temperature at each point in the disk is determined by the disk geometry, which in turn fixes the temperature in a self- consistent manner. The extinction to the protostar is unknown but constrained to be greater than 24 mag. The optical properties of the scattering grains in the disk are determined and found to imply a large scattering asymmetry, but they seem to follow the interstellar reddening law. The absolute magnitude and colors of the unseen protostar

Aggregation-induced chemical reactions: acid dissociation in growing water clusters.

PubMed

Forbert, Harald; Masia, Marco; Kaczmarek-Kedziera, Anna; Nair, Nisanth N; Marx, Dominik

2011-03-23

Understanding chemical reactivity at ultracold conditions, thus enabling molecular syntheses via interstellar and atmospheric processes, is a key issue in cryochemistry. In particular, acid dissociation and proton transfer reactions are ubiquitous in aqueous microsolvation environments. Here, the full dissociation of a HCl molecule upon stepwise solvation by a small number of water molecules at low temperatures, as relevant to helium nanodroplet isolation (HENDI) spectroscopy, is analyzed in mechanistic detail. It is found that upon successive aggregation of HCl with H(2)O molecules, a series of cyclic heteromolecular structures, up to and including HCl(H(2)O)(3), are initially obtained before a precursor state for dissociation, HCl(H(2)O)(3)···H(2)O, is observed upon addition of a fourth water molecule. The latter partially aggregated structure can be viewed as an "activated species", which readily leads to dissociation of HCl and to the formation of a solvent-shared ion pair, H(3)O(+)(H(2)O)(3)Cl(-). Overall, the process is mostly downhill in potential energy, and, in addition, small remaining barriers are overcome by using kinetic energy released as a result of forming hydrogen bonds due to aggregation. The associated barrier is not ruled by thermal equilibrium but is generated by athermal non-equilibrium dynamics. These "aggregation-induced chemical reactions" are expected to be of broad relevance to chemistry at ultralow temperature much beyond HENDI spectroscopy.

Searches for a heavy scalar boson $$ \\mathrm{H} $$ decaying to a pair of 125 GeV Higgs bosons $$ \\mathrm{ hh } $$ or for a heavy pseudoscalar boson $$ \\mathrm{A} $$ decaying to $$ \\mathrm{Zh} $$, in the final states with $$\\mathrm{h} \\to \\tau \\tau$$

DOE PAGES

Khachatryan, Vardan

2016-02-09

A search for a heavy scalar boson H decaying into a pair of lighter standard-model-like 125 GeV Higgs bosons hh and a search for a heavy pseudoscalar boson A decaying into a Z and an h boson are presented. The searches are performed on a data set corresponding to an integrated luminosity of 19.7 fb -1 of pp collision data at a centre-of-mass energy of 8 TeV, collected by CMS in 2012. A final state consisting of two τ leptons and two b jets is used to search for the H → hh decay. A final state consisting of twomore » τ leptons from the h boson decay, and two additional leptons from the Z boson decay, is used to search for the decay A → Zh. The results are interpreted in the context of two-Higgs-doublet models. No excess is found above the standard model expectation and upper limits are set on the heavy boson production cross sections in the mass ranges 260 < m H < 350 GeV and 220 < m A < 350 GeV.« less

36. INTERIOR VIEW LOOKING WEST FROM UNDERNEATH THE ORE BINS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. INTERIOR VIEW LOOKING WEST FROM UNDERNEATH THE ORE BINS LOOKING AT THE BACK SIDE OF THE HENDY CHALLENGE CONTINUOUS ORE FEEDERS, #1 IS ON THE LEFT, #2 IS CENTER, AND #3 IS ON THE RIGHT. THESE ARE USED TO KEEP A CONTINUOUS FLOW OF ORE INTO THE STAMP MILLS. NOTE THE SPARE FEEDER DISKS ON THE FLOOR BOTTOM CENTER AND SPARE STAMP HEADS AND SHOES ON THE FLOOR BOTTOM LEFT OF THE IMAGE. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA

Nucleotide sequence of the beta-lactamase gene from Enterococcus faecalis HH22 and its similarity to staphylococcal beta-lactamase genes.

PubMed Central

Zscheck, K K; Murray, B E

1991-01-01

The nucleotide sequence of the constitutively produced beta-lactamase (Bla) gene from Enterococcus faecalis HH22 was shown to be identical to the published sequences of three of four staphylococcal type A beta-lactamase genes; more differences were seen with the genes for staphylococcal type C and D enzymes. One hundred forty nucleotides upstream of the beta-lactamase start codon were determined for an inducible staphylococcal beta-lactamase and were identical to those of the constitutively expressed enterococcal gene, indicating that the changes resulting in constitutive expression are not due to changes in the promoter or operator region. Moreover, complementation studies indicated that production of the enterococcal enzyme could be repressed. The genes for the enterococcal Bla and an inducible staphylococcal Bla were each cloned into a shuttle vector and transformed into enterococcal and staphylococcal recipients. The major difference between the backgrounds of the two hosts was that more enzyme was produced by the staphylococcal host, regardless of the source of the gene. The location of the enzyme was found to be host dependent, since each cloned gene generated extracellular (free) enzyme in the staphylococcus and cell-bound enzyme in the enterococcus. On the basis of the identities of the enterococcal Bla and several staphylococcal Bla sequences, these data suggest the recent spread of beta-lactamase to enterococci and also suggest the loss of a functional repressor. PMID:1952840

Temperature-dependent transitions between normal and inverse isotope effects pertaining to the interaction of H-H and C-H bonds with transition metal centers.

PubMed

Parkin, Gerard

2009-02-17

Deuterium kinetic isotope effects (KIEs) serve as versatile tools to infer details about reaction mechanisms and the nature of transition states, while equilibrium isotope effects (EIEs) associated with the site preferences of hydrogen and deuterium enable researchers to study aspects of molecular structure. Researchers typically interpret primary deuterium isotope effects based on two simple guidelines: (i) the KIE for an elementary reaction is normal (k(H)/k(D) > 1) and (ii) the EIE is dictated by deuterium preferring to be located in the site corresponding to the highest frequency oscillator. In this Account, we evaluate the applicability of these rules to the interactions of H-H and C-H bonds with a transition metal center. Significantly, experimental and computational studies question the predictability of primary EIEs in these systems based on the notion that deuterium prefers to occupy the highest frequency oscillator. In particular, the EIEs for (i) formation of sigma-complexes by coordination of H-H and C-H bonds and (ii) oxidative addition of dihydrogen exhibit unusual temperature dependencies, such that the same system may demonstrate both normal (i.e., K(H)/K(D) > 1) and inverse (i.e., K(H)/K(D) < 1) values. The transition between a normal and inverse EIE indicates that these systems do not demonstrate the typical monotonic variation predicted by the van't Hoff relationship. Instead, the calculated EIEs in these systems are 0 at 0 K, increase to a value greater than 1, and then decrease to unity at infinite temperature. This unusual behavior may be rationalized by considering the individual factors that contribute to the EIE. Specifically, the EIE may be expressed in the form EIE = SYM x MMI x EXC x ZPE (where SYM is the symmetry factor, MMI is the mass-moment of inertia term, EXC is the excitation term, and ZPE is the zero-point energy term), and the distinctive temperature profile results from the inverse ZPE (enthalpy) and normal [SYM x MMI x EXC

Quantitative analysis of Hedgehog gradient formation using an inducible expression system

PubMed Central

Su, Vivian F; Jones, Kelly A; Brodsky, Michael; The, Inge

2007-01-01

Background The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. Results We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. Conclusion We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh

Quantitative analysis of Hedgehog gradient formation using an inducible expression system.

PubMed

Su, Vivian F; Jones, Kelly A; Brodsky, Michael; The, Inge

2007-05-07

The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh across target cells, indicating

New Herbig-Haro objects in the L1617 and L1646 dark clouds

NASA Astrophysics Data System (ADS)

Wang, H.; Stecklum, B.; Henning, Th.

2005-07-01

Optical imaging towards L1617 and L1646 revealed three new Herbig-Haro (HH) objects, HH 182, 439, and 866. Spectroscopic observations of HH 182 A and 439 A confirmed their HH object nature. Molecular hydrogen v = 1-0 S(1) narrow band imaging revealed three H2 emission features in the HH 182 region which coincide with the optical emission. Based on the position angles of the different parts of the HH 111 flow and that of HH 182, HH 182 may be the outermost southeastern part of the giant HH 111 flow. One deeply embedded star is revealed in our near-infrared imaging of the HH 439 region. HH 439 A and the associated bow shock are probably driven by the newly detected embedded star. HH 439 B-D are probably driven by the Herbig AeBe star candidate GSC 04794-00827 (IRAS 06045-0554). The embedded source IRAS 06046-0603 is identified to be the exciting source of HH 866.

Nicotinamide nucleotide transhydrogenase from Rhodobacter capsulatus; the H+/H- ratio and the activation state of the enzyme during reduction of acetyl pyridine adenine dinucleotide.

PubMed

Palmer, T; Jackson, J B

1992-02-21

Chromatophores from Rhodobacter capsulatus were incubated in the dark with NADPH and acetylpyridineadenine dinucleotide (AcPdAD+) in the presence of different concentrations of myxothiazol. The transhydrogenase activity was monitored until an appropriate mass action ratio, [AcPdAD+][NADPH]/[AcPdADH][NADP+], was reached. The sample was then illuminated and the initial rate of either AcPdAD+ reduction by NADPH or AcPdADH oxidation by NADP+ was recorded. The ratio of H+ translocated per H- equivalent transferred by transhydrogenase was calculated from the value of the membrane potential (delta pH = 0) at which illumination caused no net reaction in either direction. The mean value for the H+/H- ratio was 0.55. At greater values of [AcPdAD+][NADPH]/[AcPdADH][NADP+] than were employed in the above experiments and over a wider range of concentrations of myxothiazol, it was found that incremental increases in the membrane potential always gave rise to a decrease, never an increase in the rate of AcPdAD+ reduction. In contrast to the H(+)-ATP synthase, there is no evidence of any activation/deactivation of H(+)-transhydrogenase by the protonmotive force.

New Herbig-Haro objects in star-forming regions

NASA Technical Reports Server (NTRS)

Reipurth, BO; Graham, J. A.

1988-01-01

A list of 25 new Herbig-Haro objects, HH 58 to HH 82, in the Orion molecular clouds and in southern molecular cloud complexes has been compiled. CCD images in the S II 6717, 6731 forbidden lines are presented for the objects, together with a few spectra and some IR observations. The individual objects and, when identified, their energy sources are discussed. HH 65 is located in the red lobe of the bipolar outflow associated with the highly variable reflection nebula Re 50. HH 67 is a 22-arcsec long sinusoidal jet. HH 68/69 consists of a long, linear chain of four HH knots. HH 72 emerges from a 120-solar luminosity IRAS source embedded in a Bok globule. HH 79 is the first HH object discovered in the Ophiuchus clouds. HH 80/81 in Sagittarius are among the brightest HH objects known, have complex velocities, high excitation conditions and emerge from a 6000-solar luminosity young B-star. HH 82 is associated with the bright variable star S Coronae Australis.

Fast Magic-Angle Spinning Three-Dimensional NMR Experiment for Simultaneously Probing H-H and N-H Proximities in Solids.

PubMed

Reddy, G N Manjunatha; Malon, Michal; Marsh, Andrew; Nishiyama, Yusuke; Brown, Steven P

2016-12-06

A fast magic-angle spinning (MAS, 70 kHz) solid-state NMR experiment is presented that combines 1 H Double-Quantum (DQ) and 14 N- 1 H HMQC (Heteronuclear Multiple-Quantum Coherence) pulse-sequence elements, so as to simultaneously probe H-H and N-H proximities in molecular solids. The proposed experiment can be employed in both two-dimensional (2D) and three-dimensional (3D) versions: first, a 2D 14 N HMQC-filtered 1 H-DQ experiment provides specific DQ-SQ correlation peaks for proton pairs that are in close proximities to the nitrogen sites, thereby achieving spectral filtration. Second, a proton-detected three-dimensional (3D) 1 H(DQ)- 14 N(SQ)- 1 H(SQ) experiment correlates 1 H(DQ)- 1 H(SQ) chemical shifts with 14 N shifts such that longer range N···H-H correlations are observed between protons and nitrogen atoms with internuclear NH distances exceeding 3 Å. Both 2D and 3D versions of the proposed experiment are demonstrated for an amino acid hydrochloride salt, l-histidine·HCl·H 2 O, and a DNA nucleoside, guanosine·2H 2 O. In the latter case, the achieved spectral filtration ensures that DQ cross peaks are only observed for guanine NH and CH8 1 H resonances and not ribose and water 1 H resonances, thus providing insight into the changes in the solid-state structure of this hydrate that occur over time; significant changes are observed in the NH and NH 2 1 H chemical shifts as compared to the freshly recrystallized sample previously studied by Reddy et al., Cryst. Growth Des. 2015, 15, 5945.

Challenges to sustainability of hand hygiene at a rural hospital in Rwanda.

PubMed

Holmen, Ian C; Niyokwizerwa, Dan; Nyiranzayisaba, Berthine; Singer, Timothy; Safdar, Nasia

2017-08-01

Many hand hygiene (HH) programs have been implemented across Sub-Saharan Africa (SSA); however, most of these have been in large, referral hospitals. Our objective was to assess the impact of HH programs aimed at improving compliance at a rural hospital, and to identify unique challenges to HH sustainability. Interventions to improve HH through providing handwashing stations, health care worker (HCW) training, and alcohol handrub were completed in 2014 and 2015. HH infrastructure, compliance, and glove use were assessed among HCWs after the intervention in 2015 and 2016. HCWs were interviewed about challenges to sustainability of HH compliance. Total HH compliance decreased 32.1% between 2015 and 2016 (P < .001). HH for patient protection was completed significantly less than HH for HCW protection in 2016, and HCWs appeared to substitute HH for patient protection with glove use. A high rate of physician turnover was associated with a larger decrease in HH compliance compared with nurses, and interviews suggested recruiting and retention of key personnel might play a role in HH sustainability. Availability of alcohol-based handrub in patient rooms decreased from 100% in 2015 to 79.5% in 2016 (P < .01). Many challenges exist to sustaining HH compliance in SSA. In rural settings, difficulty recruiting and retaining trained personnel, inconsistent availability in HH infrastructure, and variability in HCW HH training may be contributing factors. Copyright © 2017. Published by Elsevier Inc.

Implementation of Geometric Algebra in MATLAB (registered trademark) with Applications

DTIC Science & Technology

2014-09-01

HHH HHHH HHHH HH HHH HHH HHHH P r C r O 6 HHHj ~A ~B Figure 1: Pinhole...is given by the similar map L 7→ P ∨ (C ∧ L) . (66) The result is the unique line of intersection of two planes. HHH HHH HHHH HH H HHH HHH HHH HH Pα...Pβ r Cα r Cβ rOαβ rOβα HH HHH HHH HHH HHH HH H HH H HH rX rXα rXβ A A A A

ALMA Cycle 1 Observations of the HH46/47 Molecular Outflow: Structure, Entrainment, and Core Impact

NASA Astrophysics Data System (ADS)

Zhang, Yichen; Arce, Héctor G.; Mardones, Diego; Cabrit, Sylvie; Dunham, Michael M.; Garay, Guido; Noriega-Crespo, Alberto; Offner, Stella S. R.; Raga, Alejandro C.; Corder, Stuartt A.

2016-12-01

We present Atacama Large Millimeter/sub-millimeter Array Cycle 1 observations of the HH 46/47 molecular outflow using combined 12 m array and Atacama Compact Array observations. The improved angular resolution and sensitivity of our multi-line maps reveal structures that help us study the entrainment process in much more detail and allow us to obtain more precise estimates of outflow properties than in previous observations. We use {}13{{CO}} (1-0) and {{{C}}}18{{O}} (1-0) emission to correct for the {}12{{CO}} (1-0) optical depth to accurately estimate the outflow mass, momentum, and kinetic energy. This correction increases the estimates of the mass, momentum, and kinetic energy by factors of about 9, 5, and 2, respectively, with respect to estimates assuming optically thin emission. The new {}13{{CO}} and {{{C}}}18{{O}} data also allow us to trace denser and slower outflow material than that traced by the {}12{{CO}} maps, and they reveal an outflow cavity wall at very low velocities (as low as 0.2 {\\text{km s}}-1 with respect to the core’s central velocity). Adding the slower material traced only by {}13{{CO}} and {{{C}}}18{{O}}, there is another factor of three increase in the mass estimate and 50% increase in the momentum estimate. The estimated outflow properties indicate that the outflow is capable of dispersing the parent core within the typical lifetime of the embedded phase of a low-mass protostar and that it is responsible for a core-to-star efficiency of 1/4 to 1/3. We find that the outflow cavity wall is composed of multiple shells associated with a series of jet bow-shock events. Within about 3000 au of the protostar the {}13{{CO}} and {{{C}}}18{{O}} emission trace a circumstellar envelope with both rotation and infall motions, which we compare with a simple analytic model. The CS (2-1) emission reveals tentative evidence of a slowly moving rotating outflow, which we suggest is entrained not only poloidally but also toroidally by a disk wind that

Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium

PubMed Central

Callejo, Ainhoa; Bilioni, Aphrodite; Mollica, Emanuela; Gorfinkiel, Nicole; Andrés, Germán; Ibáñez, Carmen; Torroja, Carlos; Doglio, Laura; Sierra, Javier; Guerrero, Isabel

2011-01-01

Hedgehog (Hh) moves from the producing cells to regulate the growth and development of distant cells in a variety of tissues. Here, we have investigated the mechanism of Hh release from the producing cells to form a morphogenetic gradient in the Drosophila wing imaginal disk epithelium. We describe that Hh reaches both apical and basolateral plasma membranes, but the apical Hh is subsequently internalized in the producing cells and routed to the basolateral surface, where Hh is released to form a long-range gradient. Functional analysis of the 12-transmembrane protein Dispatched, the glypican Dally-like (Dlp) protein, and the Ig-like and FNNIII domains of protein Interference Hh (Ihog) revealed that Dispatched could be involved in the regulation of vesicular trafficking necessary for basolateral release of Hh, Dlp, and Ihog. We also show that Dlp is needed in Hh-producing cells to allow for Hh release and that Ihog, which has been previously described as an Hh coreceptor, anchors Hh to the basolateral part of the disk epithelium. PMID:21690386

Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates

PubMed Central

Chen, Miao-Hsueh; Li, Ya-Jun; Kawakami, Takatoshi; Xu, Shan-Mei; Chuang, Pao-Tien

2004-01-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh signaling. These results suggest that soluble Hh multimeric complex travels in the morphogenetic field to activate Hh signaling in distant Hh-responsive cells. PMID:15075292

Impact of changes in Medicare Home Health care reimbursement on month-to-month Home Health utilization between 1996 and 2001 for a national sample of patients undergoing orthopedic procedures.

PubMed

FitzGerald, John D; Mangione, Carol M; Boscardin, John; Kominski, Gerald; Hahn, Bevra; Ettner, Susan L

2006-09-01

Beginning October 1, 1997, Medicare implemented a series of major changes to the Home Health (HH) reimbursement system. Reimbursements were first significantly reduced under the Interim Payment System (IPS) and then relaxed slightly until implementation of the HH Prospective Payment System (PPS) on October 1, 2000. The objective of this study was to examine the impact of reimbursement policy on HH care utilization. We postulated that in response to the initial changes, there would be reductions in both the probability of any HH use and the number of HH visits per HH user. Under PPS, we postulated there would be further reduction in number of HH visits. We tested whether the policy response differed by HH agency structure and whether subgroups of patients were differentially affected. An interrupted time-series analysis was conducted to examine month-to-month probability of HH selection and the number of HH visits among users. A 100% sample of all Medicare recipients undergoing either elective joint replacement (1.6 million hospital discharges) or surgical management of hip fracture (1.2 million hospital discharges) between January 1996 and December 2001 was selected. Under the IPS, the probability of any HH use and number of visits per episode of HH care fell until the IPS was refined in October 1998. With implementation of the PPS, HH visits fell commensurately. Differentially larger reductions in care were noted at for-profit HH agencies, for the elderly, women, patients receiving state assistance, and patients first discharged to skilled nursing facility or rehabilitation hospitals. Changes in month-to-month utilization of HH services were sharp and well correlated with policy implementation dates, strengthening the evidence for a causal association between policy and patient care in the midst of a sea of concurrent policy changes. Greater reductions in HH visits were noted for vulnerable groups.

Implementation of WHO multimodal strategy for improvement of hand hygiene: a quasi-experimental study in a Traditional Chinese Medicine hospital in Xi'an, China.

PubMed

Shen, Li; Wang, Xiaoqing; An, Junming; An, Jialu; Zhou, Ning; Sun, Lu; Chen, Hong; Feng, Lin; Han, Jing; Liu, Xiaorong

2017-01-01

Hand hygiene (HH) is an essential component for preventing and controlling of healthcare-associated infection (HAI), whereas compliance with HH among health care workers (HCWs) is frequently poor. This study aimed to assess compliance and correctness with HH before and after the implementation of a multimodal HH improvement strategy launched by the World Health Organization (WHO). A quasi-experimental study design including questionnaire survey generalizing possible factors affecting HH behaviors of HCWs and direct observation method was used to evaluate the effectiveness of WHO multimodal HH strategy in a hospital of Traditional Chinese Medicine. Multimodal HH improvement strategy was drawn up according to the results of questionnaire survey. Compliance and correctness with HH among HCWs were compared before and after intervention. Also HH practices for different indications based on WHO "My Five Moments for Hand Hygiene" were recorded. In total, 553 HCWs participated in the questionnaire survey and multimodal HH improvement strategy was developed based on individual, environment and management levels. A total of 5044 observations in 23 wards were recorded in this investigation. The rate of compliance and correctness with HH improved from 66.27% and 47.75% at baseline to 80.53% and 88.35% after intervention. Doctors seemed to have better compliance with HH after intervention (84.04%) than nurses and other HCWs (81.07% and 69.42%, respectively). When stratified by indication, compliance with HH improved for all indications after intervention ( P  < 0.05) except for "after body fluid exposure risk" and "after touching patient surroundings". Implementing the WHO multimodal HH strategy can significantly improve HH compliance and correctness among HCWs.

Unique features of esophagogastric junction pressure topography in hiatus hernia patients with dysphagia.

PubMed

Pandolfino, John E; Kwiatek, Monika A; Ho, Kim; Scherer, John R; Kahrilas, Peter J

2010-01-01

Our aim was to assess pressure dynamics within the esophagogastric junction (EGJ) in sliding hiatus hernia (HH) during normal peristalsis and to compare the pressure profiles of HH patients with gastroesophageal reflux disease (GERD) symptoms (HH-GERD) to HH patients with dysphagia (HH-dysphagia). High-resolution manometry studies in 230 consecutive patients and 68 controls were reviewed. HH patients were defined by a >or=1.5 cm separation between the lower esophageal sphincter (LES) and crural diaphragm (CD) on pressure topography plots. The HH population was further culled to eliminate those patients with motor disorders or stricture. The study groups were composed of 18 HH patients with only reflux symptoms and 10 HH patients with only dysphagia. Analysis of the pressure dynamics within the EGJ was performed at rest and after swallowing to independently quantify the LES and CD contributions to residual EGJ pressure, as well as the magnitude and genesis of distal esophageal intrabolus pressure (IBP). Differences among study groups were analyzed with analysis of variance. After swallows, HH-dysphagia patients had greater residual CD pressure (9 mmHg; standard deviation [SD], 4) and IBP pressure (19 mmHg; SD, 4) compared to HH-GERD patients (5 mmHg; SD, 2; and 12 mmHg; SD, 2, respectively; P<.001) or normal subjects (NA; 11 mmHg; SD, 3; P<.001). Sliding HH alters the pressure dynamics through the EGJ and can lead to a functional obstruction. Patients with HH and dysphagia have greater pressures through the CD compared to HH patients with GERD symptoms, supporting the hypothesis that sliding HH in and of itself may be responsible for dysphagia. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Multimodal strategy to improve the adherence to hand hygiene and self-assessment of the institution for the promotion and practice of hand hygiene.

PubMed

Oliveira, A C; Gama, C S; Paula, A O

2018-03-01

Hand hygiene (HH) has a low rate of adherence worldwide. This study aimed to estimate the HH adherence rate before and after the implementation of the multimodal strategy and to perform a self-assessment of an institution for promotion and practice of HH. Before and after study, conducted in a university hospital. Professionals of the medical and nursing staff were included. Data collection was from October 2013 to July 2015, through observations of the HH opportunities and application of the HH self-assessment instrument for the institution. Descriptive and univariate analysis were performed. A total of 9500 HH opportunities were observed. The rate of adherence to HH in pre-intervention period was 20.8%, compared to 16.2% and 15.7% in post-intervention. Regarding the evaluation of the institution, it did not have an established ongoing program of training of professionals, no feedback of HH rates to professionals. The low rate of HH adherence reflected the evaluation of the institution in relation to its investment in the practice and promotion of HH, showing that the investment policy for HH adherence needs to be reviewed, considering that before the study the hospital has not been trained in the 'My Five Moments for HH'.

Neuropilins are positive regulators of Hedgehog signal transduction

PubMed Central

Hillman, R. Tyler; Feng, Brian Y.; Ni, Jun; Woo, Wei-Meng; Milenkovic, Ljiljana; Hayden Gephart, Melanie G.; Teruel, Mary N.; Oro, Anthony E.; Chen, James K.; Scott, Matthew P.

2011-01-01

The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal transduction during mouse development. Using cell lines lacking key Hh pathway components, we show that Nrps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 overexpression increases maximal Hh target gene activation, indicating the existence of a positive feedback circuit. The regulation of Hh signal transduction by Nrps is conserved between mammals and bony fish, as we show that morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and highly penetrant Hh pathway loss-of-function phenotype. These findings enhance our knowledge of Hh pathway regulation and provide evidence for a conserved nexus between Nrps and this important developmental signaling system. PMID:22051878

Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung.

PubMed

Chuang, Pao-Tien; Kawcak, T'Nay; McMahon, Andrew P

2003-02-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue is how negative regulation of Hh signaling might contribute to generating differential responses over tens of cell diameters. In cells that respond to Hh, two proteins that are up-regulated are Patched1 (Ptch1), the Hh receptor, a general target in both invertebrate and vertebrate organisms, and Hip1, a Hh-binding protein that is vertebrate specific. To address the developmental role of Hip1 in the context of Hh signaling, we generated Hip1 mutants in the mouse. Loss of Hip1 function results in specific defects in two Hh target issues, the lung, a target of Sonic hedgehog (Shh) signaling, and the endochondral skeleton, a target of Indian hedgehog (Ihh) signaling. Hh signaling was up-regulated in Hip1 mutants, substantiating Hip1's general role in negatively regulating Hh signaling. Our studies focused on Hip1 in the lung. Here, a dynamic interaction between Hh and fibroblast growth factor (Fgf) signaling, modulated at least in part by Hip1, controls early lung branching.

Phenotypic analysis of hemochromatosis subtypes reveals variations in severity of iron overload and clinical disease.

PubMed

Sandhu, Kam; Flintoff, Kaledas; Chatfield, Mark D; Dixon, Jeannette L; Ramm, Louise E; Ramm, Grant A; Powell, Lawrie W; Subramaniam, V Nathan; Wallace, Daniel F

2018-05-09

The clinical progression of HFE-related hereditary hemochromatosis (HH) and its phenotypic variability has been well studied. Less is known about the natural history of non-HFE HH caused by mutations in the HJV , HAMP or TFR2 genes. The purpose of this study was to compare the phenotypic and clinical presentations of hepcidin-deficient forms of HH. A literature review of all published cases of genetically confirmed HJV, HAMP and TFR2 HH was performed. Phenotypic and clinical data from a total of 156 subjects with non-HFE HH was extracted from 53 publications and compared with data from 984 subjects with HFE -p.C282Y homozygous HH from the QIMR Berghofer Hemochromatosis Database. Analyses confirmed that non-HFE forms of HH have an earlier age of onset and a more severe clinical course than HFE HH. HJV and HAMP HH are phenotypically and clinically very similar and have the most severe presentation, with cardiomyopathy and hypogonadism being particularly prevalent findings. TFR2 HH is more intermediate in its age of onset and severity. All clinical outcomes analyzed were more prevalent in the juvenile forms of HH, with the exception of arthritis and arthropathy which were more commonly seen in HFE HH. This is the first comprehensive analysis comparing the different phenotypic and clinical aspects of the genetic forms of HH and the results will be valuable for the differential diagnosis and management of these conditions. Importantly, our analyses indicate that factors other than iron overload may be contributing to joint pathology in subjects with HFE HH. Copyright © 2018 American Society of Hematology.

HERBIG-HARO OBJECTS IN THE LUPUS I AND III MOLECULAR CLOUDS

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

Wang Hongchi; Henning, Thomas

2009-10-15

We performed a deep search for Herbig-Haro (HH) objects toward the Lupus I and III clouds, covering a sky area of {approx} 1 and {approx} 0.5 deg{sup 2}, respectively. In total, 11 new HH objects, HH 981--991, are discovered. The HH objects both in Lupus I and in Lupus III tend to be concentrated in small areas. The HH objects detected in Lupus I are located in a region of radius 0.26 pc near the young star Sz 68. The abundance of HH objects shows that this region of the cloud is active in on-going star formation. HH objects inmore » the Lup III cloud are concentrated in the central part of the cloud around the Herbig Ae/Be stars HR 5999 and 6000. HH 981 and 982 in Lupus I are probably driven by the young brown dwarf SSTc2d J154457.9-342340 which has a mass of 50 M{sub J} . HH 990 and 991 in Lup III align well with the HH 600 jet emanating from the low-mass star Par-Lup3-4, and are probably excited by this low-mass star of spectral type M5. High proper motions for HH 228 W, E, and E2 are measured, which confirms that they are excited by the young star Th 28. In contrast, HH 78 exhibits no measurable proper motion in the time span of 18 years, indicating that HH 78 is unlikely part of the HH 228 flow. The HH objects in Lup I and III are generally weak in terms of brightness and dimension in comparison to HH objects we detected with the same technique in the R CrA and Cha I clouds. Through a comparison with the survey results from the Spitzer c2d program, we find that our optical survey is more sensitive, in terms of detection rate, than the Spitzer IRAC survey to high-velocity outflows in the Lup I and III clouds.« less

Hedgehog signaling and laminin play unique and synergistic roles in muscle development.

PubMed

Peterson, Matthew T; Henry, Clarissa A

2010-03-01

Hedgehog (Hh) signaling and laminin-111, a basement membrane protein, are required for early muscle development. Hh signaling specifies different populations of muscle fibers and laminin-111 is critical for early muscle morphogenesis. However, additional requirements for Hh signaling and laminin during later phases of muscle development are not known. Furthermore, interactions between Hh signaling and laminin in this context are unknown. We used laminin gamma1 mutant zebrafish and cyclopamine to block Hh signal transduction separately and in combination to investigate their functions and interactions. We found that both Hh signaling and laminin are required for normal myosin chain expression. In addition, Hh signaling and laminin act synergistically during fast-twitch fiber elongation: fast muscle cells do not elongate in embryos deficient for both Hh signaling and laminin. Finally, we present evidence that suggests that Hh signaling is indirectly required via slow fiber specification for recovery of fast fiber elongation in laminin gamma1 mutant embryos. Copyright (c) 2010 Wiley-Liss, Inc.

Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.

PubMed

Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

2015-09-15

Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors.

Assessing hand hygiene resources and practices at a large african teaching hospital.

PubMed

Owusu-Ofori, Alex; Jennings, Rebecca; Burgess, Jennifer; Prasad, Priya A; Acheampong, Faustina; Coffin, Susan E

2010-08-01

To gather baseline data on hand hygiene (HH) practices in an African hospital with a newly established infection prevention and control team. Cross-sectional, observational study. Setting. Komfo Anokye Teaching Hospital, a large teaching hospital in Ghana with approximately 1,000 beds. All hospital staff with patient contact were eligible for assessment of HH practices. HH observations were conducted using a standardized data collection tool and method based on the World Health Organization's "5 Moments of Hand Hygiene." Small-group interviews were conducted to gather additional information on perceptions of HH and barriers to its use. HH resource needs were also assessed using a standardized tool. HH was attempted in 12% of the opportunities and was performed appropriately in 4% of the opportunities. Most main wards (89%) had at least 1 functional HH station. The most commonly identified barriers to HH were limited resources and lack of knowledge on appropriate times to perform HH. We developed and applied tools to evaluate HH resources and practices in a large African hospital. These assessments were undertaken to guide future efforts to improve HH at this hospital but can also serve as a model of the way to perform a systematic assessment at acute care hospitals in developing countries.

The Hedgehog Signal Transduction Network

PubMed Central

Robbins, David J.; Fei, Dennis Liang; Riobo, Natalia A.

2013-01-01

Hedgehog (Hh) proteins regulate the development of a wide range of metazoan embryonic and adult structures, and disruption of Hh signaling pathways results in various human diseases. Here, we provide a comprehensive review of the signaling pathways regulated by Hh, consolidating data from a diverse array of organisms in a variety of scientific disciplines. Similar to the elucidation of many other signaling pathways, our knowledge of Hh signaling developed in a sequential manner centered on its earliest discoveries. Thus, our knowledge of Hh signaling has for the most part focused on elucidating the mechanism by which Hh regulates the Gli family of transcription factors, the so-called “canonical” Hh signaling pathway. However, in the past few years, numerous studies have shown that Hh proteins can also signal through Gli-independent mechanisms collectively referred to as “noncanonical” signaling pathways. Noncanonical Hh signaling is itself subdivided into two distinct signaling modules: (i) those not requiring Smoothened (Smo) and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, Hh signaling is now proposed to occur through a variety of distinct context-dependent signaling modules that have the ability to crosstalk with one another to form an interacting, dynamic Hh signaling network. PMID:23074268

Liver Cell-Derived Microparticles Activate Hedgehog Signaling and Alter Gene Expression in Hepatic Endothelial Cells

PubMed Central

Witek, Rafal P.; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S.; Cheong, Yeiwon; Fearing, Caitlin M.; Agboola, Kolade M.; Chen, Wei; Diehl, Anna Mae

2013-01-01

Background & Aims Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). Methods MF-HSCs and cholangiocytes were exposed to platelet-derived growth factor (PDGF) to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy (TEM) and immunoblots, and applied to Hh-reporter containing cells. Microparticles were also obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, a Hh signaling inhibitor. Effects on SEC gene expression were evaluated by QRT-PCR and immunoblotting. Finally, Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Results PDGF-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically active Hh ligands. BDL also increased release of Hh-containing exosome-enriched microparticles into plasma and bile. TEM and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Conclusions Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy. PMID:19013163

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

PubMed

Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

2009-01-01

Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

Assessment of state- and territorial-level preparedness capacity for serving deaf and hard-of-hearing populations in disasters.

PubMed

Ivey, Susan L; Tseng, Winston; Dahrouge, Donna; Engelman, Alina; Neuhauser, Linda; Huang, Debbie; Gurung, Sidhanta

2014-01-01

Substantial evidence exists that emergency preparedness and response efforts are not effectively reaching populations with functional and access needs, especially barriers related to literacy, language, culture, or disabilities. More than 36 million Americans are Deaf or hard of hearing (Deaf/HH). These groups experienced higher risks of injury, death, and property loss in recent disasters than the general public. We conducted a participatory research study to examine national recommendations on preparedness communication for the Deaf/HH. We assessed whether previous recommendations regarding the Deaf/HH have been incorporated into state- and territorial-level emergency operations plans (EOPs), interviewed state- and territorial-level preparedness directors about capacity to serve the Deaf/HH, and proposed strategies to benefit Deaf/HH populations during emergencies. We analyzed 55 EOPs and 50 key informant (KI) interviews with state directors. Fifty-five percent of EOPs mentioned vulnerable populations; however, only 31% specifically mentioned Deaf/HH populations in their plan. Study findings indicated significant relationships among the following factors: a state-level KI's familiarity with communication issues for the Deaf/HH, making relay calls (i.e., calls to services to relay communication between Deaf and hearing people), and whether the KI's department provides trainings about serving Deaf/HH populations in emergencies. We found significant associations between a state's percentage of Deaf/HH individuals and a KI's familiarity with Deaf/HH communication issues and provision by government of any disability services to Deaf/HH populations in emergencies. Further, we found significant relationships between KIs attending training on serving the Deaf/HH and familiarity with Deaf/HH communication issues, including how to make relay calls. This study provides new knowledge that can help emergency agencies improve their preparedness training, planning, and capacity

Assessment of State- and Territorial-Level Preparedness Capacity for Serving Deaf and Hard-of-Hearing Populations in Disasters

PubMed Central

Tseng, Winston; Dahrouge, Donna; Engelman, Alina; Neuhauser, Linda; Huang, Debbie; Gurung, Sidhanta

2014-01-01

Objectives Substantial evidence exists that emergency preparedness and response efforts are not effectively reaching populations with functional and access needs, especially barriers related to literacy, language, culture, or disabilities. More than 36 million Americans are Deaf or hard of hearing (Deaf/HH). These groups experienced higher risks of injury, death, and property loss in recent disasters than the general public. We conducted a participatory research study to examine national recommendations on preparedness communication for the Deaf/HH. Methods We assessed whether previous recommendations regarding the Deaf/HH have been incorporated into state- and territorial-level emergency operations plans (EOPs), interviewed state- and territorial-level preparedness directors about capacity to serve the Deaf/HH, and proposed strategies to benefit Deaf/HH populations during emergencies. We analyzed 55 EOPs and 50 key informant (KI) interviews with state directors. Results Fifty-five percent of EOPs mentioned vulnerable populations; however, only 31% specifically mentioned Deaf/HH populations in their plan. Study findings indicated significant relationships among the following factors: a state-level KI's familiarity with communication issues for the Deaf/HH, making relay calls (i.e., calls to services to relay communication between Deaf and hearing people), and whether the KI's department provides trainings about serving Deaf/HH populations in emergencies. We found significant associations between a state's percentage of Deaf/HH individuals and a KI's familiarity with Deaf/HH communication issues and provision by government of any disability services to Deaf/HH populations in emergencies. Further, we found significant relationships between KIs attending training on serving the Deaf/HH and familiarity with Deaf/HH communication issues, including how to make relay calls. Conclusion This study provides new knowledge that can help emergency agencies improve their

The Hedgehog processing pathway is required for NSCLC growth and survival

PubMed Central

Rodriguez-Blanco, Jezabel; Schilling, Neal S.; Tokhunts, Robert; Giambelli, Camilla; Long, Jun; Liang Fei, Dennis; Singh, Samer; Black, Kendall E.; Wang, Zhiqiang; Galimberti, Fabrizio; Bejarano, Pablo A.; Elliot, Sharon; Glassberg, Marilyn K.; Nguyen, Dao M.; Lockwood, William W.; Lam, Wan L.; Dmitrovsky, Ethan; Capobianco, Anthony J.; Robbins, David J.

2013-01-01

Considerable interest has been generated from the results of recent clinical trials using SMOOTHENED (SMO) antagonists to inhibit the growth of HEDGEHOG (HH) signaling dependent tumors. This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH signaling at levels distinct from those inhibiting SMO function. Here, we demonstrate that HH dependent non-small cell lung carcinoma (NSCLC) growth is sensitive to blockade of the HH pathway upstream of SMO, at the level of HH ligand processing. Individually, the use of different lentivirally delivered shRNA constructs targeting two functionally distinct HH-processing proteins, SKINNY HEDGEHOG (SKN) or DISPATCHED-1 (DISP-1), in NSCLC cell lines produced similar decreases in cell proliferation and increased cell death. Further, providing either an exogenous source of processed HH or a SMO agonist reverses these effects. The attenuation of HH processing, by knocking down either of these gene products, also abrogated tumor growth in mouse xenografts. Finally, we extended these findings to primary clinical specimens, showing that SKN is frequently over-expressed in NSCLC and that higher DISP-1 expression is associated with an unfavorable clinical outcome. Our results show a critical role for HH processing in HH-dependent tumors, identifies two potential druggable targets in the HH pathway, and suggest that similar therapeutic strategies could be explored to treat patients harboring HH ligand dependent cancers. PMID:22733134

Studying the outflow-core interaction with ALMA Cycle 1 observations of the HH 46/47 molecular outflow

NASA Astrophysics Data System (ADS)

Zhang, Yichen; Arce, Hector G.; Mardones, Diego; Dunham, Michael; Garay, Guido; Noriega-Crespo, Alberto; Corder, Stuartt; Offner, Stella; Cabrit, Sylvie

2016-01-01

We present ALMA Cycle 1 observations of the HH 46/47 molecular outflow which is driven by a low-mass Class 0/I protostar. Previous ALMA Cycle 0 12CO observation showed outflow cavities produced by the entrainment of ambient gas by the protostellar jet and wide-angle wind. Here we present analysis of observation of 12CO, 13CO, C18O and other species using combined 12m array and ACA observations. The improved angular resolution and sensitivity allow us to detect details of the outflow structure. Specially, we see that the outflow cavity wall is composed of two or more layers of outflowing gas, which separately connect to different shocked regions along the outflow axis inside the cavity, suggesting the outflow cavity wall is composed of multiple shells entrained by a series of jet bow-shock events. The new 13CO and C18O data also allow us to trace relatively denser and slower outflow material than that traced by the 12CO. These species are only detected within about 1 to 2 km/s from the cloud velocity, tracing the outflow to lower velocities than what is possible using only the 12CO emission. Interestingly, the cavity wall of the red lobe appears at very low outflow velocities (as low as ~0.2 km/s). In addition, 13CO and C18O allow us to correct for the CO optical depth, allowing us to obtain more accurate estimates of the outflow mass, momentum and kinetic energy. Applying the optical depth correction significantly increases the previous mass estimate by a factor of 14. The outflow kinetic energy distribution shows that even though the red lobe is mainly entrained by jet bow-shocks, most of the outflow energy is being deposited into the cloud at the base of the outflow cavity rather than around the heads of the bow shocks. The estimated total mass, momentum, and energy of the outflow indicate that the outflow has the ability to disperse the parent core. We found possible evidence for a slowly moving rotating outflow in CS. Our 13CO and C18O observations also trace a

Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung

PubMed Central

Chuang, Pao-Tien; Kawcak, T'Nay; McMahon, Andrew P.

2003-01-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue is how negative regulation of Hh signaling might contribute to generating differential responses over tens of cell diameters. In cells that respond to Hh, two proteins that are up-regulated are Patched1 (Ptch1), the Hh receptor, a general target in both invertebrate and vertebrate organisms, and Hip1, a Hh-binding protein that is vertebrate specific. To address the developmental role of Hip1 in the context of Hh signaling, we generated Hip1 mutants in the mouse. Loss of Hip1 function results in specific defects in two Hh target issues, the lung, a target of Sonic hedgehog (Shh) signaling, and the endochondral skeleton, a target of Indian hedgehog (Ihh) signaling. Hh signaling was up-regulated in Hip1 mutants, substantiating Hip1's general role in negatively regulating Hh signaling. Our studies focused on Hip1 in the lung. Here, a dynamic interaction between Hh and fibroblast growth factor (Fgf) signaling, modulated at least in part by Hip1, controls early lung branching. PMID:12569124

Apollo’s Warriors: United States Air Force Special Operations during the Cold War

DTIC Science & Technology

1997-01-01

er, and that was the unique manner in which they were packed for long-term storage. "Seal and peel " was a technique developed specifically to...for the aerial refueling leg. Refueling silently, ing the president’s approval would pick the the helos watched their tankers peel away, to be exact...130E C-130E HC-130P HC-130P HH-3 HH-53 HH-53 HH-53 HH-53 HH-53 A-1E Call Sign Cherry 1 Cherry 2 Lime 01 Lime 02 Banana 1 Apple 1

Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus.

PubMed

van Dop, Willemijn A; Rosekrans, Sanne L; Uhmann, Anja; Jaks, Viljar; Offerhaus, G Johan A; van den Bergh Weerman, Marius A; Kasper, Maria; Heijmans, Jarom; Hardwick, James C H; Verspaget, Hein W; Hommes, Daan W; Toftgård, Rune; Hahn, Heidi; van den Brink, Gijs R

2013-03-01

In the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus. The authors used transgenic mice in which the Hh receptor Patched1 (Ptch1) could be conditionally inactivated in a body-wide manner and mice in which Gli1 could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR. Sonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets GLI1, HHIP and PTCH1 were increased in SCC compared with normal tissue from the same patients. Here the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation.

Common fold in helix–hairpin–helix proteins

PubMed Central

Shao, Xuguang; Grishin, Nick V.

2000-01-01

Helix–hairpin–helix (HhH) is a widespread motif involved in non-sequence-specific DNA binding. The majority of HhH motifs function as DNA-binding modules, however, some of them are used to mediate protein–protein interactions or have acquired enzymatic activity by incorporating catalytic residues (DNA glycosylases). From sequence and structural analysis of HhH-containing proteins we conclude that most HhH motifs are integrated as a part of a five-helical domain, termed (HhH)2 domain here. It typically consists of two consecutive HhH motifs that are linked by a connector helix and displays pseudo-2-fold symmetry. (HhH)2 domains show clear structural integrity and a conserved hydrophobic core composed of seven residues, one residue from each α-helix and each hairpin, and deserves recognition as a distinct protein fold. In addition to known HhH in the structures of RuvA, RadA, MutY and DNA-polymerases, we have detected new HhH motifs in sterile alpha motif and barrier-to-autointegration factor domains, the α-subunit of Escherichia coli RNA-polymerase, DNA-helicase PcrA and DNA glyco­s­y­lases. Statistically significant sequence similarity of HhH motifs and pronounced structural conservation argue for homology between (HhH)2 domains in different protein families. Our analysis helps to clarify how non-symmetric protein motifs bind to the double helix of DNA through the formation of a pseudo-2-fold symmetric (HhH)2 functional unit. PMID:10908318

Does haemochromatosis predispose to coeliac disease? A study of 29,096 coeliac disease patients

PubMed Central

Ludvigsson, Jonas F; Murray, Joseph A; Adams, Paul C; Elmberg, Maria

2013-01-01

Background and aim Case reports suggest an association between hereditary haemochromatosis (HH) and coeliac disease (CD), but estimates of association are lacking. We estimated the association between HH and CD in a population-based study. Materials and methods Case-control study. We identified 29,096 individuals with biopsy-verified CD (equal to villous atrophy, Marsh stage III) through biopsy reports from all 28 pathology departments in Sweden. We then investigated the risk of a clinical diagnosis of HH in CD and in 144,522 controls matched for age, sex, county and calendar year. Conditional logistic regression was used to calculate odds ratios (ORs) for CD in patients with HH. Results HH was seen in 30 patients with CD and in 60 matched controls. HH was hence associated with an increased risk of CD (OR=2.30; 95%CI=1.53–3.25). Restricting HH to individuals with at least 2 records of HH, the OR for CD was 2.54 (95%CI=1.57–4.11), with a similar risk estimate when we only looked at HH diagnosed before CD (and matched date in controls) (OR=2.64; 95%CI=1.24–5.60). Conclusion HH seems to be associated with an increased risk of CD. PMID:23256862

Development of Lead Hammerhead Ribozyme Candidates against Human Rod Opsin mRNA for Retinal Degeneration Therapy

PubMed Central

Abdelmaksoud, Heba E.; Yau, Edwin H.; Zuker, Michael; Sullivan, Jack M.

2011-01-01

To identify lead candidate allele-independent hammerhead ribozymes (hhRz) for the treatment of autosomal dominant mutations in the human rod opsin (RHO) gene, we tested a series of hhRzs for potential to significantly knockdown human RHO gene expression in a human cell expression system. Multiple computational criteria were used to select target mRNA regions likely to be single stranded and accessible to hhRz annealing and cleavage. Target regions are tested for accessibility in a human cell culture expression system where the hhRz RNA and target mRNA and protein are coexpressed. The hhRz RNA is embedded in an adenoviral VAI RNA chimeric RNA of established structure and properties which are critical to the experimental paradigm. The chimeric hhRz-VAI RNA is abundantly transcribed so that the hhRzs are expected to be in great excess over substrate mRNA. HhRz-VAI traffics predominantly to the cytoplasm to colocalize with the RHO mRNA target. Colocalization is essential for second-order annealing reactions. The VAI chimera protects the hhRz RNA from degradation and provides for a long half life. With cell lines chosen for high transfection efficiency and a molar excess of hhRz plasmid over target plasmid, the conditions of this experimental paradigm are specifically designed to evaluate for regions of accessibility of the target mRNA in cellulo. Western analysis was used to measure the impact of hhRz expression on RHO protein expression. Three lead candidate hhRz designs were identified that significantly knockdown target protein expression relative to control (p < 0.05). Successful lead candidates (hhRz CUC↓ 266, hhRz CUC↓ 1411, hhRz AUA↓ 1414) targeted regions of human RHO mRNA that were predicted to be accessible by a bioinformatics approach, whereas regions predicted to be inaccessible supported no knockdown. The maximum opsin protein level knockdown is approximately 30% over a 48 hr paradigm of testing. These results validate a rigorous computational

Hand hygiene compliance rates in the United States--a one-year multicenter collaboration using product/volume usage measurement and feedback.

PubMed

McGuckin, Maryanne; Waterman, Richard; Govednik, John

2009-01-01

Hand hygiene (HH) is the single most important factor in the prevention of health care-acquired infections. The 3 most frequently reported methods of measuring HH compliance are: (1) direct observation, (2) self-reporting by health care workers (HCWs), and (3) indirect calculation based on HH product usage. This article presents the results of a 12-month multicenter collaboration assessing HH compliance rates at US health care facilities by measuring product usage and providing feedback about HH compliance. Our results show that HH compliance at baseline was 26% for intensive care units (ICUs) and 36% for non-ICUs. After 12 months of measuring product usage and providing feedback, compliance increased to 37% for ICUs and 51% for non-ICUs. (ICU, P = .0119; non-ICU, P < .001). HH compliance in the United States can increase when monitoring is combined with feedback. However, HH still occurs at or below 50% compli- ance for both ICUs and non-ICUs.

The Effects of Social Influence on Nurses' Hand Hygiene Behaviors.

PubMed

Piras, Susan E; Minnick, Ann; Lauderdale, Jana; Dietrich, Mary S; Vogus, Timothy J

2018-04-01

The aim of this article is to describe the associations of nurses' hand hygiene (HH) attitudes, subjective norms, and perceived behavioral control with observed and self-reported HH behavior. Hand hygiene is an essential strategy to prevent healthcare-associated infections. Despite tremendous efforts, nurses' HH adherence rates remain suboptimal. This quantitative descriptive study of ICU nurses in the southeastern United States was guided by the theory of planned behavior. The self-administered Patient Safety Opinion Survey and iScrub application, which facilitates observation, comprised the data set. Nurses' observed HH median was 55%; tendency to self-report was a much higher 90%. Subjective norm and perceived control scores were associated with observed and self-reported HH (P < .05) but not attitude scores or reports of intention. Nurses' subjective norm and perceived control are associated with observed and self-reported HH performance. Healthcare workers overestimate their HH performance. Findings suggest future research to explore manipulators of these variables to change nurses' HH behavior.

A multifaceted approach to education, observation, and feedback in a successful hand hygiene campaign.

PubMed

Doron, Shira I; Kifuji, Kayoko; Hynes, Brooke Tyson; Dunlop, Dan; Lemon, Tricia; Hansjosten, Karen; Cheung, Teresa; Curley, Barbara; Snydman, David R; Fairchild, David G

2011-01-01

Prevention of health care-associated infections starts with scrupulous hand hygiene (HH). Improving HH compliance is a major target for the World Health Organization Patient Safety Challenge and is one of The Joint Commission's National Patient Safety Goals. Yet, adherence to HH protocols is generally poor for health care professionals, despite interventions designed to improve compliance. At Tufts Medical Center (Boston), HH compliance rates were consistently low despite the presence of a traditional HH campaign that used communication and education. A comprehensive program incorporated strong commitment by hospital leadership-who were actively involved in responsibilities previously only performed by infection preventionists and quality and patient safety staff-dedication of financial resources, including securing a grant; collaborating with a private advertising firm in a marketing campaign; and employing a multifaceted approach to education, observation, and feedback. This campaign resulted in a rapid and sustained improvement in HH compliance: Compared with the mean HH compliance rate for the six months before the campaign (72%), postcampaign HH compliance (mean = 94%) was significantly greater (p < .0001). Factors contributing to the success of the campaign included the development of the marketing campaign to fit this academic medical center's particular culture, strong support from the medical center leadership, a multifaceted educational approach, and monthly feedback on HH compliance. A comprehensive campaign resulted in rapid and sustained improvement in HH compliance at an academic medical center after traditional communication and education strategies failed to improve HH performance.

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

PubMed Central

Laitinen, Eeva-Maria; Tommiska, Johanna; Sane, Timo; Vaaralahti, Kirsi; Toppari, Jorma; Raivio, Taneli

2012-01-01

Background Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. Methods and Findings Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A). Conclusions Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal. PMID:22724017

Home Health Nursing Care and Hospital Use for Medically Complex Children.

PubMed

Gay, James C; Thurm, Cary W; Hall, Matthew; Fassino, Michael J; Fowler, Lisa; Palusci, John V; Berry, Jay G

2016-11-01

Home health nursing care (HH) may be a valuable approach to long-term optimization of health for children, particularly those with medical complexity who are prone to frequent and lengthy hospitalizations. We sought to assess the relationship between HH services and hospital use in children. Retrospective, matched cohort study of 2783 hospitalized children receiving postdischarge HH services by BAYADA Home Health Care across 19 states and 7361 matched controls not discharged to HH services from the Children's Hospital Association Case Mix database between January 2004 and September 2012. Subsequent hospitalizations, hospital days, readmissions, and costs of hospital care were assessed over the 12-month period after the initial hospitalization. Nonparametric Wilcoxon signed rank tests were used for comparisons between HH and non-HH users. Although HH cases had a higher percentage of complex chronic conditions (68.5% vs 65.4%), technology assistance (40.5% vs 35.7%), and neurologic impairment (40.7% vs 37.3%) than matched controls (P ≤ .003 for all), 30-day readmission rates were lower in HH patients (18.3% vs 21.5%, P = .001). At 12 months after the index admission, HH patients averaged fewer admissions (0.8 vs 1.0, P < .001), fewer days in the hospital (6.4 vs 6.6, P < .001), and lower hospital costs ($22 511 vs $24 194, P < .001) compared with matched controls. Children discharged to HH care experienced less hospital use than children with similar characteristics who did not use HH care. Further investigation is needed to understand how HH care affects the health and health services of children. Copyright © 2016 by the American Academy of Pediatrics.

Studies on comonomer compositional distribution of bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)s and thermal characteristics of their factions.

PubMed

Feng, Lidan; Watanabe, Takumi; Wang, Yi; Kichise, Tomoyasu; Fukuchi, Takeshi; Chen, Guo-Qiang; Doi, Yoshiharu; Inoue, Yoshio

2002-01-01

The comonomer-unit compositional distributions have been investigated for bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HH)] samples with 3HH unit content of 13.8, 18.0, 22.0, and 54.0 mol %. They were comonomer compositionally fractionated using chloroform/n-heptane mixed solvent at ambient temperature. The fractionation of P(3HB-co-18.0 mol %3HH) and P(3HB-co-22.0 mol % 3HH), which could not be carried out effectively at room temperature, were refractionated at 70 degrees C in the mixed solvent. Fractions with different 3HH unit content in a wide range (from 4.4 to 80.7 mol %) were obtained. By use of these fractions with narrow compositional distribution, the comonomer composition dependence of thermal properties was investigated by differential scanning calorimetry. The melting point (T(m)) and heat of fusion (DeltaH) decreased as the 3HH unit content increased in the range of low 3HH content (<40 mol %), while they increased as the 3HH unit content increased in the high 3HH content range (>70 mol %). The minimum T(m) and DeltaH values were found to exist at 3HH unit content of about 60 mol %. The glass transition temperature (T(g)) decreased linearly with the increase of 3HH unit content. The values of T(m), DeltaH, and T(g) of P(3HB-co-3HH)s were compared with those of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxypropionate), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), and the effects of comonomer types on the thermal properties were revealed.

Hedgehog participates in the establishment of left-right asymmetry during amphioxus development by controlling Cerberus expression.

PubMed

Hu, Guangwei; Li, Guang; Wang, Hui; Wang, Yiquan

2017-12-15

Correct patterning of left-right (LR) asymmetry is essential during the embryonic development of bilaterians. Hedgehog (Hh) signaling is known to play a role in LR asymmetry development of mouse, chicken and sea urchin embryos by regulating Nodal expression. In this study, we report a novel regulatory mechanism for Hh in LR asymmetry development of amphioxus embryos. Our results revealed that Hh -/- embryos abolish Cerberus ( Cer ) transcription, with bilaterally symmetric expression of Nodal , Lefty and Pitx In consequence, Hh -/- mutants duplicated left-side structures and lost right-side characters, displaying an abnormal bilaterally symmetric body plan. These LR defects in morphology and gene expression could be rescued by Hh mRNA injection. Our results indicate that Hh participates in amphioxus LR patterning by controlling Cer gene expression. Curiously, however, upregulation of Hh signaling failed to alter the Cer expression pattern or LR morphology in amphioxus embryos, indicating that Hh might not provide an asymmetric cue for Cer expression. In addition, Hh is required for mouth opening in amphioxus, hinting at a homologous relationship between amphioxus and vertebrate mouth development. © 2017. Published by The Company of Biologists Ltd.

Molecular determinants for the high constitutive activity of the human histamine H4 receptor: functional studies on orthologues and mutants

PubMed Central

Wifling, D; Löffel, K; Nordemann, U; Strasser, A; Bernhardt, G; Dove, S; Seifert, R; Buschauer, A

2015-01-01

Background and Purpose Some histamine H4 receptor ligands act as inverse agonists at the human H4 receptor (hH4R), a receptor with exceptionally high constitutive activity, but as neutral antagonists or partial agonists at the constitutively inactive mouse H4 receptor (mH4R) and rat H4 receptor (rH4R). To study molecular determinants of constitutive activity, H4 receptor reciprocal mutants were constructed: single mutants: hH4R-F169V, mH4R-V171F, hH4R-S179A, hH4R-S179M; double mutants: hH4R-F169V+S179A, hH4R-F169V+S179M and mH4R-V171F+M181S. Experimental Approach Site-directed mutagenesis with pVL1392 plasmids containing hH4 or mH4 receptors were performed. Wild-type or mutant receptors were co-expressed with Gαi2 and Gβ1γ2 in Sf9 cells. Membranes were studied in saturation and competition binding assays ([3H]-histamine), and in functional [35S]-GTPγS assays with inverse, partial and full agonists of the hH4 receptor. Key Results Constitutive activity decreased from the hH4 receptor via the hH4R-F169V mutant to the hH4R-F169V+S179A and hH4R-F169V+S179M double mutants. F169 alone or in concert with S179 plays a major role in stabilizing a ligand-free active state of the hH4 receptor. Partial inverse hH4 receptor agonists like JNJ7777120 behaved as neutral antagonists or partial agonists at species orthologues with lower or no constitutive activity. Some partial and full hH4 receptor agonists showed decreased maximal effects and potencies at hH4R-F169V and double mutants. However, the mutation of S179 in the hH4 receptor to M as in mH4 receptor or A as in rH4 receptor did not significantly reduce constitutive activity. Conclusions and Implications F169 and S179 are key amino acids for the high constitutive activity of hH4 receptors and may also be of relevance for other constitutively active GPCRs. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update published in volume 170 issue 1. To view the other articles in this issue visit

Incidence and Risk Factors of Symptomatic Hiatal Hernia Following Resection for Gastric and Esophageal Cancer.

PubMed

Andreou, Andreas; Pesthy, Sina; Struecker, Benjamin; Dadras, Mehran; Raakow, Jonas; Knitter, Sebastian; Duwe, Gregor; Sauer, Igor M; Beierle, Anika Sophie; Denecke, Christian; Chopra, Sascha; Pratschke, Johann; Biebl, Matthias

2017-12-01

Symptomatic hiatal hernia (HH) following resection for gastric or esophageal cancer is a potentially life-threatening event that may lead to emergent surgery. However, the incidence and risk factors of this complication remain unclear. Data of patients who underwent resection for gastric or esophageal cancer between 2005 and 2012 were assessed and the incidence of symptomatic HH was evaluated. Factors associated with an increased risk for HH were investigated. Resection of gastric or esophageal cancer was performed in 471 patients. The primary tumor was located in the stomach, cardia and esophagus in 36%, 24%, and 40% of patients, respectively. The incidence of symptomatic HH was 2.8% (n=13). All patients underwent surgical hernia repair, 8 patients (61.5%) required emergent procedure, and 3 patients (23%) underwent bowel resection. Morbidity and mortality after HH repair was 38% and 8%, respectively. Factors associated with increased risk for symptomatic HH included Body-Mass-Index (median BMI with HH 27 (23-35) vs. BMI without HH 25 (15-51), p=0.043), diabetes (HH rate: with diabetes, 6.3% vs. without diabetes, 2%, p=0.034), tumor location (HH rate: stomach, 1.2% vs. esophagus, 1.1% vs. cardia, 7.9%, p=0.001), and resection type (HH rate: total/subtotal gastrectomy, 0.7% vs. transthoracic esophagectomy, 2.7% vs. extended gastrectomy, 6.1%, p=0.038). HH is a major adverse event after resection for gastric or esophageal cancer especially among patients undergoing extended gastrectomy for cardia cancer requiring a high rate of repeat surgery. Therefore, intensive follow-up examinations for high-risk patients and early diagnosis of asymptomatic patients are essential for selecting patients for elective surgery to avoid unpredictable emergent events with high morbidity and mortality. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Hedgehog restricts its expression domain in the Drosophila wing

PubMed Central

Bejarano, Fernando; Pérez, Lidia; Apidianakis, Yiorgos; Delidakis, Christos; Milán, Marco

2007-01-01

The stable subdivision of Drosophila limbs into anterior and posterior compartments is a consequence of asymmetrical signalling by Hedgehog (Hh), from the posterior to anterior cells. The activity of the homeodomain protein Engrailed in posterior cells helps to generate this asymmetry by inducing the expression of Hh in the posterior compartment and, at the same time, repressing the expression of the essential downstream component Cubitus interruptus (Ci). Therefore, only anterior cells that receive the Hh signal across the compartment boundary will respond by stabilizing Ci. Here, we describe a new molecular mechanism that helps to maintain the Hh-expressing and Hh-responding cells in different non-overlapping cell populations. Master of thickveins (mtv)—a target of Hh activity encoding a nuclear zinc-finger protein—is required to repress hh expression in anterior cells. Mtv exerts this action in a protein complex with Groucho (Gro)—the founding member of a superfamily of transcriptional corepressors that are conserved throughout eukaryotes. Therefore, Hh restricts its own expression domain in the Drosophila wing through the activity of Mtv and Gro. PMID:17571073

mTORC1-Mediated Inhibition of 4EBP1 Is Essential for Hedgehog Signaling-Driven Translation and Medulloblastoma.

PubMed

Wu, Chang-Chih; Hou, Shirui; Orr, Brent A; Kuo, Bryan R; Youn, Yong Ha; Ong, Taren; Roth, Fanny; Eberhart, Charles G; Robinson, Giles W; Solecki, David J; Taketo, Makoto M; Gilbertson, Richard J; Roussel, Martine F; Han, Young-Goo

2017-12-18

Mechanistic target of rapamycin (MTOR) cooperates with Hedgehog (HH) signaling, but the underlying mechanisms are incompletely understood. Here we provide genetic, biochemical, and pharmacologic evidence that MTOR complex 1 (mTORC1)-dependent translation is a prerequisite for HH signaling. The genetic loss of mTORC1 function inhibited HH signaling-driven growth of the cerebellum and medulloblastoma. Inhibiting translation or mTORC1 blocked HH signaling. Depleting 4EBP1, an mTORC1 target that inhibits translation, alleviated the dependence of HH signaling on mTORC1. Consistent with this, phosphorylated 4EBP1 levels were elevated in HH signaling-driven medulloblastomas in mice and humans. In mice, an mTORC1 inhibitor suppressed medulloblastoma driven by a mutant SMO that is inherently resistant to existing SMO inhibitors, prolonging the survival of the mice. Our study reveals that mTORC1-mediated translation is a key component of HH signaling and an important target for treating medulloblastoma and other cancers driven by HH signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk perception and perceived self-efficacy of deaf and hard-of-hearing seniors and young adults in emergencies.

PubMed

Engelman, Alina; Ivey, Susan L; Tseng, Winston; Neuhauser, Linda

2017-01-01

The authors explored the factors influencing risk perception and perceived self-efficacy before and during an emergency for deaf and hard-of-hearing (Deaf/HH) seniors and young adults. The authors collected demographic survey data and conducted four focus groups with 38 Deaf/HH residents of the San Francisco Bay Area; two groups were with young adults (ages 18-35), including one group of college students and one group of young professionals, and two were with older adults (ages 50-90). Significant differences were found between Deaf/HH young adults and seniors in both the sources of self-efficacy and risk perception and their attitudes toward preparedness. All groups demonstrated high resilience. Deaf/HH young professionals expressed more concern about their risk in an emergency than Deaf/HH college students. Alternately, the risk perception of Deaf/HH older adults was often rooted in their past experiences (survival of past emergencies, inaccessibility of communications during drills). Policy implications include the need to dedicate more resources to increasing accessibility and relevance of emergency communications technology for Deaf/HH populations. This could help increase adaptability before, during, and after emergencies among all groups of Deaf/HH people, particularly among young Deaf/HH professionals.

Impact of a multicomponent hand hygiene intervention strategy in reducing infection rates at a university hospital in Saudi Arabia.

PubMed

Al Kuwaiti, Ahmed

2017-09-01

Few studies have reported the correlation between hand hygiene (HH) practices and infection rates in Saudi Arabia. This work was aimed to study the effect of a multicomponent HH intervention strategy in improving HH compliance and reducing infection rates at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia between January 2014 and December 2016. A yearlong multicomponent HH intervention, which included various strategies recommended by the World Health Organization, was introduced. HH compliance among staff and infection rates observed in the inpatient wards were assessed and compared at pre- and post-interventional phases. There was a significant increase in mean HH compliance from 50.17% to 71.75% after the intervention ( P  < 0.05). Hospital-acquired infection (HAI) and catheter-associated urinary tract infection (CAUTI) rates decreased from 3.37 to 2.59 and from 3.73 to 1.75, respectively ( P  < 0.05). HH compliance was found to be negatively correlated with HAI ( r  = -0.278) and CAUTI ( r  = -0.523) rates. Results show that multicomponent intervention is effective in improving HH compliance, and that an increase in HH compliance among hospital staff decreases infection rates. Further studies on cost-effectiveness of such a model could augment to these findings.

Risk perception and perceived self-efficacy of deaf and hard-of-hearing seniors and young adults in emergencies.

PubMed

Engelman, Alina; Ivey, Susan L; Tseng, Winston; Neuhauser, Linda

The authors explored the factors influencing risk perception and perceived self-efficacy before and during an emergency for deaf and hard-of-hearing (Deaf/HH) seniors and young adults. The authors collected demographic survey data and conducted four focus groups with 38 Deaf/HH residents of the San Francisco Bay Area; two groups were with young adults (ages 18-35), including one group of college students and one group of young professionals, and two were with older adults (ages 50-90). Significant differences were found between Deaf/HH young adults and seniors in both the sources of self-efficacy and risk perception and their attitudes toward preparedness. All groups demonstrated high resilience. Deaf/HH young professionals expressed more concern about their risk in an emergency than Deaf/HH college students. Alternately, the risk perception of Deaf/HH older adults was often rooted in their past experiences (survival of past emergencies, inaccessibility of communications during drills). Policy implications include the need to dedicate more resources to increasing accessibility and relevance of emergency communications technology for Deaf/HH populations. This could help increase adaptability before, during, and after emergencies among all groups of Deaf/HH people, particularly among young Deaf/HH professionals.

Feasibility of a real-time hand hygiene notification machine learning system in outpatient clinics.

PubMed

Geilleit, R; Hen, Z Q; Chong, C Y; Loh, A P; Pang, N L; Peterson, G M; Ng, K C; Huis, A; de Korne, D F

2018-04-09

Various technologies have been developed to improve hand hygiene (HH) compliance in inpatient settings; however, little is known about the feasibility of machine learning technology for this purpose in outpatient clinics. To assess the effectiveness, user experiences, and costs of implementing a real-time HH notification machine learning system in outpatient clinics. In our mixed methods study, a multi-disciplinary team co-created an infrared guided sensor system to automatically notify clinicians to perform HH just before first patient contact. Notification technology effects were measured by comparing HH compliance at baseline (without notifications) with real-time auditory notifications that continued till HH was performed (intervention I) or notifications lasting 15 s (intervention II). User experiences were collected during daily briefings and semi-structured interviews. Costs of implementation of the system were calculated and compared to the current observational auditing programme. Average baseline HH performance before first patient contact was 53.8%. With real-time auditory notifications that continued till HH was performed, overall HH performance increased to 100% (P < 0.001). With auditory notifications of a maximum duration of 15 s, HH performance was 80.4% (P < 0.001). Users emphasized the relevance of real-time notification and contributed to technical feasibility improvements that were implemented in the prototype. Annual running costs for the machine learning system were estimated to be 46% lower than the observational auditing programme. Machine learning technology that enables real-time HH notification provides a promising cost-effective approach to both improving and monitoring HH, and deserves further development in outpatient settings. Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Differential involvement of Hedgehog signaling in butterfly wing and eyespot development.

PubMed

Tong, Xiaoling; Lindemann, Anna; Monteiro, Antónia

2012-01-01

Butterfly eyespots may have evolved from the recruitment of pre-existent gene circuits or regulatory networks into novel locations on the wing. Gene expression data suggests one such circuit, the Hedgehog (Hh) signaling pathway and its target gene engrailed (en), was recruited from a role in patterning the anterior-posterior insect wing axis to a role patterning butterfly eyespots. However, while Junonia coenia expresses hh and en both in the posterior compartment of the wing and in eyespot centers, Bicyclus anynana lacks hh eyespot-specific expression. This suggests that Hh signaling may not be functioning in eyespot development in either species or that it functions in J. coenia but not in B. anynana. In order to test these hypotheses, we performed functional tests of Hh signaling in these species. We investigated the effects of Hh protein sequestration during the larval stage on en expression levels, and on wing size and eyespot size in adults. Hh sequestration led to significantly reduced en expression and to significantly smaller wings and eyespots in both species. But while eyespot size in B. anynana was reduced proportionately to wing size, in J. coenia, eyespots were reduced disproportionately, indicating an independent role of Hh signaling in eyespot development in J. coenia. We conclude that while Hh signaling retains a conserved role in promoting wing growth across nymphalid butterflies, it plays an additional role in eyespot development in some, but not all, lineages of nymphalid butterflies. We discuss our findings in the context of alternative evolutionary scenarios that led to the differential expression of hh and other Hh pathway signaling members across nymphalid species.

Drosophila melanogaster Hedgehog cooperates with Frazzled to guide axons through a non-canonical signalling pathway.

PubMed

Ricolo, Delia; Butí, Elisenda; Araújo, Sofia J

2015-08-01

We report that the morphogen Hedgehog (Hh) is an axonal chemoattractant in the midline of Drosophila melanogaster embryos. Hh is present in the ventral nerve cord during axonal guidance and overexpression of hh in the midline causes ectopic midline crossing of FasII-positive axonal tracts. In addition, we show that Hh influences axonal guidance via a non-canonical signalling pathway dependent on Ptc. Our results reveal that the Hh pathway cooperates with the Netrin/Frazzled pathway to guide axons through the midline in invertebrates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Roles for Hedgehog signaling in adult organ homeostasis and repair

PubMed Central

Petrova, Ralitsa; Joyner, Alexandra L.

2014-01-01

The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

Defining Causative Factors Contributing in the Activation of Hedgehog Signaling in Diffuse Large B-Cell Lymphoma

PubMed Central

Ramirez, Elisa; Singh, Rajesh R; Kunkalla, Kranthi; Liu, Yadong; Qu, Changju; Cain, Christine; Multani, Asha S.; Lennon, Patrick A; Jackacky, Jared; Ho, Michael; Dawud, Sity; Gu, Jun; Yang, Su; Hu, Peter C; Vega, Francisco

2012-01-01

Hedgehog (Hh) signaling pathway is activated in diffuse large B-cell lymphoma (DLBCL). Genetic abnormalities that explain activation of Hh signaling in DLBCL are unknown. We investigate the presence of amplifications of Hh genes that might result in activation of this pathway in DLBCL. Our data showed few extra copies of GLI1 and SMO due to chromosomal aneuploidies in a subset of DLBCL cell lines. We also showed that pharmacologic inhibition of PI3K/AKT and NF-KB pathways resulted in decreased expression of GLI1 and Hh ligands. In conclusion, our data support the hypothesis that aberrant activation of Hh signaling in DLBCL mainly results from integration of deregulated oncogenic signaling inputs converging into Hh signaling. PMID:22809693

Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia

PubMed Central

Huang, Peng; Schier, Alexander F.

2009-01-01

Summary Cilia have been implicated in Hedgehog (Hh) and Wnt signaling in mouse but not in Drosophila. To determine whether the role of cilia is conserved in zebrafish, we generated maternal-zygotic (MZ) oval (ovl; ift88) mutants that lack all cilia. MZovl mutants display normal canonical and non-canonical Wnt signaling but show defects in Hh signaling. As in mouse, zebrafish cilia are required to mediate the activities of Hh, Ptc, Smo and PKA. However, in contrast to mouse Ift88 mutants, which show a dramatic reduction in Hh signaling, zebrafish MZovl mutants display dampened, but expanded, Hh pathway activity. This activity is largely due to gli1, the expression of which is fully dependent on Hh signaling in mouse but not in zebrafish. These results reveal a conserved requirement for cilia in transducing the activity of upstream regulators of Hh signaling but distinct phenotypic effects due to differential regulation and differing roles of transcriptional mediators. PMID:19700616

Clinical implications of hedgehog signaling pathway inhibitors

PubMed Central

Liu, Hailan; Gu, Dongsheng; Xie, Jingwu

2011-01-01

Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and Carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated Carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications. PMID:21192841

Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle

PubMed Central

Cardozo, Marcos Julián; Sánchez-Arrones, Luisa; Sandonis, África; Sánchez-Camacho, Cristina; Gestri, Gaia; Wilson, Stephen W.; Guerrero, Isabel; Bovolenta, Paola

2014-01-01

Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hedgehog (Hh) signalling, which promotes stalk specification. In the absence of Hh signalling, the stalks are not specified, causing cyclopia. Recent studies showed that the cell adhesion molecule Cdon forms a heteromeric complex with the Hh receptor Patched 1 (Ptc1). This receptor complex binds Hh and enhances signalling activation, indicating that Cdon positively regulates the pathway. Here we show that in the developing zebrafish and chick optic vesicle, in which cdon and ptc1 are expressed with a complementary pattern, Cdon acts as a negative Hh signalling regulator. Cdon predominantly localizes to the basolateral side of neuroepithelial cells, promotes the enlargement of the neuroepithelial basal end-foot and traps Hh protein, thereby limiting its dispersion. This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. PMID:25001599

Effect of hypobaric hypoxia on the P2X receptors of pyramidal cells in the immature rat hippocampus CA1 sub-field.

PubMed

Zhao, Yan-Dong; Cheng, Sai-Yu; Ou, Shan; Xiao, Zhi; He, Wen-Juan; Jian-Cui; Ruan, Huai-Zhen

2012-01-01

This study was designed to evaluate the effect of hypobaric hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus CA1 pyramidal cells. The functional changes of P2X receptors were investigated through the cell HH model and the expressional alterations of P2X receptors were observed through the animal HH model. P2X receptors mediated currents were recorded from the freshly dissociated CA1 pyramidal cells of 7-day-old SD rats by whole cell patch clamp recording. The expression and distribution of P2X receptors were observed through immunohistochemistry and western blot at HH 3-day and 7-day. In acute HH conditions, the amplitudes of ATP evoked peak currents were decreased compared to control. The immunohistochemistry and western blot results reflected there was no change in P2X receptors expression after 3 days HH injury, while P2X receptors expression was up-regulated in response to 7 days HH injury. These findings supported the possibility that the function of P2X receptors was sensitive to HH damage and long-term function decrease should result in the expression increase of P2X receptors.

Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.

PubMed

Chen, Weitao; Huang, Hai; Hatori, Ryo; Kornberg, Thomas B

2017-09-01

Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous , SCAR , N euroglian and S ynaptobrevin , and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained. © 2017. Published by The Company of Biologists Ltd.

PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail

PubMed Central

Zhang, Jie; Li, Xiang-An; Evers, B. Mark; Zhu, Haining; Jia, Jianhang

2016-01-01

In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an essential component for enriching PI(4)P and facilitating Smo activation. PI(4)P also binds mouse Smo (mSmo) and promotes its phosphorylation and ciliary accumulation. Finally, Hh treatment increases the interaction between Smo and PI(4)P but decreases the interaction between Ptc and PI(4)P, indicating that, in addition to promoting PI(4)P production, Hh regulates the pool of PI(4)P associated with Ptc and Smo. PMID:26863604

Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating Hedgehog signaling

PubMed Central

Shi, Wen; Capurro, Mariana

2011-01-01

Glypican-5 (GPC5) is one of the six members of the glypican family. It has been previously reported that GPC5 stimulates the proliferation of rhabdomyosarcoma cells. In this study, we show that this stimulatory activity of GPC5 is a result of its ability to promote Hedgehog (Hh) signaling. We have previously shown that GPC3, another member of the glypican family, inhibits Hh signaling by competing with Patched 1 (Ptc1) for Hh binding. Furthermore, we showed that GPC3 binds to Hh through its core protein but not to Ptc1. In this paper, we demonstrate that GPC5 increases the binding of Sonic Hh to Ptc1. We also show that GPC5 binds to both Hh and Ptc1 through its glycosaminoglycan chains and that, unlike GPC3, GPC5 localizes to the primary cilia. Interestingly, we found that the heparan sulfate chains of GPC5 display a significantly higher degree of sulfation than those of GPC3. Based on these results, we propose that GPC5 stimulates Hh signaling by facilitating/stabilizing the interaction between Hh and Ptc1. PMID:21339334

Cryobacterium flavum sp. nov. and Cryobacterium luteum sp. nov., isolated from glacier ice.

PubMed

Liu, Qing; Liu, Hongcan; Wen, Ying; Zhou, Yuguang; Xin, Yuhua

2012-06-01

Gram-positive, rod-shaped bacteria, strains Hh8(T), Hh15(T) and Hh40-2, were isolated from the No. 1 glacier in Xinjiang, north-west China. Colonies of strain Hh8(T) were orange-yellow, convex and round on PYG plates. Strain Hh8(T) grew at 0-19 °C and pH 5.5-10.5. Colonies of strain Hh15(T), which was able to grow at 0-20 °C and pH 5.5-12, were lemon yellow, convex and round on PYG plates. Phylogenetic analysis based on 16S rRNA gene sequences showed that these three strains were related to members of the genus Cryobacterium. The major cellular fatty acids of the novel strains were anteiso-C(15:0), iso-C(16:0), iso-C(15:0) and anteiso-C(15:1) A. On the basis of phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness data, two novel species, Cryobacterium flavum sp. nov. (type strain Hh8(T) = CGMCC 1.11215(T) = NBRC 107879(T)) and Cryobacterium luteum sp. nov. (type strain Hh15(T) = CGMCC 1.11210(T) = NBRC 107880(T)), are proposed.

Impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene approach in three cities of Colombia.

PubMed

Barahona-Guzmán, Nayide; Rodríguez-Calderón, María Eugenia; Rosenthal, Victor D; Olarte, Narda; Villamil-Gómez, Wilmer; Rojas, Catherine; Rodríguez-Ferrer, Marena; Sarmiento-Villa, Guillermo; Lagares-Guzmán, Alfredo; Valderrama, Alberto; Menco, Antonio; Arrieta, Patrick; Dajud-Cassas, Luis Enrique; Mendoza, Mariela; Sabogal, Alejandra; Carvajal, Yulieth; Silva, Edwin

2014-02-01

To assess the feasibility and effectiveness of the International Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene (HH) approach in Colombia, and analyze predictors of poor HH compliance. An observational, prospective, interventional, before-and-after study was conducted from May 2003 through September 2010 in 10 intensive care units (ICUs) of six hospitals in three cities. The study was divided into two periods: a baseline and a follow-up period. Observations for HH compliance were done in each ICU during randomly selected 30-min periods. The multidimensional HH approach included: (1) administrative support, (2) supplies availability, (3) education and training, (4) reminders in the workplace, (5) process surveillance, and (6) performance feedback. A total of 13 187 opportunities for HH were observed. Overall HH compliance increased from 50% to 77% (relative risk 1.55, 95% confidence interval 1.43-1.68; p=0.0001). Multivariate and univariate analyses showed that several variables were significantly associated with poor HH compliance: males vs. females (67% vs. 77%; p=0.0001), physicians vs. nurses (59% vs. 78%; p<0.0001), and adult vs. pediatric ICUs (76% vs. 42%; p<0.001), among others. Adherence to HH was increased by 55% with the INICC approach. Programs targeted at improving HH in variables found to be predictors of poor compliance should be implemented. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene approach in 3 cities in Brazil.

PubMed

Medeiros, Eduardo A; Grinberg, Gorki; Rosenthal, Victor D; Bicudo Angelieri, Daniela; Buchner Ferreira, Iselde; Bauer Cechinel, Raquel; Zanandrea, Bruna Boaria; Rohnkohl, Carolina; Regalin, Marcos; Spessatto, Jamile Leda; Scopel Pasini, Ricardo; Ferla, Shaline

2015-01-01

Hand hygiene (HH) is the main tool for cross-infection prevention, but adherence to guidelines is low in limited-resource countries, and there are not available published data from Brazil. This is an observational, prospective, interventional, before-and-after study conducted in 4 intensive care units in 4 hospitals, which are members of the International Nosocomial Infection Control Consortium (INICC), from June 2006-April 2008. The study was divided into a 3-month baseline period and a follow-up period. A multidimensional HH approach was introduced, which included administrative support, supplies availability, education and training, reminders in the workplace, process surveillance, and performance feedback. Health care workers were observed for HH practices in each intensive care unit during randomly selected 30-minute periods. We recorded 4,837 opportunities for HH, with an overall HH compliance that increased from 27%-58% (P < .01). Multivariate analysis showed that some variables were associated with poor HH compliance: men versus women (49% vs 38%, P < .001), nurses versus doctors (55% vs 48%, P < .02), among others. With the implementation of the INICC approach, adherence to HH was significantly increased. Programs should be aimed at improving HH in variables found to be predictors of poor HH compliance. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

It's in Your Hands: An Educational Initiative to Improve Parent/Family Hand Hygiene Compliance.

PubMed

Chandonnet, Celeste J; Boutwell, Kristan M; Spigel, Nadine; Carter, Judith; DeGrazia, Michele; Ozonoff, Al; Flaherty, Kathleen

Health care-associated infections contribute to increased morbidity and mortality, increased resource use, higher costs, and extended hospitalizations. Proper hand hygiene (HH) is essential to health care-associated infection prevention. Low compliance among parents in our neonatal intensive care unit (NICU) was identified and prompted development of an HH initiative. The objective of this quality improvement project was to improve parent HH practices with the ultimate goal of achieving 100% compliance with parent HH. Between December 2011 and November 2014, our NICU Infection Prevention Committee developed and implemented the parent/family HH initiative entitled "It's in Your Hands" and created learning materials based on the World Health Organization and Centers for Disease Control and Prevention recommendations. Materials included information sheets, posters, stickers, and checklists. Audits, based on the World Health Organization's Five Moments for Hand Hygiene, were performed several times per week to monitor compliance. Before the intervention, only 71% (n = 1143) of all observed parents and family members performed proper HH. After the intervention, proper HH increased to 89% (n = 939). An average compliance of 89% was maintained throughout the intervention phase. This initiative led to sustained improvements in HH compliance among NICU parents. It has empowered parents to speak up and request proper HH from health care providers when interacting with their child. This initiative has been adopted as a hospital-wide standard of care.

Hitchhiker: Customer Accommodations and Requirements Specifications (CARS)

NASA Technical Reports Server (NTRS)

1992-01-01

In 1984, NASA Headquarters established projects at the Goddard Space Flight Center (GSFC) and the Marshall Space Flight Center (MSFC) to develop quick-reaction carrier systems for low-cost 'flight of opportunity' or secondary payloads on the Space Transportation System (STS). One of these projects is the Hitchhiker (HH) Program. GSFC has developed a family of carrier equipment known as the Shuttle Payload of Opportunity Carrier (SPOC) system for mounting small payloads such as HH to the side of the Orbiter payload bay. The side-mounted HHs are referred to as Hitchhiker-G (HH-G). MSFC developed a cross-bay 'bridge-type' carrier structure called the Hitchhiker-M (HH-M). In 1987, responsibility for the HH-M carrier was transferred to and is now managed by the HH Project Office at the GSFC. The HH-M carrier now uses the same interchangeable SPOC avionics unit and the same electrical interfaces and services developed for HH-G. National Aeronautics and Space Administration (NASA) has created this document to acquaint potential HH system customers with the facilities NASA provides and the requirements which customers must satisfy to use these facilities. This publication defines interface items required for integrating customer equipment with the HH carrier system. Those items such as mounting equipment and electrical inputs and outputs; configuration, environmental, command, telemetry, and operational constraints are described as well as weight, power, and communications. The purpose of this publication is to help the customer understand essential integration documentation requirements and to prepare a Customer Payload Requirements (CPR) document.

Study on differentiation during embryonic development across selective and ancestral breeds.

PubMed

An, Fengli; Wang, Jianlin

2017-06-01

In order to explore the effect of strain on diverging post-hatch muscle properties, muscle regulation during embryo development was investigated in selected and unselected breeds. Four broiler strains were used: JingNing (JN) chicken (a Chinese native chicken), HuangYu (HY) broiler, BaiYu (BY) broiler and Hyline layer (commercial crossbred chickens). Results showed that the four breeds had almost the same characteristic during different incubation periods. BY broilers moved more than JN and Hyline layers from Hamburger & Hamilton stage (HH)24 to HH31 (P < 0.05). HY broilers moved more than JN and Hyline layers from HH27 to HH31 (P < 0.01). All the embryos were heavier daily from HH24 to ED18 (P < 0.05); broilers presented greater body weights than JN and hyline layers (P > 0.05); broilers presented smaller fiber diameter than JN chickens before HH31 (P > 0.05). From then on, JN chicken exhibited smaller fiber diameter compared to the broilers (P > 0.05). Western blotting indicated all the breeds had continuous insulin-like growth factor-I (IGF-I) expression, with the highest expression level in broilers from HH19 to HH24 and highest expression level in JN chicks from HH27 to HH31. The results indicated that the diverging growth among breeds was already shown in embryonic stages; the different expression patterns of IGF-I may be involved in cell proliferation and differentiation. © 2016 Japanese Society of Animal Science.

The effects of an environmentally relevant 58-congener polychlorinated biphenyl (PCB) mixture on cardiac development in the chick embryo.

PubMed

Carro, Tiffany; Taneyhill, Lisa A; Ann Ottinger, Mary

2013-06-01

Chicken (Gallus domesticus) embryonic exposure in ovo to a 58-congener polychlorinated biphenyl (PCB) mixture resulted in teratogenic heart defects in chick embryos at critical heart developmental stages Hamburger-Hamilton (HH) stages 10, 16, and 20. The 58-congener mixture contained relative proportions of primary congeners measured in belted sandpiper (Megaceryle alcyon) and spotted sandpiper (Actitis macularia) eggs collected along the upper Hudson River, New York, USA, and chicken doses were well below observed environmental exposure levels. Embryos were injected with 0.08 µg PCBs/g egg weight and 0.50 µg PCBs/g egg weight (0.01 and 0.064 ng toxic equivalent/g, respectively) at embryonic day 0, prior to incubation. Mortality of exposed embryos was increased at all developmental stages, with a marked rise in cardiomyopathies at HH16 and HH20 (p < 0.05). Heart abnormalities occurred across all treatments, including abnormal elongation and expansion of the heart tube at HH10, improper looping and orientation, indentations in the emerging ventricular wall (HH16 and HH20), and irregularities in overall heart shape (HH10, HH16, and HH20). Histology was conducted on 2 cardiac proteins critical to embryonic heart development, ventricular myosin heavy chain and titin, to investigate potential mechanistic effects of PCBs on heart development, but no difference was observed in spatiotemporal expression. Similarly, cellular apoptosis in the developing heart was not affected by exposure to the PCB mixture. Conversely, cardiomyocyte proliferation rates dramatically declined (p < 0.01) at HH16 and HH20 as PCB exposure concentrations increased. Early embryonic cardiomyocyte proliferation contributes to proper formation of the morphology and overall thickness of the ventricular wall. Therefore, in ovo exposure to this 58-congener PCB mixture at critical stages adversely affects embryonic heart development. Copyright © 2013 SETAC.

Distinct Effects of the mesenchymal dysplasia Gene Variant of Murine Patched-1 Protein on Canonical and Non-canonical Hedgehog Signaling Pathways*

PubMed Central

Harvey, Malcolm C.; Fleet, Andrew; Okolowsky, Nadia; Hamel, Paul A.

2014-01-01

Hedgehog (Hh) signaling requires regulation of the receptor Patched-1 (Ptch1), which, in turn, regulates Smoothened activity (canonical Hh signaling) as well as other non-canonical signaling pathways. The mutant Ptch1 allele mesenchymal dysplasia (mes), which truncates the Ptch1 C terminus, produces a limited spectrum of developmental defects in mice as well as deregulation of canonical Hh signaling in some, but not all, affected tissues. Paradoxically, mes suppresses canonical Hh signaling and binds to Hh ligands with an affinity similar to wild-type mouse Ptch1 (mPtch1). We characterized the distinct activities of the mes variant of mPtch1 mediating Hh signaling through both canonical and non-canonical pathways. We demonstrated that mPtch1 bound c-src in an Hh-regulated manner. Stimulation with Sonic Hedgehog (Shh) of primary mammary mesenchymal cells from wild-type and mes animals activated Erk1/2. Although Shh activated c-src in wild-type cells, c-src was constitutively activated in mes mesenchymal cells. Transient assays showed that wild-type mPtch1, mes, or mPtch1 lacking the C terminus repressed Hh signaling in Ptch1-deficient mouse embryo fibroblasts and that repression was reversed by Shh, revealing that the C terminus was dispensable for mPtch1-dependent regulation of canonical Hh signaling. In contrast to these transient assays, constitutively high levels of mGli1 but not mPtch1 were present in primary mammary mesenchymal cells from mes mice, whereas the expression of mPtch1 was similarly induced in both mes and wild-type cells. These data define a novel signal transduction pathway involving c-src that is activated by the Hh ligands and reveals the requirement for the C terminus of Ptch in regulation of canonical and non-canonical Hh signaling pathways. PMID:24570001

“The 3/3 Strategy”: A Successful Multifaceted Hospital Wide Hand Hygiene Intervention Based on WHO and Continuous Quality Improvement Methodology

PubMed Central

Mestre, Gabriel; Berbel, Cristina; Tortajada, Purificación; Alarcia, Margarita; Coca, Roser; Gallemi, Gema; Garcia, Irene; Fernández, Mari Mar; Aguilar, Mari Carmen; Martínez, José Antonio; Rodríguez-Baño, Jesús

2012-01-01

Background Only multifaceted hospital wide interventions have been successful in achieving sustained improvements in hand hygiene (HH) compliance. Methodology/Principal Findings Pre-post intervention study of HH performance at baseline (October 2007– December 2009) and during intervention, which included two phases. Phase 1 (2010) included multimodal WHO approach. Phase 2 (2011) added Continuous Quality Improvement (CQI) tools and was based on: a) Increase of alcohol hand rub (AHR) solution placement (from 0.57 dispensers/bed to 1.56); b) Increase in frequency of audits (three days every three weeks: “3/3 strategy”); c) Implementation of a standardized register form of HH corrective actions; d) Statistical Process Control (SPC) as time series analysis methodology through appropriate control charts. During the intervention period we performed 819 scheduled direct observation audits which provided data from 11,714 HH opportunities. The most remarkable findings were: a) significant improvements in HH compliance with respect to baseline (25% mean increase); b) sustained high level (82%) of HH compliance during intervention; c) significant increase in AHRs consumption over time; c) significant decrease in the rate of healthcare-acquired MRSA; d) small but significant improvements in HH compliance when comparing phase 2 to phase 1 [79.5% (95% CI: 78.2–80.7) vs 84.6% (95% CI:83.8–85.4), p<0.05]; e) successful use of control charts to identify significant negative and positive deviations (special causes) related to the HH compliance process over time (“positive”: 90.1% as highest HH compliance coinciding with the “World hygiene day”; and “negative”:73.7% as lowest HH compliance coinciding with a statutory lay-off proceeding). Conclusions/Significance CQI tools may be a key addition to WHO strategy to maintain a good HH performance over time. In addition, SPC has shown to be a powerful methodology to detect special causes in HH performance (positive

Hedgehog signal transduction: key players, oncogenic drivers, and cancer therapy

PubMed Central

Pak, Ekaterina; Segal, Rosalind A.

2016-01-01

Summary The Hedgehog (Hh) signaling pathway governs complex developmental processes, including proliferation and patterning within diverse tissues. These activities rely on a tightly-regulated transduction system that converts graded Hh input signals into specific levels of pathway activity. Uncontrolled activation of Hh signaling drives tumor initiation and maintenance. However, recent entry of pathway-specific inhibitors into the clinic reveals mixed patient responses and thus prompts further exploration of pathway activation and inhibition. In this review, we share emerging insights on regulated and oncogenic Hh signaling, supplemented with updates on the development and use of Hh pathway-targeted therapies. PMID:27554855

The dynamics of histone H2A ubiquitination in HeLa cells exposed to rapamycin, ethanol, hydroxyurea, ER stress, heat shock and DNA damage.

PubMed

Nakata, Shiori; Watanabe, Tadashi; Nakagawa, Koji; Takeda, Hiroshi; Ito, Akihiro; Fujimuro, Masahiro

2016-03-25

Polyubiquitination plays key roles in proteasome-dependent and independent cellular events, whereas monoubiquitination is involved in gene expression, DNA repair, protein-protein interaction, and protein trafficking. We previously developed an FK2 antibody, which specifically recognizes poly-Ub moieties but not free Ub. To elucidate the role of Ub conjugation in response to cellular stress, we used FK2 to investigate whether chemical stress (rapamycin, ethanol, or hydroxyurea), ER stress (thapsigargin or tunicamycin), heat shock or DNA damage (H2O2 or methyl methanesulfonate) affect the formation of Ub conjugates including histone H2A (hH2A) ubiquitination. First, we found that all forms of stress tested increased poly-ubiquitinated proteins in HeLa cells. Furthermore, rapamycin and hydroxyurea treatment, and ER stress increased ubiquitination of hH2A, while methyl methanesulfonate (MMS) treatment induced deubiquitination of hH2A. The ethanol and H2O2 treatments, and heat shock transiently induced hH2A de-ubiquitination, although deubiquitinated hH2A were ubiquitinated again by subsequent cultivation. We also revealed that FK2 reacts with not only polyubiquitinated proteins but also mono-ubiquitinated hH2A. With the exception of MMS, all forms of stress tested increased the acetylation of K5-hH2A, K9-hH3 and K8-hH4 in addition to ubiquitination. K118 and K119 of hH2A were ubiquitinated in cells under normal conditions, and K119 was the major ubiquitination site. The MMS-treatment and heat shock induced the deubiquitination of both K118 and K119-histone H2A. Interestingly, MMS treatment did not affect cell HeLa cell viability expressing double-mutant hH2A (KK118,119AA-hH2A), while heat shock slightly but significantly decreased viability of double-mutant hH2A expressing cells, indicating that ubiquitination of both sites associates with recovery from heat shock but not MMS treatment. Thus, we characterized FK2 reactivity and demonstrated that various stresses alter

Recent Advances in Nanostructured Thermoelectric Half-Heusler Compounds

PubMed Central

Xie, Wenjie; Weidenkaff, Anke; Tang, Xinfeng; Zhang, Qingjie; Poon, Joseph; Tritt, Terry M.

2012-01-01

Half-Heusler (HH) alloys have attracted considerable interest as promising thermoelectric (TE) materials in the temperature range around 700 K and above, which is close to the temperature range of most industrial waste heat sources. The past few years have seen nanostructuing play an important role in significantly enhancing the TE performance of several HH alloys. In this article, we briefly review the recent progress and advances in these HH nanocomposites. We begin by presenting the structure of HH alloys and the different strategies that have been utilized for improving the TE properties of HH alloys. Next, we review the details of HH nanocomposites as obtained by different techniques. Finally, the review closes by highlighting several promising strategies for further research directions in these very promising TE materials. PMID:28348315

Do physicians clean their hands? Insights from a covert observational study.

PubMed

Kovacs-Litman, Adam; Wong, Kimberly; Shojania, Kaveh G; Callery, Sandra; Vearncombe, Mary; Leis, Jerome A

2016-12-01

Physicians are notorious for poor hand hygiene (HH) compliance. We wondered if lower performance by physicians compared with other health professionals might reflect differences in the Hawthorne effect. We introduced covert HH observers to see if performance differences between physicians and nurses decreased and to gain further insights into physician HH behaviors. Following training and validation with a hospital HH auditor, 2 students covertly measured HH during clinical rotations. Students rotated off clinical services every week to increase exposure to different providers and minimize risk of exposing the covert observation. We compared covertly measured HH compliance with data from overt observation by hospital auditors during the same time period. Covert observation produced much lower HH compliance than recorded by hospital auditors during the same time period: 50.0% (799/1597) versus 83.7% (2769/3309) (P < 0.0002). The difference in physician compliance between hospital auditors and covert observers was 19.0% (73.2% vs 54.2%); for nurses this difference was much higher at 40.7% (85.8% vs 45.1%) (P < 0.0001). Physician trainees showed markedly better compliance when attending staff cleaned their hands compared with encounters when attending did not (79.5% vs 18.9%; P < 0.0002). Our study suggests that traditional HH audits not only overstate HH performance overall, but can lead to inaccurate inferences about performance by professional groupings due to relative differences in the Hawthorne effect. We suggest that future improvement efforts will rely on more accurate HH monitoring systems and strong attending physician leadership to set an example for trainees. Journal of Hospital Medicine 2015;11:862-864. © 2015 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.

Barium swallow for hiatal hernia detection is unnecessary prior to primary sleeve gastrectomy.

PubMed

Goitein, David; Sakran, Nasser; Rayman, Shlomi; Szold, Amir; Goitein, Orly; Raziel, Asnat

2017-02-01

Hiatal hernia (HH) is common in the bariatric population. Its presence imposes various degrees of difficulty in performing laparoscopic sleeve gastrectomy (LSG). Preoperative upper gastrointestinal evaluation consists of fluoroscopic and or endoscopic studies OBJECTIVES: To evaluate the efficacy of routine, preoperative barium swallow in identifying HH in patients undergoing LSG, and determine if such foreknowledge changes operative and immediate postoperative course regarding operative time, intraoperative adverse events, and length of hospital stay (LOS). In addition, to quantify HH prevalence in these patients and correlate preoperative patient characteristics with its presence. High-volume bariatric practice in a private hospital in Israel METHODS: Retrospective analysis of prospectively collected data between October 2010 and March 2015: anthropometrics, co-morbidities, previous barium swallow, preoperative HH workup (type and result), operative and immediate postoperative course. Primary LSG was performed in 2417 patients. The overall prevalence of HH was 7.3%. Preoperative diagnosis of gastroesophageal reflux disease and female gender were independent risk factors for HH presence. Operative times were significantly longer when HH was concomitantly repaired but "foreknowledge" thereof did not assist in shortening this time. Looking for an HH that was suggested in preoperative upper gastrointestinal evaluation slightly prolonged surgery. LOS was not changed in a significant fashion by HH presence and repair, whether suspected or incidentally found. Routine, pre-LSG barium swallow does not seem to offer an advantage over selective intraoperative hiatal exploration, in the discovery and management of HH. Conversely, when preoperative workup yields a false-positive result, surgery is slightly prolonged. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

An Overview of Food Patterns and Diet Quality in Qatar: Findings from the National Household Income Expenditure Survey.

PubMed

Al-Thani, Mohammed; Al-Thani, Al-Anoud; Al-Mahdi, Nasser; Al-Kareem, Hefzi; Barakat, Darine; Al-Chetachi, Walaa; Tawfik, Afaf; Akram, Hammad

2017-05-15

Availability of accurate data pertaining to a population's dietary patterns and associated health outcomes is critical for proper development and implementation of related policies. This article is a first attempt to share the food patterns, amounts and diet quality among households (HH) in Qatar. Data from the 2012-2013 Qatar National Household Income and Expenditure Survey (HIES) was used. This cross-sectional survey included 3723 HH (1826 Qatari HH and 1897 non-Qatari HH). Dietary data on monthly amounts food items available at HH according to the nationality was used. The food items were expressed in terms of grams per capita per day and aggregated into groups to examine the food patterns, energy, and adequacy. The overall average amount of purchased food at HH in Qatar was 1885 g/capita/day. Qatari HH purchased more food (2118 g/capita/day) versus non-Qataris (1373 g/capita/day); however, the percentages of the amounts purchased by food types were similar among both nationalities. Average daily energy (kcal) per capita was almost double among Qatari HH (4275 kcal) vs. non-Qatari HH (2424 kcal). The food items under subsidy program for Qatari citizens provided 1753 kcal/capita/day and accounted for 41% of total daily energy. Proteins (29.2), fats (39.2), sodium (3.3), and vitamin C (32.5) had higher than recommended levels of nutrient density (grams per 1000 kcal). Calcium (227), vitamin A (302.3), fiber (2.0), and carbohydrates (132.6) had lower than recommended levels of nutrient energy density (g/1000 kcal). The study predicts unhealthy dietary habits among HH in Qatar and provides useful information for policy makers and healthcare community.

Low-dose gonadotropin induction of ovulation in anovulatory women - still needed in the age of IVF.

PubMed

White, Davinia; Hardy, Kate; Lovelock, Suzannah; Franks, Stephen

2018-02-19

Low-dose, step-up gonadotropin is the treatment of choice for women with PCOS who have not conceived after anti-estrogen treatment, and as an effective alternative to pulsatile GnRH in women with hypogonadotropic hypogonadism (HH). There has been, however, no large-scale, comparative study between the two groups using low-dose gonadotropins. Here we performed a retrospective, comparative analysis, in a single clinic database, of efficacy and safety of induction of ovulation using low-dose gonadotropins in 364 Women with PCOS and 80 women with HH. The rate of ovulation was high in both PCOS (83%) and HH (84%) but mono-follicular, ovulatory cycles were more prevalent in PCOS than in HH (77% vs 53%, p<0.0001) and the proportion of cycles that were abandoned was higher in HH than in PCOS (25% vs 15%, p<0.0001). The median threshold dose of gonadotropin required to induce ovulation was 75iu/day in PCOS and 113iu/day in HH (p<0.001) and the range of doses was greater in HH women. Forty-nine percent of women with PCOS and 65% of those with HH conceived (more than 90% within 6 cycles of treatment) and had a least one pregnancy. Multiple pregnancies (all twins) occurred in only 4% of women with PCOS and 5% of those with HH. These findings emphasise the efficacy and safety of low-dose gonadotropin treatment for both clomiphene-resistant women with PCOS and those with HH. These results highlight the importance of choosing the more physiological approach of gonadotropin induction of ovulation in both groups as the most appropriate treatment, in preference to IVF.

Subpart HH Training Presentations

EPA Pesticide Factsheets

EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach in five intensive care units in three cities of China.

PubMed

Su, D; Hu, B; Rosenthal, V D; Li, R; Hao, C; Pan, W; Tao, L; Gao, X; Liu, K

2015-07-01

To evaluate the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene (HH) Approach in three hospitals in three cities of China, and analyze predictors of poor hand hygiene compliance. A prospective before-after study from May 2009 to December 2010 in five intensive care units members of the INICC in China. The study was divided into two periods: a 3-month baseline period and a follow-up period. A Multidimensional HH Approach was implemented, which included the following elements: 1- administrative support, 2- supplies availability, 3- education and training, 4- reminders in the workplace, 5- process surveillance and 6- performance feedback. Observations were done for HH compliance in each ICU, during randomly selected 30-min periods. A total of 2079 opportunities for HH were recorded. Overall HH compliance increased from 51.5% to 80.1% (95% CI 73.2-87.8; P = 0.004). Multivariate analysis indicated that several variables were significantly associated with poor HH compliance: females vs males (64% vs 55%; 95% CI 0.81-0.94; P = 0.0005), nurses vs physicians (64% vs 57%, P = 0.004), among others. Adherence to HH was increased significantly with the INICC multidimensional approach. Specific programs directed to improve HH in variables found to be predictors of poor HH compliance should be implemented. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Impact of implementation of the World Health Organization multimodal hand hygiene improvement strategy in a teaching hospital in Taiwan.

PubMed

Chen, Jui-Kuang; Wu, Kuan-Sheng; Lee, Susan Shin-Jung; Lin, Huey-Shyan; Tsai, Hung-Chin; Li, Ching-Hsien; Chao, Hsueh-Lan; Chou, Hsueh-Chih; Chen, Yueh-Ju; Huang, Yu-Hsiu; Ke, Chin-Mei; Sy, Cheng Len; Tseng, Yu-Ting; Chen, Yao-Shen

2016-02-01

Hand hygiene (HH) is considered to be the most simple, rapid, and economic way to prevent health care-associated infection (HAI). However, poor HH compliance has been repeatedly reported. Our objective was to evaluate the impact of implementing the updated World Health Organization (WHO) multimodal HH guidelines on HH compliance and HAI in a tertiary hospital in Taiwan. We conducted a before-and-after interventional study during 2010-2011. A multimodal HH promotion campaign was initiated. Key strategies included providing alcohol-based handrub dispensers at points of care, designing educational programs tailored to the needs of different health care workers, placement of general and individual reminders in the workplace, and establishment of evaluation and feedback for HH compliance and infection rates. Overall HH compliance increased from 62.3% to 73.3% after 1 year of intervention (P < .001). The rate of overall HAI decreased from 3.7% to 3.1% (P < .05), urinary tract infection rate decreased from 1.5% to 1.2% (P < .05), and respiratory tract infection rate decreased from 0.53% to 0.35% (P < .05). This campaign saved an estimated $940,000 and 3,564 admission patient days per year. The WHO multimodal HH guidelines are feasible and effective for the promotion of HH compliance and are associated with the reduction of HAIs. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors.

PubMed

Didiasova, Miroslava; Singh, Rajeev; Wilhelm, Jochen; Kwapiszewska, Grazyna; Wujak, Lukasz; Zakrzewicz, Dariusz; Schaefer, Liliana; Markart, Philipp; Seeger, Werner; Lauth, Matthias; Wygrecka, Malgorzata

2017-05-01

Pirfenidone is an antifibrotic drug, recently approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Although pirfenidone exhibits anti-inflammatory, antioxidant, and antifibrotic properties, the molecular mechanism underlying its protective effects remains unknown. Here, we link pirfenidone action with the regulation of the profibrotic hedgehog (Hh) signaling pathway. We demonstrate that pirfenidone selectively destabilizes the glioma-associated oncogene homolog (GLI)2 protein, the primary activator of Hh-mediated gene transcription. Consequently, pirfenidone decreases overall Hh pathway activity in patients with IPF and in patient-derived primary lung fibroblasts and leads to diminished levels of Hh target genes, such as GLI1, Hh receptor Patched-1, α-smooth muscle actin, and fibronectin, and to reduced cell migration and proliferation. Interestingly, Hh-triggered TGF-β1 expression potentiated Hh responsiveness of primary lung fibroblasts by elevating the available pool of glioma-associated oncogene homolog (GLI)1/GLI2, thus creating a vicious cycle of amplifying fibrotic processes. Because GLI transcription factors are not only crucial for Hh-mediated changes but are also required as mediators of TGF-β signaling, our findings suggest that pirfenidone exerts its clinically beneficial effects through dual Hh/TGF-β inhibition by targeting the GLI2 protein.-Didiasova, M., Singh, R., Wilhelm, J., Kwapiszewska, G., Wujak, L., Zakrzewicz, D., Schaefer, L., Markart, P., Seeger, W., Lauth, M., Wygrecka, M. Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors. © FASEB.

Hand hygiene compliance in patients under contact precautions and in the general hospital population.

PubMed

Almaguer-Leyva, Martín; Mendoza-Flores, Lidia; Medina-Torres, Ana Gabriela; Salinas-Caballero, Ana Gabriela; Vidaña-Amaro, Jose Antonio; Garza-Gonzalez, Elvira; Camacho-Ortiz, Adrián

2013-11-01

Hand hygiene (HH) is the single most important intervention for preventing hospital-acquired infections. Contact precautions are a series of actions that infection control units take to reduce the transmission of nosocomial pathogens. We conducted an observational study of HH compliance. Observations were stratified as opportunities in patients under contact precautions and in the general hospital population. Trained infection control personnel performed all direct evaluations. A total of 3,270 opportunities were recorded. HH compliance was statistically higher in patients on contact precautions than in the overall population (70.3% vs 60.4%; P = .0001). Critical care areas had higher HH compliance when patients were isolated by contact precautions. Medical wards were statistically lower in HH when patients were under contact precautions. Respiratory technicians had the highest HH compliance in both overall performance and in patients under contact precautions. Medical students had a lower HH compliance in both evaluations (P < .001). We noted greater compliance with HH practices when patients were under contact precaution in comparison with the overall hospital population. The difference was stronger in intensive care areas and lower among medical students. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Upper limb joint kinetics of three sitting pivot wheelchair transfer techniques in individuals with spinal cord injury.

PubMed

Kankipati, Padmaja; Boninger, Michael L; Gagnon, Dany; Cooper, Rory A; Koontz, Alicia M

2015-07-01

Repeated measures design. This study compared the upper extremity (UE) joint kinetics between three transfer techniques. Research laboratory. Twenty individuals with spinal cord injury performed three transfer techniques from their wheelchair to a level tub bench. Two of the techniques involved a head-hips method with leading hand position close (HH-I) and far (HH-A) from the body, and the third technique with the trunk upright (TU) and hand far from body. Motion analysis equipment recorded upper body movements and force sensors recorded their hand and feet reaction forces during the transfers. Several significant differences were found between HH-A and HH-I and TU and HH-I transfers indicating that hand placement was a key factor influencing the UE joint kinetics. Peak resultant hand, elbow, and shoulder joint forces were significantly higher for the HH-A and TU techniques at the trailing arm (P < 0.036) and lower at the leading arm (P < 0.021), compared to the HH-I technique. Always trailing with the same arm if using HH-A or TU could predispose that arm to overuse related pain and injuries. Technique training should focus on initial hand placement close to the body followed by the amount of trunk flexion needed to facilitate movement.

A national survey of hemochromatosis patients.

PubMed

Mainous, Arch G; Knoll, Michele E; Everett, Charles J; Hulihan, Mary M; Grant, Althea M; Garrison, Cheryl; Koenig, Gerald; Sayers, Cynthia; Allen, Kelsey W

2012-01-01

Hereditary hemochromatosis (HH) is a common genetic disease in the United States, but little is known about the diagnosis from the patient's perspective. The purpose of this study was to characterize the circumstances surrounding the diagnosis of HH and assess treatments and health information needs. We surveyed US adults aged 18 years and older who were diagnosed with HH after 1996. Response rate was 46%, with a total sample size of 979. Respondents were asked about the use of genetic and clinical markers in their diagnosis, current treatments, and health information needs. Results were stratified by age, education, and income status. Total of 90.0% of women and 75.5% of men were genetically tested for HH (P < .01). Approximately half (52.5%) were diagnosed by a gastroenterologist, hematologist, or other specialty physician and half were diagnosed by a primary care provider. Most of the respondents thought their HH had improved with the initial treatment and most patients were still receiving treatment for HH. Patient interest in learning more about specific hemochromatosis topics was generally high. Since the introduction of genetic identification of HH, these tests have been used in the diagnosis of the majority of patients. Primary care physicians may need to be more aware HH and strategies for diagnosis.

The simultaneous use of a heat and moisture exchanger and a heated humidifier causes critical airway occlusion in less than 24 hours.

PubMed

Doyle, Alexander; Mariyaselvam, Maryanne; Wijewardena, Gayathri; English, Natalie; Gent, Emma; Young, Peter

2015-08-01

Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) may be used together inadvertently. Such an incident occurred at our institution resulting in airway occlusion. A bench-top study was conducted to compare the incidence of airway occlusion when using (1) no airway humidification, (2) HME alone, (3) HH alone, and (4) both HME and HH in combination as part of a standard breathing circuit. The simultaneous use of a HME and a HH was associated with a reduction in tidal volume (no airway humidification, P ≤ .05; HME alone, P ≤ .01; and HH alone, P ≤ .01) and an increased incidence of airway occlusion (no airway humidification, 0/7; HME alone, 0/7; HH alone, 0/7; and HME and HH in combination, 7/7; P < .0001). The use of a HME and a HH in combination is likely to result in airway occlusion. Precautions should be taken to ensure that both systems are not used together in clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Training infection control and hospital hygiene professionals in Europe, 2010: agreed core competencies among 33 European countries.

PubMed

Brusaferro, S; Cookson, B; Kalenic, S; Cooper, T; Fabry, J; Gallagher, R; Hartemann, P; Mannerquist, K; Popp, W; Privitera, G; Ruef, C; Viale, P; Coiz, F; Fabbro, E; Suetens, C; Varela Santos, C

2014-12-11

The harmonisation of training programmes for infection control and hospital hygiene (IC/HH) professionals in Europe is a requirement of the Council recommendation on patient safety. The European Centre for Disease Prevention and Control commissioned the 'Training Infection Control in Europe' project to develop a consensus on core competencies for IC/HH professionals in the European Union (EU). Core competencies were drafted on the basis of the Improving Patient Safety in Europe (IPSE) project's core curriculum (CC), evaluated by questionnaire and approved by National Representatives (NRs) for IC/HH training. NRs also re-assessed the status of IC/HH training in European countries in 2010 in comparison with the situation before the IPSE CC in 2006. The IPSE CC had been used to develop or update 28 of 51 IC/HH courses. Only 10 of 33 countries offered training and qualification for IC/HH doctors and nurses. The proposed core competencies are structured in four areas and 16 professional tasks at junior and senior level. They form a reference for standardisation of IC/HH professional competencies and support recognition of training initiatives.

An investigation of age and yield of fresh fruit bunches of oil palm based on ALOS PALSAR 2

NASA Astrophysics Data System (ADS)

Darmawan, S.; Takeuchi, W.; Haryati, A.; M, R. Najib A.; Na'aim, M.

2016-06-01

The objective on this study is to investigate age and yield of FFB of oil palms based on ALOS PALSAR 2. Study areas in oil palm plantations areas of Jerantut, Pahang Malaysia. Methodology consists collecting of ALOS PALSAR 2 and tabular data on the study area, processing of ALOS PALSAR 2 including of converting digital numbers to normalize radar cross sections (NRCS), topography correction and filtering, making of regions of interest according to areas of age and yield of FFB of oil palms and making of relationship analysis between backscatter value of HH, HV and age and yield of FFB of oil palm. The results have showed relationship between HH, HV and age of oil palm which R2 of 0.63 for HH and 0.42 for HV that indicated increasing of age of oil palm as increasing of HH and HV value. Also relationship between HH, HV and yield of FFB of oil palm which R2 of 0.26 for HH and 0.15 for HV, that indicated increasing of yield of FFB as decreasing of HH and HV value.

Hedgehog Signaling in Prostate Cancer and Its Therapeutic Implication

PubMed Central

Gonnissen, Annelies; Isebaert, Sofie; Haustermans, Karin

2013-01-01

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition. PMID:23880852

The effect of random voice hand hygiene messages delivered by medical, nursing, and infection control staff on hand hygiene compliance in intensive care.

PubMed

McGuckin, Maryanne; Shubin, Arlene; McBride, Patricia; Lane, Stephen; Strauss, Kevin; Butler, Donna; Pitman, Andrew

2006-12-01

Hand hygiene (HH) compliance in the intensive care unit has been studied extensively, with short-term, nonsustained compliance often because of lack of ongoing reinforcement. HH messages delivered by health care workers responsible for overseeing staff in the intensive care unit provided continuous reinforcement of HH. Compliance measured through product usage and reported as HH/bed-days increased by 60% for soap and sanitizer combined and 25% for sanitizer usage (P < 001).

Swallow-induced esophageal shortening in patients without hiatal hernia is associated with gastroesophageal reflux.

PubMed

Masuda, T; Singhal, S; Akimoto, S; Bremner, R M; Mittal, S K

2018-05-01

Longitudinal esophageal body shortening with swallow-induced peristalsis has been reported in healthy individuals. Esophageal shortening is immediately followed by esophageal re-elongation, and the lower esophageal sphincter (LES) returns to the baseline position. High-resolution manometry (HRM) allows for objective assessment of extent of shortening and duration of shortening. In patients without hiatal hernia at rest, swallow-induced esophageal shortening can lead to transient hiatal hernia (tHH) which at times may persist after the completion of swallow. This manometric finding has not been investigated in the literature, but a question arises whether this swallow-induced transient herniation can effect on the likelihood of gastroesophageal reflux. This study aims to assess the relationship between gastroesophageal reflux and the subtypes of swallow-induced esophageal shortening, i.e. tHH and non-tHH, in patients without hiatal hernia at rest. After Institutional Review Board (IRB) approval, we queried a prospectively maintained database to identify patients who underwent HRM evaluation and 24-hour pH study between January to December 2015. Patients with type-I esophagogastric junction (EGJ) morphology (i.e. no hiatal hernia) according to the Chicago classification v3.0 were included. The patterns of the esophageal shortening with swallows were divided into two subtypes, i.e. tHH and non-tHH. tHH was defined as an EGJ double high-pressure zones (≥1 cm) at the second inspiration after the termination of swallow-induced esophageal body contraction. The number of episodes of tHH was counted per 10 swallows and tHH size was measured for each patient. In total, 41 patients with EGJ morphology Type-I met the inclusion criteria. The mean age was 47.2 years, 35 patients (85.4%) were women, and the mean body mass index was 33.9 kg/m2. The mean number of tHH episodes was 3 out of 10 swallows; mean maximal tHH size was 1.3 cm. Patients who had tHH in ≥3 out of 10

40 CFR Table Hh-3 to Subpart Hh of... - Landfill Gas Collection Efficiencies

Code of Federal Regulations, 2011 CFR

2011-07-01

...: Area with daily soil cover and active gas collection CE3: 60%. A4: Area with an intermediate soil cover, or a final soil cover not meeting the criteria for A5 below, and active gas collection CE4: 75%. A5: Area with a final soil cover of 3 feet or thicker of clay and/or geomembrane cover system and active...

40 CFR Table Hh-3 to Subpart Hh of... - Landfill Gas Collection Efficiencies

Code of Federal Regulations, 2013 CFR

2013-07-01

...: Area with daily soil cover and active gas collection CE3: 60%. A4: Area with an intermediate soil cover, or a final soil cover not meeting the criteria for A5 below, and active gas collection CE4: 75%. A5: Area with a final soil cover of 3 feet or thicker of clay and/or geomembrane cover system and active...

40 CFR Table Hh-3 to Subpart Hh of... - Landfill Gas Collection Efficiencies

Code of Federal Regulations, 2014 CFR

2014-07-01

...: Area with daily soil cover and active gas collection CE3: 60%. A4: Area with an intermediate soil cover, or a final soil cover not meeting the criteria for A5 below, and active gas collection CE4: 75%. A5: Area with a final soil cover of 3 feet or thicker of clay and/or geomembrane cover system and active...

40 CFR Table Hh-3 to Subpart Hh of... - Landfill Gas Collection Efficiencies

Code of Federal Regulations, 2012 CFR

2012-07-01

...: Area with daily soil cover and active gas collection CE3: 60%. A4: Area with an intermediate soil cover, or a final soil cover not meeting the criteria for A5 below, and active gas collection CE4: 75%. A5: Area with a final soil cover of 3 feet or thicker of clay and/or geomembrane cover system and active...

40 CFR Table Hh-4 to Subpart Hh of... - Landfill Methane Oxidation Fractions

Code of Federal Regulations, 2014 CFR

2014-07-01

... gas sent off-site). If a single monitoring location is used to monitor volumetric flow and CH4... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Landfill Methane Oxidation Fractions... (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Municipal Solid Waste Landfills Pt...

Occupational Safety and Health and Healthy Housing: A Review of Opportunities and Challenges.

PubMed

Jacobs, David E; Forst, Linda

Occupational safety and health (OSH) risks in construction of healthy housing (HH) have not been examined and collaboration between HH and OSH professionals is inadequate. The World Health Organization is developing international HH guidelines and the International Labour Organization is working to improve OSH in construction globally. We searched for exemplary reports (including gray literature) on construction hazards; preventive measures for occupants and workers; OSH frameworks, laws, and regulations; definitions; and HH. Healthy housing construction typically improves ventilation, moisture and mold, pest control, injury hazards, cleanability, maintenance, accessibility, thermal conditioning, and avoidance of toxic building materials. To date, this work is done without explicit requirements for worker health. Construction is among the most hazardous sectors around the globe, although protective measures are well known, including engineering and administrative controls and provision of personal protective equipment. Residential construction, renovation, repair, and maintenance are fragmented, consisting mostly of small companies without proper OSH training, equipment, and knowledge of HH principles. Residential construction is often undertaken by informal or unauthorized workers, putting them at high risk. Reduced exposure to toxic building materials is an example of a benefit for both workers and occupants if OSH and HH collaboration can be improved. By recognizing that homes under new construction or renovation are both a workplace and a residence, HH and OSH initiatives can apply public health principles to occupants and workers simultaneously. This article publishes key definitions, hazards and interventions common to both fields. A global increase in residential construction and renewed global interest in HH poses both risks and opportunities for primary prevention. Policy and practice interventions can benefit the health of occupants and those who work on

The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD.

PubMed

Beaumont, Hanneke; Bennink, Roelof J; de Jong, Jan; Boeckxstaens, Guy E

2010-04-01

Gastro-oesophageal reflux occurs twice as much during transient lower oesophageal sphincter relaxations (TLOSRs) in patients with gastro-oesophageal reflux disease (GORD) compared to healthy volunteers (HVs). Our aim was to assess whether the localisation of the postprandial acid pocket and its interaction with a hiatal hernia (HH) play a role in the occurrence of acidic reflux during TLOSRs. Ten HVs and 22 patients with GORD (12 with HH<3 cm (s-HH), 10 with HH > or =3 cm (l-HH)) were studied. The squamocolumnar junction and diaphragmatic impression were marked with a radioactively labelled clip. To visualise the acid pocket, (99m)Tc-pertechnetate was injected intravenously and images were acquired up to 2 h postprandial. Concurrently, combined manometry/impedance and four-channel pH-metry were performed, with pH pull-through at multiple time-points. The rate of TLOSRs and the per cent associated with reflux was comparable between all groups. However, acidic reflux was significantly increased in patients, especially in patients with l-HH. Acid pocket length was significantly enlarged in patients. Moreover, immediately before a TLOSR, the acid pocket was more frequently located within the hiatus or above the diaphragm in patients with GORD (s-HH, 54%; l-HH, 77%) compared to HVs (22% of TLOSRs). Acidic reflux was significantly increased when the acid pocket was located above the diaphragm in all groups compared to a sub-diaphragmatic localisation. The position of the acid pocket is largely determined by the presence of a HH. Entrapment of the pocket above the diaphragm, especially in patients with l-HH, is a major risk factor underlying the increased occurrence of acidic reflux during a TLOSR in patients with GORD.

An Overview of Food Patterns and Diet Quality in Qatar: Findings from the National Household Income Expenditure Survey

PubMed Central

Al-Thani, Mohammed; Al-Thani, Al-Anoud; Al-Mahdi, Nasser; Al-Kareem, Hefzi; Barakat, Darine; Al-Chetachi, Walaa; Tawfik, Afaf

2017-01-01

Introduction Availability of accurate data pertaining to a population’s dietary patterns and associated health outcomes is critical for proper development and implementation of related policies. This article is a first attempt to share the food patterns, amounts and diet quality among households (HH) in Qatar. Methods Data from the 2012-2013 Qatar National Household Income and Expenditure Survey (HIES) was used. This cross-sectional survey included 3723 HH (1826 Qatari HH and 1897 non-Qatari HH). Dietary data on monthly amounts food items available at HH according to the nationality was used. The food items were expressed in terms of grams per capita per day and aggregated into groups to examine the food patterns, energy, and adequacy. Results The overall average amount of purchased food at HH in Qatar was 1885 g/capita/day. Qatari HH purchased more food (2118 g/capita/day) versus non-Qataris (1373 g/capita/day); however, the percentages of the amounts purchased by food types were similar among both nationalities. Average daily energy (kcal) per capita was almost double among Qatari HH (4275 kcal) vs. non-Qatari HH (2424 kcal). The food items under subsidy program for Qatari citizens provided 1753 kcal/capita/day and accounted for 41% of total daily energy. Proteins (29.2), fats (39.2), sodium (3.3), and vitamin C (32.5) had higher than recommended levels of nutrient density (grams per 1000 kcal). Calcium (227), vitamin A (302.3), fiber (2.0), and carbohydrates (132.6) had lower than recommended levels of nutrient energy density (g/1000 kcal). Conclusions The study predicts unhealthy dietary habits among HH in Qatar and provides useful information for policy makers and healthcare community. PMID:28630807

The Extracellular Loop 2 (ECL2) of the Human Histamine H4 Receptor Substantially Contributes to Ligand Binding and Constitutive Activity

PubMed Central

Wifling, David; Bernhardt, Günther; Dove, Stefan; Buschauer, Armin

2015-01-01

In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R) shows extraordinarily high constitutive activity. In the extracellular loop (ECL), replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R. PMID:25629160

Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load.

PubMed

Carroll, G J; Breidahl, W H; Bulsara, M K; Olynyk, J K

2011-01-01

To determine the frequency and character of arthropathy in hereditary hemochromatosis (HH) and to investigate the relationship between this arthropathy, nodal interphalangeal osteoarthritis, and iron load. Participants were recruited from the community by newspaper advertisement and assigned to diagnostic confidence categories for HH (definite/probable or possible/unlikely). Arthropathy was determined by use of a predetermined clinical protocol, radiographs of the hands of all participants, and radiographs of other joints in which clinical criteria were met. An arthropathy considered typical for HH, involving metacarpophalangeal joints 2-5 and bilateral specified large joints, was observed in 10 of 41 patients with definite or probable HH (24%), all of whom were homozygous for the C282Y mutation in the HFE gene, while only 2 of 62 patients with possible/unlikely HH had such an arthropathy (P=0.0024). Arthropathy in definite/probable HH was more common with increasing age and was associated with ferritin concentrations>1,000 μg/liter at the time of diagnosis (odds ratio 14.0 [95% confidence interval 1.30-150.89], P=0.03). A trend toward more episodes requiring phlebotomy was also observed among those with arthropathy, but this was not statistically significant (odds ratio 1.03 [95% confidence interval 0.99-1.06], P=0.097). There was no significant association between arthropathy in definite/probable HH and a history of intensive physical labor (P=0.12). An arthropathy consistent with that commonly attributed to HH was found to occur in 24% of patients with definite/probable HH. The association observed between this arthropathy, homozygosity for C282Y, and serum ferritin concentrations at the time of diagnosis suggests that iron load is likely to be a major determinant of arthropathy in HH and to be more important than occupational factors. Copyright © 2011 by the American College of Rheumatology.

[HAND HYGIENE BELIEFS AND PERCEPTIONS OF NURSING STUDENTS].

PubMed

Hernández-García, Ignacio; Cardoso-Muñoz, Antonio Manuel

2016-05-01

A key element to promote the compliance of hand hygiene (HH) among health care workers (HCWs) is to analyze their perceptions of it. Our objective was to evaluate the beliefs and perceptions that nursing students have on HH. A cross-sectional study was performed during the 2011-2012 school year. It included all enrolled nursing students from a Spanish University. The information was obtained by a self-administered questionnaire, which assessed the importance of HH to control nosocomial infections (NI), beliefs (by Hand Hygiene Beliefs Scale-HHBS) and perceptions of the importance given to HH in the curriculum (by Hand Hygiene Importance Scale-HHIS). Associations were analyzed using logistic regression. 146 students of the 270 (54.1%) completed the questionnaire. Assessing the importance of HH as NI control measure ranged from 4 to 10 points (median = 9). The more agreement HHIS item was to consider HH as an important part of the curriculum (76.1%), while HHBS item was to believe that hands washing after going to the toilet reduces the transmission of infectious diseases (100%). Importance of HH to control NI valued with > 9 points was associated with the agreement to consider it as an relevant part of the curriculum (OR:2.5), and to believe that HCWs play an important role in preventing NI (OR: 4.3). HH was rated as an important NI control measure. Educational programs should be carried out at universities to students do HH, whether they observe poor compliance among HCWs in their practices.

Driving with hemianopia: IV. Head scanning and detection at intersections in a simulator.

PubMed

Bowers, Alex R; Ananyev, Egor; Mandel, Aaron J; Goldstein, Robert B; Peli, Eli

2014-03-13

Using a driving simulator, we examined the effects of homonymous hemianopia (HH) on head scanning behaviors at intersections and evaluated the role of inadequate head scanning in detection failures. Fourteen people with complete HH and without cognitive decline or visual neglect and 12 normally sighted (NV) current drivers participated. They drove in an urban environment following predetermined routes, which included multiple intersections. Head scanning behaviors were quantified at T-intersections (n = 32) with a stop or yield sign. Participants also performed a pedestrian detection task. The relationship between head scanning and detection was examined at 10 intersections. For HH drivers, the first scan was more likely to be toward the blind than the seeing hemifield. They also made a greater proportion of head scans overall to the blind side than did the NV drivers to the corresponding side (P = 0.003). However, head scan magnitudes of HH drivers were smaller than those of the NV group (P < 0.001). Drivers with HH had impaired detection of blind-side pedestrians due either to not scanning in the direction of the pedestrian or to an insufficient scan magnitude (left HH detected only 46% and right HH 8% at the extreme left and right of the intersection, respectively). Drivers with HH demonstrated compensatory head scan patterns, but not scan magnitudes. Inadequate scanning resulted in blind-side detection failures, which might place HH drivers at increased risk for collisions at intersections. Scanning training tailored to specific problem areas identified in this study might be beneficial.

Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia

PubMed Central

Irvine, David A.; Zhang, Bin; Kinstrie, Ross; Tarafdar, Anuradha; Morrison, Heather; Campbell, Victoria L.; Moka, Hothri A.; Ho, Yinwei; Nixon, Colin; Manley, Paul W.; Wheadon, Helen; Goodlad, John R.; Holyoake, Tessa L.; Bhatia, Ravi; Copland, Mhairi

2016-01-01

Targeting the Hedgehog (Hh) pathway represents a potential leukaemia stem cell (LSC)-directed therapy which may compliment tyrosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic myeloid leukaemia (CML). We set out to elucidate the role of Hh signaling in CP-CML and determine if inhibition of Hh signaling, through inhibition of smoothened (SMO), was an effective strategy to target CP-CML LSC. Assessment of Hh pathway gene and protein expression demonstrated that the Hh pathway is activated in CD34+ CP-CML stem/progenitor cells. LDE225 (Sonidegib), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with nilotinib, inhibited the Hh pathway in CD34+ CP-CML cells, reducing the number and self-renewal capacity of CML LSC in vitro. The combination had no effect on normal haemopoietic stem cells. When combined, LDE225 + nilotinib reduced CD34+ CP-CML cell engraftment in NSG mice and, upon administration to EGFP+ /SCLtTA/TRE-BCR-ABL mice, the combination enhanced survival with reduced leukaemia development in secondary transplant recipients. In conclusion, the Hh pathway is deregulated in CML stem and progenitor cells. We identify Hh pathway inhibition, in combination with nilotinib, as a potentially effective therapeutic strategy to improve responses in CP-CML by targeting both stem and progenitor cells. PMID:27157927

Upper limb joint kinetics of three sitting pivot wheelchair transfer techniques in individuals with spinal cord injury

PubMed Central

Kankipati, Padmaja; Boninger, Michael L.; Gagnon, Dany; Cooper, Rory A.; Koontz, Alicia M.

2015-01-01

Study design Repeated measures design. Objective This study compared the upper extremity (UE) joint kinetics between three transfer techniques. Setting Research laboratory. Methods Twenty individuals with spinal cord injury performed three transfer techniques from their wheelchair to a level tub bench. Two of the techniques involved a head–hips method with leading hand position close (HH-I) and far (HH-A) from the body, and the third technique with the trunk upright (TU) and hand far from body. Motion analysis equipment recorded upper body movements and force sensors recorded their hand and feet reaction forces during the transfers. Results Several significant differences were found between HH-A and HH-I and TU and HH-I transfers indicating that hand placement was a key factor influencing the UE joint kinetics. Peak resultant hand, elbow, and shoulder joint forces were significantly higher for the HH-A and TU techniques at the trailing arm (P < 0.036) and lower at the leading arm (P < 0.021), compared to the HH-I technique. Conclusion Always trailing with the same arm if using HH-A or TU could predispose that arm to overuse related pain and injuries. Technique training should focus on initial hand placement close to the body followed by the amount of trunk flexion needed to facilitate movement. PMID:25130053

Anosmia predicts hypogonadotropic hypogonadism in CHARGE syndrome.

PubMed

Bergman, Jorieke E H; Bocca, Gianni; Hoefsloot, Lies H; Meiners, Linda C; van Ravenswaaij-Arts, Conny M A

2011-03-01

To test the hypothesis that a smell test could predict the occurrence of hypogonadotropic hypogonadism (HH) in patients with CHARGE syndrome, which is a variable combination of ocular coloboma, heart defects, choanal atresia, retardation of growth/development, genital hypoplasia, and ear anomalies or hearing loss caused by mutations in the CHD7 (chromodomain helicase DNA binding protein 7) gene. We performed endocrine studies and smell testing (University of Pennsylvania Smell Identification Test) in 35 adolescent patients with molecularly confirmed CHARGE syndrome. Complete data on smell and puberty were available for 15 patients; 11 patients had both anosmia and HH, whereas 4 patients had normosmia/hyposmia and spontaneous puberty. In addition, 7 boys were highly suspected of having HH (they were too young for definite HH diagnosis, but all had cryptorchidism, micropenis, or both) and had anosmia. The type of CHD7 mutation could not predict HH because a father and daughter with the same CHD7 mutation were discordant for HH and anosmia. Anosmia and HH were highly correlated in our cohort, and therefore smell testing seems to be an attractive method for predicting the occurrence of HH in patients with CHARGE syndrome. The use of this test could prevent delay of hormonal pubertal induction, resulting in an age-appropriate puberty. Copyright © 2011 Mosby, Inc. All rights reserved.

Academic and Social Benefits of a Co-enrollment Model of Inclusive Education for Deaf and Hard-of-Hearing Children.

PubMed

Kreimeyer, K H; Crooke, P; Drye, C; Egbert, V; Klein, B

2000-01-01

Deaf and hard-of-hearing (d/hh) students are traditionally educated within self-contained programs at residential or special day schools, within self-contained or resource classrooms in public schools, or within regular education classrooms with support provided by an itinerant teacher. The co-enrollment model offers a promising alternative in which these students are educated within a regular education classroom composed of both d/hh and hearing students and team-taught by a teacher of the deaf and a regular education teacher. This article examines the development of one such program and the social and academic performance of the d/hh students within the program. Data on social interaction between d/hh and hearing classmates suggest that specific instructional strategies that promoted students' sign language development, identified d/hh students as "sign language specialists" and grouped d/hh and hearing students during academic activities resulted in increased interaction between these two groups of students. Stanford Achievement Test scores in the areas of reading vocabulary, reading comprehension, mathematical problem solving and procedures indicate that although d/hh students scored below the national normative hearing group, reading comprehension levels exceeded the national normative sample of d/hh students during both years two and three of the program. We discuss the challenges of implementing a co-enrollment program.

Determining next steps in a hand hygiene improvement initiative by examining variation in hand hygiene compliance rates.

PubMed

Homa, Karen; Kirkland, Kathryn B

2011-01-01

Health care worker hand hygiene (HH) is a major quality and safety concern since poor hand hygiene has been linked with hospital associated infections. Dartmouth-Hitchcock Medical Center has been involved in a 4-year initiative to improve hand hygiene. In 2006, HH compliance occurred 41% of the time and by 2009, it had improved to 91%. We wanted to understand some of the unexplained variability in HH to help determine where to target more specific strategies. To help determine where some of the variability in HH compliance rates occurred, an analysis of means chart was used to determine whether role type of the health care worker and hospital areas had significantly different HH rates compared with the overall HH rate. The overall HH rate between March 2008 and December 2009 was 87%. There was a wide and significant variation between the 16 groups of 2 types of health care workers in 8 hospital areas from the lowest rate of 64% to a high of 96%. Analysis of means revealed significant differences in HH rates relative to the type of worker and hospital areas. Although the method does not inform the organization of what type of intervention will work where and why, it allows high and low performing groups to be identified, so that organizations can learn from them to generate and test theories.

Cryobacterium aureum sp. nov., a psychrophilic bacterium isolated from glacier ice collected from the ice tongue surface.

PubMed

Liu, Qing; Xin, Yu-Hua; Chen, Xiu-Ling; Liu, Hong-Can; Zhou, Yu-Guang; Chen, Wen-Xin

2018-04-01

A psychrophilic, Gram-stain-positive, rod-shaped bacterium, designated strain Hh31 T , was isolated from Xinjiang No. 1 Glacier in China. Strain Hh31 T was catalase-positive, oxidase-negative and able to grow at between 0-18 °C. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Hh31 T belonged to the genus Cryobacterium and was most closely related to the type strains of Cryobacterium levicorallinum, Cryobacterium luteum and Cryobacterium flavum. DNA-DNA hybridization, calculation of average nucleotide identity and digital DNA-DNA hybridization revealed that strain Hh31 T was distinct from its closest phylogenetic neighbours. The major cellular fatty acids of strain Hh31 T were anteiso-C15 : 0, anteiso-C15 : 1, iso-C15:0, iso-C16 : 0 and anteiso-C17 : 0. The predominant menaquinones of strain Hh31 T were MK-9 and MK-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid, one unidentified glycolipid and another unidentified lipid. Physiological tests such as carbon source utilization, showed phenotypic differentiation of strain Hh31 T from the closest related phylogenetic neighbours. Based on a polyphasic approach, a novel species, Cryobacterium aureum sp. nov., is proposed, with Hh31 T (=NBRC 107882 T =CGMCC 1.11213 T ) as the type strain.

MODELING SUPERSONIC-JET DEFLECTION IN THE HERBIG–HARO 110-270 SYSTEM WITH HIGH-POWER LASERS

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

Yuan, Dawei; Li, Yutong; Lu, Xin

Herbig–Haro (HH) objects associated with newly born stars are typically characterized by two high Mach number jets ejected in opposite directions. However, HH 110 appears to only have a single jet instead of two. Recently, Kajdi et al. measured the proper motions of knots in the whole system and noted that HH 110 is a continuation of the nearby HH 270. It has been proved that the HH 270 collides with the surrounding mediums and is deflected by 58°, reshaping itself as HH 110. Although the scales of the astrophysical objects are very different from the plasmas created in themore » laboratory, similarity criteria of physical processes allow us to simulate the jet deflection in the HH 110/270 system in the laboratory with high power lasers. A controllable and repeatable laboratory experiment could give us insight into the deflection behavior. Here we show a well downscaled experiment in which a laser-produced supersonic-jet is deflected by 55° when colliding with a nearby orthogonal side-flow. We also present a two-dimensional hydrodynamic simulation with the Euler program, LARED-S, to reproduce the deflection. Both are in good agreement. Our results show that the large deflection angle formed in the HH 110/270 system is probably due to the ram pressure from a flow–flow collision model.« less

[Clinical correlation of hypnagogic hypersynchrony during sleep in normal children and those with learning disability].

PubMed

Olmos G de Alba, G; Fraire-Martínez, M I; Valenzuela-Romero, R

One of the electroencephalographic (EEG) patterns that can be mistaken for paroxysmal clinical activity, when not taken into account and especially in children, is hypnagogic hypersynchrony (HH). This consists in generalised, paroxysmal, synchronic, symmetrical, slow, high voltage waves lasting 2 8 seconds, which appear in drowsiness and in stage I. It was observed that this pattern often appeared in children with learning disability (LD). AIMS. To correlate clinical data with the presence of HH during sleep in normal children and those with LD. We assessed 180 children between the ages of 6 12 years with normal neurological development, 130 of which suffered LD and 50 who did not have LD. EEG was performed with sleep deprivation, following the International Federation of Clinical Neurophysiology guidelines. The presence or absence of HH, together with its characteristics, was assessed. Of the children with LD, 35.38% displayed HH and of the children without LD, only 4% displayed HH. Since the characteristics of HH in the children with LD were different to previous descriptions, we put forward criteria with which to evaluate those differences. HH appeared more often in children with LD than in normal children. Qualitative, quantitative (p< 0.05) and morphological changes were found in the paroxysmal activity of HH during the stages of sleep in children with LD.

Detection of radio continuum emission from Herbig-Haro objects 1 and 2 and from their central exciting source

NASA Technical Reports Server (NTRS)

Pravdo, S. H.; Rodriguez, L. F.; Curiel, S.; Canto, J.; Torrelles, J. M.; Becker, R. H.; Sellgren, K.

1985-01-01

The region in Orion containing HH 1 and HH 2 was observed with the VLA at 20, 6, and 2 cm on several occasions from 1981 to 1984. At lower resolution, four continuum sources were detected. Two of these sources coincide positionally with HH 1 and HH 2. At 6 cm and higher resolution, HH 1 is resolved into at least two components. The emission is probably bremsstrahlung originating in the same region where the visible line emission is produced. This is the first detection of radio continuum from classic Herbig-Haro objects. At a position closely centered between HH 1 and HH 2, an object that can be interpreted as the energy source of the system was detected. The central source spectrum is S(nu) of about nu to the alpha power, where alpha = 0.4 + or - 0.2, suggesting a stellar wind. Finally, the fourth radio continuum source coincides positionally with an H2O maser and is probably excited by an independent star. There is evidence of time variability in its radio flux. No emission was detected from the Cohen-Schwartz (1979) star at the 0.1 mJy level.

Contribution of hiatal hernia to asthma in patients with gastroesophageal reflux disease.

PubMed

Li, Zhi-Tong; Ji, Feng; Han, Xin-Wei; Gu, Lin-Xia; Wang, Li; Yue, Yong-Qiang; Wang, Zhong-Gao

2018-05-01

To determine the correlation between asthma and hiatal hernia (HH) in patients with gastroesophageal reflux disease (GERD)-related asthma requiring laparoscopic anti-reflux surgery. One hundred and thirty-six GERD patients with medically refractory asthma with (80 patients) or without HH (56 patients) were enrolled. Gastroesophageal reflux disease was assessed by endoscopy, esophageal manometry, reflux monitoring and symptom questionnaires, and treated with laparoscopic Nissen fundoplication (LNF) or LNF with concomitant hiatal hernia repair (LNF-HHR). The outcome measures included patients' satisfaction and drug independence. The patients with HH had lower esophageal sphincters (P = .005) and higher DeMeester scores (P = .014) than those without HH. After an average follow-up of 24 months, symptom scores were significantly decreased from the preoperative values (P < .05). Compared to LNF, LNF-HHR showed a better improvement in both esophageal and asthmatic symptoms (P < .0001 and P = .016, respectively). The patients with GERD with asthma have a high prevalence of HH. The presence of HH maybe correlated with asthma and severe GERD. Actively treating HH not only improved reflux, but also controlled asthma symptoms. © 2017 John Wiley & Sons Ltd.

Symmetry-controlled time structure of high-harmonic carrier fields from a solid

PubMed Central

Langer, F.; Hohenleutner, M.; Huttner, U.; Koch, S. W.; Kira, M.; Huber, R.

2017-01-01

High-harmonic (HH) generation in crystalline solids1–6 marks an exciting development, with potential applications in high-efficiency attosecond sources7, all-optical bandstructure reconstruction8,9, and quasiparticle collisions10,11. Although the spectral1–4 and temporal shape5 of the HH intensity has been described microscopically1–6,12, the properties of the underlying HH carrier wave have remained elusive. Here we analyse the train of HH waveforms generated in a crystalline solid by consecutive half cycles of the same driving pulse. Extending the concept of frequency combs13–15 to optical clock rates, we show how the polarization and carrier-envelope phase (CEP) of HH pulses can be controlled by crystal symmetry. For some crystal directions, we can separate two orthogonally polarized HH combs mutually offset by the driving frequency to form a comb of even and odd harmonic orders. The corresponding CEP of successive pulses is constant or offset by π, depending on the polarization. In the context of a quantum description of solids, we identify novel capabilities for polarization- and phase-shaping of HH waveforms that cannot be accessed with gaseous sources. PMID:28572835

Recent progress in half-Heusler thermoelectric materials

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

Huang, Lihong; Zhang, Qinyong; Yuan, Bo

2016-04-15

Highlights: • Summarize the recent progress and advances in HH thermoelectric materials. • Preparing nanocomposites could reduce thermal conductivity. • Introducing enhance phonon scattering could further reduce the thermal conductivity. • Forming ternary systems to reducing the cost effectively. • The new class of HHs presents another opportunity to further optimize the HH system. - Abstract: Half-Heusler (HH) thermoelectric (TE) materials have been attracting extensive research interest over the last two decades, owing to their thermal stability, mechanical strength, and moderate ZT. This material system are potential candidates for medium to high temperature applications, which is close to the temperaturemore » range of most industrial waste heat sources. In this mini-review article, we briefly summarize the recent progress and advances in HH thermoelectric materials. Some effectively available approaches, such as HH nanocomposites to reduce thermal conductivity, using larger atomic mass and size differences to enhance phonon scattering to further reduce the thermal conductivity, forming ternary systems following the cost effective approach. In addition, new thermoelectric HH members are also discussed in this article, which points out that many new HH compounds may be possible for TE applications.« less

A case study of healthcare professional views on the meaning of data produced by hand hygiene auditing.

PubMed

Dawson, Carolyn H

2015-11-01

Measurement of hand hygiene (HH), crucial for patient safety, has acknowledged flaws stemming from methods available. Even direct observation, the World Health Organization gold standard, may lead to behaviour changes which can affect outcome validity. However, it remains important to understand current levels of HH to allow targeted interventions to be developed. This has resulted in wider adoption of auditing processes. This study addressed how healthcare professionals perceive data generated by HH auditing processes. Qualitative study involving participatory observation and semi-structured interviews with 30 healthcare professionals recruited from a large National Health Service (NHS) two-hospital site in England. Healthcare professionals perceived two main problems with HH measurement, both associated with feedback: (1) lack of clarity with regard to feedback; and (2) lack of association between training and measurement. In addition, concerns about data accuracy led the majority of participants (22/30) to conclude audit feedback is often 'meaningless'. Healthcare professionals require meaningful data on compliance with HH to engender change, as part of a multimodal strategy. Currently healthcare professionals perceive that data lack meaning, and are not seen as drivers to improve HH performance. Potential opportunities to change practice and improve HH are being missed.

The Discovery of Herbig–Haro Objects in LDN 673

NASA Astrophysics Data System (ADS)

Rector, T. A.; Shuping, R. Y.; Prato, L.; Schweiker, H.

2018-01-01

We report the discovery of 12 faint Herbig–Haro (HH) objects in LDN 673 found using a novel color-composite imaging method that reveals faint Hα emission in complex environments. Follow-up observations in [S II] confirmed their classification as HH objects. Potential driving sources are identified from the Spitzer c2d Legacy Program catalog and other infrared observations. The 12 new HH objects can be divided into three groups: four are likely associated with a cluster of eight young stellar object class I/II IR sources that lie between them; five are colinear with the T Tauri multiple star system AS 353, and are likely driven by the same source as HH 32 and HH 332 and three are bisected by a very red source that coincides with an infrared dark cloud. We also provide updated coordinates for the three components of HH 332. Inaccurate numbers were given for this object in the discovery paper. The discovery of HH objects and associated driving sources in this region provides new evidence for star formation in the Aquila clouds, implying a much larger T Tauri population in a seldom-studied region.

Decoding the phosphorylation code in Hedgehog signal transduction

PubMed Central

Chen, Yongbin; Jiang, Jin

2013-01-01

Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis, and its deregulation leads to numerous human disorders including cancer. Binding of Hh to Patched (Ptc), a twelve-transmembrane protein, alleviates its inhibition of Smoothened (Smo), a seven-transmembrane protein related to G-protein-coupled receptors (GPCRs), leading to Smo phosphorylation and activation. Smo acts through intracellular signaling complexes to convert the latent transcription factor Cubitus interruptus (Ci)/Gli from a truncated repressor to a full-length activator, leading to derepression/activation of Hh target genes. Increasing evidence suggests that phosphorylation participates in almost every step in the signal relay from Smo to Ci/Gli, and that differential phosphorylation of several key pathway components may be crucial for translating the Hh morphogen gradient into graded pathway activities. In this review, we focus on the multifaceted roles that phosphorylation plays in Hh signal transduction, and discuss the conservation and difference between Drosophila and mammalian Hh signaling mechanisms. PMID:23337587

Herbig-Haro objects in the Chamaeleon II dark cloud

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

Graham, J.A.; Hartigan, P.

1988-04-01

A new photograph and some spectra have been obtained for the group of HH objects HH 52, 53, 54. A long, gaseous streamer extends from HH 54 and produces an appearance very similar to that of HH 12. The spectra provide some additional radial velocities and line-intensity measurements for the group. It is confirmed that HH 54D is a star with no unusual photometric or spectroscopic characteristics. Attention is drawn to the distance of 400 pc derived by FitzGerald (1974, 1976) for a globule in the Cha II cloud, and it is suggested that the whole complex of gas, dust,more » and stars may well be further away than the 140 pc generally assumed. The spatial and velocity characteristics of this group of HH objects are discussed. The data do not support the identifications proposed by Sandell et al. (1987) as sources for the observed flows. 32 references.« less

Evaluation of Radar Vegetation Indices for Vegetation Water Content Estimation Using Data from a Ground-Based SMAP Simulator

NASA Technical Reports Server (NTRS)

Srivastava, Prashant K.; O'Neill, Peggy; Cosh, Michael; Lang, Roger; Joseph, Alicia

2015-01-01

Vegetation water content (VWC) is an important component of microwave soil moisture retrieval algorithms. This paper aims to estimate VWC using L band active and passive radar/radiometer datasets obtained from a NASA ground-based Soil Moisture Active Passive (SMAP) simulator known as ComRAD (Combined Radar/Radiometer). Several approaches to derive vegetation information from radar and radiometer data such as HH, HV, VV, Microwave Polarization Difference Index (MPDI), HH/VV ratio, HV/(HH+VV), HV/(HH+HV+VV) and Radar Vegetation Index (RVI) are tested for VWC estimation through a generalized linear model (GLM). The overall analysis indicates that HV radar backscattering could be used for VWC content estimation with highest performance followed by HH, VV, MPDI, RVI, and other ratios.

Zebrafish zic2a patterns the forebrain through modulation of Hedgehog-activated gene expression

PubMed Central

Sanek, Nicholas A.; Taylor, Aaron A.; Nyholm, Molly K.; Grinblat, Yevgenya

2009-01-01

Summary Holoprosencephaly (HPE) is the most common congenital malformation of the forebrain in human. Several genes with essential roles during forebrain development have been identified because they cause HPE when mutated. Among these are genes that encode the secreted growth factor Sonic hedgehog (Shh) and the transcription factors Six3 and Zic2. In the mouse, Six3 and Shh activate each other's transcription, but a role for Zic2 in this interaction has not been tested. We demonstrate that in zebrafish, as in mouse, Hh signaling activates transcription of six3b in the developing forebrain. zic2a is also activated by Hh signaling, and represses six3b non-cell-autonomously, i.e. outside of its own expression domain, probably through limiting Hh signaling. Zic2a repression of six3b is essential for the correct formation of the prethalamus. The diencephalon-derived optic stalk (OS) and neural retina are also patterned in response to Hh signaling. We show that zebrafish Zic2a limits transcription of the Hh targets pax2a and fgf8a in the OS and retina. The effects of Zic2a depletion in the forebrain and in the OS and retina are rescued by blocking Hh signaling or by increasing levels of the Hh antagonist Hhip, suggesting that in both tissues Zic2a acts to attenuate the effects of Hh signaling. These data uncover a novel, essential role for Zic2a as a modulator of Hh-activated gene expression in the developing forebrain and advance our understanding of a key gene regulatory network that, when disrupted, causes HPE. PMID:19855021

Zebrafish zic2a patterns the forebrain through modulation of Hedgehog-activated gene expression.

PubMed

Sanek, Nicholas A; Taylor, Aaron A; Nyholm, Molly K; Grinblat, Yevgenya

2009-11-01

Holoprosencephaly (HPE) is the most common congenital malformation of the forebrain in human. Several genes with essential roles during forebrain development have been identified because they cause HPE when mutated. Among these are genes that encode the secreted growth factor Sonic hedgehog (Shh) and the transcription factors Six3 and Zic2. In the mouse, Six3 and Shh activate each other's transcription, but a role for Zic2 in this interaction has not been tested. We demonstrate that in zebrafish, as in mouse, Hh signaling activates transcription of six3b in the developing forebrain. zic2a is also activated by Hh signaling, and represses six3b non-cell-autonomously, i.e. outside of its own expression domain, probably through limiting Hh signaling. Zic2a repression of six3b is essential for the correct formation of the prethalamus. The diencephalon-derived optic stalk (OS) and neural retina are also patterned in response to Hh signaling. We show that zebrafish Zic2a limits transcription of the Hh targets pax2a and fgf8a in the OS and retina. The effects of Zic2a depletion in the forebrain and in the OS and retina are rescued by blocking Hh signaling or by increasing levels of the Hh antagonist Hhip, suggesting that in both tissues Zic2a acts to attenuate the effects of Hh signaling. These data uncover a novel, essential role for Zic2a as a modulator of Hh-activated gene expression in the developing forebrain and advance our understanding of a key gene regulatory network that, when disrupted, causes HPE.

Expression of hLAMP-1-Positive Particles During Early Heart Development in the Chick.

PubMed

Abd-Elhamid, T H; Conway, M L; Sinning, A R

2017-10-01

Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 (hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton (HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube. © 2017 Blackwell Verlag GmbH.

First Large-scale Herbig-Haro Jet Driven by a Proto-brown Dwarf

NASA Astrophysics Data System (ADS)

Riaz, B.; Briceño, C.; Whelan, E. T.; Heathcote, S.

2017-07-01

We report the discovery of a new Herbig-Haro jet, HH 1165, in SOAR narrow-band imaging of the vicinity of the σ Orionis cluster. HH 1165 shows a spectacular extended and collimated spatial structure, with a projected length of 0.26 pc, a bent C-shaped morphology, multiple knots, and fragmented bow shocks at the apparent ends of the flow. The Hα image shows a bright halo with a clumpy distribution of material seen around the driving source, and curved reflection nebulosity tracing the outflow cavities. The driving source of HH 1165 is a Class I proto-brown dwarf, Mayrit 1701117 (M1701117), with a total (dust+gas) mass of ˜36 M Jup and a bolometric luminosity of ˜0.1 L ⊙. High-resolution VLT/UVES spectra of M1701117 show a wealth of emission lines indicative of strong outflow and accretion activity. SOAR/Goodman low-resolution spectra along the jet axis show an asymmetrical morphology for HH 1165. We find a puzzling picture wherein the northwest part exhibits a classical HH jet running into a pre-dominantly neutral medium, while the southern part resembles an externally irradiated jet. The C-shaped bending in HH 1165 may be produced by the combined effects from the massive stars in the ionization front to the east, the σ Orionis core to the west, and the close proximity to the B2-type star HR 1950. HH 1165 shows all of the signatures to be considered as a scaled-down version of parsec-length HH jets, and can be termed as the first sub-stellar analog of a protostellar HH jet system.

Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other selected GPCRs.

PubMed

Naporra, Franziska; Gobleder, Susanne; Wittmann, Hans-Joachim; Spindler, Julia; Bodensteiner, Michael; Bernhardt, Günther; Hübner, Harald; Gmeiner, Peter; Elz, Sigurd; Strasser, Andrea

2016-11-01

Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H 1 /H 4 receptor ligand (pK i : 8.11 (human H 1 R (hH 1 R)), 7.55 (human H 4 R (hH 4 R))), four known and 28 new oxazepine and related oxepine derivatives were synthesised and pharmacologically characterized at histamine receptors and selected aminergic GPCRs. In contrast to the oxazepine series, within the oxepine series, the new compounds showed high affinity to the hH 1 R (pK i : 6.8-8.7), but no or moderate affinity to the hH 4 R (pK i :≤5.3). For one oxepine derivative (1-(2-Chloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were separated and the R-enantiomer was identified as the eutomer at the hH 1 R (pK i : 8.83 (R), 7.63 (S)) and the guinea-pig H 1 R (gpH 1 R) (pK i : 8.82 (R), 7.41 (S)). Molecular dynamic studies suggest that the tricyclic core of the compounds is bound in a similar mode into the binding pocket, as described for doxepine in the hH 1 R crystal structure. Moreover, docking studies of all oxepine derivatives at the hH 1 R indicate that the oxygen and the position of the chlorine in the tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the same range as to hH 1 R or hH 4 R, thus, those compounds have to be classified as dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH 1 /h5-HT 2A receptor ligand (pK i : 9.23 (hH 1 R), 8.74 (h5-HT 2A R), ≤7 at other analysed GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective hH 1 R antagonist (pK i : 8.44 (hH 1 R), ≤6.7 at other analyzed GPCRs). Thus, the pharmacological results suggest that the oxazepine/oxepine moiety and additionally the chlorine substitution pattern toggles

Considering genetic characteristics in German Holstein breeding programs.

PubMed

Segelke, D; Täubert, H; Reinhardt, F; Thaller, G

2016-01-01

Recently, several research groups have demonstrated that several haplotypes may cause embryonic loss in the homozygous state. Up to now, carriers of genetic disorders were often excluded from mating, resulting in a decrease of genetic gain and a reduced number of sires available for the breeding program. Ongoing research is very likely to identify additional genetic defects causing embryonic loss and calf mortality by genotyping a large proportion of the female cattle population and sequencing key ancestors. Hence, a clear demand is present to develop a method combining selection against recessive defects (e.g., Holstein haplotypes HH1-HH5) with selection for economically beneficial traits (e.g., polled) for mating decisions. Our proposed method is a genetic index that accounts for the allele frequencies in the population and the economic value of the genetic characteristic without excluding carriers from breeding schemes. Fertility phenotypes from routine genetic evaluations were used to determine the economic value per embryo lost. Previous research has shown that embryo loss caused by HH1 and HH2 occurs later than the loss for HH3, HH4, and HH5. Therefore, an economic value of € 97 was used against HH1 and HH2 and € 70 against HH3, HH4, and HH5. For polled, € 7 per polled calf was considered. Minor allele frequencies of the defects ranged between 0.8 and 3.3%. The polled allele has a frequency of 4.1% in the German Holstein population. A genomic breeding program was simulated to study the effect of changing the selection criteria from assortative mating based on breeding values to selecting the females using the genetic index. Selection for a genetic index on the female path is a useful method to control the allele frequencies by reducing undesirable alleles and simultaneously increasing economical beneficial characteristics maintaining most of the genetic gain in production and functional traits. Additionally, we applied the genetic index to real data and

CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis.

PubMed

Jia, Guiquan; Chandriani, Sanjay; Abbas, Alexander R; DePianto, Daryle J; N'Diaye, Elsa N; Yaylaoglu, Murat B; Moore, Heather M; Peng, Ivan; DeVoss, Jason; Collard, Harold R; Wolters, Paul J; Egen, Jackson G; Arron, Joseph R

2017-09-01

Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor. Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was CXCL14 , which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. CXCL14 expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment. CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF. Post-results, NCT00968981. 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/.

Inhibition of the hedgehog pathway targets the tumor-associated stroma in pancreatic cancer.

PubMed

Hwang, Rosa F; Moore, Todd T; Hattersley, Maureen Mertens; Scarpitti, Meghan; Yang, Bin; Devereaux, Erik; Ramachandran, Vijaya; Arumugam, Thiruvengadam; Ji, Baoan; Logsdon, Craig D; Brown, Jeffrey L; Godin, Robert

2012-09-01

The Hedgehog (Hh) pathway has emerged as an important pathway in multiple tumor types and is thought to be dependent on a paracrine signaling mechanism. The purpose of this study was to determine the role of pancreatic cancer-associated fibroblasts (human pancreatic stellate cells, HPSCs) in Hh signaling. In addition, we evaluated the efficacy of a novel Hh antagonist, AZD8542, on tumor progression with an emphasis on the role of the stroma compartment. Expression of Hh pathway members and activation of the Hh pathway were analyzed in both HPSCs and pancreatic cancer cells. We tested the effects of Smoothened (SMO) inhibition with AZD8542 on tumor growth in vivo using an orthotopic model of pancreatic cancer containing varying amounts of stroma. HPSCs expressed high levels of SMO receptor and low levels of Hh ligands, whereas cancer cells showed the converse expression pattern. HPSC proliferation was stimulated by Sonic Hedgehog with upregulation of downstream GLI1 mRNA. These effects were abrogated by AZD8542 treatment. In an orthotopic model of pancreatic cancer, AZD8542 inhibited tumor growth only when HPSCs were present, implicating a paracrine signaling mechanism dependent on stroma. Further evidence of paracrine signaling of the Hh pathway in prostate and colon cancer models is provided, demonstrating the broader applicability of our findings. Based on the use of our novel human-derived pancreatic cancer stellate cells, our results suggest that Hh-targeted therapies primarily affect the tumor-associated stroma, rather than the epithelial compartment.

Effect of a children's at-home nursing team on reducing emergency admissions.

PubMed

Farnham, Laura; Harwood, Hannah; Robertson, Meredith

2017-12-05

This article explores the effect of a children's at-home nursing team, Hospital at Home (H@H), which aimed to reduce demand on acute hospital beds, support families to improve patient experience, and empower parents to care safely for their unwell children and help prevent emergency department (ED) reattendance. Data on demographics and clinical presentation of H@H and ED attendances were collected and compared. A survey measuring parents' confidence in managing their unwell children was also conducted. Of 72 patients treated by the H@H service between May and July 2016, 32 (44%) would have been admitted to hospital from the ED if the H@H service had not existed. This is equivalent to a saving of 64 bed days. Patients treated by the H@H service had similar demographics to those discharged from the ED to usual care. The H@H service took on patients with higher Bedside Paediatric Early Warning System scores before discharge. Parents reported that they would be more confident caring for their children after discharge from the H@H service. The H@H service decreased the number of unnecessary ED admissions. The service promotes a positive patient experience and increases parents' confidence when caring for unwell children at home. ©2017 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Differential homologous desensitization of the human histamine H3 receptors of 445 and 365 amino acids expressed in CHO-K1 cells.

PubMed

García-Gálvez, Ana-Maricela; Escamilla-Sánchez, Juan; Flores-Maldonado, Catalina; Contreras, Rubén-Gerardo; Arias, Juan-Manuel; Arias-Montaño, José-Antonio

2018-01-01

Histamine H 3 receptors (H 3 Rs) signal through Gα i/o proteins and are found in neuronal cells as auto- and hetero-receptors. Alternative splicing of the human H 3 R (hH 3 R) originates 20 isoforms, and the mRNAs of two receptors of 445 and 365 amino acids (hH 3 R 445 and hH 3 R 365 ) are widely expressed in the human brain. We previously showed that the hH 3 R 445 stably expressed in CHO-K1 cells experiences homologous desensitization. The hH 3 R 365 lacks 80 residues in the third intracellular loop, and in this work we therefore studied whether this isoform also experiences homologous desensitization and the possible differences with the hH 3 R 445 . In clones of CHO-K1 cells stably expressing similar receptor levels (211 ± 12 and 199 ± 16 fmol/mg protein for hH 3 R 445 and hH 3 R 365 , respectively), there were no differences in receptor affinity for selective H 3 R ligands or for agonist-induced [ 35 S]-GTPγS binding to membranes and inhibition of forskolin-stimulated cAMP accumulation in intact cells. For both cell clones, pre-incubation with the H 3 R agonist RAMH (1 μM) resulted in functional receptor desensitization, as indicated by cAMP accumulation assays, and loss of receptors from the cell surface and reduced affinity for the agonist immepip in cell membranes, evaluated by radioligand binding. However, functional desensitization differed in the maximal extent (96 ± 15% and 58 ± 8% for hH 3 R 445 and hH 3 R 365 , respectively) and the length of pre-exposure required to reach the maximum desensitization (60 and 30 min, respectively). Furthermore, the isoforms differed in their recovery from desensitization. These results indicate that the hH 3 R 365 experiences homologous desensitization, but that the process differs between the isoforms in time-course, magnitude and re-sensitization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of alginate in patients with GERD hiatal hernia matters.

PubMed

Vardar, R; Keskin, M; Valitova, E; Bayrakci, B; Yildirim, E; Bor, S

2017-10-01

Alginate-based formulations are frequently used as add-on proton pump inhibitor (PPI) therapy to help control of heartburn and regurgitation. There are limited data regarding the mechanisms and effects of alginate-based formulations. We aimed to evaluate the effects of the sodium alginate intake and its likely temporal relations on intraesophageal reflux events by MII-pH in patients with and without hiatal hernia (HH). Fifty GERD patients (18 with HH, 32 without HH) with heartburn or regurgitation once a week or more common were included. After combined multichannel intraluminal impedance and pH-metry (MII-pH) had been performed, all patients were asked to eat the same standard meal (double cheeseburger, 1 banana, 100 g regular yoghurt, and 200 mL water with total energy value of 744 kcal: 37.6% of carbohydrates, 21.2% of proteins, and 41.2% of lipids) during two consecutive days. On separate random two consecutive days, all patients took 10 mL of sodium alginate (GA; Gaviscon Advance; Reckitt Benckiser Healthcare, Hull, UK) or 10 mL of water, 30 minutes after the refluxogenic meal. After eating refluxogenic meal, patients were examined ½ hour for basal conditions, 1 hour in upright, and 1 hour in supine positions. Alginate significantly decreased acid reflux after intake at the first hour in comparison to water in patients with HH (6.1 vs. 13.7, P = 0.004) and without HH (3.5 vs. 5.5, P = 0.001). Weakly acid reflux were increased at the first hour in patients with HH (3.4 vs. 1.3, P = 0.019) and without HH (1.7 vs. 5, P = 0.02) compared to water. There was no distinctive effect of alginate on the height of proximal migration of reflux events in patients with HH and without HH. Alginate decreases acid reflux events within a limited time period, especially at the first hour both in patients with and without HH. Alginate has no effect on the height of reflux events along the esophagus both in patients with and without HH. © The Authors 2017. Published by Oxford

SHOC1 is a ERCC4-(HhH)2-like protein, integral to the formation of crossover recombination intermediates during mammalian meiosis

PubMed Central

Almeida, Luciana P.; Parikh, Aniruddha; de Castro, Rodrigo O.

2018-01-01

Chromosome segregation errors during meiosis result in the formation of aneuploid gametes and are the leading cause of pregnancy loss and birth defects in humans. Proper chromosome segregation requires pairwise associations of maternal and paternal homologous chromosomes. Chiasmata, which are the cytological manifestations of crossovers (COs), provide a physical link that holds the homologs together as a pair, facilitating their orientation on the spindle at meiosis I. Although CO-promoting activities ensure a balanced number and position of COs, their identity and mechanism of action in mammals remain understudied. Previous work in yeast and Arabidopsis has shown that Zip2 and Shoc1 are ortholog proteins with an important role in promoting the formation of COs. Our work is the first study in mammals showing the in vivo and in vitro function of mouse and human SHOC1. We show that purified recombinant human SHOC1, an XPF/MUS81 family member, preferentially binds branched DNA molecules but apparently lacks in vitro endonuclease activity, despite its conserved ERCC4-(HhH)2 core structure. Cytological observations suggest that initial steps of recombination are normal in a majority of spermatocytes from SHOC1 hypomorphic mice. However, late stages of recombination appear abnormal, as chromosomal localization of MLH1 is reduced. In agreement, chiasma formation is reduced, and cells arrest at metaphase I with a few lagging chromosomes and subsequent apoptosis. This analysis of SHOC1-deficient mice and the selective localization of SHOC1 to a subset of recombination sites show that SHOC1 acts at key mid-stage steps of the CO formation process. The formation of chromosome axial elements and homologous pairing are apparently normal, but synapsis is altered with SYCP1 frequently failing to extend the full length of the chromosome axes. Finally, we describe that SHOC1 interacts with TEX11, another protein important for the formation of COs, connecting SHOC1 to chromosome axis

SHOC1 is a ERCC4-(HhH)2-like protein, integral to the formation of crossover recombination intermediates during mammalian meiosis.

PubMed

Guiraldelli, Michel F; Felberg, Anna; Almeida, Luciana P; Parikh, Aniruddha; de Castro, Rodrigo O; Pezza, Roberto J

2018-05-01

Chromosome segregation errors during meiosis result in the formation of aneuploid gametes and are the leading cause of pregnancy loss and birth defects in humans. Proper chromosome segregation requires pairwise associations of maternal and paternal homologous chromosomes. Chiasmata, which are the cytological manifestations of crossovers (COs), provide a physical link that holds the homologs together as a pair, facilitating their orientation on the spindle at meiosis I. Although CO-promoting activities ensure a balanced number and position of COs, their identity and mechanism of action in mammals remain understudied. Previous work in yeast and Arabidopsis has shown that Zip2 and Shoc1 are ortholog proteins with an important role in promoting the formation of COs. Our work is the first study in mammals showing the in vivo and in vitro function of mouse and human SHOC1. We show that purified recombinant human SHOC1, an XPF/MUS81 family member, preferentially binds branched DNA molecules but apparently lacks in vitro endonuclease activity, despite its conserved ERCC4-(HhH)2 core structure. Cytological observations suggest that initial steps of recombination are normal in a majority of spermatocytes from SHOC1 hypomorphic mice. However, late stages of recombination appear abnormal, as chromosomal localization of MLH1 is reduced. In agreement, chiasma formation is reduced, and cells arrest at metaphase I with a few lagging chromosomes and subsequent apoptosis. This analysis of SHOC1-deficient mice and the selective localization of SHOC1 to a subset of recombination sites show that SHOC1 acts at key mid-stage steps of the CO formation process. The formation of chromosome axial elements and homologous pairing are apparently normal, but synapsis is altered with SYCP1 frequently failing to extend the full length of the chromosome axes. Finally, we describe that SHOC1 interacts with TEX11, another protein important for the formation of COs, connecting SHOC1 to chromosome axis

Acute Mountain Sickness Symptoms Depend on Normobaric versus Hypobaric Hypoxia

PubMed Central

Strangman, Gary E.; Harris, N. Stuart; Muza, Stephen R.

2016-01-01

Acute mountain sickness (AMS), characterized by headache, nausea, fatigue, and dizziness when unacclimatized individuals rapidly ascend to high altitude, is exacerbated by exercise and can be disabling. Although AMS is observed in both normobaric (NH) and hypobaric hypoxia (HH), recent evidence suggests that NH and HH produce different physiological responses. We evaluated whether AMS symptoms were different in NH and HH during the initial stages of exposure and if the assessment tool mattered. Seventy-two 8 h exposures to normobaric normoxia (NN), NH, or HH were experienced by 36 subjects. The Environmental Symptoms Questionnaire (ESQ) and Lake Louise Self-report (LLS) were administered, resulting in a total of 360 assessments, with each subject answering the questionnaire 5 times during each of their 2 exposure days. Classification tree analysis indicated that symptoms contributing most to AMS were different in NH (namely, feeling sick and shortness of breath) compared to HH (characterized most by feeling faint, appetite loss, light headedness, and dim vision). However, the differences were not detected using the LLS. These results suggest that during the initial hours of exposure (1) AMS in HH may be a qualitatively different experience than in NH and (2) NH and HH may not be interchangeable environments. PMID:27847819

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

PubMed

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

Hedgehog signaling plays roles in epithelial cell proliferation in neonatal mouse uterus and vagina.

PubMed

Nakajima, Tadaaki; Iguchi, Taisen; Sato, Tomomi

2012-04-01

Both the uterus and vagina develop from the Müllerian duct but are quite distinct in morphology and function. To investigate factors controlling epithelial differentiation and cell proliferation in neonatal uterus and vagina, we focused on Hedgehog (HH) signaling. In neonatal mice, Sonic hh (Shh) was localized in the vaginal epithelium and Indian hh (Ihh) was slightly expressed in the uterus and vagina, whereas all Glioma-associated oncogene homolog (Gli) genes were mainly expressed in the stroma. The expression of target genes of HH signaling was high in the neonatal vagina and in the uterus, it increased with growth. Thus, in neonatal mice, Shh in the vaginal epithelium and Ihh in the uterus and vagina activated HH signaling in the stroma. Tissue recombinants showed that vaginal Shh expression was inhibited by the vaginal stroma and uterine Ihh expression was stimulated by the uterine stroma. Addition of a HH signaling inhibitor decreased epithelial cell proliferation in organ-cultured uterus and vagina and increased stromal cell proliferation in organ-cultured uterus. However, it did not affect epithelial differentiation or the expression of growth factors in organ-cultured uterus and vagina. Thus, activated HH signaling stimulates epithelial cell proliferation in neonatal uterus and vagina but inhibits stromal cell proliferation in neonatal uterus.

H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

PubMed Central

Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

2016-01-01

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study

PubMed Central

2018-01-01

Objectives To assess the nurses’ hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in small- and medium-sized hospitals after Middle East Respiratory Syndrome outbreak. Methods The structured questionnaire was adapted from the World Health Organization’s survey. Data were collected between June 26 and July 14, 2017. Results Nurses showed scores on knowledge (17.6±2.5), perception (69.3±0.8), self-reported HH performance of non-self (86.0±11.0), self-reported performance of self (88.2±11.0), and attitude (50.5±5.5). HH performance rate of non-self was Y1=36.678+ 0.555X1 (HH performance rate of self) (adjusted R2=0.280, p<0.001). The regression model for performance was Y4=18.302+0.247X41 (peception)+0.232X42 (attitude)+0.875X42 (role model); coefficients were significant statistically except attitude, and this model significant statistically (adjusted R2=0.191, p<0.001). Conclusions Advanced HH education program would be developed and operated continuously. Perception, attitude, role model was found to be a significant predictors of HH performance of self. So these findings could be used in future HH promotion strategies for nurses. PMID:29886707

Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study.

PubMed

Oh, Hyang Soon

2018-05-01

To assess the nurses' hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in small- and medium-sized hospitals after Middle East Respiratory Syndrome outbreak. The structured questionnaire was adapted from the World Health Organization's survey. Data were collected between June 26 and July 14, 2017. Nurses showed scores on knowledge (17.6±2.5), perception (69.3±0.8), self-reported HH performance of non-self (86.0±11.0), self-reported performance of self (88.2±11.0), and attitude (50.5±5.5). HH performance rate of non-self was Y 1 =36.678+ 0.555X1 (HH performance rate of self) (adjusted R 2 =0.280, p <0.001). The regression model for performance was Y 4 =18.302+0.247 X 41 (peception)+0.232 X 42 (attitude)+0.875 X 42 (role model); coefficients were significant statistically except attitude, and this model significant statistically (adjusted R 2 =0.191, p <0.001). Advanced HH education program would be developed and operated continuously. Perception, attitude, role model was found to be a significant predictors of HH performance of self. So these findings could be used in future HH promotion strategies for nurses.

Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.

PubMed

Riedlinger, Dorothee; Bahra, Marcus; Boas-Knoop, Sabine; Lippert, Steffen; Bradtmöller, Maren; Guse, Katrin; Seehofer, Daniel; Bova, Roberta; Sauer, Igor M; Neuhaus, Peter; Koch, Arend; Kamphues, Carsten

2014-08-01

Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells in vitro and in vivo. Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS-833923 was evaluated in vitro. In addition, the effect of BMS-833923, alone or in combination with gemcitabine, was analyzed in vivo in a murine subcutaneous xenograft model. Expression analysis revealed a significant activation of the Hh-signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a significant decrease in cell proliferation of CCC cells. Moreover, a distinct inhibition of tumor growth could be seen as a result of a combined therapy with BMS-833923 and gemcitabine in CCC xenografts. The results of our study suggest that the Hh pathway plays a relevant role at least in a subset of human CCC. Inhibition of this pathway may represent a possible treatment option for CCC patients in which the Hh pathway is activated. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

A case study of healthcare professional views on the meaning of data produced by hand hygiene auditing

PubMed Central

2015-01-01

Background: Measurement of hand hygiene (HH), crucial for patient safety, has acknowledged flaws stemming from methods available. Even direct observation, the World Health Organization gold standard, may lead to behaviour changes which can affect outcome validity. However, it remains important to understand current levels of HH to allow targeted interventions to be developed. This has resulted in wider adoption of auditing processes. Aim: This study addressed how healthcare professionals perceive data generated by HH auditing processes. Methods: Qualitative study involving participatory observation and semi-structured interviews with 30 healthcare professionals recruited from a large National Health Service (NHS) two-hospital site in England. Findings: Healthcare professionals perceived two main problems with HH measurement, both associated with feedback: (1) lack of clarity with regard to feedback; and (2) lack of association between training and measurement. In addition, concerns about data accuracy led the majority of participants (22/30) to conclude audit feedback is often ‘meaningless’. Conclusion: Healthcare professionals require meaningful data on compliance with HH to engender change, as part of a multimodal strategy. Currently healthcare professionals perceive that data lack meaning, and are not seen as drivers to improve HH performance. Potential opportunities to change practice and improve HH are being missed. PMID:28989439

31 CFR 353.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT REGULATIONS GOVERNING DEFINITIVE UNITED STATES SAVINGS BONDS, SERIES EE AND HH General Information § 353.2 Definitions. (a) Bond, or Series EE or HH savings bond, as used in this part, means a definitive United States Savings Bond of Series EE or HH. (b...

Hypothalamic hamartoma: Epileptogenesis beyond the lesion?

PubMed

Scholly, Julia; Staack, Anke Maren; Kahane, Philippe; Scavarda, Didier; Régis, Jean; Hirsch, Edouard; Bartolomei, Fabrice

2017-06-01

The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10 years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography [SEEG]) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible "kindling-like" relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic

Analysis of synthetic aperture radar data acquired over a variety of land cover

NASA Technical Reports Server (NTRS)

Wu, S.-T.

1984-01-01

The results of Synthetic Aperture Radar (SAR) measurements over Kershaw County, South Carolina, using HH, HV, and VV polarization and two-incidence angle X-band airborne SAR system and over Baldwin County, Alabama, using HH polarization L-band Shuttle Imaging Radar (SIR-A) are presented. The X-band data indicate higher HH than VV radar return for cypress forest with standing water. Multipolarization (HH, HV, and VV) data help delineate several land-cover types that are difficult to delineate by the single polarization (HH) data. The L-band data indicate that radar return signal strength is highly correlated with tree height or age for three types of pine forest. It is found that delineation of urban/residential from deciduous forest is significantly improved by the inclusion of Landsat multispectral scanner data.

Jaundice increases the rate of complications and one-year mortality in patients with hypoxic hepatitis.

PubMed

Jäger, Bernhard; Drolz, Andreas; Michl, Barbara; Schellongowski, Peter; Bojic, Andja; Nikfardjam, Miriam; Zauner, Christian; Heinz, Gottfried; Trauner, Michael; Fuhrmann, Valentin

2012-12-01

Hypoxic hepatitis (HH) is the most frequent cause of acute liver injury in critically ill patients. No clinical data exist about new onset of jaundice in patients with HH. This study aimed to evaluate the incidence and clinical effect of jaundice in critically ill patients with HH. Two hundred and six consecutive patients with HH were screened for the development of jaundice during the course of HH. Individuals with preexisting jaundice or liver cirrhosis at the time of admission (n = 31) were excluded from analysis. Jaundice was diagnosed in patients with plasma total bilirubin levels >3 mg/dL. One-year-survival, infections, and cardiopulmonary, gastrointestinal (GI), renal, and hepatic complications were prospectively documented. New onset of jaundice occurred in 63 of 175 patients with HH (36%). In patients who survived the acute event of HH, median duration of jaundice was 6 days (interquartile range, 3-8). Patients who developed jaundice (group 1) needed vasopressor treatment (P < 0.05), renal replacement therapy (P < 0.05), and mechanical ventilation (P < 0.05) more often and had a higher maximal administered dose of norepinephrine (P < 0.05), compared to patients without jaundice (group 2). One-year survival rate was significantly lower in group 1, compared to group 2 (8% versus 25%, respectively; P < 0.05). Occurrence of jaundice was associated with an increased frequency of complications during follow-up (54% in group 1 versus 35% in group 2; P < 0.05). In particular, infections as well as renal and GI complications occurred more frequently in group 1 during follow-up. Jaundice is a common finding during the course of HH. It leads to an increased rate of complications and worse outcome in patients with HH. Copyright © 2012 American Association for the Study of Liver Diseases.

The impact of the International Nosocomial Infection Control Consortium (INICC) multicenter, multidimensional hand hygiene approach in two cities of India.

PubMed

Chakravarthy, Murali; Myatra, Sheila Nainan; Rosenthal, Victor D; Udwadia, F E; Gokul, B N; Divatia, J V; Poojary, Aruna; Sukanya, R; Kelkar, Rohini; Koppikar, Geeta; Pushparaj, Leema; Biswas, Sanjay; Bhandarkar, Lata; Raut, Sandhya; Jadhav, Shital; Sampat, Sulochana; Chavan, Neeraj; Bahirune, Shweta; Durgad, Shilpa

2015-01-01

The fundamental tool for preventing and controlling healthcare-acquired infections is hand hygiene (HH). Nonetheless, adherence to HH guidelines is often low. Our goal was to assess the effect of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach (IMHHA) in three intensive care units of three INICC member hospitals in two cities of India and to analyze the predictors of compliance with HH. From August 2004 to July 2011, we carried out an observational, prospective, interventional study to evaluate the implementation of the IMHHA, which included the following elements: (1) administrative support, (2) supplies availability, (3) education and training, (4) reminders in the workplace, (5) process surveillance and (6) performance feedback. The practices of health care workers were monitored during randomly selected 30-min periods. We observed 3612 opportunities for HH. Overall adherence to HH increased from 36.9% to 82% (95% CI 79.3-84.5; P=0.0001). Multivariate analysis indicated that certain variables were significantly associated with poor HH adherence: nurses vs. physicians (70.5% vs. 74%; 95% CI 0.62-0.96; P=0.018), ancillary staff vs. physicians (43.6% vs. 74.0%; 95% CI 0.48-0.72; P<0.001), ancillary staff vs. nurses (43.6% vs. 70.5%; 95% CI 0.51-0.75; P<0.001) and private vs. academic hospitals (74.2% vs. 66.3%; 95% CI 0.83-0.97; P<0.001). It is worth noticing that in India, the HH compliance of physicians is higher than in nurses. Adherence to HH was significantly increased by implementing the IMHHA. Programs targeted at improving HH are warranted to identify predictors of poor compliance. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Understanding the Needs of Families of Children Who Are Deaf/Hard of Hearing with an Autism Spectrum Disorder.

PubMed

Wiley, Susan; Meinzen-Derr, Jareen; Hunter, Lisa; Hudock, Rebekah; Murphy, Dora; Bentley, Katie; Williams, Tanishia

2018-05-01

There is a significant lack of evidence guiding our understanding of the needs of families of children who are deaf/hard of hearing (Deaf/HH) with an autism spectrum disorder (ASD). Much of our current knowledge is founded in case report studies with very small numbers of children with the dual diagnosis. The purpose of this study was to gain an understanding of the factors relating to caregiver stress and needs (i.e., supports and interventions) in families of children who are Deaf/HH with ASD. Comparison groups of families of children who were Deaf/HH, families with a hearing child with ASD, and families of children who were Deaf/HH with ASD were administered standardized questionnaires of stress with brief qualitative questionnaires focusing on family-identified needs. Six families of children with the dual diagnosis, four families of children who were Deaf/HH, and three families of children with ASD. Surveys included demographic and support questionnaires, the Parenting Stress Index (PSI), the Pediatric Hearing Impairment Caregiver Experience, and a qualitative questionnaire. Families of children who were Deaf/HH with ASD had a higher median total stress score on the PSI as compared to families of children who were Deaf/HH only (58.5 versus 41.5, respectively; p = 0.02) and higher Child Domain scores (60 versus 43, respectively; p = 0.02), indicating higher levels of stress in families of children with the dual diagnosis. The families of children who were Deaf/HH with ASD reported similar levels of stress as families of children with ASD. Families of children who are Deaf/HH with an ASD experience stress and describe similar needs and priorities as families of hearing children with ASD. This suggests the needs related to having an autism spectrum disorder are of high priority in families of children with the dual diagnosis. American Academy of Audiology.

Clinical factors affecting inspired gas humidification and oral dryness during noninvasive ventilation.

PubMed

Oto, Jun; Imanaka, Hideaki; Nishimura, Masaji

2011-10-01

Oral dryness is a common complication during noninvasive ventilation (NIV). We measured the oral dryness of patients and performed a bench study to investigate factors related to humidification during NIV. Patients were randomly assigned into 2 groups: medium (Med group) and maximum (Max group) heated humidifier (HH) settings. Oral moistness was measured using an oral moisture-checking device, and the feeling of oral dryness was evaluated using a 0 to 10 numerical rating scale (NRS) at 0, 12, and 24 hours from the beginning of NIV and at 12 and 24 hours after NIV was discontinued. A bench study was performed to assess the effects of positive end-expiratory pressure (PEEP), the fraction of inspired oxygen (F(I)O(2)), and air leaks on absolute humidity. We evaluated 3 HH settings: no HH, HH at the medium setting, and HH at the maximum setting. The temperature in the outlet chamber was 31°C to 32°C for the medium HH setting and 38°C to 41°C for the maximum HH setting. In the clinical study, 12 patients were assigned to the Med group and 11 to the Max group. In the Med group, oral moistness decreased and NRS increased at 12 and 24 hours compared with 0 hours (P < .05). In the Max group, neither the oral moistness nor the NRS changed throughout the study period, whereas in the bench study, high F(I)O(2), high PEEP, and air leak decreased the absolute humidity for both HH settings (P < .01). However, it is not clear to what extent these factors affected the patients' oral dryness because the ranges of F(I)O(2) and PEEP were narrow. Oral dryness was a common problem in our patients. The HH setting significantly affected humidification and oral dryness during NIV. Copyright © 2011 Elsevier Inc. All rights reserved.

Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype.

PubMed

Onodera, Shoko; Saito, Akiko; Hasegawa, Daigo; Morita, Nana; Watanabe, Katsuhito; Nomura, Takeshi; Shibahara, Takahiko; Ohba, Shinsuke; Yamaguchi, Akira; Azuma, Toshifumi

2017-01-01

Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1) mutations. PTCH1 is a hedgehog (Hh) receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported. Recently, mutations in Suppressor of fused homolog (SUFU) or PTCH2 were reported in patients with Gorlin syndrome. These facts suggest that multi-layered mutations in Hh pathway may contribute to the development of Gorlin syndrome. We demonstrated multiple mutations of Hh-related genes in addition to PTCH1, which possibly act in an additive or multiplicative manner and lead to Gorlin syndrome. High-throughput sequencing was performed to analyze exome sequences in four unrelated Gorlin syndrome patient genomes. Mutations in PTCH1 gene were detected in all four patients. Specific nucleotide variations or frameshift variations of PTCH1 were identified along with the inferred amino acid changes in all patients. We further filtered 84 different genes which are closely related to Hh signaling. Fifty three of these had enough coverage of over ×30. The sequencing results were filtered and compared to reduce the number of sequence variants identified in each of the affected individuals. We discovered three genes, PTCH2, BOC, and WNT9b, with mutations with a predicted functional impact assessed by MutationTaster2 or PolyPhen-2 (Polymorphism Phenotyping v2) analysis. It is noticeable that PTCH2 and BOC are Hh receptor molecules. No significant mutations were observed in SUFU. Multi-layered mutations in Hh pathway may change the activation level of the Hh signals, which may explain the wide phenotypic variability of Gorlin syndrome.

A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development.

PubMed

Bohnenpoll, Tobias; Wittern, Anna B; Mamo, Tamrat M; Weiss, Anna-Carina; Rudat, Carsten; Kleppa, Marc-Jens; Schuster-Gossler, Karin; Wojahn, Irina; Lüdtke, Timo H-W; Trowe, Mark-Oliver; Kispert, Andreas

2017-08-01

The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH) family of secreted proteins, Sonic hedgehog (SHH) as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO) to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development. We showed that HH signaling is not only required for proliferation and SMC differentiation of cells of the inner mesenchymal region but also for survival of cells of the outer mesenchymal region, and for epithelial proliferation and differentiation. We identified the Forkhead transcription factor gene Foxf1 as a target of HH signaling in the ureteric mesenchyme. Expression of a repressor version of FOXF1 in this tissue completely recapitulated the mesenchymal and epithelial proliferation and differentiation defects associated with loss of HH signaling while re-expression of a wildtype version of FOXF1 in the inner mesenchymal layer restored these cellular programs when HH signaling was inhibited. We further showed that expression of Bmp4 in the ureteric mesenchyme depends on HH signaling and Foxf1, and that exogenous BMP4 rescued cell proliferation and epithelial differentiation in ureters with abrogated HH signaling or FOXF1 function. We conclude that SHH uses a FOXF1-BMP4 module to coordinate the cellular programs for ureter elongation and differentiation, and suggest that deregulation of this signaling axis occurs in human congenital anomalies of the kidney and urinary tract (CAKUT).

Comparative genomics identification of a novel set of temporally regulated hedgehog target genes in the retina.

PubMed

McNeill, Brian; Perez-Iratxeta, Carol; Mazerolle, Chantal; Furimsky, Marosh; Mishina, Yuji; Andrade-Navarro, Miguel A; Wallace, Valerie A

2012-03-01

The hedgehog (Hh) signaling pathway is involved in numerous developmental and adult processes with many links to cancer. In vertebrates, the activity of the Hh pathway is mediated primarily through three Gli transcription factors (Gli1, 2 and 3) that can serve as transcriptional activators or repressors. The identification of Gli target genes is essential for the understanding of the Hh-mediated processes. We used a comparative genomics approach using the mouse and human genomes to identify 390 genes that contained conserved Gli binding sites. RT-qPCR validation of 46 target genes in E14.5 and P0.5 retinal explants revealed that Hh pathway activation resulted in the modulation of 30 of these targets, 25 of which demonstrated a temporal regulation. Further validation revealed that the expression of Bok, FoxA1, Sox8 and Wnt7a was dependent upon Sonic Hh (Shh) signaling in the retina and their regulation is under positive and negative controls by Gli2 and Gli3, respectively. We also show using chromatin immunoprecipitation that Gli2 binds to the Sox8 promoter, suggesting that Sox8 is an Hh-dependent direct target of Gli2. Finally, we demonstrate that the Hh pathway also modulates the expression of Sox9 and Sox10, which together with Sox8 make up the SoxE group. Previously, it has been shown that Hh and SoxE group genes promote Müller glial cell development in the retina. Our data are consistent with the possibility for a role of SoxE group genes downstream of Hh signaling on Müller cell development. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury.

PubMed

Grzelak, Candice Alexandra; Martelotto, Luciano Gastón; Sigglekow, Nicholas David; Patkunanathan, Bramilla; Ajami, Katerina; Calabro, Sarah Ruth; Dwyer, Benjamin James; Tirnitz-Parker, Janina Elke Eleonore; Watkins, D Neil; Warner, Fiona Jane; Shackel, Nicholas Adam; McCaughan, Geoffrey William

2014-01-01

In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration, however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)-induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. C57BL/6 mice (wild-type or Ptc1(+/-)) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO-dependent/independent activation of GLI-mediated transcriptional response in Pc-positive (Pc(+)) cells were studied in vitro. In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2(+). Pc(+) cells increased following TAA, but only EpCAM(+)/GLI2(+) progenitors were Pc(+)/SMO(+). In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc(+) progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1(+/-) mice exhibited increased progenitor, myofibroblast and fibrosis responses. In chronic liver injury, Pc(+) progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc(-)/GLI2(+) cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with

Computational Fluid Dynamics of Developing Avian Outflow Tract Heart Valves

PubMed Central

Bharadwaj, Koonal N.; Spitz, Cassie; Shekhar, Akshay; Yalcin, Huseyin C.; Butcher, Jonathan T.

2012-01-01

Hemodynamic forces play an important role in sculpting the embryonic heart and its valves. Alteration of blood flow patterns through the hearts of embryonic animal models lead to malformations that resemble some clinical congenital heart defects, but the precise mechanisms are poorly understood. Quantitative understanding of the local fluid forces acting in the heart has been elusive because of the extremely small and rapidly changing anatomy. In this study, we combine multiple imaging modalities with computational simulation to rigorously quantify the hemodynamic environment within the developing outflow tract (OFT) and its eventual aortic and pulmonary valves. In vivo Doppler ultrasound generated velocity profiles were applied to Micro-Computed Tomography generated 3D OFT lumen geometries from Hamburger-Hamilton (HH) stage 16 to 30 chick embryos. Computational fluid dynamics simulation initial conditions were iterated until local flow profiles converged with in vivo Doppler flow measurements. Results suggested that flow in the early tubular OFT (HH16 and HH23) was best approximated by Poiseuille flow, while later embryonic OFT septation (HH27, HH30) was mimicked by plug flow conditions. Peak wall shear stress (WSS) values increased from 18.16 dynes/cm2 at HH16 to 671.24 dynes/cm2 at HH30. Spatiotemporally averaged WSS values also showed a monotonic increase from 3.03 dynes/cm2 at HH16 to 136.50 dynes/cm2 at HH30. Simulated velocity streamlines in the early heart suggest a lack of mixing, which differed from classical ink injections. Changes in local flow patterns preceded and correlated with key morphogenetic events such as OFT septation and valve formation. This novel method to quantify local dynamic hemodynamics parameters affords insight into sculpting role of blood flow in the embryonic heart and provides a quantitative baseline dataset for future research. PMID:22535311

Cost-Effectiveness Analysis of Heat and Moisture Exchangers in Mechanically Ventilated Critically Ill Patients.

PubMed

Menegueti, Mayra Goncalves; Auxiliadora-Martins, Maria; Nunes, Altacilio Aparecido

2016-08-01

Moisturizing, heating and filtering gases inspired via the mechanical ventilation (MV) circuits help to reduce the adverse effects of MV. However, there is still no consensus regarding whether these measures improve patient prognosis, shorten MV duration, decrease airway secretion and lower the incidence of ventilator associated pneumonia (VAP) and other complications. The aim of this study was to study the incremental cost-effectiveness ratio associated with the use of heat and moisture exchangers (HME) filter to prevent VAP compared with the heated humidifiers (HH) presently adopted by intensive care unit (ICU) services within the Brazilian Healthcare Unified System. This study was a cost-effectiveness analysis (CEA) comparing HME and HH in preventing VAP (outcome) in mechanically ventilated adult patients admitted to an ICU of a public university hospital. The analysis considered a period of 12 months; MV duration of 11 and 12 days for patients in HH and HME groups, respectively and a daily cost of R$ 16.46 and R$ 13.42 for HH and HME, respectively. HME was more attractive; costs ranged from R$ 21,000.00 to R$ 22,000.00 and effectiveness was close to 0.71, compared with a cost of R$ 30,000.00 and effectiveness between 0.69 and 0.70 for HH. HME and HH differed significantly for incremental effectiveness. Even after an effectiveness gain of 1.5% in favor of HH, and despite the wide variation in the VAP rate, the HME effectiveness remained stable. The mean HME cost-effectiveness was lower than the mean HH cost-effectiveness, being the HME value close to R$ 44,000.00. Our findings revealed that HH and HME differ very little regarding effectiveness, which makes interpretation of the results in the context of clinical practice difficult. Nonetheless, there is no doubt that HME is advantageous. This technology incurs lower direct cost.

Photochemical Properties and Reactivity of a Ru Compound Containing an NAD/NADH-Functionalized 1,10-Phenanthroline Ligand.

PubMed

Kobayashi, Katsuaki; Ohtsu, Hideki; Nozaki, Koichi; Kitagawa, Susumu; Tanaka, Koji

2016-03-07

An NAD/NADH-functionalized ligand, benzo[b]pyrido[3,2-f][1,7]-phenanthroline (bpp), was newly synthesized. A Ru compound containing the bpp ligand, [Ru(bpp)(bpy)2](2+), underwent 2e(-) and 2H(+) reduction, generating the NADH form of the compound, [Ru(bppHH)(bpy)2](2+), in response to visible light irradiation in CH3CN/TEA/H2O (8/1/1). The UV-vis and fluorescent spectra of both [Ru(bpp)(bpy)2](2+) and [Ru(bppHH)(bpy)2](2+) resembled the spectra of [Ru(bpy)3](2+). Both complexes exhibited strong emission, with quantum yields of 0.086 and 0.031, respectively; values that are much higher than those obtained from the NAD/NADH-functionalized complexes [Ru(pbn)(bpy)2](2+) and [Ru(pbnHH)(bpy)2](2+) (pbn = (2-(2-pyridyl)benzo[b]-1.5-naphthyridine, pbnHH = hydrogenated form of pbn). The reduction potential of the bpp ligand in [Ru(bpp)(bpy)2](2+) (-1.28 V vs SCE) is much more negative than that of the pbn ligand in [Ru(pbn)(bpy)2](2+) (-0.74 V), although the oxidation potentials of bppHH and pbnHH are essentially equal (0.95 V). These results indicate that the electrochemical oxidation of the dihydropyridine moiety in the NADH-type ligand was independent of the π system, including the Ru polypyridyl framework. [Ru(bppHH)(bpy)2](2+) allowed the photoreduction of oxygen, generating H2O2 in 92% yield based on [Ru(bppHH)(bpy)2](2+). H2O2 production took place via singlet oxygen generated by the energy transfer from excited [Ru(bppHH)(bpy)2](2+) to triplet oxygen.

Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

PubMed

Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

2012-03-15

It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. Published by Elsevier Inc.

First Large-scale Herbig–Haro Jet Driven by a Proto-brown Dwarf

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

Riaz, B.; Briceño, C.; Heathcote, S.

2017-07-20

We report the discovery of a new Herbig–Haro jet, HH 1165, in SOAR narrow-band imaging of the vicinity of the σ Orionis cluster. HH 1165 shows a spectacular extended and collimated spatial structure, with a projected length of 0.26 pc, a bent C-shaped morphology, multiple knots, and fragmented bow shocks at the apparent ends of the flow. The H α image shows a bright halo with a clumpy distribution of material seen around the driving source, and curved reflection nebulosity tracing the outflow cavities. The driving source of HH 1165 is a Class I proto-brown dwarf, Mayrit 1701117 (M1701117), withmore » a total (dust+gas) mass of ∼36 M {sub Jup} and a bolometric luminosity of ∼0.1 L {sub ⊙}. High-resolution VLT/UVES spectra of M1701117 show a wealth of emission lines indicative of strong outflow and accretion activity. SOAR/Goodman low-resolution spectra along the jet axis show an asymmetrical morphology for HH 1165. We find a puzzling picture wherein the northwest part exhibits a classical HH jet running into a pre-dominantly neutral medium, while the southern part resembles an externally irradiated jet. The C-shaped bending in HH 1165 may be produced by the combined effects from the massive stars in the ionization front to the east, the σ Orionis core to the west, and the close proximity to the B2-type star HR 1950. HH 1165 shows all of the signatures to be considered as a scaled-down version of parsec-length HH jets, and can be termed as the first sub-stellar analog of a protostellar HH jet system.« less

Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats.

PubMed

Rajia, S; Chen, H; Morris, M J

2013-06-01

Physical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring. Sprague-Dawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CC(EX), HC(EX), HH(EX); n=10-12). Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P<0.05). These were exaggerated by postweaning HFD (HH vs HC; P<0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P<0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HC(EX) (vs HC; P<0.05) and HH(EX) (vs HH; P<0.01). Values in HC(EX) were indistinguishable from CC, however in HH(EX) these metabolic parameters remained higher than the sedentary HC and CC rats (P<0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor α and 11β-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HH(EX) (vs HH; P<0.05). While voluntary exercise almost completely reversed the metabolic effects of maternal obesity in chow fed offspring, it did not fully attenuate the increased adiposity, glucose intolerance and insulin resistance in offspring weaned onto HFD. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

PubMed

Robertson, Elaine V; Derakhshan, Mohammad H; Wirz, Angela A; Mitchell, David R; Going, James J; Kelman, Andrew W; Ballantyne, Stuart A; McColl, Kenneth E L

2017-07-01

Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux. 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/.

Metabolites in vertebrate Hedgehog signaling.

PubMed

Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

2014-04-11

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Perspectives on Intra- and Intercellular Trafficking of Hedgehog for Tissue Patterning

PubMed Central

Simon, Eléanor; Aguirre-Tamaral, Adrián; Aguilar, Gustavo; Guerrero, Isabel

2016-01-01

Intercellular communication is a fundamental process for correct tissue development. The mechanism of this process involves, among other things, the production and secretion of signaling molecules by specialized cell types and the capability of these signals to reach the target cells in order to trigger specific responses. Hedgehog (Hh) is one of the best-studied signaling pathways because of its importance during morphogenesis in many organisms. The Hh protein acts as a morphogen, activating its targets at a distance in a concentration-dependent manner. Post-translational modifications of Hh lead to a molecule covalently bond to two lipid moieties. These lipid modifications confer Hh high affinity to lipidic membranes, and intense studies have been carried out to explain its release into the extracellular matrix. This work reviews Hh molecule maturation, the intracellular recycling needed for its secretion and the proposed carriers to explain Hh transportation to the receiving cells. Special focus is placed on the role of specialized filopodia, also named cytonemes, in morphogen transport and gradient formation. PMID:29615597

Perspectives on Intra- and Intercellular Trafficking of Hedgehog for Tissue Patterning.

PubMed

Simon, Eléanor; Aguirre-Tamaral, Adrián; Aguilar, Gustavo; Guerrero, Isabel

2016-12-02

Intercellular communication is a fundamental process for correct tissue development. The mechanism of this process involves, among other things, the production and secretion of signaling molecules by specialized cell types and the capability of these signals to reach the target cells in order to trigger specific responses. Hedgehog (Hh) is one of the best-studied signaling pathways because of its importance during morphogenesis in many organisms. The Hh protein acts as a morphogen, activating its targets at a distance in a concentration-dependent manner. Post-translational modifications of Hh lead to a molecule covalently bond to two lipid moieties. These lipid modifications confer Hh high affinity to lipidic membranes, and intense studies have been carried out to explain its release into the extracellular matrix. This work reviews Hh molecule maturation, the intracellular recycling needed for its secretion and the proposed carriers to explain Hh transportation to the receiving cells. Special focus is placed on the role of specialized filopodia, also named cytonemes, in morphogen transport and gradient formation.

Extensions of suspension systems to measure effects of hypokinesia/hypodynamia and antiorthostasis in rats

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, J. M.

1984-01-01

Suspension systems are used to simulate hypokinetic/hypodynamic (H/H) and anitorthostatic (AO) responses seen under conditions of weightlessness. Growing rats in H/H suspension with unloaded hindlimbs for one and two weeks respond with muscle atrophy and increased excretion of nitrogenous end products such as urea, NH3 and 3 methyl histidine. Since muscle is in a dynamic state of synthesis and breakdown of protein, relationships between protein, RNA and DNA contents in the four muscles which reflect weight bearing and non-weight bearing functions were assessed. Protein and RNA progressively decreased over a one and two week period of H/H suspension: soleus gastrocnemius=plantaris EDL. Concommitant analysis of DNA contents showed there were no changes. The interpretation was that protein synthesis was slowed during H/H. As with muscle mass, protein and RNA levels recovered rapidly after removal from H/H. The AO rats (which are also H/H) respond with diuresis, natriuresis and kaliuresis in a manner comparable to responses seen when thoracic blood vessels are volume loaded.

VCAM-1 serum levels are associated with arthropathy in hereditary haemochromatosis.

PubMed

Nell-Duxneuner, Valerie; Axmann, Roland; Husar-Memmer, Emma; Dallos, Tomás; Datz, Christian; Stadlmayr, Andreas; Aigner, Elmar; Englbrecht, Matthias; Schett, Georg; Zwerina, Jochen

2013-12-01

The aim of this study was to assess the role of vascular adhesion molecule 1 (VCAM-1) in patients with hereditary haemochromatosis (HH) with or without arthropathy. Sera from a large cross-sectional cohort of unselected HH patients (n=147) were obtained and compared to an age-matched and sex-matched control group. Serum levels of VCAM-1 were measured by ELISA and were correlated with clinical measures. VCAM-1 serum levels were elevated in HH patients as compared to matched controls (mean 913±456 vs 654±451 ng/ml, p<0.0001). Within the HH patient group, VCAM-1 levels were much higher in patients with arthropathy and joint replacement surgery. VCAM-1 levels correlated well with radiographic measures of HH arthropathy (r=0.36, p<0.0001). Multivariate regression analysis confirmed a highly significant association of VCAM-1 serum levels and the presence of HH arthropathy, independent from diabetes, body mass index and age. VCAM-1 serum levels emerge as a biomarker for haemochromatosis arthropathy.

Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification

PubMed Central

Regard, Jean B.; Malhotra, Deepti; Gvozdenovic-Jeremic, Jelena; Josey, Michelle; Chen, Min; Weinstein, Lee S.; Lu, Jianming; Shore, Eileen M.; Kaplan, Frederick S.; Yang, Yingzi

2014-01-01

Bone formation is exquisitely controlled in space and time. Heterotopic ossification (HO), the pathologic formation of extra-skeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and lethal. However, the underlying molecular mechanisms are largely unknown. Here we demonstrate that Gαs restricts bone formation to the skeleton by inhibiting Hedgehog (Hh) signaling in mesenchymal progenitor cells. In progressive osseous heteroplasia (POH), a human disease caused by null mutations in GNAS that encodes Gαs, HH signaling is upregulated in ectopic osteoblasts and progenitor cells. Ectopic Hh signaling is sufficient to induce HO, while Hh signaling inhibition blocks HO in animal models. As our previous work has shown that GNAS gain of function mutations upregulate WNT/β-Catenin signaling in fibrous dysplasia (FD), our findings identify Gαs as a critical regulator of osteoblast differentiation by maintaining a balance between two key signaling pathways: Wnt/β-catenin and Hh. HH signaling inhibitors developed for cancer therapy may be repurposed to treat HO and other diseases caused by GNAS inactivation. PMID:24076664

Academic Engagement of Deaf and Hard of Hearing Students in a Co-Enrollment Program

ERIC Educational Resources Information Center

Metz, Kelly Kathleen

2013-01-01

In this observational study the researcher examined the Academic Engagement of deaf and hard of hearing (D/HH) students in a co-enrollment setting. Academic Engagement refers to attention, class participation, and time-on-task. Co-Enrollment is a model of group inclusion that provides D/HH students with access to a D/HH peer group as well as…

40 CFR Table A-6 to Subpart A of... - Data Elements That Are Inputs to Emission Equations and for Which the Reporting Deadline Is March...

Code of Federal Regulations, 2012 CFR

2012-07-01

...) used in the calculation. HH 98.346(c) All. HH 98.346(d)(1) Only degradable organic carbon (DOC) value, methane correction factor (MCF) values, and fraction of DOC dissimilated (DOCF) values. HH 98.346(d)(2...) All. TT 98.466(d)(1) All. TT 98.466(d)(2) Only degradable organic carbon (DOCX) value used in...

Mainstream Teachers about Including Deaf or Hard of Hearing Students

ERIC Educational Resources Information Center

Vermeulen, Jorine A.; Denessen, Eddie; Knoors, Harry

2012-01-01

This study is aimed at teachers' classroom practices and their beliefs and emotions regarding the inclusion of deaf or hard of hearing (d/hh) students in mainstream secondary schools. Nine teachers in two schools were interviewed about the inclusion of d/hh students. These teachers were found to consider the d/hh students' needs in their teaching…

Helix–hairpin–helix motifs confer salt resistance and processivity on chimeric DNA polymerases

PubMed Central

Pavlov, Andrey R.; Belova, Galina I.; Kozyavkin, Sergei A.; Slesarev, Alexei I.

2002-01-01

Helix–hairpin–helix (HhH) is a widespread motif involved in sequence-nonspecific DNA binding. The majority of HhH motifs function as DNA-binding modules with typical occurrence of one HhH motif or one or two (HhH)2 domains in proteins. We recently identified 24 HhH motifs in DNA topoisomerase V (Topo V). Although these motifs are dispensable for the topoisomerase activity of Topo V, their removal narrows the salt concentration range for topoisomerase activity tenfold. Here, we demonstrate the utility of Topo V's HhH motifs for modulating DNA-binding properties of the Stoffel fragment of TaqDNA polymerase and Pfu DNA polymerase. Different HhH cassettes fused with either NH2 terminus or COOH terminus of DNA polymerases broaden the salt concentration range of the polymerase activity significantly (up to 0.5 M NaCl or 1.8 M potassium glutamate). We found that anions play a major role in the inhibition of DNA polymerase activity. The resistance of initial extension rates and the processivity of chimeric polymerases to salts depend on the structure of added HhH motifs. Regardless of the type of the construct, the thermal stability of chimeric Taq polymerases increases under the optimal ionic conditions, as compared with that of TaqDNA polymerase or its Stoffel fragment. Our approach to raise the salt tolerance, processivity, and thermostability of Taq and Pfu DNA polymerases may be applied to all pol1- and polB-type polymerases, as well as to other DNA processing enzymes. PMID:12368475

A comparison between urban livestock production strategies in Burkina Faso, Mali and Nigeria in West Africa.

PubMed

Amadou, Hamadoun; Dossa, Luc Hippolyte; Lompo, Désiré Jean-Pascal; Abdulkadir, Aisha; Schlecht, Eva

2012-10-01

We undertook a comparative analysis of (peri-)urban livestock production strategies across three West African cities. Using a semi-structured questionnaire, livestock-keeping households (HH) were interviewed in Kano/Nigeria (84 HH), Bobo Dioulasso/Burkina Faso (63 HH) and Sikasso/Mali (63 HH). Questions covered livestock species kept, herd sizes and structure, feeds used, manure management, livestock marketing and production constraints. Sheep and goats dominated (p < 0.001) in Kano (76 and 75 % of HH) compared to Bobo Dioulasso (48 and 40 %) and Sikasso (28 and 40 %), while cattle and poultry were more frequent (p < 0.001) in Bobo Dioulasso (82 and 69 % of HH) and Sikasso (65 and 79 %) than in Kano (29 and 20 %). Across cities, ruminant feeding relied on grazing and homestead supplementation with fresh grasses, crop residues, cereal brans and cottonseed cake; cereal grains and brans were major ingredients of poultry feeds. Cattle and sheep fetched highest prices in Kano, unit prices for goats and chicken were highest in Sikasso. Across cities there was little association of gardens and livestock, whereas field cropping and livestock were integrated. There was no relation between the education of the HH head and the adoption of improved management practices (p > 0.05), but the proportion of HH heads with a long-term experience in UPA activities was higher in Kano and in Bobo Dioulasso than in Sikasso (p < 0.001). We therefore postulate that the high illiteracy rate among (peri-)urban livestock keepers in West Africa does not threaten the acceptance of improved technologies and innovations supporting the sustainability of their livestock production.

Evolutionary Genomics and Adaptive Evolution of the Hedgehog Gene Family (Shh, Ihh and Dhh) in Vertebrates

PubMed Central

Pereira, Joana; Johnson, Warren E.; O’Brien, Stephen J.; Jarvis, Erich D.; Zhang, Guojie; Gilbert, M. Thomas P.; Vasconcelos, Vitor; Antunes, Agostinho

2014-01-01

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we used comparative genomic and adaptive evolutionary analyses to characterize the evolution of the Hh genes in vertebrates following the two major whole genome duplication (WGD) events. To overcome the lack of Hh-coding sequences on avian publicly available databases, we used an extensive dataset of 45 avian and three non-avian reptilian genomes to show that birds have all three Hh paralogs. We find suggestions that following the WGD events, vertebrate Hh paralogous genes evolved independently within similar linkage groups and under different evolutionary rates, especially within the catalytic domain. The structural regions around the ion-binding site were identified to be under positive selection in the signaling domain. These findings contrast with those observed in invertebrates, where different lineages that experienced gene duplication retained similar selective constraints in the Hh orthologs. Our results provide new insights on the evolutionary history of the Hh gene family, the functional roles of these paralogs in vertebrate species, and on the location of mutational hotspots. PMID:25549322

The History of Hiatal Hernia Surgery

PubMed Central

Stylopoulos, Nicholas; Rattner, David W.

2005-01-01

Objective: This review addresses the historical evolution of hiatal hernia (HH) repair and reports in a chronological fashion the major milestones in HH surgery before the laparoscopic era. Methods: The medical literature and the collections of the History of Medicine Division of the National Library of Medicine were searched. Secondary references from all sources were studied. The senior author's experience and personal communications are also reported. Results: The first report of HH was published in 1853 by Bowditch. Rokitansky in 1855 demonstrated that esophagitis was due to gastroesophageal reflux, and Hirsch in 1900 diagnosed an HH using x-rays. Eppinger diagnosed an HH in a live patient, and Friedenwald and Feldman related the symptoms to the presence of an HH. In 1926, Akerlund proposed the term hiatus hernia and classified HH into the 3 types that we use today. The first elective surgical repair was reported in 1919 by Soresi. The physiologic link between HH and gastroesophageal reflux was made at the second half of the 20th century by Allison and Barrett. In the midst of a physiologic revolution, Nissen and Belsey developed their famous operations. In 1957, Collis published his innovative operation. Thal described his technique in 1965, and in 1967, Hill published his procedure. Many modifications of these procedures were published by Pearson and Henderson, Orringer and Sloan, Rossetti, Dor, and Toupet. Donahue and Demeester significantly improved Nissen's operation, and they were the first to truly understand its physiologic mechanism. Conclusion: Hiatal hernia surgery has evolved from anatomic repair to physiological restoration. PMID:15622007

The history of hiatal hernia surgery: from Bowditch to laparoscopy.

PubMed

Stylopoulos, Nicholas; Rattner, David W

2005-01-01

This review addresses the historical evolution of hiatal hernia (HH) repair and reports in a chronological fashion the major milestones in HH surgery before the laparoscopic era. The medical literature and the collections of the History of Medicine Division of the National Library of Medicine were searched. Secondary references from all sources were studied. The senior author's experience and personal communications are also reported. The first report of HH was published in 1853 by Bowditch. Rokitansky in 1855 demonstrated that esophagitis was due to gastroesophageal reflux, and Hirsch in 1900 diagnosed an HH using x-rays. Eppinger diagnosed an HH in a live patient, and Friedenwald and Feldman related the symptoms to the presence of an HH. In 1926, Akerlund proposed the term hiatus hernia and classified HH into the 3 types that we use today. The first elective surgical repair was reported in 1919 by Soresi. The physiologic link between HH and gastroesophageal reflux was made at the second half of the 20 century by Allison and Barrett. In the midst of a physiologic revolution, Nissen and Belsey developed their famous operations. In 1957, Collis published his innovative operation. Thal described his technique in 1965, and in 1967, Hill published his procedure. Many modifications of these procedures were published by Pearson and Henderson, Orringer and Sloan, Rossetti, Dor, and Toupet. Donahue and Demeester significantly improved Nissen's operation, and they were the first to truly understand its physiologic mechanism. Hiatal hernia surgery has evolved from anatomic repair to physiological restoration.

brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish

PubMed Central

Bergeron, Sadie A.; Tyurina, Oksana V.; Miller, Emily; Bagas, Andrea; Karlstrom, Rolf O.

2011-01-01

The transmembrane protein Brother of Cdo (Boc) has been implicated in Shh-mediated commissural axon guidance, and can both positively and negatively regulate Hedgehog (Hh) target gene transcription, however, little is known about in vivo requirements for Boc during vertebrate embryogenesis. The zebrafish umleitung (umlty54) mutant was identified by defects in retinotectal axon projections. Here, we show that the uml locus encodes Boc and that Boc function is cell-autonomously required for Hh-mediated neural patterning. Our phenotypic analysis suggests that Boc is required as a positive regulator of Hh signaling in the spinal cord, hypothalamus, pituitary, somites and upper jaw, but that Boc might negatively regulate Hh signals in the lower jaw. This study reveals a role for Boc in ventral CNS cells that receive high levels of Hh and uncovers previously unknown roles for Boc in vertebrate embryogenesis. PMID:21115611

An Automated Scheme for the Large-Scale Survey of Herbig-Haro Objects

NASA Astrophysics Data System (ADS)

Deng, Licai; Yang, Ji; Zheng, Zhongyuan; Jiang, Zhaoji

2001-04-01

Owing to their spectral properties, Herbig-Haro (HH) objects can be discovered using photometric methods through a combination of filters, sampling the characteristic spectral lines and the nearby continuum. The data are commonly processed through direct visual inspection of the images. To make data reduction more efficient and the results more uniform and complete, an automated searching scheme for HH objects is developed to manipulate the images using IRAF. This approach helps to extract images with only intrinsic HH emissions. By using this scheme, the pointlike stellar sources and extended nebulous sources with continuum emission can be eliminated from the original images. The objects with only characteristic HH emission become prominent and can be easily picked up. In this paper our scheme is illustrated by a sample field and has been applied to our surveys for HH objects.

Observations of the 63 micron forbidden O I line in Herbig-Haro objects

NASA Technical Reports Server (NTRS)

Cohen, Martin; Hollenbach, David J.; Haas, Michael R.; Erickson, Edwin F.

1988-01-01

The paper presents observations of the 63 micron forbidden O I line from Herbig-Haro objects and their exciting stars. Forbidden O I 63 micron emission is detected toward the HH-exciting stars T Tau, DG Tau, L1551 IRS 5, and toward the HH objects HH 7-11, HH 42A, and HH 43 which are displaced from their exciting stars. The forbidden O I emission is associated with these flows on the basis of its spatial coincidence and its negative radial velocities. If the exciting stars drive bipolar flows in which the 63 micron emission follows that at 6300 A, the absence of redshifted 63 micron lines from the three exciting stars might indicate that the disks hypothesized to overlie the receding lobes of these flows are still optically thick in the far-infrared.

Contraction kinetics of ventricular muscle from hibernating and nonhibernating mammals.

NASA Technical Reports Server (NTRS)

South, F. E.; Jacobs, H. K.

1973-01-01

Temperature-dependent studies of excitability and tension-production kinetics were made on isolated trabecular strips from hibernating hamsters (HH), nonhibernating hamsters (CH), and from rats (R). The strips were electrically driven and isometric tension along with its first time derivative (dP/dt) were recorded. Excitabilities of both hamster tissues were greater than that of rat tissue from 5 to 38 C with HH greater than CH. Peak tension production followed the order of HH greater than CH greater than R at all temperatures below 24 C. Rat preparations showed an optimum peak tension production at about 31 C while HH and CH showed optima between 17 and 24 C. Times to maximal rates of tension rise showed significant variation. In this respect, the order of sensitivity to decreasing temperature was HH greater than CH greater than R.

Finding friends online: online activities by deaf students and their well-being.

PubMed

Blom, Helen; Marschark, Marc; Vervloed, Mathijs P J; Knoors, Harry

2014-01-01

Generally, deaf and hard of hearing (D/HH) children have fewer friends than hearing peers and their friendships are of a lower quality. The research hypothesis was that using the computer to communicate with new online friends through social network sites or playing games with offline friends is associated with D/HH friendship qualities, because it removes certain communication barriers D/HH face in offline communication settings. With online questionnaires the relation between computer use and online, mixed (offline friend who you also speak in online settings), and offline friendship quality of D/HH and hearing students (18-25 years) was compared in both the Netherlands (n = 100) and the United States (n = 122). In addition, the study examined whether the different friendship qualities were related to the participants' well-being. Results showed that, in general, D/HH students' friendship qualities and levels of well-being were similar to their hearing peers. The quality of the mixed friendships was positively related to well-being. Furthermore, the frequency of pc use with both online and offline friends was positively related to friendships qualities in both hearing and D/HH students. A combination of the online and offline friendship seems to be the most important friendship type for both hearing and D/HH students and it is worthwhile to encourage this friendship type.

A Systematic Review and Narrative Synthesis of Health Economic Studies Conducted for Hereditary Haemochromatosis.

PubMed

de Graaff, Barbara; Neil, Amanda; Sanderson, Kristy; Si, Lei; Yee, Kwang Chien; Palmer, Andrew J

2015-10-01

Hereditary haemochromatosis (HH) is a common genetic condition amongst people of northern European heritage. HH is associated with increased iron absorption leading to parenchymal organ damage and multiple arthropathies. Early diagnosis and treatment prevents complications. Population screening may increase early diagnosis, but no programmes have been introduced internationally: a paucity of health economic data is often cited as a barrier. To conduct a systematic review of all health economic studies in HH. Studies were identified through electronic searching of economic/biomedical databases. Any study on HH with original economic component was included. Study quality was formally assessed. Health economic data were extracted and analysed through narrative synthesis. Thirty-eight studies met the inclusion criteria. The majority of papers reported on costs or cost effectiveness of screening programmes. Whilst most concluded screening was cost effective compared with no screening, methodological flaws limit the quality of these findings. Assumptions regarding clinical penetrance, effectiveness of screening, health-state utility values (HSUVs), exclusion of early symptomatology (such as fatigue, lethargy and multiple arthropathies) and quantification of costs associated with HH were identified as key limitations. Treatment studies concluded therapeutic venepuncture was the most cost-effective intervention. There is a paucity of high-quality health economic studies relating to HH. The development of a comprehensive HH cost-effectiveness model utilising HSUVs is required to determine whether screening is worthwhile.

The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.

PubMed

Wallace, Daniel F; Subramaniam, V Nathan

2016-06-01

The prevalence of HFE-related hereditary hemochromatosis (HH) among European populations has been well studied. There are no prevalence data for atypical forms of HH caused by mutations in HFE2, HAMP, TFR2, or SLC40A1. The purpose of this study was to estimate the population prevalence of these non-HFE forms of HH. A list of HH pathogenic variants in publically available next-generation sequence (NGS) databases was compiled and allele frequencies were determined. Of 161 variants previously associated with HH, 43 were represented among the NGS data sets; an additional 40 unreported functional variants also were identified. The predicted prevalence of HFE HH and the p.Cys282Tyr mutation closely matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. We have, for the first time, estimated the population prevalence of non-HFE HH. This methodology could be applied to estimate the population prevalence of a wide variety of genetic disorders.Genet Med 18 6, 618-626.

Finding Friends Online: Online Activities by Deaf Students and Their Well-Being

PubMed Central

Blom, Helen; Marschark, Marc; Vervloed, Mathijs P. J.; Knoors, Harry

2014-01-01

Generally, deaf and hard of hearing (D/HH) children have fewer friends than hearing peers and their friendships are of a lower quality. The research hypothesis was that using the computer to communicate with new online friends through social network sites or playing games with offline friends is associated with D/HH friendship qualities, because it removes certain communication barriers D/HH face in offline communication settings. With online questionnaires the relation between computer use and online, mixed (offline friend who you also speak in online settings), and offline friendship quality of D/HH and hearing students (18–25 years) was compared in both the Netherlands (n = 100) and the United States (n = 122). In addition, the study examined whether the different friendship qualities were related to the participants' well-being. Results showed that, in general, D/HH students' friendship qualities and levels of well-being were similar to their hearing peers. The quality of the mixed friendships was positively related to well-being. Furthermore, the frequency of pc use with both online and offline friends was positively related to friendships qualities in both hearing and D/HH students. A combination of the online and offline friendship seems to be the most important friendship type for both hearing and D/HH students and it is worthwhile to encourage this friendship type. PMID:24520373

High Phosphohistone H3 Expression Correlates with Adverse Clinical, Biological, and Pathological Factors in Neuroblastomas

PubMed Central

Ramani, Pramila; Taylor, Scott; Miller, Elizabeth; Sowa-Avugrah, Emile; May, Margaret T.

2015-01-01

Phosphohistone H3 (pHH3), a biomarker of the late G2- and M-phase of the cell cycle, provides a powerful indication of the proliferative state of many cancers. We investigated the prognostic significance of pHH3 by immunostaining 80 neuroblastomas and counting the average number of strongly stained nuclei and mitotic figures. The median and 75th percentile pHH3 proliferation indices (PIs) were 0.54% and 1.06% (range, 0.01% to 2.23%) respectively. pHH3 expression was significantly higher in neuroblastomas from patients with adverse clinical characteristics, all unfavorable pathological factors including high mitosis karyorrhexis index (MKI), and adverse biological factors including MYCN oncogene amplification. High pHH3-PIs, at 1% threshold, were significantly associated with a shorter overall survival (OS) and event-free survival (EFS) in the univariable Cox regression analyses. In the multivariable models, high pHH3 counts were significantly associated with worse OS after adjustment for age but were not independent of either high MKI or MYCN amplification. In children less than 18 months of age, high MKIs and high PHH3-PIs were associated with significantly worse OS and EFS. In conclusion, high pHH3 expression correlates strongly with high MKI and MYCN amplification and indicates poor prognosis in neuroblastomas. PMID:25711230

Comparing handheld and hands-free cell phone usage behaviors while driving.

PubMed

Soccolich, Susan A; Fitch, Gregory M; Perez, Miguel A; Hanowski, Richard J

2014-01-01

The goal of this study was to compare cell phone usage behaviors while driving across 3 types of cell phones: handheld (HH) cell phones, portable hands-free (PHF) cell phones, and integrated hands-free (IHF) cell phones. Naturalistic driving data were used to observe HH, PHF, and IHF usage behaviors in participants' own vehicles without any instructions or manipulations by researchers. In addition to naturalistic driving data, drivers provided their personal cell phone call records. Calls during driving were sampled and observed in naturalistically collected video. Calls were reviewed to identify cell phone type used for, and duration of, cell phone subtasks, non-cell phone secondary tasks, and other use behaviors. Drivers in the study self-identified as HH, PHF, or IHF users if they reported using that cell phone type at least 50% of the time. However, each sampled call was classified as HH, PHF, or IHF if the talking/listening subtask was conducted using that cell phone type, without considering the driver's self-reported group. Drivers with PHF or IHF systems also used HH cell phones (IHF group used HH cell phone in 53.2% of the interactions, PHF group used HH cell phone for 55.5% of interactions). Talking/listening on a PHF phone or an IHF phone was significantly longer than talking/listening on an HH phone (P <.05). HH dialing was significantly longer in duration than PHF or IHF begin/answer tasks. End phone call task for HH phones was significantly longer in duration than the end phone call task for PHF and IHF phones. Of all the non-cell phone-related secondary tasks, eating or drinking was found to occur significantly more often during IHF subtasks (0.58%) than in HH subtasks (0.15%). Drivers observed to reach for their cell phone mostly kept their cell phone in the cup holder (36.3%) or in their seat or lap (29.0% of interactions); however, some observed locations may have required drivers to move out of position. Hands-free cell phone technologies reduce

A Review of Educational Practices for Deaf/Hard of Hearing Students with Comorbid Autism

ERIC Educational Resources Information Center

Borders, Christina M.; Jones Bock, Stacey; Probst, Kristi M.

2016-01-01

The population of students who are deaf/hard of hearing (D/HH) that have additional disabilities remains at over 40 per cent. One population of particular concern is the group of D/HH students with a comorbid diagnosis of autism spectrum disorders (ASD). The prevalence of ASD in the D/HH population is 1 in 59 (Szymanski et al., 2012. "Deaf…

Self-Esteem of Deaf and Hard of Hearing Students in Regular and Special Schools

ERIC Educational Resources Information Center

Lesar, Irena; Smrtnik Vitulic, Helena

2014-01-01

The study focuses on the self-esteem of deaf and hard of hearing (D/HH) students from Slovenia. A total of 80 D/HH students from regular and special primary schools (grades 6-9) and from regular and special secondary schools (grades 1-4) completed the Self-Esteem Questionnaire (Lamovec 1994). For the entire group of D/HH students, the results of…

31 CFR 353.35 - Payment (redemption).

Code of Federal Regulations, 2014 CFR

2014-07-01

..., 2003, or earlier, will be paid at any time after 6 months from its issue date. A Series EE bond issued... Service Series No. 1-80 (31 CFR part 351). (c) Series HH. A Series HH bond will be paid at any time after... STATES SAVINGS BONDS, SERIES EE AND HH General Provisions for Payment § 353.35 Payment (redemption). (a...

31 CFR 353.35 - Payment (redemption).

Code of Federal Regulations, 2013 CFR

2013-07-01

..., 2003, or earlier, will be paid at any time after 6 months from its issue date. A Series EE bond issued... Debt Series No. 1-80 (31 CFR part 351). (c) Series HH. A Series HH bond will be paid at any time after... STATES SAVINGS BONDS, SERIES EE AND HH General Provisions for Payment § 353.35 Payment (redemption). (a...

31 CFR 353.35 - Payment (redemption).

Code of Federal Regulations, 2011 CFR

2011-07-01

..., 2003, or earlier, will be paid at any time after 6 months from its issue date. A Series EE bond issued... Debt Series No. 1-80 (31 CFR part 351). (c) Series HH. A Series HH bond will be paid at any time after... STATES SAVINGS BONDS, SERIES EE AND HH General Provisions for Payment § 353.35 Payment (redemption). (a...

31 CFR 353.35 - Payment (redemption).

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 2003, or earlier, will be paid at any time after 6 months from its issue date. A Series EE bond issued... Debt Series No. 1-80 (31 CFR part 351). (c) Series HH. A Series HH bond will be paid at any time after... STATES SAVINGS BONDS, SERIES EE AND HH General Provisions for Payment § 353.35 Payment (redemption). (a...

31 CFR 353.35 - Payment (redemption).

Code of Federal Regulations, 2012 CFR

2012-07-01

..., 2003, or earlier, will be paid at any time after 6 months from its issue date. A Series EE bond issued... Debt Series No. 1-80 (31 CFR part 351). (c) Series HH. A Series HH bond will be paid at any time after... STATES SAVINGS BONDS, SERIES EE AND HH General Provisions for Payment § 353.35 Payment (redemption). (a...

Hyperhidrosis Prevalence and Demographical Characteristics in Dermatology Outpatients in Shanghai and Vancouver

PubMed Central

Kalia, Sunil; Huang, Rachel Yuanshen; Phillips, Arlie; Su, Mingwan; Yang, Sen; Zhang, Xuejun; Zhou, Pingyu; Zhou, Youwen

2016-01-01

Background There is a wide variation in the reported prevalence of primary hyperhidrosis in the literature. Further, it is unknown if primary hyperhidrosis is a lifelong condition, or if demographical factors influence hyperhidrosis prevalence. Objectives This study aims to examine the prevalence of hyperhidrosis in multiple ethnic groups from two ethnically diverse cities and to determine if the prevalence of primary hyperhidrosis changes according to age, gender, ethnicity, body mass index, and geographical locations. Methods In total, 1010 consecutive subjects attending dermatology outpatient clinics in Shanghai Skin Disease Hospital and 1018 subjects in Skin Care Center of Vancouver General Hospital were invited to fill out a questionnaire on their presenting concerns, demographical information, and sweating symptoms. The subjects were then classified to have primary hyperhidrosis using the criteria of International Hyperhidrosis Society, late-onset hyperhidrosis, or no-hyperhidrosis. The prevalence of primary HH and late-onset HH was calculated for the entire study population and in subgroups stratified according to age of examination, sex, ethnicity, presenting diagnosis, body mass index, and specific study cities. Multivariate logistic regression analyses were performed to assess the impact of these factors on HH prevalence. Results The prevalence of primary hyperhidrosis is very similar in Shanghai and in Vancouver, at 14.5% and 12.3% respectively. In addition, 4.0% of subjects in Shanghai and 4.4% subjects in Vancouver suffer from late-onset HH. Primary HH has highest prevalence in those younger than 30 years of age, decreasing dramatically in later years. Caucasian subjects are at least 2.5 times more likely to develop axillary hyperhidrosis compared to Chinese subjects. Obesity does not have much influence on primary HH presentation, although it does increase significantly the development of late-onset HH. Finally, there is no major difference of

Hyperhidrosis Prevalence and Demographical Characteristics in Dermatology Outpatients in Shanghai and Vancouver.

PubMed

Liu, Yudan; Bahar, Rayeheh; Kalia, Sunil; Huang, Rachel Yuanshen; Phillips, Arlie; Su, Mingwan; Yang, Sen; Zhang, Xuejun; Zhou, Pingyu; Zhou, Youwen

2016-01-01

There is a wide variation in the reported prevalence of primary hyperhidrosis in the literature. Further, it is unknown if primary hyperhidrosis is a lifelong condition, or if demographical factors influence hyperhidrosis prevalence. This study aims to examine the prevalence of hyperhidrosis in multiple ethnic groups from two ethnically diverse cities and to determine if the prevalence of primary hyperhidrosis changes according to age, gender, ethnicity, body mass index, and geographical locations. In total, 1010 consecutive subjects attending dermatology outpatient clinics in Shanghai Skin Disease Hospital and 1018 subjects in Skin Care Center of Vancouver General Hospital were invited to fill out a questionnaire on their presenting concerns, demographical information, and sweating symptoms. The subjects were then classified to have primary hyperhidrosis using the criteria of International Hyperhidrosis Society, late-onset hyperhidrosis, or no-hyperhidrosis. The prevalence of primary HH and late-onset HH was calculated for the entire study population and in subgroups stratified according to age of examination, sex, ethnicity, presenting diagnosis, body mass index, and specific study cities. Multivariate logistic regression analyses were performed to assess the impact of these factors on HH prevalence. The prevalence of primary hyperhidrosis is very similar in Shanghai and in Vancouver, at 14.5% and 12.3% respectively. In addition, 4.0% of subjects in Shanghai and 4.4% subjects in Vancouver suffer from late-onset HH. Primary HH has highest prevalence in those younger than 30 years of age, decreasing dramatically in later years. Caucasian subjects are at least 2.5 times more likely to develop axillary hyperhidrosis compared to Chinese subjects. Obesity does not have much influence on primary HH presentation, although it does increase significantly the development of late-onset HH. Finally, there is no major difference of hyperhidrosis between Chinese subjects in

Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo.

PubMed

Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U; Pinto, Jorge; Porto, Graça

2015-01-01

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH.

Lymphocyte Gene Expression Signatures from Patients and Mouse Models of Hereditary Hemochromatosis Reveal a Function of HFE as a Negative Regulator of CD8+ T-Lymphocyte Activation and Differentiation In Vivo

PubMed Central

Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U.; Pinto, Jorge; Porto, Graça

2015-01-01

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe -/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe -/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe -/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH. PMID

A hand hygiene intervention to decrease infections among children attending day care centers: design of a cluster randomized controlled trial.

PubMed

Zomer, Tizza P; Erasmus, Vicki; Vlaar, Nico; van Beeck, Ed F; Tjon-A-Tsien, Aimée; Richardus, Jan Hendrik; Voeten, Hélène A C M

2013-06-03

Day care center attendance has been recognized as a risk factor for acquiring gastrointestinal and respiratory infections, which can be prevented with adequate hand hygiene (HH). Based on previous studies on environmental and sociocognitive determinants of caregivers' compliance with HH guidelines in day care centers (DCCs), an intervention has been developed aiming to improve caregivers' and children's HH compliance and decrease infections among children attending DCCs. The aim of this paper is to describe the design of a cluster randomized controlled trial to evaluate the effectiveness of this intervention. The intervention will be evaluated in a two-arm cluster randomized controlled trial among 71 DCCs in the Netherlands. In total, 36 DCCs will receive the intervention consisting of four components: 1) HH products (dispensers and refills for paper towels, soap, alcohol-based hand sanitizer, and hand cream); 2) training to educate about the Dutch national HH guidelines; 3) two team training sessions aimed at goal setting and formulating specific HH improvement activities; and 4) reminders and cues to action (posters/stickers). Intervention DCCs will be compared to 35 control DCCs continuing usual practice. The primary outcome measure will be observed HH compliance of caregivers and children, measured at baseline and one, three, and six months after start of the intervention. The secondary outcome measure will be the incidence of gastrointestinal and respiratory infections in 600 children attending DCCs, monitored over six months by parents using a calendar to mark the days their child has diarrhea and/or a cold. Multilevel logistic regression will be performed to assess the effect of the intervention on HH compliance. Multilevel poisson regression will be performed to assess the incidence of gastrointestinal and respiratory infections in children attending DCCs. This is one of the first DCC intervention studies to assess HH compliance of both caregivers and

A hand hygiene intervention to decrease infections among children attending day care centers: design of a cluster randomized controlled trial

PubMed Central

2013-01-01

Background Day care center attendance has been recognized as a risk factor for acquiring gastrointestinal and respiratory infections, which can be prevented with adequate hand hygiene (HH). Based on previous studies on environmental and sociocognitive determinants of caregivers’ compliance with HH guidelines in day care centers (DCCs), an intervention has been developed aiming to improve caregivers’ and children’s HH compliance and decrease infections among children attending DCCs. The aim of this paper is to describe the design of a cluster randomized controlled trial to evaluate the effectiveness of this intervention. Methods/design The intervention will be evaluated in a two-arm cluster randomized controlled trial among 71 DCCs in the Netherlands. In total, 36 DCCs will receive the intervention consisting of four components: 1) HH products (dispensers and refills for paper towels, soap, alcohol-based hand sanitizer, and hand cream); 2) training to educate about the Dutch national HH guidelines; 3) two team training sessions aimed at goal setting and formulating specific HH improvement activities; and 4) reminders and cues to action (posters/stickers). Intervention DCCs will be compared to 35 control DCCs continuing usual practice. The primary outcome measure will be observed HH compliance of caregivers and children, measured at baseline and one, three, and six months after start of the intervention. The secondary outcome measure will be the incidence of gastrointestinal and respiratory infections in 600 children attending DCCs, monitored over six months by parents using a calendar to mark the days their child has diarrhea and/or a cold. Multilevel logistic regression will be performed to assess the effect of the intervention on HH compliance. Multilevel poisson regression will be performed to assess the incidence of gastrointestinal and respiratory infections in children attending DCCs. Discussion This is one of the first DCC intervention studies to assess

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head.

PubMed

Bekri, Abdelhamid; Billaud, Marc; Thélu, Jacques

2014-01-01

Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development.

Walking speed is associated with self-perceived hearing handicap in high-functioning older adults: The Fujiwara-kyo study.

PubMed

Tomioka, Kimiko; Harano, Akihiro; Hazaki, Kan; Morikawa, Masayuki; Iwamoto, Junko; Saeki, Keigo; Okamoto, Nozomi; Kurumatani, Norio

2015-06-01

The present study investigated whether physical performance and musculoskeletal pain (MSP) are associated with self-perceived hearing handicap (HH) among high-functioning older adults. We analyzed a total of 3982 community-dwelling high-functioning older adults (age 65 years and older). HH was assessed using the Hearing Handicap Inventory for Elderly-Screening. Self-reported hearing impairment (HI) was evaluated using a single question. We measured handgrip strength, walking speed (WS) and standing balance for assessments of physical performance. The severity of MSP assessed by interviews took into account its duration, limitation of daily activity and frequency. The prevalence of HH and HI in our sample was 22.2% and 28.1%, respectively. After adjusting for other two physical performance measures, MSP, sex, age, education, marital status, risk factors for hearing loss, instrumental activity of daily living, depression, cognitive function and self-reported HI, the odds ratios for HH in the second fastest, the second slowest, and the slowest WS quartile were 1.14 (95% CI = 0.81-1.58), 1.29 (95% CI = 0.92-1.79), and 1.58 (95% CI = 1.11-2.23), respectively, compared with the fastest WS quartile. A significant dose-response relationship was found between slower WS and HH (P for trend = 0.01). No significant association with HH was found in handgrip strength, standing balance and MSP. WS is associated with self-perceived HH in high-functioning older adults. The present study suggests that exercise programs to improve walking ability might be effective in preventing HH of self-sustainable older adults. © 2014 Japan Geriatrics Society.

Inbreeding trends and pedigree analysis of Bavarian mountain hounds, Hanoverian hounds and Tyrolean hounds.

PubMed

Voges, S; Distl, O

2009-10-01

The objective of this study was to analyse genetic diversity for the three scent-hound breeds Bavarian mountain hound (BMH), Hanoverian hound (HH) and Tyrolean hound (TH) using all available pedigree information from scent-hound kennel clubs for these three breeds throughout Europe. The pedigree data of the BMH and the HH date back to 1912 and 1894, respectively. Pedigree data of the TH were available from the 1960s onwards. The reference populations included all BMH (n = 3231), HH (n = 1371) and TH (n = 1167) dogs registered between 1992 and 2004. Average generation intervals were 5.3 years for the BMH and 5.0 years for the HH and TH. Average inbreeding coefficients for the reference populations were 4.5%, 6.8% and 9.5% for the BMH, HH and TH. The effective numbers of founders, ancestors and founder genomes were lowest for the TH and highest for the BMH. The effective numbers of founder genomes were 10.9, 5.6 and 4.3 for the BMH, HH and TH. Effective population size was largest for the BMH with 72.7 effective breeding animals, followed by the HH with 50.9 and TH with 26.5. The most important ten ancestors had genetic contributions to the reference populations of 54.4%, 65.2% and 77.9% in the BMH, HH and TH. The results of our study indicate the need for careful breed management in these highly specialized hound breeds to maintain genetic diversity. European stud books should be established for these dog breeds in order to avoid inbreeding due to missing pedigree records.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

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

Zhu, Zhong Xin; Sun, Cong Cong; Wenzhou People's Hospital, Wenzhou, Zhejiang

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Westernmore » blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.« less

Genetic Analysis of Hedgehog Signaling in Ventral Body Wall Development and the Onset of Omphalocele Formation

PubMed Central

Matsumaru, Daisuke; Haraguchi, Ryuma; Miyagawa, Shinichi; Motoyama, Jun; Nakagata, Naomi; Meijlink, Frits; Yamada, Gen

2011-01-01

Background An omphalocele is one of the major ventral body wall malformations and is characterized by abnormally herniated viscera from the body trunk. It has been frequently found to be associated with other structural malformations, such as genitourinary malformations and digit abnormalities. In spite of its clinical importance, the etiology of omphalocele formation is still controversial. Hedgehog (Hh) signaling is one of the essential growth factor signaling pathways involved in the formation of the limbs and urogenital system. However, the relationship between Hh signaling and ventral body wall formation remains unclear. Methodology/Principal Findings To gain insight into the roles of Hh signaling in ventral body wall formation and its malformation, we analyzed phenotypes of mouse mutants of Sonic hedgehog (Shh), GLI-Kruppel family member 3 (Gli3) and Aristaless-like homeobox 4 (Alx4). Introduction of additional Alx4Lst mutations into the Gli3Xt/Xt background resulted in various degrees of severe omphalocele and pubic diastasis. In addition, loss of a single Shh allele restored the omphalocele and pubic symphysis of Gli3Xt/+; Alx4Lst/Lst embryos. We also observed ectopic Hh activity in the ventral body wall region of Gli3Xt/Xt embryos. Moreover, tamoxifen-inducible gain-of-function experiments to induce ectopic Hh signaling revealed Hh signal dose-dependent formation of omphaloceles. Conclusions/Significance We suggest that one of the possible causes of omphalocele and pubic diastasis is ectopically-induced Hh signaling. To our knowledge, this would be the first demonstration of the involvement of Hh signaling in ventral body wall malformation and the genetic rescue of omphalocele phenotypes. PMID:21283718

Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells

PubMed Central

Wang, Feng; Ma, Ling; Zhang, Zhengkui; Liu, Xiaoran; Gao, Hongqiao; Zhuang, Yan; Yang, Pei; Kornmann, Marko; Tian, Xiaodong; Yang, Yinmo

2016-01-01

Hedgehog (Hh) signaling is crucially involved in tumorigenesis. This study aimed to assess the role of Hh signaling in the regulation of epithelial-mesenchymal transition (EMT), stemness properties and chemoresistance of human pancreatic Panc-1 cancer stem cells (CSCs). Panc-1 cells were transfected with recombinant lentiviral vectors to silence SMO and serum-free floating-culture system was used to isolate Panc-1 tumorspheres. The expression of CSC and EMT markers was detected by flow cytometry, real-time RT-PCR and Western blot analysis. Malignant behaviors of Panc-1 CSC were evaluated by tumorigenicity assays and nude mouse lung metastasis model. We found that tumorspheres derived from pancreatic cancer cell line Panc-1 possessed self-renewal, differentiation and stemness properties. Hh pathway and EMT were active in Panc-1 tumorspheres. Inhibition of Hh signaling by SMO knockdown inhibited self-renewal, EMT, invasion, chemoresistance, pulmonary metastasis, tumorigenesis of pancreatic CSCs. In conclusion, Hh signaling contributes to the maintenance of stem-like properties and chemoresistance of pancreatic CSC and promotes the tumorigenesis and metastasis of pancreatic cancer. Hh pathway is a potential molecular target for the development of therapeutic strategies for pancreatic CSCs. PMID:26918054

Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach During 3 Years in 6 Hospitals in 3 Mexican Cities.

PubMed

Miranda-Novales, María Guadalupe; Sobreyra-Oropeza, Martha; Rosenthal, Víctor Daniel; Higuera, Francisco; Armas-Ruiz, Alberto; Pérez-Serrato, Irma; Torres-Hernández, Héctor; Zamudio-Lugo, Irma; Flores-Ruiz, Eric M; Campuzano, Roberto; Mena-Brito, Jorge; Sánchez-López, Martha; Chávez-Gómez, Amalia; Rivera-Morales, Jaime; Valero-Rodríguez, Julián E

2015-06-10

To evaluate the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene (HH) approach in Mexico, and analyze predictors of poor HH compliance. From June 2002 to April 2006, we conducted a prospective, observational, before-and-after study in 8 intensive care units (ICUs) from 6 hospitals in 3 cities of Mexico. The approach included administrative support, availability of supplies, education and training, reminders in the workplace, process surveillance, and performance feedback. A total of 13,201 observations for HH opportunities were done in each ICU, during randomly selected 30-minute periods. Overall, HH compliance increased from 45% to 79% (95% confidence interval [CI], 69.1-86.5; P = 0.01). Univariate and multivariate analyses showed that several variables were significantly associated with poor HH compliance: males versus females (61% versus 66%; 95% CI, 0.91-0.96; P = 0.0001), physicians versus nurses (62% versus 67%; 95% CI, 0.91-0.97; P = 0.0001), and adult versus neonatal ICUs (67% versus 54%; 95% CI, 0.79-0.84; P = 0.0001), among others. Hand hygiene programs should focus on variables found to be predictors of poor HH compliance.

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

PubMed

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-04-25

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells.

PubMed

Wang, Feng; Ma, Ling; Zhang, Zhengkui; Liu, Xiaoran; Gao, Hongqiao; Zhuang, Yan; Yang, Pei; Kornmann, Marko; Tian, Xiaodong; Yang, Yinmo

2016-01-01

Hedgehog (Hh) signaling is crucially involved in tumorigenesis. This study aimed to assess the role of Hh signaling in the regulation of epithelial-mesenchymal transition (EMT), stemness properties and chemoresistance of human pancreatic Panc-1 cancer stem cells (CSCs). Panc-1 cells were transfected with recombinant lentiviral vectors to silence SMO and serum-free floating-culture system was used to isolate Panc-1 tumorspheres. The expression of CSC and EMT markers was detected by flow cytometry, real-time RT-PCR and Western blot analysis. Malignant behaviors of Panc-1 CSC were evaluated by tumorigenicity assays and nude mouse lung metastasis model. We found that tumorspheres derived from pancreatic cancer cell line Panc-1 possessed self-renewal, differentiation and stemness properties. Hh pathway and EMT were active in Panc-1 tumorspheres. Inhibition of Hh signaling by SMO knockdown inhibited self-renewal, EMT, invasion, chemoresistance, pulmonary metastasis, tumorigenesis of pancreatic CSCs. In conclusion, Hh signaling contributes to the maintenance of stem-like properties and chemoresistance of pancreatic CSC and promotes the tumorigenesis and metastasis of pancreatic cancer. Hh pathway is a potential molecular target for the development of therapeutic strategies for pancreatic CSCs.

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

PubMed Central

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-01-01

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

Hereditary hemochromatosis: awareness and genetic testing acceptability in Western Romania.

PubMed

Neghina, Adriana Maria; Anghel, Andrei

2010-12-01

a public health strategy to promote early diagnosis of hemochromatosis gene (HFE)-related hemochromatosis (HFE-HH) largely depends on people's acceptance of available screening tests. The present study aimed at evaluating patient awareness of HFE-HH and their acceptance of DNA testing in western Romania. a total of 221 participants were randomly recruited from the ambulatory unit of the Emergency County Hospital in Timisoara, Romania. They received brief information on HFE-HH and were assessed for the signs and symptoms of hemochromatosis. HFE genotyping was offered to all of them. Only two cases (0.9%) had previous knowledge of HFE-HH. Twenty-one cases (9.5%) underwent genetic testing. Characteristics associated with test acceptance were age <45 years, male gender, and educational attainment. Acceptance was associated with a desire to know if they had HFE-HH (85.7%). The most prevalent refusal reason was a desire for more information (41%). larger educational programs are required to increase people's awareness about HFE-HH in western Romania. Nevertheless, within health care settings, the importance of disease detection and patient's educational background appear to be essential for achieving high rates of participation in the genetic test.

Arcticibacter pallidicorallinus sp. nov. isolated from glacier ice.

PubMed

Liu, Qing; Kim, Song-gun; Liu, Hong-can; Xin, Yu-hua; Zhou, Yu-guang

2014-07-01

A Gram-stain-negative, rod-shaped bacterium (strain Hh36(T)) was isolated from the No. 1 glacier in Xinjiang, north-west China. Colonies of strain Hh36(T) were pink, convex and round on PYG medium plates. Strain Hh36(T) was able to grow at 4-30 °C and pH 6.0-8.0. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Hh36(T) was related to members of the genus Arcticibacter. The major cellular fatty acids of the novel strain were iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and iso-C17 : 0 3-OH. The G+C content of the genomic DNA was 44.0 mol%. On the basis of phenotypic characteristics and phylogenetic analysis, strain Hh36(T) is considered to represent a novel species of the genus Arcticibacter, for which the name Arcticibacter pallidicorallinus sp. nov. is proposed. The type strain is Hh36(T) ( = CGMCC 1.9313(T)  = KCTC 32542(T)). © 2014 Institute of Microbiology, Chinese Academy of Sciences.

The treatment of hyperinsulinemic hypoglycaemia in adults: an update.

PubMed

Davi, M V; Pia, A; Guarnotta, V; Pizza, G; Colao, A; Faggiano, A

2017-01-01

Treatment of hyperinsulinemic hypoglycaemia (HH) is challenging due to the rarity of this condition and the difficulty of differential diagnosis. The aim of this article is to give an overview of the recent literature on the management of adult HH. A search for reviews, original articles, original case reports between 1995 and 2016 in PubMed using the following keywords: hyperinsulinemic hypoglycaemia, insulinoma, nesidioblastosis, gastric bypass, autoimmune hypoglycaemia, hyperinsulinism, treatment was performed. One hundred and forty articles were selected and analysed focusing on the most recent treatments of HH. New approaches to treatment of HH are available including mini-invasive surgical techniques and alternative local-regional ablative therapy for benign insulinoma and everolimus for malignant insulinoma. A correct differential diagnosis is of paramount importance to avoid unnecessary surgical operations and to implement the appropriate treatment mainly in the uncommon forms of HH, such as nesidioblastosis and autoimmune hypoglycaemia.

Unraveling the Pathogenesis of Hoyeraal-Hreidarsson Syndrome, a Complex Telomere Biology Disorder

PubMed Central

Glousker, Galina; Touzot, Fabien; Revy, Patrick; Tzfati, Yehuda; Savage, Sharon A.

2015-01-01

SUMMARY Hoyeraal-Hreidarsson (HH) syndrome is a multisystem genetic disorder characterized by very short telomeres and considered a clinically severe variant of dyskeratosis congenita (DC). The main cause of mortality, usually in early childhood, is bone marrow failure. Mutations in several telomere biology genes have been reported to cause HH in about 60% of the HH patients, but the genetic defects in the rest of the patients are still unknown. Understanding the aetiology of HH and its diverse manifestations is challenging because of the complexity of telomere biology and the multiple telomeric and non-telomeric functions played by telomere-associated proteins in processes such as telomere replication, telomere protection, DNA damage response and ribosome and spliceosome assembly. Here we review the known clinical complications, molecular defects and germline mutations associated with HH, and elucidate possible mechanistic explanations and remaining questions in our understanding of the disease. PMID:25940403

New physics in resonant production of Higgs boson pairs.

PubMed

Barger, Vernon; Everett, Lisa L; Jackson, C B; Peterson, Andrea D; Shaughnessy, Gabe

2015-01-09

We advocate a search for an extended scalar sector at the LHC via hh production, where h is the 125 GeV Higgs boson. A resonance feature in the hh invariant mass is a smoking gun of an s-channel heavy Higgs resonance, H. With one h decaying to two photons and the other decaying to b quarks, the resonant signal may be discoverable above the hh continuum background for M(H)<1  TeV. The product of the scalar and top Yukawa couplings can be measured to better than 10%-20% accuracy, and its sign can be inferred from the hh line shape via interference effects.

Using Workflow Diagrams to Address Hand Hygiene in Pediatric Long-Term Care Facilities1

PubMed Central

Carter, Eileen J.; Cohen, Bevin; Murray, Meghan T.; Saiman, Lisa; Larson, Elaine L.

2015-01-01

Hand hygiene (HH) in pediatric long-term care settings has been found to be sub-optimal. Multidisciplinary teams at three pediatric long-term care facilities developed step-by-step workflow diagrams of commonly performed tasks highlighting HH opportunities. Diagrams were validated through observation of tasks and concurrent diagram assessment. Facility teams developed six workflow diagrams that underwent 22 validation observations. Four main themes emerged: 1) diagram specificity, 2) wording and layout, 3) timing of HH indications, and 4) environmental hygiene. The development of workflow diagrams is an opportunity to identify and address the complexity of HH in pediatric long-term care facilities. PMID:25773517

Inhibition of Hedgehog-Signaling Driven Genes in Prostate Cancer Cells by Sutherlandia frutescens Extract

PubMed Central

Lu, Yuan; Starkey, Nicholas; Lei, Wei; Li, Jilong; Cheng, Jianlin; Folk, William R.; Lubahn, Dennis B.

2015-01-01

Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk. PMID:26710108

Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells.

PubMed

Macedo, M F; Porto, G; Costa, M; Vieira, C P; Rocha, B; Cruz, E

2010-03-01

Low CD8(+) T lymphocyte numbers have long been described in hereditary haemochromatosis (HH). Recently, two conserved haplotypes localized near the microsatellite D6S105 at the major histocompatibility complex (MHC) class I region were described predicting the clinical expression of HH and the CD8(+) T lymphocyte numbers. The A-A-T haplotype was associated with a severe clinical expression of HH and low CD8(+) T lymphocyte numbers, while the G-G-G haplotype was associated with a milder clinical expression of HH and high CD8(+) T lymphocyte numbers. As CD8(+) T lymphocytes are a very heterogeneous population, in this study we analysed the CD8(+) subpopulations of naive, central memory (T(CM)) and effector memory (T(EM)), and further subsets of CD8(+) T(EM) cells in 47 HH patients and 68 controls. In addition, association studies were conducted between the conserved haplotypes and the CD8(+) T cell subpopulations in HH. Variations of the numbers of naive and central memory cells with age were similar between HH patients and controls. For T(EM) cells and the T(EM) CD27(-)CD28(-) subset no effect of age was observed in HH [R(2) = 0.001, not significant (n.s.) and R(2) = 0.01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R(2) = 0.09, P = 0.017 and R(2) = 0.22, P = 0.0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8(+) T(EM) cells due especially to lower numbers of T(EM) CD27(-)CD28(-) (0.206 +/- 0.119 and 0.066 +/- 0.067 x 10(6) cells/ml, respectively) than patients carrying the G-G-G haplotype (0.358 +/- 0.195 and 0.246 +/- 0.202 x 10(6) cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8(+) T cells into the most mature phenotype.

The Hedgehog Signal Induced Modulation of Bone Morphogenetic Protein Signaling: An Essential Signaling Relay for Urinary Tract Morphogenesis

PubMed Central

Nakagata, Naomi; Miyagawa, Shinichi; Suzuki, Kentaro; Kitazawa, Sohei; Yamada, Gen

2012-01-01

Background Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects in such progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. Methodology/Principal Findings To elucidate the pathogenic mechanisms of upper urinary tract malformations, we analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh−/− displayed hydroureter and hydronephrosis phenotypes and reduced expression of several developmental markers. In addition, we suggested that Shh modulation at an early embryonic stage is responsible for such phenotypes by analyzing the Shh conditional mutants. Tissue contribution assays of Hh-responsive cells revealed that peri-cloacal mesenchymal cells, which received Hh signal secreted from cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss-of-functional mutants for Hh signaling revealed a correlation between Hh signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell lineages. This system thus made it possible to analyze the primary functions of the growth factor signaling relay. The defective Hh-to-Bmp signaling relay resulted in severe urinary tract phenotypes with a decrease in the number of Hh-responsive cells. Conclusions/Significance This study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh

HFE gene mutations in patients with primary iron overload: is there a significant improvement in molecular diagnosis yield with HFE sequencing?

PubMed

Santos, Paulo C J L; Pereira, Alexandre C; Cançado, Rodolfo D; Schettert, Isolmar T; Sobreira, Tiago J P; Oliveira, Paulo S L; Hirata, Rosario D C; Hirata, Mario H; Figueiredo, Maria Stella; Chiattone, Carlos S; Krieger, Jose E; Guerra-Shinohara, Elvira M

2010-12-15

Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation>50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n=11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and β2-microglobulin (β2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion, screening of HFE through direct sequencing, as compared to p.C282Y/p.H63D genotyping, was not able to increase the molecular diagnosis yield of HH. The novel p.V256I mutation could not be implicated in the molecular basis of the HH phenotype, although its role cannot be completely excluded in HH-phenotype development. Our molecular modeling analysis can help in the analysis of novel, previously undescribed, HFE mutations. Copyright © 2010 Elsevier Inc. All rights reserved.

Evaluation of a contact lens-embedded sensor for intraocular pressure measurement.

PubMed

Twa, Michael D; Roberts, Cynthia J; Karol, Huikai J; Mahmoud, Ashraf M; Weber, Paul A; Small, Robert H

2010-08-01

To evaluate a novel contact lens-embedded pressure sensor for continuous measurement of intraocular pressure (IOP). Repeated measurements of IOP and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in sitting and supine positions using 3 configurations of the dynamic contour tonometer: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded sensor (CL). The IOP and OPA for each condition were compared using repeated measures ANOVA and the 95% limits of agreement were calculated. The sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to 17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3 mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg). Supine IOP and OPA measurements with the CL and HH sensors were both greater than their corresponding sitting measurements, but were significantly less with the CL sensor than the HH sensor. The mean difference and 95% Limits of Agreement were smallest for the DCT and CL sensor comparisons (0.7+/-3.9 mm Hg) and widest for the CL and HH sensors (-1.9+/-7.25 mm Hg); these wider limits were attributed to greater HH measurement variability. The CL sensor was comparable to HH and DCT sensors with sitting subjects and is a viable method for measuring IOP and OPA. Supine measurements of IOP and OPA were greater than sitting conditions and were comparatively lower with the CL sensor. HH measurements were more variable than CL measurements and this influenced the Limits of Agreement for both sitting and supine conditions.

Humidification in the intensive care unit. Prospective study of a new protocol utilizing heated humidification and a hygroscopic condenser humidifier.

PubMed

Branson, R D; Davis, K; Campbell, R S; Johnson, D J; Porembka, D T

1993-12-01

Determine the utility of a proposed algorithm in allowing safe, efficient humidification in mechanically ventilated patients using both a hygroscopic condenser humidifier (HCH) and heated humidifier (HH). A prospective study using an algorithm to chose humidification devices based on physical examination and sputum characteristics. All patients admitted to the surgical ICU. One hundred twenty consecutive patients requiring mechanical ventilation (MV) were studied. Patients were examined by the attending respiratory care practitioner and given either an HCH or HH. If patients demonstrated any of the following--thick or tenacious secretions, core temperature < 32 degrees C, or bloody secretions--they were given an HH. All others used an HCH. If any of the above conditions occurred during HCH use, the patient was given an HH. Duration of ventilation, incidence of nosocomial pneumonia, ventilator circuit colonization, and mortality were determined for patients in each group. Cost of humidification devices, number of suctioning procedures per day, and volume of saline solution instilled were also recorded. Initially, 27 percent (32/120) of patients used an HH and 73 percent (88/120) used an HCH. During the study, ten patients required changing to an HH during HCH use. Patients in the HH group were more likely to have preexisting lung disease and had a longer duration of ventilation (83 +/- 21 h) and higher mortality (21 percent). Patients in the HCH group were more likely to be postoperative, had shorter durations of ventilation (38 +/- 14 h), and lower mortality (9 percent). There was no difference in the incidence of nosocomial pneumonia between the two groups (9 percent vs 6 percent) and endotracheal tube occlusion did not occur in either group. Circuit colonization was common in the HH group (64 percent) but rate in the HCH group (5 percent). Cost per day was significantly less for the HCH group ($4 vs $19.80). Patients who required a change from HCH to HH did so at

Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

PubMed

Shin, Jeong-Oh; Ankamreddy, Harinarayana; Jakka, Naga Mahesh; Lee, Seokwon; Kim, Un-Kyung; Bok, Jinwoong

2017-01-01

The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.

Effects of the location of distal histidine in the reaction of myoglobin with hydrogen peroxide.

PubMed

Matsui, T; Ozaki, S i; Liong, E; Phillips, G N; Watanabe, Y

1999-01-29

To clarify how the location of distal histidine affects the activation process of H2O2 by heme proteins, we have characterized reactions with H2O2 for the L29H/H64L and F43H/H64L mutants of sperm whale myoglobin (Mb), designed to locate the histidine farther from the heme iron. Whereas the L29H/H64L double substitution retarded the reaction with H2O2, an 11-fold rate increase versus wild-type Mb was observed for the F43H/H64L mutant. The Vmax values for 1-electron oxidations by the myoglobins correlate well with the varied reactivities with H2O2. The functions of the distal histidine as a general acid-base catalyst were examined based on the reactions with cumene hydroperoxide and cyanide, and only the histidine in F43H/H64L Mb was suggested to facilitate heterolysis of the peroxide bond. The x-ray crystal structures of the mutants confirmed that the distal histidines in F43H/H64L Mb and peroxidase are similar in distance from the heme iron, whereas the distal histidine in L29H/H64L Mb is located too far to enhance heterolysis. Our results indicate that the proper positioning of the distal histidine is essential for the activation of H2O2 by heme enzymes.

Accuracy of a radiofrequency identification (RFID) badge system to monitor hand hygiene behavior during routine clinical activities.

PubMed

Pineles, Lisa L; Morgan, Daniel J; Limper, Heather M; Weber, Stephen G; Thom, Kerri A; Perencevich, Eli N; Harris, Anthony D; Landon, Emily

2014-02-01

Hand hygiene (HH) is a critical part of infection prevention in health care settings. Hospitals around the world continuously struggle to improve health care personnel (HCP) HH compliance. The current gold standard for monitoring compliance is direct observation; however, this method is time-consuming and costly. One emerging area of interest involves automated systems for monitoring HH behavior such as radiofrequency identification (RFID) tracking systems. To assess the accuracy of a commercially available RFID system in detecting HCP HH behavior, we compared direct observation with data collected by the RFID system in a simulated validation setting and to a real-life clinical setting over 2 hospitals. A total of 1,554 HH events was observed. Accuracy for identifying HH events was high in the simulated validation setting (88.5%) but relatively low in the real-life clinical setting (52.4%). This difference was significant (P < .01). Accuracy for detecting HCP movement into and out of patient rooms was also high in the simulated setting but not in the real-life clinical setting (100% on entry and exit in simulated setting vs 54.3% entry and 49.5% exit in real-life clinical setting, P < .01). In this validation study of an RFID system, almost half of the HH events were missed. More research is necessary to further develop these systems and improve accuracy prior to widespread adoption. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Hypobaric hypoxia impairs cued and contextual fear memory in rats.

PubMed

Kumari, Punita; Kauser, Hina; Wadhwa, Meetu; Roy, Koustav; Alam, Shahnawaz; Sahu, Surajit; Kishore, Krishna; Ray, Koushik; Panjwani, Usha

2018-04-26

Fear memory is essential for survival, and its dysregulation leads to disorders. High altitude hypobaric hypoxia (HH) is known to induce cognitive decline. However, its effect on fear memory is still an enigma. We aimed to investigate the temporal effect of HH on fear conditioning and the underlying mechanism. Adult male Sprague-Dawley rats were trained for fear conditioning and exposed to simulated HH equivalent to 25,000 ft for different durations (1, 3, 7, 14 and 21 days). Subsequently, rats were tested for cued and contextual fear conditioning. Neuronal morphology, apoptosis and DNA fragmentation were studied in the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). We observed significant deficit in cued and contextual fear acquisition (at 1, 3 and 7 days) and consolidation (cued at 1 and 3 days and contextual fear at 1, 3 and 7 days) under HH. HH exposure with retraining showed the earlier restoration of contextual fear memory. Further, we found a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in mPFC, hippocampus, and BLA up to 7 days of HH exposure. The present study concludes that HH exposure equivalent to 25000 ft induced cued and contextual fear memory deficit (acquisition and consolidation) which is found to be correlated with the neurodegenerative changes in the limbic brain regions. Copyright © 2018. Published by Elsevier B.V.

Post-translational modifications of linker histone H1 variants in mammals

NASA Astrophysics Data System (ADS)

Starkova, T. Yu; Polyanichko, A. M.; Artamonova, T. O.; Khodorkovskii, M. A.; Kostyleva, E. I.; Chikhirzhina, E. V.; Tomilin, A. N.

2017-02-01

The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2-H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

PubMed

Omenetti, Alessia; Yang, Liu; Li, Yin-Xiong; McCall, Shannon J; Jung, Youngmi; Sicklick, Jason K; Huang, Jiawen; Choi, Steve; Suzuki, Ayako; Diehl, Anna Mae

2007-05-01

In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The proximity of the myofibroblasts and cholangiocytes suggests that mesenchymal-epithelial crosstalk promotes the fibroproliferative response to cholestatic liver injury. Studying BDL mice, we found that bile duct obstruction induces activity of the Hedgehog (Hh) pathway, a system that regulates the viability and differentiation of various progenitors during embryogenesis. After BDL, many bile ductular cells and fibroblastic-appearing cells in the portal stroma express Hh ligands, receptor and/or target genes. Transwell cocultures of an immature cholangiocyte line that expresses the Hh receptor, Patched (Ptc), with liver myofibroblastic cells demonstrated that both cell types produced Hh ligands that enhanced each other's viability and proliferation. Further support for the concept that Hh signaling modulates the response to BDL was generated by studying PtcLacZ mice, which have an impaired ability to constrain Hh signaling due to a heterozygous deficiency of Ptc. After BDL, PtcLacZ mice upregulated fibrosis gene expression earlier than wild-type controls and manifested an unusually intense ductular reaction, more expanded fibrotic portal areas, and a greater number of lobular necrotic foci. Our findings reveal that adult livers resurrect developmental signaling systems, such as the Hh pathway, to guide remodeling of the biliary epithelia and stroma after cholestatic injury.

Automated Performance Monitoring and Assessment for DCS Digital Systems.

DTIC Science & Technology

1977-10-01

5.2 Analog Radio Systems 439 A.6 Group Data Modem (AN/USC-26) 453 A.6.1 Data Rates 453 vii ^II^^^IH^^^H^^^ HH ^ HH ^MflH^MBHBIEiiH^B^B&99S&_ 7...in U. 03 ÜJ 03 1 is «r V X V 1 ts ro O O M O 1 rs CM ^r 1- 1 rs TI o _i ! is o *•* OI- hh -Hhh- «c o> s Ci ÜJ li’ UJ UJ ÜJ u i •o o IS H d Ci Ci...j 0) tOOOOQiklkHH 03 03 UI0)BfiSSAAHI> HH ttaaAuuuuoocccs s E z xi 03 o^i a a i- 2: x x x x cß<:ffi<:ä<i:ä<:a«iB<c« s- 1- > r> z r: z z u u M M x

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1985. Part 1. IDSCR Inc. - Amjet Aerospace Inc).

DTIC Science & Technology

1985-01-01

Hioinu)H M H in in co co co C* HH -H*H H •-OOOO O 0«H—<W*H H » JB HCMCMCMCMHCMCM H « a CO CO CO CO CO CO CO CM CM CM CM CM CM CM CM CM...OK- JB (/lb0b0C/>b0C/IO cor^Pic or to £«00-1 »f^CMP»^00PlO-JZ J:«CM_I « CM CM CO « 0O _l z CO—1—1—1—1—«—l_J UMO-JZ •o-O »--^PO 3 CM-H CM CM CM CM...QHH CM • HH CM CM CM CM CM CM CM CM CM CM CO CM CM OHO H CM CM CM « m ^^ CO CO CO CO « « CM m o o> f~ HH H H H r^rv NNNN -4 f- H H o CO CD H P1HH

Reading strategies of Chinese students with severe to profound hearing loss.

PubMed

Cheung, Ka Yan; Leung, Man Tak; McPherson, Bradley

2013-01-01

The present study investigated the significance of auditory discrimination and the use of phonological and orthographic codes during the course of reading development in Chinese students who are deaf or hard of hearing (D/HH). In this study, the reading behaviors of D/HH students in 2 tasks-a task on auditory perception of onset rime and a synonym decision task-were compared with those of their chronological age-matched and reading level (RL)-matched controls. Cross-group comparison of the performances of participants in the task on auditory perception suggests that poor auditory discrimination ability may be a possible cause of reading problems for D/HH students. In addition, results of the synonym decision task reveal that D/HH students with poor reading ability demonstrate a significantly greater preference for orthographic rather than phonological information, when compared with the D/HH students with good reading ability and their RL-matched controls. Implications for future studies and educational planning are discussed.

Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development.

PubMed

Rodenfels, Jonathan; Lavrynenko, Oksana; Ayciriex, Sophie; Sampaio, Julio L; Carvalho, Maria; Shevchenko, Andrej; Eaton, Suzanne

2014-12-01

In Drosophila larvae, growth and developmental timing are regulated by nutrition in a tightly coordinated fashion. The networks that couple these processes are far from understood. Here, we show that the intestine responds to nutrient availability by regulating production of a circulating lipoprotein-associated form of the signaling protein Hedgehog (Hh). Levels of circulating Hh tune the rates of growth and developmental timing in a coordinated fashion. Circulating Hh signals to the fat body to control larval growth. It regulates developmental timing by controlling ecdysteroid production in the prothoracic gland. Circulating Hh is especially important during starvation, when it is also required for mobilization of fat body triacylglycerol (TAG) stores. Thus, we demonstrate that Hh, previously known only for its local morphogenetic functions, also acts as a lipoprotein-associated endocrine hormone, coordinating the response of multiple tissues to nutrient availability. © 2014 Rodenfels et al.; Published by Cold Spring Harbor Laboratory Press.

Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age.

PubMed

Arya, Ved Bhushan; Flanagan, Sarah E; Kumaran, Anitha; Shield, Julian P; Ellard, Sian; Hussain, Khalid; Kapoor, Ritika R

2013-07-01

To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. Serum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients.

Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis.

PubMed

Infante, Paola; Faedda, Roberta; Bernardi, Flavia; Bufalieri, Francesca; Lospinoso Severini, Ludovica; Alfonsi, Romina; Mazzà, Daniela; Siler, Mariangela; Coni, Sonia; Po, Agnese; Petroni, Marialaura; Ferretti, Elisabetta; Mori, Mattia; De Smaele, Enrico; Canettieri, Gianluca; Capalbo, Carlo; Maroder, Marella; Screpanti, Isabella; Kool, Marcel; Pfister, Stefan M; Guardavaccaro, Daniele; Gulino, Alberto; Di Marcotullio, Lucia

2018-03-07

Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/β-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. This process increases the association of SuFu with Gli3, promoting the conversion of Gli3 into a repressor, which keeps Hh signalling off. Activation of Hh signalling antagonises the Itch-dependent polyubiquitylation of SuFu. Notably, different SuFu mutations occurring in medulloblastoma patients are insensitive to Itch activity, thus leading to deregulated Hh signalling and enhancing medulloblastoma cell growth. Our findings uncover mechanisms controlling the tumour suppressive functions of SuFu and reveal that their alterations are implicated in medulloblastoma tumorigenesis.

Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age

PubMed Central

Arya, Ved Bhushan; Flanagan, Sarah E; Kumaran, Anitha; Shield, Julian P; Ellard, Sian; Hussain, Khalid; Kapoor, Ritika R

2013-01-01

Objective To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). Methods Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. Results There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. Conclusions Serum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients. PMID:23362136

Handheld Sensor for UXO Discrimination:

DTIC Science & Technology

2006-06-01

between buried UXO and clutter. This project demonstrated the use of commercially available technology (Geonics EM61-HH handheld metal detector ) for...determine whether each target was UXO or clutter. The Geonics EM61-HH handheld metal detector is a pulsed electromagnetic induction (EMI) sensor. The...processing, the EM61-HH handheld metal detector can 2 be used in a cued identification mode to reliably discriminate between buried UXO and clutter

Current and emerging therapeutic modalities for hyperhidrosis, part 1: conservative and noninvasive treatments.

PubMed

Ram, Ramin; Lowe, Nicholas J; Yamauchi, Paul S

2007-03-01

Approximately 1% to 3% of the US population has hyperhidrosis (HH). HH can be an incapacitating medical condition because it not only hinders patient quality of life but also causes the secondary effect of excess cutaneous sweat. There is a broad spectrum of treatment modalities including topical and systemic therapies, iontophoresis, localized neuroinhibitory injections, and surgical interventions. This article reviews HH and the conservative treatments for the condition.

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

Samarzija, Ivana; Beard, Peter, E-mail: peter.beard@epfl.ch

Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervical cancer cells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of themore » Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.« less

Effect of APAP and heated humidification with a heated breathing tube on adherence, quality of life, and nasopharyngeal complaints.

PubMed

Nilius, Georg; Franke, Karl J; Domanski, Ulrike; Schroeder, Maik; Ruhle, Karl H

2016-03-01

Positive airway pressure (PAP) therapy adherence can be affected by rhinitis sicca and xerostomia complaints. Additional heated humidification (HH) is the appropriate method when such complaints arise. The aim of this study was to determine if HH with a supplementary heated breathing tube can increase adherence, reduce subjective nasopharyngeal complaints (NPC), and improve sleepiness (ESS: Epworth Sleepiness Scale) and quality of life (FOSQ: Functional Outcome of Sleep Questionnaire). We subdivided 72 obstructive sleep apnea (OSA) patients into two groups before therapy initiation. The NPC risk group consists of subjects with NPC and the low-risk group without. The risk group was identified by a score of >9 in a 5-item 25-point NPC questionnaire and pathological ESS. All patients were eligible for automatic CPAP devices (APAP), which were randomly configured with or without HH during 6 weeks. The adherence differences with and without HH were not significant in the NPC risk group (330 ± 103 vs. 281 ± 118 min/night) and in the low-risk group (330 ± 116 vs. 321 ± 89). NPC and ESS scores in the risk group were both significantly reduced with HH. Daily function (FOSQ) in the risk group was significantly improved with HH (90.0 ± 11.9 vs. 82.0 ± 12.0 (p < 0.05)). HH showed a tendency to improve APAP adherence. The adherence in both groups was quite high, and for that reason, it is difficult to show a statistically significant effect. A differentiation into NPC risk groups before starting PAP treatment is useful. HH reduces side effects and sleepiness and improves quality of life in an NPC risk group.

A review of hedgehog signaling in cranial bone development

PubMed Central

Pan, Angel; Chang, Le; Nguyen, Alan; James, Aaron W.

2013-01-01

During craniofacial development, the Hedgehog (HH) signaling pathway is essential for mesodermal tissue patterning and differentiation. The HH family consists of three protein ligands: Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Desert Hedgehog (DHH), of which two are expressed in the craniofacial complex (IHH and SHH). Dysregulations in HH signaling are well documented to result in a wide range of craniofacial abnormalities, including holoprosencephaly (HPE), hypotelorism, and cleft lip/palate. Furthermore, mutations in HH effectors, co-receptors, and ciliary proteins result in skeletal and craniofacial deformities. Cranial suture morphogenesis is a delicate developmental process that requires control of cell commitment, proliferation and differentiation. This review focuses on both what is known and what remains unknown regarding HH signaling in cranial suture morphogenesis and intramembranous ossification. As demonstrated from murine studies, expression of both SHH and IHH is critical to the formation and fusion of the cranial sutures and calvarial ossification. SHH expression has been observed in the cranial suture mesenchyme and its precise function is not fully defined, although some postulate SHH to delay cranial suture fusion. IHH expression is mainly found on the osteogenic fronts of the calvarial bones, and functions to induce cell proliferation and differentiation. Unfortunately, neonatal lethality of IHH deficient mice precludes a detailed examination of their postnatal calvarial phenotype. In summary, a number of basic questions are yet to be answered regarding domains of expression, developmental role, and functional overlap of HH morphogens in the calvaria. Nevertheless, SHH and IHH ligands are integral to cranial suture development and regulation of calvarial ossification. When HH signaling goes awry, the resultant suite of morphologic abnormalities highlights the important roles of HH signaling in cranial development. PMID:23565096

Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia.

PubMed

Senniappan, Senthil; Sadeghizadeh, Atefeh; Flanagan, Sarah E; Ellard, Sian; Hashemipour, Mahin; Hosseinzadeh, Majid; Salehi, Mansour; Hussain, Khalid

2015-08-13

Hyperinsulinaemic hypoglycaemia (HH) is a group of clinically and genetically heterogeneous disorders characterized by unregulated insulin secretion. Abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, UCP2 and HNF1A) have been reported in HH, the most common being ABCC8 and KCNJ11. We describe the genetic aetiology and phenotype of Iranian patients with HH. Retrospective clinical, biochemical and genetic information was collected on 23 patients with biochemically confirmed HH. Mutation analysis was carried out for the ATP-sensitive potassium (K(ATP)) channel genes (ABCC8 and KCNJ11), GLUD1, GCK, HADH and HNF4A. 78% of the patients were identified to have a genetic cause for HH. 48% of patients had mutation in HADH, whilst ABCC8/KCNJ11 mutations were identified in 30% of patients. Among the diazoxide-responsive patients (18/23), mutations were identified in 72%. These include two novel homozygous ABCC8 mutations. Of the five patients with diazoxide-unresponsive HH, three had homozygous ABCC8 mutation, one had heterozygous ABCC8 mutation inherited from an unaffected father and one had homozygous KCNJ11 mutation. 52% of children in our cohort were born to consanguineous parents. Patients with ABCC8/KCNJ11 mutations were noted to be significantly heavier than those with HADH mutation (p = 0.002). Our results revealed neurodevelopmental deficits in 30% and epilepsy in 52% of all patients. To the best of our knowledge, this is the first study of its kind in Iran. We found disease-causing mutations in 78% of HH patients. The predominance of HADH mutation might be due to a high incidence of consanguineous marriage in this population. Further research involving a larger cohort of HH patients is required in Iranian population.

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes

PubMed Central

Dhindsa, Sandeep; Ghanim, Husam; Batra, Manav; Kuhadiya, Nitesh D.; Abuaysheh, Sanaa; Sandhu, Sartaj; Green, Kelly; Makdissi, Antoine; Hejna, Jeanne; Chaudhuri, Ajay; Punyanitya, Mark

2016-01-01

OBJECTIVE One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (−3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P < 0.05 for all). CONCLUSIONS Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat. PMID:26622051

Assessing the impact of budget controls on the prescribing behaviours of physicians treating dialysis-dependent patients.

PubMed

Chang, Ray-E; Tsai, Ya-Hsing; Myrtle, Robert C

2015-11-01

This study examined whether outpatient haemodialysis providers changed their treatment practices with the establishment of an outpatient dialysis global budget (ODGB) through analysing the outpatient visits and medication received by those patients. A sample of 4668 observations (patient year) of 1350 haemodialysis with hypertension (HH) patients and 4668 observations of 1436 non-HH (NHH) patients were drawn from the National Health Insurance Research Database over the years from 1999 to 2005. The impact of ODGB on hypertension-related outpatient utilization of HH was estimated using the difference in difference (DID) method and examined in three stages: (1) the fee for service stage, the pre-ODGB (2000), (2) the phase-in stage (2001-2002) and (3) the post-ODGB stage (2003-2005). ODGB implementation did not affect the number of dialysis visits for HH patients. However, it did lead to a reduction in fees for antihypertension drugs used by haemodialysis facilities. There was an increase of 4.06 visits per patient per year (P < 0.001) in the number of non-dialysis outpatient with antihypertensive drugs visits for HH patients compared with the control group. The total fees for antihypertensive drugs for HH patients increased by New Taiwan Dollars (NT$)13 008 (P < 0.001) per patient per year relative to the control group after the implementation of ODGB. As ODGB was implemented, HH patients received fewer antihypertensive drugs during their dialysis visit. In addition, there was an increase in the number of non-dialysis outpatient visits by HH patients as well as increased payment in the drugs associated with their non-dialysis outpatient visits compared with the control group. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

Alcohol Activates the Hedgehog Pathway and Induces Related Pro-carcinogenic Processes in the Alcohol-Preferring Rat Model of Hepatocarcinogenesis

PubMed Central

Chan, Isaac S.; Guy, Cynthia D.; Machado, Mariana V.; Wank, Abigail; Kadiyala, Vishnu; Michelotti, Gregory; Choi, Steve; Swiderska-Syn, Marzena; Karaca, Gamze; Pereira, Thiago A.; Yip-Schneider, Michele T.; Schmidt, C. Max; Diehl, Anna Mae

2014-01-01

Background Alcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is hepatotoxic, habitual alcohol ingestion evokes a recurrent demand for hepatic regeneration. The alcohol-preferring (P) rat model mimics the level of alcohol consumption by humans who habitually abuse alcohol. Previously, we showed that habitual heavy alcohol ingestion amplified age-related hepatocarcinogenesis in P-rats, with over 80% of alcohol-consuming P rats developing HCCs after 18 months of alcohol exposure, compared to only 5% of water-drinking controls. Methods Herein, we used quantitative real time PCR and quantitative immunocytochemistry to compare liver tissues from alcohol-consuming P rats and water-fed P rat controls after 6, 12, or 18 months of drinking. We aimed to identify potential mechanisms that might underlie the differences in liver cancer formation, and hypothesized that chronic alcohol ingestion would activate Hedgehog (HH), a regenerative signaling pathway that is over-activated in HCC. Results Chronic alcohol ingestion amplified age-related degenerative changes in hepatocytes, but did not cause appreciable liver inflammation or fibrosis even after 18 months of heavy drinking. HH signaling was also enhanced by alcohol exposure, as evidenced by increased levels of mRNAs encoding HH ligands, HH-regulated transcription factors, and HH-target genes. Immunocytochemistry confirmed increased alcohol-related accumulation of HH ligand-producing cells and HH-responsive target cells. HH-related regenerative responses were also induced in alcohol-exposed rats. Three of these processes (i.e., deregulated progenitor expansion, the reverse-Warburg effect, and epithelial-to-mesenchymal transitions) are known to promote cancer growth in other tissues. Conclusions Alcohol-related changes in Hedgehog signaling

40 CFR Table Hh-1 to Subpart Hh of... - Emissions Factors, Oxidation Factors and Methods

Code of Federal Regulations, 2011 CFR

2011-07-01

... evapotranspiration rate exceeds the mean annual precipitation rate plus recirculated leachate. Use the greater value when the potential evapotranspiration rate does not exceed the mean annual precipitation rate plus... value rather than assessing the potential evapotranspiration rate or recirculated leachate rate. [75 FR...

40 CFR Table Hh-1 to Subpart Hh of... - Emissions Factors, Oxidation Factors and Methods

Code of Federal Regulations, 2014 CFR

2014-07-01

... value when the potential evapotranspiration rate exceeds the mean annual precipitation rate plus recirculated leachate. Use the greater value when the potential evapotranspiration rate does not exceed the... recirculation can elect to use the greater value rather than assessing the potential evapotranspiration rate or...

40 CFR Table Hh-1 to Subpart Hh of... - Emissions Factors, Oxidation Factors and Methods

Code of Federal Regulations, 2013 CFR

2013-07-01

... evapotranspiration rate exceeds the mean annual precipitation rate plus recirculated leachate. Use the greater value when the potential evapotranspiration rate does not exceed the mean annual precipitation rate plus... value rather than assessing the potential evapotranspiration rate or recirculated leachate rate. [75 FR...

40 CFR Table Hh-1 to Subpart Hh of... - Emissions Factors, Oxidation Factors and Methods

Code of Federal Regulations, 2012 CFR

2012-07-01

... evapotranspiration rate exceeds the mean annual precipitation rate plus recirculated leachate. Use the greater value when the potential evapotranspiration rate does not exceed the mean annual precipitation rate plus... value rather than assessing the potential evapotranspiration rate or recirculated leachate rate. [75 FR...

The Anatomy of the Young Protostellar Outflow HH 211: Strong Evidence for CO v = 1-0 Fundamental Band Emission from Dense Gas in the Terminal Shock

NASA Astrophysics Data System (ADS)

Tappe, Achim; Forbrich, J.; Martín, S.; Lada, C. J.

2011-05-01

We present Spitzer Space Telescope 5-37 µm spectroscopic mapping observations toward the southeastern lobe of the young protostellar outflow HH 211 (part of IC 348 in Perseus, 260 pc). The terminal shock of the outflow shows a rich atomic and molecular spectrum with emission lines from OH, H2O, HCO+, CO2, H2, HD, [Fe II], [Si II], [Ne II], [S I], and [Cl I]. The spectrum also shows a rising continuum towards 5 µm, which we interpret as unresolved emission lines from highly excited rotational levels of the CO v=1-0 fundamental band. This interpretation is confirmed by a strong excess flux observed in the Spitzer IRAC 4-5 µm channel 2 image. We also observed the terminal outflow shock of this lobe with the Submillimeter Array (SMA) and detected pure rotational emission from CO 2-1, HCO+ 3-2, and HCN 3-2. The rotationally excited CO traces the collimated outflow and the terminal shock, whereas the vibrationally excited CO seen with Spitzer follows the continuation of the collimated outflow backbone in the terminal shock. The extremely high critical densities of the CO v=1-0 rovibrational lines indicate terminal shock jet densities larger than 107 cm-3. The unique combination of mid-infrared, submillimeter, and previous near-infrared observations allow us to gain detailed insights into the interaction of one of the youngest known protostellar outflows with its surrounding molecular cloud. Our results help to understand the nature of some of the so-called `green fuzzies’ (Extended Green Objects) identified by their Spitzer IRAC channel 2 excess and association with star-forming regions. They also provide a critical observational test to models of pulsed protostellar jets.

Effectiveness of a multimodal hand hygiene improvement strategy in the emergency department.

PubMed

Arntz, P R H; Hopman, J; Nillesen, M; Yalcin, E; Bleeker-Rovers, C P; Voss, A; Edwards, M; Wei, A

2016-11-01

Hand hygiene (HH) is essential in preventing nosocomial infection. The emergency department (ED) is an open portal of entry for pathogens into the hospital system, hence the important sentinel function of the ED personnel. The main objective of this study was to assess the effect of a multimodal improvement strategy on hand hygiene compliance in the ED. Our study was a prospective before-and-after study to determine the effect of a multimodal improvement strategy on the compliance of HH in the ED according to the My 5 Moments of Hand Hygiene defined by the World Health Organization. Interventions such as education, reminders, and regular feedback on HH performance and role models were planned during the 3 intervention weeks. In total, 57 ED nurses and ED physicians were observed in this study, and approximately 1,000 opportunities for handrubs were evaluated during the 3 intervention periods. HH compliance increased significantly from baseline from 18% (74/407) to 41% (77/190) after the first intervention and stabilized to 50% (99/200) and 46% (96/210) after the second and third interventions, respectively. Implementing a multimodal HH improvement program significantly improved the HH compliance of ED personnel. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

International Ultraviolet Explorer (IUE)

NASA Technical Reports Server (NTRS)

Boehm, Karl-Heinz

1992-01-01

The observation, data reduction, and interpretation of ultraviolet spectra (obtained with the International Ultraviolet Explorer) of Herbig-Haro objects, stellar jets, and (in a few cases) reflection nebulae in star-forming regions is discussed. Intermediate results have been reported in the required semi-annual reports. The observations for this research were obtained in 23 (US1) IUE shifts. The spectra were taken in the low resolution mode with the large aperture. The following topics were investigated: (1) detection of UV spectra of high excitation Herbig-Haro (HH) objects, identification of emission lines, and a preliminary study of the energy distribution of the ultraviolet continuum; (2) details of the continuum energy distribution of these spectra and their possible interpretation; (3) the properties of the reddening (extinction) of HH objects; (4) the possible time variation of strong emission lines in high excitation HH objects; (5) the ultraviolet emission of low excitation HH objects, especially in the fluorescent lines of the H2 molecule; (6) the ultraviolet emission in the peculiar object HH24; (7) the spatial emission distribution of different lines and different parts of the continuum in different HH objects; and (8) some properties of reflection nebula, in the environment of Herbig-Haro objects. Each topic is discussed.

Hand hygiene practices of veterinary support staff in small animal private practice.

PubMed

Nakamura, R K; Tompkins, E; Braasch, E L; Martinez, J G; Bianco, D

2012-03-01

To evaluate the hand hygiene (HH) practices among veterinary technicians (VT) and veterinary support staff (VSS) in small animal private practice. This was a prospective questionnaire-based study involving 182 VT and VSS from 18 small animal hospitals in the USA. Questions asked included gender, number of animals handled per work shift, frequency of hand washing, reason for not washing more frequently, most common available hand washing agent, education regarding the importance of HH and frequency of ring wearing. Less than half of the respondents [76 of 182 (41·7%)] reported washing their hands regularly between handling patients and 154 of 182 (85·6%) believed they should have washed more frequently. The most commonly employed HH agent was hand soap [154 of 182 (84·6%)] and the most common reason cited for not washing more frequently was being too busy [132 of 182 (72·5%)]. Only 96 of 182 (52·7%) respondents were educated by doctors at their hospital regarding the importance of HH. The HH practices among VT and VSS in small animal private practice is poor. Hand soap was the most commonly employed agent among respondents in this study. Education of VT and VSS regarding the importance of HH requires improvement. © 2012 British Small Animal Veterinary Association.

Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

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

Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta

The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and themore » underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.« less

Implementing an electronic hand hygiene monitoring system: Lessons learned from community hospitals.

PubMed

Edmisten, Catherine; Hall, Charles; Kernizan, Lorna; Korwek, Kimberly; Preston, Aaron; Rhoades, Evan; Shah, Shalin; Spight, Lori; Stradi, Silvia; Wellman, Sonia; Zygadlo, Scott

2017-08-01

Measuring and providing feedback about hand hygiene (HH) compliance is a complicated process. Electronic HH monitoring systems have been proposed as a possible solution; however, there is little information available about how to successfully implement and maintain these systems for maximum benefit in community hospitals. An electronic HH monitoring system was implemented in 3 community hospitals by teams at each facility with support from the system vendor. Compliance rates were measured by the electronic monitoring system. The implementation challenges, solutions, and drivers of success were monitored within each facility. The electronic HH monitoring systems tracked on average more than 220,000 compliant HH events per facility per month, with an average monthly compliance rate >85%. The sharing of best practices between facilities was valuable in addressing challenges encountered during implementation and maintaining a high rate of use. Drivers of success included a collaborative environment, leadership commitment, using data to drive improvement, consistent and constant messaging, staff empowerment, and patient involvement. Realizing the full benefit of investments in electronic HH monitoring systems requires careful consideration of implementation strategies, planning for ongoing support and maintenance, and presenting data in a meaningful way to empower and inspire staff. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Sonic Hedgehog in pancreatic cancer: From bench to bedside, then back to the bench

PubMed Central

Rosow, David E.; Liss, Andrew S.; Strobel, Oliver; Fritz, Stefan; Bausch, Dirk; Valsangkar, Nakul P.; Alsina, Janivette; Kulemann, Birte; Park, Joo Kyung; Yamaguchi, Junpei; LaFemina, Jennifer; Thayer, Sarah P.

2013-01-01

Developmental genes are known to regulate cell proliferation, migration, and differentiation; thus, it comes as no surprise that the misregulation of developmental genes plays an important role in the biology of human cancers. One such pathway that has received an increasing amount of attention for its function in carcinogenesis is the Hedgehog (Hh) pathway. Initially the domain of developmental biologists, the Hh pathway and one of its ligands, Sonic Hedgehog (Shh), have been shown to play an important role in body planning and organ development, particularly in the foregut endoderm. Their importance in human disease became known to cancer biologists when germline mutations that resulted in the unregulated activity of the Hh pathway were found to cause basal cell carcinoma and medulloblastoma. Since then, misexpression of the Hh pathway has been shown to play an important role in many other cancers, including those of the pancreas. In many institutions, investigators are targeting misexpression of the Hh pathway in clinical trials, but there is still much fundamental knowledge to be gained about this pathway that can shape its clinical utility. This review will outline the evolution of our understanding of this pathway as it relates to the pancreas, as well as how the Hh pathway came to be a high-priority target for treatment. PMID:22770959

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

PubMed Central

Gerber, AN; Wilson, CW; Li, Y-J; Chuang, P-T

2012-01-01

The mechanism by which activation of the Hedgehog (Hh) pathway modulates differentiation and promotes oncogenesis in specific tissues is poorly understood. We therefore, analysed rhabdomyosarcomas from mice that were haploinsufficient for the Hh-binding protein, Hip1, or for the Hh receptor, Patched 1 (Ptch1). Transfection of the Hh-regulated transcription factor Gli1, which is expressed in a subset of mouse and human rhabdomyosarcomas, suppressed differentiation of myogenic rhabdomyosarcoma lines generated from Hip1+/− and Ptch1+/− mice. The closely related factor, Gli2, had similar effects. Gli1 and Gli2 inhibited myogenesis by repressing the capacity of MyoD to activate transcription. Deletion analysis of Gli1 indicated that multiple domains of Gli1 are required for efficient inhibition of MyoD. Gli1 reduced the ability of MyoD to heterodimerize with E12 and bind DNA, providing one mechanism whereby the Gli proteins modulate the activity of MyoD. This novel activity of Gli proteins provides new insights into how Hh signaling modulates terminal differentiation through inhibition of tissue-specific factors such as MyoD. This mechanism may contribute to the broad role of Hh signaling and the Gli proteins in differentiation decisions and cancer formation. PMID:16964293

Aging jets from low-mass stars

NASA Technical Reports Server (NTRS)

Graham, J. A.; Chen, W. P.

1994-01-01

An extended faint optical jet is associated with the compact emission region plus faint star known as HH 55. HH 55 is located in the Lupus 2 cloud 2 min SW of the well studied T Tauri star RU Lupi. The HH 55 jet extends 55 sec N and 35 sec S in PA 160 deg. The HH 55 star is an emission line star of spectral type M3.5. Its image in the emission lines of H-alpha and (S II) is slightly elongated by 2 sec - 3 sec to the S but in continuum light is symmetrical and pointlike ((full width at half maximum) (FWHM) = 1.7 sec). The star and jet have several features in common with the star and jet known as Sz 102 = Th 28 in the nearby Lupus 3 cloud. We suggest that these objects are representative of the late evolutionary stage of the HH jet-outflow phenomenon and point out that such objects may be quite common although difficult to detect. With L(sub bol) approximately = 0.005 solar luminosity, and log T(sub e) approximately = 3.5, the HH 55 star is close to the main sequence and evolutionary tracks suggest an age of 3 x 10(exp 7) yr.

The government of Kenya cash transfer for orphaned and vulnerable children: cross-sectional comparison of household and individual characteristics of those with and without

PubMed Central

2014-01-01

Background The ‘Cash Transfer to Orphans and Vulnerable Children’ (CT-OVC) in Kenya is a government-supported program intended to provide regular and predictable cash transfers (CT) to poor households taking care of OVC. CT programs can be an effective means of alleviating poverty and facilitating the attainment of an adequate standard of living for people’s health and well-being and other international human rights. The objective of this analysis was to compare the household socioeconomic status, school enrolment, nutritional status, and future outlook of orphaned and separated children receiving the CT compared to those not receiving a CT. Methods This project analyzes baseline data from a cohort of orphaned and separated children aged <19 years and non-orphaned children living in 300 randomly selected households (HH) in 8 Locations of Uasin Gishu County, Kenya. Baseline data were analyzed using multivariable logistic and Poisson regression comparing children in CT-HH vs. non-CT HH. Odds ratios are adjusted (AOR) with 95% confidence intervals (CI) for guardian age and sex, child age and sex, and intra-HH correlation. Results Included in this analysis were data from 1481 children and adolescents in 300 HH (503 participants in CT, 978 in non-CT households). Overall there were 922 (62.3%) single orphans, 324 (21.9%) double orphans, and 210 (14.2%) participants had both parents alive and were living with them. Participants in CT-HH were less likely to have ≥2 pairs of clothes compared to non-CT HH (AOR: 0.32, 95% CI: 0.16-0.63). Those in CT HH were less likely to have missed any days of school in the preceding month (AOR: 0.62, 95% CI: 0.42-0.94) and those aged <1-18 years in CT-HH were less likely to have height stunting for their age (AOR: 0.65, 95% CI: 0.47-0.89). Participants aged at least 10 years in CT-HH were more likely to have a positive future outlook (AOR: 1.72, 95% CI: 1.12-2.65). Conclusions Children and adolescents in households receiving the CT

Good to Great: Quality-Improvement Initiative Increases and Sustains Pediatric Health Care Worker Hand Hygiene Compliance.

PubMed

McLean, Heather S; Carriker, Charlene; Bordley, William Clay

2017-04-01

The Joint Commission, the Centers for Disease Control and Prevention, and the World Health Organization challenge hospitals to achieve and sustain compliance with effective hand hygiene (HH) practice; however, many inpatient units fail to achieve a high level of reliability. The aim of the project was to increase and sustain health care worker (HCW) compliance with HH protocols from 87% (level of reliability [LOR] 1) to ≥95% (LOR 2) within 9 months on 2 pediatric inpatient units in an academic children's hospital. This study was a time-series, quality-improvement project. Interventions were tested through multiple plan-do-study-act cycles on 2 pediatric inpatient units. HH compliance audits of HCWs on these units were performed randomly each week by the hospital infection prevention program. Control charts of percentages of HCW HH compliance were constructed with 3-σ (data within 3 SDs from a mean) control limits. These control limits were adjusted after achieving significant improvements in performance over time. Charts were annotated with interventions including (1) increasing awareness, (2) providing timely feedback, (3) empowering patients and families to participate in mitigation, (4) providing focused education, and (5) developing interdisciplinary HH champions. HH compliance rates improved from an average of 87% (LOR 1) to ≥95% (LOR 2) within 9 months, and this improvement has been sustained for >2 years on both pediatric inpatient units. Significant and sustained gains in HH compliance rates of ≥95% (LOR 2) can be achieved by applying high-reliability human-factor interventions. Copyright © 2017 by the American Academy of Pediatrics.

Mutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism.

PubMed

Känsäkoski, Johanna; Fagerholm, Rainer; Laitinen, Eeva-Maria; Vaaralahti, Kirsi; Hackman, Peter; Pitteloud, Nelly; Raivio, Taneli; Tommiska, Johanna

2014-05-01

Congenital hypogonadotropic hypogonadism (HH), a rare disorder characterized by absent, partial, or delayed puberty, can be caused by the lack or deficient number of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. SEMA3A was recently implicated in the etiology of the disorder, and Sema7A-deficient mice have a reduced number of GnRH neurons in their brains. SEMA3A and SEMA7A were screened by Sanger sequencing in altogether 50 Finnish HH patients (34 with Kallmann syndrome (KS; HH with hyposmia/anosmia) and 16 with normosmic HH (nHH)). In 20 patients, mutation(s) had already been found in genes known to be implicated in congenital HH. Three heterozygous variants (c.458A>G (p.Asn153Ser), c.1253A>G (p.Asn418Ser), and c.1303G>A (p.Val435Ile)) were found in SEMA3A in three KS patients, two of which also had a mutation in FGFR1. Two rare heterozygous variants (c.442C>T (p.Arg148Trp) and c.1421G>A (p.Arg474Gln)) in SEMA7A were found in one male nHH patient with a previously identified KISS1R nonsense variant and one male KS patient with a previously identified mutation in KAL1, respectively. Our results suggest that heterozygous missense variants in SEMA3A and SEMA7A may modify the phenotype of KS but most likely are not alone sufficient to cause the disorder.

DISRUPTION OF THE PACAP GENE PROMOTES MEDULLOBLASTOMA IN PTC1 MUTANT MICE

PubMed Central

Lelievre, Vincent; Seksenyan, Akop; Nobuta, Hiroko; Yong, William H.; Chhith, Seririthanar; Niewiadomski, Pawel; Cohen, Joseph R.; Dong, Hongmei; Flores, Avegail; Liau, Linda M.; Kornblum, Harley I.; Scott, Matthew P.; Waschek, James A.

2008-01-01

Hedgehog (Hh) proteins and cAMP-dependent protein kinase A (PKA) generally play opposing roles in developmental patterning events. Humans and mice heterozygous for mutations in the Sonic hedgehog (Shh) receptor gene patched-1 (ptc1) have an increased incidence of certain types of cancer, including medulloblastoma (MB), a highly aggressive tumor of the cerebellum. Despite the importance of PKA in Hh signaling, little is known about how PKA activity is regulated in the context of Hh signaling, or the consequences of improper regulation. One molecule that can influence PKA activity is pituitary adenylyl cyclase activating peptide (PACAP), which has been shown to regulate cerebellar granule precursor proliferation in vitro, a cell population thought to give rise to MB. To test for a PACAP/Hh interaction in the initiation or propagation of these tumors, we introduced a PACAP mutation into ptc1 mutant mice. Deletion of a single copy of PACAP increased MB incidence approximate 2.5-fold, to 66%, thereby demonstrating that PACAP exerts a powerful inhibitory action on the induction, growth or survival of these tumors. Tumors from PACAP/ptc1 mutant mice retained PACAP receptor gene expression, and exhibited superinduction of Hh target genes compared to those from ptc1+/− mice. Moreover, PACAP inhibited proliferation of cell lines derived from tumors in a PKA-dependent manner, and inhibited expression of the Hh target gene gli1. The results provide genetic evidence that PACAP acts as a physiological factor that regulates the pathogenesis of Hh pathway-associated MB tumors. PMID:18036580

Status gelasticus after temporal lobectomy: ictal FDG-PET findings and the question of dual pathology involving hypothalamic hamartomas.

PubMed

Palmini, Andre; Van Paesschen, Wim; Dupont, Patrick; Van Laere, Koen; Van Driel, Guido

2005-08-01

To present the first ictal fluorodeoxyglucose-positron emission tomography (FDG-PET) evidence of the hypothalamic origin of gelastic seizures in a patient with a hypothalamic hamartoma (HH) and to raise the issue of true dual pathology related to this entity. Ictal FDG-PET was acquired during an episode of status gelasticus with preserved consciousness, in a patient previously operated on for complex partial seizures (CPSs) due to a temporal lobe epileptogenic cyst. Ictal hypermetabolism was localized to the region of the HH during the status gelasticus. CPSs had been completely eliminated after temporal lobe surgery. Ictal FDG-PET independently confirmed that gelastic seizures in patients with HH do originate in the diencephalic lesion. An HH may coexist with another epileptogenic lesion, in a context of dual pathology.

Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

PubMed

Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

2014-06-01

The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

Measuring hepatic functional reserve using T1 mapping of Gd-EOB-DTPA enhanced 3T MR imaging: A preliminary study comparing with 99mTc GSA scintigraphy and signal intensity based parameters.

PubMed

Nakagawa, Masataka; Namimoto, Tomohiro; Shimizu, Kie; Morita, Kosuke; Sakamoto, Fumi; Oda, Seitaro; Nakaura, Takeshi; Utsunomiya, Daisuke; Shiraishi, Shinya; Yamashita, Yasuyuki

2017-07-01

To determine the utility of liver T1-mapping on gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance (MR) imaging for the measurement of liver functional reserve compared with the signal intensity (SI) based parameters, technetium-99m-galactosyl serum albumin ( 99m Tc-GSA) scintigraphy and indocyanine green (ICG) clearance. This retrospective study included 111 patients (Child-Pugh-A 90; -B 21) performed with both Gd-EOB-DTPA enhanced liver MR imaging and 99m Tc-GSA (76 patients with ICG). Receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic performances of T1-relaxation-time parameters [pre-(T1pre) and post-contrast (T1hb) Gd-EOB-DTPA], SI based parameters [relative enhancement (RE), liver-to-muscle-ratio (LMR), liver-to-spleen-ratio (LSR)] and 99m Tc-GSA scintigraphy blood clearance index (HH15)] for Child-Pugh classification. Pearson's correlation was used for comparisons among T1-relaxation-time parameters, SI-based parameters, HH15 and ICG. A significant difference was obtained for Child-Pugh classification with T1hb, ΔT1, all SI based parameters and HH15. T1hb had the highest AUC followed by RE, LMR, LSR, ΔT1, HH15 and T1pre. The correlation coefficients with HH15 were T1pre 0.22, T1hb 0.53, ΔT1 -0.38 of T1 relaxation parameters; RE -0.44, LMR -0.45, LSR -0.43 of SI-based parameters. T1hb was highest for correlation with HH15. The correlation coefficients with ICG were T1pre 0.29, T1hb 0.64, ΔT1 -0.42 of T1 relaxation parameters; RE -0.50, LMR -0.61, LSR -0.58 of SI-based parameters; 0.64 of HH15. Both T1hb and HH15 were highest for correlation with ICG. T1 relaxation time at post-contrast of Gd-EOB-DTPA (T1hb) was strongly correlated with ICG clearance and moderately correlated HH15 with 99m Tc-GSA. T1hb has the potential to provide robust parameter of liver functional reserve. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high-fat diet experimental rabbit animal model.

PubMed

Morelli, Annamaria; Vignozzi, Linda; Maggi, Mario

2016-06-01

The etiology of metabolic syndrome (MetS) is complex and involves the interplay between environmental, lifestyle and genetic determinants. MetS in men can be associated with a biochemical pattern of partial hypogonadotropic hypogonadism (HH). A similar pattern has been noted in both men and women with a variety of acute illnesses and chronic diseases, and there is ongoing debate regarding whether this phenomenon might adaptive (e.g. diverting resources from reproduction into survival), or maladaptive (e.g. anemia, sarcopenia, osteopenia and fatigue of androgen-deficiency amplify and widen the adverse consequences of the original disease-trigger). In women with hypothalamic amenorrhea (HA-HH secondary to chronic bioenergetic deficit from dietary restriction and/or intensive exercise), a genetic link to congenital HH (CHH) was recently established; women carrying monoallelic CHH gene mutations will typically not develop CHH, but are significantly more susceptible to HA. However, the male reproductive axis seems to be more resistant to similar environmental insults. In contrast, MetS-associated HH (mHH) is specifically a male phenomenon; the reproductive phenotype of females with MetS tending instead towards hyperandrogenism, rather than hypogonadism. The underlying pathogenic mechanisms responsible for mHH have not been clearly identified and, as yet, there has been no investigation of a potential role for CHH mutation carriage in its etiology. Over the decades, the use of either genetic- or diet-induced obesity and/or MetS animal models has greatly helped to illuminate the complex etiology of metabolic dysregulation, but the strong relationship between obesity/MetS and mHH in males has been largely neglected, with little or no information about the regulation of reproductive function by metabolic factors under conditions of bioenergetic excess. However, the pathogenic link between MetS and HH in males has been recently investigated in an animal model of high fat

Distribution of impurity states and charge transport in Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} nanocomposites

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

Liu, Yuanfeng; Makongo, Julien P.A.; Page, Alexander

Energy filtering of charge carriers in a semiconducting matrix using atomically coherent nanostructures can lead to a significant improvement of the thermoelectric figure of merit of the resulting composite. In this work, several half-Heusler/full-Heusler (HH/FH) nanocomposites with general compositions Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} (0≤x≤0.15 and y=0.005, 0.01 and 0.025) were synthesized in order to investigate the behavior of extrinsic carriers at the HH/FH interfaces. Electronic transport data showed that energy filtering of carriers at the HH/FH interfaces in Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} samples strongly depends on the doping level (y value) as well as the energymore » levels occupied by impurity states in the samples. For example, it was found that carrier filtering at HH/FH interfaces is negligible in Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} (y=0.01 and 0.025) composites where donor states originating from Sb dopant dominate electronic conduction. However, we observed a drastic decrease in the effective carrier density upon introduction of HH/FH interfaces for the mechanically alloyed Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 0.995}Sb{sub 0.005} samples where donor states from unintentional Fe impurities contribute the largest fraction of conduction electrons. This work demonstrates the ability to synergistically integrate the concepts of doping and energy filtering through nanostructuring for the optimization of electronic transport in semiconductors. - Graphical abstract: Electronic transport in semiconducting half-Heusler (HH) matrices containing full-Heusler (FH) nanoinclusions strongly depends on the energy distribution of impurity states within the HH matrix with respect to the magnitude of the potential energy barrier at the HH/FH interfaces. - Highlights: • Coherent nanostructures enhanced thermoelectric behavior of half-Heusler alloys. • Nanostructures act as energy

Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells

PubMed Central

Macedo, M F; Porto, G; Costa, M; Vieira, C P; Rocha, B; Cruz, E

2010-01-01

Low CD8+ T lymphocyte numbers have long been described in hereditary haemochromatosis (HH). Recently, two conserved haplotypes localized near the microsatellite D6S105 at the major histocompatibility complex (MHC) class I region were described predicting the clinical expression of HH and the CD8+ T lymphocyte numbers. The A-A-T haplotype was associated with a severe clinical expression of HH and low CD8+ T lymphocyte numbers, while the G-G-G haplotype was associated with a milder clinical expression of HH and high CD8+ T lymphocyte numbers. As CD8+ T lymphocytes are a very heterogeneous population, in this study we analysed the CD8+ subpopulations of naive, central memory (TCM) and effector memory (TEM), and further subsets of CD8+ TEM cells in 47 HH patients and 68 controls. In addition, association studies were conducted between the conserved haplotypes and the CD8+ T cell subpopulations in HH. Variations of the numbers of naive and central memory cells with age were similar between HH patients and controls. For TEM cells and the TEM CD27−CD28− subset no effect of age was observed in HH [R2 = 0·001, not significant (n.s.) and R2 = 0·01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R2 = 0·09, P = 0·017 and R2 = 0·22, P = 0·0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8+ TEM cells due especially to lower numbers of TEM CD27−CD28− (0·206 ± 0·119 and 0·066 ± 0·067 × 106 cells/ml, respectively) than patients carrying the G-G-G haplotype (0·358 ± 0·195 and 0·246 ± 0·202 × 106 cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8+ T cells into the most mature phenotype. PMID:20015273

The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution.

PubMed

Matus, David Q; Magie, Craig R; Pang, Kevin; Martindale, Mark Q; Thomsen, Gerald H

2008-01-15

Hedgehog signaling is an important component of cell-cell communication during bilaterian development, and abnormal Hedgehog signaling contributes to disease and birth defects. Hedgehog genes are composed of a ligand ("hedge") domain and an autocatalytic intein ("hog") domain. Hedgehog (hh) ligands bind to a conserved set of receptors and activate downstream signal transduction pathways terminating with Gli/Ci transcription factors. We have identified five intein-containing genes in the anthozoan cnidarian Nematostella vectensis, two of which (NvHh1 and NvHh2) contain definitive hedgehog ligand domains, suggesting that to date, cnidarians are the earliest branching metazoan phylum to possess definitive Hh orthologs. Expression analysis of NvHh1 and NvHh2, the receptor NvPatched, and a downstream transcription factor NvGli (a Gli3/Ci ortholog) indicate that these genes may have conserved roles in planar and trans-epithelial signaling during gut and germline development, while the three remaining intein-containing genes (NvHint1,2,3) are expressed in a cell-type-specific manner in putative neural precursors. Metazoan intein-containing genes that lack a hh ligand domain have previously only been identified within nematodes. However, we have identified intein-containing genes from both Nematostella and in two newly annotated lophotrochozoan genomes. Phylogenetic analyses suggest that while nematode inteins may be derived from an ancestral true hedgehog gene, the newly identified cnidarian and lophotrochozoan inteins may be orthologous, suggesting that both true hedgehog and hint genes may have been present in the cnidarian-bilaterian ancestor. Genomic surveys of N. vectensis suggest that most of the components of both protostome and deuterostome Hh signaling pathways are present in anthozoans and that some appear to have been lost in ecdysozoan lineages. Cnidarians possess many bilaterian cell-cell signaling pathways (Wnt, TGFbeta, FGF, and Hh) that appear to act in

In silico modeling techniques for predicting the tertiary structure of human H4 receptor.

PubMed

Zaid, Hilal; Raiyn, Jamal; Osman, Midhat; Falah, Mizied; Srouji, Samer; Rayan, Anwar

2016-01-01

First cloned in 2000, the human Histamine H4 Receptor (hH4R) is the last member of the histamine receptors family discovered so far, it belongs to the GPCR super-family and is involved in a wide variety of immunological and inflammatory responses. Potential hH4R antagonists are proposed to have therapeutic potential for the treatment of allergies, inflammation, asthma and colitis. So far, no hH4R ligands have been successfully introduced to the pharmaceutical market, which creates a strong demand for new selective ligands to be developed. in silico techniques and structural based modeling are likely to facilitate the achievement of this goal. In this review paper we attempt to cover the fundamental concepts of hH4R structure modeling and its implementations in drug discovery and development, especially those that have been experimentally tested and to highlight some ideas that are currently being discussed on the dynamic nature of hH4R and GPCRs, in regards to computerized techniques for 3-D structure modeling.

Small dead space heat and moisture exchangers do not impede gas exchange during noninvasive ventilation: a comparison with a heated humidifier.

PubMed

Boyer, Alexandre; Vargas, Frederic; Hilbert, Gilles; Gruson, Didier; Mousset-Hovaere, Maud; Castaing, Yves; Dreyfuss, Didier; Ricard, Jean Damien

2010-08-01

Adverse respiratory and gasometrical effects have been described in patients with acute respiratory failure (ARF) undergoing noninvasive ventilation (NIV) with standard heat and moisture exchangers (HME). We decided to evaluate respiratory parameters and arterial blood gases (ABG) of patients during NIV with small dead space HME compared with heated humidifier (HH). Prospective randomized crossover study. A 16-bed medical intensive care unit (ICU). Fifty patients receiving NIV for ARF. The effects of HME and HH on respiratory rate, minute ventilation, EtCO(2), oxygen saturation, airway occlusion pressure at 0.1 s, ABG, and comfort perception were compared during two randomly determined NIV periods of 30 min. The relative impact of HME and HH on these parameters was successively compared with or without addition of a flex tube (40 and 10 patients, respectively). No difference was observed between HME and HH regarding any of the studied parameters, whether or not a flex tube was added. If one decides to humidify patients' airways during NIV, one may do so with small dead space HME or HH without altering respiratory parameters.

Knowledge-based decision tree approach for mapping spatial distribution of rice crop using C-band synthetic aperture radar-derived information

NASA Astrophysics Data System (ADS)

Mishra, Varun Narayan; Prasad, Rajendra; Kumar, Pradeep; Srivastava, Prashant K.; Rai, Praveen Kumar

2017-10-01

Updated and accurate information of rice-growing areas is vital for food security and investigating the environmental impact of rice ecosystems. The intent of this work is to explore the feasibility of dual-polarimetric C-band Radar Imaging Satellite-1 (RISAT-1) data in delineating rice crop fields from other land cover features. A two polarization combination of RISAT-1 backscatter, namely ratio (HH/HV) and difference (HH-HV), significantly enhanced the backscatter difference between rice and nonrice categories. With these inputs, a QUEST decision tree (DT) classifier is successfully employed to extract the spatial distribution of rice crop areas. The results showed the optimal polarization combination to be HH along with HH/HV and HH-HV for rice crop mapping with an accuracy of 88.57%. Results were further compared with a Landsat-8 operational land imager (OLI) optical sensor-derived rice crop map. Spatial agreement of almost 90% was achieved between outputs produced from Landsat-8 OLI and RISAT-1 data. The simplicity of the approach used in this work may serve as an effective tool for rice crop mapping.

Effectiveness of an integrated hatchery program: Can genetic-based performance differences between hatchery and wild Chinook salmon be avoided?

USGS Publications Warehouse

Hayes, Michael C.; Reisenbichler, Reginald R.; Rubin, Stephen P.; Drake, Deanne C.; Stenberg, Karl D.; Young, Sewall F.

2013-01-01

Performance of wild (W) and hatchery (H) spring Chinook salmon (Oncorhynchus tshawytscha) was evaluated for a sixth generation hatchery program. Management techniques to minimize genetic divergence from the wild stock included regular use of wild broodstock and volitional releases of juveniles. Performance of HH, WW, and HW (hatchery female spawned with wild male) crosses was compared in hatchery and stream environments. The WW juveniles emigrated from the hatchery at two to three times the rate of HH fish in the fall (HW intermediate) and 35% more HH than WW adults returned (27% more HW than WW adults). Performance in the stream did not differ statistically between HH and WW fish, but outmigrants (38% WW, 30% HW, and 32% HH fish) during the first 39 days of the 16-month sampling period composed 74% of total outmigrants. Differences among hatchery-reared crosses were partially due to additive genetic effects, were consistent with domestication (increased fitness for the hatchery population in the hatchery program), and suggested that selection against fall emigration from the hatchery was a possible mechanism of domestication.

A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts

PubMed Central

Casso, David J.; Liu, Songmei; Iwaki, D. David; Ogden, Stacey K.; Kornberg, Thomas B.

2008-01-01

Signaling by Hedgehog (Hh) proteins shapes most tissues and organs in both vertebrates and invertebrates, and its misregulation has been implicated in many human diseases. Although components of the signaling pathway have been identified, key aspects of the signaling mechanism and downstream targets remain to be elucidated. We performed an enhancer/suppressor screen in Drosophila to identify novel components of the pathway and identified 26 autosomal regions that modify a phenotypic readout of Hh signaling. Three of the regions include genes that contribute constituents to the pathway—patched, engrailed, and hh. One of the other regions includes the gene microtubule star (mts) that encodes a subunit of protein phosphatase 2A. We show that mts is necessary for full activation of Hh signaling. A second region includes the gene second mitotic wave missing (swm). swm is recessive lethal and is predicted to encode an evolutionarily conserved protein with RNA binding and Zn+ finger domains. Characterization of newly isolated alleles indicates that swm is a negative regulator of Hh signaling and is essential for cell polarity. PMID:18245841

Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site

PubMed Central

Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

2016-01-01

Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide. PMID:26908655

The Fanconi anemia associated protein FAAP24 uses two substrate specific binding surfaces for DNA recognition

PubMed Central

Wienk, Hans; Slootweg, Jack C.; Speerstra, Sietske; Kaptein, Robert; Boelens, Rolf; Folkers, Gert E.

2013-01-01

To maintain the integrity of the genome, multiple DNA repair systems exist to repair damaged DNA. Recognition of altered DNA, including bulky adducts, pyrimidine dimers and interstrand crosslinks (ICL), partially depends on proteins containing helix-hairpin-helix (HhH) domains. To understand how ICL is specifically recognized by the Fanconi anemia proteins FANCM and FAAP24, we determined the structure of the HhH domain of FAAP24. Although it resembles other HhH domains, the FAAP24 domain contains a canonical hairpin motif followed by distorted motif. The HhH domain can bind various DNA substrates; using nuclear magnetic resonance titration experiments, we demonstrate that the canonical HhH motif is required for double-stranded DNA (dsDNA) binding, whereas the unstructured N-terminus can interact with single-stranded DNA. Both DNA binding surfaces are used for binding to ICL-like single/double-strand junction-containing DNA substrates. A structural model for FAAP24 bound to dsDNA has been made based on homology with the translesion polymerase iota. Site-directed mutagenesis, sequence conservation and charge distribution support the dsDNA-binding model. Analogous to other HhH domain-containing proteins, we suggest that multiple FAAP24 regions together contribute to binding to single/double-strand junction, which could contribute to specificity in ICL DNA recognition. PMID:23661679

HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

PubMed Central

Evangelista, Andreia Silva; de Araújo, Thiago Ferreira; Abrantes-Lemos, Clarice Pires; Deguti, Marta Mitiko; Cançado, Eduardo Luiz Rachid

2015-01-01

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population. PMID:25654085

Hedgehog signal inhibitor forskolin suppresses cell proliferation and tumor growth of human rhabdomyosarcoma xenograft.

PubMed

Yamanaka, Hiroaki; Oue, Takaharu; Uehara, Shuichiro; Fukuzawa, Masahiro

2011-02-01

We have previously reported that the Hedgehog (Hh) signaling pathway is activated in pediatric malignancies. In this study, we examined the effect of the Hh signal inhibitor forskolin on the growth of rhabdomyosarcoma (RMS) in vivo and in vitro and thereby elucidated the possibility of considering Hh signaling pathway as a therapeutic target for RMS. We evaluated the messenger RNA expressions of Hh signal mediators in 3 human RMS cell lines using reverse transcriptase-polymerase chain reaction method. The effect of forskolin on the tumor cell proliferation was investigated using WST-1 assay (Dojindo Co, Kumamoto, Japan). We inoculated 10(7) tumor cells into the back of nude mice to create RMS xenograft tumor models. Forskolin was subcutaneously administered in the region around the tumor, and the effect on the tumor growth was evaluated. The messenger RNA expression of glioma-associated oncogene homolog 1, the marker of Hh signaling activation, was expressed at various levels in RMS cell lines. The proliferation of RMS cells was inhibited in a dose-dependent fashion by forskolin. Similarly, in the xenograft model, tumor growth was also significantly reduced by forskolin treatment. Our findings suggest that the Hh signaling pathway plays an important role in the tumorigenesis of RMS and that this pathway can be considered to be a potential molecular target of new treatment strategies for RMS. Copyright © 2011 Elsevier Inc. All rights reserved.

A change in humidification system can eliminate endotracheal tube occlusion.

PubMed

Doyle, Alex; Joshi, Manasi; Frank, Peter; Craven, Thomas; Moondi, Parvez; Young, Peter

2011-12-01

Inadequate airway humidification can result in endotracheal tube occlusion. There is evidence that heat and moisture exchangers (HMEs) are more prone to endotracheal tube occlusion than heated humidifiers (HHs) that contain a heated wire circuit. We aimed to compare the incidence of endotracheal tube occlusion while introducing a new dual-heated wire circuit HH in place of an established hydrophobic HME. This was a prospective observational study. All patients who required intubation were included in our analysis. Univariate statistical analysis was performed using a Fisher exact test. P < .05 was considered statistically significant. There were 158 patients in the HME group and 88 patients in the HH group. The incidence of endotracheal tube occlusion was 5.7% in the HME group and 0% in the HH group. Statistical analysis revealed a significant difference between the 2 groups (P = .02). In light of this finding, we changed our practice to provide humidification exclusively by HH. In the subsequent 18-month period, there were no further episodes of endotracheal tube occlusion. Our study demonstrates that there is a significant increase in the incidence of endotracheal tube occlusion when using a hydrophobic HME compared with an HH and that using a dual-heated wire circuit HH can eliminate endotracheal tube occlusion. Copyright © 2011 Elsevier Inc. All rights reserved.

Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer

PubMed Central

Sheh, A; Muthupalani, S; Bryant, EM; Puglisi, DA; Holcombe, H; Conaway, EA; Parry, NAP; Bakthavatchalu, V; Short, SP; Williams, CS; Wogan, GN; Tannenbaum, SR; Fox, JG; Horwitz, BH

2017-01-01

The risk of colon cancer is increased in patients with Crohn's disease and ulcerative colitis. Inflammation-induced DNA damage could be an important link between inflammation and cancer, although the pathways that link inflammation and DNA damage are incompletely defined. RAG2-deficient mice infected with Helicobacter hepaticus (Hh) develop colitis that progresses to lower bowel cancer. This process depends on nitric oxide (NO), a molecule with known mutagenic potential. We have previously hypothesized that production of NO by macrophages could be essential for Hh-driven carcinogenesis, however, whether Hh-infection induces DNA damage in this model and whether this depends on NO has not been determined. Here, we demonstrate that Hh infection of RAG2-deficient mice rapidly induces expression of iNOS and the development of DNA double-stranded breaks (DSBs) specifically in proliferating crypt epithelial cells. Generation of DSBs depended on iNOS activity, and further, induction of iNOS, the generation of DSBs, and the subsequent development of dysplasia were inhibited by depletion of the Hh-induced cytokine IL-22. These results demonstrate a strong association between Hh-induced DNA damage and the development of dysplasia, and further suggest that IL-22 dependent induction of iNOS within crypt epithelial cells rather than macrophages is a driving force in this process. PMID:28198364

Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett’s metaplasia

PubMed Central

Wang, David H.; Tiwari, Anjana; Kim, Monica E.; Clemons, Nicholas J.; Regmi, Nanda L.; Hodges, William A.; Berman, David M.; Montgomery, Elizabeth A.; Watkins, D. Neil; Zhang, Xi; Zhang, Qiuyang; Jie, Chunfa; Spechler, Stuart J.; Souza, Rhonda F.

2014-01-01

Metaplasia can result when injury reactivates latent developmental signaling pathways that determine cell phenotype. Barrett’s esophagus is a squamous-to-columnar epithelial metaplasia caused by reflux esophagitis. Hedgehog (Hh) signaling is active in columnar-lined, embryonic esophagus and inactive in squamous-lined, adult esophagus. We showed previously that Hh signaling is reactivated in Barrett’s metaplasia and overexpression of Sonic hedgehog (SHH) in mouse esophageal squamous epithelium leads to a columnar phenotype. Here, our objective was to identify Hh target genes involved in Barrett’s pathogenesis. By microarray analysis, we found that the transcription factor Foxa2 is more highly expressed in murine embryonic esophagus compared with postnatal esophagus. Conditional activation of Shh in mouse esophageal epithelium induced FOXA2, while FOXA2 expression was reduced in Shh knockout embryos, establishing Foxa2 as an esophageal Hh target gene. Evaluation of patient samples revealed FOXA2 expression in Barrett’s metaplasia, dysplasia, and adenocarcinoma but not in esophageal squamous epithelium or squamous cell carcinoma. In esophageal squamous cell lines, Hh signaling upregulated FOXA2, which induced expression of MUC2, an intestinal mucin found in Barrett’s esophagus, and the MUC2-processing protein AGR2. Together, these data indicate that Hh signaling induces expression of genes that determine an intestinal phenotype in esophageal squamous epithelial cells and may contribute to the development of Barrett’s metaplasia. PMID:25083987

Hypothyroidism Attenuates SCH 23390-mediated Depression of Breathing and Decreases D1 Receptor Expression in Carotid Bodies, PVN and Striatum of Hamsters

PubMed Central

Schlenker, Evelyn H.; Schultz, Harold D.

2011-01-01

Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)–induced hypothyroidism in hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for three months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390, a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O2 in N2), hypoxic (10% O2 in N2) and hypercapnic (5% CO2 in O2) air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH 23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH 23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH. PMID:21669406

Hedgehog Is a Positive Regulator of FGF Signalling during Embryonic Tracheal Cell Migration

PubMed Central

Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J.

2014-01-01

Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration. PMID:24651658

Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration.

PubMed

Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J

2014-01-01

Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration.

The dawn of hedgehog inhibitors: Vismodegib

PubMed Central

Sandhiya, Selvarajan; Melvin, George; Kumar, Srinivasamurthy Suresh; Dkhar, Steven Aibor

2013-01-01

Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib. PMID:23662017

The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

PubMed

Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

2015-12-04

The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Expression and characterization of a recombinant single-domain monoclonal antibody against MUC1 mucin in tobacco plants.

PubMed

Rajabi-Memari, H; Jalali-Javaran, M; Rasaee, M J; Rahbarizadeh, F; Forouzandeh-Moghadam, M; Esmaili, A

2006-08-01

A promising alternative to conventional antibodies is the single-domain antibody fragment of the Camelidae (V(HH)), which (because of features such as small length, high expression, solubility, and stability) is preferred to other antibody derivatives. In this report, a recombinant single-domain antibody (V(HH)) against MUC1 mucin in the tobacco plant, which may be considered as a suitable and economical alternative expression system, was produced. This antibody was expressed under the control of a strong constitutive promoter, CaMV35S, and NOS terminator. A plant high-expression sequence (Kozak sequence) was linked at the 5' end for overexpression of the V(HH) gene. The constructed cassette (pBIV(HH)) was transferred to agrobacterium, and the VHH gene was inserted into the plant genome by agrobacterium-mediated transformation. Transgenic lines were selected on kanamycin (100 mg/L) and maintained in soil, and subsequent generations were obtained. The presence and expression of the transgene was confirmed in the transformants by polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot. Tobacco transgenic lines leave expressed V(HH) at levels varying from 1.12% to 1.63% of the total soluble protein. This report examines the transformation and expression of recombinant single-domain antibody (V(HH)) against antigen-associated tumor in tobacco plants.

Medicare and Medicaid programs; CY 2015 Home Health Prospective Payment System rate update; Home Health Quality Reporting Requirements; and survey and enforcement requirements for home health agencies. Final rule.

PubMed

2014-11-06

This final rule updates Home Health Prospective Payment System (HH PPS) rates, including the national, standardized 60-day episode payment rates, the national per-visit rates, and the non-routine medical supply (NRS) conversion factor under the Medicare prospective payment system for home health agencies (HHAs), effective for episodes ending on or after January 1, 2015. As required by the Affordable Care Act, this rule implements the second year of the four-year phase-in of the rebasing adjustments to the HH PPS payment rates. This rule provides information on our efforts to monitor the potential impacts of the rebasing adjustments and the Affordable Care Act mandated face-to-face encounter requirement. This rule also implements: Changes to simplify the face-to-face encounter regulatory requirements; changes to the HH PPS case-mix weights; changes to the home health quality reporting program requirements; changes to simplify the therapy reassessment timeframes; a revision to the Speech-Language Pathology (SLP) personnel qualifications; minor technical regulations text changes; and limitations on the reviewability of the civil monetary penalty provisions. Finally, this rule also discusses Medicare coverage of insulin injections under the HH PPS, the delay in the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), and a HH value-based purchasing (HH VBP) model.

Effectiveness of multifaceted hand hygiene interventions in long-term care facilities in Hong Kong: a cluster-randomized controlled trial.

PubMed

Ho, Mei-lin; Seto, Wing-hong; Wong, Lai-chin; Wong, Tin-yau

2012-08-01

To determine the effectiveness of World Health Organization (WHO) multimodal strategy in promoting hand hygiene (HH) among healthcare workers (HCWs) in long-term care facilities (LTCFs). Cluster-randomized controlled trial. Eighteen homes for the elderly in Hong Kong were randomly allocated to 2 intervention arms and a control arm. Direct observation of HH practice was conducted by trained nurses. Either handrubbing with alcohol-based handrub (ABHR) or handwashing with liquid soap and water was counted as a compliant action. Disease notification data during 2007-2010 were used to calculate incidence rate ratio (IRR). Managers and HCWs of the participating homes. The WHO multimodal strategy was employed. All intervention homes were supplied with ABHR (WHO formulation I), ABHR racks, pull reels, HH posters and reminders, a health talk, video clips, training materials, and performance feedback. The only difference was that intervention arms 1 and 2 were provided with slightly powdered and powderless gloves, respectively. A total of 11,669 HH opportunities were observed. HH compliance increased from 27.0% to 60.6% and from 22.2% to 48.6% in intervention arms 1 and 2, respectively. Both intervention arms showed increased HH compliance after intervention compared to controls, at 21.6% compliance (both [Formula: see text]). Provision of slightly powdered versus powderless gloves did not have any significant impact on ABHR usage. Respiratory outbreaks (IRR, 0.12; 95% confidence interval [CI], 0.01-0.93; [Formula: see text]) and methicillin-resistant Staphylococcus aureus infections requiring hospital admission (IRR, 0.61; 95% CI, 0.38-0.97; [Formula: see text]) were reduced after intervention. A promotion program applying the WHO multimodal strategy was effective in improving HH among HCWs in LTCFs.

The use of real-time feedback via wireless technology to improve hand hygiene compliance.

PubMed

Marra, Alexandre R; Sampaio Camargo, Thiago Zinsly; Magnus, Thyago Pereira; Blaya, Rosangela Pereira; Dos Santos, Gilson Batista; Guastelli, Luciana Reis; Rodrigues, Rodrigo Dias; Prado, Marcelo; Victor, Elivane da Silva; Bogossian, Humberto; Monte, Julio Cesar Martins; dos Santos, Oscar Fernando Pavão; Oyama, Carlos Kazume; Edmond, Michael B

2014-06-01

Hand hygiene (HH) is widely regarded as the most effective preventive measure for health care-associated infection. However, there is little robust evidence on the best interventions to improve HH compliance or whether a sustained increase in compliance can reduce rates of health care-associated infection. To evaluate the effectiveness of a real-time feedback to improve HH compliance in the inpatient setting, we used a quasiexperimental study comparing the effect of real-time feedback using wireless technology on compliance with HH. The study was conducted in two 20-bed step-down units at a private tertiary care hospital. Phase 1 was a 3-month baseline period in which HH counts were performed by electronic handwash counters. After a 1-month washout period, a 7-month intervention was performed in one step-down unit while the other unit served as a control. HH, as measured by dispensing episodes, was significantly higher in the intervention unit (90.1 vs 73.1 dispensing episodes/patient-day, respectively, P = .001). When the intervention unit was compared with itself before and after implementation of the wireless technology, there was also a significant increase in HH after implementation (74.5 vs 90.1 episodes/patient-day, respectively, P = .01). There was also an increase in mean alcohol-based handrub consumption between the 2 phases (68.9 vs 103.1 mL/patient-day, respectively, P = .04) in the intervention unit. We demonstrated an improvement in alcohol gel usage via implementation of real-time feedback via wireless technology. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Differences in psychosocial determinants of hand hygiene between health care professional groups: Insights from a mixed-methods analysis.

PubMed

Ibrahim, Muhamad Alif Bin; Chow, Chengzi; Poh, Bee Fong; Ang, Brenda; Chow, Angela

2018-03-01

Good hand hygiene (HH) prevents health care-associated infections. We compared psychosocial and organizational factors associated with HH compliance and perceived need for improvement among physicians, nurses, and allied health professionals (AHPs). We conducted a mixed-methods study in a 1,600-bed adult tertiary-care hospital in Singapore. Seven focus group discussions were conducted and data were analyzed using thematic analysis. The subsequent cross-sectional survey involved 1,064 staff members. Principal components analysis was performed to derive the latent factor structure that was applied in multivariable analyses. All staff members acknowledged that HH was an integral part of their work, but were noncompliant due to competing priorities. Physicians were forgetful but appreciated reminders. Nurses were intrinsically motivated for HH. After adjusting for gender, staff category, seniority, and dermatitis history, having positive knowledge-attitudes-behaviors (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.23-1.69), personal motivators-enablers (OR, 1.60; 95% CI, 1.38-1.86), and emotional motivators (OR, 1.62; 95% CI 1.40-1.88) were positively associated with good HH compliance. Women (OR, 3.91; 95% CI, 1.37-11.11), seniors (OR, 2.88; 95% CI, 1.08-7.68), nurses (OR, 4.05; 95% CI, 1.51-10.87), and staff with personal motivators-enablers for HH (OR, 1.60; 95% CI, 1.08-2.37) were more likely to perceive a need for improvement. Factors influencing self-reported HH differed between health care professional groups. Group-specific interventions are needed to improve compliance. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Identification of Hedgehog signaling outcomes in mouse testis development using a hanging drop-culture system.

PubMed

Szczepny, Anette; Hogarth, Cathryn A; Young, Julia; Loveland, Kate L

2009-02-01

The Hedgehog (Hh) signaling pathway affects fetal testis growth. Recently, we described the dynamic cellular production of Hh signaling pathway components in juvenile and adult rodent testes. The Hh signaling is understood to regulate cord formation in the fetal testis, but minimal knowledge exists regarding how Hh signaling impacts the postnatal testis. To investigate this, we employed hanging drop cultures, which are used routinely in embryoid body formation. This approach has the advantage of using small media volume, and we examined its suitability for short-term culture of both murine embryonic gonads and adult testis tubules. The effects of cyclopamine, a specific Hh signaling inhibitor, were examined following culture of Embryonic Day 11.5 urogenital ridges (as control) and adult seminiferous tubule fragments for 24-48 h using histological, cell proliferation, and gene expression analyses. Cultured embryonic testes displayed generally normal cord structure, anti-Müllerian hormone (Amh) expression, and cell proliferation; known Hh target gene expression (Gli1, osteopontin, official symbol Spp1, and Amh) was altered in response to cyclopamine. Cultured adult tubules exhibited some loss of seminiferous epithelium organization over 48 h. Spermatogonia continued to proliferate, however, and no significant loss of viability was noted overall. Addition of cyclopamine significantly affected levels of Gli1, Igfbp6, Ccnd2 (cyclin D2), Ccnb1 (cyclin B1), Spp1, Kit, and Amh mRNAs; these genes have been shown previously to be expressed in Sertoli and germ cells. These novel results identify Hh target genes in the testis and demonstrate this signaling pathway likely affects cell survival and differentiation in the context of normal adult testis.

Identification of Hedgehog Signaling Outcomes in Mouse Testis Development Using a Hanging Drop-Culture System1

PubMed Central

Szczepny, Anette; Hogarth, Cathryn A.; Young, Julia; Loveland, Kate L.

2008-01-01

The Hedgehog (Hh) signaling pathway affects fetal testis growth. Recently, we described the dynamic cellular production of Hh signaling pathway components in juvenile and adult rodent testes. The Hh signaling is understood to regulate cord formation in the fetal testis, but minimal knowledge exists regarding how Hh signaling impacts the postnatal testis. To investigate this, we employed hanging drop cultures, which are used routinely in embryoid body formation. This approach has the advantage of using small media volume, and we examined its suitability for short-term culture of both murine embryonic gonads and adult testis tubules. The effects of cyclopamine, a specific Hh signaling inhibitor, were examined following culture of Embryonic Day 11.5 urogenital ridges (as control) and adult seminiferous tubule fragments for 24–48 h using histological, cell proliferation, and gene expression analyses. Cultured embryonic testes displayed generally normal cord structure, anti-Müllerian hormone (Amh) expression, and cell proliferation; known Hh target gene expression (Gli1, osteopontin, official symbol Spp1, and Amh) was altered in response to cyclopamine. Cultured adult tubules exhibited some loss of seminiferous epithelium organization over 48 h. Spermatogonia continued to proliferate, however, and no significant loss of viability was noted overall. Addition of cyclopamine significantly affected levels of Gli1, Igfbp6, Ccnd2 (cyclin D2), Ccnb1 (cyclin B1), Spp1, Kit, and Amh mRNAs; these genes have been shown previously to be expressed in Sertoli and germ cells. These novel results identify Hh target genes in the testis and demonstrate this signaling pathway likely affects cell survival and differentiation in the context of normal adult testis. PMID:18843087

Hedgehog pathway blockade with the cancer drug LDE225 disrupts taste organs and taste sensation.

PubMed

Kumari, Archana; Ermilov, Alexandre N; Allen, Benjamin L; Bradley, Robert M; Dlugosz, Andrzej A; Mistretta, Charlotte M

2015-02-01

Taste sensation on the anterior tongue requires chorda tympani nerve function and connections with continuously renewing taste receptor cells. However, it is unclear which signaling pathways regulate the receptor cells to maintain chorda tympani sensation. Hedgehog (HH) signaling controls cell proliferation and differentiation in numerous tissues and is active in taste papillae and taste buds. In contrast, uncontrolled HH signaling drives tumorigenesis, including the common skin cancer, basal cell carcinoma. Systemic HH pathway inhibitors (HPIs) lead to basal cell carcinoma regression, but these drugs cause severe taste disturbances. We tested the hypothesis that taste disruption by HPIs reflects a direct requirement for HH signaling in maintaining taste organs and gustatory sensation. In mice treated with the HPI LDE225 up to 28 days, HH-responding cells were lost in fungiform papilla epithelium, and papillae acquired a conical apex. Taste buds were either absent or severely reduced in size in more than 90% of aberrant papillae. Taste bud remnants expressed the taste cell marker keratin 8, and papillae retained expression of nerve markers, neurofilament and P2X3. Chorda tympani nerve responses to taste stimuli were markedly reduced or absent in LDE225-treated mice. Responses to touch were retained, however, whereas cold responses were retained after 16 days of treatment but lost after 28 days. These data identify a critical, modality-specific requirement for HH signaling in maintaining taste papillae, taste buds and neurophysiological taste function, supporting the proposition that taste disturbances in HPI-treated patients are an on-target response to HH pathway blockade in taste organs. Copyright © 2015 the American Physiological Society.

Biomarkers of the Hedgehog/Smoothened pathway in healthy volunteers

PubMed Central

Kadam, Sunil K; Patel, Bharvin K R; Jones, Emma; Nguyen, Tuan S; Verma, Lalit K; Landschulz, Katherine T; Stepaniants, Sergey; Li, Bin; Brandt, John T; Brail, Leslie H

2012-01-01

The Hedgehog (Hh) pathway is involved in oncogenic transformation and tumor maintenance. The primary objective of this study was to select surrogate tissue to measure messenger ribonucleic acid (mRNA) levels of Hh pathway genes for measurement of pharmacodynamic effect. Expression of Hh pathway specific genes was measured by quantitative real time polymerase chain reaction (qRT-PCR) and global gene expression using Affymetrix U133 microarrays. Correlations were made between the expression of specific genes determined by qRT-PCR and normalized microarray data. Gene ontology analysis using microarray data for a broader set of Hh pathway genes was performed to identify additional Hh pathway-related markers in the surrogate tissue. RNA extracted from blood, hair follicle, and skin obtained from healthy subjects was analyzed by qRT-PCR for 31 genes, whereas 8 samples were analyzed for a 7-gene subset. Twelve sample sets, each with ≤500 ng total RNA derived from hair, skin, and blood, were analyzed using Affymetrix U133 microarrays. Transcripts for several Hh pathway genes were undetectable in blood using qRT-PCR. Skin was the most desirable matrix, followed by hair follicle. Whether processed by robust multiarray average or microarray suite 5 (MAS5), expression patterns of individual samples showed co-clustered signals; both normalization methods were equally effective for unsupervised analysis. The MAS5- normalized probe sets appeared better suited for supervised analysis. This work provides the basis for selection of a surrogate tissue and an expression analysis-based approach to evaluate pathway-related genes as markers of pharmacodynamic effect with novel inhibitors of the Hh pathway. PMID:22611475

A Review of Electronic Hand Hygiene Monitoring: Considerations for Hospital Management in Data Collection, Healthcare Worker Supervision, and Patient Perception.

PubMed

McGuckin, Maryanne; Govednik, John

2015-01-01

Healthcare-associated infections (HAIs) in U.S. acute care hospitals lead to a burden of $96-$147 billion annually on the U.S. health system and affect 1 in 20 hospital patients (Marchetti & Rossiter, 2013). Hospital managers are charged with reducing and eliminating HAIs to cut costs and improve patient outcomes. Healthcare worker (HCW) hand hygiene (HH) practice is the most effective means of preventing the spread of HAIs, but compliance is at or below 50% (McGuckin, Waterman, & Govednik, 2009). For managers to increase the frequency of HCW HH occurrences and improve the quality of HH performance, companies have introduced electronic technologies to assist managers in training, supervising, and gathering data in the patient care setting. Although these technologies offer valuable feedback regarding compliance, little is known in terms of capabilities in the clinical setting. Less is known about HCW or patient attitudes if the system allows feedback to be shared. Early-adopting managers have begun to examine their experiences with HH technologies and publish their findings. We review peer-reviewed research on infection prevention that focused on the capabilities of these electronic systems, as well as the related research on HCW and patient interactions with electronic HH systems. Research suggests that these systems are capable of collecting data, but the results are mixed regarding their impact on HH compliance, reducing HAIs, or both and their costs. Research also indicates that HCWs and patients may not regard the technology as positively as industry or healthcare managers may have intended. When considering the adoption of electronic HH monitoring systems, hospital administrators should proceed with caution.

Insights into the binding behavior of native and non-native cytochromes to photosystem I from Thermosynechococcus elongatus.

PubMed

Kölsch, Adrian; Hejazi, Mahdi; Stieger, Kai R; Feifel, Sven C; Kern, Jan F; Müh, Frank; Lisdat, Fred; Lokstein, Heiko; Zouni, Athina

2018-06-08

The binding of photosystem I (PS I) from Thermosynechococcus elongatus to the native cytochrome (cyt) c 6 and cyt c from horse heart (cyt c HH ) was analyzed by oxygen consumption measurements, isothermal titration calorimetry (ITC), and rigid body docking combined with electrostatic computations of binding energies. Although PS I has a higher affinity for cyt c HH than for cyt c 6 , the influence of ionic strength and pH on binding is different in the two cases. ITC and theoretical computations revealed the existence of unspecific binding sites for cyt c HH besides one specific binding site close to P 700 Binding to PS I was found to be the same for reduced and oxidized cyt c HH Based on this information, suitable conditions for cocrystallization of cyt c HH with PS I were found, resulting in crystals with a PS I:cyt c HH ratio of 1:1. A crystal structure at 3.4-Å resolution was obtained, but cyt c HH cannot be identified in the electron density map because of unspecific binding sites and/or high flexibility at the specific binding site. Modeling the binding of cyt c 6 to PS I revealed a specific binding site where the distance and orientation of cyt c 6 relative to P 700 are comparable with cyt c 2 from purple bacteria relative to P 870 This work provides new insights into the binding modes of different cytochromes to PS I, thus facilitating steps toward solving the PS I-cyt c costructure and a more detailed understanding of natural electron transport processes.

Frequent Deregulations in the Hedgehog Signaling Network and Cross-Talks with the Epidermal Growth Factor Receptor Pathway Involved in Cancer Progression and Targeted Therapies

PubMed Central

Mimeault, Murielle

2010-01-01

The hedgehog (Hh)/glioma-associated oncogene (GLI) signaling network is among the most important and fascinating signal transduction systems that provide critical functions in the regulation of many developmental and physiological processes. The coordinated spatiotemporal interplay of the Hh ligands and other growth factors is necessary for the stringent control of the behavior of diverse types of tissue-resident stem/progenitor cells and their progenies. The activation of the Hh cascade might promote the tissue regeneration and repair after severe injury in numerous organs, insulin production in pancreatic β-cells, and neovascularization. Consequently, the stimulation of the Hh pathway constitutes a potential therapeutic strategy to treat diverse human disorders, including severe tissue injuries; diabetes mellitus; and brain, skin, and cardiovascular disorders. In counterbalance, a deregulation of the Hh signaling network might lead to major tissular disorders and the development of a wide variety of aggressive and metastatic cancers. The target gene products induced through the persistent Hh activation can contribute to the self-renewal, survival, migration, and metastasis of cancer stem/progenitor cells and their progenies. Moreover, the pivotal role mediated through the Hh/GLI cascade during cancer progression also implicates the cooperation with other oncogenic products, such as mutated K-RAS and complex cross-talk with different growth factor pathways, including tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), Wnt/β-catenin, and transforming growth factor-β (TGF-β)/TGF-β receptors. Therefore, the molecular targeting of distinct deregulated gene products, including Hh and EGFR signaling components and other signaling elements that are frequently deregulated in highly tumorigenic cancer-initiating cells and their progenies, might constitute a potential therapeutic strategy to eradicate the total cancer cell mass. Of clinical

Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

PubMed

Chandra, Vikas; Das, Tapojyoti; Gulati, Puneet; Biswas, Nidhan K; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N; Deb, Sumit; Saha, Suniti K; Chowdhury, Anup K; Ghosh, Subhashish; Rudin, Charles M; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

2015-01-01

Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution-unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh" cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28- T cells.

PubMed

Arosa, F A; Oliveira, L; Porto, G; da Silva, B M; Kruijer, W; Veltman, J; de Sousa, M

1997-03-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28- T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population 'to expand', coinciding with an 'expansion' of CD8+ CD28- T cells in peripheral blood of HLA-A3+ but not HLA-A3- HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28- T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells

PubMed Central

AROSA, F A; OLIVEIRA, L; PORTO, G; DA SILVA, B M; KRUIJER, W; VELTMAN, J; DE SOUSA, M

1997-01-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28− T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population ‘to expand’, coinciding with an ‘expansion’ of CD8+ CD28− T cells in peripheral blood of HLA-A3+ but not HLA-A3− HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28− T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH. PMID:9067531

Comparison of Sleep Disorders between Real and Simulated 3,450-m Altitude.

PubMed

Heinzer, Raphaël; Saugy, Jonas J; Rupp, Thomas; Tobback, Nadia; Faiss, Raphael; Bourdillon, Nicolas; Rubio, José Haba; Millet, Grégoire P

2016-08-01

Hypoxia is known to generate sleep-disordered breathing but there is a debate about the pathophysiological responses to two different types of hypoxic exposure: normobaric hypoxia (NH) and hypobaric hypoxia (HH), which have never been directly compared. Our aim was to compare sleep disorders induced by these two types of altitude. Subjects were exposed to 26 h of simulated (NH) or real altitude (HH) corresponding to 3,450 m and a control condition (NN) in a randomized order. The sleep assessments were performed with nocturnal polysomnography (PSG) and questionnaires. Thirteen healthy trained males subjects volunteered for this study (mean ± SD; age 34 ± 9 y, body weight 76.2 ± 6.8 kg, height 179.7 ± 4.2 cm). Mean nocturnal oxygen saturation was further decreased during HH than in NH (81.2 ± 3.1 versus 83.6 ± 1.9%; P < 0.01) when compared to NN (95.5 ± 0.9%; P < 0.001). Heart rate was higher in HH than in NH (61 ± 10 versus 55 ± 6 bpm; P < 0.05) and NN (48 ± 5 bpm; P < 0.001). Total sleep time was longer in HH than in NH (351 ± 63 versus 317 ± 65 min, P < 0.05), and both were shorter compared to NN (388 ± 50 min, P < 0.05). Breathing frequency did not differ between conditions. Apnea-hypopnea index was higher in HH than in NH (20.5 [15.8-57.4] versus 11.4 [5.0-65.4]; P < 0.01) and NN (8.2 [3.9-8.8]; P < 0.001). Subjective sleep quality was similar between hypoxic conditions but lower than in NN. Our results suggest that HH has a greater effect on nocturnal breathing and sleep structure than NH. In HH, we observed more periodic breathing, which might arise from the lower saturation due to hypobaria, but needs to be confirmed. © 2016 Associated Professional Sleep Societies, LLC.

Ursolic acid suppresses TGF-β1-induced quiescent HSC activation and transformation by inhibiting NADPH oxidase expression and Hedgehog signaling

PubMed Central

Yu, Shan-Shan; Chen, Biao; Huang, Chen-Kai; Zhou, Juan-Juan; Huang, Xin; Wang, An-Jiang; Li, Bi-Min; He, Wen-Hua; Zhu, Xuan

2017-01-01

Activation of quiescent hepatic stellate cells (q-HSCs) and their transformation to myofibroblasts (MFBs) is a key event in liver fibrosis. Hedgehog (Hh) signaling stimulates q-HSCs to differentiate into MFBs, and NADPH oxidase (NOX) may be involved in regulating Hh signaling. The author's preliminary study demonstrated that ursolic acid (UA) selectively induces apoptosis in activated HSCs and inhibits their proliferation in vitro via negative regulation of NOX activity and expression. However, the effect of UA on q-HSCs remains to be elucidated. The present study aimed to investigate the effect of UA on q-HSC activation and HSC transformation and to observe alterations in the NOX and Hh signaling pathways during q-HSC activation. q-HSC were isolated from adult male Sprague-Dawley rats. Following culture for 3 days, the cells were treated with or without transforming growth factor-β1 (TGF-β1; 5 µg/l); intervention groups were pretreated with UA (40 µM) or diphenyleneiodonium chloride (DPI; 10 µM) for 30 min prior to addition of TGF-β1. mRNA and protein expression of NOX and Hh signaling components and markers of q-HSC activation were examined by western blotting and reverse transcription-polymerase chain reaction. TGF-β1 induced activation of q-HSCs, with increased expression of α-smooth muscle actin (α-SMA) and type I collagen. In addition, expression of NOX subunits (gp91phox, p67phox, p22phox, and Rac1) and Hh signaling components, including sonic Hh, sterol-4-alpha-methyl oxidase, and Gli family zinc finger 2, were upregulated in activated HSCs. Pretreatment of q-HSCs with UA or DPI prior to TGF-β1 significantly downregulated expression of NOX subunits and Hh signaling components and additionally inhibited expression of α-SMA and type I collagen, thereby preventing transformation to MFBs. UA inhibited TGF-β1-induced activation of q-HSCs and their transformation by inhibiting expression of NOX subunits and the downstream Hh pathway. PMID:29042951

The effect of hand hygiene compliance on hospital-acquired infections in an ICU setting in a Kuwaiti teaching hospital.

PubMed

Salama, Mona F; Jamal, Wafaa Y; Mousa, Haifa Al; Al-Abdulghani, Khaled A; Rotimi, Vincent O

2013-02-01

Hand washing is widely accepted as the cornerstone of infection control in the intensive care unit (ICU). Nosocomial infections are frequently viewed as indicating poor compliance with hand washing guidelines. To determine the hand hygiene (HH) compliance rate among healthcare workers (HCWs) and its effect on the nosocomial infection rates in the ICU of our hospital, we conducted an interventional study. The study spanned a period of 7 months (February 2011-August 2011) and consisted of education about HH indications and techniques, workplace reminder posters, focused group sessions, and feedback on the HH compliance and infection rates. The WHO HH observation protocol was used both before and after a hospital-wide HH campaign directed at all staff members, particularly those in the ICU. Compliance was measured by direct observation of the HCWs, using observation record forms in a patient-directed manner, with no more than two patients observed simultaneously. The overall HH compliance rate was calculated by dividing the number of HH actions by the total number of HH opportunities. The nosocomial infection rates for the pre- and post-interventional periods were also compared to establish the effect of the intervention on rate of infections acquired within the unit. The overall rate of HH compliance by all the HCWs increased from 42.9% pre-intervention to 61.4% post-intervention, P<0.001. Individually, the compliance was highest among the nurses, 49.9 vs. 82.5%, respectively (P<0.001) and lowest among the doctors, 38.6 vs. 43.2%, respectively (P=0.24). The effect of the increase in the HH compliance rate on the nosocomial infection rate was remarkable. There were significant reductions in the following: the rate of overall health care-associated infections/1000 patient-days, which fell from 37.2 pre-intervention to 15.1 post-intervention (P<0.001); the rate of bloodstream infections, which fell from 18.6 to 3.4/1000 central-line-days (P<0.001); and the rate of lower

In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch.

PubMed

Hanke, Alexander A; Maschler, Stephanie; Schöchl, Herbert; Flöricke, Felix; Görlinger, Klaus; Zanger, Klaus; Kienbaum, Peter

2011-02-10

Hypertonic saline hydroxyethyl starch (HH) has been recommended for first line treatment of hemorrhagic shock. Its effects on coagulation are unclear. We studied in vitro effects of HH dilution on whole blood coagulation and platelet function. Furthermore 7.2% hypertonic saline, 6% hydroxyethylstarch (as ingredients of HH), and 0.9% saline solution (as control) were tested in comparable dilutions to estimate specific component effects of HH on coagulation. The study was designed as experimental non-randomized comparative in vitro study. Following institutional review board approval and informed consent blood samples were taken from 10 healthy volunteers and diluted in vitro with either HH (HyperHaes, Fresenius Kabi, Germany), hypertonic saline (HT, 7.2% NaCl), hydroxyethylstarch (HS, HAES6%, Fresenius Kabi, Germany) or NaCl 0.9% (ISO) in a proportion of 5%, 10%, 20% and 40%. Coagulation was studied in whole blood by rotation thrombelastometry (ROTEM) after thromboplastin activation without (ExTEM) and with inhibition of thrombocyte function by cytochalasin D (FibTEM), the latter was performed to determine fibrin polymerisation alone. Values are expressed as maximal clot firmness (MCF, [mm]) and clotting time (CT, [s]). Platelet aggregation was determined by impedance aggregrometry (Multiplate) after activation with thrombin receptor-activating peptide 6 (TRAP) and quantified by the area under the aggregation curve (AUC [aggregation units (AU)/min]). Scanning electron microscopy was performed to evaluate HyperHaes induced cell shape changes of thrombocytes. 2-way ANOVA for repeated measurements, Bonferroni post hoc test, p < 0.01. Dilution impaired whole blood coagulation and thrombocyte aggregation in all dilutions in a dose dependent fashion. In contrast to dilution with ISO and HS, respectively, dilution with HH as well as HT almost abolished coagulation (MCFExTEM from 57.3 ± 4.9 mm (native) to 1.7 ± 2.2 mm (HH 40% dilution; p < 0.0001) and to 6.6 ± 3.4 mm (HT

Testing for genetic differences in survival and growth between hatchery and wild Chinook salmon from Warm Springs River, Oregon (Study sites: Warm Springs Hatchery and Little White Salmon River; Stocks: Warm Springs hatchery and Warm Springs River wild; Year classes: 1992 and 1996): Chapter 8

USGS Publications Warehouse

Rubin, Stephen P.; Reisenbichler, Reginald R.; Wetzel, Lisa A.; Leonetti,; Rubin, Stephen P.; Reisenbichler, Reginald R.; Wetzel, Lisa A.; Hayes, Michael C.

2012-01-01

The program at Warm Springs National Fish Hatchery in north - central Oregon was initiated with spring Chinook salmon Oncorhynchus tshawytscha from the Warm Springs River. Managers included wild fish in the broodstock most years and avoided artificial selection to minimize genetic divergence from the wild founder population. We tested for genetic differences in survival and growth between the hatchery and wild populations to ascertain whether this goal has been achieved. Progeny of hatchery x hatchery (HH), hatchery female x wild male (HW), and wild x wild (WW) crosses were genetically marked at the sSOD - 1* allozyme locus and released together as unfed fry in hatchery ponds in 1992 and 1996 and in the Little White Salmon River, in south - central Washington, in 1996. Fish were evaluated to returning adult at the hatchery and over their freshwater residence of 16 months in the stream. The three crosses differed on several measures including survival to outmigration in the stream (WW>HH>HW) and juvenile growth in the hatchery (1992 year - class; WW>HW>HH); however, results may have been confounded. The genetic marks were found to differentially effect survival in a companion study (HH mark favored over WW mark; HW mark intermediate). Furthermore, HW survival in the current study was neither intermediate, as would be expect ed from additive genetic effects, nor similar to that of HH fish as would be expected from maternal effects since HW and HH fish were maternal half - siblings. Finally, the unexpected performance of HW fish precludes ruling out maternal differences between hatchery and wild mothers as the cause of differences between HH and WW fish. The key finding that survival of HH fish in a stream was 0.91 that for WW fish, indicating a small loss of fitness for natural rearing in the hatchery population, is valid only if three conditions hold: (1) any selection on the genetic marks was in the same direction as in the companion study, (2) lower survival in

The relationship between hypnotizability, internal imagery, and efficiency of neurolinguistic programming.

PubMed

Kirenskaya, Anna V; Novototsky-Vlasov, Vladimir Y; Chistyakov, Andrey N; Zvonikov, Vyacheslav M

2011-04-01

Subjective scoring and autonomic variables (heart rate, skin conduction span) were used to verify the reality of inner experience during recollection of emotionally neutral, positive, and negative past events in 19 high (HH) and 12 low (LH) hypnotizable subjects in hypnotic and nonhypnotic experimental sessions. Also, the influence of hypnotizability on the effectiveness of an imagery-based neurolinguistic programming (NLP) technique was evaluated. Results demonstrated that subjective scores of image vividness and emotional intensity were significantly higher in the HH subjects compared to LH in both sessions. The past-events recollection was followed by increased autonomic activity only in the HH subjects. The NLP procedure was followed by decreased negative emotional intensity in both groups, but autonomic activity decline was observed in the HH subjects and not in the LH.

Regulation of Hedgehog Signalling Inside and Outside the Cell

PubMed Central

Ramsbottom, Simon A.; Pownall, Mary E.

2016-01-01

The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis. Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known to act as a morphogen that diffuses to elicit pattern formation. Heparan sulfate proteoglycans (HSPGs) play a major role in the regulation of Hh distribution outside the cell. Inside the cell, the primary cilium provides an important hub for processing the Hh signal in vertebrates. This review will summarise the current understanding of how the Hh pathway is regulated from ligand production, release, and diffusion, through to signal reception and intracellular transduction. PMID:27547735

Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2

PubMed Central

Han, Myoung-Eun; Lee, Young-Suk; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae-Ock

2009-01-01

Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. PMID:19742123

31 CFR 353.92 - Supplements, amendments, or revisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... UNITED STATES SAVINGS BONDS, SERIES EE AND HH Miscellaneous Provisions § 353.92 Supplements, amendments, or revisions. The Secretary of the Treasury may at any time, or from time to time, prescribe... of Series EE and HH. ...

31 CFR 353.92 - Supplements, amendments, or revisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... UNITED STATES SAVINGS BONDS, SERIES EE AND HH Miscellaneous Provisions § 353.92 Supplements, amendments, or revisions. The Secretary of the Treasury may at any time, or from time to time, prescribe... of Series EE and HH. ...

31 CFR 353.92 - Supplements, amendments, or revisions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... UNITED STATES SAVINGS BONDS, SERIES EE AND HH Miscellaneous Provisions § 353.92 Supplements, amendments, or revisions. The Secretary of the Treasury may at any time, or from time to time, prescribe... of Series EE and HH. ...

31 CFR 353.92 - Supplements, amendments, or revisions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... UNITED STATES SAVINGS BONDS, SERIES EE AND HH Miscellaneous Provisions § 353.92 Supplements, amendments, or revisions. The Secretary of the Treasury may at any time, or from time to time, prescribe... of Series EE and HH. ...

31 CFR 353.92 - Supplements, amendments, or revisions.

Code of Federal Regulations, 2013 CFR