Search for CP Violation in the decays D+ -> K_S pi+ and D+ -> K_S K+

A high statistics sample of photo-produced charm from the FOCUS(E831) experiment at Fermilab has been used to search for direct CP violation in the decays D+->K_S pi+ and D+ -> K_S K+. We have measured the following asymmetry parameters relative to D+->K-pi+pi+: A_CP(K_S pi+) = (-1.6 +/- 1.5 +/- 0.9)%, A_CP(K_S K+) = (+6.9 +/- 6.0 +/- 1.5)% and A_CP(K_S K+) = (+7.1 +/- 6.1 +/- 1.2)% relative to D+->K_S pi+. The first errors quoted are statistical and the second are systematic. We also measure the relative branching ratios: \Gamma(D+->\bar{K0}pi+)/\Gamma(D+->K-pi+pi+) = (30.60 +/- 0.46 +/- 0.32)%, \Gamma(D+->\bar{K0}K+)/\Gamma(D+->K-pi+pi+) = (6.04 +/- 0.35 +/- 0.30)% and \Gamma(D+->\bar{K0}K+)/\Gamma(D+->\bar{K0}pi+) = (19.96 +/- 1.19 +/- 0.96)%.Comment: 4 pages, 3 figure

A High Statistics Measurement of the Lambdac+ Lifetime

A high statistics measurement of the Lambdac+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat.) +/- 2.5 (syst.) fs from 8034 +/- 122 Lambdac -> pKpi decays represents a significant improvement over the present world average.Comment: Submitted to Physical Review Letter

A measurement of branching ratios of D+D^+ and Ds+D^+_s hadronic decays to four-body final states containing a KSK_S

We have studied hadronic four-body decays of $D^+$ and $D^+_s$ mesons with a $K_S$ in the final state using data recorded during the 1996-1997 fixed-target run at Fermilab high energy photoproduction experiment FOCUS. We report a new branching ratio measurement of $\Gamma(D^+\to K_S K^-\pi^+\pi^+)/\Gamma(D^+\to K_S \pi^+\pi^+\pi^-)=0.0768\pm0.0041\pm0.0032$. We make the first observation of three new decay modes with branching ratios $\Gamma(D^+\to K_S K^+\pi^+\pi^-)/\Gamma(D^+\to K_S \pi^+\pi^+\pi^-)=0.0562\pm0.0039\pm0.0040$, \Gamma(D^+\to\K_S K^+ K^-\pi^+)/\Gamma(D^+\to K_S \pi^+\pi^+\pi^-)=0.0077\pm0.0015\pm0.0009, and $\Gamma(D^+_s\to K_S K^+\pi^+\pi^-)/\Gamma(D^+_s\to K_S K^-\pi^+\pi^+)=0.586\pm0.052\pm0.043$, where in each case the first error is statistical and the second error is systematic.Comment: 4 pages, 1 table, 2 figures, submitted to Physical Review Letter

Targeting UBC9-Mediated Protein Hyper-SUMOylation in Cystic Cholangiocytes Halts Polycystic Liver Disease in Experimental Models

BACKGROUND & AIMS: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of multiple fluid-filled biliary cysts. Most PLD-causative genes participate in protein biogenesis and/or transport. Post-translational modifications (PTMs) are implicated in protein stability, localization and activity, contributing to human pathobiology; however, their role in PLD is unknown. Herein, we aimed to unveil the role of protein SUMOylation in PLD and its potential therapeutic targeting. METHODS: Levels and functional effects of SUMOylation, along with response to S-adenosylmethionine (SAMe, inhibitor of the SUMOylation enzyme UBC9) and/or short-hairpin RNAs (shRNAs) against UBE2I (UBC9), were evaluated invitro, invivo and/or in patients with PLD. SUMOylated proteins were determined by immunoprecipitation and proteomic analyses by mass spectrometry. RESULTS: Most SUMOylation-related genes were found overexpressed (mRNA) in polycystic human and rat liver tissue, as well as in cystic cholangiocytes in culture compared to controls. Increased SUMOylated protein levels were also observed in cystic human cholangiocytes in culture, which decreased after SAMe administration. Chronic treatment of polycystic (PCK: Pkdh1-mut) rats with SAMe halted hepatic cystogenesis and fibrosis, and reduced liver/body weight ratio and liver volume. Invitro, both SAMe and shRNA-mediated UBE2I knockdown increased apoptosis and reduced cell proliferation of cystic cholangiocytes. High-throughput proteomic analysis of SUMO1-immunoprecipitated proteins in cystic cholangiocytes identified candidates involved in protein biogenesis, ciliogenesis and proteasome degradation. Accordingly, SAMe hampered proteasome hyperactivity in cystic cholangiocytes, leading to activation of the unfolded protein response and stress-related apoptosis. CONCLUSIONS: Cystic cholangiocytes exhibit increased SUMOylation of proteins involved in cell survival and proliferation, thus promoting hepatic cystogenesis. Inhibition of protein SUMOylation with SAMe halts PLD, representing a novel therapeutic strategy. LAY SUMMARY: Protein SUMOylation is a dynamic post-translational event implicated in numerous cellular processes. This study revealed dysregulated protein SUMOylation in polycystic liver disease, which promotes hepatic cystogenesis. Administration of S-adenosylmethionine (SAMe), a natural UBC9-dependent SUMOylation inhibitor, halted polycystic liver disease in experimental models, thus representing a potential therapeutic agent for patients.Spanish Carlos III Health Institute (ISCIII) [J.M. Banales (FIS PI12/00380, PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008); M.J. Perugorria (FIS PI14/00399, PI17/00022 and PI20/00186); P.M. Rodrigues (Sara Borrell CD19/00254)] cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); Ministerio de Ciencia, Innovación y Universidades (MICINN; M.L. Martinez-Chantar: SAF2017-87301-R); “Instituto de Salud Carlos III” [CIBERehd: J.M. Banales, M.J. Perugorria, M.L. Martinez-Chantar and L. Bujanda], Spain; “Diputación Foral Gipuzkoa” (J.M. Banales: DFG15/010, DFG16/004), Department of Health of the Basque Country (M.J. Perugorria: 2019111024, 2015111100 and J.M. Banales: 2017111010), “Euskadi RIS3” (J.M. Banales: 2016222001, 2017222014, 2018222029, 2019222054, 2020333010), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales and M.L. Martinez-Chantar) and Department of Industry of the Basque Country (J.M. Banales: Elkartek: KK-2020/00008). La Caixa Scientific Foundation (J.M. Banales and M.L. Martinez-Chantar: HR17-00601). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to J.M. Banales and M.L. Martinez-Chantar). “Ayudas para apoyar grupos de investigación del Sistema Universitario Vasco” (IT971-16 to P.A.). Università Politecnica delle Marche PSA2017_UNIVPM grant (to M. Marzioni). National Institutes of Health (NIH) of United States of America (DK24031 to N.F. LaRusso). MJ Perugorria was funded by the Spanish Ministry of Economy and Competitiveness (MINECO: “Ramón y Cajal” Program RYC-2015-17755), P.Y. Lee-Law by the European Association for the Study of the Liver (EASL; Sheila Sherlock Award 2017), F.J. Caballero-Camino by the Spanish Ministry of Science and Innovation (BES-2014-069148), and P. Olaizola and A. Santos-Laso by the Basque Government (PRE_2016_1_0269, PRE_2015_1_0126). We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). The funding sources had no involvement in study design, data collection and analysis, decision to publish, or preparation of the article

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

The Target Silicon Detector for the FOCUS Spectrometer

We describe a silicon microstrip detector interleaved with segments of a beryllium oxide target which was used in the FOCUS photoproduction experiment at Fermilab. The detector was designed to improve the vertex resolution and to enhance the reconstruction efficiency of short-lived charm particles.Comment: 18 pages, 14 figure

Measurement of the relative branching ratio BR(\Xi_c^+ \to p^+ K^-\pi^+)\BR(\Xi_c^+ \to \Xi^- \pi^+ \pi^+)

We report the observation of the Cabibbo suppressed decay \Xi_c^+ \to p K^-\pi^+ using data collected with the FOCUS spectrometer during the 1996--97 Fermilab fixed target run. We find a \Xi_c^+ signal peak of 202\pm35 events. We have measured the relative branching ratios BR(\Xi^+_c\to p K^-\pi^+)/BR(\Xi^+_c\to\Xi^-\pi^+\pi^+)= 0.234 \pm 0.047 \pm 0.022 and BR(\Xi^+_c\to p \bar{K}^*(892)^0)/BR(\Xi^+_c\to p K^-\pi^+)= 0.54 \pm 0.09 \pm 0.05 .Comment: 9 pages, 4 figure

Study of Hadronic Five-Body Decays of Charmed Mesons

We study the decay of D+ and Ds+ mesons into charged five body final states, and report the discovery of the decay mode D+ -> K+K-Pi+Pi+Pi-, as well as measurements of the decay modes D+ -> K-Pi+Pi+Pi+Pi-, Ds+ -> K+K-Pi+Pi+Pi-, Ds+ -> PhiPi+Pi+Pi- and D+/Ds+ -> Pi+Pi+Pi+Pi-Pi-. An analysis of the resonant substructure is also included, with evidence suggesting that both decays proceed primarily through an a1 vector resonance.Comment: 11 pages, 3 figure

New FOCUS results on charm mixing and CP violation

We present a summary of recent results on CP violation and mixing in the charm quark sector based on a high statistics sample collected by photoproduction experiment FOCUS (E831 at Fermilab). We have measured the difference in lifetimes for the $D^0$ decays: $D^0 \to K^-\pi^+$ and $D^0 \to K^-K^+$. This translates into a measurement of the $y_{CP}$ mixing parameter in the \d0d0 system, under the assumptions that $K^-K^+$ is an equal mixture of CP odd and CP even eigenstates, and CP violation is negligible in the neutral charm meson system. We verified the latter assumption by searching for a CP violating asymmetry in the Cabibbo suppressed decay modes $D^+ \to K^-K^+\pi^+$, $D^0 \to K^-K^+$ and $D^0 \to \pi^-\pi^+$. We show preliminary results on a measurement of the branching ratio $\Gamma(D^{*+}\to \pi^+ (K^+\pi^-))/\Gamma(D^{*+}\to \pi^+ (K^-\pi^+))$.Comment: 9 pages, 6 figures, requires espcrc2.sty. Presented by S.Bianco at CPConf2000, September 2000, Ferrara (Italy). In this revision, fixed several stylistic flaws, add two significant references, fixed a typo in Tab.