Ovarian folliclesin vivoare cooler than surrounding abdominal and ovarian tissues. This study inv... more Ovarian folliclesin vivoare cooler than surrounding abdominal and ovarian tissues. This study investigated whether typical follicular temperatures influence the maturation and developmental potential of pig oocytesin vitro. Oocytes were synchronised at the germinal vesicle (GV) stage and incubated at 39, 37 or 35.5 °C. When compared with 39 °C, which is often used forin vitrostudies, lower temperatures delayed spontaneous progression to the metaphase I and II (MI and MII) stages of meiosis. The MII was delayed by about 12 h per °C. All oocytes had normal morphology. Oocytes reaching GV breakdown (GVBD) at 39 °C were subsequently unaffected by cooling, demonstrating thermal sensitivity during the pre-GVBD stage only. Simultaneous assay of maturation-controlling kinases (maturation promoting factor (MPF) and MAPK) showed that cooling delayed kinase activation, provided it was applied prior to GVBD. Activity profiles remained coupled to the stage of meiosis. Neither enzyme was directly...
We present preliminary updated measurements of the CP-violating parameters S ππ and C ππ in B 0 →... more We present preliminary updated measurements of the CP-violating parameters S ππ and C ππ in B 0 → π + π − decays. Using a sample of 227 million Υ (4S) → BB decays collected with the BABAR detector at the PEP-II asymmetric-energy e + e − collider at SLAC, we observe 467±33 signal decays and measure S ππ = −0.30 ± 0.17 (stat) ± 0.03 (syst), and C ππ = −0.09 ± 0.15 (stat) ± 0.04 (syst).
Polarized Th1 cells show a stable phenotype: they become insensitive to IL-4 stimulation and lose... more Polarized Th1 cells show a stable phenotype: they become insensitive to IL-4 stimulation and lose the potential to produce IL-4. Previously, we reported that IFN-γ played a critical role in stabilizing Th1 phenotype. However, the mechanism by which IFN-γ stabilizes Th1 phenotype is not clear. In this study, we compared STAT6 phosphorylation in wild-type (WT) and IFN-γ receptor knockout (IFNGR−/−) Th1 cells. We found a striking diminution of STAT6 phosphorylation in differentiated WT Th1 cells, but not in differentiated IFNGR−/− Th1 cells. The impairment of STAT6 phosphorylation in differentiated WT Th1 cells was not due to a lack of IL-4R expression or phosphorylation. Jak1 and Jak3 expression and phosphorylation were comparable in both cell types. No differential expression of suppressor of cytokine signaling 1 (SOCS1), SOCS3, or SOCS5 was observed in the two cell types. In addition, Src homology 2-containing phosphatase mutation did not affect IL-4-induced STAT6 phosphorylation in...
The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous s... more The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous structure. We identified rtn1Δ in a systematic screen for yeast mutants with altered ER morphology. The ER in rtn1Δ cells is predominantly cisternal rather than reticular, yet the net surface area of ER is not significantly changed. Rtn1-green fluorescent protein (GFP) associates with the reticular ER at the cell cortex and with the tubules that connect the cortical ER to the nuclear envelope, but not with the nuclear envelope itself. Rtn1p overexpression also results in an altered ER structure. Rtn proteins are found on the ER in a wide range of eukaryotes and are defined by two membrane-spanning domains flanking a conserved hydrophilic loop. Our results suggest that Rtn proteins may direct the formation of reticulated ER. We independently identified Rtn1p in a proteomic screen for proteins associated with the exocyst vesicle tethering complex. The conserved hydophilic loop of Rtn1p bind...
We establish improved upper limits on branching fractions for B 0 decays to final states where th... more We establish improved upper limits on branching fractions for B 0 decays to final states where the decay products are purely invisible (i.e., no observable final state particles) and for final states where the only visible product is a photon. Within the Standard Model, these decays have branching fractions that are below the current experimental sensitivity, but various models of physics beyond the Standard Model predict significant contributions for these channels. Using 471 Â 10 6 B " B pairs collected at the Çð4SÞ resonance by the BABAR experiment at the PEP-II e þ e À storage ring at the SLAC National Accelerator Laboratory, we establish upper limits at the 90% confidence level of 2:4 Â 10 À5 for the branching fraction of B 0 ! invisible and 1:7 Â 10 À5 for the branching fraction of B 0 ! invisible þ .
The use of delivery systems in the human body for positioning and deploying implants, such as clo... more The use of delivery systems in the human body for positioning and deploying implants, such as closure devices, dilation balloons, stents, coils and sterilization devices, are gaining more importance to preclude surgical incisions and general anesthesia. The majorities of the nonsurgical medical devices are delivered in a low profile into human body form and subsequently require specialized operations for their deployment and release. An analogous procedure for permanent female sterilization is the transcervical approach that does not require either general anesthesia or surgical incision and uses a normal body passage. The objective of this paper is to detail the design, development and verification of an ergonomic actuator for a medical application. In particular, this actuator is designed for the deployment and release of an implant to achieve instant permanent female sterilization via the transcervical approach. This implant is deployed under hysteroscopic visualization and requires a sequence of rotary and linear operations for its deployment and release. More specifically, this manually operated actuator is a hand held device designed to transmit the required forces in a particular sequence to effect both implant deployment and release at a target location. In order to design the actuator and to investigate its mechanical behavior, a three-dimensional (3D) Computer Aided Design (CAD) model was developed and Finite Element Method (FEM) was used for simulations and optimization. Actuator validation was performed following a number of successful bench-top inair deployments and in-vitro deployments in animal tissue and explanted human uteri. During these deployments it was observed that the actuator applied the required forces to the implant resulting in successful deployment. Initial results suggest that this actuator can be used single handedly during the deployment phase. The ongoing enhancement of this actuator is moving towards "first-in-man" clinical trials.
A recent theory of transverse centroid oscillations in solenoidally focused beam transport lattic... more A recent theory of transverse centroid oscillations in solenoidally focused beam transport lattices presented in Ref. [1] is applied to statistically analyze properties of the centroid orbit in the Neutralized Drift Compression Experiment (NDCX) at the Lawrence Berkeley National Laboratory. Contributions to the amplitude of the centroid oscillations from mechanical misalignments and initial centroid errors exiting the injector are analyzed.
Operation of the JLab IR Upgrade FEL at CW powers in excess of 10 kW requires sustained productio... more Operation of the JLab IR Upgrade FEL at CW powers in excess of 10 kW requires sustained production of high electron beam powers by the driver ERL. This in turn demands attention to numerous issues and effects, including: cathode lifetime; control of beamline and RF system vacuum during high current operation; longitudinal space charge; longitudinal and transverse matching of irregular/large volume phase space distributions; halo management; management of remnant dispersive effects; resistive wall, wake-field, and RF heating of beam vacuum chambers; the beam break up instability; the impact of coherent synchrotron radiation (both on beam quality and the performance of laser optics); magnetic component stability and reproducibility; and RF stability and reproducibility. We discuss our experience with these issues and describe the modus vivendi that has evolved during prolonged high current, high power beam and laser operation.
Longitudinal compression of a velocity-tailored, intense neutralized K beam at 300 keV, 25 mA has... more Longitudinal compression of a velocity-tailored, intense neutralized K beam at 300 keV, 25 mA has been demonstrated. The compression takes place in a 1-2 m drift section filled with plasma to provide space-charge neutralization. An induction cell produces a head-to-tail velocity ramp that longitudinally compresses the neutralized beam, enhancing the beam peak current by a factor of 50 and producing a pulse duration of about 3 ns. This measurement has been confirmed independently with two different diagnostic systems.
Nuclear Instruments & Methods in Physics Research Section A-Accelerators Spectrometers Detectors and Associated Equipment, 2011
The T2K experiment is a long-baseline neutrino oscillation experiment. Its main goal is to measur... more The T2K experiment is a long-baseline neutrino oscillation experiment. Its main goal is to measure the last unknown lepton sector mixing angle θ 13 by observing ν e appearance in a ν µ beam. It also aims to make a precision measurement of the known oscillation parameters, ∆m 2 23 and sin 2 2θ 23 , via ν µ disappearance studies. Other goals of the experiment include various neutrino cross section measurements and sterile neutrino searches. The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC. This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem.
The ultimate goal in nuclear facility and nuclear power plant operations is operating safely duri... more The ultimate goal in nuclear facility and nuclear power plant operations is operating safely during normal operations and maintaining core cooling capabilities during off-normal events including external hazards. Understanding the impact of external hazards, such as flooding and earthquakes, have on nuclear facilities and NPPs is critical to deciding how to manage these hazards to expectable levels of risk. From a seismic risk perspective the goal is to manage seismic risk. Seismic risk is determined by convolving the seismic hazard with seismic fragilities (capacity of systems, structures, and components (SSCs)). There are large uncertainties associated with evolving nature of the seismic hazard curves. Additionally there are requirements within DOE and potential requirements within NRC to reconsider updated seismic hazard curves every 10 years. Therefore opportunity exists for engineered solutions to manage this seismic uncertainty. One engineered solution is seismic isolation. Current seismic isolation (SI) designs (used in commercial industry) reduce horizontal earthquake loads and protect critical infrastructure from the potentially destructive effects of large earthquakes. The benefit of SI application in the nuclear industry is being recognized and SI systems have been proposed, in the American Society of Civil Engineers (ASCE) 4 standard, to be released in 2014, for Light Water Reactors (LWR) facilities using commercially available technology. However, there is a lack of industry application to the nuclear industry and uncertainty with implementing the procedures outlined in ASCE-4. Opportunity exists to determine barriers associated with implementation of current ASCE-4 standard language. Based on discussions with nuclear vendors there is opportunity to apply SI solutions for systems and components in nuclear facilities and NPPs. There may be a need to seismically isolate systems and components such as diesel generators and reactor pressure vessels. However, SI procedures and designs proposed for SI of an entire facility may not be appropriate because the mass of many systems and/or components is relatively small, and their geometry is very different. For these systems and/or components there may be a need to provide three-dimensional seismic isolation in addition to lateral SI. To start this activity a working meeting was convened on August 19 th 2014 with representatives from DOE, National Laboratories, Industry, EPRI, and NRC to discuss three SI topics: 1) general background on current SI progress in the U.S., 2) limitations associated with implementing procedures outlined in ASCE-4 for SI solutions of entire nuclear power plant, and 3) to determine potential SI solutions for systems and components and gaps associated with developing standardized technologies, methods, and numerical tools for these solutions. Additionally, the working meeting highlights what systems and/or components could benefit from SI. Issues related to implementation of SI were discussed at the meeting and these issues help in identification of areas and needs to perform research and development (R&D).
Ovarian folliclesin vivoare cooler than surrounding abdominal and ovarian tissues. This study inv... more Ovarian folliclesin vivoare cooler than surrounding abdominal and ovarian tissues. This study investigated whether typical follicular temperatures influence the maturation and developmental potential of pig oocytesin vitro. Oocytes were synchronised at the germinal vesicle (GV) stage and incubated at 39, 37 or 35.5 °C. When compared with 39 °C, which is often used forin vitrostudies, lower temperatures delayed spontaneous progression to the metaphase I and II (MI and MII) stages of meiosis. The MII was delayed by about 12 h per °C. All oocytes had normal morphology. Oocytes reaching GV breakdown (GVBD) at 39 °C were subsequently unaffected by cooling, demonstrating thermal sensitivity during the pre-GVBD stage only. Simultaneous assay of maturation-controlling kinases (maturation promoting factor (MPF) and MAPK) showed that cooling delayed kinase activation, provided it was applied prior to GVBD. Activity profiles remained coupled to the stage of meiosis. Neither enzyme was directly...
We present preliminary updated measurements of the CP-violating parameters S ππ and C ππ in B 0 →... more We present preliminary updated measurements of the CP-violating parameters S ππ and C ππ in B 0 → π + π − decays. Using a sample of 227 million Υ (4S) → BB decays collected with the BABAR detector at the PEP-II asymmetric-energy e + e − collider at SLAC, we observe 467±33 signal decays and measure S ππ = −0.30 ± 0.17 (stat) ± 0.03 (syst), and C ππ = −0.09 ± 0.15 (stat) ± 0.04 (syst).
Polarized Th1 cells show a stable phenotype: they become insensitive to IL-4 stimulation and lose... more Polarized Th1 cells show a stable phenotype: they become insensitive to IL-4 stimulation and lose the potential to produce IL-4. Previously, we reported that IFN-γ played a critical role in stabilizing Th1 phenotype. However, the mechanism by which IFN-γ stabilizes Th1 phenotype is not clear. In this study, we compared STAT6 phosphorylation in wild-type (WT) and IFN-γ receptor knockout (IFNGR−/−) Th1 cells. We found a striking diminution of STAT6 phosphorylation in differentiated WT Th1 cells, but not in differentiated IFNGR−/− Th1 cells. The impairment of STAT6 phosphorylation in differentiated WT Th1 cells was not due to a lack of IL-4R expression or phosphorylation. Jak1 and Jak3 expression and phosphorylation were comparable in both cell types. No differential expression of suppressor of cytokine signaling 1 (SOCS1), SOCS3, or SOCS5 was observed in the two cell types. In addition, Src homology 2-containing phosphatase mutation did not affect IL-4-induced STAT6 phosphorylation in...
The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous s... more The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous structure. We identified rtn1Δ in a systematic screen for yeast mutants with altered ER morphology. The ER in rtn1Δ cells is predominantly cisternal rather than reticular, yet the net surface area of ER is not significantly changed. Rtn1-green fluorescent protein (GFP) associates with the reticular ER at the cell cortex and with the tubules that connect the cortical ER to the nuclear envelope, but not with the nuclear envelope itself. Rtn1p overexpression also results in an altered ER structure. Rtn proteins are found on the ER in a wide range of eukaryotes and are defined by two membrane-spanning domains flanking a conserved hydrophilic loop. Our results suggest that Rtn proteins may direct the formation of reticulated ER. We independently identified Rtn1p in a proteomic screen for proteins associated with the exocyst vesicle tethering complex. The conserved hydophilic loop of Rtn1p bind...
We establish improved upper limits on branching fractions for B 0 decays to final states where th... more We establish improved upper limits on branching fractions for B 0 decays to final states where the decay products are purely invisible (i.e., no observable final state particles) and for final states where the only visible product is a photon. Within the Standard Model, these decays have branching fractions that are below the current experimental sensitivity, but various models of physics beyond the Standard Model predict significant contributions for these channels. Using 471 Â 10 6 B " B pairs collected at the Çð4SÞ resonance by the BABAR experiment at the PEP-II e þ e À storage ring at the SLAC National Accelerator Laboratory, we establish upper limits at the 90% confidence level of 2:4 Â 10 À5 for the branching fraction of B 0 ! invisible and 1:7 Â 10 À5 for the branching fraction of B 0 ! invisible þ .
The use of delivery systems in the human body for positioning and deploying implants, such as clo... more The use of delivery systems in the human body for positioning and deploying implants, such as closure devices, dilation balloons, stents, coils and sterilization devices, are gaining more importance to preclude surgical incisions and general anesthesia. The majorities of the nonsurgical medical devices are delivered in a low profile into human body form and subsequently require specialized operations for their deployment and release. An analogous procedure for permanent female sterilization is the transcervical approach that does not require either general anesthesia or surgical incision and uses a normal body passage. The objective of this paper is to detail the design, development and verification of an ergonomic actuator for a medical application. In particular, this actuator is designed for the deployment and release of an implant to achieve instant permanent female sterilization via the transcervical approach. This implant is deployed under hysteroscopic visualization and requires a sequence of rotary and linear operations for its deployment and release. More specifically, this manually operated actuator is a hand held device designed to transmit the required forces in a particular sequence to effect both implant deployment and release at a target location. In order to design the actuator and to investigate its mechanical behavior, a three-dimensional (3D) Computer Aided Design (CAD) model was developed and Finite Element Method (FEM) was used for simulations and optimization. Actuator validation was performed following a number of successful bench-top inair deployments and in-vitro deployments in animal tissue and explanted human uteri. During these deployments it was observed that the actuator applied the required forces to the implant resulting in successful deployment. Initial results suggest that this actuator can be used single handedly during the deployment phase. The ongoing enhancement of this actuator is moving towards "first-in-man" clinical trials.
A recent theory of transverse centroid oscillations in solenoidally focused beam transport lattic... more A recent theory of transverse centroid oscillations in solenoidally focused beam transport lattices presented in Ref. [1] is applied to statistically analyze properties of the centroid orbit in the Neutralized Drift Compression Experiment (NDCX) at the Lawrence Berkeley National Laboratory. Contributions to the amplitude of the centroid oscillations from mechanical misalignments and initial centroid errors exiting the injector are analyzed.
Operation of the JLab IR Upgrade FEL at CW powers in excess of 10 kW requires sustained productio... more Operation of the JLab IR Upgrade FEL at CW powers in excess of 10 kW requires sustained production of high electron beam powers by the driver ERL. This in turn demands attention to numerous issues and effects, including: cathode lifetime; control of beamline and RF system vacuum during high current operation; longitudinal space charge; longitudinal and transverse matching of irregular/large volume phase space distributions; halo management; management of remnant dispersive effects; resistive wall, wake-field, and RF heating of beam vacuum chambers; the beam break up instability; the impact of coherent synchrotron radiation (both on beam quality and the performance of laser optics); magnetic component stability and reproducibility; and RF stability and reproducibility. We discuss our experience with these issues and describe the modus vivendi that has evolved during prolonged high current, high power beam and laser operation.
Longitudinal compression of a velocity-tailored, intense neutralized K beam at 300 keV, 25 mA has... more Longitudinal compression of a velocity-tailored, intense neutralized K beam at 300 keV, 25 mA has been demonstrated. The compression takes place in a 1-2 m drift section filled with plasma to provide space-charge neutralization. An induction cell produces a head-to-tail velocity ramp that longitudinally compresses the neutralized beam, enhancing the beam peak current by a factor of 50 and producing a pulse duration of about 3 ns. This measurement has been confirmed independently with two different diagnostic systems.
Nuclear Instruments & Methods in Physics Research Section A-Accelerators Spectrometers Detectors and Associated Equipment, 2011
The T2K experiment is a long-baseline neutrino oscillation experiment. Its main goal is to measur... more The T2K experiment is a long-baseline neutrino oscillation experiment. Its main goal is to measure the last unknown lepton sector mixing angle θ 13 by observing ν e appearance in a ν µ beam. It also aims to make a precision measurement of the known oscillation parameters, ∆m 2 23 and sin 2 2θ 23 , via ν µ disappearance studies. Other goals of the experiment include various neutrino cross section measurements and sterile neutrino searches. The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC. This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem.
The ultimate goal in nuclear facility and nuclear power plant operations is operating safely duri... more The ultimate goal in nuclear facility and nuclear power plant operations is operating safely during normal operations and maintaining core cooling capabilities during off-normal events including external hazards. Understanding the impact of external hazards, such as flooding and earthquakes, have on nuclear facilities and NPPs is critical to deciding how to manage these hazards to expectable levels of risk. From a seismic risk perspective the goal is to manage seismic risk. Seismic risk is determined by convolving the seismic hazard with seismic fragilities (capacity of systems, structures, and components (SSCs)). There are large uncertainties associated with evolving nature of the seismic hazard curves. Additionally there are requirements within DOE and potential requirements within NRC to reconsider updated seismic hazard curves every 10 years. Therefore opportunity exists for engineered solutions to manage this seismic uncertainty. One engineered solution is seismic isolation. Current seismic isolation (SI) designs (used in commercial industry) reduce horizontal earthquake loads and protect critical infrastructure from the potentially destructive effects of large earthquakes. The benefit of SI application in the nuclear industry is being recognized and SI systems have been proposed, in the American Society of Civil Engineers (ASCE) 4 standard, to be released in 2014, for Light Water Reactors (LWR) facilities using commercially available technology. However, there is a lack of industry application to the nuclear industry and uncertainty with implementing the procedures outlined in ASCE-4. Opportunity exists to determine barriers associated with implementation of current ASCE-4 standard language. Based on discussions with nuclear vendors there is opportunity to apply SI solutions for systems and components in nuclear facilities and NPPs. There may be a need to seismically isolate systems and components such as diesel generators and reactor pressure vessels. However, SI procedures and designs proposed for SI of an entire facility may not be appropriate because the mass of many systems and/or components is relatively small, and their geometry is very different. For these systems and/or components there may be a need to provide three-dimensional seismic isolation in addition to lateral SI. To start this activity a working meeting was convened on August 19 th 2014 with representatives from DOE, National Laboratories, Industry, EPRI, and NRC to discuss three SI topics: 1) general background on current SI progress in the U.S., 2) limitations associated with implementing procedures outlined in ASCE-4 for SI solutions of entire nuclear power plant, and 3) to determine potential SI solutions for systems and components and gaps associated with developing standardized technologies, methods, and numerical tools for these solutions. Additionally, the working meeting highlights what systems and/or components could benefit from SI. Issues related to implementation of SI were discussed at the meeting and these issues help in identification of areas and needs to perform research and development (R&D).
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Papers by J Coleman PhD