Pressure-temperature phase diagrams of CaK(Fe1 -xNix)4As4 superconductors

NASA Astrophysics Data System (ADS)

Xiang, Li; Meier, William R.; Xu, Mingyu; Kaluarachchi, Udhara S.; Bud'ko, Sergey L.; Canfield, Paul C.

2018-05-01

The pressure dependence of the magnetic and superconducting transitions and that of the superconducting upper critical field are reported for CaK (Fe1-xNix) 4As4 , the first example of an Fe-based superconductor with spin-vortex-crystal-type magnetic ordering. Resistance measurements were performed on single crystals with two substitution levels (x =0.033 ,0.050 ) under hydrostatic pressures up to 5.12 GPa and in magnetic fields up to 9 T. Our results show that, for both compositions, magnetic transition temperatures TN are suppressed upon applying pressure; the superconducting transition temperatures Tc are suppressed by pressure as well, except for x =0.050 in the pressure region where TN and Tc cross. Furthermore, the pressure associated with the crossing of the TN and Tc lines also coincides with a minimum in the normalized slope of the superconducting upper critical field, consistent with a likely Fermi-surface reconstruction associated with the loss of magnetic ordering. Finally, at p ˜4 GPa, both Ni-substituted CaK (Fe1-xNix) 4As4 samples likely go through a half-collapsed-tetragonal phase transition, similar to the parent compound CaKFe4As4 .

PhysicsFun4K24

DTIC Science & Technology

2012-07-31

2012 2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4 . TITLE AND SUBTITLE PhysicsFun4K24 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c... 4 3.1 Story Space– Navy Leap Frogs ............................................................................................ 4 ...3.2 Curriculum Space - Force and Motion ................................................................................ 4 3.2.1 First Grade, parts

Zn/Cd/Cu- frameworks constructed by 3,3‧-diphenyldicarboxylate and 1,4-bis(1,2,4-triazol-1-yl)butane: Syntheses, structure, luminescence and luminescence sensing for metal ion in aqueous medium

NASA Astrophysics Data System (ADS)

Zhang, Mei-Na; Fan, Ting-Ting; Wang, Qiu-Shuang; Han, Hong-Liang; Li, Xia

2018-02-01

Three metal-organic frameworks (MOFs), [M(dpdc)(btb)0.5]n (M = Zn 1, Cd 2; dpdc = 3,3‧-diphenyldicarboxylate and btb = 1,4-bis(1,2,4-triazol-1-yl)butane) and [Cu3(dpdc)3(btb)2]n (3) were prepared and structurally determined. 1 is a 2D structure with the topology of {33·47·54·6}, while 2 possesses a 3D framework with the {312·429·514} topology. Complex 3 displays a 3D framework with the topology of {315.435.55}2{36.48.512.6.7}. 1-2 exhibit intense blue luminescence and high stability in water, which make them highly promising candidates as sensors using in aqueous medium. Complex 1 is a potential bi-functional chemosensor for Fe3+ and Al3+ ions while 2 displays a selective sensing ability to Fe3+ ion. Quenching mechanism of Fe3+ on the luminescence of 1-2 is attributed to the charge transfer process LMCT. 1 and 2 have same compositions but have different structures, thermally stabilities and different luminescence sensing functions. The relationship between MOF structures and luminescence sensing toward metal ions are further discussed.

Are the 'cave' minerals archerite (K,NH 4)H 2PO 4 and biphosphammite (K,NH 4)H 2PO 4 identical? A molecular structural study

NASA Astrophysics Data System (ADS)

Frost, Ray L.; Xi, Yunfei; Palmer, Sara J.

2011-08-01

The molecular structure of the mineral archerite ((K,NH 4)H 2PO 4) has been determined and compared with that of biphosphammite ((NH 4,K)H 2PO 4). Raman spectroscopy and infrared spectroscopy has been used to characterise these 'cave' minerals. Both minerals originated from the Murra-el-elevyn Cave, Eucla, Western Australia. The mineral is formed by the reaction of the chemicals in bat guano with calcite substrates. Raman and infrared bands are assigned to HPO4-, OH and NH stretching vibrations. The Raman band at 981 cm -1 is assigned to the HOP stretching vibration. Bands in the 1200-1800 cm -1 region are associated with NH4+ bending modes. The molecular structure of the two minerals appear to be very similar, and it is therefore concluded that the two minerals are identical.

A Versatile Low Temperature Synthetic Route to Zintl Phase Precursors: Na4Si4, Na4Ge4 and K4Ge4 as Examples

PubMed Central

Ma, Xuchu; Xu, Fen; Atkins, Tonya; Goforth, Andrea M.; Neiner, Doinita; Navrotsky, Alexandra; Kauzlarich, Susan M.

2010-01-01

Na4Si4 and Na4Ge4 are ideal chemical precursors for inorganic clathrate structures, clusters, and nanocrystals. The monoclinic Zintl phases, Na4Si4 and Na4Ge4, contain isolated homo-tetrahedranide [Si4]4− and [Ge4]4− clusters surrounded by alkali metal cations. In this study, a simple scalable route has been applied to prepare Zintl phases of composition Na4Si4 and Na4Ge4 using the reaction between NaH and Si or Ge at low temperature (420 °C for Na4Si4 and 270 °C for Na4Ge4). The method was also applied to K4Ge4, using KH and Ge as raw materials, to show the versatility of this approach. The influence of specific reaction conditions on the purity of these Zintl phases has been studied by controlling five factors: the method of reagent mixing (manual or ball milled), the stoichiometry between raw materials, the reaction temperature, the heating time and the gas flow rate. Moderate ball-milling and excess NaH or KH facilitate the formation of pure Na4Si4, Na4Ge4 or K4Ge4 at 420 °C (Na4Si4) or 270 °C (both M4Ge4 compounds, M = Na, K). TG/DSC analysis of the reaction of NaH and Ge indicates that ball milling reduces the temperature for reaction and confirms the formation temperature. This method provides large quantities of high quality Na4Si4 and Na4Ge4 without the need for specialized laboratory equipment, such as Schlenk lines, niobium/tantalum containers, or an arc welder, thereby expanding the accessibility and chemical utility of these phases by making them more convenient to prepare. This new synthetic method may also be extended to lithium-containing Zintl phases (LiH is commercially available) as well as to alkali metal-tetrel Zintl compounds of other compositions, e.g. K4Ge9. PMID:19921060

Chemical and Electrochemical Asymmetric Dihydroxylation of Olefins in I(2)-K(2)CO(3)-K(2)OsO(2)(OH)(4) and I(2)-K(3)PO(4)/K(2)HPO(4)-K(2)OsO(2)(OH)(4) Systems with Sharpless' Ligand.

PubMed

Torii, Sigeru; Liu, Ping; Bhuvaneswari, Narayanaswamy; Amatore, Christian; Jutand, Anny

1996-05-03

Iodine-assisted chemical and electrochemical asymmetric dihydroxylation of various olefins in I(2)-K(2)CO(3)-K(2)OsO(2)(OH)(4) and I(2)-K(3)PO(4)/K(2)HPO(4)-K(2)OsO(2)(OH)(4) systems with Sharpless' ligand provided the optically active glycols in excellent isolated yields and high enantiomeric excesses. Iodine (I(2)) was used stoichiometrically for the chemical dihydroxylation, and good results were obtained with nonconjugated olefins in contrast to the case of potassium ferricyanide as a co-oxidant. The potentiality of I(2) as a co-oxidant under stoichiometric conditions has been proven to be effective as an oxidizing mediator in electrolysis systems. Iodine-assisted asymmetric electro-dihydroxylation of olefins in either a t-BuOH/H(2)O(1/1)-K(2)CO(3)/(DHQD)(2)PHAL-(Pt) or t-BuOH/H(2)O(1/1)-K(3)PO(4)/K(2)HPO(4)/(DHQD)(2)PHAL-(Pt) system in the presence of potassium osmate in an undivided cell was investigated in detail. Irrespective of the substitution pattern, all the olefins afforded the diols in high yields and excellent enantiomeric excesses. A plausible mechanism is discussed on the basis of cyclic voltammograms as well as experimental observations.

The binary system K2SO4CaSO4

USGS Publications Warehouse

Rowe, J.J.; Morey, G.W.; Hansen, I.D.

1965-01-01

The binary system K2SO4CaSO4 was studied by means of heating-cooling curves, differential thermal analysis, high-temperature quenching technique and by means of a heating stage mounted on an X-ray diffractometer. Compositions and quench products were identified optically and by X-ray. Limited solid solution of CaSO4 in K2SO4 was found. There is a eutectic at 875??C and 34 wt. per cent CaSO4. Calcium langbeinite melts incongruently at 1011??C. The melting-point of CaSO4 (1462??C) was determined by the quenching technique using sealed platinum tubes. The only intermediate crystalline phase found in the system is K2SO4??2CaSO4 (calcium langbeinite). ?? 1965.

Investigation of phase transitions in LiK 1- x(NH 4) xSO 4 mixed crystal

NASA Astrophysics Data System (ADS)

Freire, P. T. C.; Paraguassu, W.; Silva, A. P.; Pilla, O.; Teixeira, A. M. R.; Sasaki, J. M.; Mendes Filho, J.; Guedes, I.; Melo, F. E. A.

1999-02-01

We present Raman scattering results on LiK 1- x(NH 4) xSO 4 mixed crystal for temperatures between 100 and 300 K. We observed that in this temperature range the crystal undergoes two different phase transitions, which we call Bansal and Tomaszewski phase transitions. The introduction of ammonium ions in the potassium sites increases the C 66→C 3v4 (Bansal) phase transition temperature and decreases the Tomaszewski phase transition temperature. Finally, the most impressive effect of the presence of ammonium impurity in the LiKSO 4 structure is the decrease in the temperature hysteresis of Bansal phase transition and the almost complete destruction of hysteresis in the Tomaszewski phase transition, leading to a high temperature range of stability of the trigonal phase.

Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia.

PubMed

Roth Flach, Rachel J; Danai, Laura V; DiStefano, Marina T; Kelly, Mark; Menendez, Lorena Garcia; Jurczyk, Agata; Sharma, Rohit B; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Bortell, Rita; Alonso, Laura C; Czech, Michael P

2016-07-29

Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced β cell mass, fewer proliferating β cells and reduced islet-specific gene mRNA expression compared with controls, although insulin content was normal. Interestingly, the reduced plasma insulin in M4K4 iKO mice exposed to chronic (16 weeks) HFD was not observed in response to acute HFD challenge or short term treatment with the insulin receptor antagonist S961. Furthermore, the improved insulin sensitivity in obese M4K4 iKO mice was abrogated by high exogenous insulin over the course of a euglycemic clamp study, indicating that hypoinsulinemia promotes insulin sensitivity in chronically obese M4K4 iKO mice. These results demonstrate that protein kinase Map4k4 drives obesity-induced hyperinsulinemia and insulin resistance in part by promoting insulin secretion from β cells in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis

PubMed Central

Roth Flach, Rachel J.; Skoura, Athanasia; Matevossian, Anouch; Danai, Laura V.; Zheng, Wei; Cortes, Christian; Bhattacharya, Samit K.; Aouadi, Myriam; Hagan, Nana; Yawe, Joseph C.; Vangala, Pranitha; Menendez, Lorena Garcia; Cooper, Marcus P.; Fitzgibbons, Timothy P.; Buckbinder, Leonard; Czech, Michael P.

2015-01-01

Signalling pathways that control endothelial cell (EC) permeability, leukocyte adhesion and inflammation are pivotal for atherosclerosis initiation and progression. Here we demonstrate that the Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), which has been implicated in inflammation, is abundantly expressed in ECs and in atherosclerotic plaques from mice and humans. On the basis of endothelial-specific MAP4K4 gene silencing and gene ablation experiments in Apoe−/− mice, we show that MAP4K4 in ECs markedly promotes Western diet-induced aortic macrophage accumulation and atherosclerotic plaque development. Treatment of Apoe−/− and Ldlr−/− mice with a selective small-molecule MAP4K4 inhibitor also markedly reduces atherosclerotic lesion area. MAP4K4 silencing in cultured ECs attenuates cell surface adhesion molecule expression while reducing nuclear localization and activity of NFκB, which is critical for promoting EC activation and atherosclerosis. Taken together, these results reveal that MAP4K4 is a key signalling node that promotes immune cell recruitment in atherosclerosis. PMID:26688060

Mössbauer spectroscopy measurements on the 35.5 K superconductor Rb1 -δEuFe4As4

NASA Astrophysics Data System (ADS)

Albedah, Mohammed A.; Nejadsattari, Farshad; Stadnik, Zbigniew M.; Liu, Yi; Cao, Guang-Han

2018-04-01

The results of x-ray diffraction and 57Fe and 151Eu Mössbauer spectroscopy measurements, supplemented with ab initio hyperfine-interaction parameter calculations, on the new 35.5 K superconductor Rb1 -δEuFe4As4 are presented. The superconductor crystallizes in the tetragonal space group P 4 /m m m with the lattice parameters a =3.8849 (1 ) Å and c =13.3370 (3 ) Å. It is shown that there is no magnetic order of the Fe magnetic moments down to 2.1 K and that the ferromagnetic order is associated solely with the Eu magnetic moments. The Curie temperature TC=16.54 (8 ) K is determined from the temperature dependence of both the hyperfine magnetic field at 151Eu nuclei and the transferred hyperfine magnetic field at 57Fe nuclei that is induced by the ferromagnetically ordered Eu sublattice. The Eu magnetic moments are demonstrated to be perpendicular to the crystallographic c axis. The temperature dependence of the principal component of the electric field gradient tensor, at both Fe and Eu sites, is well described by a T3 /2 power-law relation. Good agreement between the calculated and measured hyperfine-interaction parameters is observed. The Debye temperature of Rb1 -δEuFe4As4 is found to be 391(8) K.

Pressure-temperature phase diagrams of CaK ( Fe 1 – x Ni x ) 4 As 4 superconductors

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

Xiang, Li; Meier, William R.; Xu, Mingyu

Here, the pressure dependence of the magnetic and superconducting transitions and that of the superconducting upper critical field are reported for CaK(Fe 1–xNi x) 4As 4, the first example of an Fe-based superconductor with spin-vortex-crystal-type magnetic ordering. Resistance measurements were performed on single crystals with two substitution levels (x = 0.033,0.050) under hydrostatic pressures up to 5.12 GPa and in magnetic fields up to 9 T. Our results show that, for both compositions, magnetic transition temperatures T N are suppressed upon applying pressure; the superconducting transition temperatures T c are suppressed by pressure as well, except for x = 0.050more » in the pressure region where T N and T c cross. Furthermore, the pressure associated with the crossing of the T N and T c lines also coincides with a minimum in the normalized slope of the superconducting upper critical field, consistent with a likely Fermi-surface reconstruction associated with the loss of magnetic ordering. Lastly, at p ~ 4 GPa, both Ni-substituted CaK(Fe 1–xNi x) 4As 4 samples likely go through a half-collapsed-tetragonal phase transition, similar to the parent compound CaKFe 4As 4.« less

Pressure-temperature phase diagrams of CaK ( Fe 1 – x Ni x ) 4 As 4 superconductors

DOE PAGES

Xiang, Li; Meier, William R.; Xu, Mingyu; ...

2018-05-22

Here, the pressure dependence of the magnetic and superconducting transitions and that of the superconducting upper critical field are reported for CaK(Fe 1–xNi x) 4As 4, the first example of an Fe-based superconductor with spin-vortex-crystal-type magnetic ordering. Resistance measurements were performed on single crystals with two substitution levels (x = 0.033,0.050) under hydrostatic pressures up to 5.12 GPa and in magnetic fields up to 9 T. Our results show that, for both compositions, magnetic transition temperatures T N are suppressed upon applying pressure; the superconducting transition temperatures T c are suppressed by pressure as well, except for x = 0.050more » in the pressure region where T N and T c cross. Furthermore, the pressure associated with the crossing of the T N and T c lines also coincides with a minimum in the normalized slope of the superconducting upper critical field, consistent with a likely Fermi-surface reconstruction associated with the loss of magnetic ordering. Lastly, at p ~ 4 GPa, both Ni-substituted CaK(Fe 1–xNi x) 4As 4 samples likely go through a half-collapsed-tetragonal phase transition, similar to the parent compound CaKFe 4As 4.« less

The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons.

PubMed

Larhammar, Martin; Huntwork-Rodriguez, Sarah; Rudhard, York; Sengupta-Ghosh, Arundhati; Lewcock, Joseph W

2017-11-15

The c-Jun- N -terminal kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration after acute injury or in chronic neurodegenerative disease. Dual leucine zipper kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, misshapen-like kinase 1 (MINK1 or MAP4K6) and TNIK Traf2- and Nck-interacting kinase (TNIK or MAP4K7), as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, MINK1, and TNIK act redundantly to regulate DLK activation and downstream JNK-dependent phosphorylation of c-Jun in response to stress. Targeting MAP4K4, MINK1, and TNIK, but not any of these kinases individually, is sufficient to protect neurons potently from degeneration. Pharmacological inhibition of MAP4Ks blocks stabilization and phosphorylation of DLK within axons and subsequent retrograde translocation of the JNK signaling complex to the nucleus. These results position MAP4Ks as important regulators of the DLK/JNK signaling pathway. SIGNIFICANCE STATEMENT Neuronal degeneration occurs in disparate circumstances: during development to refine neuronal connections, after injury to clear damaged neurons, or pathologically during disease. The dual leucine zipper kinase (DLK)/c-Jun- N -terminal kinase (JNK) pathway represents a conserved regulator of neuronal injury signaling that drives both neurodegeneration and axon regeneration, yet little is known about the factors that initiate DLK activity. Here, we uncover a novel role for a subfamily of MAP4 kinases consisting of MAP4K4, Traf2- and Nck-interacting kinase (TNIK or MAP4K7), and misshapen-like kinase 1 (MINK1 or MAP4K6) in regulating DLK/JNK signaling in neurons. Inhibition of

Pharmacokinetics, Pharmacodynamics, and Stereoselective Metabolism of the 1,2,4-Triazole Fungicide, Triadimefon, in Vertebrate Species

EPA Science Inventory

Questions Agricultural and pharmaceutical 1,2,4-triazole fungicides are potent cytochrome P450 modulators that can disrupt mammalian steroid biosynthesis. Triadimefon [(RS)-1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one] is unique with respect to tumorige...

CALCULATED REGENERATOR PERFORMANCE AT 4 K WITH HELIUM-4 AND HELIUM-3

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

Radebaugh, Ray; Huang Yonghua; O'Gallagher, Agnes

2008-03-16

The helium-4 working fluid in regenerative cryocoolers operating with the cold end near 4 K deviates considerably from an ideal gas. As a result, losses in the regenerator, given by the time-averaged enthalpy flux, are increased and are strong functions of the operating pressure and temperature. Helium-3, with its lower boiling point, behaves somewhat closer to an ideal gas in this low temperature range and can reduce the losses in 4 K regenerators. An analytical model is used to find the fluid properties that strongly influence the regenerator losses as well as the gross refrigeration power. The thermodynamic and transportmore » properties of helium-3 were incorporated into the latest NIST regenerator numerical model, known as REGEN3.3, which was used to model regenerator performance with either helium-4 or helium-3. With this model we show how the use of helium-3 in place of helium-4 can improve the performance of 4 K regenerative cryocoolers. The effects of operating pressure, warm-end temperature, and frequency on regenerators with helium-4 and helium-3 are investigated and compared. The results are used to find optimum operating conditions. The frequency range investigated varies from 1 Hz to 30 Hz, with particular emphasis on higher frequencies.« less

Regulation of human adenovirus alternative RNA splicing by the adenoviral L4-33K and L4-22K proteins.

PubMed

Biasiotto, Roberta; Akusjärvi, Göran

2015-01-28

Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced viral mRNAs. Studies aimed at characterizing the interactions between the virus and the host cell RNA splicing machinery have identified three viral proteins of special significance for the control of late viral gene expression: L4-33K, L4-22K, and E4-ORF4. L4-33K is a viral alternative RNA splicing factor that controls L1 alternative splicing via an interaction with the cellular protein kinases Protein Kinase A (PKA) and DNA-dependent protein kinase (DNA-PK). L4-22K is a viral transcription factor that also has been implicated in the splicing of a subset of late viral mRNAs. E4-ORF4 is a viral protein that binds the cellular protein phosphatase IIA (PP2A) and controls Serine/Arginine (SR)-rich protein activity by inducing SR protein dephosphorylation. The L4-33K, and most likely also the L4-22K protein, are highly phosphorylated in vivo. Here we will review the function of these viral proteins in the post-transcriptional control of adenoviral gene expression and further discuss the significance of potential protein kinases phosphorylating the L4-33K and/or L4-22K proteins.

Synthesis of 2,3-trans-3,4-cis- and 2,3-trans-3,4-trans-2,3,4-triphenyltetrahydrofurans.

PubMed

Munshi, K L; Dikshit, D K; Kapil, R S; Anand, N

1974-04-01

The synthesis of 2,3-trans-3,4-cis- and 2,3-trans-3,4-trans-2,3,4-triphenyltetrahydrofurans was undertaken because these compounds incorportae the essential structural features of certain 2,3-diphenyl-benzofurans and 1,2,3-triphenylalkanones reported earlier to have marked antifertility activity. The synthesis of the 2 tetrahydrofurans was achieved by the cyclization of corresponding 2,3,4-triphenylbutane-1,4-diols upon heating with dimethyl sulfoxide (DMSO). The butane 1,4-diols were in turn prepared either by direct litium aluminum hydride (LAH) reduction of methyl 3-benzoyl-2,3-diphenylpropionates or by conversion of these propionates to delta-3,4-butryrolactones followed by LAH reduction. The propionates were prepared from the Fiedel-Crafts reaction of 2,3-diphenylsuccinic anhydride with benzene. Tetrahydrofurans were tested for their antiimplantation activity in rats. 2,3-trans-3,4-cis-2,4-diphenyl-3-p -(beta-pyrrolidinoethoxy) phenyltetrahydrofuran oxalate was found to inhibit implantation completely at 50 mg/kg, but was inefective at a lower dose.

Contributions of the Na+/K+-ATPase, NKCC1, and Kir4.1 to hippocampal K+ clearance and volume responses

PubMed Central

Larsen, Brian Roland; Assentoft, Mette; Cotrina, Maria L.; Hua, Susan Z.; Nedergaard, Maiken; Kaila, Kai; Voipio, Juha; MacAulay, Nanna

2015-01-01

Bursts of network activity in the brain are associated with a transient increase in extracellular K+ concentration. The excess K+ is removed from the extracellular space by mechanisms proposed to involve Kir4.1-mediated spatial buffering, the Na+/K+/2Cl− cotransporter (NKCC1), and/or Na+/K+-ATPase activity. Their individual contribution to [K+]o management has been of extended controversy. The present study aimed, by several complementary approaches, to delineate the transport characteristics of Kir4.1, NKCC1, and Na+/K+-ATPase and to resolve their involvement in clearance of extracellular K+ transients. Primary cultures of rat astrocytes displayed robust NKCC1 activity with [K+]o increases above basal levels. Increased [K+]o produced NKCC1-mediated swelling of cultured astrocytes and NKCC1 could thereby potentially act as a mechanism of K+ clearance while concomitantly mediate the associated shrinkage of the extracellular space. In rat hippocampal slices, inhibition of NKCC1 failed to affect the rate of K+ removal from the extracellular space while Kir4.1 enacted its spatial buffering only during a local [K+]o increase. In contrast, inhibition of the different isoforms of Na+/K+-ATPase reduced post-stimulusclearance of K+ transients. The glia-specific α2/β2 subunit composition of Na+/K+-ATPase, when expressed in Xenopus oocytes, displayed a K+ affinity and voltage-sensitivity that would render this astrocyte-specific subunit composition specifically geared for controlling [K+]o during neuronal activity. In rat hippocampal slices, simultaneous measurements of the extracellular space volume revealed that neither Kir4.1, NKCC1, nor Na+/K+-ATPase accounted for the stimulus-induced shrinkage of the extracellular space. Thus, NKCC1 plays no role in activity-induced extracellular K+ recovery in native hippocampal tissue while Kir4.1 and Na+/K+-ATPase serve temporally distinct roles. PMID:24482245

40 CFR Table K-1 to Subpart K of... - Electric Arc Furnace (EAF) CH4 Emission Factors

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Electric Arc Furnace (EAF) CH4 Emission Factors K Table K-1 to Subpart K of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION.... 98, Subpt. K, Table K-1 Table K-1 to Subpart K of Part 98—Electric Arc Furnace (EAF) CH4 Emission...

40 CFR Table K-1 to Subpart K of... - Electric Arc Furnace (EAF) CH4 Emission Factors

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Electric Arc Furnace (EAF) CH4 Emission Factors K Table K-1 to Subpart K of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION.... 98, Subpt. K, Table K-1 Table K-1 to Subpart K of Part 98—Electric Arc Furnace (EAF) CH4 Emission...

40 CFR Table K-1 to Subpart K of... - Electric Arc Furnace (EAF) CH4 Emission Factors

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Electric Arc Furnace (EAF) CH4 Emission Factors K Table K-1 to Subpart K of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION.... 98, Subpt. K, Table K-1 Table K-1 to Subpart K of Part 98—Electric Arc Furnace (EAF) CH4 Emission...

40 CFR Table K-1 to Subpart K of... - Electric Arc Furnace (EAF) CH4 Emission Factors

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Electric Arc Furnace (EAF) CH4 Emission Factors K Table K-1 to Subpart K of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION.... 98, Subpt. K, Table K-1 Table K-1 to Subpart K of Part 98—Electric Arc Furnace (EAF) CH4 Emission...

Optical and electrical properties of Mn1.56Co0.96Ni0.48O4 thin films

NASA Astrophysics Data System (ADS)

Gao, Y. Q.; Huang, Z. M.; Hou, Y.; Wu, J.; Chu, J. H.

2013-12-01

Mn1.56Co0.96Ni0.48O4 (MCN) films with different layers have been prepared on Al2O3 substrate by chemical solution deposition method. The microstructures, optical and electrical properties of the films are investigated. X-ray diffraction and microstructure analyses show good crystallization and both the crystalline quality and the grain size are improved with the increasing thickness of the films. Mid-infrared optical properties of MCN films have been investigated using transmission spectra. The results show the red shift of absorption with the increasing film thickness and the energy gap Eg decrease from 0.6422 eV to 0.6354 eV. All the MCN films show an exponential decrease in the resistivity with increasing temperature within the measured range. The temperature dependence resistivity can be described by the small polarons hopping model. Using this model, the characteristic temperature T0 and activation energy E of the MCN films were derived. With the film thickness increase, the T0 and E of the MCN films increase. The calculated room temperature coefficient of resistance (TCR) of MCN film with 100 layers is -3.5% K-1. The MCN films showed appropriate resistance and high value of TCR, these advantages make them very preponderant for thermal sensors.

Magnetism of the 35 K superconductor CsEuFe4As4

NASA Astrophysics Data System (ADS)

Albedah, Mohammed A.; Nejadsattari, Farshad; Stadnik, Zbigniew M.; Liu, Yi; Cao, Guang-Han

2018-04-01

The results of ab initio hyperfine-interaction parameters calculations, and of x-ray diffraction and 57Fe and 151Eu Mössbauer spectroscopy study of the new 35 K superconductor CsEuFe4As4 are reported. The superconductor crystallizes in the tetragonal space group P4/mmm with the lattice parameters a = 3.8956(1) Å and c = 13.6628(5) Å. It is demonstrated unequivocally that there is no magnetic order of the Fe magnetic moments down to 2.1 K and that the ferromagnetic order is associated with the Eu magnetic moments. The Curie temperature TC = 15.97(8) K determined from the temperature dependence of the hyperfine magnetic field at 151Eu nuclei is shown to be compatible with the temperature dependence of the transferred hyperfine magnetic field at 57Fe nuclei that is induced by the ferromagnetically ordered Eu sublattice. The Eu magnetic moments are shown to be perpendicular to the crystallographic c-axis. The temperature dependence of the principal component of the electric field gradient tensor, both at Fe and Eu sites, is well described by a T 3/2 power-law relation. Good agreement between the calculated and measured hyperfine-interaction parameters is observed. The Debye temperature of CsEuFe4As4 is found to be 295(3) K.

Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4

PubMed Central

Dhar, Shilpa S.; Lee, Sung-Hun; Kan, Pu-Yeh; Voigt, Philipp; Ma, Li; Shi, Xiaobing; Reinberg, Danny; Lee, Min Gyu

2012-01-01

Mixed-lineage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3), a hallmark of gene activation. However, how MLL4-deposited H3K4me3 interplays with other histone marks in epigenetic processes remains largely unknown. Here, we show that MLL4 plays an essential role in differentiating NT2/D1 stem cells by activating differentiation-specific genes. A tandem plant homeodomain (PHD4–6) of MLL4 recognizes unmethylated or asymmetrically dimethylated histone H4 Arg 3 (H4R3me0 or H4R3me2a) and is required for MLL4's nucleosomal methyltransferase activity and MLL4-mediated differentiation. Kabuki syndrome mutations in PHD4–6 reduce PHD4–6's binding ability and MLL4's catalytic activity. PHD4–6's binding strength is inhibited by H4R3 symmetric dimethylation (H4R3me2s), a gene-repressive mark. The protein arginine methyltransferase 7 (PRMT7), but not PRMT5, represses MLL4 target genes by up-regulating H4R3me2s levels and antagonizes MLL4-mediated differentiation. Consistently, PRMT7 knockdown increases MLL4-catalyzed H3K4me3 levels. During differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes, including many HOXA and HOXB genes. These findings indicate that the trans-tail inhibition of MLL4-generated H3K4me3 by PRMT7-regulated H4R3me2s may result from H4R3me2s's interference with PHD4–6's binding activity and is a novel epigenetic mechanism that underlies opposing effects of MLL4 and PRMT7 on cellular differentiation. PMID:23249737

Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4.

PubMed

Dhar, Shilpa S; Lee, Sung-Hun; Kan, Pu-Yeh; Voigt, Philipp; Ma, Li; Shi, Xiaobing; Reinberg, Danny; Lee, Min Gyu

2012-12-15

Mixed-lineage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3), a hallmark of gene activation. However, how MLL4-deposited H3K4me3 interplays with other histone marks in epigenetic processes remains largely unknown. Here, we show that MLL4 plays an essential role in differentiating NT2/D1 stem cells by activating differentiation-specific genes. A tandem plant homeodomain (PHD(4-6)) of MLL4 recognizes unmethylated or asymmetrically dimethylated histone H4 Arg 3 (H4R3me0 or H4R3me2a) and is required for MLL4's nucleosomal methyltransferase activity and MLL4-mediated differentiation. Kabuki syndrome mutations in PHD(4-6) reduce PHD(4-6)'s binding ability and MLL4's catalytic activity. PHD(4-6)'s binding strength is inhibited by H4R3 symmetric dimethylation (H4R3me2s), a gene-repressive mark. The protein arginine methyltransferase 7 (PRMT7), but not PRMT5, represses MLL4 target genes by up-regulating H4R3me2s levels and antagonizes MLL4-mediated differentiation. Consistently, PRMT7 knockdown increases MLL4-catalyzed H3K4me3 levels. During differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes, including many HOXA and HOXB genes. These findings indicate that the trans-tail inhibition of MLL4-generated H3K4me3 by PRMT7-regulated H4R3me2s may result from H4R3me2s's interference with PHD(4-6)'s binding activity and is a novel epigenetic mechanism that underlies opposing effects of MLL4 and PRMT7 on cellular differentiation.

Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

PubMed

Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S; Liang, Kaiwei; Takahashi, Yoh-Hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C Peter; Shilatifard, Ali

2012-12-01

Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.

Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4

PubMed Central

Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S.; Liang, Kaiwei; Takahashi, Yoh-hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C. Peter; Shilatifard, Ali

2012-01-01

Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers. PMID:23166019

A double B1-mode 4-layer laminated piezoelectric linear motor.

PubMed

Li, Xiaotian; Chen, Zhijiang; Dong, Shuxiang

2012-12-01

We report a miniature piezoelectric ultrasonic linear motor that is made of four Pb(Zr,Ti)O(3) (PZT) piezoelectric ceramic layers for low-voltage work. The 4-layer piezoelectric laminate works in two orthogonal first-bending modes for producing elliptical oscillations, which are then used to drive a contacting slider into continuous linear motion. Experimental results show that the miniature linear motor (size: 4 × 4 × 12 mm, weight: 1.7 g) can generate a large driving force of 0.48 N and a linear motion speed of up to 160 mm/s, using a 40 V(pp)/mm voltage drive at its resonance frequency of 64.5 kHz. The maximum efficiency of the linear motor is 30%.

PhysicsFun4k24

DTIC Science & Technology

2013-01-11

DATE 01 OCT 2013 2. REPORT TYPE 3. DATES COVERED 01-08-2012 to 31-12-2012 4 . TITLE AND SUBTITLE PhysicsFun4k24 5a. CONTRACT NUMBER 5b. GRANT...3  3.2  Curriculum Space ‐ Force and Motion ................................................................................  4   3.3  Game Space...Virtual World of “Tadpoles” ........................................................................  4   4   Measurement and Assessment

Low-Temperature Rate Coefficients of C2H with CH4 and CD4 from 154 to 359 K

NASA Technical Reports Server (NTRS)

Opansky, Brian J.; Leone, Stephen R.

1996-01-01

Rate coefficients for the reaction C2H + CH4 yields C2H2 + CH3 and C2H + CD4 yields C2HD + CD3 are measured over the temperature range 154-359 K using transient infrared laser absorption spectroscopy. Ethynyl radicals are produced by pulsed laser photolysis of C2H2 in a variable temperature flow cell, and a tunable color center laser probes the transient removal of C2H (Chi(exp 2) Sigma(+) (0,0,0)) in absorption. The rate coefficients for the reactions of C2H with CH4 and CD4 both show a positive temperature dependence over the range 154-359 K, which can be expressed as k(sub CH4) = (1.2 +/- 0.1) x 10(exp -11) exp((-491 +/- 12)/T) and k(sub CD4) = (8.7 +/- 1.8) x 10(exp -12) exp((-650 +/- 61)/T) cm(exp 3) molecule(exp -1) s(exp -1), respectively. The reaction of C2H + CH4 exhibits a significant kinetic isotope effect at 300 K of k(sub CH4)/k(sub CD4) = 2.5 +/- 0.2. Temperature dependent rate constants for C2H + C2H2 were also remeasured over an increased temperature range from 143 to 359 K and found to show a slight negative temperature dependence, which can be expressed as k(sub C2H2) = 8.6 x 10(exp -16) T(exp 1.8) exp((474 +/- 90)/T) cm(exp 3) molecule(exp -1) s(exp -1).

Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation

PubMed Central

Wooster, David G; Maruvada, Ravi; Blom, Anna M; Prasadarao, Nemani V

2006-01-01

Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood–brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA–E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum. PMID:16556262

Ammonium–cobalt–nickel phosphates, NH{sub 4}[Co{sub 1−x}Ni{sub x}PO{sub 4}]·H{sub 2}O

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

Torre-Fernández, Laura; Trobajo, Camino; Pedro, Imanol de

The ammonium–cobalt–nickel phosphates, NH{sub 4}[Co{sub 1−x}Ni{sub x}PO{sub 4}]·H{sub 2}O (x=0.00, 0.34, 0.59, 0.70, 1.00), and the deuterated forms, ND{sub 4}[Co{sub 1−x}Ni{sub x}PO{sub 4}]·D{sub 2}O (x=0.00, 0.38, 0.48, 0.69, 0.85), have been synthesized under mild hydrothermal conditions and characterised using X-ray and neutron diffraction, chemical and thermal analysis, and magnetic measurements. Their crystal structures, including hydrogen positions, were determined by Rietveld refinement using single-crystal X-ray and neutron powder diffraction data. The space group of these orthorhombic crystals modifies as a function of their composition. The magnetic susceptibility and magnetization measurements of these ammonium–cobalt–nickel phosphates show antiferromagnetic behaviour, and the Neel temperaturemore » evolves from 5.5 K (x=0.00) up to 13.2 K (x=1.00). - Graphical abstract: We obtained single crystals for all the members of the family. In this series, although all crystals are orthorhombic, the space group changes as a function of the composition, showing how the single-crystal diffraction data is capable to manifest structural subtleties that had not been described before for this group of materials. All the investigated materials behave antiferromagnetically with ordering temperatures from 5.5 K up to 13.2 K. Display Omitted - Highlights: • The ammonium–cobalt–nickel phosphates, NH{sub 4}[Co{sub 1−x}Ni{sub x}PO{sub 4}]·H{sub 2}O (x=0.00, 0.34, 0.59, 0.70, 1.00) and the deuterated forms ND4[Co1-xNixPO4]·D{sub 2}O (x=0.00, 0.38, 0.49, 0.68, 0.85) have synthesized by hydrothermal synthesis. • The structural studies of these compounds are introduced as a function of the composition. • The magnetic studies show an antiferromagnetically behavior with ordering temperatures from 5.5 K to 13.2 K.« less

4 CFR 4.1 - Training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 4 Accounts 1 2011-01-01 2011-01-01 false Training. 4.1 Section 4.1 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM EMPLOYEE PERFORMANCE AND UTILIZATION § 4.1 Training. The provisions of chapter 41, of title 5, United States Code, and Office of Personnel Management implementing regulations...

4 CFR 4.1 - Training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 4 Accounts 1 2010-01-01 2010-01-01 false Training. 4.1 Section 4.1 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM EMPLOYEE PERFORMANCE AND UTILIZATION § 4.1 Training. The provisions of chapter 41, of title 5, United States Code, and Office of Personnel Management implementing regulations...

Crystal structures of 4-meth-oxy-benzoic acid-1,3-bis-(pyridin-4-yl)propane (2/1) and biphenyl-4,4'-di-carb-oxy-lic acid-4-meth-oxy-pyridine (1/2).

PubMed

Gotoh, Kazuma; Ishida, Hiroyuki

2017-07-01

The crystal structures of two hydrogen-bonded compounds, namely 4-meth-oxy-benzoic acid-1,3-bis-(pyridin-4-yl)propane (2/1), C 13 H 14.59 N 2 ·C 8 H 7.67 O 3 ·C 8 H 7.74 O 3 , (I), and biphenyl-4,4'-di-carb-oxy-lic acid-4-meth-oxy-pyridine (1/2), C 14 H 9.43 O 4 ·C 6 H 7.32 NO·C 6 H 7.25 NO, (II), have been determined at 93 K. In (I), the asymmetric unit consists of two crystallographically independent 4-meth-oxy-benzoic acid mol-ecules and one 1,3-bis-(pyridin-4-yl)propane mol-ecule. The asymmetric unit of (II) comprises one biphenyl-4,4'-di-carb-oxy-lic acid mol-ecule and two independent 4-meth-oxy-pyridine mol-ecules. In each crystal, the acid and base mol-ecules are linked by short O-H⋯N/N-H⋯O hydrogen bonds, in which H atoms are disordered over the acid O-atom and base N-atom sites, forming a linear hydrogen-bonded 2:1 or 1:2 unit of the acid and the base. The 2:1 units of (I) are linked via C-H⋯π, π-π and C-H⋯O inter-actions into a tape structure along [101], while the 1:2 units of (II) form a double-chain structure along [-101] through π-π and C-H⋯O inter-actions.

46 CFR 160.048-4 - Construction and workmanship.

Code of Federal Regulations, 2014 CFR

2014-10-01

... provide buoyancy to aid a person in keeping afloat in the water. No hooks, snaps, or other means shall be... displacement of the individual heat-sealed pad inserts shall be 51/2 pounds each, plus or minus 1/2 pound, when tested in accordance with the method set forth in § 160.048-5(e)(1), except that the pad covers shall not...

46 CFR 160.048-4 - Construction and workmanship.

Code of Federal Regulations, 2013 CFR

2013-10-01

... provide buoyancy to aid a person in keeping afloat in the water. No hooks, snaps, or other means shall be... displacement of the individual heat-sealed pad inserts shall be 51/2 pounds each, plus or minus 1/2 pound, when tested in accordance with the method set forth in § 160.048-5(e)(1), except that the pad covers shall not...

Crystal structure of 4,4′-(disulfanediyl)dibutanoic acid–4,4′-bipyridine (1/1)

PubMed Central

Atria, Ana María; Garland, Maria Teresa; Baggio, Ricardo

2014-01-01

4,4′-(Disulfanediyl)dibutanoic acid (dtba) and 4,4′-bipyridine (4,4′-bpy) crystallize in an 1:1 ratio, leading to the title co-crystal with composition C8H14O4S2·C10H8N2. A distinctive feature of the crystal structure is the geometry of the dtba moiety, which appears to be stretched [with a 9.98 (1) Å span between outermost carbons] and acts as an hydrogen-bonding connector, forming linear chains along [-211] with the 4,4′-bpy moiety by way of O—H⋯N hydrogen bonds and C—H⋯O interactions. The influence of the mol­ecular shape on the hydrogen-bonding pattern is analysed by comparing the title compound and two other 4,4′-bpy co-crystals with closely related mol­ecules of similar formulation but different geometry, showing the way in which this correlates with the packing arrangement. PMID:25309167

Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.

PubMed

Dennis, Michael D; Jefferson, Leonard S; Kimball, Scot R

2012-12-14

Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.

The system K2Mg2(SO4)3 (langbeinite)-K2Ca2(SO4)3 (calcium-langbeinite)

USGS Publications Warehouse

Morey, G.W.; Rowe, J.J.; Fournier, R.O.

1964-01-01

The join between the compositions K2Mg2(SO4)3 and K2Ca2(SO4)3 was studied by means of high-temperature equilibrium quenching techniques and by means of a heating stage mounted on an X-ray diffractometer. Complete solid solution exists in the system, but at 25??C members of the solid solution series are isometric only in the composition range 0-73??5 wt. per cent K2Ca2(SO4)3. At compositions richer in K2Ca2(SO4)3 than 73??5 wt. per cent, members of the series are optically biaxial. At higher temperatures members of the solid solution series are isometric at successively more calcium-rich compositions and pure K2Ca2(SO4)3 is isometric above about 200 ?? 2??C. The system is not binary, as mixtures richer in K2Ca2(SO4)3 than 42 wt. per cent decompose with the formation of liquid and CaSO4. ?? 1964.

46 CFR 160.048-4 - Construction and workmanship.

Code of Federal Regulations, 2010 CFR

2010-10-01

... cover material will be allowed provided it is for decorative purposes only. Gusset or boxing materials..., boxing or gusset, they shall be attached by a double row of stitching of the type shown in Federal... permitted for the cover, but the boxing or gusset shall be a cotton fabric as specified by § 160.048-3(c)(1...

The 4 K Stirling cryocooler demonstration

NASA Technical Reports Server (NTRS)

Stacy, W. Dodd

1992-01-01

This report briefly summarizes the results and conclusions from an SBIR program intended to demonstrate an innovative Stirling cycle cryocooler concept for efficiently lifting heat from 4 K. Refrigeration at 4 K, a temperature useful for superconductors and sensitive instruments, is beyond the reach of conventional regenerative thermodynamic cycles due to the rapid loss of regenerator matrix heat capacity at temperatures below about 20 K. To overcome this fundamental limit, the cryocooler developed under this program integrated three unique features: recuperative regeneration between the displacement gas flow streams of two independent Stirling cycles operating at a 180 degree phase angle, tailored distortion of the two expander volume waveforms from sinusoidal to perfectly match the instantaneous regenerator heat flux from the two cycles and thereby unload the regenerator, and metal diaphragm working volumes to promote near isothermal expansion and compression processes. Use of diaphragms also provides unlimited operating life potential and eliminates bearings and high precision running seals. A phase 1 proof-of-principle experiment demonstrated that counterflow regenerator operation between 77 K and 4 K increases regenerator effectiveness by minimizing metal temperature transient cycling. In phase 2, a detailed design package for a breadboard cryocooler was completed. Fabrication techniques were successfully developed for manufacturing high precision miniature parallel plate recuperators, and samples were produced and inspected. Process development for fabricating suitably flat diaphragms proved more difficult and expensive than anticipated, and construction of the cryocooler was suspended at a completion level of approximately 75%. Subsequent development efforts on other projects have successfully overcome diaphragm fabrication difficulties, and alternate funding is currently being sought for completion and demonstration testing of the 4 K Stirling cryocooler.

46 CFR 160.048-4 - Construction and workmanship.

Code of Federal Regulations, 2012 CFR

2012-10-01

... provide buoyancy to aid a person in keeping afloat in the water. No hooks, snaps, or other means shall be... less than 5 ounces of kapok or 9 ounces of fibrous glass each; and the volume displacement of the... accordance with the method set forth in § 160.048-5(e)(1), except that the pad covers shall not be slit open...

Thermopower behavior in the Gd5(Si0.1Ge0.9)4 magnetocaloric compound from 4 to 300 K

NASA Astrophysics Data System (ADS)

Sousa, J. B.; Braga, M. E.; Correia, F. C.; Carpinteiro, F.; Morellon, L.; Algarabel, P. A.; Ibarra, R.

2002-04-01

Recent studies on the orthorhombic Gd5(Si0.1Ge0.9)4 compound show, upon heating, a ferromagnetic to antiferromagnetic-like (AFM*) transition at TS=78 K, coupled with a first-order structural martensitic transformation keeping the orthorhombic symmetry but producing a large increase in the interlayer Si(Ge) distances leading to covalent bond-pair breaking. A second-order AFM*→(paramagnetic)PM transition occurs at TN=125 K. We report thermopower (S) measurements for the Gd5(SixGe1-x)4 series, performed on an x=0.1 sample, from 4 to 300 K, with increasing and decreasing temperatures through successive thermal cycling. Resistivity measurements show a systematic increase in the residual resistivity and a dramatic change in the ρ(T) behavior upon thermal cycling. In spite of this, the thermopower data show a common intrinsic behavior both in the ferromagnetic phase (TK) and above ˜230 K, i.e., independent of the number of thermal cycles, increasing or decreasing temperature, and of the particular residual resistivity. Also no drastic differences are seen in S(T) from TS to TN, upon thermal cycling. The structural transition is marked (upon heating) by a sharp increase in the S magnitude, reaching a deep negative minimum of -23 μV K-1 at ˜95 K. Then S(T) rises with increasing slope as T approaches TN, where dS/dT exhibits a singularity. S(T) hysteresis sets in at TS, reaches a maximum around 100 K, does not disapear at TN but persists in the PM phase up to ˜230 K. The later feature correlates well with a similar effect observed in ρ(T). The striking differences between S(T) and ρ(T) behavior under thermal cycling are analyzed.

Synthesis of Some Novel Fused Pyrimido[4″,5″:5',6']-[1,2,4]triazino[3',4':3,4] [1,2,4]triazino[5,6-b]indoles with Expected Anticancer Activity.

PubMed

Ali, Rania S; Saad, Hosam A

2018-03-19

Our current goal is the synthesis of polyheterocyclic compounds starting from 3-amino-[1,2,4]triazino[5,6- b ]indole 1 and studying their anticancer activity to determine whether increasing of the size of the molecules increases the anticancer activity or not. 1-Amino[1,2,4]triazino[3',4':3,4]-[1,2,4]triazino[5,6- b ]indole-2-carbonitrile ( 4 ) was prepared by the diazotization of 3-amino[1,2,4]-triazino[5,6- b ]indole 1 followed by coupling with malononitrile in basic medium then cyclization under reflux to get 4 . Also, new fused pyrimido[4″,5″:5',6'][1,2,4]triazino-[3',4':3,4][1,2,4]triazino[5,6- b ]indole derivative 6 was prepared and used to obtain polycyclic heterocyclic systems. Confirmation of the synthesized compounds' structures was carried out using elemental analyses and spectral data (IR, ¹H-NMR and 13 C-NMR and mass spectra). The anticancer activity of some of the synthesized compounds was tested against HepG2, HCT-116 and MCF-7 cell lines. The anticancer screening results showed that some derivatives display good activity which was more potent than that of the reference drug used. Molecular docking was used to predict the binding between some of the synthesized compounds and the prostate cancer 2q7k hormone and breast ‎cancer 3hb5 receptors.

A new set of K3Fe3(PO4)4·yH2O (0 ≤ y ≤ 1) layered phases obtained by topotactic reactions

NASA Astrophysics Data System (ADS)

Trad, Khiem; Wattiaux, Alain; Ben Amara, Mongi; Delmas, Claude; Carlier, Dany

2018-06-01

K3Fe3(PO4)4·H2O powder was synthesized by Na+/K+ exchange reaction from Na3Fe3(PO4)4 in aqueous medium. The replacement of the sodium cations by the potassium larger ones and water molecules causes a structural distortion leading to P2/n monoclinic K3Fe3(PO4)4·H2O. This new layered phase was characterized by XRD, Mössbauer spectroscopy and magnetic measurements. The study of its thermal stability reveals that other new layered K3Fe3(PO4)4·yH2O with (0 ≤ y ≤ 1) phases can be stabilized up to 600 °C and finally at higher temperature a new K3Fe3(PO4)4 polymorph with a different structural type is irreversibility formed.

Crystal structures of three co-crystals of 1,2-bis-(pyridin-4-yl)ethane with 4-alk-oxy-benzoic acids: 4-eth-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), 4-n-propoxybenzoic acid-1,2-bis(pyridin-4-yl)ethane (2/1) and 4-n-but-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1).

PubMed

Tabuchi, Yohei; Gotoh, Kazuma; Ishida, Hiroyuki

2015-11-01

The crystal structures of three hydrogen-bonded co-crystals of 4-alk-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), namely, 2C9H10O3·C12H12N2, (I), 2C10H12O3·C12H12N2, (II), and 2C11H14O3·C12H12N2, (III), have been determined at 93, 290 and 93 K, respectively. In (I), the asymmetric unit consists of one 4-eth-oxy-benzoic acid mol-ecule and one half-mol-ecule of 1,2-bis-(pyridin-4-yl)ethane, which lies on an inversion centre. In (II) and (III), the asymmetric units each comprise two crystallographically independent 4-alk-oxy-benzoic acid mol-ecules and one 1,2-bis-(pyridin-4-yl)ethane mol-ecule. In each crystal, the two components are linked by O-H⋯N hydrogen bonds, forming a linear hydrogen-bonded 2:1unit of the acid and the base. Similar to the structure of 2:1 unit of (I), the units of (II) and (III) adopt nearly pseudo-inversion symmetry. The 2:1 units of (I), (II) and (III) are linked via C-H⋯O hydrogen bonds, forming tape structures.

GABARAP-mediated targeting of PI4K2A/PI4KIIα to autophagosomes regulates PtdIns4P-dependent autophagosome-lysosome fusion.

PubMed

Albanesi, Joseph; Wang, Hanzhi; Sun, Hui-Qiao; Levine, Beth; Yin, Helen

2015-11-02

For decades, phosphatidylinositol 4-phosphate (PtdIns4P) was considered primarily as a precursor in the synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P 2 ). More recently, specific functions for PtdIns4P itself have been identified, particularly in the regulation of intracellular membrane trafficking. PI4K2A/PI4KIIα (phosphatidylinositol 4-kinase type 2 α), one of the 4 enzymes that catalyze PtdIns4P production in mammalian cells, promotes vesicle formation from the trans-Golgi network (TGN) and endosomes. We recently identified a novel function for PI4K2A-derived PtdIns4P, as a facilitator of autophagosome-lysosome (A-L) fusion. We further showed that that this function requires the presence of the autophagic adaptor protein GABARAP (GABA[A] receptor-associated protein), which binds to PI4K2A and recruits it to autophagosomes. The mechanism whereby GABARAP-PI4K2A-PtdIns4P promotes A-L fusion remains to be defined. Based on other examples of phosphoinositide involvement in membrane trafficking, we speculate that it acts by recruiting elements of the membrane docking and fusion machinery.

FOXP3 Orchestrates H4K16 Acetylation and H3K4 Tri-Methylation for Activation of Multiple Genes through Recruiting MOF and Causing Displacement of PLU-1

PubMed Central

Katoh, Hiroto; Qin, Zhaohui S.; Liu, Runhua; Wang, Lizhong; Li, Weiquan; Li, Xiangzhi; Wu, Lipeng; Du, Zhanwen; Lyons, Robert; Liu, Chang-Gong; Liu, Xiuping; Dou, Yali; Zheng, Pan; Liu, Yang

2011-01-01

SUMMARY Both H4K16 acetylation and H3K4 tri-methylation are required for gene activation. However, it is still largely unclear how these modifications are orchestrated by transcriptional factors. Here we analyzed the mechanism of the transcriptional activation by FOXP3, an X-linked suppressor of autoimmune diseases and cancers. FOXP3 binds near transcriptional start sites of its target genes. By recruiting MOF and displacing histone H3K4 demethylase PLU-1, FOXP3 increases both H4K16 acetylation and H3K4 tri-methylation at the FOXP3-associated chromatins of multiple FOXP3-activated genes. RNAi-mediated silencing of MOF reduced both gene activation and tumor suppression by FOXP3, while both somatic mutations in clinical cancer samples and targeted mutation of FOXP3 in mouse prostate epithelial disrupted nuclear localization of MOF. Our data demonstrate a pull-push model in which a single transcription factor orchestrates two epigenetic alterations necessary for gene activation and provide a mechanism for somatic inactivation of the FOXP3 protein function in cancer cells. PMID:22152480

UCT943, a next generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria.

PubMed

Brunschwig, Christel; Lawrence, Nina; Taylor, Dale; Abay, Efrem; Njoroge, Mathew; Basarab, Gregory S; Le Manach, Claire; Paquet, Tanya; Gonzàlez Cabrera, Diego; Nchinda, Aloysius T; de Kock, Carmen; Wiesner, Lubbe; Denti, Paolo; Waterson, David; Blasco, Benjamin; Leroy, Didier; Witty, Michael J; Donini, Cristina; Duffy, James; Wittlin, Sergio; White, Karen L; Charman, Susan A; Jiménez-Díaz, Maria Belén; Angulo-Barturen, Iñigo; Herreros, Esperanza; Gamo, Francisco Javier; Rochford, Rosemary; Mancama, Dalu; Coetzer, Theresa L; van der Watt, Mariëtte E; Reader, Janette; Birkholtz, Lyn-Marie; Marsh, Kennan C; Solapure, Suresh M; Vanaerschot, Manu; Fidock, David A; Fish, Paul V; Siegl, Peter; Smith, Dennis A; Wirjanata, Grennady; Noviyanti, Rintis; Price, Ric N; Marfurt, Jutta; Silue, Kigbafori D; Street, Leslie J; Chibale, Kelly

2018-06-25

The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite lifecycle, leading to the 2-aminopyrazine UCT943. The compound displayed higher asexual blood stage, transmission-blocking, and liver stage activity than MMV048 and was more potent against resistant P. falciparum and P. vivax clinical isolates. Excellent in vitro antiplasmodial activity translated into high efficacy in P. berghei and humanized P. falciparum NOD- scid IL-2Rγ null mouse models. The high passive permeability and high aqueous solubility of UCT943, combined with low to moderate in vitro intrinsic clearance, resulted in sustained exposure and high bioavailability in preclinical species. In addition, the predicted human dose for a curative single administration using monkey and dog pharmacokinetics was low, ranging from 50 to 80 mg. As a next generation Plasmodium PI4K inhibitor, the combined preclinical data suggest that UCT943 has the potential to form part of a single-exposure radical cure and prophylaxis (SERCaP) to treat, prevent and block the transmission of malaria. Copyright © 2018 American Society for Microbiology.

E4orf1 Limits the Oncolytic Potential of the E1B-55K Deletion Mutant Adenovirus▿

PubMed Central

Thomas, Michael A.; Broughton, Robin S.; Goodrum, Felicia D.; Ornelles, David A.

2009-01-01

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G1 phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G1 restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3′-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function. PMID:19129452

E4orf1 limits the oncolytic potential of the E1B-55K deletion mutant adenovirus.

PubMed

Thomas, Michael A; Broughton, Robin S; Goodrum, Felicia D; Ornelles, David A

2009-03-01

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G(1) phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G(1) restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3'-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function.

K(2)MM'(3)Se(6) (M = Cu, Ag; M' = Ga, In), A new series of metal chalcogenides with chain-sublayer-chain slabs: (infinity)(1)[M'Se(4)]-(infinity)(2)[(MSe(4))(M'Se(4))]-(infinity)(1)[M'Se(4)].

PubMed

Ma, Hong-Wei; Guo, Guo-Cong; Wang, Ming-Sheng; Zhou, Guo-Wei; Lin, Shan-Hou; Dong, Zhen-Chao; Huang, Jin-Shun

2003-02-24

A new series of novel isostructural metal chalcogenides, K(2)CuIn(3)Se(6) (1), K(2)CuGa(3)Se(6) (2), and K(2)AgIn(3)Se(6) (3), were obtained by a reactive flux technique and structurally characterized. Compounds 1, 2, and 3 crystallize in the space group C2/c of the monoclinic system with eight formula units in a cell: a = 11.445(2) A, b = 11.495(2) A, c = 21.263(4) A, beta = 97.68(3) degrees, V = 2772(1) A(3), R1/wR2 = 0.0676/0.1652 for 1; a = 11.031(2) A, b = 11.050(4) A, c = 20.808(7) A, beta = 97.71(2) degrees, V = 2513(1) A(3), R1/wR2 = 0.0301/0.0511 for 2; and a = 11.633(1) A, b = 11.587(1) A, c = 21.355(1) A, beta = 98.010(8) degrees, V = 2850.4(4) A(3), R1/wR2 = 0.0471/0.0732 for 3. These isostructural compounds are characterized by a chain-sublayer-chain slab structure. The sublayer, composed of alternative corner-sharing mixed-metal tetrahedra, is sandwiched by parallel corner-sharing tetrahedral chains. Optical absorption spectra of compounds 1, 2, and 3 reveal the presence of a sharp optical gap of 1.68, 1.72, and 1.64 eV, respectively, suggesting that these materials are semiconductors and suitable for efficient absorption of solar radiation in solar cell applications. IR spectra show no obvious absorption in the range 800-4000 cm(-)(1).

dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase Throughout Drosophila Development

PubMed Central

Hallson, Graham; Hollebakken, Robert E.; Li, Taosui; Syrzycka, Monika; Kim, Inho; Cotsworth, Shawn; Fitzpatrick, Kathleen A.; Sinclair, Donald A. R.; Honda, Barry M.

2012-01-01

In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a “global” or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di- and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans. PMID:22048023

Ultracold-neutron production and up-scattering in superfluid helium between 1.1 K and 2.4 K

NASA Astrophysics Data System (ADS)

Leung, K. K. H.; Ivanov, S.; Piegsa, F. M.; Simson, M.; Zimmer, O.

2016-02-01

Ultracold neutrons (UCNs) were produced in superfluid helium using the PF1B cold-neutron beam facility at the Institut Laue-Langevin. A 4-liter beryllium-coated converter volume with a mechanical valve and windowless stainless-steel extraction system were used to accumulate and guide UCNs to a detector at room temperature. At a converter temperature of 1.08 K the total storage time constant in the vessel was (20.3 ±1.2 )s and the number of UCNs counted after accumulated was 91 700 ±300 . From this, we derive a volumetric UCN production rate of (6.9 ±1.7 ) cm-3s-1 , which includes a correction for losses in the converter during UCN extraction caused by the short storage time, but not accounting for UCN transport and detection efficiencies. The up-scattering rate of UCNs caused by excitations in the superfluid was studied by scanning the temperature between 1.2 K and 2.4 K . Using the temperature-dependent UCN production rate calculated from inelastic neutron scattering data, the only UCN up-scattering process found to occur was from two-phonon scattering. Our analysis for T <1.95 K rules out the contributions from roton-phonon scattering to <29 % (95% C.I.) and from one-phonon absorption to <47 % (95% C.I.) of their predicted levels.

Experimental and theoretical studies of (FT-IR, FT-Raman, UV-Visible and DFT) 4-(6-methoxynaphthalen-2-yl) butan-2-one.

PubMed

Govindasamy, P; Gunasekaran, S

2015-01-01

In this work, the vibrational spectral analysis was carried out by using FT-Raman and FT-IR spectroscopy in the range 4000-50 cm(-1) and 4000-450 cm(-1) respectively for 4-(6-methoxynaphthalen-2-yl) butan-2-one (abbreviated as 4MNBO) molecule. Theoretical calculations were performed by density functional theory (DFT/B3LYP) method using 6-311G(d,p) and 6-311++G(d,p) basis sets. The difference between the observed and calculated wavenumber value of most of the fundamentals were very small. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution (PED). The UV-Vis spectrum was recorded in the methanol solution. The energy, wavelength and oscillator's strength were calculated by Time Dependent Density Functional Theory (TD-DFT) and matched to the experimental findings. The intramolecular contacts have been interpreted using natural bond orbital (NBO) and natural localized molecular orbital (NLMO) analysis. Thermodynamic properties of 4MNBO at different temperature have been calculated. The molecular electrostatic potential surface (MESP) and Frontier molecular orbital's (FMO's) analysis were investigated using theoretical calculations. Copyright © 2015 Elsevier B.V. All rights reserved.

Measurement of e+e-→K K ¯J /ψ cross sections at center-of-mass energies from 4.189 to 4.600 GeV

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Albrecht, M.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, P. L.; Chen, S. J.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Farinelli, R.; Fava, L.; Fegan, S.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Y. G.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, S.; Gu, Y. T.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y. P.; Haddadi, Z.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Khan, T.; Kiese, P.; Kliemt, R.; Koch, L.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kuemmel, M.; Kuhlmann, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Lavezzi, L.; Leiber, S.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, J. Q.; Li, Jin; Li, Kang; Li, Ke; Li, Lei; Li, P. L.; Li, P. R.; Li, Q. Y.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. M.; Liu, Huanhuan; Liu, Huihui; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, Ke; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Morello, G.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Mustafa, A.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Papenbrock, M.; Patteri, P.; Pelizaeus, M.; Pellegrino, J.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, J. J.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Richter, M.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, J. J.; Song, W. M.; Song, X. Y.; Sosio, S.; Sowa, C.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. K.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, G. Y.; Tang, X.; Tapan, I.; Tiemens, M.; Tsednee, B.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, Dan; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, Meng; Wang, P.; Wang, P. L.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, X.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Y. J.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiong, X. A.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. H.; Yang, Y. X.; Yang, Yifan; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yang; Zhang, Yao; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhou, Y. X.; Zhu, J.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2018-04-01

We investigate the process e+e-→K K ¯J /ψ at center-of-mass energies from 4.189 to 4.600 GeV using 4.7 fb-1 of data collected by the BESIII detector at the BEPCII collider. The Born cross sections for the reactions e+e-→K+K-J /ψ and KS0KS0J /ψ are measured as a function of center-of-mass energy. The energy dependence of the cross section for e+e-→K+K-J /ψ is shown to differ from that for π+π-J /ψ in the region around the Y (4260 ). In addition, there is evidence for a structure around 4.5 GeV in the e+e-→K+K-J /ψ cross section that is not present in π+π-J /ψ .

SmoXYB1C1Z of Mycobacterium sp. Strain NBB4: a Soluble Methane Monooxygenase (sMMO)-Like Enzyme, Active on C2 to C4 Alkanes and Alkenes

PubMed Central

Martin, Kiri E.; Ozsvar, Jazmin

2014-01-01

Monooxygenase (MO) enzymes initiate the aerobic oxidation of alkanes and alkenes in bacteria. A cluster of MO genes (smoXYB1C1Z) of thus-far-unknown function was found previously in the genomes of two Mycobacterium strains (NBB3 and NBB4) which grow on hydrocarbons. The predicted Smo enzymes have only moderate amino acid identity (30 to 60%) to their closest homologs, the soluble methane and butane MOs (sMMO and sBMO), and the smo gene cluster has a different organization from those of sMMO and sBMO. The smoXYB1C1Z genes of NBB4 were cloned into pMycoFos to make pSmo, which was transformed into Mycobacterium smegmatis mc2-155. Cells of mc2-155(pSmo) metabolized C2 to C4 alkanes, alkenes, and chlorinated hydrocarbons. The activities of mc2-155(pSmo) cells were 0.94, 0.57, 0.12, and 0.04 nmol/min/mg of protein with ethene, ethane, propane, and butane as substrates, respectively. The mc2-155(pSmo) cells made epoxides from ethene, propene, and 1-butene, confirming that Smo was an oxygenase. Epoxides were not produced from larger alkenes (1-octene and styrene). Vinyl chloride and 1,2-dichloroethane were biodegraded by cells expressing Smo, with production of inorganic chloride. This study shows that Smo is a functional oxygenase which is active against small hydrocarbons. M. smegmatis mc2-155(pSmo) provides a new model for studying sMMO-like monooxygenases. PMID:25015887

Cryogenic test of the 4 K / 2 K insert for the ARIEL e-Linac cryomodule

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

Laxdal, R. E.; Ma, Y.; Harmer, P.

2014-01-29

The ARIEL project at TRIUMF requires a 50 MeV superconducting electron linac consisting of five nine cell 1.3 GHz cavities divided into three cryomodules with one, two and two cavities in each module respectively. LHe is distributed in parallel to each module at 4 K and at ∼1.2 bar. Each module has a cryogenic insert on board that receives the 4 K liquid and produces 2 K into a cavity phase separator. The module combines a 4 K phase separator, a plate and fin heat exchanger from DATE and a J-T valve expanding into the 2 K phase separator. Themore » unit also supplies 4 K liquid to thermal intercepts in the module in siphon loops that return the vaporized liquid to the 4 K reservoir. For testing purposes the unit is outfitted with a dummy 2 K phase separator and thermal intercepts with variable heaters that mimic the final heat loads in order to test the cryogenic performance. The design of the 4 K / 2 K insert, the results of the cold tests and a summary of the test infrastructure including cryogenics services will be presented.« less

JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.

PubMed

Yin, T; Tsang, M L; Yang, Y C

1994-10-28

Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocytes through interactions with their receptors. Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9. Here we show that IL-4 and IL-9 induce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lymphocytes. We further identify the 170-kDa tyrosine-phosphorylated protein as 4PS/insulin receptor substrate-1-like (IRS-1L) protein and 130-kDa protein as JAK1 kinase. Furthermore, we demonstrate for the first time that JAK1 forms complexes with the IL-4 receptor and 4PS/IRS-1L protein following ligand-receptor interaction. In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor. The overlapping and distinct protein tyrosine phosphorylation and activation of the same JAK1 kinase in T lymphocytes strongly suggests that IL-4 and IL-9 share the common signal transduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines.

Continuous Cooling from 10 K to 4 K Using a Toroidal ADR

NASA Technical Reports Server (NTRS)

DiPirro, Michael J.; Canavan, Edgar R.; Shirron, Peter J.; Tuttle, James G.

2003-01-01

Future large infrared space telescopes will require cooling to 4K to achieve background limited performance for submillimeter wavelengths. These observatories will require lifetimes of many years and will have relatively large cooling requirements making stored helium dewars impractical. We have designed and are building an adiabatic demagnetization refrigerator (ADR) for use in cooling relatively large loads (10- 100 mW) at 4K and rejecting that heat to a cryocooler operating at 1 OK. Cryocoolers below 1 OK have poor thermodynamic efficiency and ADRs can operate in this temperature range with an efficiency of 75% of Carnot or better. Overall, this can save as much as 2/3 of the input power required to operate a 4K cryocooler. The ADR magnet consists of 8 short coils wired in series and arranged in a toroid to provide self shielding of its magnetic field. This will save mass (about 30% of the mass or about 1.5 kg in our small version, higher percentages in higher cooling power, larger versions) that would have been used for passive or active shields in an ordinary solenoid. The toroid has a 100 mm outer diameter and will produce an approximately 3T average field. In the initial demonstration model the toroid coils will be wound with ordinary NbTi wire and operated at 4K. A second version will then use Nb3Sn wire to provide complete 10K operation. As a refrigerant for this temperature range we will use either GdLiF4 or GdF3 crystals, pending tests of these crystals' cooling capacity per field and thermal conductance. Preliminary indications are that these materials are superior to GGG. We will use gas gap heat switches to alternately connect the toroid to the cold load and the warm heat sink. A small continuous stage will maintain the cold end at 4K while the main toroid is recycled.

Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

NASA Astrophysics Data System (ADS)

Lorefice, S.; Becerra, L. O.

2017-01-01

Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Processes of Molecular Relaxation in Binary Crystalline Systems KNO3-KClO4, KNO3-KNO2, and K2CO3-K2SO4

NASA Astrophysics Data System (ADS)

Aliev, A. R.; Akhmedov, I. R.; Kakagasanov, M. G.; Aliev, Z. A.; Gafurov, M. M.; Rabadanov, K. Sh.; Amirov, A. M.

2018-03-01

The processes of molecular relaxation in binary crystalline systems KNO3-KClO4, KNO3-KNO2, and K2CO3-K2SO4 are studied via differential thermal analysis and Raman spectroscopy. It is found that the relaxation time of the vibrations ν1( A) of anions NO- 3 and CO2- 3 in systems KNO3-KClO4, KNO3-KNO2, and K2CO3-K2SO4 is less than that in KNO3 and K2CO3, respectively. It is shown that the increased rate of relaxation is explained by an additional relaxation mechanism presented in the system. This mechanism is associated with the excitation of vibrations of anions ClO- 4, NO- 2, and SO2- 4 and the lattice phonons that emerge. It is found that this relaxation mechanism requires correspondence of the frequency difference of these vibrations to the region of sufficiently high density of states of the phonon spectrum.

Neutron scattering studies of K3H(SO4)2 and K3D(SO4)2: the particle-in-a-box model for the quantum phase transition.

PubMed

Fillaux, François; Cousson, Alain

2012-08-21

In the crystal of K(3)H(SO(4))(2) or K(3)D(SO(4))(2), dimers SO(4)···H···SO(4) or SO(4)···D···SO(4) are linked by strong centrosymmetric hydrogen or deuterium bonds whose O···O length is ≈2.50 Å. We address two open questions. (i) Are H or D sites split or not? (ii) Is there any structural counterpart to the phase transition observed for K(3)D(SO(4))(2) at T(c) ≈ 85.5 K, which does not exist for K(3)H(SO(4))(2)? Neutron diffraction by single-crystals at cryogenic or room temperature reveals no structural transition and no resolvable splitting of H or D sites. However, the width of the probability densities suggest unresolved splitting of the wavefunctions suggesting rigid entities H(L1/2)-H(R1/2) or D(L1/2)-D(R1/2) whose separation lengths are l(H) ≈ 0.16 Å or l(D) ≈ 0.25 Å. The vibrational eigenstates for the center of mass of H(L1/2)-H(R1/2) revealed by inelastic neutron scattering are amenable to a square-well and we suppose the same potential holds for D(L1/2)-D(R1/2). In order to explain dielectric and calorimetric measurements of mixed crystals K(3)D((1-ρ))H(ρ)(SO(4))(2) (0 ≤ ρ ≤ 1), we replace the classical notion of order-disorder by the quantum notion of discernible (e.g., D(L1/2)-D(R1/2)) or indiscernible (e.g., H(L1/2)-H(R1/2)) components depending on the separation length of the split wavefunction. The discernible-indiscernible isostructural transition at finite temperatures is induced by a thermal pure quantum state or at 0 K by ρ.

Synthesis and crystal structures of (2 E )-1,4-bis(4-chlorophenyl)but-2-ene-1,4-dione and (2 E )-1,4-bis(4-bromophenyl)but-2-ene-1,4-dione

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

Lastovickova, Dominika N.; La Scala, John J.; Sausa, Rosario C.

The molecular structure of (2 E )-1,4-bis(4-chlorophenyl)but-2-ene-1,4-dione [C 16 H 10 Cl 2 O 2 , ( 1 )] is composed of two p -chlorophenyl rings, each bonded on opposite ends to a near planar 1,4- trans enedione moiety [–C(=O)—CH=CH—(C=O)–] [r.m.s. deviation = 0.003 (1) Å]. (2 E )-1,4-Bis(4-bromophenyl)but-2-ene-1,4-dione [C 16 H 10 Br 2 O 2 , ( 2 )] has a similar structure to ( 1 ), but with two p -bromophenyl rings and a less planar enedione group [r.m.s. deviation = 0.011 (1) Å]. Both molecules sit on a center of inversion, thus Z ′ = 0.5. The dihedral angles between themore » ring and the enedione group are 16.61 (8) and 15.58 (11)° for ( 1 ) and ( 2 ), respectively. In the crystal, molecules of ( 1 ) exhibit C—Cl...Cl type I interactions, whereas molecules of ( 2 ) present C—Br...Br type II interactions. van der Waals-type interactions contribute to the packing of both molecules, and the packing reveals face-to-face ring stacking with similar interplanar distances of approximately 3.53 Å.« less

Synthesis and crystal structures of (2 E )-1,4-bis(4-chlorophenyl)but-2-ene-1,4-dione and (2 E )-1,4-bis(4-bromophenyl)but-2-ene-1,4-dione

DOE PAGES

Lastovickova, Dominika N.; La Scala, John J.; Sausa, Rosario C.

2018-02-13

The molecular structure of (2 E )-1,4-bis(4-chlorophenyl)but-2-ene-1,4-dione [C 16 H 10 Cl 2 O 2 , ( 1 )] is composed of two p -chlorophenyl rings, each bonded on opposite ends to a near planar 1,4- trans enedione moiety [–C(=O)—CH=CH—(C=O)–] [r.m.s. deviation = 0.003 (1) Å]. (2 E )-1,4-Bis(4-bromophenyl)but-2-ene-1,4-dione [C 16 H 10 Br 2 O 2 , ( 2 )] has a similar structure to ( 1 ), but with two p -bromophenyl rings and a less planar enedione group [r.m.s. deviation = 0.011 (1) Å]. Both molecules sit on a center of inversion, thus Z ′ = 0.5. The dihedral angles between themore » ring and the enedione group are 16.61 (8) and 15.58 (11)° for ( 1 ) and ( 2 ), respectively. In the crystal, molecules of ( 1 ) exhibit C—Cl...Cl type I interactions, whereas molecules of ( 2 ) present C—Br...Br type II interactions. van der Waals-type interactions contribute to the packing of both molecules, and the packing reveals face-to-face ring stacking with similar interplanar distances of approximately 3.53 Å.« less

Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans

PubMed Central

Kramer, Maxwell; Kranz, Anna-Lena; Su, Amanda; Winterkorn, Lara H.; Albritton, Sarah Elizabeth; Ercan, Sevinc

2015-01-01

In Caenorhabditis elegans, the dosage compensation complex (DCC) specifically binds to and represses transcription from both X chromosomes in hermaphrodites. The DCC is composed of an X-specific condensin complex that interacts with several proteins. During embryogenesis, DCC starts localizing to the X chromosomes around the 40-cell stage, and is followed by X-enrichment of H4K20me1 between 100-cell to comma stage. Here, we analyzed dosage compensation of the X chromosome between sexes, and the roles of dpy-27 (condensin subunit), dpy-21 (non-condensin DCC member), set-1 (H4K20 monomethylase) and set-4 (H4K20 di-/tri-methylase) in X chromosome repression using mRNA-seq and ChIP-seq analyses across several developmental time points. We found that the DCC starts repressing the X chromosomes by the 40-cell stage, but X-linked transcript levels remain significantly higher in hermaphrodites compared to males through the comma stage of embryogenesis. Dpy-27 and dpy-21 are required for X chromosome repression throughout development, but particularly in early embryos dpy-27 and dpy-21 mutations produced distinct expression changes, suggesting a DCC independent role for dpy-21. We previously hypothesized that the DCC increases H4K20me1 by reducing set-4 activity on the X chromosomes. Accordingly, in the set-4 mutant, H4K20me1 increased more from the autosomes compared to the X, equalizing H4K20me1 level between X and autosomes. H4K20me1 increase on the autosomes led to a slight repression, resulting in a relative effect of X derepression. H4K20me1 depletion in the set-1 mutant showed greater X derepression compared to equalization of H4K20me1 levels between X and autosomes in the set-4 mutant, indicating that H4K20me1 level is important, but X to autosomal balance of H4K20me1 contributes only slightly to X-repression. Thus H4K20me1 by itself is not a downstream effector of the DCC. In summary, X chromosome dosage compensation starts in early embryos as the DCC localizes to

A dispersive treatment of K ι4 decays

DOE PAGES

Stoffer, Peter; Colangelo, Gilberto; Passemar, Emilie

2017-01-01

K ι4 decays have several features of interest: they allow an accurate measurement of ππ-scattering lengths; the decay is the best source for the determination of some low-energy constants of chiral perturbation theory (χPT); one form factor of the decay is connected to the chiral anomaly. Here, we present the results of our dispersive analysis of K ι4 decays, which provides a resummation of ππ- and Kπ-rescattering effects. The free parameters of the dispersion relation are fitted to the data of the high-statistics experiments E865 and NA48/2. By matching to χPT at NLO and NNLO, we determine the low-energy constantsmore » and L r 1, L r 2, and L r 3. In contrast to a pure chiral treatment, the dispersion relation describes the observed curvature of one of the K ι4 form factors, which we understand as an effect of rescattering beyond NNLO.« less

Phosphorus K4 Crystal: A New Stable Allotrope

PubMed Central

Liu, Jie; Zhang, Shunhong; Guo, Yaguang; Wang, Qian

2016-01-01

The intriguing properties of phosphorene motivate scientists to further explore the structures and properties of phosphorus materials. Here, we report a new allotrope named K4 phosphorus composed of three-coordinated phosphorus atoms in non-layered structure which is not only dynamically and mechanically stable, but also possesses thermal stability comparable to that of the orthorhombic black phosphorus (A17). Due to its unique configuration, K4 phosphorus exhibits exceptional properties: it possesses a band gap of 1.54 eV which is much larger than that of black phosphorus (0.30 eV), and it is stiffer than black phosphorus. The band gap of the newly predicted phase can be effectively tuned by appling hydrostastic pressure. In addition, K4 phosphorus exibits a good light absorption in visible and near ultraviolet region. These findings add additional features to the phosphorus family with new potential applications in nanoelectronics and nanomechanics. PMID:27857232

MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes.

PubMed

Dhar, Shilpa S; Zhao, Dongyu; Lin, Tao; Gu, Bingnan; Pal, Khusboo; Wu, Sarah J; Alam, Hunain; Lv, Jie; Yun, Kyuson; Gopalakrishnan, Vidya; Flores, Elsa R; Northcott, Paul A; Rajaram, Veena; Li, Wei; Shilatifard, Ali; Sillitoe, Roy V; Chen, Kaifu; Lee, Min Gyu

2018-06-07

Super-enhancers are large clusters of enhancers that activate gene expression. Broad trimethyl histone H3 lysine 4 (H3K4me3) often defines active tumor suppressor genes. However, how these epigenomic signatures are regulated for tumor suppression is little understood. Here we show that brain-specific knockout of the H3K4 methyltransferase MLL4 (a COMPASS-like enzyme, also known as KMT2D) in mice spontaneously induces medulloblastoma. Mll4 loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. MLL4 enhances DNMT3A-catalyzed DNA methylation and SIRT1/BCL6-mediated H4K16 deacetylation, which antagonize expression of Ras activators and Notch pathway components, respectively. Notably, Mll4 loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6) by diminishing broad H3K4me3 and super-enhancers and also causes widespread impairment of these epigenomic signatures during medulloblastoma genesis. These findings suggest an anti-tumor role for super-enhancers and provide a unique tumor-suppressive mechanism in which MLL4 is necessary to maintain broad H3K4me3 and super-enhancers at tumor suppressor genes. Copyright © 2018 Elsevier Inc. All rights reserved.

1-[5-(4-Bromo­phen­yl)-3-(4-fluoro­phen­yl)-4,5-dihydro-1H-pyrazol-1-yl]butan-1-one

PubMed Central

Fun, Hoong-Kun; Loh, Wan-Sin; Sapnakumari, M.; Narayana, B.; Sarojini, B. K.

2012-01-01

In the title compound, C19H18BrFN2O, the benzene rings form dihedral angles of 5.38 (7) and 85.48 (7)° with the mean plane of the 4,5-dihydro-1H-pyrazole ring (r.m.s. deviation = 0.0849 Å), which approximates to an envelope conformation with the –CH2– group as the flap. The dihedral angle between the benzene rings is 82.86 (7)°. In the crystal, C—H⋯F and C—H⋯O hydrogen bonds link the mol­ecules to form inversion dimers and together these generate chains along [011]. The crystal packing also features C—H⋯π inter­actions. PMID:22969553

Characterization of a Multimodular Endo-β-1,4-Glucanase (Cel9K) from Paenibacillus sp. X4 with a Potential Additive for Saccharification.

PubMed

Lee, Jae Pil; Kim, Yoon A; Kim, Sung Kyum; Kim, Hoon

2018-04-28

An endo-β-1,4-glucanase gene, cel 9K, was cloned using the shot-gun method from Paenibacillus sp. X4, which was isolated from alpine soil. The gene was 2,994 bp in length, encoding a protein of 997 amino acid residues with a predicted signal peptide composed of 32 amino acid residues. Cel9K was a multimodular enzyme, and the molecular mass and theoretical pI of the mature Cel9K were 103.5 kDa and 4.81, respectively. Cel9K contains the GGxxDAGD, PHHR, GAxxGG, YxDDI, and EVxxDYN motifs found in most glycoside hydrolase family 9 (GH9). The protein sequence showed the highest similarity (88%) with the cellulase of Bacillus sp. BP23 in comparison to the enzymes with reported properties. The enzyme was purified by chromatography using HiTrap Q, CHT-II, and HiTrap Butyl HP. Using SDS-PAGE/activity staining, the molecular mass of Cel9K was estimated to be 93 kDa, which is a truncated form produced by the proteolytic cleavage of its C-terminus. Cel9K was optimally active at pH 5.5 and 50°C and showed a half-life of 59.2 min at 50°C. The CMCase activity was increased to more than 150% in the presence of 2 mM Na⁺, K⁺, and Ba²⁺, but decreased significantly to less than 50% by Mn²⁺ and Co²⁺. The addition of Cel9K to a commercial enzyme set (Celluclast 1.5L + Novozym 188) increased the saccharification of the pretreated reed and rice straw powders by 30.4 and 15.9%, respectively. The results suggest that Cel9K can be used to enhance the enzymatic conversion of lignocellulosic biomass to reducing sugars as an additive.

Rotenone Induction of Hydrogen Peroxide Inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E Pathways, Leading to Neuronal Apoptosis

PubMed Central

Zhou, Qian; Liu, Chunxiao; Liu, Wen; Zhang, Hai; Zhang, Ruijie; Liu, Jia; Zhang, Jinfei; Xu, Chong; Liu, Lei; Huang, Shile; Chen, Long

2015-01-01

Rotenone, a common pesticide and inhibitor of mitochondrial complex I, induces loss of dopaminergic neurons and consequential aspects of Parkinson’s disease (PD). However, the exact mechanism of rotenone neurotoxicity is not fully elucidated. Here, we show that rotenone induced reactive oxygen species (ROS), leading to apoptotic cell death in PC12 cells and primary neurons. Pretreatment with catalase (CAT), a hydrogen peroxide-scavenging enzyme, attenuated rotenone-induced ROS and neuronal apoptosis, implying hydrogen peroxide (H2O2) involved, which was further verified by imaging intracellular H2O2 using a peroxide-selective probe H2DCFDA. Using thenoyltrifluoroacetone (TTFA), antimycin A, or Mito-TEMPO, we further demonstrated rotenone-induced mitochondrial H2O2-dependent neuronal apoptosis. Rotenone dramatically inhibited mTOR-mediated phosphorylation of S6K1 and 4E-BP1, which was also attenuated by CAT in the neuronal cells. Of interest, ectopic expression of wild-type mTOR or constitutively active S6K1, or downregulation of 4E-BP1 partially prevented rotenone-induced H2O2 and cell apoptosis. Furthermore, we noticed that rotenone-induced H2O2 was linked to the activation of caspase-3 pathway. This was evidenced by the finding that pretreatment with CAT partially blocked rotenone-induced cleavages of caspase-3 and poly (ADP-ribose) polymerase. Of note, zVAD-fmk, a pan caspase inhibitor, only partially prevented rotenone-induced apoptosis in PC12 cells and primary neurons. Expression of mTOR-wt, S6K1-ca, or silencing 4E-BP1 potentiated zVAD-fmk protection against rotenone-induced apoptosis in the cells. The results indicate that rotenone induction of H2O2 inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, resulting in caspase-dependent and -independent apoptosis in neuronal cells. Our findings suggest that rotenone-induced neuronal loss in PD may be prevented by activating mTOR signaling and/or administering antioxidants. PMID:25304210

Measurement of e + e - → K K ¯ J / ψ cross sections at center-of-mass energies from 4.189 to 4.600 GeV

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

We investigate the process e +e - → Kmore » $$\\bar{K}$$J/ψ at center-of-mass energies from 4.189 to 4.600 GeV using 4.7 fb -1 of data collected by the BESIII detector at the BEPCII collider. The Born cross sections for the reactions e +e - → K +K -J/ψ and $$K_s^0$$$K_s^0$$J/ψ are measured as a function of center-of-mass energy. The energy dependence of the cross section for e +e -→ K +K -J/ψ is shown to differ from that for π +π -J/ψ in the region around the Y(4260). In addition, there is evidence for a structure around 4.5 GeV in the e +e - → K +K -J/ψ cross section that is not present in π +π -J/ψ.« less

Measurement of e + e - → K K ¯ J / ψ cross sections at center-of-mass energies from 4.189 to 4.600 GeV

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2018-04-10

We investigate the process e +e - → Kmore » $$\\bar{K}$$J/ψ at center-of-mass energies from 4.189 to 4.600 GeV using 4.7 fb -1 of data collected by the BESIII detector at the BEPCII collider. The Born cross sections for the reactions e +e - → K +K -J/ψ and $$K_s^0$$$K_s^0$$J/ψ are measured as a function of center-of-mass energy. The energy dependence of the cross section for e +e -→ K +K -J/ψ is shown to differ from that for π +π -J/ψ in the region around the Y(4260). In addition, there is evidence for a structure around 4.5 GeV in the e +e - → K +K -J/ψ cross section that is not present in π +π -J/ψ.« less

Temperature dependence of alpha-induced scintillation in the 1,1,4,4-tetraphenyl-1,3-butadiene wavelength shifter

NASA Astrophysics Data System (ADS)

Veloce, L. M.; Kuźniak, M.; Di Stefano, P. C. F.; Noble, A. J.; Boulay, M. G.; Nadeau, P.; Pollmann, T.; Clark, M.; Piquemal, M.; Schreiner, K.

2016-06-01

Liquid noble based particle detectors often use the organic wavelength shifter 1,1,4,4-tetraphenyl-1,3-butadiene (TPB) which shifts UV scintillation light to the visible regime, facilitating its detection, but which also can scintillate on its own. Dark matter searches based on this type of detector commonly rely on pulse-shape discrimination (PSD) for background mitigation. Alpha-induced scintillation therefore represents a possible background source in dark matter searches. The timing characteristics of this scintillation determine whether this background can be mitigated through PSD. We have therefore characterized the pulse shape and light yield of alpha induced TPB scintillation at temperatures ranging from 300 K down to 4 K, with special attention given to liquid noble gas temperatures. We find that the pulse shapes and light yield depend strongly on temperature. In addition, the significant contribution of long time constants above ~50 K provides an avenue for discrimination between alpha decay events in TPB and nuclear-recoil events in noble liquid detectors.

Mechanism of the modulation of Kv4:KChIP-1 channels by external K+.

PubMed

Kaulin, Yu A; De Santiago-Castillo, J A; Rocha, C A; Covarrubias, M

2008-02-15

In response to a prolonged membrane depolarization, inactivation autoregulates the activity of voltage-gated ion channels. Slow inactivation involving a localized constriction of the selectivity filter (P/C-type mechanism) is prevalent in many voltage-gated K(+) channels of the Kv1 subfamily. However, the generalization of this mechanism to other Kv channel subfamilies has remained uncertain and controversial. In agreement with a "foot-in-the-door" mechanism and the presence of ion-ion interactions in the pore, elevated external K(+) slows the development of P/C-type inactivation and accelerates its recovery. In sharp contrast and resembling the regulation of the hippocampal A-type K(+) current, we found that Kv4.x channels associated with KChIP-1 (an auxiliary subunit) exhibit accelerated inactivation and unaffected recovery from inactivation when exposed to elevated external K(+). This regulation depends on the ability of a permeant ion to enter the selectivity filter (K(+) = Rb(+) = NH4(+) > Cs(+) > Na(+)); and the apparent equilibrium dissociation constant of a single regulatory site is 8 mM for K(+). By applying a robust quantitative global kinetic modeling approach to all macroscopic properties over a 210-mV range of membrane potentials, we determined that elevated external K(+) inhibits unstable closed states outside the main activation pathway and thereby promotes preferential closed-state inactivation. These results suggest the presence of a vestigial and unstable P/C-type mechanism of inactivation in Kv4 channels and strengthen the concept of novel mechanisms of closed-state inactivation. Regulation of Kv4 channel inactivation by hyperkalemia may help to explain the pathophysiology of electrolyte imbalances in excitable tissues.

Robust s± pairing in CaK (Fe1-xNix) 4As4 (x =0 and 0.05) from the response to electron irradiation

NASA Astrophysics Data System (ADS)

Teknowijoyo, S.; Cho, K.; Kończykowski, M.; Timmons, E. I.; Tanatar, M. A.; Meier, W. R.; Xu, M.; Bud'ko, S. L.; Canfield, P. C.; Prozorov, R.

2018-04-01

Controlled pointlike disorder introduced by 2.5-MeV electron irradiation was used to probe the superconducting state of single crystals of CaK (Fe1-xNix) 4As4 superconductor at x =0 and 0.05 doping levels. Both compositions show an increase of the residual resistivity and a decrease of the superconducting transition temperature, Tc, at the rate of d Tc/d ρ (Tc) ≈0.19 K/(μ Ω cm ) for x =0 and 0.38 K/(μ Ω cm ) for x =0.05 , respectively. In the Ni-doped compound (x =0.05 ), the coexisting spin-vortex crystal (SVC) magnetic phase is suppressed at the rate of d TN/d ρ (TN) ≈ 0.16 K/(μ Ω cm ). The low-temperature variation of London penetration depth is well approximated by the power-law function, Δ λ (T ) =A Tn , with n ≈2.5 for x =0 and n ≈1.9 for x =0.05 in the pristine state. Detailed analysis of λ (T ) and Tc evolution with disorder is consistent with two effective nodeless energy gaps in the density of states due to robust s± pairing. Overall the behavior of CaK (Fe1-xNix) 4As4 at x =0 is similar to a slightly overdoped Ba1 -yKyFe2As2 at y ≈ 0.5, and at x =0.05 to an underdoped composition at y ≈ 0.2.

E1B-55K mediated regulation of RNF4 STUbL promotes HAdV gene expression.

PubMed

Müncheberg, Sarah; Hay, Ron T; Ip, Wing H; Meyer, Tina; Weiß, Christina; Brenke, Jara; Masser, Sawinee; Hadian, Kamyar; Dobner, Thomas; Schreiner, Sabrina

2018-04-25

HAdV E1B-55K is a multifunctional regulator of productive viral replication and oncogenic transformation in non-permissive mammalian cells. These functions depend on E1B-55K's posttranslational modification with the SUMO protein and its binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to form an E3 Ubiquitin ligase complex that targets antiviral host substrates for proteasomal degradation. Recently, we reported that the PML-NB-associated factor Daxx represses efficient HAdV productive infection and is proteasomally degraded via a SUMO-E1B-55K-dependent, E4orf6-independent pathway, the details of which remained to be established.RNF4, a cellular SUMO-targeted Ubiquitin ligase (STUbL), induces ubiquitinylation of specific SUMOylated proteins and plays an essential role during DNA repair. Here, we show that E1B-55K recruits RNF4 to the insoluble nuclear matrix fraction of the infected cell to support RNF4/Daxx association, promoting Daxx PTM, and thus inhibiting this antiviral factor. Removing RNF4 from infected cells using RNAi resulted in blocking the proper establishment of viral replication centers and significantly diminished viral gene expression. These results provide a model for how HAdV antagonize the antiviral host responses by exploiting the functional capacity of cellular STUbLs. Thus, RNF4 and its STUbL function represent a positive factor during lytic infection and a novel candidate for future therapeutic antiviral intervention strategies. IMPORTANCE Daxx is a PML-NB-associated transcription factor, which was recently shown to repress efficient HAdV productive infection. To counteract this antiviral measurement during infection, Daxx is degraded via a novel pathway including viral E1B-55K and host proteasomes. This virus-mediated degradation is independent of the classical HAdV E3 Ubiquitin ligase complex, which is essential during viral infection to target other host antiviral substrates. To maintain productive viral life

MICROWAVE SPECTROSCOPY OF THE CALCIUM 4snf→4s(n+1)d, 4sng, 4snh, 4sni, AND 4snk TRANSITIONS

NASA Astrophysics Data System (ADS)

Nunkaew, Jirakan; Gallagher, Tom

2015-06-01

We use a delayed field ionization technique to observe the microwave transitions of calcium Rydberg states, from the 4snf states to the 4s(n+1)d, 4sng, 4snh, 4sni, and 4snk states for 18≤ n≤23. We analyze the observed intervals between the ℓ and (ℓ+1), ℓ≥5, states of the same n to determine the Ca^+ 4s dipole and quadrupole polarizabilities. We show that the adiabatic core polarization model is not adequate to extract the Ca^+ 4s dipole and quadrupole polarizabilities and a non adiabatic treatment is required. We use the non adiabatic core polarization model to determine the ionic dipole and quadrupole polarizabilities to be α_d=76.9(3);a_0^3 and α_q=206(9);a_0^5, respectively.

Measurement of e + e − → K K ¯ J / ψ cross sections at center-of-mass energies from 4.189 to 4.600 GeV

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

2018-04-01

We investigate the process e+e ! K K J= at center-of-mass energies from 4.189 to 4.600 GeV using 4.7 fb1 of data collected by the BESIII detector at the BEPCII collider. The Born cross sections for the reactions e+e ! K+KJ= and K0S K0S J= are measured as a function of center- of-mass energy. The energy dependence of the cross section for e+e ! K+KJ= is shown to di er from that for +J= in the region around the Y (4260). In addition, there is evidence for a structure around 4.5 GeV in the e+e ! K+KJ= cross section thatmore » is not present in +J= .« less

Association between H3K4 methylation and cancer prognosis: A meta-analysis.

PubMed

Li, Simin; Shen, Luyan; Chen, Ke-Neng

2018-05-08

Histone H3 lysine 4 methylation (H3K4 methylation), including mono-methylation (H3K4me1), di-methylation (H3K4me2), or tri-methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta-analysis to examine the association between H3K4 methylation and cancer prognosis. A comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. A total of 1474 patients in 10 studies were enrolled in this meta-analysis. The pooled HR of 1.52 (95% CI 1.02-2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27-0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival. This meta-analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

ORC1 BAH domain links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome

PubMed Central

Kuo, Alex J.; Song, Jikui; Cheung, Peggie; Ishibe-Murakami, Satoko; Yamazoe, Sayumi; Chen, James K.; Patel, Dinshaw J.; Gozani, Or

2012-01-01

Recognition of distinctly modified histones by specialized “effector” proteins constitutes a key mechanism for transducing molecular events at chromatin to biological outcomes1. Effector proteins influence DNA-templated processes, including transcription, DNA recombination, and DNA repair; however, no effector functions have yet been identified within the mammalian machinery that regulates DNA replication. Here we show that ORC1 – a component of ORC (origin of replication complex), which mediates pre-DNA replication licensing2 – contains a BAH (bromo adjacent homology) domain that specifically recognizes histone H4 dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property common to BAH domains present within diverse metazoan ORC1 proteins. Structural studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by a dynamic aromatic dimethyllysine-binding cage and multiple intermolecular contacts involving the bound peptide. H4K20me2 is enriched at replication origins and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1 occupancy at origins, ORC chromatin loading, and cell-cycle progression. Mutation of the ORC1 BAH domain has been implicated in the etiology of Meier-Gorlin syndrome (MGS)3,4, a form of primordial dwarfism5, and ORC1 depletion in zebrafish results in an MGS-like phenotype4. We find that wild-type human ORC1, but not ORC1 H4K20me2-binding mutants, rescues the growth retardation of orc1 morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size, mirroring the phenotype of orc1 morphants. Together, our results identify the BAH domain as a novel methyllysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal etiologic role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism. PMID:22398447

Effect of cationic substitution on the double-well hydrogen-bond potential in [K1-x(NH4)x]3H(SO4)2 proton conductors: a single-crystal neutron diffraction study.

PubMed

Choudhury, R R; Chitra, R; Selezneva, E V; Makarova, I P

2017-10-01

The structure of the mixed crystal [K 1-x (NH 4 ) x ] 3 H(SO 4 ) 2 as obtained from single-crystal neutron diffraction is compared with the previously reported room-temperature neutron structure of crystalline K 3 H(SO 4 ) 2 . The two structures are very similar, as indicated by the high value of their isostructurality index (94.8%). It was found that the replacement of even a small amount (3%) of K + with NH 4 + has a significant influence on the short strong hydrogen bond connecting the two SO 4 2- ions. Earlier optical measurements had revealed that the kinetics of the superionic transition in the solid solution [K 1-x (NH 4 ) x ] 3 H(SO 4 ) 2 are much faster than in K 3 H(SO 4 ) 2 ; this reported difference in the kinetics of the superionic phase transition in this class of crystal is explained on the basis of the difference in strength of the hydrogen-bond interactions in the two structures.

Structure determination of two structural analogs, named 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) by synchrotron X-ray powder diffraction

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

Gündoğdu, Gülsüm; Aytaç, Sevim Peri; Müller, Melanie

Two novel compounds, 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C 23H 16F 2N 4S) (1) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C 23H 16ClFN 4S) (2), have been designed and synthesized as cytotoxic agents. The compounds were characterized by infrared, proton nuclear magnetic resonance, mass spectral data, elemental analysis and X-ray powder diffraction. The present study comprises spectral data and crystal structures of these novel compounds determined from synchrotron X-ray powder diffraction data. The structure solutions were obtained by simulated annealing. The final structures were achieved by Rietveld refinement using soft restraints for all bond lengths, bond angles, and planar groups. Both compounds crystallize in space groupmore » $$P\\bar 1$$,Z= 2, with the unit-cell parametersa= 6.37433(9),b= 11.3641(2),c= 14.09115(19) Å,α= 80.1740(8)°,β= 85.1164(8)°,γ= 80.9831(10)°,V= 991.55(3) Å 3of compound (1) anda= 6.53736(6),b= 11.55725(15),c= 14.01373(13) Å,α= 80.3323(7)°,β= 84.8939(6)°,γ= 79.3954(8)°,V= 1024.08(2) Å 3of compound (2). Structural analyses reveal that the title compounds are isostructural.« less

Crystal structures of 4-meth­oxy­benzoic acid–1,3-bis­(pyridin-4-yl)propane (2/1) and biphenyl-4,4′-di­carb­oxy­lic acid–4-meth­oxy­pyridine (1/2)

PubMed Central

Gotoh, Kazuma; Ishida, Hiroyuki

2017-01-01

The crystal structures of two hydrogen-bonded compounds, namely 4-meth­oxy­benzoic acid–1,3-bis­(pyridin-4-yl)propane (2/1), C13H14.59N2·C8H7.67O3·C8H7.74O3, (I), and biphenyl-4,4′-di­carb­oxy­lic acid–4-meth­oxy­pyridine (1/2), C14H9.43O4·C6H7.32NO·C6H7.25NO, (II), have been determined at 93 K. In (I), the asymmetric unit consists of two crystallographically independent 4-meth­oxy­benzoic acid mol­ecules and one 1,3-bis­(pyridin-4-yl)propane mol­ecule. The asymmetric unit of (II) comprises one biphenyl-4,4′-di­carb­oxy­lic acid mol­ecule and two independent 4-meth­oxy­pyridine mol­ecules. In each crystal, the acid and base mol­ecules are linked by short O—H⋯N/N—H⋯O hydrogen bonds, in which H atoms are disordered over the acid O-atom and base N-atom sites, forming a linear hydrogen-bonded 2:1 or 1:2 unit of the acid and the base. The 2:1 units of (I) are linked via C—H⋯π, π–π and C—H⋯O inter­actions into a tape structure along [101], while the 1:2 units of (II) form a double-chain structure along [-101] through π–π and C—H⋯O inter­actions. PMID:28932435

Aging and the 4 kHz Air-bone Gap

PubMed Central

Nondahl, David M.; Tweed, Ted S.; Cruickshanks, Karen J.; Wiley, Terry L.; Dalton, Dayna S.

2011-01-01

Purpose To assess age- and gender-related patterns in the prevalence and 10-year incidence of 4 kHz air-bone gaps, and associated factors. Method Data were obtained as part of the longitudinal, population-based Epidemiology of Hearing Loss Study. An air-bone gap at 4 kHz was defined as an air-conduction threshold ≥15 dB higher than the bone-conduction threshold in the right ear. Results Among 3,553 participants aged 48 to 92 years at baseline (1993-1995), 3.4% had a 4 kHz air-bone gap in the right ear. The prevalence increased with age. Among the 120 participants with an air-bone gap, 60.0% did not have a flat tympanogram or an air-bone gap at .5 kHz. Ten years later we assessed 2093 participants who did not have a 4 kHz air-bone gap at baseline; 9.2% had developed a 4 kHz air-bone gap in the right ear. The incidence increased with age. Among the 192 participants who had developed an air-bone gap, 60.9% did not have a flat tympanogram or air-bone gaps at other frequencies. Conclusions These results suggest that a finding of a 4 kHz air-bone gap may reflect a combination of aging and other factors and not necessarily exclusively abnormal middle ear function. PMID:22232408

4,4'-([4,4'-Bipyridine]-1,1'-diium-1,1'-diyl)dibenzoate dihydrate

DOE PAGES

Rodriguez, Mark A.; Sava Gallis, Dorina F.; Chavez, James S.; ...

2016-06-01

We report here the synthesis of a neutral viologen derivative, C 24H 16N 2O 4·2H 2O. The non-solvent portion of the structure (Z-Lig) is a zwitterion, consisting of two positively charged pyridinium cations and two negatively charged carboxylate anions. The carboxylate group is almost coplanar [dihedral angle = 2.04 (11)°] with the benzene ring, whereas the dihedral angle between pyridine and benzene rings is 46.28 (5)°. TheZ-Lig molecule is positioned on a center of inversion (Fig. 1). The presence of the twofold axis perpendicular to thec-glide plane in space groupC2/c generates a screw-axis parallel to thebaxis that is shifted from themore » origin by 1/4 in theaandcdirections. This screw-axis replicates the molecule (and solvent water molecules) through space. TheZ-Lig molecule links to adjacent moleculesviaO—H...O hydrogen bonds involving solvent water molecules as well as intermolecular C—H...O interactions. There are also π–π interactions between benzene rings on adjacent molecules.« less

Efficient UV-emitting X-ray phosphors: octahedral Zr(PO 4) 6 luminescence centers in potassium hafnium-zirconium phosphates K 2Hf 1- xZr x(PO 4) 2 and KHf 2(1- x) Zr 2 x(PO 4) 3

NASA Astrophysics Data System (ADS)

Torardi, C. C.; Miao, C. R.; Li, J.

2003-02-01

Potassium hafnium-zirconium phosphates, K 2Hf 1- xZr x(PO 4) 2 and KHf 2(1- x) Zr 2 x(PO 4) 3, are broad-band UV-emitting phosphors. At room temperature, they have emission peak maxima at approximately 322 and 305 nm, respectively, under 30 kV peak molybdenum X-ray excitation. Both phosphors demonstrate luminescence efficiencies that make them up to ˜60% as bright as commercially available CaWO 4 Hi-Plus. The solid-state and flux synthesis conditions, and X-ray excited UV luminescence of these two phosphors are discussed. Even though the two compounds have different atomic structures, they contain zirconium in the same active luminescence environment as that found in highly efficient UV-emitting BaHf 1- xZr x(PO 4) 2. All the three materials have hafnium and zirconium in octahedral coordination via oxygen-atom corner sharing with six separate PO 4 tetrahedra. This octahedral Zr(PO 4) 6 moiety appears to be an important structural element for efficient X-ray excited luminescence, as are the edge-sharing octahedral TaO 6 chains for tantalate emission.

Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor.

PubMed

Chaki, Shigeyuki; Hirota, Shiho; Funakoshi, Takeo; Suzuki, Yoshiko; Suetake, Sayoko; Okubo, Taketoshi; Ishii, Takaaki; Nakazato, Atsuro; Okuyama, Shigeru

2003-02-01

We investigated the effects of a novel melanocortin-4 (MC4) receptor antagonist,1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine (MCL0129) on anxiety and depression in various rodent models. MCL0129 inhibited [(125)I][Nle(4)-D-Phe(7)]-alpha-melanocyte-stimulating hormone (alpha-MSH) binding to MC4 receptor with a K(i) value of 7.9 nM, without showing affinity for MC1 and MC3 receptors. MCL0129 at 1 microM had no apparent affinity for other receptors, transporters, and ion channels related to anxiety and depression except for a moderate affinity for the sigma(1) receptor, serotonin transporter, and alpha(1)-adrenoceptor, which means that MCL0129 is selective for the MC4 receptor. MCL0129 attenuated the alpha-MSH-increased cAMP formation in COS-1 cells expressing the MC4 receptor, whereas MCL0129 did not affect basal cAMP levels, thereby indicating that MCL0129 acts as an antagonist at the MC4 receptor. Swim stress markedly induced anxiogenic-like effects in both the light/dark exploration task in mice and the elevated plus-maze task in rats, and MCL0129 reversed the stress-induced anxiogenic-like effects. Under nonstress conditions, MCL0129 prolonged time spent in the light area in the light/dark exploration task and suppressed marble-burying behavior. MCL0129 shortened immobility time in the forced swim test and reduced the number of escape failures in inescapable shocks in the learned helplessness test, thus indicating an antidepressant potential. In contrast, MCL0129 had negligible effects on spontaneous locomotor activity, Rotarod performance, and hexobarbital-induced anesthesia. These observations indicate that MCL0129 is a potent and selective MC4 antagonist with anxiolytic- and antidepressant-like activities in various rodent models. MC4 receptor antagonists may prove effective for treating subjects with stress-related disorders such as depression and/or anxiety.

Experimental study on the responsivity enhancement of Mn1.56Co0.96Ni0.48O4 detector under moderate bias field

NASA Astrophysics Data System (ADS)

Zhou, Wei; Hou, Yun; Gao, Yan Qing; Zhang, Leibo; Huang, Zhi Ming

2011-08-01

As a typical thermal sensitive material, Mn1.56Co0.96Ni0.48O4 (MCN) has achieved widely applications in uncooled bolometer. In this paper, we report that a large increase in electrical conductivity of MCN is obtained with moderate electric-field strengths (E~103V/cm) applied at room temperature (about 300K). Great enhancement in the responsivity is observed when operating with a proper electric bias field, which corresponds to a threshold voltage VTh. MCN bulk materials are prepared by using the sintering method. Micro MCN detector is fabricated by scribing the bulk material into pieces sized 200×100×10μm. The detector is clinged to an Al2O3 substrate with some electrical insulated epoxy glue which is mounted onto a Cu sink. The surrounding temperature is controlled precisely by a temperature controller with a precision of 1mK. Voltage-current characteristics at 270-330K are carefully examined. Different sweeping speeds of the bias-voltage are applied in different orders so as to find out a proper scanning rate, in which the electrical measurement is proceeded in a state of quasi-thermal equilibrium. According to quasi-thermal equilibrium and the time dependent nominal D.C. power, the temperature increase during the measurement is estimated. The conduction mechanism can be well explained with small polaron theory. Empirical equations are used to describe the thermal dynamic process in the pulsed mode, and the process is also simply simulated via numerical calculations. The experimental results and simulation works will be of some referential value to future studies in uncooled microbolometer made in transition metal oxides.

Evaluation of Spin Hamiltonian Parameters and Local Structure of Cu2+-doped Ion in xK2SO4-(50 - x)Na2SO4-50ZnSO4 Glasses with Various K2SO4 Concentrations

NASA Astrophysics Data System (ADS)

Ding, Ch.-Ch.; Wu, Sh.-Y.; Xu, Y.-Q.; Zhang, L.-J.; He, J.-J.

2018-03-01

The spin Hamiltonian parameters (SHPs), i.e., g factors and hyperfine structure constants, and local structures are theoretically studied by analyzing tetragonally elongated 3d9 clusters for Cu2+ in xK2SO4-(50 - x)Na2SO4-50ZnSO4 glasses with various K2SO4 concentrations x. The concentration dependences of the SHPs are attributed to the parabolic decreases of the cubic field parameter Dq, orbital reduction factor k, relative tetragonal elongation ratio τ, and core polarization constant κ with x. The [CuO6]10- clusters are found to undergo significant elongations of about 17% due to the Jahn-Teller effect. The calculated cubic field splittings and the SHPs at various concentrations agree well with the experimental data.

Targeting Plasmodium PI(4)K to eliminate malaria.

PubMed

McNamara, Case W; Lee, Marcus Cs; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Simon, Oliver; Yeung, Bryan Ks; Chatterjee, Arnab K; McCormack, Susan L; Manary, Micah J; Zeeman, Anne-Marie; Dechering, Koen J; Kumar, Tr Santha; Henrich, Philipp P; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L; Fischli, Christoph; Nagle, Advait; Rottmann, Matthias; Plouffe, David M; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C; Kocken, Clemens Hm; Glynne, Richard J; Bodenreider, Christophe; Fidock, David A; Diagana, Thierry T; Winzeler, Elizabeth A

2013-12-12

Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

Targeting Plasmodium PI(4)K to eliminate malaria

NASA Astrophysics Data System (ADS)

McNamara, Case W.; Lee, Marcus C. S.; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Nagle, Advait; Simon, Oliver; Yeung, Bryan K. S.; Chatterjee, Arnab K.; McCormack, Susan L.; Manary, Micah J.; Zeeman, Anne-Marie; Dechering, Koen J.; Kumar, T. R. Santha; Henrich, Philipp P.; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L.; Fischli, Christoph; Rottmann, Matthias; Plouffe, David M.; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W.; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C.; Kocken, Clemens H. M.; Glynne, Richard J.; Bodenreider, Christophe; Fidock, David A.; Diagana, Thierry T.; Winzeler, Elizabeth A.

2013-12-01

Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

Association of Common Genetic Variants in the MAP4K4 Locus with Prediabetic Traits in Humans

PubMed Central

Ketterer, Caroline; Heni, Martin; Machicao, Fausto; Guilherme, Adilson; Grallert, Harald; Schulze, Matthias B.; Boeing, Heiner; Stefan, Norbert; Fritsche, Andreas; Czech, Michael P.; Häring, Hans-Ulrich

2012-01-01

Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is expressed in all diabetes-relevant tissues and mediates cytokine-induced insulin resistance. We investigated whether common single nucleotide polymorphisms (SNPs) in the MAP4K4 locus associate with glucose intolerance, insulin resistance, impaired insulin release, or elevated plasma cytokines. The best hit was tested for association with type 2 diabetes. Subjects (N = 1,769) were recruited from the Tübingen Family (TÜF) study for type 2 diabetes and genotyped for tagging SNPs. In a subgroup, cytokines were measured. Association with type 2 diabetes was tested in a prospective case-cohort study (N = 2,971) derived from the EPIC-Potsdam study. Three SNPs (rs6543087, rs17801985, rs1003376) revealed nominal and two SNPs (rs11674694, rs11678405) significant associations with 2-hour glucose levels. SNPs rs6543087 and rs11674694 were also nominally associated with decreased insulin sensitivity. Another two SNPs (rs2236936, rs2236935) showed associations with reduced insulin release, driven by effects in lean subjects only. Three SNPs (rs11674694, rs13003883, rs2236936) revealed nominal associations with IL-6 levels. SNP rs11674694 was significantly associated with type 2 diabetes. In conclusion, common variation in MAP4K4 is associated with insulin resistance and β-cell dysfunction, possibly via this gene’s role in inflammatory signalling. This variation’s impact on insulin sensitivity may be more important since its effect on insulin release vanishes with increasing BMI. PMID:23094072

Mechanism of thermal decomposition of K2FeO4 and BaFeO4: A review

NASA Astrophysics Data System (ADS)

Sharma, Virender K.; Machala, Libor

2016-12-01

This paper presents thermal decomposition of potassium ferrate(VI) (K2FeO4) and barium ferrate(VI) (BaFeO4) in air and nitrogen atmosphere. Mössbauer spectroscopy and nuclear forward scattering (NFS) synchrotron radiation approaches are reviewed to advance understanding of electron-transfer processes involved in reduction of ferrate(VI) to Fe(III) phases. Direct evidences of Fe V and Fe IV as intermediate iron species using the applied techniques are given. Thermal decomposition of K2FeO4 involved Fe V, Fe IV, and K3FeO3 as intermediate species while BaFeO3 (i.e. Fe IV) was the only intermediate species during the decomposition of BaFeO4. Nature of ferrite species, formed as final Fe(III) species, of thermal decomposition of K2FeO4 and BaFeO4 under different conditions are evaluated. Steps of the mechanisms of thermal decomposition of ferrate(VI), which reasonably explained experimental observations of applied approaches in conjunction with thermal and surface techniques, are summarized.

Serosal Cavities Contain Two Populations of Innate-like integrin α4highCD4+ T Cells, Integrin α4β1+α6β1+α4β7- and α4β1+α6β1-α4β7+ Cells.

PubMed

Yang, Jeong In; Park, Chanho; Kho, Inseong; Lee, Sujin; Suh, Kyung-Suk; Kim, Tae Jin

2017-12-01

We previously reported peritoneal innate-like integrin α4 (CD49d) high CD4 + T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4 high CD4 + T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4 high CD4 + T cells to integrin α4 low CD4 + T cells than peritoneal cavity, but the pleural integrin α4 high CD4 + T cells have the same characteristics of the peritoneal integrin α4 high CD4 + T cells. Most of integrin α4 high CD4 + T cells were integrin β1 high β7 - , but a minor population of integrin α4 high CD4 + T cells was integrin β1 + β7 + . Interestingly, the integrin α4 high β1 high β7 - CD4 + T cells expressed high levels of integrin α4β1 and α6β1, whereas integrin α4 high β1 + β7 + CD4 + T cells expressed high levels of integrin α4β1 and α4β7, suggesting an alternative expression of integrin α6β1 or α4β7 in combination with α4β1 in respective major and minor populations of integrin α4 high CD4 + T cells. The minor population, integrin α4 high β1 + β7 + CD4 + T cells, were different from the integrin α4 high β1 high β7 - CD4 + T cells in that they secreted a smaller amount of Th1 cytokines upon stimulation and expressed lower levels of Th1-related chemokine receptors CCR5 and CXCR3 than the integrin α4 high β 1 high β 7 - CD4 + T cells. In summary, the innate-like integrin α4 high CD4 + T cells could be divided into 2 populations, integrin α4β1 + α6β1 + α4β7 - and α4β1 + α6β1 - α4β7 + cells. The functional significance of serosal integrin α4β7 + CD4 + T cells needed to be investigated especially in view of mucosal immunity.

Large hydrogen-bonded pre-nucleation (HSO4-)(H2SO4)m(H2O)k and (HSO4-)(NH3)(H2SO4)m(H2O)k clusters in the earth's atmosphere.

PubMed

Herb, Jason; Xu, Yisheng; Yu, Fangqun; Nadykto, A B

2013-01-10

The importance of pre-nucleation cluster stability as the key parameter controlling nucleation of atmospheric airborne ions is well-established. In this Article, large ternary ionic (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(H(2)O)(n) clusters have been studied using Density Functional Theory (DFT) and composite ab initio methods. Twenty classes of clusters have been investigated, and thermochemical properties of common atmospheric (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(0)(H(2)O)(k) and (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(1)(H(2)O)(n) clusters (with m, k, and n up to 3) have been obtained. A large amount of new themochemical and structural data ready-to-use for constraining kinetic nucleation models has been reported. We have performed a comprehensive thermochemical analysis of the obtained data and have investigated the impacts of ammonia and negatively charged bisulfate ion on stability of binary clusters in some detail. The comparison of theoretical predictions and experiments shows that the PW91PW91/6-311++G(3df,3pd) results are in very good agreement with both experimental data and high level ab initio CCSD(T)/CBS values and suggest that the PW91PW91/6-311++G(3df,3pd) method is a viable alternative to higher level ab initio methods in studying large pre-nucleation clusters, for which the higher level computations are prohibitively expensive. The uncertainties in both theory and experiments have been investigated, and possible ways of their reduction have been proposed.

Thermogravimetric analysis, kinetic study, and pyrolysis-GC/MS analysis of 1,1'-azobis-1,2,3-triazole and 4,4'-azobis-1,2,4-triazole.

PubMed

Jia, Chenhui; Li, Yuchuan; Zhang, Shujuan; Fei, Teng; Pang, Siping

2018-03-01

In general, the greater the number of directly linked nitrogen atoms in a molecule, the better its energetic performance, while the stability will be accordingly lower. But 1,1'-azobis-1,2,3-triazole (1) and 4,4'-azobis-1,2,4-triazole (2) show remarkable properties, such as high enthalpies of formation, high melting points, and relatively high stabilities. In order to rationalize this unexpected behavior of the two compounds, it is necessary to study their thermal decompositions and pyrolyses. Although a great deal of research has been focused on the synthesis and characterization of energetic materials with 1 and 2 as the backbone, a complete report on their fundamental thermodynamic parameters and thermal decomposition properties has not been published. Thermogravimetric-differential scanning calorimetry were used to obtain the thermal decomposition data of the title compounds. Kissinger and Ozawa-Doyle methods, the two selected non-isothermal methods, are presented for analysis of the solid-state kinetic data. Pyrolysis-gas chromatography/mass spectrometry was used to study the pyrolysis process of the title compounds. The DSC curves show that the thermal decompositions of 1 and 2 are at different heating rates involved a single exothermic process. The TG curves provide insight into the total weight losses from the compounds associated with this process. At different pyrolysis temperatures, the compositions and types of the pyrolysis products differ greatly and the pyrolysis reaction at 500 °C is more thorough than 400 °C. Apparent activation energies (E) and pre-exponential factors (lnA/s -1 ) are 291.4 kJ mol -1 and 75.53 for 1; 396.2 kJ mol -1 and 80.98 for 2 (Kissinger). The values of E are 284.5 kJ mol -1 for 1 and 386.1 kJ mol -1 for 2 (Ozawa-Doyle). The critical temperature of thermal explosion (T b ) is evaluated as 187.01 °C for 1 and 282.78 °C for 2. The title compounds were broken into small fragment ions under the pyrolysis conditions

Low PIP4K2B expression in human breast tumors correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression.

PubMed

Keune, Willem-Jan; Sims, Andrew H; Jones, David R; Bultsma, Yvette; Lynch, James T; Jirström, Karin; Landberg, Goran; Divecha, Nullin

2013-12-01

Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase β (PIP4K2B) directly regulates the levels of two important phosphoinositide second messengers, PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2]. PIP4K2B has been linked to the regulation of gene transcription, to TP53 and AKT activation, and to the regulation of cellular reactive oxygen accumulation. However, its role in human tumor development and on patient survival is not known. Here, we have interrogated the expression of PIP4K2B in a cohort (489) of patients with breast tumor using immunohistochemical staining and by a meta-analysis of gene expression profiles from 2,999 breast tumors, both with associated clinical outcome data. Low PIP4K2B expression was associated with increased tumor size, high Nottingham histological grade, Ki67 expression, and distant metastasis, whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan-Meier curves showed that both high and low PIP4K2B expression correlated with poorer patient survival compared with intermediate expression. In normal (MCF10A) and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression, using short hairpin RNA interference-mediated knockdown, led to a decrease in the transcription and expression of the tumor suppressor protein E-cadherin (CDH1). In MCF10A cells, knockdown of PIP4K2B enhanced TGF-β-induced epithelial to mesenchymal transition (EMT), a process required during the development of metastasis. Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and enhancement of TGF-β-induced EMT by reduced PIP4K2B expression might, in part, explain the association between low PIP4K2B expression and poor patient survival.

Ammonium iron(III) phosphate(V) fluoride, (NH4)0.5[(NH4)0.375K0.125]FePO4F, with ammonium partially substituted by potassium

PubMed Central

Wang, Lei; Zhou, Yan; Huang, Ya-Xi; Mi, Jin-Xiao

2009-01-01

The title compound, ammonium potassium iron(III) phosphate fluoride, (NH4)0.875K0.125FePO4F, is built from zigzag chains ∞ 1{[FeO4F2]7−}, with Fe3+ in a distorted octahedral coordination, extending along both the [011] and [01] directions. These chains are made up of alternating trans-[FeO4F2] and cis-[FeO4F2] octa­hedra via shared F-atom corners, and are linked by PO4 tetra­hedra, resulting in an open-framework structure with channels along the [010] and [100] directions. There are two crystallographically independent ammonium sites: one in the [010] channels and the other, partially substituted by K+ ions, in the [100] channels. The ammonium in the [010] channels is fixed to the framework via eight hydrogen bonds (six N—H⋯O and two N—H⋯F). PMID:21581466

Dimerization of Nitrophorin 4 at Low pH and Comparison to the K1A Mutant of Nitrophorin 1

DOE PAGES

Berry, Robert E.; Yang, Fei; Shokhireva, Tatiana K.; ...

2014-12-09

Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a K d of ~8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer–dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0more » and 1H{ 15N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The “closed loop” form of the A–B and G–H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. Lastly, the homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer.« less

A high level computational study of the CH4/CF4 dimer: how does it compare with the CH4/CH4 and CF4/CF4 dimers?

NASA Astrophysics Data System (ADS)

Biller, Matthew J.; Mecozzi, Sandro

2012-04-01

The interaction within the methane-methane (CH4/CH4), perfluoromethane-perfluoromethane (CF4/CF4) methane-perfluoromethane dimers (CH4/CF4) was calculated using the Hartree-Fock (HF) method, multiple orders of Møller-Plesset perturbation theory [MP2, MP3, MP4(DQ), MP4(SDQ), MP4(SDTQ)], and coupled cluster theory [CCSD, CCSD(T)], as well as the PW91, B97D, and M06-2X density functional theory (DFT) functionals. The basis sets of Dunning and coworkers (aug-cc-pVxZ, x = D, T, Q), Krishnan and coworkers [6-311++G(d,p), 6-311++G(2d,2p)], and Tsuzuki and coworkers [aug(df, pd)-6-311G(d,p)] were used. Basis set superposition error (BSSE) was corrected via the counterpoise method in all cases. Interaction energies obtained with the MP2 method do not fit with the experimental finding that the methane-perfluoromethane system phase separates at 94.5 K. It was not until the CCSD(T) method was considered that the interaction energy of the methane-perfluoromethane dimer (-0.69 kcal mol-1) was found to be intermediate between the methane (-0.51 kcal mol-1) and perfluoromethane (-0.78 kcal mol-1) dimers. This suggests that a perfluoromethane molecule interacts preferentially with another perfluoromethane (by about 0.09 kcal mol-1) than with a methane molecule. At temperatures much lower than the CH4/CF4 critical solution temperature of 94.5 K, this energy difference becomes significant and leads perfluoromethane molecules to associate with themselves, forming a phase separation. The DFT functionals yielded erratic results for the three dimers. Further development of DFT is needed in order to model dispersion interactions in hydrocarbon/perfluorocarbon systems.

Molecular dynamics and residual entropy in the soft crystal, SmE phase, of 4-butyl-4'-isothiocyano-1,1'-biphenyl.

PubMed

Ishimaru, Shin'ichi; Saito, Kazuya; Ikeuchi, Satoaki; Massalska-Arodz, Maria; Witko, Waclaw

2005-05-26

Molecular dynamics and resulting disorder in the soft crystal, smectic E (SmE) phase, were studied in detail for the title compound, 4-butyl-4'-isothiocyano-1,1'-biphenyl (4TCB), by (1)H NMR spectroscopy and adiabatic calorimetry. The ordered crystal phase of 4TCB was realized for the first time under ambient pressure after long two-step annealing and used as the reference state in the analysis of the experimental results. Four motional modes were identified in the SmE phase through the analysis of the (1)H NMR T(1). The residual entropy was determined as ca. 6 J K(-1) mol(-1). This magnitude implies that most of the disorder in the SmE phase at high temperatures is removed on cooling except for the head-to-tail disorder of the rod-shaped 4TCB molecule. Standard thermodynamic functions are tabulated below 375 K.

A miniaturized 4 K platform for superconducting infrared photon counting detectors

NASA Astrophysics Data System (ADS)

Gemmell, Nathan R.; Hills, Matthew; Bradshaw, Tom; Rawlings, Tom; Green, Ben; Heath, Robert M.; Tsimvrakidis, Konstantinos; Dobrovolskiy, Sergiy; Zwiller, Val; Dorenbos, Sander N.; Crook, Martin; Hadfield, Robert H.

2017-11-01

We report on a miniaturized platform for superconducting infrared photon counting detectors. We have implemented a fibre-coupled superconducting nanowire single photon detector in a Stirling/Joule-Thomson platform with a base temperature of 4.2 K. We have verified a cooling power of 4 mW at 4.7 K. We report 20% system detection efficiency at 1310 nm wavelength at a dark count rate of 1 kHz. We have carried out compelling application demonstrations in single photon depth metrology and singlet oxygen luminescence detection.

Dimerization of nitrophorin 4 at low pH and comparison to the K1A mutant of nitrophorin 1.

PubMed

Berry, Robert E; Yang, Fei; Shokhireva, Tatiana K; Amoia, Angela M; Garrett, Sarah A; Goren, Allena M; Korte, Stephanie R; Zhang, Hongjun; Weichsel, Andrzej; Montfort, William R; Walker, F Ann

2015-01-20

Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a Kd of ∼8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer-dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0 and (1)H{(15)N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The "closed loop" form of the A-B and G-H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. The homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer.

Dimerization of Nitrophorin 4 at Low pH and Comparison to the K1A Mutant of Nitrophorin 1

PubMed Central

2015-01-01

Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a Kd of ∼8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer–dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0 and 1H{15N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The “closed loop” form of the A–B and G–H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. The homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer. PMID:25489673

Synthesis, characterization, thermal properties and theoretical investigation on Bis(guanidinium) 4,4‧- Azo-1H-1,2,4-triazol-5-one

NASA Astrophysics Data System (ADS)

Cao, Wen-li; Guo, Jia-jia; Chen, Xiang; Ding, Zi-mei; Xu, Kang-zhen; Song, Ji-rong; Fan, An; Huang, Jie

2017-11-01

Bis(guanidinium) 4,4‧-Azo-1H-1,2,4-triazol-5-one [G2(ZTO)] was synthesized and characterized by X-ray single crystal diffraction, elemental analyzer and Fourier Transform Infrared (FT-IR) spectrometer. The result from X-ray single crystal diffraction indicates that G2(ZTO) crystallizes in the monoclinic space group P2(1)/c with parameters of a = 4.779(2) Å, b = 9.081(4) Å, c = 14.676(6) Å, α = 90.00°, β = 92.43(7)°, γ = 90.00°, V = 636.4(5) Å3, Z = 2, μ(Mo Kα) = 0.131, F(000) = 328, S = 1.071, Dc = 1.640 g·cm-3, R1 = 0.0510 and wR2 = 0.1389. Interestingly enough, its structure does not contain crystallization water, which is a unique characteristic in this material. Besides, the molecular geometry of the compound was optimized by using Density Functional Theory (DFT) method at B3LYP/6-31G (d, p) level in the ground state, revealing that the obtained geometric parameters are in accordance with the X-ray result of the structure. The experimental vibrational spectrum was compared with the calculated spectrum. Besides, molecular electrostatic potential (MEP) of G2(ZTO) was computed with the same method in gas phase, theoretically. The thermal properties of this compound were investigated by DSC, TG/DTG and micro-DSC methods. The results manifest that its thermal behavior can be divided into two main decomposition stages, the first intense decomposition peak temperature is 248.11 °C at the heating rate of 10 °C·min-1, which is higher than that of RDX (219 °C) but slightly lower than that of G(ZTO)·H2O (252.08 °C). The constant-volume combustion heat (ΔcU) of G2(ZTO), G(ZTO)·H2O and ZTO were determined and then the enthalpy of formation were calculated. The results show that G2(ZTO) possesses the highest standard molar enthalpy of formation, which may be explained by the fact that G2(ZTO) contains no water and possesses the highest nitrogen content in all guanidine salts. Moreover, the apparent activation energy (E), thermal stability and safety

Association of MAP4K4 gene single nucleotide polymorphism with mastitis and milk traits in Chinese Holstein cattle.

PubMed

Bhattarai, Dinesh; Chen, Xing; Ur Rehman, Zia; Hao, Xingjie; Ullah, Farman; Dad, Rahim; Talpur, Hira Sajjad; Kadariya, Ishwari; Cui, Lu; Fan, Mingxia; Zhang, Shujun

2017-02-01

The objective of the studies presented in this Research Communication was to investigate the association of single nucleotide polymorphisms present in the MAP4K4 gene with different milk traits in dairy cows. Based on previous QTL fine mapping results on bovine chromosome 11, the MAP4K4 gene was selected as a candidate gene to evaluate its effect on somatic cell count and milk traits in ChineseHolstein cows. Milk production traits including milk yield, fat percentage, and protein percentage of each cow were collected using 305 d lactation records. Association between MAP4K4 genotype and different traits and Somatic Cell Score (SCS) was performed using General Linear Regression Model of R. Two SNPs at exon 18 (c.2061T > G and c.2196T > C) with genotype TT in both SNPs were found significantly higher for somatic SCS. We found the significant effect of exon 18 (c.2061T > G) on protein percentage, milk yield and SCS. We identified SNPs at different location of MAP4K4 gene of the cattle and several of them were significantly associated with the somatic cell score and other different milk traits. Thus, MAP4K4 gene could be a useful candidate gene for selection of dairy cattle against mastitis and the identified polymorphisms might potentially be strong genetic markers.

Möhnite, (NH4)K2Na(SO4)2, a new guano mineral from Pabellón de Pica, Chile

NASA Astrophysics Data System (ADS)

Chukanov, Nikita V.; Aksenov, Sergey M.; Rastsvetaeva, Ramiza K.; Pekov, Igor V.; Belakovskiy, Dmitry I.; Britvin, Sergey N.

2015-10-01

The new mineral möhnite, ideally (NH4)K2Na(SO4)2, the ammonium analogue of aphthitalite, is found in a guano deposit on the Pabellón de Pica mountain, near Chanabaya, Iquique Province, Tarapacá Region, Chile. It is associated with salammoniac, halite, joanneumite, natroxalate, nitratine, chanabayaite, and a clay mineral. Möhnite occurs as random aggregates and clusters of brown imperfect bipyramidal or spindle-shaped crystals. The mineral is brittle, with Mohs' hardness of 3; Dmeas is 2.4(1) g/cm3 and Dcalc is 2.461 g/cm3. The IR spectrum shows the presence of NH4 + cations (the bands at 1431, 3076 and 3240 cm-1). Möhnite is almost isotropic, optically neutral; ɛ = ω = 1.505(2). The chemical composition (electron-microprobe data, N determined by gas chromatography of products of ignition, H calculated by stoichiometry, wt%) is: (NH4)2O 7.99, Na2O 9.49, K2O 32.34, SO3 51.32, total 101.14. The empirical formula is (NH4)0.95Na0.95 K2.14S1.99O8. The crystal structure was solved and refined to R = 0.049 based on 241 unique reflections with I > 2σ( I). Möhnite is trigonal, space group P m1, a = 5.7402(3) Å, c = 7.435(1) Å, V = 212.16(4) Å3, Z = 1. The strongest reflections of the powder X-ray diffraction pattern [ d, Å ( I,%) ( hkl)] are: 4.955 (27) (100), 4.122 (37) (101, 011), 3.708 (29) (002), 2.969 (74) (102, 012), 2.861 (100) (110), 2.474 (20) (003), 2.060 (33) (022). The mineral is named in honour of the German amateur mineralogist Gerhard Möhn (born 1959).

Thermodynamic and acoustical properties of mixtures p-anisaldehyde—alkanols (C1-C4)—2-methyl-1-propanol at 303.15 K

NASA Astrophysics Data System (ADS)

Saini, Balwinder; Kumar, Ashwani; Rani, Ruby; Bamezai, Rajinder K.

2016-07-01

The density, viscosity and speed of sound of pure p-anisaldehyde and some alkanols, for example, methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, butan-2-ol, 2-methylpropan-1-ol, and the binary mixtures of p-anisaldehyde with these alkanols were measured over the entire composition range at 303.15 K. From the experimental data, various thermodynamic parameters such as excess molar volume ( V E), excess Gibbs free energy of activation (Δ G*E), and deviation parameters like viscosity (Δη), speed of sound (Δ u), isentropic compressibility (Δκs), are calculated. The excess as well as deviation parameters are fitted to Redlich—Kister equation. Additionally, the viscosity data for the systems has been used to correlate the application of empirical relation given by Grunberg and Nissan, Katti and Chaudhari, and Hind et al. The results are discussed in terms of specific interactions present in the mixtures.

Synthesis and crystal structures of (2E)-1,4-bis-(4-chloro-phen-yl)but-2-ene-1,4-dione and (2E)-1,4-bis-(4-bromo-phen-yl)but-2-ene-1,4-dione.

PubMed

Lastovickova, Dominika N; La Scala, John J; Sausa, Rosario C

2018-03-01

The mol-ecular structure of (2 E )-1,4-bis-(4-chloro-phen-yl)but-2-ene-1,4-dione [C 16 H 10 Cl 2 O 2 , ( 1 )] is composed of two p -chlorophenyl rings, each bonded on opposite ends to a near planar 1,4- trans enedione moiety [-C(=O)-CH=CH-(C=O)-] [r.m.s. deviation = 0.003 (1) Å]. (2 E )-1,4-Bis(4-bromo-phen-yl)but-2-ene-1,4-dione [C 16 H 10 Br 2 O 2 , ( 2 )] has a similar structure to ( 1 ), but with two p -bromophenyl rings and a less planar enedione group [r.m.s. deviation = 0.011 (1) Å]. Both mol-ecules sit on a center of inversion, thus Z ' = 0.5. The dihedral angles between the ring and the enedione group are 16.61 (8) and 15.58 (11)° for ( 1 ) and ( 2 ), respectively. In the crystal, mol-ecules of ( 1 ) exhibit C-Cl⋯Cl type I inter-actions, whereas mol-ecules of ( 2 ) present C-Br⋯Br type II inter-actions. van der Waals-type inter-actions contribute to the packing of both mol-ecules, and the packing reveals face-to-face ring stacking with similar inter-planar distances of approximately 3.53 Å.

Crystal structure of the human 4-1BB/4-1BBL complex.

PubMed

Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

2018-05-02

4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

K+ and NH4(+) modulate gill (Na+, K+)-ATPase activity in the blue crab, Callinectes ornatus: fine tuning of ammonia excretion.

PubMed

Garçon, D P; Masui, D C; Mantelatto, F L M; McNamara, J C; Furriel, R P M; Leone, F A

2007-05-01

To better comprehend the mechanisms of ionic regulation, we investigate the modulation by Na+, K+, NH4(+) and ATP of the (Na+, K+)-ATPase in a microsomal fraction from Callinectes ornatus gills. ATP hydrolysis obeyed Michaelis-Menten kinetics with KM=0.61+/-0.03 mmol L(-1) and maximal rate of V=116.3+/-5.4 U mg(-1). Stimulation by Na+ (V=110.6+/-6.1 U mg(-1); K0.5=6.3+/-0.2 mmol L(-1)), Mg2+ (V=111.0+/-4.7 U mg(-1); K0.5=0.53+/-0.03 mmol L(-1)), NH4(+) (V=173.3+/-6.9 U mg(-1); K0.5=5.4+/-0.2 mmol L(-1)) and K+ (V=116.0+/-4.9 U mg(-1); K0.5=1.5+/-0.1 mmol L(-1)) followed a single saturation curve, although revealing site-site interactions. In the absence of NH4(+), ouabain (K(I)=74.5+/-1.2 micromol L(-1)) and orthovanadate inhibited ATPase activity by up to 87%; the inhibition patterns suggest the presence of F0F1 and K+-ATPases but not Na+-, V- or Ca2+-ATPase as contaminants. (Na+, K+)-ATPase activity was synergistically modulated by K+ and NH4(+). At 10 mmol L(-1) K+, increasing NH4(+) concentrations stimulated maximum activity to V=185.9+/-7.4 U mg(-1). However, at saturating NH4(+) (50 mmol L(-1)), increasing K+ concentrations did not stimulate activity further. Our findings provide evidence that the C. ornatus gill (Na+, K+)-ATPase may be particularly well suited for extremely efficient active NH4(+) excretion. At elevated NH4(+) concentrations, the enzyme is fully active, regardless of hemolymph K+ concentration, and K+ cannot displace NH4(+) from its exclusive binding sites. Further, the binding of NH4(+) to its specific sites induces an increase in enzyme apparent affinity for K+, which may contribute to maintaining K+ transport, assuring that exposure to elevated ammonia concentrations does not lead to a decrease in intracellular potassium levels. This is the first report of modulation by ammonium ions of C. ornatus gill (Na+, K+)-ATPase, and should further our understanding of NH4(+) excretion in benthic crabs.

Synthesis, crystal structure, thermal analysis and dielectric properties of Rb4(SO4)(HSO4)2(H3AsO4) compound

NASA Astrophysics Data System (ADS)

Belhaj Salah, M.; Nouiri, N.; Jaouadi, K.; Mhiri, T.; Zouari, N.

2018-01-01

A new inorganic Rb4(SO4)(HSO4)2(H3AsO4) compound was prepared. It was found to crystallize in the monoclinic system (P21 space group) with the following lattice parameters: a = 5868 (1) Å, b = 13,579(2) Å, c = 11,809 (3) Å and β = 94,737 (1)°. The structure is characterized by SO42-, HSO4- and H3AsO4 tetrahedra connected by hydrogen bridge to form two types of dimmer (H(8)S(2)O4- … S(1)O42- and H(12)S(2)O4- … H3AsO4). These dimmers are interconnected by both hydrogen bonds O(14)sbnd H(14)· · ·O(4) and O(15)sbnd H(15)· · ·O(2). They are also linked by the hydrogen bridge assured by the hydrogen atoms H(2), H(3) and H(4) of the H3AsO4 group to build the chain S(1)O4⋯H3AsO4 which are parallel to the ''a'',direction. The rubidium cations are coordinated by eight oxygen atoms with Rbsbnd O distance ranging from 2893(8) to 3.415(6) Å. The existence of Osbnd H and (S/As)sbnd O bonds in the structure at room temperature has been confirmed by IR and Raman spectroscopy in the frequency ranges 4000-400 cm-1and 1200 - 50 cm-1, respectively. Thermal analysis of Rb4(HSO4)(HSO4)2(H3AsO4) showed that the transformation to high temperature phase occurs at 407 K by one-step process. Thermal decomposition of the product takes place at much higher temperatures, with an onset of approximately 522 K. The first transition detected by differential scanning calorimetry (DSC) was also analyzed by dielectric and conductivity measurements using the impedance spectroscopy techniques. The conductivity in the high temperature phase at 428 K is 1.04 × 10-3 Ω-1 cm-1, and the activation energy for the proton transport is 0.36 eV. The conductivity relaxation parameters associated with the high disorder protonic conduction have been examined from analysis of the M"/M"max spectrum measured in a wide temperature range. Transport properties of this material appear to be due to the proton hopping mechanism. The obtained results show that this transition is protonic by nature.

Chiral-pool synthesis of 1,2,4-trisubstituted 1,4-diazepanes as novel σ1 receptor ligands.

PubMed

Fanter, Lena; Müller, Christoph; Schepmann, Dirk; Bracher, Franz; Wünsch, Bernhard

2017-09-01

Starting from enantiomerically pure amino acids, 1,4-diazepanes with various substituents in 1, 2, and 4-position were synthesized following the late stage diversification strategy. The key step in the formation of the seven-membered ring was the intramolecular EDC coupling of amino acids 15, 26, and 39. The configuration in 2-position does not influence the σ 1 affinity and selectivity over related receptors. A cyclohexylmethyl or a butyl group are the preferred substituents in 4-position, whereas a methyl moiety in 2-position and a (substituted) benzyl moiety in 1-position result in the highest σ 1 affinity. These results fit nicely to the reported σ 1 pharmacophore models. The compounds did not inhibit the structurally related fungal enzyme sterol Δ 8,7 -isomerase, but showed inhibition of diverse enzymes in late cholesterol biosynthesis at high concentrations. In a screening against more than 50 target proteins, (2S)-1-benzyl-4-(4-methoxybenzyl)-2-methyl-1,4-diazepane ((S)-28b, K i (σ 1 )=0.86nM) showed a clean receptor profile. The dose dependent potentiation of electrically stimulated contractions of guinea pig vas deferens indicates σ 1 agonistic activity of (S)-28b. Even at a dose of 100mg/kg (S)-28b did not induce severe toxic or behavioral effects in the Irwin screen. Clear cognition enhancing effects were observed for (S)-28b after inducing amnesia by scopolamine. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cross-sectional study examining the expression of splice variants K-RAS4A and K-RAS4B in advanced non-small-cell lung cancer patients.

PubMed

Aran, Veronica; Masson Domingues, Pedro; Carvalho de Macedo, Fabiane; Moreira de Sousa, Carlos Augusto; Caldas Montella, Tatiane; de Souza Accioly, Maria Theresa; Ferreira, Carlos Gil

2018-02-01

Mammalian cells differently express 4 RAS isoforms: H-RAS, N-RAS, K-RAS4A and K-RAS4B, which are important in promoting oncogenic processes when mutated. In lung cancer, the K-RAS isoform is the most frequently altered RAS protein, being also a difficult therapeutic target. Interestingly, there are two K-RAS splice variants (K-RAS4A and K-RAS4B) and little is known about the role of K-RAS4A. Most studies targeting K-RAS, or analysing it as a prognostic factor, have not taken into account the two isoforms. Consequently, the in-depth investigation of them is needed. The present study analysed 98 specimens from advanced non-small cell lung cancer (NSCLC) adenocarcinoma patients originated from Brazil. The alterations present in K-RAS at the DNA level (Sanger sequencing) as well as the expression of the splicing isoforms at the RNA (qRT-PCR) and protein levels (immunohistochemistry analysis), were evaluated. Possible associations between clinicopathological features and the molecular findings were also investigated. Our results showed that in the non-smoking population, the cancer incidence was higher among women. In contrast, in smokers and former smokers, the incidence was higher among men. Regarding sequencing results, 10.5% of valid samples presented mutations in exon 2, being all wild-type for exon 3, and the most frequently occurring base change was the transversion G → T. Our qRT-PCR and immunohistochemical analysis showed that both, K-RAS4A and K-RAS4B, were differently expressed in NSCLC tumour samples. For example, tumour specimens showed higher K-RAS4A mRNA expression in relation to commercial normal lung control than did K-RAS4B. In addition, K-RAS4B protein expression was frequently stronger than K-RAS4A in the patients analysed. Our results highlight the differential expression of K-RAS4A and K-RAS4B in advanced adenocarcinoma NSCLC patients and underline the need to further clarify the enigma behind their biological significance in various cancer

Geometric validation of self-gating k-space-sorted 4D-MRI vs 4D-CT using a respiratory motion phantom

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

Yue, Yong, E-mail: yong.yue@cshs.org; Yang, Wensha; McKenzie, Elizabeth

Purpose: MRI is increasingly being used for radiotherapy planning, simulation, and in-treatment-room motion monitoring. To provide more detailed temporal and spatial MR data for these tasks, we have recently developed a novel self-gated (SG) MRI technique with advantage of k-space phase sorting, high isotropic spatial resolution, and high temporal resolution. The current work describes the validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory motion phantom and comparison to 4D-CT. Methods: The 4D-MRI sequence is based on a spoiled gradient echo-based 3D projection reconstruction sequence with self-gating for 4D-MRI at 3 T. Respiratory phase is resolved by usingmore » SG k-space lines as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins with spatial resolution 1.56 × 1.56 × 1.56 mm{sup 3}. A MRI-CT compatible phantom was designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration gadolinium (Gd) gel is embedded into a plastic box (35 × 40 × 63 mm{sup 3}) and stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is able to produce human-type breathing patterns between 4 and 30 respiratory cycles/min. 4D-CT of the phantom has been acquired in cine mode, and reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets were imported into a treatment planning software for target contouring. The geometrical accuracy of the 4D MRI and CT images has been quantified using target volume, flattening, and eccentricity. The target motion was measured by tracking the centroids of the spheres in each individual phase. Motion ground-truth was obtained from input signals and real-time video recordings. Results: The dynamic phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and 20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target

Robust s ± pairing in CaK ( Fe 1 – x Ni x ) 4 As 4 ( x = 0 and 0.05) from the response to electron irradiation

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

Teknowijoyo, S.; Cho, K.; Konczykowski, M.

Here, controlled pointlike disorder introduced by 2.5-MeV electron irradiation was used to probe the superconducting state of single crystals of CaK(Fe 1–xNi x) 4As 4 superconductor at x = 0 and 0.05 doping levels. Both compositions show an increase of the residual resistivity and a decrease of the superconducting transition temperature, T c, at the rate of dT c/dρ(T c) ≈ 0.19 K/(μΩcm) for x = 0 and 0.38 K/(μΩcm) for x = 0.05, respectively. In the Ni-doped compound (x = 0.05), the coexisting spin-vortex crystal (SVC) magnetic phase is suppressed at the rate of dT N/dρ(T N) ≈ 0.16more » K/(μΩcm). The low-temperature variation of London penetration depth is well approximated by the power-law function, Δλ(T) = AT n, with n ≈ 2.5 for x = 0 and n ≈ 1.9 for x = 0.05 in the pristine state. Detailed analysis of λ(T) and T c evolution with disorder is consistent with two effective nodeless energy gaps in the density of states due to robust s± pairing. Overall the behavior of CaK(Fe 1–xNi x) 4As 4 at x = 0 is similar to a slightly overdoped Ba 1–yK yFe 2As 2 at y ≈ 0.5, and at x = 0.05 to an underdoped composition at y ≈ 0.2.« less

Robust s ± pairing in CaK ( Fe 1 – x Ni x ) 4 As 4 ( x = 0 and 0.05) from the response to electron irradiation

DOE PAGES

Teknowijoyo, S.; Cho, K.; Konczykowski, M.; ...

2018-04-27

Here, controlled pointlike disorder introduced by 2.5-MeV electron irradiation was used to probe the superconducting state of single crystals of CaK(Fe 1–xNi x) 4As 4 superconductor at x = 0 and 0.05 doping levels. Both compositions show an increase of the residual resistivity and a decrease of the superconducting transition temperature, T c, at the rate of dT c/dρ(T c) ≈ 0.19 K/(μΩcm) for x = 0 and 0.38 K/(μΩcm) for x = 0.05, respectively. In the Ni-doped compound (x = 0.05), the coexisting spin-vortex crystal (SVC) magnetic phase is suppressed at the rate of dT N/dρ(T N) ≈ 0.16more » K/(μΩcm). The low-temperature variation of London penetration depth is well approximated by the power-law function, Δλ(T) = AT n, with n ≈ 2.5 for x = 0 and n ≈ 1.9 for x = 0.05 in the pristine state. Detailed analysis of λ(T) and T c evolution with disorder is consistent with two effective nodeless energy gaps in the density of states due to robust s± pairing. Overall the behavior of CaK(Fe 1–xNi x) 4As 4 at x = 0 is similar to a slightly overdoped Ba 1–yK yFe 2As 2 at y ≈ 0.5, and at x = 0.05 to an underdoped composition at y ≈ 0.2.« less

X-ray structural studies and physicochemical characterization of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl- 3,4-dihydro-2(1H)-pyrimidinone polymorphs.

PubMed

Miyamae, A; Kitamura, S; Tada, T; Koda, S; Yasuda, T

1991-10-01

The polymorphism of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-di hydro- 2(1 H)-pyrimidinone (FK664; 1) was characterized by using X-ray powder diffractometry, differential scanning calorimetry (DSC), and IR spectroscopy. Structures of two polymorphs (Forms A and B) were determined by X-ray crystallographic analysis. Form A crystallized in the monoclinic space group P2(1)/c, with a = 13.504(2), b = 6.733(1), c = 24.910(8) A, beta = 96.55(4) degrees, z = 4, and dcal = 1.203 g/cm3, while Form B crystallized in the same space group, with a = 8.067(2), b = 15.128(4), c = 18.657(4) A, beta = 102.34(3) degrees, z = 4, and dcal = 1.216 g/cm3. The conformational features of 1 were very similar between the two polymorphs. Compound 1, in both crystal forms, took an energetically reasonable conformation in three rigid planes, such as 2-pyrimidone, trimethylphenyl, and dimethoxyphenyl rings, but the molecules were packed in different ways between the two polymorphs. In the Form B crystal, a short contact was possible, to form pi-pi interactions between two dimethoxyphenyl groups related with the inversion center in the crystal lattice; this interaction seems to contribute to stabilizing the crystal structure of Form B. Both Forms A and B showed only one endothermic peak due to fusion at 115 and 140 degrees C, respectively, on the DSC thermograms; therefore, it is suggested that there are no transition points between the two polymorphs. The heats of fusion obtained from the DSC thermograms were 33.2(2) kJ/mol for Form A and 36.8(1) kJ/mol for Form B.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors

PubMed Central

2016-01-01

We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay. PMID:26741168

ESSEA K-4 Online Course: Polar Connections

NASA Astrophysics Data System (ADS)

Blaney, L.; Myers, R. J.; Schwerin, T.

2007-12-01

The Earth System Science Education Alliance (ESSEA) is a National Science Foundation-supported program implemented by the Institute for Global Environmental Strategies (IGES) to improve the quality of geoscience instruction for pre-service, middle, and high school teachers. ESSEA increases teachers' access to quality materials, standards-based instructional methods and content knowledge. Started in 2000 and based on a trio of online courses (for elementary, middle, and high school teachers), the courses have been used by 40 faculty at 20 institutions educating over 1,700 teachers in Earth system science. Program evaluation of original course participants indicated that the courses had significant impact on teachers Earth system content knowledge and beliefs about teaching and learning. Seventeen of the original participating institutions have continued to use the courses and many have developed new programs that incorporate the courses in Earth science education opportunities for teachers. Today the ESSEA program lists nearly 40 colleges and universities as participants. The original K-4 course and modules have been revised to include topics and resources focusing on the International Polar Year. The new K-4 Land, Living Things, Water and Air modules contain inquiry-based investigations exploring our polar regions. Each module lists a set of essential questions that guide teachers and their students as they build content knowledge. The course structure requires teachers to work individually and in teams to build content knowledge and pedagogical understanding of how their students learn. This group investigation approach and a "Teacher as Researcher" theme promote reflection and collaboration to develop criteria for effective concept building. By exploring the characteristics of polar landscapes, atmosphere, and polar life, teachers and their students will develop new understandings about the interactions and dependencies of the Earth spheres and our polar regions

$$ \\mathcal{N} $$ = 4 superconformal bootstrap of the K 3 CFT

DOE PAGES

Lin, Ying-Hsuan; Shao, Shu-Heng; Simmons-Duffin, David; ...

2017-05-23

We study two-dimensional (4; 4) superconformal eld theories of central charge c = 6, corresponding to nonlinear sigma models on K3 surfaces, using the superconformal bootstrap. This is made possible through a surprising relation between the BPS N = 4 superconformal blocks with c = 6 and bosonic Virasoro conformal blocks with c = 28, and an exact result on the moduli dependence of a certain integrated BPS 4-point function. Nontrivial bounds on the non-BPS spectrum in the K3 CFT are obtained as functions of the CFT moduli, that interpolate between the free orbifold points and singular CFT points. Wemore » observe directly from the CFT perspective the signature of a continuous spectrum above a gap at the singular moduli, and fi nd numerically an upper bound on this gap that is saturated by the A1 N = 4 cigar CFT. We also derive an analytic upper bound on the fi rst nonzero eigenvalue of the scalar Laplacian on K3 in the large volume regime, that depends on the K3 moduli data. As two byproducts, we find an exact equivalence between a class of BPS N = 2 superconformal blocks and Virasoro conformal blocks in two dimensions, and an upper bound on the four-point functions of operators of sufficiently low scaling dimension in three and four dimensional CFTs.« less

$$ \\mathcal{N} $$ = 4 superconformal bootstrap of the K 3 CFT

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

Lin, Ying-Hsuan; Shao, Shu-Heng; Simmons-Duffin, David

We study two-dimensional (4; 4) superconformal eld theories of central charge c = 6, corresponding to nonlinear sigma models on K3 surfaces, using the superconformal bootstrap. This is made possible through a surprising relation between the BPS N = 4 superconformal blocks with c = 6 and bosonic Virasoro conformal blocks with c = 28, and an exact result on the moduli dependence of a certain integrated BPS 4-point function. Nontrivial bounds on the non-BPS spectrum in the K3 CFT are obtained as functions of the CFT moduli, that interpolate between the free orbifold points and singular CFT points. Wemore » observe directly from the CFT perspective the signature of a continuous spectrum above a gap at the singular moduli, and fi nd numerically an upper bound on this gap that is saturated by the A1 N = 4 cigar CFT. We also derive an analytic upper bound on the fi rst nonzero eigenvalue of the scalar Laplacian on K3 in the large volume regime, that depends on the K3 moduli data. As two byproducts, we find an exact equivalence between a class of BPS N = 2 superconformal blocks and Virasoro conformal blocks in two dimensions, and an upper bound on the four-point functions of operators of sufficiently low scaling dimension in three and four dimensional CFTs.« less

MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes.

PubMed

Chuang, Huai-Chia; Tan, Tse-Hua

2017-01-07

Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6 + Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.

Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication.

PubMed

Brustel, Julien; Kirstein, Nina; Izard, Fanny; Grimaud, Charlotte; Prorok, Paulina; Cayrou, Christelle; Schotta, Gunnar; Abdelsamie, Alhassan F; Déjardin, Jérôme; Méchali, Marcel; Baldacci, Giuseppe; Sardet, Claude; Cadoret, Jean-Charles; Schepers, Aloys; Julien, Eric

2017-09-15

Among other targets, the protein lysine methyltransferase PR-Set7 induces histone H4 lysine 20 monomethylation (H4K20me1), which is the substrate for further methylation by the Suv4-20h methyltransferase. Although these enzymes have been implicated in control of replication origins, the specific contribution of H4K20 methylation to DNA replication remains unclear. Here, we show that H4K20 mutation in mammalian cells, unlike in Drosophila , partially impairs S-phase progression and protects from DNA re-replication induced by stabilization of PR-Set7. Using Epstein-Barr virus-derived episomes, we further demonstrate that conversion of H4K20me1 to higher H4K20me2/3 states by Suv4-20h is not sufficient to define an efficient origin per se , but rather serves as an enhancer for MCM2-7 helicase loading and replication activation at defined origins. Consistent with this, we find that Suv4-20h-mediated H4K20 tri-methylation (H4K20me3) is required to sustain the licensing and activity of a subset of ORCA/LRWD1-associated origins, which ensure proper replication timing of late-replicating heterochromatin domains. Altogether, these results reveal Suv4-20h-mediated H4K20 tri-methylation as a critical determinant in the selection of active replication initiation sites in heterochromatin regions of mammalian genomes. © 2017 The Authors.

Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4.

PubMed

Gupta, Rajaneesh Kumar; Kanungo, Madhusudan

2013-02-01

Glial cells, besides participating as passive supporting matrix, are also proposed to be involved in the optimization of the interstitial space for synaptic transmission by tight control of ionic and water homeostasis. In adult mouse brain, inwardly rectifying K+ (Kir4.1) and aquaporin-4 (AQP4) channels localize to astroglial endfeets in contact with brain microvessels and glutamate synapses, optimizing clearance of extracellular K(+) and water from the synaptic layers. However, it is still unclear whether there is an age-dependent difference in the expressions of Kir4.1 and AQP4 channels specifically during postnatal development and aging when various marked changes occur in brain and if these changes region specific. RT-PCR and immunoblotting was conducted to compare the relative expression of Kir4.1 and AQP4 mRNA and protein in the early and mature postnatal (0-, 15-, 45-day), adult (20-week), and old age (70-week) mice cerebral and cerebellar cortices. Expressions of Kir4.1 and AQP4 mRNA and protein are very low at 0-day. A pronounced and continuous increase was observed by mature postnatal ages (15-, 45-days). However, in the 70-week-old mice, expressions are significantly up-regulated as compared to 20-week-old mice. Both genes follow the same age-related pattern in both cerebral and cerebellar cortices. The time course and expression pattern suggests that Kir4.1 and AQP4 channels may play an important role in brain K(+) and water homeostasis in early postnatal weeks after birth and during aging.

CCM key comparison CCM.D-K4 'Hydrometer'

NASA Astrophysics Data System (ADS)

Lorefice, S.; Becerra, L. O.; Lenard, E.; Lee, Y. J.; Lee, W. G.; Madec, T.; Meury, P. A.; Caceres, J.; Santos, C.; Vamossy, C.; Man, J.; Fen, K.; Toda, K.; Wright, J.; Bettin, H.; Toth, H.

2016-01-01

This report presents the comparison philosophy, methodology, analysis and the results of the designed CCM.D-K4 key comparison that covered the calibration of high resolution hydrometers for liquid and alcoholometers in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20°C. The main purpose of this comparison was not only to evaluate the degree of equivalence in the calibration of high accuracy hydrometers between NMI participants, but also to link, were it is possible, the results of previous comparisons to Key Comparison Reference Values (KCRVs) of CCM.D-K4. Eleven NMI laboratories took part in the CCM.D-K4 divided in two groups (petals). With the CCM.D-K4 purpose, two similar sets consisting of three hydrometers for liquid density determinations and an alcoholometer were circulated to the NMI participants as a travelling standard in the time interval from January 2011 to April 2012. Twelve Key Comparison Reference Values (KCRVs) for each petal have been obtained at the density values related to the tested density marks of the transfer standards by the results of participants. The KCRVs and corresponding uncertainties were calculated by the weighted mean in the case of consistent results, otherwise the median was used. The degree of equivalence (DoE) with respect to the corresponding KCRV was determined for each participant and, in this particular comparison, the Weighted Least Squares (WLS) method was used to link the individual DoE of each participant by a continuous function. Significant drift of the transfer standards was not detected. This report also gives instructions on calculating pair-wise degrees of equivalence, with the addition of any information on correlations that may be necessary to estimate more accurately as well as the procedure for linking international comparisons to the CCM.D-K4. Finally an example of linkage to the CCM.D-K4 is given by dealing with the results of the bilateral comparison between INRiM and NMIA, which was

Crystal structures of three 1-[4-(4-bromo-but-oxy)-phen-yl] chalcone derivatives: (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-phenyl-prop-2-en-1-one, (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(4-meth-oxy-phen-yl)prop-2-en-1-one and (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.

PubMed

Maragatham, Gunasekaran; Selvarani, Sivasamy; Rajakumar, Perumal; Lakshmi, Srinivasakannan

2017-07-01

The crystal structures of three chalcones with a bromo-substituted but-oxy side chain, viz . ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-phenyl-prop-2-en-1-one, C 19 H 19 BrO 2 , (I), ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(4-meth-oxy-phen-yl)prop-2-en-1-one, C 20 H 21 BrO 3 , (II), and ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one, C 21 H 23 BrO 4 , (III), are reported. In all mol-ecules, the conformation of the keto group with respect to the olefinic bond is s - cis . Mol-ecules of (I) and (II) are nearly planar, while mol-ecule (III) is not planar. In the crystal of compounds (I) and (II), mol-ecules are linked into chains parallel to the c axis by C-H⋯π inter-actions. In the crystal of compound (III), mol-ecules are linked by a pairs of C-H⋯O hydrogen bonds, forming inversion dimers. Weak C-Br⋯π inter-actions are also observed in (III).

Cyclic guanidines: synthesis and antiplatelet activity of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones.

PubMed

Ferroni, R; Simoni, D; Orlandini, P; Bardi, A; Franze, G P; Guarneri, M

1990-12-01

A series of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo [3,4-d]pyrimidin-7-ones (1b-n) and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido [2,1-c][1,2,4]triazin-7-ones (2a-d) has been synthesized. In view of their potential anti-aggregating activity the compounds were tested in vitro for inhibitory activity towards ADP- and collagen-induced aggregation of human platelets. Among the compounds studied, 8-benzyl-1-(2,5-dichlorophenyl)-4,6,7,8-tetrahydro-1H-imidazo [1,2-a]pyrazolo[3,4-d]pyrimidin-7-one (1n) exhibited the most favorable activity. The 2,5-dichlorophenyl side chain is an important lipophilic and/or steric pharmacophore.

40 CFR 721.7160 - 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 2-Oxepanone, polymer with 4,4â²-(1... Substances § 721.7160 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1... new uses subject to reporting. (1) The chemical substance 2-oxepanone, polymer with 4,4′(1-meth-yl-eth...

[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

PubMed

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B cell growth (P < 0.05). (1) [12Asp]K-ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.

Construction and 13C NMR signal-amplification efficiency of a dynamic nuclear polarizer at 6.4 T and 1.4 K

NASA Astrophysics Data System (ADS)

Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Ferguson, Sarah; Taylor, David; McDonald, George; Lumata, Lloyd

Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging technique in biomedical and metabolic imaging since it amplifies the liquid-state nuclear magnetic resonance (NMR) and imaging (MRI) signals by >10,000-fold. Originally used in nuclear scattering experiments, DNP works by creating a non-Boltzmann nuclear spin distribution by transferring the high electron (γ = 28,000 MHz/T) thermal polarization to the nuclear spins via microwave irradiation of the sample at high magnetic field and low temperature. A dissolution device is used to rapidly dissolve the frozen sample and consequently produces an injectable ``hyperpolarized'' liquid at physiologically-tolerable temperature. Here we report the construction and performance evaluation of a dissolution DNP hyperpolarizer at 6.4 T and 1.4 K using a continuous-flow cryostat. The solid and liquid-state 13C NMR signal enhancement levels of 13C acetate samples doped with trityl OX063 and 4-oxo-TEMPO free radicals will be discussed and compared with the results from the 3.35 T commercial hyperpolarizer. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

RbEu (Fe1-xNix) 4As4 : From a ferromagnetic superconductor to a superconducting ferromagnet

NASA Astrophysics Data System (ADS)

Liu, Yi; Liu, Ya-Bin; Yu, Ya-Long; Tao, Qian; Feng, Chun-Mu; Cao, Guang-Han

2017-12-01

The intrinsically hole-doped RbEuFe4As4 exhibits bulk superconductivity at Tsc=36.5 K and ferromagnetic ordering in the Eu sublattice at Tm=15 K. Here we present a hole-compensation study by introducing extra itinerant electrons via a Ni substitution in the ferromagnetic superconductor RbEuFe4As4 with Tsc>Tm . With the Ni doping, Tsc decreases rapidly, and the Eu-spin ferromagnetism and its Tm remain unchanged. Consequently, the system RbEu (Fe1-xNix) 4As4 transforms into a superconducting ferromagnet with Tm>Tsc for 0.07 ≤x ≤0.08 . The occurrence of superconducting ferromagnets is attributed to the decoupling between Eu2 + spins and superconducting Cooper pairs. The superconducting and magnetic phase diagram is established, which additionally includes a recovered yet suppressed spin-density-wave state.

Inelastic neutron scattering investigation of low temperature phase transition in Rb2ZnCl4 and K2ZnCl4

NASA Astrophysics Data System (ADS)

Quilichini, M.; Dvořák, V.; Boutrouille, P.

1991-09-01

Inelastic scattering of neutrons has revealed soft optic modes at the T point frac{1}{2}({b}^*+{c}^*) of the Brillouin zone both in Rb2ZnCl4 and K2ZnCl4 which are responsible for the phase transition from the ferroelectric to the lowest temperature phase of these materials. Moreover, in K2ZnCl4 near the T point a minimum on the soft optic branch in the direction (μ{b}^*+frac{1}{2}{c}^*) has been found which confirms the existence of a new incommensurate phase recently discovered by Gesi. The origin of this incommensurate phase is discussed from a phenomenological point of view and formulae for elastic constants are derived describing their behaviour near transition into incommensurate phase. Des mesures de diffusion inélastique des neutrons ont mis en évidence l'existence d'un mode optique mou au point T(frac{1}{2}({b}^*+{c}^*)) de la zone de Brillouin responsable de la transition de la phase ferroélectrique vers la phase basse température dans les deux composés Rb2ZnCl4 and K2ZnCl4. Pour K2ZnCl4 on montre que la branche optique molle présente un minimum au voisinage de T dans la direction (μ{b}^*+frac{1}{2}{c}^*), ce qui confirme l'existence de la nouvelle phase incommensurable récemment trouvée par Gesi. L'origine de cette phase est discutée sur la base d'un modèle phénoménologique dont on dérive aussi les formules des constantes élastiques et leur comportement au voisinage de la transition vers la phase incommensurable.

Spectral Analysis of 3-(Adamantan-1-yl)-4-Ethyl-1-[(4-Phenylpiperazin-1-yl) Methyl]-1 H-1,2,4-Triazole-5(4 H)-Thione

NASA Astrophysics Data System (ADS)

Mindarava, Y. L.; Shundalau, M. B.; Al-Wahaibi, L. H.; El-Emam, A. A.; Matsukovich, A. S.; Gaponenko, S. V.

2018-05-01

Vibrational IR (3200-650 cm-1) and Raman spectra (3200-150 cm-1) of adamantane-containing 3-(adamantan-1-yl)-4-ethyl-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione, which is promising for drug design, were examined. The UV/Vis spectrum (450-200 nm) of the compound in EtOH was measured. Full geometry optimization using density functional theory (DFT) in the B3LYP/cc-pVDZ approximation allowed the equilibrium configuration of the molecule to be determined and IR and Raman spectra to be calculated. Based on these, the experimental vibrational IR and Raman spectra were interpreted and the biological activity indices were predicted. The UV/Vis spectrum of the title compound was simulated at the time-dependent DFT/CAM-B3LYP/cc-pVDZ level with and without solvent effects and at the ab initio multi-reference perturbation theory XMCQDPT2 level. The UV/Vis spectrum that was simulated using the multi-reference XMCQDPT2 approximation agreed very successfully with the experimental data, in contrast to the single-reference DFT method. This was probably a consequence of intramolecular charge transfer.

Spectral Analysis of 3-(Adamantan-1-yl)-4-Ethyl-1-[(4-Phenylpiperazin-1-yl) Methyl]-1H-1,2,4-Triazole-5(4H)-Thione

NASA Astrophysics Data System (ADS)

Mindarava, Y. L.; Shundalau, M. B.; Al-Wahaibi, L. H.; El-Emam, A. A.; Matsukovich, A. S.; Gaponenko, S. V.

2018-05-01

Vibrational IR (3200-650 cm-1) and Raman spectra (3200-150 cm-1) of adamantane-containing 3-(adamantan-1-yl)-4-ethyl-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione, which is promising for drug design, were examined. The UV/Vis spectrum (450-200 nm) of the compound in EtOH was measured. Full geometry optimization using density functional theory (DFT) in the B3LYP/cc-pVDZ approximation allowed the equilibrium configuration of the molecule to be determined and IR and Raman spectra to be calculated. Based on these, the experimental vibrational IR and Raman spectra were interpreted and the biological activity indices were predicted. The UV/Vis spectrum of the title compound was simulated at the time-dependent DFT/CAM-B3LYP/cc-pVDZ level with and without solvent effects and at the ab initio multi-reference perturbation theory XMCQDPT2 level. The UV/Vis spectrum that was simulated using the multi-reference XMCQDPT2 approximation agreed very successfully with the experimental data, in contrast to the single-reference DFT method. This was probably a consequence of intramolecular charge transfer.

Parameter estimation for mathematical models of a nongastric H+(Na+)-K(+)(NH4+)-ATPase.

PubMed

Nadal-Quirós, Mónica; Moore, Leon C; Marcano, Mariano

2015-09-01

The role of nongastric H(+)-K(+)-ATPase (HKA) in ion homeostasis of macula densa (MD) cells is an open question. To begin to explore this issue, we developed two mathematical models that describe ion fluxes through a nongastric HKA. One model assumes a 1H(+):1K(+)-per-ATP stoichiometry; the other assumes a 2H(+):2K(+)-per-ATP stoichiometry. Both models include Na+ and NH4+ competitive binding with H+ and K+, respectively, a characteristic observed in vitro and in situ. Model rate constants were obtained by minimizing the distance between model and experimental outcomes. Both 1H(+)(1Na(+)):1K(+)(1NH4 (+))-per-ATP and 2H(+)(2Na(+)):2K(+)(2NH4 (+))-per-ATP models fit the experimental data well. Using both models, we simulated ion net fluxes as a function of cytosolic or luminal ion concentrations typical for the cortical thick ascending limb and MD region. We observed that (1) K+ and NH4+ flowed in the lumen-to-cytosol direction, (2) there was competitive behavior between luminal K+ and NH4+ and between cytosolic Na+ and H+, 3) ion fluxes were highly sensitive to changes in cytosolic Na+ or H+ concentrations, and 4) the transporter does mostly Na+ / K+ exchange under physiological conditions. These results support the concept that nongastric HKA may contribute to Na+ and pH homeostasis in MD cells. Furthermore, in both models, H+ flux reversed at a luminal pH that was <5.6. Such reversal led to Na+ / H+ exchange for a luminal pH of <2 and 4 in the 1:1-per-ATP and 2:2-per-ATP models, respectively. This suggests a novel role of nongastric HKA in cell Na+ homeostasis in the more acidic regions of the renal tubules. Copyright © 2015 the American Physiological Society.

Parameter estimation for mathematical models of a nongastric H+(Na+)-K+(NH4+)-ATPase

PubMed Central

Nadal-Quirós, Mónica; Moore, Leon C.

2015-01-01

The role of nongastric H+-K+-ATPase (HKA) in ion homeostasis of macula densa (MD) cells is an open question. To begin to explore this issue, we developed two mathematical models that describe ion fluxes through a nongastric HKA. One model assumes a 1H+:1K+-per-ATP stoichiometry; the other assumes a 2H+:2K+-per-ATP stoichiometry. Both models include Na+ and NH4+ competitive binding with H+ and K+, respectively, a characteristic observed in vitro and in situ. Model rate constants were obtained by minimizing the distance between model and experimental outcomes. Both 1H+(1Na+):1K+(1NH4+)-per-ATP and 2H+(2Na+):2K+(2NH4+)-per-ATP models fit the experimental data well. Using both models, we simulated ion net fluxes as a function of cytosolic or luminal ion concentrations typical for the cortical thick ascending limb and MD region. We observed that 1) K+ and NH4+ flowed in the lumen-to-cytosol direction, 2) there was competitive behavior between luminal K+ and NH4+ and between cytosolic Na+ and H+, 3) ion fluxes were highly sensitive to changes in cytosolic Na+ or H+ concentrations, and 4) the transporter does mostly Na+/K+ exchange under physiological conditions. These results support the concept that nongastric HKA may contribute to Na+ and pH homeostasis in MD cells. Furthermore, in both models, H+ flux reversed at a luminal pH that was <5.6. Such reversal led to Na+/H+ exchange for a luminal pH of <2 and 4 in the 1:1-per-ATP and 2:2-per-ATP models, respectively. This suggests a novel role of nongastric HKA in cell Na+ homeostasis in the more acidic regions of the renal tubules. PMID:26109090

Comparative study on the radiolytic degradation of 4-hydroxybenzoate and 4-hydroxybenzoic ethyl ester

NASA Astrophysics Data System (ADS)

Swoboda, F.; Solar, S.

1999-09-01

The radiolytic degradation of 4-hydroxybenzoic acid ethyl ester (4-HBAEE) and 4-hydroxybenzoate (4-HBA) and the subsequent product formation in N 2O-saturated and aerated solutions has been studied as a function of dose. The rate constants of OH • radicals with the substrates are k(OH •+4-HBAEE)=7.5×10 9 dm 3 mol -1 s -1 and k(OH • +4-HBA)=6.7×10 9 dm 3 mol -1 s -1. Irradiation of 5×10 -4 mol dm -3 aqueous solutions (N 2O, pH 6.0) of 4-HBA leads to the products 3,4-dihydroxybenzoic acid (3,4-DHBA) and hydroquinone (HQ). In the case of 4-HBAEE neither hydroxylation nor decarboxylation products are observable. The predominating reaction pathway with 4-HBAEE is water elimination from the primarily formed dihydroxycyclohexadienyl radicals. By pulse radiolysis a protonation equilibrium of these transients with pK=8.0 could be determined. The protonated OH •-adducts (λ max=385 nm, ɛ=300 m 2 mol -1) decay with k=7×10 4 s -1, the radical anions (λ max=425 nm, ɛ=240 m 2 mol -1) with k=4×10 5 s -1, yielding phenoxyl radicals λ max 405 nm, ɛ=160 m 2 mol -1 and 425 nm, ɛ=175 m 2 mol -1, 2 k=3.6×10 8 dm 3 mol -1 s -1, which do not form phenolic compounds. With 4-HBA OH •-adducts water splitting at pH 6 is very slow, k=4×10 3 s -1, therefore second order decay reactions can compete. At pH 10, where base catalysed water elimination takes place, no hydroxylation products are observable either. In aerated solutions dihydroxy-compounds are formed with both substrates, due to the fast addition of oxygen to the OH •-adducts. In the case of 4-HBA 68% of the OH • radicals result in 3,4-dihydroxyderivatives; for 4-HBAEE these are only 25%. The decarboxylation product hydroquinone is generated only from 4-HBA, its yield corresponds to 18% of the OH • radicals. Comparison of the initial degradation yields demonstrates 4-HBAEE to be 1.6 times more stable towards radiation, for a 50% decomposition of the ester a 2.3 times higher dose as for 4-HBA is required

Calorimetric measurements on Li4C60 and Na4C60

NASA Astrophysics Data System (ADS)

Inaba, Akira; Miyazaki, Yuji; Michałowski, Paweł P.; Gracia-Espino, Eduardo; Sundqvist, Bertil; Wâgberg, Thomas

2015-04-01

We show specific heat data for Na4C60 and Li4C60 in the range 0.4-350 K for samples characterized by Raman spectroscopy and X-ray diffraction. At high temperatures, the two different polymer structures have very similar specific heats both in absolute values and in general trend. The specific heat data are compared with data for undoped polymeric and pristine C60. At high temperatures, a difference in specific heat between the intercalated and undoped C60 polymers of 100 J K-1 mol-1 is observed, in agreement with the Dulong-Petit law. At low temperatures, the specific heat data for Li4C60 and Na4C60 are modified by the stiffening of vibrational and librational molecular motion induced by the polymer bonds. The covalent twin bonds in Li4C60 affect these motions to a somewhat higher degree than the single intermolecular bonds in Na4C60. Below 1 K, the specific heats of both materials become linear in temperature, as expected from the effective dimensionality of the structure. The contribution to the total specific heat from the inserted metal ions can be well described by Einstein functions with TE = 386 K for Li4C60 and TE = 120 K for Na4C60, but for both materials we also observe a Schottky-type contribution corresponding to a first approximation to a two-level system with ΔE = 9.3 meV for Li4C60 and 3.1 meV for Na4C60, probably associated with jumps between closely spaced energy levels inside "octahedral-type" ionic sites. Static magnetic fields up to 9 T had very small effects on the specific heat below 10 K.

Sachon AFS K-4, Sacheon, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO)

DTIC Science & Technology

1968-04-11

FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OESERVATIONS) 41240 -- SACHON KflREALROK AFS K-4 55-67_________ APR UT"If STATION MANZ TSARS SON ?") ALL...KOREA/ROI( AFS K-4 55-67 ____APR SAINSTATION NAME YEARS MOSN ALL WEATHER 1500-1700 ~ LA $S NOUN$ (LST I ONITIOW (KNTSI 1 .3 4.6 7.10 11.-16 17.21 22...4S 1209 c~ ~iC4 1V/ . $ I - - ’~-4 V ~’ *-** La DATA PROCESSING DIVISION ElAc, UJSAF SURFACE WINDS ASHEVILLE, N. C. 28801 PERCENTAGE FREQUENCY OF

[Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function].

PubMed

Komai, Michio; Shirakawa, Hitoshi

2007-11-01

Phylloquinone (vitamin K(1) = VK(1)) and the menaquinones (MK-n, or vitamin K(2) = VK(2)) are naturally occurring forms of VK. Most of the menaquinone series are synthesized by microorganisms, but we have reported that MK-4 is usual in being synthesized by the conversion of orally ingested VK(1) or MK-n in the major tissues of germfree rats and mice which lack their intestinal microflora. This result led us to deny 1960's Martius' hypothesis that described the participation of bacterial enzyme of the intestinal flora to this conversion. VK acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic acid (Gla) from glutamic acid (Glu) residues in the nascent Gla-protein molecule. Therefore, VK is essential for blood coagulation (various clotting factors) and bone structure (as osteocalcin [OC = BGP] and matrix Gla-protein [MGP] in mammals. In addition to the liver, VK is found in the bone, brain, heart, testis, kidney, pancreas and salivary glands mainly as MK-4, and it has been reported that MK-4 itself has specific biological activities in these tissues beside Gla-protein formation. However, the physiological role of MK-4 in these organs has not been fully understood yet. Recently MK-4 has been attracted the attention of researchers due to its activities such as apoptotic activity on the osteoclast cells and leukemia cells, SXR/PXR ligand, and so on. We further review the potent important physiological role of MK-4 in the bone as well as other major tissues.

Ada Compiler Validation Summary Report: Certificate Number: 901129W1. 11097 Verdix Corporation, VADS Sun-4= 68k, Sun OS 4.0, VAda-110-40125, Version 6.0, Sun-4/260 (Host) to MVME 147 (Motorola 68030) (Target)

DTIC Science & Technology

1991-08-01

VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 901129W1.11097 Verdix Corporation VADS Sun-4 => 63K, Sun OS 4.0, VAda-110-40125...68030) (bare machine) Customer Agreement Number: 90-09-25- VRX See Section 3.1 for any additional information about the testing environment. As a

K and Ba distribution in the structures of the clathrate compounds K(x)Ba(16-x)(Ga,Sn)136 (x = 0.8, 4.4, and 12.9) and K(x)Ba(8-x)(Ga,Sn)46 (x = 0.3).

PubMed

Schäfer, Marion C; Bobev, Svilen

2013-04-01

Studies of the K-Ba-Ga-Sn system produced the clathrate compounds K(0.8(2))Ba(15.2(2))Ga(31.0(5))Sn(105.0(5)) [a = 17.0178 (4) Å], K(4.3(3))Ba(11.7(3))Ga(27.4(4))Sn(108.6(4)) [a = 17.0709 (6) Å] and K(12.9(2))Ba(3.1(2))Ga(19.5(4))Sn(116.5(4)) [a = 17.1946 (8) Å], with the type-II structure (cubic, space group Fd3m), and K(7.7(1))Ba(0.3(1))Ga(8.3(4))Sn(37.7(4)) [a = 11.9447 (4) Å], with the type-I structure (cubic, space group Pm3n). For the type-II structures, only the smaller (Ga,Sn)24 pentagonal dodecahedral cages are filled, while the (Ga,Sn)28 hexakaidecahedral cages remain empty. The unit-cell volume is directly correlated with the K:Ba ratio, since an increasing amount of monovalent K occupying the cages causes a decreasing substitution of the smaller Ga in the framework. All three formulae have an electron count that is in good agreement with the Zintl-Klemm rules. For the type-I compound, all framework sites are occupied by a mixture of Ga and Sn atoms, with Ga showing a preference for Wyckoff site 6c. The (Ga,Sn)20 pentagonal dodecahedral cages are occupied by statistically disordered K and Ba atoms, while the (Ga,Sn)24 tetrakaidecahedral cages encapsulate only K atoms. Large anisotropic displacement parameters for K in the latter cages suggest an off-centering of the guest atoms.

A dispersive treatment of K l4 decays

DOE PAGES

Colangelo, Gilberto; Passemar, Emilie; Stoffer, Peter

2015-04-28

K l4 decays offer several reasons of interest: they allow an accurate measurement of ππ-scattering lengths; they provide the best source for the determination of some low-energy constants of xPT; one form factor is directly related to the chiral anomaly, which can be measured here. We present a dispersive treatment of K l4 decays that provides a resummation of ππ- and K π-rescattering effects. In addition, the free parameters of the dispersion relation are fitted to the data of the high-statistics experiments E865 and NA48/2. The matching to xPT at NLO and NNLO enables us to determine the LECs Lmore » r 1, L r 2 and L r 3. With recently published data from NA48/2, the LEC L r 9 can be determined as well. In contrast to a pure chiral treatment, the dispersion relation describes the observed curvature of one of the form factors, which we understand as a rescattering effect beyond NNLO.« less

Cryogen free cooling of ASTRO-H SXS Helium Dewar from 300 K to 4 K

NASA Astrophysics Data System (ADS)

Kanao, Ken'ichi; Yoshida, Seiji; Miyaoka, Mikio; Tsunematsu, Shoji; Otsuka, Kiyomi; Hoshika, Shunji; Narasaki, Katsuhiro; Mitsuda, Kazuhisa; Yamasaki, Noriko; Takei, Yoh; Fujimoto, Ryuji; Sato, Yoichi; Okamoto, Atsushi; Noda, Hirofumi; DiPirro, Michel J.; Shirron, Peter J.

2017-12-01

Soft X-ray Spectrometer instrument (SXS) is one of the primary scientific instruments of ASTRO-H. SXS has a cold detector that is cooled to 50 mK by using a multi-stage Adiabatic Demagnetization Refrigerator (ADR). SXS Dewar containing ADR provides 1.3 K heat sink by using liquid helium in nominal operation. After liquid helium is dried up, 4 K heat sink is provided by using mechanical coolers. Both nominal operation and cryogen free operation were successfully demonstrated. This paper describes the test result of cryogen free operation and cool-down performance from room temperature by using only mechanical coolers without liquid helium. The coolers on the Dewar cooled down cold mass from around 300 K to 4 K with 260 W electric power in 40 days. Cold mass is 35 kg in 4 K area including the helium tank, ADR and detector assembly.

Role of the K(Ca)3.1 K+ channel in auricular lymph node CD4+ T-lymphocyte function of the delayed-type hypersensitivity model.

PubMed

Ohya, Susumu; Nakamura, Erina; Horiba, Sayuri; Kito, Hiroaki; Matsui, Miki; Yamamura, Hisao; Imaizumi, Yuji

2013-07-01

The intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) modulates the Ca(2+) response through the control of the membrane potential in the immune system. We investigated the role of K(Ca)3.1 on the pathogenesis of delayed-type hypersensitivity (DTH) in auricular lymph node (ALN) CD4(+) T-lymphocytes of oxazolone (Ox)-induced DTH model mice. The expression patterns of K(Ca)3.1 and its possible transcriptional regulators were compared among ALN T-lymphocytes of three groups [non-sensitized (Ox-/-), Ox-sensitized, but non-challenged (Ox+/-) and Ox-sensitized and -challenged (Ox+/+)] using real-time polymerase chain reaction, Western blotting and flow cytometry. KCa 3.1 activity was measured by whole-cell patch clamp and the voltage-sensitive dye imaging. The effects of K(Ca)3.1 blockade were examined by the administration of selective K(Ca)3.1 blockers. Significant up-regulation of K(Ca)3.1a was observed in CD4(+) T-lymphocytes of Ox+/- and Ox+/+, without any evident changes in the expression of the dominant-negative form, K(Ca)3.1b. Negatively correlated with this, the repressor element-1 silencing transcription factor (REST) was significantly down-regulated. Pharmacological blockade of K(Ca)3.1 resulted in an accumulation of the CD4(+) T-lymphocytes of Ox+/+ at the G0/G1 phase of the cell cycle, and also significantly recovered not only the pathogenesis of DTH, but also the changes in the K(Ca)3.1 expression and activity in the CD4(+) T-lymphocytes of Ox+/- and Ox+/+. The up-regulation of K(Ca)3.1a in conjunction with the down-regulation of REST may be involved in CD4(+) T-lymphocyte proliferation in the ALNs of DTH model mice; and K(Ca)3.1 may be an important target for therapeutic intervention in allergy diseases such as DTH. © 2013 The British Pharmacological Society.

26 CFR 1.401(a)(4)-1 - Nondiscrimination requirements of section 401(a)(4).

Code of Federal Regulations, 2010 CFR

2010-04-01

...)(4). 1.401(a)(4)-1 Section 1.401(a)(4)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE.... § 1.401(a)(4)-1 Nondiscrimination requirements of section 401(a)(4). (a) In general. Section 401(a)(4...). (b) Requirements a plan must satisfy—(1) In general. In order to satisfy section 401(a)(4), a plan...

Temperature-resolved study of three [M(M'O4)4(TBPO)4] complexes (MM' = URe, ThRe, ThTc).

PubMed

Helliwell, Madeleine; Collison, David; John, Gordon H; May, Iain; Sarsfield, Mark J; Sharrad, Clint A; Sutton, Andrew D

2006-02-01

The crystal structures of the title complexes were measured at several temperatures between room temperature and 100 K. Each sample shows reversible crystal-to-crystal phase transitions as the temperature is varied. The behaviour of [U(ReO4)4(TBPO)4] (I) and [Th(ReO4)4(TBPO)4] (II) (TBPO = tri-n-butylphosphine oxide) is very similar; at room temperature, crystals of (I) and (II) are isostructural, with space group I42m, and reducing the temperature to 100 K causes a lowering of the space-group symmetry to C-centred cells, space groups Cc for (I) and Cmc2(1) for (II). The variation of lattice symmetry of [Th(TcO4)4(TBPO)4] (III) was found to be somewhat different, with the body-centred cubic space group, I43m, occurring at 293 K, a reduction of symmetry at 230 K to the C-centred orthorhombic space group, Cmc2(1), and a further transition to the primitive orthorhombic space group, Pbc2(1), below 215 K. Elucidation of the correct space-group symmetry and the subsequent refinement was complicated in some cases by the twinning by pseudo-merohedry that arises from the lowering of the space-group symmetry, occurring as the temperature is reduced. All three of the crystal structures determined at room temperature have high atomic displacement parameters, particularly of the (n)Bu groups, and (III) shows disorder of some of the O atoms. The structures in the space group Cmc2(1), show some disorder of nBu groups, but are otherwise reasonably well ordered; the structures of (I) in Cc and (III) in Pbc2(1) are ordered, even to the ends of the alkyl chains. Inter-comparison of the structures measured below 293 K, using the program OFIT from the SHELXTL package, showed that generally, they are remarkably alike, with weighted r.m.s. deviations of the M, M' and P atoms of less than 0.1 A, as are the 293 K structures of (I) and (II) with their low-temperature counterparts. However, the structure of (III) measured in the space group Cmc2(1) is significantly different from both the

Effects of exposure to sonar playback sounds (3.5 - 4.1 kHz) on harbor porpoise (Phocoena phocoena) hearing.

PubMed

Kastelein, Ronald A; Helder-Hoek, Lean; Van de Voorde, Shirley

2017-10-01

Safety criteria for naval sonar sounds are needed to protect harbor porpoise hearing. Two porpoises were exposed to sequences of AN/SQS-53C sonar playback sounds (3.5-4.1 kHz, without significant harmonics), at a mean received sound pressure level of 142 dB re 1 μPa, with a duty cycle of 96% (almost continuous). Behavioral hearing thresholds at 4 and 5.7 kHz were determined before and after exposure to the fatiguing sound, in order to quantify temporary threshold shifts (TTSs) and hearing recovery. Control sessions were also conducted. Significant mean initial TTS 1-4 of 5.2 dB at 4 kHz and 3.1 dB at 5.7 kHz occurred after 30 min exposures (mean received cumulative sound exposure level, SEL cum : 175 dB re 1 μPa 2 s). Hearing thresholds returned to pre-exposure levels within 12 min. Significant mean initial TTS 1-4 of 5.5 dB at 4 kHz occurred after 60 min exposures (SEL cum : 178 dB re 1 μPa 2 s). Hearing recovered within 60 min. The SEL cum for AN/SQS-53C sonar sounds required to induce 6 dB of TTS 4 min after exposure (the definition of TTS onset) is expected to be between 175 and 180 dB re 1 μPa 2 s.

Cluster K Mycobacteriophages: Insights into the Evolutionary Origins of Mycobacteriophage TM4

PubMed Central

Pope, Welkin H.; Ferreira, Christina M.; Jacobs-Sera, Deborah; Benjamin, Robert C.; Davis, Ariangela J.; DeJong, Randall J.; Elgin, Sarah C. R.; Guilfoile, Forrest R.; Forsyth, Mark H.; Harris, Alexander D.; Harvey, Samuel E.; Hughes, Lee E.; Hynes, Peter M.; Jackson, Arrykka S.; Jalal, Marilyn D.; MacMurray, Elizabeth A.; Manley, Coreen M.; McDonough, Molly J.; Mosier, Jordan L.; Osterbann, Larissa J.; Rabinowitz, Hannah S.; Rhyan, Corwin N.; Russell, Daniel A.; Saha, Margaret S.; Shaffer, Christopher D.; Simon, Stephanie E.; Sims, Erika F.; Tovar, Isabel G.; Weisser, Emilie G.; Wertz, John T.; Weston-Hafer, Kathleen A.; Williamson, Kurt E.; Zhang, Bo; Cresawn, Steven G.; Jain, Paras; Piuri, Mariana; Jacobs, William R.; Hendrix, Roger W.; Hatfull, Graham F.

2011-01-01

Five newly isolated mycobacteriophages –Angelica, CrimD, Adephagia, Anaya, and Pixie – have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them – with the exception of TM4 – form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species. PMID:22053209

Structural protein 4.1 is located in mammalian centrosomes

PubMed Central

Krauss, Sharon Wald; Chasis, Joel Anne; Rogers, Catherine; Mohandas, Narla; Krockmalnic, Gabriela; Penman, Sheldon

1997-01-01

Structural protein 4.1 was first characterized as an important 80-kDa protein in the mature red cell membrane skeleton. It is now known to be a member of a family of protein isoforms detected at diverse intracellular sites in many nucleated mammalian cells. We recently reported that protein 4.1 isoforms are present at interphase in nuclear matrix and are rearranged during the cell cycle. Here we report that protein 4.1 epitopes are present in centrosomes of human and murine cells and are detected by using affinity-purified antibodies specific for 80-kDa red cell 4.1 and for 4.1 peptides. Immunofluorescence, by both conventional and confocal microscopy, showed that protein 4.1 epitopes localized in the pericentriolar region. Protein 4.1 epitopes remained in centrosomes after extraction of cells with detergent, salt, and DNase. Higher resolution electron microscopy of detergent-extracted cell whole mounts showed centrosomal protein 4.1 epitopes distributed along centriolar cylinders and on pericentriolar fibers, at least some of which constitute the filamentous network surrounding each centriole. Double-label electron microscopy showed that protein 4.1 epitopes were predominately localized in regions also occupied by epitopes for centrosome-specific autoimmune serum 5051 but were not found on microtubules. Our results suggest that protein 4.1 is an integral component of centrosome structure, in which it may play an important role in centrosome function during cell division and organization of cellular architecture. PMID:9207085

Aging and the 4-kHz Air-Bone Gap

ERIC Educational Resources Information Center

Nondahl, David M.; Tweed, Ted S.; Cruickshanks, Karen J.; Wiley, Terry L.; Dalton, Dayna S.

2012-01-01

Purpose: In this study, the authors assessed age- and sex-related patterns in the prevalence and 10-year incidence of 4-kHz air-bone gaps and associated factors. Method: Data were obtained as part of the longitudinal, population-based Epidemiology of Hearing Loss Study ( Cruickshanks et al., 1998). An air-bone gap at 4 kHz was defined as an…

[Regulation of [12Asp]K-ras4B on transcriptional activity of estrogen receptor in endometrial carcinoma HEC-1A cell lines].

PubMed

Gui, Li-ming; Wei, Li-hui; Xu, Ming-xu; Wang, Jian-liu; Zhong, Ying-cheng; Li, Xiao-ping; Tu, Zheng; Sun, Peng-ming; Ma, Da-long

2004-01-01

To investigate the effect of mutant-type [(12)Asp]K-ras4B gene on the expression of estrogen receptor (ER) alpha and beta and their transcriptional activity as a transcription factor in endometrial carcinoma HEC-1A cell line. (1) Effect of [(12)Asp]K-ras4B on the expression of ER alpha and beta were determined using Western blot assay. (2) Eukaryotic expression plasmid pGL3-luciferase-ERE containing luciferase report gene and estrogen receptor element (ERE) was constructed, and co-transfected into NIH3T3 and HEC-1A cell lines with pEGFP-N1 to examine the effect of [(12)Asp]K-ras4B on ER transcription that is regulated by estradiol. In addition, they were transfected into pSV5-HER0 (containing full length wide type ERalpha cDNA) and pCMV-rafS621A (inhibiting raf kinase) plasmids to test the effect of [(12)Asp]K-ras4B/raf signal pathway on transcriptional activity of ER proteins. (1) Protein level of ERs expressed in pcDI transfected control cells was low while it was increased for 3.6-fold (97 +/- 25, 349 +/- 67, P < 0.01) and 1.9-fold (128 +/- 37, 349 +/- 30, P < 0.05) in ERalpha and ERbeta, respectively, in pcDI-[(12)Asp]K-ras4B NIH3T3 cells after transfection. (2) In pcDI-[(12)Asp]K-ras4B NIH3T3 cells, the ratios for ERalpha and and ERbeta levels before transfection of rafS621A plasmids to that after the transfection, were 2.4:1 (724 +/- 45, 310 +/- 46, P < 0.05) and 1.8:1 (493 +/- 20, 284 +/- 20, P < 0.01), respectively; In HEC-1A cells, these ratios were 2.1:1 (566 +/- 22, 279 +/- 30, P < 0.01) and 2.4:1 (405 +/- 33, 165 +/- 15, P < 0.01), respectively. (3) In low serum (2%) culture condition, estradiol (E(2)) stimulated luciferase activity with an increase of 13-fold (130 +/- 42, 1681 +/- 242, P < 0.01) in pcDI-[(12)Asp] K-ras4B NIH3T3 cells, 19-fold (141 +/- 39, 2644 +/- 331, P < 0.001) in HEC-1A cells, respectively, when compared with those in the absence of E(2). (4) In pSV5-HER0 transfected pcDI-[(12)Asp] K-ras4B NIH3T3 cells and HEC-1A cells, compared to

Multicultural Education Resource Book, K-4.

ERIC Educational Resources Information Center

Lopes, Fatima; Tavares, Tony

A collection of creative, imaginative, classroom activity units designed for grades K-4 is presented. Using a multicultural approach, each unit is to be utilized in teaching various subjects such as language arts, mathematics, music, science, social studies, and home economics. Each section includes a source for creative ideas to enhance learning;…

The 1- to 4-K refrigeration techniques for cooling masers on a beam waveguide antenna

NASA Technical Reports Server (NTRS)

Johnson, D. L.

1986-01-01

The status of technology is reported for various 1- to 4-K commercially available refrigeration systems capable of producing 1.5-K refrigeration to cool masers and superconducting cavity oscillators on the proposed beam waveguide antenna. The design requirements for the refrigeration system and the cryostat are presented. A continuously operating evaporation refrigerator that uses capillary tubing to provide a continuous, self-regulating flow of helium at approximately 1.5 K has been selected as the first refrigerator design for the beam waveguide antenna.

Effect of the cation size on the framework structures of magnesium tungstate, A4Mg(WO4)3 (A = Na, K), R2Mg2(WO4)3 (R = Rb, Cs).

PubMed

Han, Shujuan; Wang, Ying; Jing, Qun; Wu, Hongping; Pan, Shilie; Yang, Zhihua

2015-03-28

A series of alkali metal magnesium tungstates, A4Mg(WO4)3 (A = Na, K), R2Mg2(WO4)3 (R = Rb, Cs), were synthesized from a high temperature solution, and their structures were determined by single-crystal X-ray diffraction. Interestingly, Na4Mg(WO4)3 crystallizes in the monoclinic space group C2/c, while K4Mg(WO4)3 having an identical stoichiometry with Na4Mg(WO4)3, exhibits a different framework structure belonging to triclinic symmetry with the space group P1[combining macron]. Isostructural Rb2Mg2(WO4)3 and Cs2Mg2(WO4)3 crystallize in the space group P213 of cubic symmetry and reveal a three dimensional framework composed of isolated WO4 tetrahedra, MgO6 octahedra and RO12 (R = Rb, Cs) polyhedra. The effect of the alkali metal cation size on the framework structures of magnesium tungstate has been discussed in detail. In addition, the infrared spectra, as well as the UV-Vis-NIR diffuse reflectance spectroscopy data, are reported. The first-principles theoretical studies are also carried out to aid the understanding of electronic structures and linear optical properties.

Hydrothermal Syntheses and Structures of Three-Dimensional Oxo-fluorovanadium Phosphates: [H 2N(C 2H 4) 2NH 2] 0.5[(VO) 4V(HPO 4) 2(PO 4) 2F 2(H 2O) 4] · 2H 2O and K 2[(VO) 3(PO 4) 2F 2(H 2O)] · H 2O

NASA Astrophysics Data System (ADS)

Bonavia, Grant; Haushalter, R. C.; Zubieta, Jon

1996-11-01

The hydrothermal reactions of FPO3H2with vanadium oxides result in the incorporation of fluoride into V-P-O frameworks as a consequence of metal-mediated hydrolysis of the fluorophosphoric acid to produce F-and PO3-4. By exploiting this convenient source of F-, two 3-dimensional oxo-fluorovanadium phosphate phases were isolated, [H2N(C2H4)2NH2]0.5[(VO)4V(HOP4)2(PO4)2F2(H2O)4) · 2H2O (1 · 2H2O) and K2[(VO)3(PO4)2F2(H2O)] · H2O (2 · H2O). Both anionic frameworks contain (VIVO)-F--phosphate layers, with confacial bioctahedral {(VIVO)2FO6} units as the fundamental motif. In the case of 1, the layers are linked through {VIIIO6} octahedra, while for 2 the interlayer connectivity is provided by edge-sharing {(VIVO)2F2O6} units. Crystal data are 1 · 2H2O, CH10FN0.5O13P2V2.5, monoclinicC2/m,a= 18.425(4) Å,c= 8.954(2) Å, β = 93.69(2)0,V= 1221.1(4) Å3,Z= 4,Dcalc= 2.423 g cm-3; 2 · H2O, H4F2K2O13P2V3, triclinicPoverline1,a= 7.298(1) Å,b= 8.929(2) Å,c = 10.090(2) Å, α = 104.50(2)0, β = 100.39(2)0, δ = 92.13(2)0,V= 623.8(3) Å3,Z= 2,Dcalc= 2.891 g cm-3.

A 4 K tactical cryocooler using reverse-Brayton machines

NASA Astrophysics Data System (ADS)

Zagarola, M.; Cragin, K.; McCormick, J.; Hill, R.

2017-12-01

Superconducting electronics and spectral-spatial holography have the potential to revolutionize digital communications, but must operate at cryogenic temperatures, near 4 K. Liquid helium is undesirable for military missions due to logistics and scarcity, and commercial low temperature cryocoolers are unable to meet size, weight, power, and environmental requirements for many missions. To address this need, Creare is developing a reverse turbo-Brayton cryocooler that provides refrigeration at 4.2 K and rejects heat at 77 K to an upper-stage cryocooler or through boil-off of liquid nitrogen. The cooling system is predicted to reduce size, weight, and input power by at least an order of magnitude as compared to the current state-of-the-art 4.2 K cryocooler. For systems utilizing nitrogen boil-off, the boil-off rate is reasonable. This paper reviews the design of the cryocooler, the key components, and component test results.

40 CFR 721.1925 - Substituted carboheterocyclic butane tetracarboxylate (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted carboheterocyclic butane... Specific Chemical Substances § 721.1925 Substituted carboheterocyclic butane tetracarboxylate (generic). (a... generically as substituted carboheterocyclic butane tetracarboxylate (PMNs P-90-440 and P-95-4) is subject to...

40 CFR 721.1925 - Substituted carboheterocyclic butane tetracarboxylate (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted carboheterocyclic butane... Specific Chemical Substances § 721.1925 Substituted carboheterocyclic butane tetracarboxylate (generic). (a... generically as substituted carboheterocyclic butane tetracarboxylate (PMNs P-90-440 and P-95-4) is subject to...

Career Education: [Social Studies K-4.

ERIC Educational Resources Information Center

Cortland-Madison Board of Cooperative Educational Services, Cortland, NY.

The second in a series of nine career education guides includes four social studies units for the K-4 level. In general, each of the units discusses goals, objectives, and career elements, and provides a wide variety of unit activities (including puzzles, games, and arts and crafts projects), a multimedia bibliography, and a teacher evaluation…

Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication.

PubMed

Campbell, Grant R; Bruckman, Rachel S; Herns, Shayna D; Joshi, Shweta; Durden, Donald L; Spector, Stephen A

2018-04-20

In this study, we investigated the effects of the dual phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/MTOR) inhibitor dactolisib (NVP-BEZ235), the PI3K/MTOR/bromodomain-containing protein 4 (BRD4) inhibitor SF2523, and the bromodomain and extra terminal domain inhibitor JQ1 on the productive infection of primary macrophages with human immunodeficiency type-1 (HIV). These inhibitors did not alter the initial susceptibility of macrophages to HIV infection. However, dactolisib, JQ1, and SF2523 all decreased HIV replication in macrophages in a dose-dependent manner via degradation of intracellular HIV through autophagy. Macrophages treated with dactolisib, JQ1, or SF2523 displayed an increase in LC3B lipidation combined with SQSTM1 degradation without inducing increased cell death. LC3B-II levels were further increased in the presence of pepstatin A suggesting that these inhibitors induce autophagic flux. RNA interference for ATG5 and ATG7 and pharmacological inhibitors of autophagosome-lysosome fusion and of lysosomal hydrolases all blocked the inhibition of HIV. Thus, we demonstrate that the mechanism of PI3K/MTOR and PI3K/MTOR/BRD4 inhibitor suppression of HIV requires the formation of autophagosomes, as well as their subsequent maturation into autolysosomes. These data provide further evidence in support of a role for autophagy in the control of HIV infection and open new avenues for the use of this class of drugs in HIV therapy. © 2018 Campbell et al.

Arizona Traffic Safety Education, K-8. Grade 4.

ERIC Educational Resources Information Center

Mesa Public Schools, AZ.

One in a series designed to assist Arizona elementary and junior high school teachers in developing children's traffic skills, this curriculum guide for grade 4 deals with the how and why of traffic safety. Based on the introduction to highway safety rules and laws that students have mastered in grades K through 3, the program for grades 4 through…

Superconductivity in the ternary germanide La3 Pd4 Ge4

NASA Astrophysics Data System (ADS)

Fujii, H.; Mochiku, T.; Takeya, H.; Sato, A.

2005-12-01

The ternary germanide La3Pd4Ge4 has been prepared by arc melting. This compound takes a body-centered lattice with an orthorhombic unit cell with the lattice parameters of a=4.2200(3)Å,b=4.3850(3)Å , and c=25.003(2)Å . The crystal structure of La3Pd4Ge4 is U3Ni4Si4 -type with the space group of Immm , consisting of the combination of structural units of AlB2 -type and BaAl4 -type layers. This compound is a type-II superconductor with a critical temperature (Tc) of 2.75 K. The lower critical field Hc1(0) is estimated to be 54 Oe. The upper critical field Hc2(0) estimated by linear extrapolation of the Hc2(T) curves is about 4.0 kOe, whereas the Werthamer-Hefland-Hohemberg theory gives Hc2(0)WHH=3.0kOe . This is an interesting observation of superconductivity in the compounds with U3Ni4Si4 -type structure. The coherence length ξ(0) of 330 Å and the penetration depth λ(0) of 2480 Å are derived.

AT2R (Angiotensin II Type 2 Receptor)-Mediated Regulation of NCC (Na-Cl Cotransporter) and Renal K Excretion Depends on the K Channel, Kir4.1.

PubMed

Wu, Peng; Gao, Zhong-Xiuzi; Duan, Xin-Peng; Su, Xiao-Tong; Wang, Ming-Xiao; Lin, Dao-Hong; Gu, Ruimin; Wang, Wen-Hui

2018-04-01

AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr 53 ) by a time-dependent way with the peak at 4 days. PD123319 treatment (4 days) stimulated the basolateral 40 pS K channel activity, augmented the basolateral K conductance, and increased the negativity of distal convoluted tubule membrane. The stimulation of Kir4.1 was essential for PD123319-induced increase in NCC because inhibiting AT2R increased the expression of tNCC and pNCC only in wild-type but not in the kidney-specific Kir4.1 knockout mice. Renal clearance study showed that thiazide-induced natriuretic effect was larger in PD123319-treated mice for 4 days than untreated mice. However, this effect was absent in kidney-specific Kir4.1 knockout mice which were also Na wasting under basal conditions. Finally, application of AT2R antagonist decreased the renal ability of K excretion and caused hyperkalemia in wild-type but not in kidney-specific Kir4.1 knockout mice. We conclude that AT2R-dependent regulation of NCC requires Kir4.1 in the distal convoluted tubule and that AT2R plays a role in stimulating K excretion by inhibiting Kir4.1 and NCC. © 2018 American Heart Association, Inc.

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition1)

NASA Technical Reports Server (NTRS)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

4,4′-Bipyridinium bis(perchlorate)–4-aminobenzoic acid–4,4′-bipyridine–water (1/4/2/2)

PubMed Central

Meng, Qun-Hui; Han, Lu; Hou, Jian-Dong; Luo, Yi-Fan; Zeng, Rong-Hua

2009-01-01

In the structure of the title compound, C10H10N2 2+·2ClO4 −·4C7H7NO2·2C10H8N2·2H2O, the 4,4′-bipyridinium cation has a crystallographically imposed centre of symmetry. The cation is linked by N—H⋯N hydrogen bonds to adjacent 4,4′-bipyridine mol­ecules, which in turn inter­act via O—H⋯N hydrogen bonds with 4-amino­benzoic acid mol­ecules, forming chains running parallel to [30]. The chains are further connected into a three-dimensional network by N—H⋯O and O—H⋯O hydrogen-bonding inter­actions involving the perchlorate anion, the water mol­ecules and the 4-amino­benzoic acid mol­ecules. In addition, π–π stacking inter­actions with centroid–centroid distances ranging from 3.663 (6) to 3.695 (6) Å are present. The O atoms of the perchlorate anion are disordered over two sets of positions, with refined site occupancies of 0.724 (9) and 0.276 (9). PMID:21581593

Synergistic liquid-liquid extractive spectrophotometric determination of gold(III) using 1-(2',4'-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydropyrimidine-2-thiol.

PubMed

Kamble, Ganesh S; Kolekar, Sanjay S; Han, Sung H; Anuse, Mansing A

2010-05-15

Synergistic liquid-liquid extractive spectrophotometric determination of gold(III) using 1-(2',4'-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydro pyrimidine-2-thiol [2',4'-dinitro APTPT] has been described. Equal volumes (5cm(3)) of the 2',4'-dinitro APTPT (0.02molL(-1)) in the presence of pyridine (0.5molL(-1)) form an orange-red coloured ternary complex with gold(III) of molar ratio 1:1:1 at pH 1.8-2.4 with 5min of shaking. The absorbance of coloured organic layer in 1,2-dichloroethane is measured spectrophotometrically at 445nm against reagent blank. A pronounced synergism has been observed by the binary mixture of 2',4'-dinitro APTPT and pyridine, which shows that the enhancement in the absorbance is observed in the presence of pyridine by the adduct formation in the organic phase. Beer's law was obeyed in the concentration range 2.5-20.0microgmL(-1), with molar absorptivity and Sandell's sensitivity values of 8.7x10(3)dm(3)mol(-1)cm(-1) and 0.023microgcm(-2) respectively. A repetition of the method was checked by finding relative standard deviation (R.S.D.) (n=10) which was 0.17%. The composition of the gold(III)-2',4'-dinitro APTPT-pyridine adduct was established by slope analysis, molar ratio and Job's method. The ternary complex was stable for more than 48h. The influence of various factors such as pH, 2',4'-dinitro APTPT concentration, solvent and pyridine on the degree of complexation has been established. A number of foreign ions tested for their interferences and use of suitable masking agents wherever necessary are tabulated, which show that selectivity of the method has been enhanced. The method is successfully employed for the determination of gold(III) in binary, synthetic mixtures and ayurvedic samples. The reliability of the method is assured by inter-comparison of experimental values, using an atomic absorption spectrometer.

TH-E-17A-04: Geometric Validation of K-Space Self-Gated 4D-MRI Vs. 4D-CT Using A Respiratory Motion Phantom

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

Yue, Y; Fan, Z; Yang, W

Purpose: 4D-CT is often limited by motion artifacts, low temporal resolution, and poor phase-based target definition. We recently developed a novel k-space self-gated 4D-MRI technique with high spatial and temporal resolution. The goal here is to geometrically validate 4D-MRI using a MRI-CT compatible respiratory motion phantom and comparison to 4D-CT. Methods: 4D-MRI was acquired using 3T spoiled gradient echo-based 3D projection sequences. Respiratory phases were resolved using self-gated k-space lines as the motion surrogate. Images were reconstructed into 10 temporal bins with 1.56×1.56×1.56mm3. A MRI-CT compatible phantom was designed with a 23mm diameter ball target filled with highconcentration gadolinium(Gd) gelmore » embedded in a 35×40×63mm3 plastic box stabilized with low-concentration Gd gel. The whole phantom was driven by an air pump. Human respiratory motion was mimicked using the controller from a commercial dynamic phantom (RSD). Four breathing settings (rates/depths: 10s/20mm, 6s/15mm, 4s/10mm, 3s/7mm) were scanned with 4D-MRI and 4D-CT (slice thickness 1.25mm). Motion ground-truth was obtained from input signals and real-time video recordings. Reconstructed images were imported into Eclipse(Varian) for target contouring. Volumes and target positions were compared with ground-truth. Initial human study was investigated on a liver patient. Results: 4D-MRI and 4D-CT scans for the different breathing cycles were reconstructed with 10 phases. Target volume in each phase was measured for both 4D-CT and 4D-MRI. Volume percentage difference for the 6.37ml target ranged from 6.67±5.33 to 11.63±5.57 for 4D-CT and from 1.47±0.52 to 2.12±1.60 for 4D-MRI. The Mann-Whitney U-test shows the 4D-MRI is significantly superior to 4D-CT (p=0.021) for phase-based target definition. Centroid motion error ranges were 1.35–1.25mm (4D-CT), and 0.31–0.12mm (4D-MRI). Conclusion: The k-space self-gated 4D-MRI we recently developed can accurately determine

Syntheses, crystal structure, and electronic properties of the five ABaMQ{sub 4} compounds RbBaPS{sub 4}, CsBaPS{sub 4}, CsBaVS{sub 4}, RbBaVSe{sub 4}, and CsBaVSe{sub 4}

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

Mesbah, Adel; ICSM, UMR 5257 CEA / CNRS / UM / ENSCM, Site de Marcoule-Bâtiment 426, BP 17171, 30207 Bagnols-sur-Cèze Cedex; Prakash, Jai

Five new compounds belonging to the ABaMQ{sub 4} family were synthesized by solid-state chemistry at 1123 K. The compounds RbBaPS{sub 4}, CsBaPS{sub 4}, CsBaVS{sub 4}, RbBaVSe{sub 4}, and CsBaVSe{sub 4} are isostructural and have the TlEuPS{sub 4} structure type. They crystallize in space group D{sup 16}{sub 2h} – Pnma of the orthorhombic system. Their structure consists isolated MQ{sub 4} tetrahedra separated by A and Ba atoms to form a salt-like structure. Density Functional Theory (DFT) calculations of the electronic structures with the use of the HSE functional suggest that the compounds are semiconductors with calculated band gaps of 3.3 eVmore » (RbBaPS{sub 4}), 3.4 eV (CsBaPS{sub 4}), 2.3 eV (CsBaVS{sub 4}), and 1.6 eV (RbBaVSe{sub 4}). - Graphical abstract: General view of the ABaMQ{sub 4} structure down the a axis. - Highlights: • Five new ABaMQ{sub 4} compounds were synthesized by solid-state chemistry at 1123 K. • RbBaPS{sub 4}, CsBaPS{sub 4}, CsBaVS{sub 4}, RbBaVSe{sub 4}, and CsBaVSe{sub 4} have the TlEuPS{sub 4} structure type. • The compounds are semiconductors with calculated band gaps ranging from 1.6 to 3.4 eV.« less

MoSET1 (Histone H3K4 Methyltransferase in Magnaporthe oryzae) Regulates Global Gene Expression during Infection-Related Morphogenesis

PubMed Central

Pham, Kieu Thi Minh; Inoue, Yoshihiro; Vu, Ba Van; Nguyen, Hanh Hieu; Nakayashiki, Toru; Ikeda, Ken-ichi; Nakayashiki, Hitoshi

2015-01-01

Here we report the genetic analyses of histone lysine methyltransferase (KMT) genes in the phytopathogenic fungus Magnaporthe oryzae. Eight putative M. oryzae KMT genes were targeted for gene disruption by homologous recombination. Phenotypic assays revealed that the eight KMTs were involved in various infection processes at varying degrees. Moset1 disruptants (Δmoset1) impaired in histone H3 lysine 4 methylation (H3K4me) showed the most severe defects in infection-related morphogenesis, including conidiation and appressorium formation. Consequently, Δmoset1 lost pathogenicity on wheat host plants, thus indicating that H3K4me is an important epigenetic mark for infection-related gene expression in M. oryzae. Interestingly, appressorium formation was greatly restored in the Δmoset1 mutants by exogenous addition of cAMP or of the cutin monomer, 16-hydroxypalmitic acid. The Δmoset1 mutants were still infectious on the super-susceptible barley cultivar Nigrate. These results suggested that MoSET1 plays roles in various aspects of infection, including signal perception and overcoming host-specific resistance. However, since Δmoset1 was also impaired in vegetative growth, the impact of MoSET1 on gene regulation was not infection specific. ChIP-seq analysis of H3K4 di- and tri-methylation (H3K4me2/me3) and MoSET1 protein during infection-related morphogenesis, together with RNA-seq analysis of the Δmoset1 mutant, led to the following conclusions: 1) Approximately 5% of M. oryzae genes showed significant changes in H3K4-me2 or -me3 abundance during infection-related morphogenesis. 2) In general, H3K4-me2 and -me3 abundance was positively associated with active transcription. 3) Lack of MoSET1 methyltransferase, however, resulted in up-regulation of a significant portion of the M. oryzae genes in the vegetative mycelia (1,491 genes), and during infection-related morphogenesis (1,385 genes), indicating that MoSET1 has a role in gene repression either directly or more

Magnetic properties of Zn1-zMnzGa2Se4 alloy system in the temperature range from 2 to 300 K

NASA Astrophysics Data System (ADS)

Morocoima, M.; Quintero, M.; Quintero, E.; Bocaranda, P.; Ruiz, J.; Moreno, E.

2006-10-01

Measurements of low field static magnetic susceptibility and of magnetization with pulsed magnetic fields up to 32T have been made as a function of temperature on polycrystalline samples of the Zn1-zMnzGa2Se4 alloy system, which has a defect tetragonal chalcopyrite structure in the whole composition range. The resulting data have been used to give information on the magnetic spin-flop and magnetic saturation transitions, and details of the magnetic B-T phase diagrams were determined for the phases. The zero-field Néel temperatures TN and triple points, for the Zn1-zMnzGa2Se4 alloy system, have been found to be 8.1K and (7.8K, 2.2T) for z =1, 5.8K and (5.6K, 1.7T) for z =0.85, 4.5K and (4.35K, 1.0T) for z =0.075, and 3.9K and (3.85K, 0.5T) for z =0.7. The susceptibility χ(T ) curves for B =3 and 5T show magnetothermal effects below 4.5K.

Detailed product analysis during the low temperature oxidation of n-butane

PubMed Central

Herbinet, Olivier; Battin-Leclerc, Frédérique; Bax, Sarah; Le Gall, Hervé; Glaude, Pierre-Alexandre; Fournet, René; Zhou, Zhongyue; Deng, Liulin; Guo, Huijun; Xie, Mingfeng; Qi, Fei

2013-01-01

The products obtained from the low-temperature oxidation of n-butane in a jet-stirred reactor (JSR) have been analysed using two methods: gas chromatography analysis of the outlet gas and reflectron time-of-flight mass spectrometry. The mass spectrometer was combined with tunable synchrotron vacuum ultraviolet photoionization and coupled with a JSR via a molecular-beam sampling system. Experiments were performed under quasi-atmospheric pressure, for temperatures between 550 and 800 K, at a mean residence time of 6s and with a stoichiometric n-butane/oxygen/argon mixture (composition = 4/26/70 in mol %). 36 reaction products have been quantified, including addition to the usual oxidation products, acetic acid, hydrogen peroxide, C1, C2 and C4 alkylhydroperoxides and C4 ketohydroperoxides. Evidence of the possible formation of products (dihydrofuranes, furanones) derived from cyclic ethers has also been found. The performance of a detailed kinetic model of the literature has been assessed with the simulation of the formation of this extended range of species. These simulations have also allowed the analysis of possible pathways for the formation of some obtained products. PMID:21031192

Window type: 4x4 multipaned steel window flanked by 1x4 multipaned ...

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

Window type: 4x4 multipaned steel window flanked by 1x4 multipaned steel, casements. Concrete stoop, entry overhang and pipe rail detail also illustrated. Building 36, facing northwest - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

Synthesis and anticancer evaluation of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles and Mannich bases.

PubMed

Megally Abdo, Nadia Youssef; Kamel, Mona Monir

2015-01-01

A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various secondary amines furnished the Mannich bases 6a-p. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against six human cancer cell lines and normal fibroblast cells. Sixteen of the tested compounds exhibited significant cytotoxicity against most cell lines. Among these derivatives, the Mannich bases 6j, 6m and 6p were found to exhibit the most potent activity. The Mannich base 6m showed more potent cytotoxic activity against gastric cancer NUGC (IC50=0.021 µM) than the standard CHS 828 (IC50=0.025 µM). Normal fibroblast cells WI38 were affected to a much lesser extent (IC50>10 µM).

Synthesis, Structure, and Characterization of Cu4S10(4-methylpyridine)4

NASA Technical Reports Server (NTRS)

Hepp, Aloysius F.; Richman, Robert M.; Duraj, Stan A.; Andras, Maria T.; Moore, Hall L.; Sabat, Michal; Eckles, William E.; Martuch, Robert A.

1996-01-01

The title compound, Cu4S10(4-methylpyridine)(sub 4) (dot) 4-methylpyridine was prepared by three different reactions: the oxidation of copper powder by sulfur and the reaction of copper (I) sulfide (or CuBr (dot) SMe2) with excess sulfur, both in the coordinating solvent, 4-methylpyridine. Red crystals of the compound obtained by layering with hexanes were subjected to single crystal X-ray diffraction. The structure was refined to R = 0.026 and R(sub w) = 0.036 in a space group P1bar (No. 2), with Z = 2, a = 13.983 (2) A, b = 15.384 (2) A, c = 9.660 (1) A, alpha = 93.87 (1)deg., beta = 93.38 (1)deg., gamma = 99.78 (1)deg., V = 2037.9 (9) A(exp 3). The compound has approximate S(sub 4) symmetry and consists of two pentasulfide chains linking four Cu(I) ions, each with a corrdinating 2-methylpyridine. The infrared spectrum was dominated by absorption due to coordinated 4-methylpyridine with several low-energy peaks attributable to S-S stretches, which were also observed by Raman spectroscopy. A featureless electronic absorption spectrum yielded a single peak in the near ultraviolet upon computer enhancement (lambda = 334 nm, epsilon = 10,000), most likely an intraligand transition. Cyclic voltammetry indicates that the polysulfide complex undergoes irrversible oxidation and reduction at +0.04 and -0.34 V vs. SCE, respectively, at 298 K in 4-methylpyridine when swept at 20 mV/sec. The electrochemical behavior was unvaried even at sweep rates as high as 100 V/sec.

Collision-induced dissociation of [4Fe-4S] cubane cluster complexes: [Fe4S4Cl4 - x(SC2H5)x]2-/1- (x = 0-4)

NASA Astrophysics Data System (ADS)

Fu, You-Jun; Laskin, Julia; Wang, Lai-Sheng

2006-09-01

Collision-induced dissociation (CID) experiments on a series of [4Fe-4S] cluster ions, [Fe4S4Cl4 - x(SC2H5)x]2-/1- (x = 0-4), revealed that their fragmentation channels change with the coordination environment. Among the three Coulomb repulsion related channels for the doubly charged species, the collision induced electron detachment channel was found to become more significant from x = 0 to 4 due to the decreasing electron binding energies and the magnitude of repulsion Coulomb barrier, while both the ligand detachment of Cl- and the fission of the [Fe4S4]2+ core became more and more significant with the increase of the Cl- coordination, and eventually became the dominant channel at x = 0. From the parents containing the SC2H5 ligand, neutral losses of HSC2H5 (62 u) and/or HSCHCH2 (60 u) were observed. It was proposed that inter- and intra-ligand proton transfer could happen during the CID process, resulting in hydrogen coordination to the [4Fe-4S] cluster. In the presence of O2, [Fe4S4Cl3(SC2H5)]2- and [Fe4S4Cl4]2- can form the O2-substituted products [Fe4S4Cl2(SC2H5)O2]- and [Fe4S4Cl3O2]-, respectively. It was shown that the O2 complexation occurs by coordination to the empty iron site of the [4Fe-4S] cubane core after dissociation of one Cl- ligand.

Discovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core.

PubMed

Bewley, Blake R; Spearing, Paul K; Weiner, Rebecca L; Luscombe, Vincent B; Zhan, Xiaoyan; Chang, Sichen; Cho, Hyekyung P; Rodriguez, Alice L; Niswender, Colleen M; Conn, P Jeffrey; Bridges, Thomas M; Engers, Darren W; Lindsley, Craig W

2017-09-15

This Letter details the discovery and subsequent optimization of a novel M 4 PAM scaffold based on an 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core, which represents a distinct departure from the classical M 4 PAM chemotypes. Optimized compounds in this series demonstrated improved M 4 PAM potency on both human and rat M 4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain:plasma K p =5.3, K p,uu =2.4; MDCK-MDR1 (P-gp) ER=1.1). Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystal structures of five 1-alkyl-4-aryl-1,2,4-triazol-1-ium halide salts.

PubMed

Guino-O, Marites A; Talbot, Meghan O; Slitts, Michael M; Pham, Theresa N; Audi, Maya C; Janzen, Daron E

2015-06-01

The asymmetric units for the salts 4-(4-fluoro-phen-yl)-1-isopropyl-1,2,4-triazol-1-ium iodide, C11H13FN3 (+)·I(-), (1), 1-isopropyl-4-(4-methyl-phen-yl)-1,2,4-triazol-1-ium iodide, C12H16N3 (+)·I(-), (2), 1-isopropyl-4-phenyl-1,2,4-triazol-1-ium iodide, C11H14N3 (+)·I(-), (3), and 1-methyl-4-phenyl-1,2,4-triazol-1-ium iodide, C9H10N3 (+)·I(-), (4), contain one cation and one iodide ion, whereas in 1-benzyl-4-phenyl-1,2,4-triazol-1-ium bromide monohydrate, C15H14N3 (+)·Br(-)·H2O, (5), there is an additional single water mol-ecule. There is a predominant C-H⋯X(halide) inter-action for all salts, resulting in a two-dimensional extended sheet network between the triazolium cation and the halide ions. For salts with para-substitution on the aryl ring, there is an additional π-anion inter-action between a triazolium carbon and iodide displayed by the layers. For salts without the para-substitution on the aryl ring, the π-π inter-actions are between the triazolium and aryl rings. The melting points of these salts agree with the predicted substituent inductive effects.

The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo (Dendrocalamus asper) Shoots on Kv1.4 Channel

PubMed Central

Mohamad, Fatin H.; Wong, Jia Hui; Mohamad, Habsah; Ismail, Abdul Hadi; Mohamed Yusoff, Abdul Aziz; Osman, Hasnah; Wong, Kok Tong; Idris, Zamzuri; Abdullah, Jafri Malin

2018-01-01

Background Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K+ across the cellular membrane. Methods Chemical compounds from Dendrocalamus asper bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from Xenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from −80 mV with 20 mV step-up until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with n ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control. Results All concentration showed statistically significant results with P < 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play

Antimicrobial and antioxidant activities of substituted 4H-1, 4-benzothiazines

NASA Astrophysics Data System (ADS)

Sharma, Praveen Kumar; Chaucer, Puneet; Kumar, Gulshan; Parihar, Leena

2017-07-01

Antioxidant and antimicrobial activity of substituted benzothiazine was investigated. Antioxidant activity of 3,7-dimethyl-2-(4'-morpholinylcarbonyl)-4H-1,4-benzothiazine was tested by the use of 2-diphenyl-1-picrylhydrazyl radical(DPPH). In addition 3,7-dimethyl-2-(4'-morpholinylcarbonyl)-4H-1,4-benzothiazine was examined for its antimicrobial activity against bacteria, Bacillus subtilis, B. flexus, B. alkalophilus, as well as their antifungal activity against Aspergillus nigrum, A. Flexus and show potential antimicrobial activities.

KChIP1 modulation of Kv4.3-mediated A-type K(+) currents and repetitive firing in hippocampal interneurons.

PubMed

Bourdeau, M L; Laplante, I; Laurent, C E; Lacaille, J-C

2011-03-10

Neuronal A-type K(+) channels regulate action potential waveform, back-propagation and firing frequency. In hippocampal CA1 interneurons located at the stratum lacunosum-moleculare/radiatum junction (LM/RAD), Kv4.3 mediates A-type K(+) currents and a Kv4 β-subunit of the Kv channel interacting protein (KChIP) family, KChIP1, appears specifically expressed in these cells. However, the functional role of this accessory subunit in A-type K(+) currents and interneuron excitability remains largely unknown. Thus, first we studied KChIP1 and Kv4.3 channel interactions in human embryonic kidney 293 (HEK293) cells and determined that KChIP1 coexpression modulated the biophysical properties of Kv4.3 A-type currents (faster recovery from inactivation, leftward shift of activation curve, faster rise time and slower decay) and this modulation was selectively prevented by KChIP1 short interfering RNA (siRNA) knockdown. Next, we evaluated the effects of KChIP1 down-regulation by siRNA on A-type K(+) currents in LM/RAD interneurons in slice cultures. Recovery from inactivation of A-type K(+) currents was slower after KChIP1 down-regulation but other properties were unchanged. In addition, down-regulation of KChIP1 levels did not affect action potential waveform and firing, but increased firing frequency during suprathreshold depolarizations, indicating that KChIP1 regulates interneuron excitability. The effects of KChIP1 down-regulation were cell-specific since CA1 pyramidal cells that do not express KChIP1 were unaffected. Overall, our findings suggest that KChIP1 interacts with Kv4.3 in LM/RAD interneurons, enabling faster recovery from inactivation of A-type currents and thus promoting stronger inhibitory control of firing during sustained activity. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Crystal structures of five 1-alkyl-4-aryl-1,2,4-triazol-1-ium halide salts

PubMed Central

Guino-o, Marites A.; Talbot, Meghan O.; Slitts, Michael M.; Pham, Theresa N.; Audi, Maya C.; Janzen, Daron E.

2015-01-01

The asymmetric units for the salts 4-(4-fluoro­phen­yl)-1-isopropyl-1,2,4-triazol-1-ium iodide, C11H13FN3 +·I−, (1), 1-isopropyl-4-(4-methyl­phen­yl)-1,2,4-triazol-1-ium iodide, C12H16N3 +·I−, (2), 1-isopropyl-4-phenyl-1,2,4-triazol-1-ium iodide, C11H14N3 +·I−, (3), and 1-methyl-4-phenyl-1,2,4-triazol-1-ium iodide, C9H10N3 +·I−, (4), contain one cation and one iodide ion, whereas in 1-benzyl-4-phenyl-1,2,4-triazol-1-ium bromide monohydrate, C15H14N3 +·Br−·H2O, (5), there is an additional single water mol­ecule. There is a predominant C—H⋯X(halide) inter­action for all salts, resulting in a two-dimensional extended sheet network between the triazolium cation and the halide ions. For salts with para-substitution on the aryl ring, there is an additional π–anion inter­action between a triazolium carbon and iodide displayed by the layers. For salts without the para-substitution on the aryl ring, the π–π inter­actions are between the triazolium and aryl rings. The melting points of these salts agree with the predicted substituent inductive effects. PMID:26090137

QM/MM Investigation of Substrate and Product Specificities of Suv4-20h2: How Does This Enzyme Generate Dimethylated H4K20 from Monomethylated Substrate?

PubMed

Qian, Ping; Guo, Haobo; Wang, Liang; Guo, Hong

2017-06-13

Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine residues on histone proteins in the regulation of chromatin structure and gene expression. In contrast to many other PKMTs for which unmodified lysine is the methylation target, the enzymes in the Suv4-20 family are able to generate dimethylated product (H4K20me2) based exclusively on the monomethylated H4K20 substrate (H4K20me1). The origin of such substrate/product specificity is still not clear. Here, molecular dynamics (MD) and free energy (potential of mean force) simulations are undertaken using quantum mechanical/molecular mechanical (QM/MM) potentials to understand the substrate/product specificities of Suv4-20h2, a member of the Suv4-20 family. The free energy barriers for mono-, di-, and trimethylation in Suv4-20h2 obtained from the simulations are found to be well correlated with the specificities observed experimentally with the allowed dimethylation based on the H4K20me1 substrate and prohibited monomethylation and trimethylation based on H4K20 and H4K20me2, respectively. It is demonstrated that the reason for the relatively efficient dimethylation is an effective transition state (TS) stabilization through strengthening the CH···O interactions as well as the presence of a cation-π interaction at the transition state. The simulations also show that the failures of Suv4-20h2 to catalyze monomethylation and trimethylation are due, respectively, to a less effective TS stabilization and inability of the reactant complex containing H4K20me2 to adopt a reactive (near attack) configuration for methyl transfer. The results suggest that care must be exercised in the prediction of the substrate specificity based only on the existence of near attack configurations in substrate complexes.

Crystal Chemical Substitution at Ca and La Sites in CaLa4(SiO4)3O To Design the Composition Ca1- xM xLa4-xRE x(SiO4)3O for Nuclear Waste Immobilization and Its Influence on the Thermal Expansion Behavior.

PubMed

Ravikumar, Ramya; Gopal, Buvaneswari; Jena, Hrudananda

2018-06-04

The oxysilicate apatite host CaLa 4 (SiO 4 ) 3 O has been explored for immobilization of radioactive nuclides. Divalent ion, trivalent rare earth ion, and combined ionic substitutions in the silicate oxyapatite were carried out to optimize the simulated wasteform composition. The phases were characterized by powder X-ray diffraction, FT-IR, TGA, SEM-EDS, and HT-XRD techniques. The results revealed the effect of ionic substitutions on the structure and thermal expansion behavior. The investigation resulted in the formulation of simulated wasteforms such as La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O (WF-1) and Ca 0.8 Sr 0.1 Pb 0.1 La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O (WF-2). In comparison to the average axial thermal expansion coefficients of the hexagonal unit cell of the parent CaLa 4 (SiO 4 ) 3 O measured in the temperature range 298-1073 K (α' a = 9.74 × 10 -6 K -1 and α' c = 10.10 × 10 -6 K -1 ), rare earth ion substitution decreases the thermal expansion coefficients, as in the case of La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O (α' a = 8.67 × 10 -6 K -1 and α' c = 7.94 × 10 -6 K -1 ). However, the phase Ca 0.8 Sr 0.1 Pb 0.1 La 3.4 Ce 0.1 Pr 0.1 Nd 0.1 Sm 0.1 Gd 0.1 Y 0.1 (SiO 4 ) 3 O shows an increase in the values of thermal expansion coefficients: α' a = 11.74 × 10 -6 K -1 and α' c = 11.70 × 10 -6 K -1 .

Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.

PubMed

Kim, Sung Eun; Ahn, Hye Sook; Choi, Bok Hee; Jang, Hyun-Jong; Kim, Myung-Jun; Rhie, Duck-Joo; Yoon, Shin-Hee; Jo, Yang-Hyeok; Kim, Myung-Suk; Sung, Ki-Wug; Hahn, Sang June

2007-05-01

The effects of sibutramine on voltage-gated K+ channel (Kv)4.3, Kv1.3, and Kv3.1, stably expressed in Chinese hamster ovary cells, were investigated using the whole-cell patch-clamp technique. Sibutramine did not significantly decrease the peak Kv4.3 currents, but it accelerated the rate of decay of current inactivation in a concentration-dependent manner. This phenomenon was effectively characterized by integrating the total current over the duration of a depolarizing pulse to +40 mV. The IC50 value for the sibutramine block of Kv4.3 was 17.3 microM. Under control conditions, the inactivation of Kv4.3 currents could be fit to a biexponential function, and the time constants for the fast and slow components were significantly decreased after the application of sibutramine. The association (k+1) and dissociation (k-1) rate constants for the sibutramine block of Kv 4.3 were 1.51 microM-1s-1 and 27.35 s-1, respectively. The theoretical KD value, derived from k-1/k+1, yielded a value of 18.11 microM. The block of Kv4.3 by sibutramine displayed a weak voltage dependence, increasing at more positive potentials, and it was use-dependent at 2 Hz. Sibutramine did not affect the time course for the deactivating tail currents. Neither steady-state activation and inactivation nor the recovery from inactivation was affected by sibutramine. Sibutramine caused the concentration-dependent block of the Kv1.3 and Kv3.1 currents with an IC50 value of 3.7 and 32.7 microM, respectively. In addition, sibutramine reduced the tail current amplitude and slowed the deactivation of the tail currents of Kv1.3 and Kv3.1, resulting in a crossover phenomenon. These results indicate that sibutramine acts on Kv4.3, Kv1.3, and Kv3.1 as an open channel blocker.

Welding consumable selection for cryogenic (4{degrees}K) application

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

Kane, S.F.; Siewert, T.A.

1994-12-31

Brookhaven National Laboratory (BNL) has begun construction of a large (3.8 kilometer circumference) heavy ion collider for the Department of Energy. The collider uses superconducting magnets, operating at 4{degrees}K in supercritical helium, which meets the definition of a pressure vessel. The ASME Boiler & Pressure Vessel Code grants an exemption from impact testing to certain metals, but only for operating temperatures down to 20{degrees}K. Research and the latest change to ASTM Standard E23 have invalidated Charpy testing at 4{degrees}K, thus compliance with the Code is not possible. This effort was undertaken to identify the weld process and weld material necessarymore » to comply with the intent of the Code (impact test) requirements, that is, to design a weld joint that will assure adequate fracture toughness. We will report the results of this development and testing, and conclude that nitrogen and maganese enhanced 385L provides a superior weld metal for 4{degrees}K cryogenic applications without the exaggerated purity concerns normally associated with superaustenitic weld materials. This development has been so successful that BNL has procured 15,000 pounds of this material for magnet production. Oxygen content, manifested as inclusion density, has the single most significant effect upon fracture toughness and impact strength. Finally, we report that GMAW is a viable welding process, using off-the-shelf equipment, for 4{degrees}K cryogenic applications.« less

A Genetically Encoded Probe for Live-Cell Imaging of H4K20 Monomethylation.

PubMed

Sato, Yuko; Kujirai, Tomoya; Arai, Ritsuko; Asakawa, Haruhiko; Ohtsuki, Chizuru; Horikoshi, Naoki; Yamagata, Kazuo; Ueda, Jun; Nagase, Takahiro; Haraguchi, Tokuko; Hiraoka, Yasushi; Kimura, Akatsuki; Kurumizaka, Hitoshi; Kimura, Hiroshi

2016-10-09

Eukaryotic gene expression is regulated in the context of chromatin. Dynamic changes in post-translational histone modification are thought to play key roles in fundamental cellular functions such as regulation of the cell cycle, development, and differentiation. To elucidate the relationship between histone modifications and cellular functions, it is important to monitor the dynamics of modifications in single living cells. A genetically encoded probe called mintbody (modification-specific intracellular antibody), which is a single-chain variable fragment tagged with a fluorescent protein, has been proposed as a useful visualization tool. However, the efficacy of intracellular expression of antibody fragments has been limited, in part due to different environmental conditions in the cytoplasm compared to the endoplasmic reticulum where secreted proteins such as antibodies are folded. In this study, we have developed a new mintbody specific for histone H4 Lys20 monomethylation (H4K20me1). The specificity of the H4K20me1-mintbody in living cells was verified using yeast mutants and mammalian cells in which this target modification was diminished. Expression of the H4K20me1-mintbody allowed us to monitor the oscillation of H4K20me1 levels during the cell cycle. Moreover, dosage-compensated X chromosomes were visualized using the H4K20me1-mintbody in mouse and nematode cells. Using X-ray crystallography and mutational analyses, we identified critical amino acids that contributed to stabilization and/or proper folding of the mintbody. Taken together, these data provide important implications for future studies aimed at developing functional intracellular antibodies. Specifically, the H4K20me1-mintbody provides a powerful tool to track this particular histone modification in living cells and organisms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

K0.78Na0.22MoO2AsO4

PubMed Central

Jouini, Raja; Bouzidi, Chahira; Zid, Mohamed Faouzi; Driss, Ahmed

2013-01-01

The title compound, potassium sodium dioxidomolybden­um(VI) arsenate, K0.78Na0.22MoO2AsO4, was synthesized by a solid-state reaction route. The structure is built up from corner-sharing MoO6 octa­hedra and AsO4 tetra­hedra, creating infinite [MoAsO8]∞ chains running along the b-axis direction. As, Mo and all but one O atom are on special positions (4c) with m symmetry and K (occupancy 0.78) is on a position (4a) of -1 in the tunnels. The possible motion of the alkali cations has been investigated by means of the bond-valance sum (BVS) model. The simulation shows that the Na+ motion appears to be easier mainly along the b-axis direction. Structural relationships between the different compounds of the AMoO2AsO4 (A = Ag, Li, Na, K, Rb) series and MXO8 (M = V; X = P, As) chains are discussed. PMID:24109253

Critical Temperature of Randomly Diluted Two-Dimensional Heisenberg Ferromagnet, K2CuxZn(1-x)F4

NASA Astrophysics Data System (ADS)

Okuda, Yuichi; Tohi, Yasuto; Yamada, Isao; Haseda, Taiichiro

1980-09-01

The susceptibility of randomly diluted two-dimensional Heisenberg-like ferromagnet K2CuxZn(1-x)F4 was measured down to 50 mK, using the 3He-4He dilution refrigerator and a SQUID magnetometer. The ferromagnetic critical temperature Tc(x) was obtained for x{=}0.98, 0.94, 0.85, 0.82, 0.68, 0.60, 0.54, 0.50 and 0.42. The value of [1/Tc(1)][(d/dx)Tc(x)]x=1 was approximately 3.0. The critical temperature versus x curve exhibits a noticeable tail near the critical concentration, which may stem from the second nearest-neighbor interaction. The critical concentration xc, below which concentration there is no long range order down to T{=}0 K, was estimated to be 0.45˜0.50. The susceptibility of sample with x{=}0.42 behaves as if it obeys the Curie law down to 50 mK.

40 CFR 721.7160 - 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1...

Code of Federal Regulations, 2011 CFR

2011-07-01

... new uses subject to reporting. (1) The chemical substance 2-oxepanone, polymer with 4,4′(1-meth-yl-eth-yli-dene)bi-sphen-ol and 2,2-[(1-meth-yl-eth-yli-dene) bis(4,1-phen-yl-ene-oxy-meth-ylene)]bi-soxi...

40 CFR 721.7160 - 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1...

Code of Federal Regulations, 2013 CFR

2013-07-01

... new uses subject to reporting. (1) The chemical substance 2-oxepanone, polymer with 4,4′(1-meth-yl-eth-yli-dene)bi-sphen-ol and 2,2-[(1-meth-yl-eth-yli-dene) bis(4,1-phen-yl-ene-oxy-meth-ylene)]bi-soxi...

40 CFR 721.7160 - 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1...

Code of Federal Regulations, 2014 CFR

2014-07-01

... new uses subject to reporting. (1) The chemical substance 2-oxepanone, polymer with 4,4′(1-meth-yl-eth-yli-dene)bi-sphen-ol and 2,2-[(1-meth-yl-eth-yli-dene) bis(4,1-phen-yl-ene-oxy-meth-ylene)]bi-soxi...

40 CFR 721.7160 - 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1...

Code of Federal Regulations, 2012 CFR

2012-07-01

... new uses subject to reporting. (1) The chemical substance 2-oxepanone, polymer with 4,4′(1-meth-yl-eth-yli-dene)bi-sphen-ol and 2,2-[(1-meth-yl-eth-yli-dene) bis(4,1-phen-yl-ene-oxy-meth-ylene)]bi-soxi...

Optical coherence of 166Er:7LiYF4 crystal below 1 K

NASA Astrophysics Data System (ADS)

Kukharchyk, N.; Sholokhov, D.; Morozov, O.; Korableva, S. L.; Kalachev, A. A.; Bushev, P. A.

2018-02-01

We explore optical coherence and spin dynamics of an isotopically purified 166Er:7LiYF4 crystal below 1 K and at weak magnetic fields < 0.3T. Crystals were grown in our lab and demonstrate narrow inhomogeneous optical broadening down to 16 MHz. Solid-state atomic ensembles with such narrow linewidths are very attractive for implementing of off-resonant Raman quantum memory and for the interfacing of superconducting quantum circuits and telecom C-band optical photons. Both applications require a low magnetic field of ∼10 mT. However, at conventional experimental temperatures T > 1.5 K, optical coherence of Er:LYF crystal attains ≃ 10 μ {{s}} time scale only at strong magnetic fields above 1.5 T. In the present work, we demonstrate that the deep freezing of Er:LYF crystal below 1 K results in the increase of optical coherence time to ≃ 100 μ {{s}} at weak fields.

Excretion, metabolism, and pharmacokinetics of 1-(8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl)-4-(ethylamino)piperidine-4-carboxamide, a selective cannabinoid receptor antagonist, in healthy male volunteers.

PubMed

Miao, Zhuang; Sun, Hao; Liras, Jennifer; Prakash, Chandra

2012-03-01

The disposition of 1-(8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H- purin-6-yl)-4-(ethylamino)-piperidine-4-carboxamide (CP-945,598), an orally active antagonist of the cannabinoid CB1 receptor, was studied after a single 25-mg oral dose of [(14)C]CP-945,598 to healthy human subjects. Serial blood samples and complete urine and feces were collected up to 672 h after dose. The mean total recovery of radioactivity was 60.1 ± 12.8 from the urine and feces, with the majority of the dose excreted in the feces. The absorption of CP-945,598 in humans was slow with T(max) at 6 h. Less than 2% of the dose was recovered as unchanged drug in the combined excreta, suggesting that CP-945,598 is extensively metabolized. The primary metabolic pathway of CP-945,598 involved N-de-ethylation to form an N-desethyl metabolite (M1), which was then subsequently metabolized by amide hydrolysis (M2), N-hydroxylation (M3), piperidine ring hydroxylation (M6), and ribose conjugation (M9). M3 was further metabolized to oxime (M4) and keto (M5) metabolites. M1, M4, and M5 were the major circulating metabolites, with AUC((0-48)) values 4.7-, 1.5-, and 1.1-fold greater than that of CP-945,598. M1, M2, and M9 accounted for 5.6, 33.6, and 6.30% of the dose, respectively, in excreta. The results from in vitro experiments with recombinant isoforms suggested that the oxidative metabolism of CP-945,598 to M1 is catalyzed primarily by CYP3A4/3A5. The molecular docking study showed that the N-ethyl moiety of CP-945,598 can access to the heme iron-oxo of CYP3A4 in an energetically favored orientation. Together, these data suggest that CP-945,598 is well absorbed and eliminated largely by CYP3A4/3A5-catalyzed metabolism.

Effects of Nickel Treatment on H3K4 Trimethylation and Gene Expression

PubMed Central

Tchou-Wong, Kam-Meng; Kluz, Thomas; Arita, Adriana; Smith, Phillip R.; Brown, Stuart; Costa, Max

2011-01-01

Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3), a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s) underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq) and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq). The effect of NiCl2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs) on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl2. This study may provide insights into the epigenetic mechanism(s) underlying the carcinogenicity of nickel compounds. PMID:21455298

Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2P background K+ channel TASK-2

PubMed Central

Niemeyer, María Isabel; Cid, L. Pablo; Paulais, Marc; Teulon, Jacques; Sepúlveda, Francisco V.

2017-01-01

Two-pore domain K2P K+ channels responsible for the background K+ conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K2P channels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P2, common among other classes of K+ channels, affects K2P channels is controversial. Here we show that K2P K+ channel TASK-2 requires PI(4,5)P2 for activity, a dependence that accounts for its run down in the absence of intracellular ATP and its full recovery by addition of exogenous PI(4,5)P2, its inhibition by low concentrations of polycation PI scavengers, and inhibition by PI(4,5)P2 depletion from the membrane. Comprehensive mutagenesis suggests that PI(4,5)P2 interaction with TASK-2 takes place at C-terminus where three basic aminoacids are identified as being part of a putative binding site. PMID:28358046

Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2P background K+ channel TASK-2.

PubMed

Niemeyer, María Isabel; Cid, L Pablo; Paulais, Marc; Teulon, Jacques; Sepúlveda, Francisco V

2017-03-30

Two-pore domain K 2P K + channels responsible for the background K + conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K 2P channels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P 2 , common among other classes of K + channels, affects K 2P channels is controversial. Here we show that K 2P K + channel TASK-2 requires PI(4,5)P 2 for activity, a dependence that accounts for its run down in the absence of intracellular ATP and its full recovery by addition of exogenous PI(4,5)P 2 , its inhibition by low concentrations of polycation PI scavengers, and inhibition by PI(4,5)P 2 depletion from the membrane. Comprehensive mutagenesis suggests that PI(4,5)P 2 interaction with TASK-2 takes place at C-terminus where three basic aminoacids are identified as being part of a putative binding site.

Respiratory motion resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK)

PubMed Central

Han, Fei; Zhou, Ziwu; Cao, Minsong; Yang, Yingli; Sheng, Ke; Hu, Peng

2017-01-01

Purpose To propose and validate a respiratory motion resolved, self-gated (SG) 4D-MRI technique to assess patient-specific breathing motion of abdominal organs for radiation treatment planning. Methods The proposed 4D-MRI technique was based on the balanced steady-state free-precession (bSSFP) technique and 3D k-space encoding. A novel ROtating Cartesian K-space (ROCK) reordering method was designed that incorporates repeatedly sampled k-space centerline as the SG motion surrogate and allows for retrospective k-space data binning into different respiratory positions based on the amplitude of the surrogate. The multiple respiratory-resolved 3D k-space data were subsequently reconstructed using a joint parallel imaging and compressed sensing method with spatial and temporal regularization. The proposed 4D-MRI technique was validated using a custom-made dynamic motion phantom and was tested in 6 healthy volunteers, in whom quantitative diaphragm and kidney motion measurements based on 4D-MRI images were compared with those based on 2D-CINE images. Results The 5-minute 4D-MRI scan offers high-quality volumetric images in 1.2×1.2×1.6mm3 and 8 respiratory positions, with good soft-tissue contrast. In phantom experiments with triangular motion waveform, the motion amplitude measurements based on 4D-MRI were 11.89% smaller than the ground truth, whereas a −12.5% difference was expected due to data binning effects. In healthy volunteers, the difference between the measurements based on 4D-MRI and the ones based on 2D-CINE were 6.2±4.5% for the diaphragm, 8.2±4.9% and 8.9±5.1% for the right and left kidney. Conclusion The proposed 4D-MRI technique could provide high resolution, high quality, respiratory motion resolved 4D images with good soft-tissue contrast and are free of the “stitching” artifacts usually seen on 4D-CT and 4D-MRI based on resorting 2D-CINE. It could be used to visualize and quantify abdominal organ motion for MRI-based radiation treatment

Respiratory motion-resolved, self-gated 4D-MRI using rotating cartesian k-space (ROCK).

PubMed

Han, Fei; Zhou, Ziwu; Cao, Minsong; Yang, Yingli; Sheng, Ke; Hu, Peng

2017-04-01

To propose and validate a respiratory motion resolved, self-gated (SG) 4D-MRI technique to assess patient-specific breathing motion of abdominal organs for radiation treatment planning. The proposed 4D-MRI technique was based on the balanced steady-state free-precession (bSSFP) technique and 3D k-space encoding. A novel rotating cartesian k-space (ROCK) reordering method was designed which incorporates repeatedly sampled k-space centerline as the SG motion surrogate and allows for retrospective k-space data binning into different respiratory positions based on the amplitude of the surrogate. The multiple respiratory-resolved 3D k-space data were subsequently reconstructed using a joint parallel imaging and compressed sensing method with spatial and temporal regularization. The proposed 4D-MRI technique was validated using a custom-made dynamic motion phantom and was tested in six healthy volunteers, in whom quantitative diaphragm and kidney motion measurements based on 4D-MRI images were compared with those based on 2D-CINE images. The 5-minute 4D-MRI scan offers high-quality volumetric images in 1.2 × 1.2 × 1.6 mm 3 and eight respiratory positions, with good soft-tissue contrast. In phantom experiments with triangular motion waveform, the motion amplitude measurements based on 4D-MRI were 11.89% smaller than the ground truth, whereas a -12.5% difference was expected due to data binning effects. In healthy volunteers, the difference between the measurements based on 4D-MRI and the ones based on 2D-CINE were 6.2 ± 4.5% for the diaphragm, 8.2 ± 4.9% and 8.9 ± 5.1% for the right and left kidney. The proposed 4D-MRI technique could provide high-resolution, high-quality, respiratory motion-resolved 4D images with good soft-tissue contrast and are free of the "stitching" artifacts usually seen on 4D-CT and 4D-MRI based on resorting 2D-CINE. It could be used to visualize and quantify abdominal organ motion for MRI-based radiation treatment planning. © 2017 American

Mixed-metal uranium(VI) iodates: hydrothermal syntheses, structures, and reactivity of Rb[UO(2)(CrO(4))(IO(3))(H(2)O)], A(2)[UO(2)(CrO(4))(IO(3))(2)] (A = K, Rb, Cs), and K(2)[UO(2)(MoO(4))(IO(3))(2)].

PubMed

Sykora, Richard E; McDaniel, Steven M; Wells, Daniel M; Albrecht-Schmitt, Thomas E

2002-10-07

The reactions of the molecular transition metal iodates A[CrO(3)(IO(3))] (A = K, Rb, Cs) with UO(3) under mild hydrothermal conditions provide access to four new, one-dimensional, uranyl chromatoiodates, Rb[UO(2)(CrO(4))(IO(3))(H(2)O)] (1) and A(2)[UO(2)(CrO(4))(IO(3))(2)] (A = K (2), Rb (3), Cs (4)). Under basic conditions, MoO(3), UO(3), and KIO(4) can be reacted to form K(2)[UO(2)(MoO(4))(IO(3))(2)] (5), which is isostructural with 2 and 3. The structure of 1 consists of one-dimensional[UO(2)(CrO(4))(IO(3))(H(2)O)](-) ribbons that contain uranyl moieties bound by bridging chromate and iodate anions as well as a terminal water molecule to create [UO(7)] pentagonal bipyramidal environments around the U(VI) centers. These ribbons are separated from one another by Rb(+) cations. When the iodate content is increased in the hydrothermal reactions, the terminal water molecule is replaced by a monodentate iodate anion to yield 2-4. These ribbons can be further modified by replacing tetrahedral chromate anions with MoO(4)(2)(-) anions to yield isostructural, one-dimensional [UO(2)(MoO(4))(IO(3))(2)](2)(-) ribbons. Crystallographic data: 1, triclinic, space group P(-)1, a = 7.3133(5) A, b = 8.0561(6) A, c = 8.4870(6) A, alpha = 88.740(1) degrees, beta = 87.075(1) degrees, gamma = 71.672(1) degrees, Z = 2; 2, monoclinic, space group P2(1)/c, a = 11.1337(5) A, b = 7.2884(4) A, c = 15.5661(7) A, beta = 107.977(1) degrees, Z = 4; 3, monoclinic, space group P2(1)/c, a = 11.3463(6) A, b = 7.3263(4) A, c = 15.9332(8) A, beta = 108.173(1) degrees, Z = 4; 4, monoclinic, space group P2(1)/n, a = 7.3929(5) A, b = 8.1346(6) A, c = 22.126(2) A, beta = 90.647(1) degrees, Z = 4; 5, monoclinic, space group P2(1)/c, a = 11.3717(6) A, b = 7.2903(4) A, c = 15.7122(8) A, beta = 108.167(1) degrees, Z = 4.

Oxothiomolybdenum derivatives of the superlacunary crown heteropolyanion {P8W48}: structure of [K4{Mo4O4S4(H2O)3(OH)2}2(WO2)(P8W48O184)]30– and studies in solution.

PubMed

Korenev, Vladimir S; Floquet, Sébastien; Marrot, Jérôme; Haouas, Mohamed; Mbomekallé, Israël-Martyr; Taulelle, Francis; Sokolov, Maxim N; Fedin, Vladimir P; Cadot, Emmanuel

2012-02-20

Reaction of the cyclic lacunary [H(7)P(8)W(48)O(184)](33-) anion (noted P(8)W(48)) with the [Mo(2)S(2)O(2)(H(2)O)(6)](2+) oxothiocation led to two compounds, namely, [K(4){Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(WO(2))(P(8)W(48)O(184))](30-) (denoted 1) and [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) (denoted 2), which were characterized in the solid state and solution. In the solid state, the structure of [K(4){Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(WO(2))(P(8)W(48)O(184))](30-) reveals the presence of two disordered {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) "handles" connected on both sides of the P(8)W(48) ring. Such a disorder is consistent with the presence of two geometrical isomers where the relative disposition of the two {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) handles are arranged in a perpendicular or parallel mode. Such an interpretation is fully supported by (31)P and (183)W NMR solution studies. The relative stability of both geometrical isomers appears to be dependent upon the nature of the internal alkali cations, i.e., Na(+) vs K(+), and increased lability of the two {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) handles, compared to the oxo analogous, was clearly identified by significant broadening of the (31)P and (183)W NMR lines. Solution studies carried out by UV-vis spectroscopy showed that formation of the adduct [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) occurs in the 1.5-4.7 pH range and corresponds to a fast and quantitative condensation process. Furthermore, (31)P NMR titrations in solution reveal formation of the "monohandle" derivative [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(P(8)W(48)O(184))](38-) as an intermediate prior to formation of the "bishandle" derivatives. Furthermore, the electrochemical behavior of [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) was studied in aqueous medium and compared with the parent anion P(8)W(48).

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_FM1+FM4_Edition2)

NASA Technical Reports Server (NTRS)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-31] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

CERES ERBE-like Monthly Geographical Averages (ES-4) in HDF (CER_ES4_Aqua-FM4_Edition1-CV)

NASA Technical Reports Server (NTRS)

Wielicki, Bruce A. (Principal Investigator)

The ERBE-like Monthly Geographical Averages (ES-4) product contains a month of space and time averaged Clouds and the Earth's Radiant Energy System (CERES) data for a single scanner instrument. The ES-4 is also produced for combinations of scanner instruments. For each observed 2.5-degree spatial region, the daily average, the hourly average over the month, and the overall monthly average of shortwave and longwave fluxes at the Top-of-the-Atmosphere (TOA) from the CERES ES-9 product are spatially nested up from 2.5-degree regions to 5- and 10-degree regions, to 2.5-, 5-, and 10-degree zonal averages, and to global monthly averages. For each nested area, the albedo and net flux are given. For each region, the daily average flux is estimated from an algorithm that uses the available hourly data, scene identification data, and diurnal models. This algorithm is 'like' the algorithm used for the Earth Radiation Budget Experiment (ERBE). The following CERES ES4 data sets are currently available: CER_ES4_FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition1 CER_ES4_PFM+FM1+FM2_Edition2 CER_ES4_PFM+FM1_Edition1 CER_ES4_PFM+FM2_Edition1 CER_ES4_TRMM-PFM_Edition1 CER_ES4_TRMM-PFM_Edition2 CER_ES4_Terra-FM1_Edition1 CER_ES4_Terra-FM2_Edition1 CER_ES4_FM1+FM2_Edition2 CER_ES4_Terra-FM1_Edition2 CER_ES4_Terra-FM2_Edition2 CER_ES4_Aqua-FM3_Edition1 CER_ES4_Aqua-FM4_Edition1 CER_ES4_FM1+FM2+FM3+FM4_Edition1 CER_ES4_Aqua-FM3_Edition2 CER_ES4_Aqua-FM4_Edition2 CER_ES4_FM1+FM3_Edition2 CER_ES4_FM1+FM4_Edition2 CER_ES4_PFM+FM1_Edition2 CER_ES4_PFM+FM2_Edition2 CER_ES4_Aqua-FM3_Edition1-CV CER_ES4_Aqua-FM4_Edition1-CV CER_ES4_Terra-FM1_Edition1-CV CER_ES4_Terra-FM2_Edition1-CV. [Location=GLOBAL] [Temporal_Coverage: Start_Date=1998-01-01; Stop_Date=2005-03-29] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=2.5 degree; Longitude_Resolution=2.5 degree; Horizontal

26 CFR 1.4-4 - Short taxable year caused by death.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 1 2012-04-01 2012-04-01 false Short taxable year caused by death. 1.4-4... TAXES Normal Taxes and Surtaxes § 1.4-4 Short taxable year caused by death. An individual making a... taxable year results from the death of the taxpayer. Tax on Corporations ...

26 CFR 1.4-4 - Short taxable year caused by death.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 1 2013-04-01 2013-04-01 false Short taxable year caused by death. 1.4-4... TAXES Normal Taxes and Surtaxes § 1.4-4 Short taxable year caused by death. An individual making a... taxable year results from the death of the taxpayer. Tax on Corporations ...

Bulk superconductivity in bismuth oxysulfide Bi4O4S3.

PubMed

Singh, Shiva Kumar; Kumar, Anuj; Gahtori, Bhasker; Shruti; Sharma, Gyaneshwar; Patnaik, Satyabrata; Awana, Veer P S

2012-10-10

A very recent report on the observation of superconductivity in Bi(4)O(4)S(3) [Mizuguchi, Y.; http://arxiv.org/abs/1207.3145] could potentially reignite the search for superconductivity in a broad range of layered sulfides. We report here the synthesis of Bi(4)O(4)S(3) at 500 °C by a vacuum encapsulation technique and its basic characterizations. The as-synthesized Bi(4)O(4)S(3) was contaminated with small amounts of Bi(2)S(3) and Bi impurities. The majority phase was found to be tetragonal (space group I4/mmm) with lattice parameters a = 3.9697(2) Å and c = 41.3520(1) Å. Both AC and DC magnetization measurements confirmed that Bi(4)O(4)S(3) is a bulk superconductor with a superconducting transition temperature (T(c)) of 4.4 K. Isothermal magnetization (M-H) measurements indicated closed loops with clear signatures of flux pinning and irreversible behavior. The lower critical field (H(c1)) at 2 K for the new superconductor was found to be ~15 Oe. Magnetotransport measurements showed a broadening of the resistivity (ρ) and a decrease in T(c) (ρ = 0) with increasing magnetic field. The extrapolated upper critical field H(c2)(0) was ~31 kOe with a corresponding Ginzburg-Landau coherence length of ~100 Å . In the normal state, the ρ ~ T(2) dependence was not indicated. Hall resistivity data showed a nonlinear magnetic field dependence. Our magnetization and electrical transport measurements substantiate the appearance of bulk superconductivity in as-synthesized Bi(4)O(4)S(3). On the other hand, Bi heat-treated at the same temperature is not superconducting, thus excluding the possibility of impurity-driven superconductivity in the newly discovered superconductor Bi(4)O(4)S(3).

Nanoelectronic primary thermometry below 4 mK

PubMed Central

Bradley, D. I.; George, R. E.; Gunnarsson, D.; Haley, R. P.; Heikkinen, H.; Pashkin, Yu. A.; Penttilä, J.; Prance, J. R.; Prunnila, M.; Roschier, L.; Sarsby, M.

2016-01-01

Cooling nanoelectronic structures to millikelvin temperatures presents extreme challenges in maintaining thermal contact between the electrons in the device and an external cold bath. It is typically found that when nanoscale devices are cooled to ∼10 mK the electrons are significantly overheated. Here we report the cooling of electrons in nanoelectronic Coulomb blockade thermometers below 4 mK. The low operating temperature is attributed to an optimized design that incorporates cooling fins with a high electron–phonon coupling and on-chip electronic filters, combined with low-noise electronic measurements. By immersing a Coulomb blockade thermometer in the 3He/4He refrigerant of a dilution refrigerator, we measure a lowest electron temperature of 3.7 mK and a trend to a saturated electron temperature approaching 3 mK. This work demonstrates how nanoelectronic samples can be cooled further into the low-millikelvin range. PMID:26816217

The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

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

Khan, Maruf H.; Hart, Matthew J., E-mail: HartMJ@uthscsa.edu; Rea, Shane L., E-mail: reas3@uthscsa.edu

2012-08-24

Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that hasmore » recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.« less

26 CFR 1.4-4 - Short taxable year caused by death.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Short taxable year caused by death. 1.4-4 Section... Normal Taxes and Surtaxes § 1.4-4 Short taxable year caused by death. An individual making a return for a... results from the death of the taxpayer. Tax on Corporations ...

26 CFR 1.4-4 - Short taxable year caused by death.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 1 2011-04-01 2009-04-01 true Short taxable year caused by death. 1.4-4 Section... Normal Taxes and Surtaxes § 1.4-4 Short taxable year caused by death. An individual making a return for a... results from the death of the taxpayer. Tax on Corporations ...

The two-dimensional tunnel structures of K3Sb5O14 and K2Sb4O11

NASA Technical Reports Server (NTRS)

Hong, H. Y.-P.

1974-01-01

The structures of K3Sb5O14 and K2Sb4O11 have been solved by the single-crystal X-ray direct method and the heavy-atom method, respectively. The structure of K3Sb5O14 is orthorhombic, with space group Pbam and cell parameters a = 24.247 (4), b = 7.157 (2), c = 7.334 (2) A, Z = 4. The structure of K2Sb4O11 is monoclinic, with space group C2/m and cell parameters a = 19.473 (4), b = 7.542 (1), c = 7.198 (1) A, beta = 94.82 (2) deg, Z = 4. A full-matrix least-squares refinement gave R = 0.072 and R = 0.067, respectively. In both structures, oxygen atoms form an octahedron around each Sb atom and an irregular polyhedron around each K atom. By sharing corners and edges, the octahedra form a skeleton network having intersecting b-axis and c-axis tunnels. The K(+) ions, which have more than ten oxygen near neighbors, are located in these tunnels. Evidence for K(+)-ion transport within and between tunnels comes from ion exchange of the alkali ions in molten salts and anisotropic temperature factors that are anomalously large in the direction of the tunnels.

Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron

PubMed Central

Cornelius, Ryan J.; Wen, Donghai; Hatcher, Lori I.

2012-01-01

Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH4Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia. PMID:22993067

The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer.

PubMed

Vandercappellen, Jo; Van Damme, Jo; Struyf, Sofie

2011-02-01

Chemokines are chemotactic cytokines which recruit leukocytes to inflammatory sites. They also affect tumor development and metastasis by acting as growth factor, by attracting pro- or anti-tumoral leukocytes or by influencing angiogenesis. Platelet factor-4 (CXCL4/PF-4) was the first chemokine shown to inhibit angiogenesis. CXCL4L1/PF-4var, recently isolated from thrombin-stimulated platelets, differing from authentic CXCL4/PF-4 in three carboxy-terminally located amino acids, was found to be more potent than CXCL4/PF-4 in inhibiting angiogenesis and tumor growth. Both glycosaminoglycans (GAG) and CXCR3 are implicated in the activities of the PF-4 variants. This report reviews the current knowledge on the role of CXCL4/PF-4 and CXCL4L1/PF-4var in physiological and pathological processes. In particular, the role of CXCL4/PF-4 in cancer, heparin-induced thrombocytopenia and atherosclerosis is described. Copyright © 2010 Elsevier Ltd. All rights reserved.

Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

DOE PAGES

Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; ...

2015-07-13

The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T 37/T 46, followed by T 70 and S 65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is amore » goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, 54YXXXXLΦ 60 (motif 1) but lack known phosphorylation sites. We report in this paper a 2.1-Å crystal structure of mouse eIF4E in complex with m 7GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP1 50–84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S 65 and T 70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1–mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. Finally, the binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.« less

12 CFR 4.75 - Waivers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... restrictions set forth in section 10(k) of the FDI Act (12 U.S.C. 1820(k)) and § 4.74 do not apply to any.... The post-employment restrictions set forth in section 10(k) of the FDI Act (12 U.S.C. 1820(k)) and § 4... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Waivers. 4.75 Section 4.75 Banks and Banking...

Dissociative adsorption of CCl 4 on the Fe 3O 4(1 1 1)-(2×2) selvedge of α-Fe 2O 3(0 0 0 1)

NASA Astrophysics Data System (ADS)

Adib, K.; Mullins, D. R.; Totir, G.; Camillone, N.; Fitts, J. P.; Rim, K. T.; Flynn, G. W.; Osgood, R. M.

2003-02-01

The surface reactions of CCl 4 with the Fe 3O 4(1 1 1)-(2×2) selvedge of naturally occurring α-Fe 2O 3(0 0 0 1) single-crystals have been investigated using synchrotron X-ray photoelectron spectroscopy (XPS) and temperature-programmed desorption (TPD). CCl 4 was found to dissociate on the Fe 3O 4 surface at 100 K producing chemisorbed Cl and adsorbed CCl 2. TPD shows that the large majority of the dissociatively adsorbed CCl 2 fragments extract lattice oxygen and desorb as phosgene at >275 K. However, the XPS spectra show no evidence for the formation of surface-bound phosgene, at 100 K, indicating that its formation involves two steps. The first step, dissociation, is spontaneous at 100 K, whereas the second, oxygen atom abstraction to form phosgene, requires thermal excitation. Cl chemisorption yielded two separate species, the mono- and dichloride terminations of surface iron sites. The identification of these two surface terminations is based on the coverage dependence and the surface temperature history of their Cl 2p 3/2 peak intensity. For example, heating to >450 K allows the monochloride to transform into iron dichloride, indicating Cl adatom mobility at these temperatures.

Phase transitions in (NH4)2MoO2F4 crystal

NASA Astrophysics Data System (ADS)

Krylov, Alexander; Laptash, Natalia; Vtyurin, Alexander; Krylova, Svetlana

2016-11-01

The mechanisms of temperature and high pressure phase transitions have been studied by Raman spectroscopy. Room temperature (295 K) experiments under high hydrostatic pressure up to 3.6 GPa for (NH4)2 MoO2 F4 have been carried out. Experimental data indicates a phase transition into a new high-pressure phase for (NH4)2 MoO2 F4 at 1.2 GPa. This phase transition is related to the ordering anion octahedron groups [MoO2 F4]2- and is not associated with ammonium group. Raman spectra of small non-oriented crystals ranging from 10 to 350 K have been observed. The experiment shows anion groups [MoO2 F4]2- and ammonium in high temperature phase are disordered. The phase transition at T1 = 269.8 K is of the first-order, close to the tricritical point. The first temperature phase transition is related to the ordering anion octahedron groups [MoO2 F4]2-. Second phase transitions T2 = 180 K are associated with the ordering of ammonium. The data presented within this study demonstrate that 2D correlation analysis combined with traditional Raman spectroscopy are powerful tool to study phase transitions in the crystals.

Compositions of supersaturated solutions for enhanced growth of {alpha}-NiSO{sub 4} . 6H{sub 2}O, Me{sub 2}Ni(SO{sub 4}){sub 2} . 6H{sub 2}O, MeH{sub 2}PO{sub 4} [Me = Li, Na, K, Rb, Cs, NH{sub 4}], and K(H{sub x}D{sub 1-x}){sub 2}PO{sub 4} single crystals

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

Soboleva, L. V., E-mail: afkonst@ns.crys.ras.ru

2008-05-15

The possibility of determining the optimal compositions and temperatures of supersaturated solutions for enhanced growth of single crystals of congruently and incongruently dissolving solid phases from the solubility diagrams of ternary systems is shown, and this approach is justified. The NiSO{sub 4}-H{sub 2}SO{sub 4}-H{sub 2}O, Me{sub 2}SO{sub 4}-NiSO{sub 4}-H{sub 2}O, and Me{sub 2}O-P{sub 2}O{sub 5}-H{sub 2}O(D{sub 2}O) systems have been used to determine the optimal compositions and temperatures of supersaturated solutions for growth of {alpha}-NiSO{sub 4} . 6H{sub 2}O, Me{sub 2}Ni(SO{sub 4}){sub 2} . 6H{sub 2}O, MeH{sub 2}PO{sub 4} [Me = Li, Na, K, Rb, Cs, NH{sub 4}], and Kmore » (H{sub x} D{sub 1-x}){sub 2}PO{sub 4} (D is deuterium) single crystals.« less

Water activities of NaClO4, Ca(ClO4)2, and Mg(ClO4)2 brines from experimental heat capacities: Water activity >0.6 below 200 K

NASA Astrophysics Data System (ADS)

Toner, J. D.; Catling, D. C.

2016-05-01

Perchlorate salts found on Mars are extremely hygroscopic and form low eutectic temperature aqueous solutions, which could allow liquid water to exist on Mars despite cold and dry conditions. The formation, dynamics, and potential habitability of perchlorate salt solutions can be broadly understood in terms of water activity. Water activity controls condensation and evaporation of water vapor in brines, deliquescence and efflorescence of crystalline salts, and ice formation during freezing. Furthermore, water activity is a basic parameter defining the habitability of aqueous solutions. Despite the importance of water activity, its value in perchlorate solutions has only been measured at 298.15 K and at the freezing point of water. To address this lack of data, we have determined water activities in NaClO4, Ca(ClO4)2, and Mg(ClO4)2 solutions using experimental heat capacities measured by Differential Scanning Calorimetry. Our results include concentrations up to near-saturation and temperatures ranging from 298.15 to 178 K. We find that water activities in NaClO4 solutions increase with decreasing temperature, by as much as 0.25 aw from 298.15 to 178 K. Consequently, aw reaches ∼0.6-0.7 even for concentrations up to 15 molal NaClO4 below 200 K. In contrast, water activities in Ca(ClO4)2 and Mg(ClO4)2 solutions generally decrease with decreasing temperature. The temperature dependence of water activity indicates that low-temperature NaClO4 solutions will evaporate and deliquesce at higher relative humidity, crystallize ice at higher temperature, and potentially be more habitable for life (at least in terms of water activity) compared to solutions at 298.15 K. The opposite effects occur in Ca(ClO4)2 and Mg(ClO4)2 solutions.

Anisotropic thermodynamic and transport properties of single-crystalline CaKFe 4 As 4

DOE PAGES

Meier, W. R.; Kong, T.; Kaluarachchi, U. S.; ...

2016-08-01

We grew single-crystalline, single-phase CaKFe 4As 4 out of a high-temperature, quaternary melt. Temperature-dependent measurements of x-ray diffraction, anisotropic electrical resistivity, elastoresistivity, thermoelectric power, Hall effect, magnetization, and specific heat, combined with field-dependent measurements of electrical resistivity and field and pressure-dependent measurements of magnetization indicate that CaKFe 4As 4 is an ordered, stoichiometric, Fe-based superconductor with a superconducting critical temperature, T c=35.0±0.2 K. Other than superconductivity, there is no indication of any other phase transition for 1.8K≤T≤300 K. All of these thermodynamic and transport data reveal striking similarities to those found for optimally or slightly overdoped (Ba 1-xKx)Fe 2As 2, suggesting that stoichiometric CaKFe 4As 4 is intrinsically close to what is referred to as “optimal-doped” on a generalized, Fe-based superconductor, phase diagram. Furthermore, the anisotropic superconducting upper critical field, H c2(T), of CaKFe 4As 4 was determined up to 630 kOe. The anisotropy parameter γ(T)=Hmore » $$⊥\\atop{c2}$$/H$$∥\\atop{c2}$$, for H applied perpendicular and parallel to the c axis, decreases from ≃2.5 at T c to ≃1.5 at 25 K, which can be explained by interplay of paramagnetic pair breaking and orbital effects. The slopes of dH$$∥\\atop{c2}$$/dT≃-44 kOe/K and dH$$⊥\\atop{c2}$$/dT≃-109 kOe/K at T c yield an electron mass anisotropy of m ⊥/m ∥≃1/6 and short Ginzburg-Landau coherence lengths ξ ∥(0)≃5.8Å and ξ ⊥(0)≃14.3Å. Finally, the value of H$$⊥\\atop{c2}$$(0) can be extrapolated to ≃920 kOe, well above the BCS paramagnetic limit.« less

Experimental progress of a 4K VM/PT hybrid cryocooler for pre-cooling 1K sorption cooler

NASA Astrophysics Data System (ADS)

Pan, Changzhao; Zhang, Tong; Wang, Jue; Chen, Liubiao; Guo, Jia; Zhou, Yuan; Wang, Junjie

2017-12-01

Sub-kelvin refrigerator has many applications in space detector and manned space station, such as for the transition-edge superconducting (TES) bolometers operated in the 50 mK range. In order to meet the requirement of space applications, the high efficient, vibration free and high stability refrigerator need to be designed. VM/PT hybrid cryocooler is a new type cryocooler capable of attaining temperature below 4K. As a low frequency Stirling type cryocooler, it has the advantages of high stability and high efficiency. Combined with the vibration free sorption cooler and ADR refrigerator, a novel sub-kelvin cooling chain can be designed for the TES bolometer. This paper presents the recent experimental progress of the 4K VM/PT hybrid cryocooler in our laboratory. By optimizing of regenerators, phase shifters and heat exchangers, a lowest temperature of 2.6K was attained. Based on this cryocooler, a preliminary sorption cooler could be designed.

Interferon regulatory factor 1 and histone H4 acetylation in systemic lupus erythematosus

PubMed Central

Leung, Yiu Tak; Shi, Lihua; Maurer, Kelly; Song, Li; Zhang, Zhe; Petri, Michelle; Sullivan, Kathleen E

2015-01-01

Histone acetylation modulates gene expression and has been described as increased in systemic lupus erythematosus (SLE). We investigated interferon regulatory factor 1 (IRF1) interactions that influence H4 acetylation (H4ac) in SLE. Intracellular flow cytometry for H4 acetylated lysine (K) 5, K8, K12, and K16 was performed. Histone acetylation was defined in monocytes and T cells from controls and SLE patients. RNA-Seq studies were performed on monocytes to look for an imbalance in histone acetyltransferases and histone deacetylase enzyme expression. Expression levels were validated using real-time quantitative RT-PCR. IRF1 induction of H4ac was evaluated using D54MG cells overexpressing IRF1. IRF1 protein interactions were studied using co-immunoprecipitation assays. IRF1-dependent recruitment of histone acetyltransferases to target genes was examined by ChIP assays using p300 antibody. Flow cytometry data showed significantly increased H4K5, H4K8, H4K12, and H4K16 acetylation in SLE monocytes. HDAC3 and HDAC11 gene expression were decreased in SLE monocytes. PCAF showed significantly higher gene expression in SLE than controls. IRF1-overexpressing D54MG cells were associated with significantly increased H4K5, H4K8, and H4K12 acetylation compared to vector-control D54MG cells both globally and at specific target genes. Co-immunoprecipitation studies using D54MG cells revealed IRF1 protein-protein interactions with PCAF, P300, CBP, GCN5, ATF2, and HDAC3. ChIP experiments demonstrated increased p300 recruitment to known IRF1 targets in D54MG cells overexpressing IRF1. In contrast, p300 binding to IRF1 targets decreased in D54MG cells with IRF1 knockdown. SLE appears to be associated with an imbalance in histone acetyltransferases and histone deacetylase enzymes favoring pathologic H4 acetylation. Furthermore, IRF1 directly interacts with chromatin modifying enzymes, supporting a model where recruitment to specific target genes is mediated in part by IRF1. PMID

(3-aminopropyl)-4-methylpiperazine end-capped poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based multilayer films for gene delivery.

PubMed

Li, Cuicui; Tzeng, Stephany Y; Tellier, Liane E; Green, Jordan J

2013-07-10

Biodegradable polyelectrolyte surfaces for gene delivery were created through electrospinning of biodegradable polycations combined with iterative solution-based multilayer coating. Poly(β-amino ester) (PBAE) poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-capped with 1-(3-aminopropyl)-4-methylpiperazine was utilized because of its ability to electrostatically interact with anionic molecules like DNA, its biodegradability, and its low cytotoxicity. A new DNA release system was developed for sustained release of DNA over 24 h, accompanied by high exogenous gene expression in primary human glioblastoma (GB) cells. Electrospinning a different PBAE, poly(1,4-butanediol diacrylate-co-4,4'-trimethylenedipiperidine), and its combination with polyelectrolyte 1-(3-aminopropyl)-4-methylpiperazine end-capped poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based multilayers are promising for DNA release and intracellular delivery from a surface.

(3-Aminopropyl)-4-methylpiperazine End-capped Poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based Multilayer Films for Gene Delivery

PubMed Central

Li, Cuicui; Tzeng, Stephany Y; Tellier, Liane E.; Green, Jordan J

2013-01-01

Biodegradable polyelectrolyte surfaces for gene delivery were created through electrospinning of biodegradable polycations combined with iterative solution-based multilayer coating. Poly(β-amino ester) (PBAE) poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-capped with 1-(3-aminopropyl)-4-methylpiperazine was utilized due to its ability to electrostatically interact with anionic molecules like DNA, its biodegradability, and its low cytotoxicity. A new DNA release system was developed for sustained release of DNA over 24 hours, accompanied by high exogenous gene expression in primary human glioblastoma (GB) cells. Electrospinning a different PBAE, poly(1,4-butanediol diacrylate-co-4,4′-trimethylenedipiperidine), and its combination with polyelectrolyte 1-(3-aminopropyl)-4-methylpiperazine end-capped poly(1,4-butanediol diacrylate-co-4-amino-1-butanol)-based multilayers are promising for DNA release and intracellular delivery from a surface. PMID:23755861

An Essential Role for the K+-dependent Na+/Ca2+-exchanger, NCKX4, in Melanocortin-4-receptor-dependent Satiety*

PubMed Central

Li, Xiao-Fang; Lytton, Jonathan

2014-01-01

K+-dependent Na+/Ca2+-exchangers are broadly expressed in various tissues, and particularly enriched in neurons of the brain. The distinct physiological roles for the different members of this Ca2+ transporter family are, however, not well described. Here we show that gene-targeted mice lacking the K+-dependent Na+/Ca2+-exchanger, NCKX4 (gene slc24a4 or Nckx4), display a remarkable anorexia with severe hypophagia and weight loss. Feeding and satiety are coordinated centrally by melanocortin-4 receptors (MC4R) in neurons of the hypothalamic paraventricular nucleus (PVN). The hypophagic response of Nckx4 knock-out mice is accompanied by hyperactivation of neurons in the PVN, evidenced by high levels of c-Fos expression. The activation of PVN neurons in both fasted Nckx4 knock-out and glucose-injected wild-type animals is blocked by Ca2+ removal and MC4R antagonists. In cultured hypothalamic neurons, melanocyte stimulating hormone induces an MC4R-dependent and sustained Ca2+ signal, which requires phospholipase C activity and plasma membrane Ca2+ entry. The Ca2+ signal is enhanced in hypothalamic neurons from Nckx4 knock-out animals, and is depressed in cells in which NCKX4 is overexpressed. Finally, MC4R-dependent oxytocin expression in the PVN, a key essential step in satiety, is prevented by blocking phospholipase C activation or Ca2+ entry. These findings highlight an essential, and to our knowledge previously unknown, role for Ca2+ signaling in the MC4R pathway that leads to satiety, and a novel non-redundant role for NCKX4-mediated Ca2+ extrusion in controlling MC4R signaling and feeding behavior. Together, these findings highlight a novel pathway that potentially could be exploited to develop much needed new therapeutics to tackle eating disorders and obesity. PMID:25096581

Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

PubMed Central

2015-01-01

We developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. PMID:25075558

Aminoacid N-substituted 1,4,7-triazacyclononane and 1,4,7,10-tetraazacyclododecane Zn2+, Cd2+ and Cu2+ complexes. A preparative, potentiometric titration and NMR spectroscopic study.

PubMed

Plush, Sally E; Lincoln, Stephen F; Wainwright, Kevin P

2004-05-07

The pK(a)s and Zn2+, Cd2+ and Cu2+ complexation constants (K) for 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7-triazacyclononane, 1, 1,4,7-tris[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7-triazacyclononane, H(3)2, 1,4,7-tris[(2''S)-acetamido-2''-(methyl-3''-(1H-3-indolyl)propionate)]-1,4,7-triazacyclononane, 3, and 1,4,7,10-tetrakis[(2''S)-acetamido-2''-(methyl-3''-phenylpropionate)]-1,4,7,10-tetraazacyclododecane, 4, 1,4,7,10-tetrakis[(2''S)-acetamido-2''-(1''-carboxy-3''-phenylpropane)]-1,4,7,10-tetraazacyclododecane, H(4)5, in 20 : 80 v/v water-methanol solution are reported. The pK(a)s within the potentiometric detection range for H(3)1(3+) = 8.69 and 3.59, for H(6)2(3+) = 9.06, 6.13, 4.93 and 4.52, H(3)3(3+) = 8.79 and 3.67, H(4)4(4+) = 8.50, 5.62 and 3.77 and for H(8)5(4+) = 9.89, 7.06, 5.53, 5.46, 4.44 and 4.26 where each tertiary amine nitrogen is protonated. The complexes of 1: [Zn(1)]2+(9.00), [Cd(1)]2+ (6.49), [Cd(H1)]3+ (4.54) and [Cu(1)]2+ (10.01) are characterized by the log(K/dm3 mol(-1)) values shown in parentheses. Analogous complexes are formed by 3 and 4: [Zn(3)]2+ (10.19), [Cd(3)]2+ (8.54), [Cu(3)]2+ (10.77), [Zn(4)]2+ (11.41) [Cd(4)]2+ (9.16), [Cd(H4)]3+ (6.16) and [Cu(4)]2+ (11.71). The tricarboxylic acid H(3)2 generates a greater variety of complexes as exemplified by: [Zn(2)-] (10.68) [Zn(H2)] (6.60) [Zn(H(2)2)+] (5.15), [Cd(2)](-) (4.99), [Cd(H2)] (4.64), [Cd(H2(2))]+ (3.99), [Cd(H(3)2)]2+ (3.55), [Cu(2)](-) (12.55) [Cu(H2)] (7.66), [Cu(H(2)2)]+ (5.54) and [Cu(2)2](4-) (3.23). The complexes of H(4)5 were insufficiently soluble to study in this way. The 1H and 13C NMR spectra of the ligands are consistent with formation of a predominant Zn2+ and Cd2+ Delta or Lambda diastereomer. The preparations of the new pendant arm macrocycles H(3)2, 3, 4 and H(4)5 are reported.

The PR-Set7 binding domain of Riz1 is required for the H4K20me1-H3K9me1 trans-tail 'histone code' and Riz1 tumor suppressor function.

PubMed

Congdon, Lauren M; Sims, Jennifer K; Tuzon, Creighton T; Rice, Judd C

2014-04-01

PR-Set7/Set8/KMT5a is the sole histone H4 lysine 20 monomethyltransferase (H4K20me1) in metazoans and is essential for proper cell division and genomic stability. We unexpectedly discovered that normal cellular levels of monomethylated histone H3 lysine 9 (H3K9me1) were also dependent on PR-Set7, but independent of its catalytic activity. This observation suggested that PR-Set7 interacts with an H3K9 monomethyltransferase to establish the previously reported H4K20me1-H3K9me1 trans-tail 'histone code'. Here we show that PR-Set7 specifically and directly binds the C-terminus of the Riz1/PRDM2/KMT8 tumor suppressor and demonstrate that the N-terminal PR/SET domain of Riz1 preferentially monomethylates H3K9. The PR-Set7 binding domain was required for Riz1 nuclear localization and maintenance of the H4K20me1-H3K9me1 trans-tail 'histone code'. Although Riz1 can function as a repressor, Riz1/H3K9me1 was dispensable for the repression of genes regulated by PR-Set7/H4K20me1. Frameshift mutations resulting in a truncated Riz1 incapable of binding PR-Set7 occur frequently in various aggressive cancers. In these cancer cells, expression of wild-type Riz1 restored tumor suppression by decreasing proliferation and increasing apoptosis. These phenotypes were not observed in cells expressing either the Riz1 PR/SET domain or PR-Set7 binding domain indicating that Riz1 methyltransferase activity and PR-Set7 binding domain are both essential for Riz1 tumor suppressor function.

Histone H3K4 methylation-dependent and -independent functions of Set1A/COMPASS in embryonic stem cell self-renewal and differentiation.

PubMed

Sze, Christie C; Cao, Kaixiang; Collings, Clayton K; Marshall, Stacy A; Rendleman, Emily J; Ozark, Patrick A; Chen, Fei Xavier; Morgan, Marc A; Wang, Lu; Shilatifard, Ali

2017-09-01

Of the six members of the COMPASS (complex of proteins associated with Set1) family of histone H3 Lys4 (H3K4) methyltransferases identified in mammals, Set1A has been shown to be essential for early embryonic development and the maintenance of embryonic stem cell (ESC) self-renewal. Like its familial relatives, Set1A possesses a catalytic SET domain responsible for histone H3K4 methylation. Whether H3K4 methylation by Set1A/COMPASS is required for ESC maintenance and during differentiation has not yet been addressed. Here, we generated ESCs harboring the deletion of the SET domain of Set1A (Set1A ΔSET ); surprisingly, the Set1A SET domain is dispensable for ESC proliferation and self-renewal. The removal of the Set1A SET domain does not diminish bulk H3K4 methylation in ESCs; instead, only a subset of genomic loci exhibited reduction in H3K4me3 in Set1A ΔSET cells, suggesting a role for Set1A independent of its catalytic domain in ESC self-renewal. However, Set1A ΔSET ESCs are unable to undergo normal differentiation, indicating the importance of Set1A-dependent H3K4 methylation during differentiation. Our data also indicate that during differentiation, Set1A but not Mll2 functions as the H3K4 methylase on bivalent genes and is required for their expression, supporting a model for transcriptional switch between Mll2 and Set1A during the self-renewing-to-differentiation transition. Together, our study implicates a critical role for Set1A catalytic methyltransferase activity in regulating ESC differentiation but not self-renewal and suggests the existence of context-specific H3K4 methylation that regulates transcriptional outputs during ESC pluripotency. © 2017 Sze et al.; Published by Cold Spring Harbor Laboratory Press.

A Simple Method for Visualization of Locus-Specific H4K20me1 Modifications in Living Caenorhabditis elegans Single Cells.

PubMed

Shinkai, Yoichi; Kuramochi, Masahiro; Doi, Motomichi

2018-05-03

Recently, advances in next-generation sequencing technologies have enabled genome-wide analyses of epigenetic modifications; however, it remains difficult to analyze the states of histone modifications at a single-cell resolution in living multicellular organisms because of the heterogeneity within cellular populations. Here we describe a simple method to visualize histone modifications on the specific sequence of target locus at a single-cell resolution in living Caenorhabditis elegans , by combining the LacO/LacI system and a genetically-encoded H4K20me1-specific probe, "mintbody". We demonstrate that Venus-labeled mintbody and mTurquoise2-labeled LacI can co-localize on an artificial chromosome carrying both the target locus and LacO sequences, where H4K20me1 marks the target locus. We demonstrate that our visualization method can precisely detect H4K20me1 depositions on the her-1 gene sequences on the artificial chromosome, to which the dosage compensation complex binds to regulate sex determination. The degree of H4K20me1 deposition on the her-1 sequences on the artificial chromosome correlated strongly with sex, suggesting that, using the artificial chromosome, this method can reflect context-dependent changes of H4K20me1 on endogenous genomes. Furthermore, we demonstrate live imaging of H4K20me1 depositions on the artificial chromosome. Combined with ChIP assays, this mintbody-LacO/LacI visualization method will enable analysis of developmental and context-dependent alterations of locus-specific histone modifications in specific cells and elucidation of the underlying molecular mechanisms. Copyright © 2018, G3: Genes, Genomes, Genetics.

7. Photocopy of photographca. 1927 (2 1/4 X 2 1/4' ...

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

7. Photocopy of photograph--ca. 1927 (2 1/4 X 2 1/4' negative) DETAIL SHOWING ADAPTATION THAT ALLOWED USE OF UPPER END OF ORIGINAL FLUME AND LOWER END JUST RECONSTRUCTED - Power Flume No. 1, Tacoma, La Plata County, CO

Crystallographic study of three coronary vasodilators of the nitrate ester type: 1,4- trans-cyclohexanedimethanol dinitrate, 1,4:3,6-dianhydro- D-glucitol-2,5-dinitrate and 1,4:3,6-dianhydro- D-glucitol-2-mononitrate

NASA Astrophysics Data System (ADS)

Kanters, J. A.; Schouten, A.; Sterk, G. J.; de Jong, M. H.

1993-10-01

The crystal structures of three vasodilators of the nitrate ester type have been determined by X-ray diffraction. Compound I, 1,4- trans-cyclohexanedimethanol dinitrate (CDDN), C 8H 14N 2O 6, is a recently developed nitrate ester with a promising haemodynamic profile in the treatment of ischaemic heart diseases. CDDN crystallizes in space group P2 1/a with a = 5.9443(4), b = 16.7052(9), c = 6.2022(2) Å, β = 116.669(4)°, Z = 2 and T = 295 K. The molecule lies on a centre of inversion and the structure refined to R = 0.042 for 991 reflections with I > 2.5σ( I). The cyclohexane ring approaches an ideal chair conformation and the C-O-NO 2 fragment is strictly planar. Compound II is the widely applied vasodilator in angina pectoris, isosorbide dinitrate or 1,4:3,6-dianhydro- D-glucitol-2,5-dinitrate (ISDN), C 6H 8N 2O 8. ISDN crystallizes in space group P22 12 1 with a = 5.7535(2), b = 10.9393(5), c = 14.6599(5)Å, Z = 4 and T = 295 K. The structure refined to R = 0.033 for 1104 reflections with I > 2.5σ( I). The molecular skeleton consists of two cis-fused five-membered rings, which each adopt an envelope conformation such that the torsion angels about the central CC bond are 0.3(2) and -7.8(2)°. The angle between the rings is 60.8(1)° and the two nitrate groups are planar. Compound III, isosorbide-2-mononitrate or 1,4:3,6-dianhydro- D-glucitol-2-mononitrate (IS-2MN), C 6H 9NO 6, is an active metabolite of II and crystallizes in space group P2 12 12 1 with a = 6.4318(4), b = 7.5273(4), c = 15.866(1)Å Z = 4 and T = 100 K. The structure refined to R = 0.031 for 1488 reflections with I > 2.5σ( I). The skeleton of III is very similar to that of II. The torsion angles about the central CC bond are 2.4(2) and -3.1(2)°, the interplanar angle is 61.5(1)° and the nitrate group is strictly planar.

Magnetodielectric properties of the square cupola antiferromagnet Ba(TiO)Cu4(PO4)4

NASA Astrophysics Data System (ADS)

Kimura, Kenta; Sera, Masakazu; Nakano, Takehito; Nozue, Yasuo; Kimura, Tsuyoshi

2018-05-01

Magnetodielectric properties of the tetragonal magnetic insulator Ba(TiO)Cu4(PO4)4 consisting of asymmetric Cu4O12 square cupolas have been investigated in a magnetic field along the [001] axis (B[001]), where a metamagnetic transition occurs at Bc||[001] 12 T and 1.4 K. Clear anomalies associated with the transition to the high-field phase are observed in dielectric constants both along the [100] (ε[100]) and [001] (ε[001]) axes. It is found that the B dependence of ε[001] and ε[100] across Bc||[001] is anisotropic: ε[001] decreases while ε[100] increases. The origin of this anisotropic magnetodielectric response is discussed.

Antitumor activity of JS-K [O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and related O2-aryl diazeniumdiolates in vitro and in vivo.