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Article ; Online: K

Mahato, Karuna / Bagdi, Prasanta Ray / Khan, Abu T

2017 Volume 15, Issue 26, Page(s) 5625–5634

Abstract: ... nitrostyrenes in the presence of 10 mol% K ...

Abstract	An unprecedented and efficient method for the synthesis of useful thieno[2,3-b]thiochromen-4-one oximes is accomplished via a thio[3 + 2] cyclization reaction of 4-hydroxydithiocoumarins and trans-β-nitrostyrenes in the presence of 10 mol% K
Language	English
Publishing date	2017-07-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2097583-1
ISSN	1477-0539 ; 1477-0520
ISSN (online)	1477-0539
ISSN	1477-0520
DOI	10.1039/c7ob01033h
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Article ; Online: Phage K

Lehman, Susan M / Kongari, Rohit / Glass, Adam M / Koert, Matthew / Ray, Melissa D / Plaut, Roger D / Stibitz, Scott

Viruses

2022 Volume 15, Issue 1

Abstract: There is widespread interest in using obligately lytic bacteriophages ("phages") to treat human bacterial infections. ... ...

Abstract	There is widespread interest in using obligately lytic bacteriophages ("phages") to treat human bacterial infections. Among
MeSH term(s)	Animals ; Mice ; Humans ; Bacteriophages ; Methicillin-Resistant Staphylococcus aureus/genetics ; Staphylococcus aureus/genetics ; Temperature ; Anti-Bacterial Agents/pharmacology ; Staphylococcal Infections/therapy ; Staphylococcal Infections/microbiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2022-12-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15010017
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Article ; Online: A triple cysteine motif as major determinant of the modulation of neuronal K

Ray, Sutirtha / Stampf, Jan-Luca / Kudlacek, Oliver / Yang, Jae-Won / Schicker, Klaus W / Graf, Yvonne / Losgott, Thomas / Boehm, Stefan / Salzer, Isabella

British journal of pharmacology

2024

Abstract: Background and purpose: The analgesic action of paracetamol involves K: Experimental approach ... site-directed mutagenesis, and mass spectrometry applied to recombinant K: Key results: Currents through the cardiac ... subtype K: Conclusion and implication: The paracetamol metabolite N-acetyl-p-benzo quinone imine (NAPQI ...

Abstract	Background and purpose: The analgesic action of paracetamol involves K Experimental approach: To address this question, we used a combination of perforated patch-clamp recordings, site-directed mutagenesis, and mass spectrometry applied to recombinant K Key results: Currents through the cardiac subtype K Conclusion and implication: The paracetamol metabolite N-acetyl-p-benzo quinone imine (NAPQI) modifies cysteine residues of K
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.16380
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Article ; Online: pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model.

Dutta, Debasmita / Ray, Priyanka / De, Archana / Ghosh, Arnab / Hazra, Raj Shankar / Ghosh, Pratyusha / Banerjee, Snigdha / Diaz, Francisco J / Upadhyay, Sunil P / Quadir, Mohiuddin / Banerjee, Sushanta K

PloS one

2024 Volume 19, Issue 4, Page(s) e0297749

Abstract: ... of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers ... to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS. ...

Abstract	Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.
MeSH term(s)	Animals ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Deoxycytidine/administration & dosage ; Gemcitabine ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Mice ; Humans ; Cell Line, Tumor ; Nanoparticles/chemistry ; Hydrogen-Ion Concentration ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Disease Models, Animal ; Tumor Microenvironment/drug effects
Chemical Substances	Deoxycytidine (0W860991D6) ; Gemcitabine ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Protein Kinase Inhibitors
Language	English
Publishing date	2024-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0297749
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Article ; Online: Lead-free (Ag,K)NbO

Liu, Zhen / Lu, Teng / Xue, Fei / Nie, Hengchang / Withers, Ray / Studer, Andrew / Kremer, Felipe / Narayanan, Narendirakumar / Dong, Xianlin / Yu, Dehong / Chen, Longqing / Liu, Yun / Wang, Genshui

Science advances

2020 Volume 6, Issue 21, Page(s) eaba0367

Abstract: Explosive energy conversion materials with extremely rapid response times have broad and growing applications in energy, medical, defense, and mining areas. Research into the underlying mechanisms and the search for new candidate materials in this field ... ...

Abstract	Explosive energy conversion materials with extremely rapid response times have broad and growing applications in energy, medical, defense, and mining areas. Research into the underlying mechanisms and the search for new candidate materials in this field are so limited that environment-unfriendly Pb(Zr,Ti)O
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.aba0367
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Article ; Online: Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis.

Corbaux, Pauline / You, Benoit / Glasspool, Rosalind M / Yanaihara, Nozomu / Tinker, Anna V / Lindemann, Kristina / Ray-Coquard, Isabelle L / Mirza, Mansoor R / Subtil, Fabien / Colomban, Olivier / Péron, Julien / Karamouza, Eleni / McNeish, Iain / Kelly, Caroline / Kagimura, Tatsuo / Welch, Stephen / Lewsley, Liz-Anne / Paoletti, Xavier / Cook, Adrian

European journal of cancer (Oxford, England : 1990)

2023 Volume 191, Page(s) 112966

Abstract: ... constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed ...

Abstract	Background: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors. Methods: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model. Results: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established. Conclusion: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.
MeSH term(s)	Humans ; Female ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; CA-125 Antigen ; Disease-Free Survival ; Antineoplastic Agents/therapeutic use ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/surgery
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors ; CA-125 Antigen ; Antineoplastic Agents
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2023.112966
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Article ; Online: Beam-Energy Dependence of Directed Flow of Λ, Λ[over ¯], K^{±}, K_{s}^{0}, and ϕ in Au+Au Collisions.

Adamczyk, L / Adams, J R / Adkins, J K / Agakishiev, G / Aggarwal, M M / Ahammed, Z / Ajitanand, N N / Alekseev, I / Anderson, D M / Aoyama, R / Aparin, A / Arkhipkin, D / Aschenauer, E C / Ashraf, M U / Attri, A / Averichev, G S / Bai, X / Bairathi, V / Barish, K /

Behera, A / Bellwied, R / Bhasin, A / Bhati, A K / Bhattarai, P / Bielcik, J / Bielcikova, J / Bland, L C / Bordyuzhin, I G / Bouchet, J / Brandenburg, J D / Brandin, A V / Brown, D / Bunzarov, I / Butterworth, J / Caines, H / Calderón de la Barca Sánchez, M / Campbell, J M / Cebra, D / Chakaberia, I / Chaloupka, P / Chang, Z / Chankova-Bunzarova, N / Chatterjee, A / Chattopadhyay, S / Chen, X / Chen, J H / Cheng, J / Cherney, M / Christie, W / Contin, G / Crawford, H J / Das, S / De Silva, L C / Dedovich, T G / Deng, J / Derevschikov, A A / Didenko, L / Dilks, C / Dong, X / Drachenberg, J L / Draper, J E / Dunkelberger, L E / Dunlop, J C / Efimov, L G / Elsey, N / Engelage, J / Eppley, G / Esha, R / Esumi, S / Evdokimov, O / Ewigleben, J / Eyser, O / Fatemi, R / Fazio, S / Federic, P / Federicova, P / Fedorisin, J / Feng, Z / Filip, P / Finch, E / Fisyak, Y / Flores, C E / Fujita, J / Fulek, L / Gagliardi, C A / Garand, D / Geurts, F / Gibson, A / Girard, M / Grosnick, D / Gunarathne, D S / Guo, Y / Gupta, A / Gupta, S / Guryn, W / Hamad, A I / Hamed, A / Harlenderova, A / Harris, J W / He, L / Heppelmann, S / Hirsch, A / Horvat, S / Huang, X / Huang, B / Huang, T / Huang, H Z / Humanic, T J / Huo, P / Igo, G / Jacobs, W W / Jentsch, A / Jia, J / Jiang, K / Jowzaee, S / Judd, E G / Kabana, S / Kalinkin, D / Kang, K / Kapukchyan, D / Kauder, K / Ke, H W / Keane, D / Kechechyan, A / Khan, Z / Kikoła, D P / Kim, C / Kisel, I / Kisiel, A / Kochenda, L / Kocmanek, M / Kollegger, T / Kosarzewski, L K / Kraishan, A F / Krauth, L / Kravtsov, P / Krueger, K / Kulathunga, N / Kumar, L / Kvapil, J / Kwasizur, J H / Lacey, R / Landgraf, J M / Landry, K D / Lauret, J / Lebedev, A / Lednicky, R / Lee, J H / Li, C / Li, X / Li, Y / Li, W / Lidrych, J / Lin, T / Lisa, M A / Liu, P / Liu, H / Liu, Y / Liu, F / Ljubicic, T / Llope, W J / Lomnitz, M / Longacre, R S / Luo, S / Luo, X / Ma, Y G / Ma, L / Ma, R / Ma, G L / Magdy, N / Majka, R / Mallick, D / Margetis, S / Markert, C / Matis, H S / Meehan, K / Mei, J C / Miller, Z W / Minaev, N G / Mioduszewski, S / Mishra, D / Mizuno, S / Mohanty, B / Mondal, M M / Morozov, D A / Mustafa, M K / Nasim, Md / Nayak, T K / Nelson, J M / Nie, M / Nigmatkulov, G / Niida, T / Nogach, L V / Nonaka, T / Nurushev, S B / Odyniec, G / Ogawa, A / Oh, K / Okorokov, V A / Olvitt, D / Page, B S / Pak, R / Pandit, Y / Panebratsev, Y / Pawlik, B / Pei, H / Perkins, C / Pile, P / Pluta, J / Poniatowska, K / Porter, J / Posik, M / Pruthi, N K / Przybycien, M / Putschke, J / Qiu, H / Quintero, A / Ramachandran, S / Ray, R L / Reed, R / Rehbein, M J / Ritter, H G / Roberts, J B / Rogachevskiy, O V / Romero, J L / Roth, J D / Ruan, L / Rusnak, J / Rusnakova, O / Sahoo, N R / Sahu, P K / Salur, S / Sandweiss, J / Saur, M / Schambach, J / Schmah, A M / Schmidke, W B / Schmitz, N / Schweid, B R / Seger, J / Sergeeva, M / Seto, R / Seyboth, P / Shah, N / Shahaliev, E / Shanmuganathan, P V / Shao, M / Sharma, A / Sharma, M K / Shen, W Q / Shi, S S / Shi, Z / Shou, Q Y / Sichtermann, E P / Sikora, R / Simko, M / Singha, S / Skoby, M J / Smirnov, N / Smirnov, D / Solyst, W / Song, L / Sorensen, P / Spinka, H M / Srivastava, B / Stanislaus, T D S / Strikhanov, M / Stringfellow, B / Suaide, A A P / Sugiura, T / Sumbera, M / Summa, B / Sun, Y / Sun, X M / Sun, X / Surrow, B / Svirida, D N / Tang, Z / Tang, A H / Taranenko, A / Tarnowsky, T / Tawfik, A / Thäder, J / Thomas, J H / Timmins, A R / Tlusty, D / Todoroki, T / Tokarev, M / Trentalange, S / Tribble, R E / Tribedy, P / Tripathy, S K / Trzeciak, B A / Tsai, O D / Ullrich, T / Underwood, D G / Upsal, I / Van Buren, G / van Nieuwenhuizen, G / Vasiliev, A N / Videbæk, F / Vokal, S / Voloshin, S A / Vossen, A / Wang, G / Wang, Y / Wang, F / Webb, J C / Webb, G / Wen, L / Westfall, G D / Wieman, H / Wissink, S W / Witt, R / Wu, Y / Xiao, Z G / Xie, G / Xie, W / Xu, J / Xu, Z / Xu, Q H / Xu, Y F / Xu, N / Yang, S / Yang, Y / Yang, C / Yang, Q / Ye, Z / Yi, L / Yip, K / Yoo, I-K / Yu, N / Zbroszczyk, H / Zha, W / Zhang, Z / Zhang, J B / Zhang, J / Zhang, S / Zhang, Y / Zhang, X P / Zhao, J / Zhong, C / Zhou, C / Zhou, L / Zhu, X / Zhu, Z / Zyzak, M

Physical review letters

2018 Volume 120, Issue 6, Page(s) 62301

Abstract: Rapidity-odd directed-flow measurements at midrapidity are presented for Λ, Λ[over ¯], K^{±}, K_{s ...

Abstract	Rapidity-odd directed-flow measurements at midrapidity are presented for Λ, Λ[over ¯], K^{±}, K_{s}^{0}, and ϕ at sqrt[s_{NN}]=7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV in Au+Au collisions recorded by the Solenoidal Tracker detector at the Relativistic Heavy Ion Collider. These measurements greatly expand the scope of data available to constrain models with differing prescriptions for the equation of state of quantum chromodynamics. Results show good sensitivity for testing a picture where flow is assumed to be imposed before hadron formation and the observed particles are assumed to form via coalescence of constituent quarks. The pattern of departure from a coalescence-inspired sum rule can be a valuable new tool for probing the collision dynamics.
Language	English
Publishing date	2018-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.120.062301
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Article ; Online: Non vitamin K oral anticoagulants versus antiplatelets in embolic stroke of undetermined source: most updated evidence.

Chatterjee, Subhankar / Dubey, Souvik / Lahiri, Durjoy / Ray, Biman K

Minerva cardioangiologica

2019 Volume 67, Issue 4, Page(s) 340–347

Abstract: Recent trial data have expanded the horizons of newer indications of non-vitamin K oral ...

Abstract	Recent trial data have expanded the horizons of newer indications of non-vitamin K oral anticoagulants (NOAC). Most recently they are being evaluated for use in embolic stroke of undetermined source (ESUS). ESUS are particularly known for their recurrences. So, identifying the causes and treating those etiological factors are the keys to secondary prevention of ESUS. Although traditional experts still opine for the use of antiplatelets for secondary prevention of ESUS as for other causes of embolic stroke, there are still room for improvement in delivery of optimal treatment strategy. So, NOAC is being tried as an alternative to traditional atiplatelet therapy in head-to-head trials. Unfortunately, recent trial data (from NAVIGATE-ESUS and RESPECT-ESUS) have not shown any added benefits (with comparable bleeding risk) of NOAC compared to aspirin in prevention of ESUS. This review intends to highlight the concept of ESUS, its varied etiologies, discuss the published and ongoing trials and tries to dig the reasons why the overall trial data have been disappointing. It also discusses the arenas where NOAC may be proved to be better than antiplatelets. Overall, we have stressed on the personalized case-to-case basis decision making while choosing the appropriate therapy in secondary prevention of ESUS.
MeSH term(s)	Administration, Oral ; Anticoagulants/administration & dosage ; Anticoagulants/pharmacology ; Aspirin/administration & dosage ; Humans ; Intracranial Embolism/prevention & control ; Platelet Aggregation Inhibitors/administration & dosage ; Platelet Aggregation Inhibitors/pharmacology ; Secondary Prevention/methods ; Stroke/prevention & control
Chemical Substances	Anticoagulants ; Platelet Aggregation Inhibitors ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2019-06-20
Publishing country	Italy
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	123583-7
ISSN	1827-1618 ; 0026-4725
ISSN (online)	1827-1618
ISSN	0026-4725
DOI	10.23736/S0026-4725.19.04967-3
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Article ; Online: Search for the rare decays K(L)→π0π0μ+μ- and K(L)→π0π0X0→π0π0μ+μ-.

Abouzaid, E / Arenton, M / Barker, A R / Bellantoni, L / Blucher, E / Bock, G J / Cheu, E / Coleman, R / Corcoran, M D / Cox, B / Erwin, A R / Escobar, C O / Glazov, A / Golossanov, A / Gomes, R A / Gouffon, P / Hsiung, Y B / Jensen, D A / Kessler, R /

Kotera, K / Ledovskoy, A / McBride, P L / Monnier, E / Nguyen, H / Niclasen, R / Phillips, D G / Ping, H / Ramberg, E J / Ray, R E / Ronquest, M / Santos, E / Slater, W / Smith, D / Solomey, N / Swallow, E C / Toale, P A / Tschirhart, R / Velissaris, C / Wah, Y W / Wang, J / White, H B / Whitmore, J / Wilking, M J / Winston, R / Worcester, E T / Worcester, M / Yamanaka, T / Zimmerman, E D / Zukanovich, R F

Physical review letters

2011 Volume 107, Issue 20, Page(s) 201803

Abstract: The KTeV E799 experiment has conducted a search for the rare decays, K(L)→π(0)π(0)μ(+)μ(-) and K(L ... upper limits of Br(K(L)→π(0)π(0)X(0)→π(0)π(0)μ(+)μ(-)) < 1.0 × 10(-10) and Br(K(L)→π(0)π(0)μ(+)μ(-)) < 9 ...

Abstract	The KTeV E799 experiment has conducted a search for the rare decays, K(L)→π(0)π(0)μ(+)μ(-) and K(L)→π(0)π(0)X(0)→π(0)π(0)μ(+)μ(-), where the X(0) is a possible new neutral boson that was reported by the HyperCP experiment with a mass of (214.3 ± 0.5) MeV/c(2). We find no evidence for either decay. We obtain upper limits of Br(K(L)→π(0)π(0)X(0)→π(0)π(0)μ(+)μ(-)) < 1.0 × 10(-10) and Br(K(L)→π(0)π(0)μ(+)μ(-)) < 9.2 × 10(-11) at the 90% confidence level. This result rules out the pseudoscalar X(0) as an explanation of the HyperCP result under the scenario that the dsX(0) coupling is completely real.
Language	English
Publishing date	2011-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.107.201803
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Article ; Online: Intercalated cell BKα subunit is required for flow-induced K+ secretion.

Carrisoza-Gaytan, Rolando / Ray, Evan C / Flores, Daniel / Marciszyn, Allison L / Wu, Peng / Liu, Leah / Subramanya, Arohan R / Wang, WenHui / Sheng, Shaohu / Nkashama, Lubika J / Chen, Jingxin / Jackson, Edwin K / Mutchler, Stephanie M / Heja, Szilvia / Kohan, Donald E / Satlin, Lisa M / Kleyman, Thomas R

JCI insight

2020 Volume 5, Issue 8

Abstract: ... collecting duct (CCD) of the mammalian kidney and have been proposed to be responsible for flow-induced K+ ... secretion (FIKS) and K+ adaptation. To examine the IC-specific role of BK channels, we generated a mouse ... sensitive (ChTX-sensitive) K+ currents were readily detected in control ICs but largely absent in ICs of IC ...

Abstract	BK channels are expressed in intercalated cells (ICs) and principal cells (PCs) in the cortical collecting duct (CCD) of the mammalian kidney and have been proposed to be responsible for flow-induced K+ secretion (FIKS) and K+ adaptation. To examine the IC-specific role of BK channels, we generated a mouse with targeted disruption of the pore-forming BK α subunit (BKα) in ICs (IC-BKα-KO). Whole cell charybdotoxin-sensitive (ChTX-sensitive) K+ currents were readily detected in control ICs but largely absent in ICs of IC-BKα-KO mice. When placed on a high K+ (HK) diet for 13 days, blood [K+] was significantly greater in IC-BKα-KO mice versus controls in males only, although urinary K+ excretion rates following isotonic volume expansion were similar in males and females. FIKS was present in microperfused CCDs isolated from controls but was absent in IC-BKα-KO CCDs of both sexes. Also, flow-stimulated epithelial Na+ channel-mediated (ENaC-mediated) Na+ absorption was greater in CCDs from female IC-BKα-KO mice than in CCDs from males. Our results confirm a critical role of IC BK channels in FIKS. Sex contributes to the capacity for adaptation to a HK diet in IC-BKα-KO mice.
MeSH term(s)	Animals ; Cell Line ; Charybdotoxin/pharmacology ; Ion Transport/drug effects ; Ion Transport/genetics ; Kidney Tubules, Collecting/metabolism ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/antagonists & inhibitors ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism ; Mice ; Mice, Knockout ; Potassium/metabolism
Chemical Substances	BKCa protein, mouse ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits ; Charybdotoxin (115422-61-2) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2020-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.130553
Database	MEDical Literature Analysis and Retrieval System OnLINE

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