Environmentally Sensitive Areas Surveys Program threatened and endangered species survey: Progress report. Environmental Restoration Program

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

King, A.L.; Awl, D.J.; Gabrielsen, C.A.

The Endangered Species Act (originally passed in 1973) is a Federal statute that protects both animal and plant species. The Endangered Species Act identifies species which are, without careful management, in danger of becoming extinct and species that are considered threatened. Along with the designation of threatened or endangered, the Endangered Species Act provides for the identification of appropriate habitat for these species. Since 1993, the United States Department of Energy`s (DOE) Environmental Restoration (ER) Program has supported a program to survey the Oak Ridge Reservation (ORR) for threatened and endangered species. The Environmentally Sensitive Areas Surveys Program initiated vascularmore » plant surveys during fiscal year 1993 and vertebrate animal surveys during fiscal year 1994 to determine the baseline condition of threatened and endangered species on the ORR at the present time. Data collected during these surveys are currently aiding Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Remedial Investigations on the ORR. They also provide data for ER and Waste Management decision documents, ensure that decisions have technical and legal defensibility, provide a baseline for ensuring compliance with principal legal requirements and will increase public confidence in DOE`s adherence to all related environmental resources rules, laws, regulations, and instructions. This report discusses the progress to date of the threatened and endangered species surveys of the ORR.« less

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

Engels, J.

The Environmental Restoration (ER) Program was established for the investigation and remediation of inactive US Department of Energy (DOE) sites and facilities that have been declared surplus in terms of their previous uses. The purpose of this document is to Specify ER requirements for quality control (QC) of analytical data. Activities throughout all phases of the investigation may affect the quality of the final data product, thus are subject to control specifications. Laboratory control is emphasized in this document, and field concerns will be addressed in a companion document Energy Systems, in its role of technical coordinator and at themore » request of DOE-OR, extends the application of these requirements to all participants in ER activities. Because every instance and concern may not be addressed in this document, participants are encouraged to discuss any questions with the ER Quality Assurance (QA) Office, the Analytical Environmental Support Group (AESG), or the Analytical Project Office (APO).« less

Environmental restoration and waste management: Robotics technology development program: Robotics 5-year program plan

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

Not Available

In FY 1990 Robotics Technology Development Program (RTDP) planning teams visited five DOE sites. These sites were selected by the Office of Technology Development to provide a needs basis for developing a 5-Year Plan. Visits to five DOE sites provided identification of needs for robotics technology development to support Environmental Restoration and Waste Management (ER WM) projects at those sites. Additional site visits will be conducted in the future to expand the planning basis. This volume summarizes both the results of the site visits and the needs and requirements of the priority ER WM activities at the sites, including potentialmore » needs for robotics and remote systems technology. It also discusses hazards associated with the site activities and any problems or technical uncertainties associated with dealing with the hazards in the performance of the ER WM work. Robotic or remote systems currently under development for remediation projects or waste operations are also discussed. The information in this document is organized principally by site, activity, and priority. Section 2.0, Site Needs, is based on information from the site visit reports and provides a summary which focuses on the site needs and requirements for each priority activity. Section 2.0 also records evaluations and discussions by the RTDP team following the site visit. Section 3.0, Commonality Assessment, documents similar site needs where common, or cross-cutting, robotics technology might be applied to several activities. Section 4.0 contains a summary of the site needs and requirements in tabular form. 1 tab.« less

Installation Restoration Program. Preliminary Assessment: 115th Tactical Control Squadron, Hall Air National Guard Station, Alabama Air National Guard, Dothan, Alabama.

DTIC Science & Technology

1991-02-01

Department of Agriculture (USDA): Soil Conservation Service, February 1968). Houston County is characterized by a warm and humid climate that borders...Figur I..,1 PhUTogrpER Map. of theAre 111-2 3. EXPLANATION - Residuum -~ l Citronelle Formation Catahouia Sandstone Paynes Hammock 0 Oligocene

Health and safety plan for the Environmental Restoration Program at Oak Ridge National Laboratory

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

Clark, C. Jr.; Burman, S.N.; Cipriano, D.J. Jr.

1994-08-01

This Programmatic Health and Safety plan (PHASP) is prepared for the U.S. Department of Energy (DOE) Oak Ridge National Laboratory (ORNL) Environmental Restoration (ER) Program. This plan follows the format recommended by the U.S. Environmental Protection Agency (EPA) for remedial investigations and feasibility studies and that recommended by the EM40 Health and Safety Plan (HASP) Guidelines (DOE February 1994). This plan complies with the Occupational Safety and Health Administration (OSHA) requirements found in 29 CFR 1910.120 and EM-40 guidelines for any activities dealing with hazardous waste operations and emergency response efforts and with OSHA requirements found in 29 CFR 1926.65.more » The policies and procedures in this plan apply to all Environmental Restoration sites and activities including employees of Energy Systems, subcontractors, and prime contractors performing work for the DOE ORNL ER Program. The provisions of this plan are to be carried out whenever activities are initiated that could be a threat to human health or the environment. This plan implements a policy and establishes criteria for the development of procedures for day-to-day operations to prevent or minimize any adverse impact to the environment and personnel safety and health and to meet standards that define acceptable management of hazardous and radioactive materials and wastes. The plan is written to utilize past experience and best management practices to minimize hazards to human health and safety and to the environment from event such as fires, explosions, falls, mechanical hazards, or any unplanned release of hazardous or radioactive materials to air, soil, or surface water.« less

Oak Ridge Reservation Federal Facility Agreement. Quarterly report for the Environmental Restoration Program. Volume 4, July 1995--September 1995

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

NONE

This quarterly progress report satisfies requirements for the Environmental Restoration (ER) Program that are specified in the Oak Ridge Reservation Federal Facility Agreement (FFA) established between the U.S. Department of Energy (DOE), the U.S. Environmental Protection Agency (EPA), and the Tennessee Department of Environment and Conservation (TDEC). The reporting period covered herein is July through September 1995 (fourth quarter of FY 1995). Sections 1.1 and 1.2 provide respectively the milestones scheduled for completion during the reporting period and a list of documents that have been proposed for transmittal during the following quarter but have not been approved as FY 1995more » commitments.« less

Hydromorphological restoration stimulates river ecosystem metabolism

NASA Astrophysics Data System (ADS)

Kupilas, Benjamin; Hering, Daniel; Lorenz, Armin W.; Knuth, Christoph; Gücker, Björn

2017-04-01

Both ecosystem structure and functioning determine ecosystem status and are important for the provision of goods and services to society. However, there is a paucity of research that couples functional measures with assessments of ecosystem structure. In mid-sized and large rivers, effects of restoration on key ecosystem processes, such as ecosystem metabolism, have rarely been addressed and remain poorly understood. We compared three reaches of the third-order, gravel-bed river Ruhr in Germany: two reaches restored with moderate (R1) and substantial effort (R2) and one upstream degraded reach (D). Hydromorphology, habitat composition, and hydrodynamics were assessed. We estimated gross primary production (GPP) and ecosystem respiration (ER) using the one-station open-channel diel dissolved oxygen change method over a 50-day period at the end of each reach. Moreover, we estimated metabolic rates of the combined restored reaches (R1 + R2) using the two-station open-channel method. Values for hydromorphological variables increased with restoration intensity (D < R1 < R2). Restored reaches had lower current velocity, higher longitudinal dispersion and larger transient storage zones. However, fractions of median travel time due to transient storage were highest in R1 and lowest in R2, with intermediate values in D. The share of macrophyte cover of total wetted area was highest in R2 and lowest in R1, with intermediate values in D. Station R2 had higher average GPP and ER than R1 and D. The combined restored reaches R1 + R2 also exhibited higher GPP and ER than the degraded upstream river (station D). Restoration increased river autotrophy, as indicated by elevated GPP : ER, and net ecosystem production (NEP) of restored reaches. Temporal patterns of ER closely mirrored those of GPP, pointing to the importance of autochthonous production for ecosystem functioning. In conclusion, high reach-scale restoration effort had considerable effects on river hydrodynamics and ecosystem functioning, which were mainly related to massive stands of macrophytes. High rates of metabolism and the occurrence of dense macrophyte stands may increase the assimilation of dissolved nutrients and the sedimentation of particulate nutrients, thereby positively affecting water quality.

Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy.

PubMed

Shchors, Ksenya; Persson, Anders I; Rostker, Fanya; Tihan, Tarik; Lyubynska, Natalya; Li, Nan; Swigart, Lamorna Brown; Berger, Mitchel S; Hanahan, Douglas; Weiss, William A; Evan, Gerard I

2013-04-16

Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRas(V12) mouse model crossed into the p53ER(TAM) background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ER(TAM) allele. The p53ER(TAM) protein can be toggled reversibly in vivo between wild-type and inactive conformations by administration or withdrawal of 4-hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in GFAP-HRas(V12);p53(+/KI) mice abrogate the p53 pathway by mutating p19(ARF)/MDM2 while retaining wild-type p53 allele. Consequently, such tumors are unaffected by restoration of their p53ER(TAM) allele. By contrast, gliomas arising in GFAP-HRas(V12);p53(KI/KI) mice develop in the absence of functional p53. Such tumors retain a functional p19(ARF)/MDM2-signaling pathway, and restoration of p53ER(TAM) allele triggers p53-tumor-suppressor activity. Congruently, growth inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in human GBM cultures also requires p14(ARF)/MDM2 functionality. Notably, the antitumoral efficacy of p53 restoration in tumor-bearing GFAP-HRas(V12);p53(KI/KI) animals depends on the duration and frequency of p53 restoration. Thus, intermittent exposure to p53ER(TAM) activity mitigated the selective pressure to inactivate the p19(ARF)/MDM2/p53 pathway as a means of resistance, extending progression-free survival. Our results suggest that intermittent dosing regimes of drugs that restore wild-type tumor-suppressor function onto mutant, inactive p53 proteins will prove to be more efficacious than traditional chronic dosing by similarly reducing adaptive resistance.

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

Montoya, Amber L.; Wagner, Katrina; Goering, Teresa Lynn

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility.more » This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2004. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2005) and DOE Order 231.1A, Environment, Safety, and Health Reporting (DOE 2004b).« less

Comparison of Micro-Leakage from Resin-Modified Glass Ionomer Restorations in Cavities Prepared by Er:YAG (Erbium-Doped Yttrium Aluminum Garnet) Laser and Conventional Method in Primary Teeth

PubMed Central

Bahrololoomi, Zahra; Razavi, Forooghosadat; Soleymani, Ali Asghar

2014-01-01

Introduction: In recent years, significant developments have been taking place in caries removal and cavity preparation using laser in dentistry. As laser use is considered for cavity preparation, it is necessary to determine the quality of restoration margins. Glass ionomer cements have great applications for conservative restoration in the pediatric field. The purpose of this in vitro study was to compare resin-modified glass ionomer restorations micro-leakage in cavities prepared by Er:YAG (Erbium-Doped Yttrium Aluminum Garnet) laser irradiation and conventional method in primary teeth. Methods: This was an in vitro experimental study. Forty primary canine teeth were divided into 2 groups: group 1 represented cavities prepared by the no. 008 diamond bur, group 2 represented cavities prepared by Er:YAG laser. After cavity preparation, samples were restored by resin-modified glass ionomer. The teeth were thermocycled for 700 cycles, placed in 2% methylene blue for 24h and sectioned in the buccolingual direction. The degree of dye penetration was scored by 3 examiners. Data was analyzed using Mann-Whitney Test. Results: There was no statistical difference in micro-leakage between the two modes of cavity preparation (P=0.862) Conclusion: Since preparing conservative cavities is very important in pediatric dentistry, it is possible to use Er:YAG laser because of its novel and portable technology. However, further investigations of other restorative materials and other laser powers are required. PMID:25653819

Microleakage in Class V Composite Restorations after Desensitizing Surface Treatment with Er:YAG and CO2 Lasers.

PubMed

Mozaffari, Hamid Reza; Ehteshami, Alireza; Zallaghi, Farshad; Chiniforush, Nasim; Moradi, Zohreh

2016-12-30

Aims: Glutaraldehyde, CO 2 and Er:YAG lasers can be used for treatment of dentin hypersensitivity. However, their application may have adverse effects on the clinical service of restorations. This study aimed to assess the microleakage in composite restorations following surface treatment with Glutaraldehyde desensitizer, CO 2 and Er:YAG laser irradiation for treatment of dentin hypersensitivity. Materials and methods: This experimental study was conducted on 60 extracted sound human teeth. Class V cavities were prepared measuring 3×3 mm using a diamond bur. Specimens were randomly divided into 4 groups of 15. Group one:no surface treatment, Group two:applying Glutaraldehyde desensitizer, Groups of three and four were irradiated with CO 2 and Er:YAG lasers, respectively. Surfaces were restored with bonding agent (Single Bond 2, 3M, USA) and Z250 composite (3M, USA). Specimens were thermocycled and immersed in 1% methylene blue solution for 24 hours. Microleakage scores were assessed under a stereomicroscope at ×20 magnification. Data were analyzed using SPSS and the Kruskal Wallis test (P=0.05). Results: There was no significant difference between microleakage of groups in enamel margins (P=0.694). The difference in microleakage at the dentin margin was significant between groups (P=0.018). Conclusions: Application of Glutaraldehyde-desensitizer and CO 2 laser irradiation of surfaces prior to composite restoration do not increase microleakage at the enamel or dentin margins but tooth surface treatment with Er:YAG laser significantly increased the microleakage at the dentin margins.

ER Consolidated Qtrly Rpt_April-June 2016_October 2016

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

Cochran, John R.

2016-10-01

This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) for the April, May, and June 2016 quarterly reporting period.

Can Degradation of Adhesive Interfaces Due to Water Storage Affect Stress Distributions? A Finite-Element Stress Analysis Study.

PubMed

Belli, Sema; Eraslan, Oğuz; Eskitaşcıoğlu, Gürcan

The aim of this finite-element stress analysis (FEA) was to determine the effect of degradation due to water storage on stress distributions in root-filled premolar models restored with composite using either a self-etch (SE) or an etch-and-rinse (E&R) adhesive. Four premolar FEA models including root filling, MOD cavity, and composite restorations were created. The cavities were assumed to be treated by SE or E&R adhesives and stored in water for 18 months. The elastic properties of the adhesive-dentin interface after 24-h and 18-month water storage were obtained from the literature and applied to the FEA models. A 300-N load was applied on the functional cusps of the models. The SolidWorks/Cosmosworks structural analysis program was used and the results were presented considering the von Mises stresses. Stresses in the cervical region increased over time on the load-application side of the main tooth models (SE: 84.11 MPa to 87.51 MPa; E&R: 100.24 MPa to 120.8 MPa). When the adhesive interfaces (hybrid layer, adhesive layer) and dentin were evaluated separately, the stresses near the root canal orifices increased over time in both models; however, this change was more noticeable in the E&R models. Stresses at the cavity corners decreased in the E&R model (within the adhesive layer), while SE models showed the opposite (within the hybrid layer). Change in the elastic modulus of the adhesive layer, hybrid layer, and dentin due to water storage has an effect on stresses in root-filled premolar models. The location and the level of the stresses differed depending on the adhesive used.

Effects of erbium-and chromium-doped yttrium scandium gallium garnet and diode lasers on the surfaces of restorative dental materials: a scanning electron microscope study.

PubMed

Hatipoglu, M; Barutcigil, C

2015-01-01

The aim of this study is to evaluate the potential effects of laser irradiation, which is commonly performed in periodontal surgery, on the surfaces of restorative materials. Five different restorative dental materials were used in this study, as follows: (1) Resin composite, (2) poly acid-modified resin composite (compomer), (3) conventional glass ionomer cement (GIC), (4) resin-modified glass ionomer cement (RMGIC), and (5) amalgam. Four cylindrical samples (8 mm diameter, 2 mm height) were prepared for each restorative material. In addition, four freshly extracted, sound human incisors teeth were selected. Two different laser systems commonly used in periodontal surgery were examined in this study: A 810 nm diode laser at a setting of 1 W with continuous-phase laser irradiation for 10 s, and an erbium-and chromium-doped yttrium scandium gallium garnet (Er, Cr: YSGG) laser at settings of 2.5 W, 3.25 W, and 4 W with 25 Hz laser irradiation for 10 s. Scanning electron microscopy (SEM) analysis was performed to evaluate the morphology and surface deformation of the restorative materials and tooth surfaces. According to the SEM images, the Er, Cr: YSGG laser causes irradiation markings that appear as demineralized surfaces on tooth samples. The Er, Cr: YSGG laser also caused deep defects on composite, compomer, and RMGIC surfaces because of its high power, and the ablation was deeper for these samples. High-magnification SEM images of GIC samples showed the melting and combustion effects of the Er, Cr: YSGG laser, which increased as the laser power was increased. In amalgam samples, neither laser left significant harmful effects at the lowest power setting. The diode laser did cause irradiation markings, but they were insignificant compared with those left by the Er, Cr: YSGG laser on the surfaces of the different materials and teeth. Within the limitations of this study, it can be concluded that Er, Cr: YSGG laser irradiation could cause distortions of the surfaces of restorative materials. Diode lasers can be preferred for periodontal surgery.

Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

NASA Astrophysics Data System (ADS)

Özcan, Umut; Yilmaz, Erkan; Özcan, Lale; Furuhashi, Masato; Vaillancourt, Eric; Smith, Ross O.; Görgün, Cem Z.; Hotamisligil, Gökhan S.

2006-08-01

Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.

Calendar year 2002 annual site environmental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

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

Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie

2003-09-01

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, oversees TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility.more » This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2002. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 5400.1, General Environmental Protection Program (DOE 1990) and DOE Order 231.1, Environment, Safety, and Health Reporting (DOE 1996).« less

Calendar year 2003 : annual site enviromental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

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

Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie

2004-09-01

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility.more » This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2003. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2003) and DOE Order 231.1 Chg 2., Environment, Safety, and Health Reporting (DOE 1996).« less

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

Agogino, Karen; Sanchez, Rebecca

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE)/National Nuclear Security Administration (NNSA), through the Sandia Site Offi ce (SSO), in Albuquerque, NM, administers the contract and oversees contractor operations at TTR and KTF. Sandia manages and conducts operations at TTR in support of the DOE/NNSA’s Weapons Ordnance Program and has operated the site since 1957. Washington Group International subcontracts to Sandia in administering most of the environmental programs at TTR. Sandia operatesmore » KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2007. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia is responsible only for those environmental program activities related to its operations. The DOE/NNSA/Nevada Site Offi ce (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2007a) and DOE Manual 231.1-1A, Environment, Safety, and Health Reporting Manual (DOE 2007).« less

Environmental restoration and waste management: Robotics technology development program: Robotics 5-year program plan. [Contains glossary

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

Not Available

This plan covers robotics Research, Development, Demonstration, Testing, activities in the Program for the next five years. These activities range from bench-scale R D to fullscale hot demonstrations at DOE sites. This plan outlines applications of existing technology to near-term needs, the development and application of enhanced technology for longer-term needs, and an initiation of advanced technology development to meet those needs beyond the five-year plan. The objective of the Robotic Technology Development (RTDP) is to develop and apply robotics technologies that will enable Environmental Restoration and Waste Management operations at DOE sites to be safer, faster and cheaper. Fivemore » priority DOE sites were visited in March 1990 to identify needs for robotics technology in ER WM operations. This 5-Year Program Plan for the RTDP detailed annual plans for robotics technology development based on identified needs. This 5-Year Program Plan discusses the overall approach to be adopted by the RTDP to aggressively develop robotics technology and contains discussions of the Program Management Plan, Site Visit and Needs Summary, Approach to Needs-Directed Technical Development, Application-Specific Technical Development, and Cross-Cutting and Advanced Technology. Integrating application-specific ER WM needs, the current state of robotics technology, and the potential benefits (in terms of faster, safer, and cheaper) of new technology, the Plan develops application-specific road maps for robotics RDDT E for the period FY 1991 through FY 1995. In addition, the Plan identifies areas where longer-term research in robotics will have a high payoff in the 5- to 20-year time frame. 12 figs.« less

Microleakage of class V resin composite restorations after bur, air-abrasion or Er:YAG laser preparation.

PubMed

Corona, S A; Borsatto, M; Dibb, R G; Ramos, R P; Brugnera, A; Pécora, J D

2001-01-01

This in vitro study compared the microleakage of Class V resin composite restorations placed in cavities prepared with a high-speed dental bur, air-abrasion or Er:YAG laser. Twenty sound extracted human third molars were selected and randomly assigned to four equal Groups (n=10): Group I, cavities were cut by dental drill at high-speed; Group II, aluminum oxide air-abrasion was used for cavity preparation, and in Groups III and IV, cavities were prepared by Er:YAG laser. Following cavity preparation, Groups I and II were acid-etched, Group III was treated only by Er:YAG laser and Group IV was conditioned by Er:YAG laser followed by acid-etching. Cavities were restored (Single Bond + Z-100) and the teeth stored for seven days in distilled water. Then, the restorations were polished and the specimens thermocycled, immersed in a 0.2% Rhodamine solution, sectioned and analyzed for leakage at the occlusal (enamel) and cervical (dentin/cementum) interfaces using an optical microscope connected to a video camera. The images were digitized and software was utilized for microleakage assessment. Upon analyzing the results, statistically significant differences (p<0.01) between the occlusal and cervical regions for all groups was observed, and, as a rule, there was better marginal sealing at the enamel margins. The highest degree of infiltration was observed for cavities prepared and treated exclusively by Er:YAG (Group III). The other experimental groups showed statistical similarities in the amount of marginal leakage at the enamel margins. However, at the cervical margins, there was a significant difference (p<0.05) between Group I and the remaining groups. None of the techniques completely eliminated marginal microleakage at the dentin/ cementum margins.

A laser-powered hydrokinetic system for caries removal and cavity preparation.

PubMed

Hadley, J; Young, D A; Eversole, L R; Gornbein, J A

2000-06-01

Laser systems have been developed for the cutting of dental hard tissues. The erbium, chromium:yttrium-scandium-gallium-garnet, or Er,Cr:YSGG, laser system used in conjunction with an air-water spray has been shown to be efficacious in vitro for cavity preparation. The authors randomly selected subjects for cavity preparation with conventional air turbine/bur dental surgery or an Er,Cr:YSGG laser-powered system using a split-mouth design. They prepared Class I, III and V cavities, placed resin restorations and evaluated subjects on the day of the procedure and 30 days and six months postoperatively for pulp vitality, recurrent caries, pain and discomfort, and restoration retention. Sixty-seven subjects completed the study. There were no statistical differences between the two treatment groups for the parameters measured with one exception; there was a statistically significant decrease in discomfort levels for the laser system at the time of cavity preparation for subjects who declined to receive local anesthetic. The Er,Cr:YSGG laser system is effective for preparation of Class I, III and V cavities and resin restorations are retained by lased tooth surfaces. Hard-tissue cutting lasers are being introduced for use in operative dentistry. In this study, an Er,Cr:YSGG laser has been shown to be effective for cavity preparation and restoration replacement.

Health and safety plan for the Remedial Investigation and Site Investigation of Waste Area Grouping 2 at the Oak Ridge National Laboratory, Oak Ridge, Tennessee. Environmental Restoration Program

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

Cofer, G.H.; Holt, V.L.; Roupe, G.W.

1993-11-01

This health and safety plan (HASP) was developed by the members of the Measurement Applications and Development Group of the Health Science Research Division at the Oak Ridge National Laboratory (ORNL). This plan was prepared to ensure that health and safety related items for the Waste Area Grouping (WAG) 2 Remedial Investigation (RI)/Feasibility Study and Site Investigation projects conform with the requirements of 29 CFR 1910.120 (April 18, 1992). The RI Plan calls for the characterization, monitoring, risk assessment, and identification of remedial needs and alternatives that have been structured and staged with short-term and long-term objectives. In early FYmore » 1992, the WAG 2 RI was integrated with the ORNL Environmental Restoration (ER) Site Investigations program in order to achieve the complimentary objectives of the projects more effectively by providing an integrated basis of support. The combined effort was named the WAG 2 Remedial Investigation and Site Investigations Program (WAG 2 RI&SI). The Site Investigation activities are a series of monitoring efforts and directed investigations that support other ER activities by providing information about (1) watershed hydrogeology; (2) contaminants, pathways, and fluxes for groundwater at ORNL; (3) shallow subsurface areas that can act as secondary sources of contaminants; and (4) biological populations and contaminants in biota, in addition to other support and coordination activities.« less

WAG 2 remedial investigation and site investigation site-specific work plan/health and safety checklist for the soil and sediment task. Environmental Restoration Program

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

Holt, V.L.; Burgoa, B.B.

1993-12-01

This document is a site-specific work plan/health and safety checklist (WP/HSC) for a task of the Waste Area Grouping 2 Remedial Investigation and Site Investigation (WAG 2 RI&SI). Title 29 CFR Part 1910.120 requires that a health and safety program plan that includes site- and task-specific information be completed to ensure conformance with health- and safety-related requirements. To meet this requirement, the health and safety program plan for each WAG 2 RI&SI field task must include (1) the general health and safety program plan for all WAG 2 RI&SI field activities and (2) a WP/HSC for that particular field task.more » These two components, along with all applicable referenced procedures, must be kept together at the work site and distributed to field personnel as required. The general health and safety program plan is the Health and Safety Plan for the Remedial Investigation and Site Investigation of Waste Area Grouping 2 at the Oak Ridge National Laboratory, Oak Ridge, Tennessee (ORNL/ER-169). The WP/HSCs are being issued as supplements to ORNL/ER-169.« less

Microleakage in Class V cavities with self-etching adhesive system and conventional rotatory or laser Er,Cr:YSGG

PubMed Central

Arnabat, J; España-Tost, T

2012-01-01

Objective: To analyse microleakage in Class V cavity preparation with Er;Cr:YSGG at different parameters using a self-etching adhesive system. Background: Several studies reported microleakage around composite restorations when cavity preparation is done or treated by Er;Cr:YSGG laser. We want to compare different energy densities in order to obtain the best parameters, when using a self-etching adhesive system. Methods: A class V preparations was performed in 120 samples of human teeth were divided in 3 groups: (1) Preparation using the burr. (2) Er;Cr:YSGG laser preparation with high energy 4W, 30 Hz, 50% Water 50% Air and (3) Er;Cr:YSGG laser preparation lower energy 1.5 W, 30 Hz, 30% Water 30% Air. All the samples were restored with self-etching adhesive system and hybrid composite. Thermocycling (5000 cycles) and immersed in 0.5% fuchsin. The restorations were sectioned and evaluated the microleakage with a stereomicroscope. Results: Lower energy laser used for preparation showed significant differences in enamel and dentin. To group 3, the microleakage in the enamel was less, whilst the group 1, treated with the turbine, showed less microleakage at dentin level. Group 2 showed the highest microleakage at dentin/cement level. Conclusion: Burr preparation gives the lowest microleakage at cement/dentin level, whilst Er;Cr:YSGG laser at lower power has the low energy obtains lowest microleakage at enamel. On the contrary high-energy settings produce inferior results in terms of microleakage. PMID:24511195

Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.

PubMed

Cunard, Robyn

2015-04-20

Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.

Installation Restoration Program. Phase 1. Records Search, Lowry AFB, Colorado

DTIC Science & Technology

1983-08-01

donated to the * Federal Government by the City and County of Denver. By 1940, two hang- , ers had been constructed . Nine hundred and sixty adjoining...facility was under construccion . In 1958, preparation for the Titan I Missile began with the activa- tion of the 703rd Strategic Missile Wing at Lowry AFB...last T-29 departed from Lowry AFB, ending Lowry’s years as an active flying base. * . Since 1966 significant construction of dormatories and offices

Specific application for Oak Ridge National Laboratory dismantlement of Building 3004. Appendix A -- Quality assurance plan; Appendix B -- Records management plan

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

NONE

This quality assurance (QA) plan defines the QA requirements for the dismantlement and removal of Building 3004 at Oak Ridge National Laboratory (ORNL). The building is a four-story wooden trained structure with wooden siding, which resides approximately 150 ft west of the Bulk Shielding Reactor, and only several feet away from the visitors entrance to the Graphite Reactor museum. Complete descriptions and sketches are in the Performance Specification document for this project. This project is being conducted as a non-CERCLA maintenance action. This plan is an appendix to the QA plan for the ORNL Environmental Restoration (ER) Program. ORNL/ER-225, whichmore » is the source of the project QA requirements, tailors those QA requirements to the specific needs of this project as defined in ORNL/ER-225. Project-specific description and organization are also provided in this plan. Appendix B, Records Management Plan, is included.« less

Preliminary remediation goals for use at the US Department of Energy Oak Ridge Operations Office. Revision 1

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

NONE

1996-05-01

This technical memorandum presents Preliminary Remediation Goals (PRGs) for use in human health risk assessment efforts under the United States Department of Energy, Oak Ridge Operations Office Environmental Restoration (ER) Division. This document provides the ER Division with standardized PRGs which are integral to the Remedial Investigation/Feasibility Study process. They are used during project scooping (Data Quality Objectives development), in screening level risk assessments to support early action or No Further Investigation decisions, and in the baselines risk assessment where they are employed in the selection of chemicals of potential concern. The primary objective of this document is to standardizemore » these values and eliminate any duplication of effort by providing PRGs to all contractors involved in risk activities. In addition, by managing the assumptions and systems used in PRG derivation, the ER Risk Assessment Program will be able to control the level of quality assurance associated with these risk-based guideline values.« less

Effect of Er,Cr:YSGG laser on the surface of composite restoratives during in-office tooth bleaching.

PubMed

Dionysopoulos, Dimitrios; Strakas, Dimitrios; Tsitrou, Effrosyni; Tolidis, Kosmas; Koumpia, Effimia

2016-07-01

The aim of this in vitro study was to investigate the effect of Er,Cr:YSGG laser on the surface roughness and microhardness of various composite restoratives during in-office tooth bleaching. Five highly viscous composite restoratives and three flowable composite restoratives were investigated. Thirty cylindrical specimens of each material were made using Teflon molds. The specimens of each composite were randomly divided into three groups (n = 10). Group 1 specimens did not receive bleaching treatment, group 2 received a conventional in-office bleaching treatment, and group 3 received a laser-assisted in-office bleaching treatment using an Er,Cr:YSGG laser. Two-way ANOVA was used to determine significant interactions between materials and bleaching methods. One-way ANOVA and Tukey's post hoc test were used to compare the mean surface microhardness and roughness between materials for each treatment group (a = 0.05). Τhere were no significant differences in surface microhardness between the two bleached experimental groups for all the tested composites (p > 0.05). The reduction of surface microhardness after bleaching procedures ranged from 0.72 to 16.93 % for the specimens received conventional treatment and from 1.30 to 11.51 % for those received laser-assisted treatment. Moreover, there were no significant differences in Ra values between the experimental groups (p > 0.05) in all cases. The increase of surface roughness after the bleaching treatments was negligible and was between 0.43 and 4.78 %. The use of Er,Cr:YSGG laser during in-office tooth bleaching treatment did not affect the surface microhardness and roughness of the tested composite restorative materials.

Optical approach in characterizing dental biomaterials

NASA Astrophysics Data System (ADS)

Demoli, Nazif; Vučić, Zlatko; Milat, Ognjen; Gladić, Jadranko; Lovrić, Davorin; Pandurić, Vlatko; Marović, Danijela; Moguš-Milanković, Andrea; Ristić, Mira; Čalogović, Marina; Tarle, Zrinka

2013-04-01

The purpose of this paper is to present the current activities of a research collaborative program between three institutions from Zagreb (School of Dental Medicine, Institute of Physics, and Institute Ruđer Bo\\vsković). Within the scope of this program, it is planned to investigate and find guidelines for the refinement of the properties of dental biomaterials (DBs) and of procedures in restorative dental medicine. It is also planned to identify and model the dominant mechanisms which control polymerization of DBs. The materials to be investigated include methacrylate based composite resins, new composite materials with amorphous calcium phosphate, silorane based composite resins, glass-ionomer cements, and giomer.

Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance.

PubMed

Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito

2017-10-01

The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid-evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

23 CFR 668.105 - Policy.

Code of Federal Regulations, 2011 CFR

2011-04-01

... aid States in repairing road facilities which have suffered widespread serious damage resulting from a... feasible, the cost of permanent restoration work. (d) The approval to use available ER funds to repair or... over non-emergency work. (h) ER projects shall be promptly constructed. Any project that has not...

Cost-effectiveness of early versus delayed functional restoration for chronic disabling occupational musculoskeletal disorders.

PubMed

Theodore, Brian R; Mayer, Tom G; Gatchel, Robert J

2015-06-01

Despite extensive evidence for the treatment effectiveness of interdisciplinary functional restoration (FR) for chronic disabling occupational musculoskeletal disorders (CDOMD), there is little documentation on the cost-effectiveness of early rehabilitation using FR. A total of 1,119 CDOMD patients were classified according to duration of disability on FR entry, corresponding to early rehabilitation (ER: 4-8 months of disability, N = 373), intermediate duration (ID: 9-18 months, N = 373), and delayed rehabilitation (DR: >18 months, N = 373). Groups were matched on sex, age, ethnicity, and injured musculoskeletal region. One-year post-rehabilitation outcomes included return-to-work, work retention and healthcare utilization. Economic analyses included a cost-effectiveness analysis of the FR program, and estimation of the total cost-of-illness. At 1-year post-rehabilitation, all groups were comparable on return-to-work (overall 88%), work retention (overall 80%), and additional healthcare utilization (overall, 2.2% of patients received re-operations/new surgeries, 2 visits to new healthcare provider). Savings of up to 64% in medical costs, and up to 80% in disability benefits and productivity losses was associated with the ER group. The cost of rehabilitation was also up to 56% lower when administered early. Overall, ER resulted in estimated cost savings of up to 72% (or almost $170,000 per claim). Duration of disability does not negatively impact objective work or healthcare utilization outcomes following interdisciplinary FR. However, early rehabilitation is more likely to be a cost-effective solution compared to cases that progress >8 months and receiving FR as a treatment of "last resort".

Operable Unit B Remedial Investigation Sampling and Analysis Plan. Installation Restoration Program (IRP) McClellan Air Force Base

DTIC Science & Technology

1991-11-01

R A DIA N.... cCELA AFB CALIFRNI55259......... ... RADIAN C 0 37 54 0 z is T 1 0 10395 Old Placcrvillc Road Sacramcnto, CA 95827 191461362-5 H3 2...SAME AS r __ OTic usERs Undlassified 22a. NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE oncoude Area Code) 22c. OFFICE SYMBOL Mr. P. Haas 1 -800-821...Page 1.0 INTRODUCTION .................................... . 1 - 1 2.0 SITE DESCRIPTION .................................. 2- 1 2.1 Type of Facilities

ER Consolidated Qtrly Rpt_April thru June 2015_October 2015

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

Cochran, John

2015-10-01

This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit, and the Compliance Order on Consent. The 13 sites in the Corrective Action process are listed in Table I-1. Because the status of any Long-Term Stewardship (LTS) activity is detailed in other reports, Section I.3.0 (titled Long-Term Stewardship Work Completed) will not be presented in future ER Quarterly Reports. Section I.3.0 of this ER Quarterly Report identifies the other reports that detail LTS activities.

The effect of an erbium, chromium: yttrium-scandium-gallium-garnet laser on the microleakage and bond strength of silorane and micro-hybrid composite restorations

PubMed Central

Korkmaz, Fatih Mehmet; Baygin, Ozgul; Tuzuner, Tamer; Bagis, Bora; Arslan, Ipek

2013-01-01

Objective: The aim of this in vitro study was to compare the microleakage and bond strength of Class V silorane-based and universal micro-hybrid composite restorations prepared either with diamond bur or with an erbium, chromium: yttrium-scandium-gallium-garnet (Er, Cr:YSGG) laser. Materials and Methods: A total of 160 molar teeth were used for microleakage assessment and shear bond strength (SBS) test. The specimens were prepared using either diamond bur or 3 W-, 4 W- and 5 W-20 Hz Er, Cr:YSGG laser irradiation. All specimens were subjected to thermocycling (500 times at 5 ± 2°C to 55 ± 2°C, dwell time 15 s and transfer time 10 s). Microleakage was assessed using a 0.5% basic-fuchsin solution. The bond strengths were determined using a microtensile tester at a crosshead speed of 0.5 mm/min. The Kruskal Wallis test was used for the analysis of microleakage and a one-way analysis of variance test was used to analyze the SBS (P < 0.05). Results: No statistically significant differences were found (P > 0.05) between Er, Cr:YSGG laser and bur preparation methods regarding microleakage and bond strength values. Conclusion: Irradiation with Er, Cr:YSGG laser was confirmed to be as effective as conventional methods for preparing cavities before adhesive restorations. PMID:24966726

Evaluation of enamel mineral loss around cavities prepared by the Er,Cr:YSGG laser and restored with different materials

NASA Astrophysics Data System (ADS)

Navarro, Ricardo Scarparo; Lago, Andréa. Dias Neves; Bonifácio, Clarissa Calil; Mendes, Fausto Medeiros; de Freitas, Patrícia Moreira; Baptista, Alessandra; Nunez, Silvia Cristina; Matos, Adriana Bona; Imparato, José Carlos P.

2018-02-01

The aim of this study was to evaluate the enamel demineralization around cavities prepared by Er,Cr:YSGG laser (2780 nm) and restored with different materials after an acid challenge. The human dental enamel samples were randomly divided in 12 groups (n=10): G1- high-speed drill (HD); G2- Er,Cr:YSGG laser L (3 W, 20 Hz, 53.05 J/cm2)(air 65% - water 55%); G3- L (4 W, 20 Hz, 70.74 J/cm2); G4- L (5 W, 20 Hz, 88.43 J/cm2). Each group was divided in subgroups: 1- glass ionomer cement (GIC), 2- resin modified GIC (RMGIC), 3- composite resin (C). Samples were submitted to an acid challenge (4.8 pH) for7 days. The calcium ion contend (ppm/mm2) from demineralizing solutions were analyzed by atomic emission spectrometry. ANOVA and LSD tests were performed (α=5%). The significant lower average values of calcium loss were observed on G2 + GIC, G2 + RMGIC, G1 + RMGIC (p<0.05) the significant higher values were observed on G1 + C, G4 +GIC, G4 + C (p<0.05). The composite resin showed higher calcium loss than RMGIC and GIC (p<0.05). The lased cavities using lower fluence (53.05J/cm2) showed significant reduced demineralization than higher fluences (70.74 and 88.43J/cm2) (p<0.05). Neither the techniques nor the restorative materials used were able to avoid the enamel demineralization. The findings of this in vitro study suggest that the Er,Cr:YSGG lased cavities restored with GIC or RMGIC or conventional drill cavities with RMGIC were effective on reducing the demineralization around restorations, showing an important potential in preventing secondary caries.

A Comparative Study of Microleakage on Dental Surfaces Bonded with Three Self-Etch Adhesive Systems Treated with the Er:YAG Laser and Bur

PubMed Central

Sanhadji El Haddar, Youssef; Cetik, Sibel; Bahrami, Babak; Atash, Ramin

2016-01-01

Aim. This study sought to compare the microleakage of three adhesive systems in the context of Erbium-YAG laser and diamond bur cavity procedures. Cavities were restored with composite resin. Materials and Methods. Standardized Class V cavities were performed in 72 extracted human teeth by means of diamond burs or Er-YAG laser. The samples were randomly divided into six groups of 12, testing three adhesive systems (Clearfil s3 Bond Plus, Xeno® Select, and Futurabond U) for each method used. Cavities were restored with composite resin before thermocycling (methylene blue 2%, 24 h). The slices were prepared using a microtome. Optical microscope photography was employed to measure the penetration. Results. No statistically significant differences in microleakage were found in the use of bur or laser, nor between adhesive systems. Only statistically significant values were observed comparing enamel with cervical walls (p < 0.001). Conclusion. It can be concluded that the Er:YAG laser is as efficient as diamond bur concerning microleakage values in adhesive restoration procedures, thus constituting an alternative tool for tooth preparation. PMID:27419128

A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis.

PubMed

Joshi, Amit S; Huang, Xiaofang; Choudhary, Vineet; Levine, Tim P; Hu, Junjie; Prinz, William A

2016-11-21

Saccharomyces cerevisiae contains three conserved reticulon and reticulon-like proteins that help maintain ER structure by stabilizing high membrane curvature in ER tubules and the edges of ER sheets. A mutant lacking all three proteins has dramatically altered ER morphology. We found that ER shape is restored in this mutant when Pex30p or its homologue Pex31p is overexpressed. Pex30p can tubulate membranes both in cells and when reconstituted into proteoliposomes, indicating that Pex30p is a novel ER-shaping protein. In contrast to the reticulons, Pex30p is low abundance, and we found that it localizes to subdomains in the ER. We show that these ER subdomains are the sites where most preperoxisomal vesicles (PPVs) are generated. In addition, overproduction or deletion of Pex30p or Pex31p alters the size, shape, and number of PPVs. Our findings suggest that Pex30p and Pex31p help shape and generate regions of the ER where PPV biogenesis occurs.

Endoplasmic Reticulum Stress and Type 2 Diabetes

PubMed Central

Back, Sung Hoon; Kaufman, Randal J.

2013-01-01

Given the functional importance of the endoplasmic reticulum (ER), an organelle that performs folding, modification, and trafficking of secretory and membrane proteins to the Golgi compartment, the maintenance of ER homeostasis in insulin-secreting β-cells is very important. When ER homeostasis is disrupted, the ER generates adaptive signaling pathways, called the unfolded protein response (UPR), to maintain homeostasis of this organelle. However, if homeostasis fails to be restored, the ER initiates death signaling pathways. New observations suggest that both chronic hyperglycemia and hyperlipidemia, known as important causative factors of type 2 diabetes (T2D), disrupt ER homeostasis to induce unresolvable UPR activation and β-cell death. This review examines how the UPR pathways, induced by high glucose and free fatty acids (FFAs), interact to disrupt ER function and cause β-cell dysfunction and death. PMID:22443930

Bioassay criteria for environmental restoration workers

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

Carbaugh, E.H.; Bihl, D.E.

1993-01-01

Environmental restoration (ER) work at the U. S. Department of Energy Hanford Site posed questions concerning when to perform bioassay monitoring of workers for potential intakes of radioactivity. Application of criteria originally developed for use inside radionuclide processing facilities to ER work resulted in overly restrictive bioassay requirements. ER work typically involves site characterization or, excavating large quantities of potentially contaminated soil, rather than working with concentrated quantities of radioactivity as in a processing facility. An improved approach, tailored to ER work, provided soil contamination concentrations above which worker bioassay would be required. Soil concentrations were derived assuming acute ormore » chronic intakes of 2% of an Annual Limit on Intake (ALI), or a potential committed effective dose equivalent of 100 mrem, and conservative dust loading of air from the work. When planning ER work, the anticipated soil concentration and corresponding need for bioassay could be estimated from work-site historical records. Once site work commenced, soil sampling and work-place surveys could be used to determine bioassay needs. This approach substantially reduced the required number of bioassay samples with corresponding reductions in analytical costs, schedules, and more flexible work-force management. (Work supported by the US Department of Energy under contract DOE-AC06-76RLO 1830.)« less

Does ErbiumiYttrium-Aluminum-Garnet Laser to Enamel improve the Performance of Etch-and-rinse and Universal Adhesives?

PubMed

De Jesus Tavarez, Rudys R; Rodrigues, Lorrany Lc; Diniz, Ana C; Lage, Lucas M; Torres, Carlos Rg; Bandeca, Matheus C; Firoozmand, Leily M

2018-03-01

This study aims to evaluate the effect of erbium: Yttrium-aluminum-garnet (Er:YAG) laser irradiation on the enamel microshear bond strength (μSBS), followed by the utilization of etch-and-rinse and universal adhesive systems. A total of 32 molars were sectioned in the mesiodistal direction producing 64 samples that were randomized into two groups (n = 32): single bond 2 (SB2) (etch-and-rinse system; 3M), SB universal (SBU) (universal etching system; The SB2 and SBU groups were then divided into two subgroups (n = 16): (i) enamel was irradiated with an Er:YAG laser (λ = 2.94 μm, 60 mJ, 10 Hz), and (ii) enamel served as a control. The samples were restored with TPH3 (Dentsply), stored in artificial saliva for 24 hours, and subjected to a micro-shear test. Kruskal-Wallis (p < 0.05) and Mann-Whitney U tests indicated no significant differences in uSBS between the groups, and the fractures were predominately at the resin-enamel interface. The previous irradiation of enamel with Er:YAG laser does not interfere with the performance of simplified two-step etch-and-rinse and universal adhesive systems. The increasing use of Er:YAG laser is important to evaluate the influence of this irradiation on the adhesion of restorative materials. Thus, to obtain the longevity of the restorative procedures, it is necessary to know the result of the association of the present adhesive systems to the irradiated substrate.

Pathological study of pulp treated with chemicals after Er:YAG laser preparation.

PubMed

Akashi, Go; Kato, Junji; Hirai, Yoshito

2006-12-01

The aim of this study was to clarify pulp reaction following cavity preparation with an Er:YAG laser and subsequent treatment with topically applied chemicals to achieve a high resin bond strength. The application of chemicals has been found to effectively remove or reform the denatured layer produced by Er:YAG laser irradiation and has been proposed as a new strategy for improving resin bond strength. However, very little is known about pulp reaction to chemical procedures. Class 5 dentin cavities were prepared with an Er:YAG laser in 128 teeth in nine adult dogs. The teeth were then coated with glutaraldehyde (GA group), or phosphoric acid and sodium hypochlorite (PA group) to reform or remove the denatured layer. All the cavities were then restored with composite resin. In the control group, no chemical application was carried out prior to restoration. The animals were sacrificed immediately after, and at 7 and 90 days following treatment. The treated teeth were then extracted for histopathological examination of the pulp. Pathological evaluation of the pulp indicated a good condition in each group at each of the three observation time points. No bacterial growth was observed on the cavity walls or bacterial invasion into the dentinal tubules or pulp chambers in any of the groups at any of the observation periods. Our findings suggest that the application of chemicals to remove or reform denatured layers is effective in obtaining better composite resin restoration with no pulp damage.

Consolidated Quarterly Report: Number of potential release sites subject to corrective action

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

Cochran, John R.

2017-04-01

This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit and the Compliance Order on Consent. The 12 sites in the corrective action process are listed in Table I-1.

1991 Environmental monitoring report Sandia National Laboratories, Albuquerque, New Mexico

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

Culp, T.; Cox, W.; Hwang, S.

1992-11-01

This 1991 report contains monitoring data from routine radiological and nonradiological environmental surveillance activities. Summaries of significant environmental compliance programs in progress such as National Environmental Policy Act (NEPA) documentation, environmental permits, environmental restoration (ER), and various waste management programs for Sandia National Laboratories in Albuquerque (SNL, Albuquerque) are included. The maximum offsite dose impact was calculated to be 1.3 {times} 10{sup {minus}3} mrem. The total population within a 50-mile radius of SNL, Albuquerque, received a collective dose of 0.53 person-rem during 1991 from SNL, Albuquerque, operations. As in the previous year, the 1991 operations at SNL, Albuquerque, had nomore » discernible impact on the general public or on the environment.« less

Surface debris inventory at White Wing Scrap Yard, Oak Ridge Reservation, Oak Ridge, Tennessee. Environmental Restoration Program

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

Rodriguez, R.E.; Tiner, P.F.; Williams, J.K.

1992-08-01

An inventory of surface debris in designated grid blocks at the White Wing Scrap Yard [Waste Area Grouping 11 (WAG 11)] was conducted intermittently from February through June 1992 by members of the Measurement Applications and Development Group, Health and Safety Research Division, Oak Ridge National Laboratory (ORNL) at the request of ORNL Environmental Restoration (ER) Program personnel. The objectives of this project are outlined in the following four phases: (1) estimate the amount (volume) and type (e.g., glass, metal and plastics) of surface waste material in 30 designated grid blocks (100- by 100-ft grids); (2) conduct limited air samplingmore » for organic chemical pollutants at selected locations (e.g., near drums, in holes, or other potentially contaminated areas); (3) conduct a walkover gamma radiation scan extending outward (approximately 50 ft) beyond the proposed location of the WAG 11 perimeter fence; and (4) recommend one grid block as a waste staging area. This recommendation is based on location and accessibility for debris staging/transport activities and on low levels of gamma radiation in the grid block.« less

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

Griffith, Stacy Rene; Agogino, Karen; Li, Jun

Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities managed and operated by Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Field Office (SFO), in Albuquerque, New Mexico, administers the contract and oversees contractor operations at TTR and KTF. Sandia manages and conducts operations at TTR in support of the DOE/NNSA’s Weapons Ordnance Program and has operated the site since 1957. Navarro Research and Engineering subcontracts to Sandia in administering most of the environmental programsmore » at TTR. Sandia operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report summarizes data and the compliance status of the sustainability, environmental protection, and monitoring program at TTR and KTF through Calendar Year 2013. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, Environmental Restoration (ER) cleanup activities, and the National Environmental Policy Act. Sandia is responsible only for those environmental program activities related to its operations. The DOE/NNSA/Nevada Field Office retains responsibility for the cleanup and management of TTR ER sites. Environmental monitoring and surveillance programs are required by DOE Order 231.1B, Environment, Safety, and Health Reporting (DOE 2012).« less

The economics of restoration: looking back and leaping forward.

PubMed

Blignaut, James; Aronson, James; de Wit, Martin

2014-08-01

Since the publication of the Millennium Ecosystem Assessment in 2005 there has been a surge of interest in ecological restoration (ER) to recover biodiversity, re-establish ecosystem functioning and connectivity, and reactivate the delivery of ecosystem services. In policy spheres, there have also been repeated calls for expansion of restoration efforts. In many countries, new legislation now requires some form of restoration and/or a form of offset investment. All of this will require major increases in financial allocations toward restoration science, technology, and implementation, and much more detailed valuation techniques. The economics of restoration is a new field emerging to support these needs. Our paper here starts with an analysis of the articles and reviews published on this broad subject from 1928 to 2012, as captured in the Scopus academic search platform. Our goal is to present and summarize what has been said and done in this area to date. Next, we map out one possible way forward, illustrated by examples and based on a coherent bundle of decision parameters related to the economics of ER and, more broadly, to the restoration of natural capital. The restoration of natural capital is defined as activities that integrate investment in, and replenishment of, natural capital stocks to improve the flows of ecosystem goods and services, and the preservation of biodiversity, while enhancing all aspects of human well-being. We give special attention to system dynamic approaches and other promising tools and techniques. © 2014 New York Academy of Sciences.

Calendar year 2004 annual site environmental report:Sandia National Laboratories, Albuquerque, New Mexico.

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

Montoya, Amber L.; Goering, Teresa Lynn; Wagner, Katrina

2005-09-01

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned, contractor-operated facility owned by the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA) and managed by the Sandia Site Office (SSO), Albuquerque, New Mexico. Sandia Corporation, a wholly-owned subsidiary of Lockheed Martin Corporation, operates SNL/NM. This annual report summarizes data and the compliance status of Sandia Corporation's environmental protection and monitoring programs through December 31, 2004. Major environmental programs include air quality, water quality, groundwater protection, terrestrial surveillance, waste management, pollution prevention (P2), environmental restoration (ER), oil and chemical spill prevention, and the National Environmental Policy Act (NEPA). Environmentalmore » monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2005) and DOE Order 231.1A, Environment, Safety, and Health Reporting (DOE 2004a). (DOE 2004a).« less

Calendar year 2003 annual site environmental report for Sandia National Laboratories, New Mexico.

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

Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie

2004-09-01

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned, contractor-operated facility owned by the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA) and managed by the Sandia Site Office (SSO), Albuquerque, New Mexico. Sandia Corporation, a wholly-owned subsidiary of Lockheed Martin Corporation, operates SNL/NM. This annual report summarizes data and the compliance status of Sandia Corporation's environmental protection and monitoring programs through December 31, 2003. Major environmental programs include air quality, water quality, groundwater protection, terrestrial surveillance, waste management, pollution prevention (P2), environmental restoration (ER), oil and chemical spill prevention, and the National Environmental Policy Act (NEPA). Environmentalmore » monitoring and surveillance programs are required by DOE Order 450.1, ''Environmental Protection Program'' (DOE 2003a) and DOE Order 231.1 Chg.2, ''Environment, Safety, and Health Reporting'' (DOE 1996).« less

Effect of water on dental material ablation of the Er:YAG laser

NASA Astrophysics Data System (ADS)

Wigdor, Harvey A.; Visuri, Steven R.; Walsh, Joseph T., Jr.

1994-09-01

It is understood that if a laser is to replace the dental high speed handpiece it must be able to ablate dental materials which are present in teeth being treated with the laser. It is the intent of this paper to evaluate the effects of the Er:YAG laser on dental composite restorative material concentrating on the etch rate with and without waterspray. Composite dental material is used to form plugs of known thickness and the etch rate of the Er:YAG laser on this material is determined. The results are compared with those obtained from studies of the Er:YAG on dentin and enamel. In these studies the water reduced the efficiency of the Er:YAG laser 15 - 20% on these tissues.

BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

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

Watanabe, Kenta; Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588; Hirata, Michiko

Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as amore » pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.« less

Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: a potential new therapeutic approach.

PubMed

Santos-Martínez, Nancy; Díaz, Lorenza; Ordaz-Rosado, David; García-Quiroz, Janice; Barrera, David; Avila, Euclides; Halhali, Ali; Medina-Franco, Heriberto; Ibarra-Sánchez, María J; Esparza-López, José; Camacho, Javier; Larrea, Fernando; García-Becerra, Rocío

2014-03-29

Approximately 30% of breast tumors do not express the estrogen receptor (ER) α, which is necessary for endocrine therapy approaches. Studies are ongoing in order to restore ERα expression in ERα-negative breast cancer. The aim of the present study was to determine if calcitriol induces ERα expression in ER-negative breast cancer cells, thus restoring antiestrogen responses. Cultured cells derived from ERα-negative breast tumors and an ERα-negative breast cancer cell line (SUM-229PE) were treated with calcitriol and ERα expression was assessed by real time PCR and western blots. The ERα functionality was evaluated by prolactin gene expression analysis. In addition, the effects of antiestrogens were assessed by growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and Ether-à-go-go 1 (EAG1) was also evaluated in cells treated with calcitriol alone or in combination with estradiol or ICI-182,780. Statistical analyses were determined by one-way ANOVA. Calcitriol was able to induce the expression of a functional ERα in ER-negative breast cancer cells. This effect was mediated through the vitamin D receptor (VDR), since it was abrogated by a VDR antagonist. Interestingly, the calcitriol-induced ERα restored the response to antiestrogens by inhibiting cell proliferation. In addition, calcitriol-treated cells in the presence of ICI-182,780 resulted in a significant reduction of two important cell proliferation regulators CCND1 and EAG1. Calcitriol induced the expression of ERα and restored the response to antiestrogens in ERα-negative breast cancer cells. The combined treatment with calcitriol and antiestrogens could represent a new therapeutic strategy in ERα-negative breast cancer patients.

Inflammation and cellular stress: a mechanistic link between immune-mediated and metabolically driven pathologies.

PubMed

Rath, Eva; Haller, Dirk

2011-06-01

Multiple cellular stress responses have been implicated in chronic diseases such as obesity, diabetes, cardiovascular, and inflammatory bowel diseases. Even though phenotypically different, chronic diseases share cellular stress signaling pathways, in particular endoplasmic reticulum (ER) unfolded protein response (UPR). The purpose of the ER UPR is to restore ER homeostasis after challenges of the ER function. Among the triggers of ER UPR are changes in the redox status, elevated protein synthesis, accumulation of unfolded or misfolded proteins, energy deficiency and glucose deprivation, cholesterol depletion, and microbial signals. Numerous mouse models have been used to characterize the contribution of ER UPR to several pathologies, and ER UPR-associated signaling has also been demonstrated to be relevant in humans. Additionally, recent evidence suggests that the ER UPR is interrelated with metabolic and inflammatory pathways, autophagy, apoptosis, and mitochondrial stress signaling. Furthermore, microbial as well as nutrient sensing is integrated into the ER-associated signaling network. The data discussed in the present review highlight the interaction of ER UPR with inflammatory pathways, metabolic processes and mitochondrial function, and their interrelation in the context of chronic diseases.

Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster

PubMed Central

Lindström, Riitta; Lindholm, Päivi; Kallijärvi, Jukka; Palgi, Mari; Saarma, Mart; Heino, Tapio I.

2016-01-01

Disturbances in the homeostasis of endoplasmic reticulum (ER) referred to as ER stress is involved in a variety of human diseases. ER stress activates unfolded protein response (UPR), a cellular mechanism the purpose of which is to restore ER homeostasis. Previous studies show that Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) is an important novel component in the regulation of UPR. In vertebrates, MANF is upregulated by ER stress and protects cells against ER stress-induced cell death. Biochemical studies have revealed an interaction between mammalian MANF and GRP78, the major ER chaperone promoting protein folding. In this study we discovered that the upregulation of MANF expression in response to drug-induced ER stress is conserved between Drosophila and mammals. Additionally, by using a genetic in vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR. PMID:26975047

Unfolded Protein Response of the Endoplasmic Reticulum in Tumor Progression and Immunogenicity

PubMed Central

Yoo, Yoon Seon; Han, Hye Gyeong

2017-01-01

The endoplasmic reticulum (ER) is a pivotal regulator of folding, quality control, trafficking, and targeting of secreted and transmembrane proteins, and accordingly, eukaryotic cells have evolved specialized machinery to ensure that the ER enables these proteins to acquire adequate folding and maturation in the presence of intrinsic and extrinsic insults. This adaptive capacity of the ER to intrinsic and extrinsic perturbations is important for maintaining protein homeostasis, which is termed proteostasis. Failure in adaptation to these perturbations leads to accumulation of misfolded or unassembled proteins in the ER, which is termed ER stress, resulting in the activation of unfolded protein response (UPR) of the ER and the execution of ER-associated degradation (ERAD) to restore homeostasis. Furthermore, both of the two axes play key roles in the control of tumor progression, inflammation, immunity, and aging. Therefore, understanding UPR of the ER and subsequent ERAD will provide new insights into the pathogenesis of many human diseases and contribute to therapeutic intervention in these diseases. PMID:29430279

Unfolded protein response is required for Aspergillus oryzae growth under conditions inducing secretory hydrolytic enzyme production.

PubMed

Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

2015-12-01

Unfolded protein response (UPR) is an intracellular signaling pathway for adaptation to endoplasmic reticulum (ER) stress. In yeast UPR, Ire1 cleaves the unconventional intron of HAC1 mRNA, and the functional Hac1 protein translated from the spliced HAC1 mRNA induces the expression of ER chaperone genes and ER-associated degradation genes for the refolding or degradation of unfolded proteins. In this study, we constructed an ireA (IRE1 ortholog) conditionally expressing strain of Aspergillus oryzae, a filamentous fungus producing a large amount of amylolytic enzymes, and examined the contribution of UPR to ER stress adaptation under physiological conditions. Repression of ireA completely blocked A. oryzae growth under conditions inducing the production of hydrolytic enzymes, such as amylases and proteases. This growth defect was restored by the introduction of unconventional intronless hacA (hacA-i). Furthermore, UPR was observed to be induced by amylolytic gene expression, and the disruption of the transcriptional activator for amylolytic genes resulted in partial growth restoration of the ireA-repressing strain. In addition, a homokaryotic ireA disruption mutant was successfully generated using the strain harboring hacA-i as a parental host. These results indicated that UPR is required for A. oryzae growth to alleviate ER stress induced by excessive production of hydrolytic enzymes. Copyright © 2015 Elsevier Inc. All rights reserved.

Antioxidants Complement the Requirement for Protein Chaperone Function to Maintain β-Cell Function and Glucose Homeostasis

PubMed Central

Han, Jaeseok; Song, Benbo; Kim, Jiun; Kodali, Vamsi K.; Pottekat, Anita; Wang, Miao; Hassler, Justin; Wang, Shiyu; Pennathur, Subramaniam; Back, Sung Hoon; Katze, Michael G.

2015-01-01

Proinsulin misfolding in the endoplasmic reticulum (ER) initiates a cell death response, although the mechanism(s) remains unknown. To provide insight into how protein misfolding may cause β-cell failure, we analyzed mice with the deletion of P58IPK/DnajC3, an ER luminal co-chaperone. P58IPK−/− mice become diabetic as a result of decreased β-cell function and mass accompanied by induction of oxidative stress and cell death. Treatment with a chemical chaperone, as well as deletion of Chop, improved β-cell function and ameliorated the diabetic phenotype in P58IPK−/− mice, suggesting P58IPK deletion causes β-cell death through ER stress. Significantly, a diet of chow supplemented with antioxidant dramatically and rapidly restored β-cell function in P58IPK−/− mice and corrected abnormal localization of MafA, a critical transcription factor for β-cell function. Antioxidant feeding also preserved β-cell function in Akita mice that express mutant misfolded proinsulin. Therefore defective protein folding in the β-cell causes oxidative stress as an essential proximal signal required for apoptosis in response to ER stress. Remarkably, these findings demonstrate that antioxidant feeding restores cell function upon deletion of an ER molecular chaperone. Therefore antioxidant or chemical chaperone treatment may be a promising therapeutic approach for type 2 diabetes. PMID:25795214

A novel carborane analog, BE360, with a carbon-containing polyhedral boron-cluster is a new selective estrogen receptor modulator for bone

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

Hirata, Michiko; Inada, Masaki; Matsumoto, Chiho

Carboranes are a class of carbon-containing polyhedral boron-cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors. Estrogen deficiency results in marked bone loss due to increased osteoclastic bone resorption in females, but estrogen replacement therapy is not generally used for postmenopausal osteoporosis due to the risk of uterine cancer. We synthesized a novel carborane compound BE360 to clarify its anti-osteoporosis activity. BE360 showed a high binding affinity to estrogen receptors (ER), ER{alpha} and ER{beta}. In ovariectomized (OVX) mice, femoral bone volume was markedly reduced and BE360 dose-dependently restored bone loss in OVX mice. However, BE360 didmore » not exhibit any estrogenic activity in the uterus. BE360 also restored bone loss in orchidectomized mice without androgenic action in the sex organs. Therefore, BE360 is a novel selective estrogen receptor modulator (SERM) that may offer a new therapy option for osteoporosis.« less

Environmental Restoration Operations: Consolidated Quarterly Report January -March 2017

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

Cochran, John R.

This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented at Sandia National Laboratories, New Mexico (SNL/NM) during the January, February, and March 2017 quarterly reporting period. Table I-1 lists the Solid Waste Management Units (SWMUs) and Areas of Concern (AOCs) identified for corrective action at SNL/NM. Sections I.2.1 and I.2.2 summarize the work completed during this quarter. Section I.2.1 summarizes the quarterly activities at sites undergoing corrective action field activities. Field activities are conducted at the three groundwater AOCs (Burn Site Groundwater [BSG AOC], Technical Area [TA]-V Groundwatermore » [TAVG AOC], and Tijeras Arroyo Groundwater [TAG AOC]). Section I.2.2 summarizes quarterly activities at sites where the New Mexico Environment Department (NMED) Hazardous Waste Bureau (HWB) issued a certificate of completion and the sites are in the corrective action complete (CAC) regulatory process. Currently, SWMUs 8 and 58, 68, 149, 154, and 502 are in the CAC regulatory process. Corrective action activities are deferred at the Long Sled Track (SWMU 83), the Gun Facilities (SWMU 84), and the Short Sled Track (SWMU 240) because these three sites are active mission facilities. These three active mission sites are located in TA-III. This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit and the Compliance Order on Consent.« less

Dominant gain-of-function mutations in transmembrane domain III of ERS1 and ETR1 suggest a novel role for this domain in regulating the magnitude of ethylene response in Arabidopsis.

PubMed

Deslauriers, Stephen D; Alvarez, Ashley A; Lacey, Randy F; Binder, Brad M; Larsen, Paul B

2015-10-01

Prior work resulted in identification of an Arabidopsis mutant, eer5-1, with extreme ethylene response in conjunction with failure to induce a subset of ethylene-responsive genes, including AtEBP. EER5, which is a TREX-2 homolog that is part of a nucleoporin complex, functions as part of a cryptic aspect of the ethylene signaling pathway that is required for regulating the magnitude of ethylene response. A suppressor mutagenesis screen was carried out to identify second site mutations that could restore the growth of ethylene-treated eer5-1 to wild-type levels. A dominant gain-of-function mutation in the ethylene receptor ETHYLENE RESPONSE SENSOR 1 (ERS1) was identified, with the ers1-4 mutation being located in transmembrane domain III at a point nearly equivalent to the previously described etr1-2 mutation in the other Arabidopsis subfamily I ethylene receptor, ETHYLENE RESPONSE 1 (ETR1). Although both ers1-4 and etr1-2 partially suppress the ethylene hypersensitivity of eer5-1 and are at least in part REVERSION TO ETHYLENE SENSITIVITY 1 (RTE1)-dependent, ers1-4 was additionally found to restore the expression of AtEBP in ers1-4;eer5-1 etiolated seedlings after ethylene treatment in an EIN3-dependent manner. Our work indicates that ERS1-regulated expression of a subset of ethylene-responsive genes is related to controlling the magnitude of ethylene response, with hyperinduction of these genes correlated with reduced ethylene-dependent growth inhibition. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The endoplasmic reticulum stress response: A link with tuberculosis?

PubMed

Cui, Yongyong; Zhao, Deming; Barrow, Paul Andrew; Zhou, Xiangmei

2016-03-01

Tuberculosis (TB) remains a major cause of mortality and morbidity in the worldwide. The endoplasmic-reticulum stress (ERS) response constitutes a cellular process that is triggered by mycobacterial infection that disturbs the folding of proteins in the endoplasmic reticulum (ER). The unfolded protein response (UPR) is induced to suspend the synthesis of early proteins and reduce the accumulation of unfolded- or misfolded proteins in the ER restoring normal physiological cell function. Prolonged or uncontrolled ERS leads to the activation of three signaling pathways (IRE1, PERK and ATF6) which directs the cell towards apoptosis. The absence of this process facilitates spread of the mycobacteria within the body. We summarize here recent advances in understanding the signaling pathway diversity governing ERS in relation to TB. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rab7a modulates ER stress and ER morphology.

PubMed

Mateus, Duarte; Marini, Elettra Sara; Progida, Cinzia; Bakke, Oddmund

2018-05-01

The Endoplasmic Reticulum (ER) is a membranous organelle with diverse structural and functional domains. Peripheral ER includes interconnected tubules, and dense tubular arrays called "ER matrices" together with bona fide flat cisternae. Transitions between these states are regulated by membrane-associated proteins and cytosolic factors. Recently, the small GTPases Rab10 and Rab18 were reported to control ER shape by regulating ER dynamics and fusion. Here, we present evidence that another Rab protein, Rab7a, modulates the ER morphology by controlling the ER homeostasis and ER stress. Indeed, inhibition of Rab7a expression by siRNA or expression of the dominant negative mutant Rab7aT22 N, leads to enlargement of sheet-like ER structures and spreading towards the cell periphery. Notably, such alterations are ascribable neither to a direct modulation of the ER shaping proteins Reticulon-4b and CLIMP63, nor to interactions with Protrudin, a Rab7a-binding protein known to affect the ER organization. Conversely, depletion of Rab7a leads to basal ER stress, in turn causing ER membrane expansion. Both ER enlargement and basal ER stress are reverted in rescue experiments by Rab7a re-expression, as well as by the ER chemical chaperone tauroursodeoxycholic acid (TUDCA). Collectively, these findings reveal a new role of Rab7a in ER homeostasis, and indicate that genetic and pharmacological ER stress manipulation may restore ER morphology in Rab7a silenced cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription.

PubMed

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-03-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR(ER)) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPR(ER) genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPR(ER) genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPR(ER) genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. © 2015 The Authors.

OCT for early quality evaluation of tooth-composite bond in clinical trials.

PubMed

Haak, Rainer; Schmidt, Patrick; Park, Kyung-Jin; Häfer, Matthias; Krause, Felix; Ziebolz, Dirk; Schneider, Hartmut

2018-06-19

To evaluate early quality of composite restorations with a universal adhesive in different application modes clinically and with optical coherence tomography (OCT). 22 patients with four non-carious cervical lesions each received composite restorations (Filtek Supreme TM XTE, 3 M). The universal adhesive Scotchbond Universal TM (SBU, 3 M) was applied with three etching protocols: self-etch (SE), selective-enamel-etch (SEE) and etch-and-rinse (ER). The etch-and-rinse adhesive OptiBond TM FL (OFL, Kerr) served as a control. Restorations were imaged by OCT (Thorlabs) directly after application (t 0 ). After 14 days (t 1 ) and 6 month (t 2 ) OCT imaging (interfacial adhesive defects) was repeated combined with clinical assessment (FDI criteria). Groups were compared by Friedman-/Wilcoxon- and McNemar-Test. No differences were seen clinically between groups (p i ≥ 0.500). OCT assessment revealed more adhesive defects at the enamel interface with SBU/SE at t 0- t 2 compared to all groups (p i ≤ 0.016). OFL showed more defects than SBU/ER (t 1 : p = 0.01; t 2 : p = 0.083). At dentin/cementum interface OFL exhibited more adhesive defects than SBU with all conditioning modes (t 0 , t 1 , p i ≤ 0.003) and at t 2 to SBU/SE and SBU/ER (p < 0.001). Since t 1 defects with SBU were detected more frequently in the SE and SEE modes compared to ER (p i ≤ 0.037). In contrast to SBU defects increased with OFL up to t 2 (p i ≤ 0.007). In contrast to clinical evaluation, OCT revealed subtle adhesive defects directly after application that might interfere with clinical success. It was demonstrated that ER doesn't decrease initial adhesion of SBU to dentin. Copyright © 2018. Published by Elsevier Ltd.

Influence of pulse repetition rate on temperature rise and working time during composite filling removal with the Er:YAG laser.

PubMed

Correa-Afonso, Alessandra M; Pécora, Jesus Djalma; Palma-Dibb, Regina G

2008-06-01

The purpose of this study was to assess the efficacy of Er:YAG laser energy for composite resin removal and the influence of pulse repetition rate on the thermal alterations occurring during laser ablation. Composite resin filling was placed in cavities (1.0 mm deep) prepared in bovine teeth and the specimens were randomly assigned to five groups according to the technique used for composite filling removal. In group I (controls), the restorations were removed using a high-speed diamond bur. In the other groups, the composite fillings were removed using an Er:YAG laser with different pulse repetition rates: group 2-2 Hz; group 3-4 Hz; group 4-6 Hz; and group 5-10 Hz. The time required for complete removal of the restorative material and the temperature changes were recorded. Temperature rise during composite resin removal with the Er:YAG laser occurred in the substrate underneath the restoration and was directly proportional to the increase in pulse repetition rate. None of the groups had a temperature increase during composite filling removal of more than 5.6 degrees C, which is considered the critical point above which irreversible thermal damage to the pulp may result. Regarding the time for composite filling removal, all the laser-ablated groups (except for group 5 [10 Hz]) required more time than the control group for complete elimination of the material from the cavity walls. Under the tested conditions, Er:YAG laser irradiation was efficient for composite resin ablation and did not cause a temperature increase above the limit considered safe for the pulp. Among the tested pulse repetition rates, 6 Hz produced minimal temperature change compared to the control group (high-speed bur), and allowed composite filling removal within a time period that is acceptable for clinical conditions.

Transcriptional repression of ER through hMAPK dependent histone deacetylation by class I HDACs.

PubMed

Plotkin, Amy; Volmar, Claude-Henry; Wahlestedt, Claes; Ayad, Nagi; El-Ashry, Dorraya

2014-09-01

Anti-estrogen therapies are not effective in ER- breast cancers, thus identifying mechanisms underlying lack of ER expression in ER- breast cancers is imperative. We have previously demonstrated that hyperactivation of MAPK (hMAPK) downstream of overexpressed EGFR or overexpression/amplification of Her2 represses ER protein and mRNA expression. Abrogation of hMAPK in ER- breast cancer cell lines and primary cultures causes re-expression of ER and restoration of anti-estrogen responses. This study was performed to identify mechanisms of hMAPK-induced transcriptional repression of ER. We found that ER promoter activity is significantly reduced in the presence of hMAPK signaling, yet did not identify specific promoter sequences responsible for this repression. We performed an epigenetic compound screen in an ER- breast cancer cell line that expresses hMAPK yet does not exhibit ER promoter hypermethylation. A number of HDAC inhibitors were identified and confirmed to modulate ER expression and estrogen signaling in multiple ER- cell lines and tumor samples lacking ER promoter methylation. siRNA-mediated knockdown of HDACs 1, 2, and 3 reversed the mRNA repression in multiple breast cancer cell lines and primary cultures and ER promoter-associated histone acetylation increased following MAPK inhibition. These data implicate histone deacetylation downstream of hMAPK in the observed ER mRNA repression associated with hMAPK. Importantly, histone deacetylation appears to be a common mechanism in the transcriptional repression of ER between ER- breast cancers with or without ER promoter hypermethylation.

Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.

PubMed

Henis-Korenblit, Sivan; Zhang, Peichuan; Hansen, Malene; McCormick, Mark; Lee, Seung-Jae; Cary, Michael; Kenyon, Cynthia

2010-05-25

When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Structural changes in the irradiated dentin with Nd:YAG and Er:YAG lasers for cervical hypersensitivity treatment and their influence on the microtensile resistance in resin-dentin interface

NASA Astrophysics Data System (ADS)

Mota, Cláudia C. B. O.; Sena, Tatiane V. N. S.; Castro, Roseane F.; Araújo, Ana C. S.; Gomes, Anderson S. L.

2016-02-01

This study aimed to evaluate, in vitro, the structural changes in dentin surfaces irradiated with Er:YAG (2940 nm, 90 mJ, 2 Hz, 300 μs, spot diameter 0.9 mm, 60 s/cm2, using the handpiece at 6 cm of distance to surface) and Nd:YAG (1064 nm, 1 W, 10 Hz, 300 μs, optical fiber diameter 300 μm, 60 s/cm2, using the handpiece at 2 mm of distance to surface) lasers to the treatment of cervical hypersensitivity and the respective bond strength compromising of resin composite restorations over these surfaces. 45 bovine teeth were selected, and removed the enamel portion of the buccal surface for laser irradiation and restorative procedure. Samples were divided into three groups: G1: control, only fluoride therapy; G2: irradiated with Er:YAG laser; G3: irradiated with Nd:YAG laser. Samples were submitted to optical coherence tomography analysis and subsequently they were restored with resin composite and sectioned into sticks for microtensile tests of achievement. ANOVA analysis of variance for the maximum force (N) and strength (MPa), with a significance level of 5% was performed. It was observed that G3 presented lower performance of maximum force (38,8 +/- 11,3 N) and resistance (26,0 +/- 9,3 MPa), and the G2 presented better results (51,0 +/- 13,5 N and 36,5 +/- 10,1 MPa), but still lower than those one obtained for G1 (56,0 +/- 12,3 N and 43,5 +/- 8,6 MPa). Although both lasers are effective in the cervical hypersensitivity treatment, when the aesthetic factor is the priority, the use of Er:YAG is preferable.

Assessment of microleakage of class V restored by resin composite and resin-modified glass ionomer and pit and fissure resin-based sealants following Er:YAG laser conditioning and acid etching: in vitro study

PubMed Central

Luong, Emilie; Shayegan, Amir

2018-01-01

Aim The aim of this study was to make a comparison between microleakage of conventionally restored class V cavities using acid etchant and the ones conditioned by erbium-doped yttrium aluminum garnet (Er:YAG) laser, and also to assess and compare the effectiveness of enamel surface treatments of occlusal pits and fissures by acid etching and conditioned by Er:YAG laser-etch. Materials and methods Seventy-two extracted third molars were used in this study. The samples were divided into two major groups: class V cavities and pit and fissure sealants. Each subgroup was divided into conventional acid etching, Er:YAG laser conditioning and conventional acid etching, and combination with Er:YAG laser conditioning (n=12). The teeth were placed in 2% methylene blue dye solution, were sectioned, and were evaluated according to the dye penetration criteria. Two samples per subgroup were chosen for scanning electron microscopic (SEM) analysis. Results There was a significant difference between occlusal and cervical margin groups. Laser conventional composite cementum group showed more microleakage values compared to other groups. There was no significant difference between occlusal margin groups. However, there was a significant difference between cervical margin groups in terms of microleakage. In sealant groups, there was a significant difference between laser and conventional with/without laser treatment groups in terms of microleakage. Conclusion Based on the results reported in this study, it can be concluded that the application of the Er:YAG laser beneath the resin composite, the resin-modified glass ionomers (GIs), and the fissure sealant placement may be an alternative enamel and dentin etching method to acid etching. PMID:29881311

Preconditioning with Endoplasmic Reticulum Stress Ameliorates Endothelial Cell Inflammation

PubMed Central

Leonard, Antony; Paton, Adrienne W.; El-Quadi, Monaliza; Paton, James C.; Fazal, Fabeha

2014-01-01

Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2α, both markers of ER stress, which in turn resulted in blunting the activation of NF-κB, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced IκBα degradation and its resulting downstream signaling pathway involving NF-κB nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNFα-mediated NF-κB signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-κB was independent of IκBα degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-κB to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-κB activation and regulation of vascular permeability. PMID:25356743

Preconditioning with endoplasmic reticulum stress ameliorates endothelial cell inflammation.

PubMed

Leonard, Antony; Paton, Adrienne W; El-Quadi, Monaliza; Paton, James C; Fazal, Fabeha

2014-01-01

Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2α, both markers of ER stress, which in turn resulted in blunting the activation of NF-κB, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced IκBα degradation and its resulting downstream signaling pathway involving NF-κB nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNFα-mediated NF-κB signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-κB was independent of IκBα degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-κB to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-κB activation and regulation of vascular permeability.

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States

PubMed Central

Iwanicki, Janetta L.; Severtson, S. Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J.; Ellis, Matthew S.; Kurtz, Steven P.; Buttram, Mance E.; Dart, Richard C.

2016-01-01

Background Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Methods Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. Results From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Conclusions Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations. PMID:27936038

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

PubMed

Iwanicki, Janetta L; Severtson, S Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J; Ellis, Matthew S; Kurtz, Steven P; Buttram, Mance E; Dart, Richard C

2016-01-01

Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

PubMed Central

Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

2015-01-01

17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease. PMID:26074768

Distinct intracellular sAC-cAMP domains regulate ER Ca2+ signaling and OXPHOS function.

PubMed

Valsecchi, Federica; Konrad, Csaba; D'Aurelio, Marilena; Ramos-Espiritu, Lavoisier S; Stepanova, Anna; Burstein, Suzanne R; Galkin, Alexander; Magranè, Jordi; Starkov, Anatoly; Buck, Jochen; Levin, Lonny R; Manfredi, Giovanni

2017-11-01

cAMP regulates a wide variety of physiological functions in mammals. This single second messenger can regulate multiple, seemingly disparate functions within independently regulated cell compartments. We have previously identified one such compartment inside the matrix of the mitochondria, where soluble adenylyl cyclase (sAC) regulates oxidative phosphorylation (OXPHOS). We now show that sAC knockout fibroblasts have a defect in OXPHOS activity and attempt to compensate for this defect by increasing OXPHOS proteins. Importantly, sAC knockout cells also exhibit decreased probability of endoplasmic reticulum (ER) Ca 2+ release associated with diminished phosphorylation of the inositol 3-phosphate receptor. Restoring sAC expression exclusively in the mitochondrial matrix rescues OXPHOS activity and reduces mitochondrial biogenesis, indicating that these phenotypes are regulated by intramitochondrial sAC. In contrast, Ca 2+ release from the ER is only rescued when sAC expression is restored throughout the cell. Thus, we show that functionally distinct, sAC-defined, intracellular cAMP signaling domains regulate metabolism and Ca 2+ signaling. © 2017. Published by The Company of Biologists Ltd.

Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system.

PubMed

Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

2015-01-01

17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

Annual Site Environmental Report Sandia National Laboratories, Albuquerque, New Mexico, Calendar year 2007

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

Agogino, Karen; Sanchez, Rebecca

2008-09-30

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned/contractor-operated facility. Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation, manages and operates the laboratory for the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA). The DOE/NNSA Sandia Site Office (SSO) administers the contract and oversees contractor operations at the site. This annual report summarizes data and the compliance status of Sandia Corporation’s environmental protection and monitoring programs through December 31, 2007. Major environmental programs include air quality, water quality, groundwater protection, terrestrial surveillance, waste management, pollution prevention (P2), environmental restoration (ER), oil and chemical spill prevention,more » and implementation of the National Environmental Policy Act (NEPA). Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2007a) and DOE Manual 231.1-1A, Environment, Safety, and Health Reporting (DOE 2007).« less

Preliminary remediation goals for use at the U.S. Department of Energy Oak Ridge Operations Office

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

NONE

1995-06-01

This report presents Preliminary Remediation Goals (PRGs) for use in human health risk assessment efforts under the United States Department of Energy, Oak Ridge Operations Office Environmental Restoration (ER) Division. Chemical-specific PRGs are concentration goals for individual chemicals for specific medium and land use combinations. The PRGs are referred to as risk-based because they have been calculated using risk assessment procedures. Risk-based calculations set concentration limits using both carcinogenic or noncarcinogenic toxicity values under specific exposure pathways. The PRG is a concentration that is derived from a specified excess cancer risk level or hazard quotient. This report provides the ERmore » Division with standardized PRGs which are integral to the Remedial Investigation/Feasibility Study process. By managing the assumptions and systems used in PRG derivation, the Environmental Restoration Risk Assessment Program will be able to control the level of quality assurance associated with these risk-based guideline values.« less

Assessment of Microleakage of a Composite Resin Restoration in Primary Teeth Following Class III Cavity Preparation Using Er, Cr: YSGG laser: An In Vitro Study

PubMed Central

Subramaniam, Priya; Pandey, Annu

2016-01-01

Introduction: Marginal seal integrity is important for a successful adhesive dental restoration. Alterations caused by laser irradiation in the enamel and dentin surface can affect the marginal integrity of adhesive restorations. The aim of this study was to evaluate the microleakage of a composite resin restoration in primary teeth following laser irradiation of enamel and dentin. Methods: Forty freshly extracted sound human primary maxillary and mandibular anterior teeth were used in this study. The teeth were randomly divided into two groups (I and II), with 20 teeth in each. In group I, proximal cavities (Class III) were prepared using an airotor hand –piece and diamond bur. The cavities were etched for 15 seconds with 35% phosphoric acid gel, rinsed with water for 15 seconds, air dried and a bonding agent was applied onto the cavity surfaces and light cured for 20 seconds. The cavities were restored with composite resin and light cured for 40 seconds. In group II, proximal (Class III) cavities were prepared using Erbium, Chromium: Yttrium Scandium Gallium Garnet (Er,Cr:YSGG) (Er,Cr:YSGG) (Biolaseiplus, wave length 2.78 μm). The cavity was then rinsed, air dried and without etching, a bonding agent was applied and light cured for 20 seconds. The cavities were restored in the same manner as that of group I. The treated teeth were mounted on acrylic resin blocks and were subjected to a thermocycling regimen. Following, the teeth were immersed in 2% methylene blue for 24 hours. The teeth were sectioned longitudinally in a bucco-lingual direction using a diamond disc at slow speed. The sections of all the groups were examined under a stereomicroscope for micro-leakage. Results: The mean scores for microleakage in group I was 1.95 ± 1.31 and in group II it was 1.4 ± 1.27. There was no significant difference between the two groups (P = 0.882). Conclusion: No significant difference in microleakage was noticed between the composite resin bonded to lased enamel and dentin and the teeth preparedwith conventional method. PMID:28144438

Endoplasmic reticulum stress contributes to acetylcholine receptor degradation by promoting endocytosis in skeletal muscle cells.

PubMed

Du, Ailian; Huang, Shiqian; Zhao, Xiaonan; Zhang, Yun; Zhu, Lixun; Ding, Ji; Xu, Congfeng

2016-01-15

After binding by acetylcholine released from a motor neuron, a nicotinic acetylcholine receptor at the neuromuscular junction produces a localized end-plate potential, which leads to muscle contraction. Improper turnover and renewal of acetylcholine receptors contributes to the pathogenesis of myasthenia gravis. In the present study, we demonstrate that endoplasmic reticulum (ER) stress contributes to acetylcholine receptor degradation in C2C12 myocytes. We further show that ER stress promotes acetylcholine receptor endocytosis and lysosomal degradation, which was dampened by blocking endocytosis or treating with lysosome inhibitor. Knockdown of ER stress proteins inhibited acetylcholine receptor endocytosis and degradation, while rescue assay restored its endocytosis and degradation, confirming the effects of ER stress on promoting endocytosis-mediated degradation of junction acetylcholine receptors. Thus, our studies identify ER stress as a factor promoting acetylcholine receptor degradation through accelerating endocytosis in muscle cells. Blocking ER stress and/or endocytosis might provide a novel therapeutic approach for myasthenia gravis. Copyright © 2015 Elsevier B.V. All rights reserved.

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

PubMed Central

Liu, Mei-qing; Chen, Zhe; Chen, Lin-xi

2016-01-01

Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS. PMID:26838072

Restoration of Tamoxifen Sensitivity in Estrogen Receptor–Negative Breast Cancer Cells: Tamoxifen-Bound Reactivated ER Recruits Distinctive Corepressor Complexes

PubMed Central

Sharma, Dipali; Saxena, Neeraj K.; Davidson, Nancy E.; Vertino, Paula M.

2010-01-01

Breast tumors expressing estrogen receptor-α (ER) respond well to therapeutic strategies using selective ER modulators, such as tamoxifen. However, ~ 30% of invasive breast cancers are hormone independent because they lack ER expression due to hypermethylation of ER promoter. Treatment of ER-negative breast cancer cells with demethylating agents [5-aza-2′-deoxycytidine (5-aza-dC)] and histone deacetylase (HDAC) inhibitors (trichostatin A) leads to expression of ER mRNA and functional protein. Here, we examined whether epigenetically reactivated ER is a target for tamoxifen therapy. Following treatment with trichostatin A and 5-aza-dC, the formerly unresponsive ER-negative MDA-MB-231 breast cancer cells became responsive to tamoxifen. Tamoxifen-mediated inhibition of cell growth in these cells is mediated at least in part by the tamoxifen-bound ER. Tamoxifen-bound reactivated ER induces transcriptional repression at estrogen-responsive genes by ordered recruitment of multiple distinct chromatin-modifying complexes. Using chromatin immunoprecipitation, we show recruitment of two different corepressor complexes to ER-responsive promoters in a mutually exclusive and sequential manner: the nuclear receptor corepressor-HDAC3 complex followed by nucleosome remodeling and histone deacetylation complex. The mechanistic insight provided by this study might help in designing therapeutic strategies directed toward epigenetic mechanisms in the prevention or treatment of breast cancer. PMID:16778215

Unfolded protein response activation compensates endoplasmic reticulum-associated degradation deficiency in Arabidopsis.

PubMed

Li, Qingliang; Wei, Hai; Liu, Lijing; Yang, Xiaoyuan; Zhang, Xiansheng; Xie, Qi

2017-07-01

Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum (ER) stress. There is a sophisticated ER quality control (ERQC) system to mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The accumulation of misfolded proteins in the ER activates the unfolded protein response (UPR) to enhance ER protein folding and the degradation of misfolded proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic stress damage has been well studied in mammals and yeast. However, in plants, both ERAD and UPR have been studied separately and found to be critical for plant abiotic stress tolerance. In this study, we discovered that UPR-associated transcription factors AtbZIP17, AtbZIP28 and AtbZIP60 responded to tunicamycin (TM) and NaCl induced ER stress and subsequently enhanced Arabidopsis thaliana abiotic stress tolerance. They regulated the expression level of ER chaperones and the HRD1-complex components. Moreover, overexpression of AtbZIP17, AtbZIP28 and AtbZIP60 could restore stress tolerance via ERAD in the HRD1-complex mutant hrd3a-2, which suggested that UPR and ERAD have an interactive mechanism in Arabidopsis. © 2017 Institute of Botany, Chinese Academy of Sciences.

Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic fatty liver disease (NAFLD).

PubMed

Wang, Lifeng; Chen, J; Ning, C; Lei, D; Ren, Jun

2018-05-16

Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem and a common cause of chronic liver diseases. However, the underlying mechanisms leading to the development and progression of NAFLD remain elusive. Accumulating evidence has depicted an essential role for endoplasmic reticulum (ER) stress in the development of steatosis and later progression into nonalcoholic steatohepatitis and hepatocarcinoma. With the accumulation of unfolded and misfolded proteins in the ER lumen, ER stress is provoked to turn on the unfolded protein response (UPR). ER stress triggers a cascade reaction of transcriptional and translational events that restore ER homeostasis, promoting cell survival and adaptation. However, prolonged ER stress may be transit physiological mechanisms to pathological consequences, including insulin resistance, fat accumulation, inflammation, apoptosis, and autophagy, all of which with important roles in the development of NAFLD. Therefore, understanding the role of ER stress in the onset and pathogenesis of NAFLD is pertinent to the management of this devastating metabolic disease. Here we will summarize available information on recent findings linking ER stress to the pathogenesis of NAFLD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microleakage of Self-Etch Adhesive System in Class V Cavities Prepared by Using Er:YAG Laser with Different Pulse Modes.

PubMed

Phanombualert, Jutipond; Chimtim, Pijitta; Heebthamai, Thitirat; Weera-Archakul, Wilawan

2015-09-01

In vitro studies evaluated cementum surface morphology and microleakage of three different energy density parameters of Erbium: Yttrium Aluminum Garnet (Er:YAG) laser compared with diamond bur preparation on class V cavities with self-etch adhesive system and composite resin restoration. Standard class V cavities were prepared at cervical area below the cementoenamel junction (CEJ) in 80 extracted premolars, by using a diamond bur on the buccal surface. All teeth were randomly allocated into four groups: Group 1, diamond bur; Group 2, Er:YAG 50 mJ/15 Hz, 3.77 J/cm(2); Group 3, Er:YAG 75 mJ/15 Hz, 5.65 J/cm(2); and Group 4, Er:YAG 100 mJ/15 Hz, 7.53 J/cm(2). Five cavities from each group were evaluated by scanning electron microscopy (SEM). The 15 remaining cavities from each group were restored with self-etch adhesive and nano-hybrid composite. After thermocycling, all sample teeth were immersed in 0.2% methylene blue dye and sectioned buccolingually. Statistics were analyzed using the one way ANOVA and Mann-Whitney U tests with Bonferroni correction. The morphology showed micro-irregularities in the cementum surface of the laser group with the absence of a smear layer. The microstructure characteristics were increased surface roughness followed by increasing laser energy transmission. The Er:YAG laser groups were statistically significant, with less microleakage than the diamond bur group (p<0.05). There was statistically significant difference between the occlusal and gingival microleakage in all the groups (p<0.05). When the laser groups were compared, the lowest microleakage was achieved with energy density at 3.77 J/cm(2) on the occlusal and gingival cementum margin, which showed less microleakage than at energy densities of 5.65 and 7.53 J/cm(2) with Er:YAG laser. These observations indicate that the micro-irregularities of the cementum surface could facilitate the formation of a hybridization zone with a self-etch adhesive system. Therefore, the microleakage of Er:YAG laser irradiation was significantly decreased compared with diamond bur cavities.

Preconstruction Biogeochemical Analysis of Mercury in Wetlands Bordering the Hamilton Army Airfield (HAAF) Wetlands Restoration Site. Part 3

DTIC Science & Technology

2009-12-01

ER D C/ EL T R- 09 -2 1 Preconstruction Biogeochemical Analysis of Mercury in Wetlands Bordering the Hamilton Army Airfield (HAAF) Wetlands...Preconstruction Biogeochemical Analysis of Mercury in Wetlands Bordering the Hamilton Army Airfield (HAAF) Wetlands Restoration Site Part 3 Elly P. H... mercury methylation and demethylation, and biogeochemical parameters related to the mercury cycle as measured by both conventional and emerging methods

Methylmercury Screening Models for Surface Water Habitat Restoration: A Case Study in Duluth-Superior Harbor

DTIC Science & Technology

2017-11-01

three models used in this study (HERMES, WASP, and SERAFM) were applied very differently and, in some ways, comparing them in Table 10 is...ER D C/ EL T R- 17 -1 9 Dredging Innovations Group Methylmercury Screening Models for Surface Water Habitat Restoration: A Case Study in...Case Study in Duluth-Superior Harbor Philip T. Gidley, Joseph P. Kreitinger, Mansour Zakikhani, and Burton C. Suedel Environmental Laboratory

Alpha-lipoic acid attenuates endoplasmic reticulum stress-induced insulin resistance by improving mitochondrial function in HepG2 cells.

PubMed

Lei, Lin; Zhu, Yiwei; Gao, Wenwen; Du, Xiliang; Zhang, Min; Peng, Zhicheng; Fu, Shoupeng; Li, Xiaobing; Zhe, Wang; Li, Xinwei; Liu, Guowen

2016-10-01

Alpha-lipoic acid (ALA) has been reported to have beneficial effects for improving insulin sensitivity. However, the underlying molecular mechanism of the beneficial effects remains poorly understood. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are considered causal factors that induce insulin resistance. In this study, we investigated the effect of ALA on the modulation of insulin resistance in ER-stressed HepG2 cells, and we explored the potential mechanism of this effect. HepG2 cells were incubated with tunicamycin (Tun) for 6h to establish an ER stress cell model. Tun treatment induced ER stress, mitochondrial dysfunction and insulin resistance. Interestingly, ALA had no significant effect on ER stress signals. Pretreatment of the ER stress cell model with ALA for 24h improved insulin sensitivity, restored the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and increased intracellular ATP production. Moreover, ALA augmented the β-oxidation capacity of the mitochondria. Importantly, ALA treatment could decrease oligomycin-induced mitochondrial dysfunction and then improved insulin resistance. Taken together, our data suggest that ALA prevents ER stress-induced insulin resistance by enhancing mitochondrial function. Copyright © 2016 Elsevier Inc. All rights reserved.

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription

PubMed Central

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-01-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPRER) to restore ER homeostasis. The AAA+ ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPRER genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA+ ATPase, as a novel repressor of a subset of UPRER genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPRER genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. PMID:25652260

34 CFR Appendix A to Subpart C of... - Grants for Access and Persistence Program (GAP) State Grant Allotment Case Study

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Grants for Access and Persistence Program (GAP) State Grant Allotment Case Study A Appendix A to Subpart C of Part 692 Education Regulations of the Offices of...) State Grant Allotment Case Study ER29OC09.010 ER29OC09.011 ER29OC09.012 ER29OC09.013 ER29OC09.014...

β-Cell Dysfunction Due to Increased ER Stress in a Stem Cell Model of Wolfram Syndrome

PubMed Central

Shang, Linshan; Hua, Haiqing; Foo, Kylie; Martinez, Hector; Watanabe, Kazuhisa; Zimmer, Matthew; Kahler, David J.; Freeby, Matthew; Chung, Wendy; LeDuc, Charles; Goland, Robin; Leibel, Rudolph L.; Egli, Dieter

2014-01-01

Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of β-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient β-cells showed increased levels of endoplasmic reticulum (ER) stress molecules and decreased insulin content. Upon exposure to experimental ER stress, Wolfram β-cells showed impaired insulin processing and failed to increase insulin secretion in response to glucose and other secretagogues. Importantly, 4-phenyl butyric acid, a chemical protein folding and trafficking chaperone, restored normal insulin synthesis and the ability to upregulate insulin secretion. These studies show that ER stress plays a central role in β-cell failure in Wolfram syndrome and indicate that chemical chaperones might have therapeutic relevance under conditions of ER stress in Wolfram syndrome and other forms of diabetes. PMID:24227685

Potential role of surface wettability on the long-term stability of dentin bonds after surface biomodification

PubMed Central

Leme, Ariene A.; Vidal, Cristina M. P.; Hassan, Lina Saleh; Bedran-Russo, Ana K.

2015-01-01

Degradation of the adhesive interface contributes to the failure of resin composite restorations. The hydrophilicity of the dentin matrix during and after bonding procedures may result in an adhesive interface that is more prone to degradation over time. This study assessed the effect of chemical modification of dentin matrix on the wettability and the long-term reduced modulus of elasticity (Er) of the adhesive interfaces. Human molars were divided into groups according to the priming solutions: distilled water (control), 6.5% Proanthocyanidin-rich grape seed extract (PACs), 5.75% 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/1.4% n-hydroxysuccinimide (EDC/NHS) and 5% Glutaraldehyde (GA). The water-surface contact angle was verified before and after chemical modification of the dentin matrix. The demineralized dentin surface was treated with the priming solutions and restored with One Step Plus (OS) and Single Bond Plus (SB) and resin composite. The Er of the adhesive, hybrid layer and underlying dentin was evaluated after 24 h and 30 months in artificial saliva. The dentin hydrophilicity significantly decreased after application of the priming solutions. Aging significantly decreased the Er in the hybrid layer and underlying dentin of control groups. The Er of GA groups remained stable over time at the hybrid layer and underlying dentin. Significant higher Er was observed for PACs and EDC/NHS groups at the hybrid layer after 24 h. The decreased hydrophilicity of the modified dentin matrix likely influence the immediate mechanical properties of the hybrid layer. Dentin biomodification prevented substantial aging at the hybrid layer and underlying dentin after 30 months storage. PMID:25869721

Mangiferin inhibits endoplasmic reticulum stress-associated thioredoxin-interacting protein/NLRP3 inflammasome activation with regulation of AMPK in endothelial cells.

PubMed

Song, Junna; Li, Jia; Hou, Fangjie; Wang, Xiaona; Liu, Baolin

2015-03-01

Endothelial dysfunction is tightly associated with cardiovascular complications in diabetic patients. This study aims to investigate the effects of mangiferin on the regulation of endothelial homeostasis under endoplasmic reticulum stress (ER stress) conditions. High glucose (25 mmol/L) exposure induced ER stress and promoted ROS production in endothelial cells. Mangiferin effectively inhibited ER stress-associated oxidative stress by attenuating IRE1α phosphorylation and reducing ROS production. In response to ER stress, thioredoxin-interacting protein (TXNIP) expression increased, followed by NLRP3 inflammasome activation and increased IL-1β secretion. Mangiferin treatment attenuated the expressions of TXNIP and NLRP3 and reduced IL-1β and IL-6 production, demonstrating its inhibitory effects on TXNIP/NLRP3 inflammasome activation. NLRP3 inflammasome activation is responsible for mitochondrial cell death. Mangiferin restored the loss of the mitochondrial membrane potential (Δψm) and inhibited caspase-3 activity, and thereby protected cells from high glucose-induced apoptosis. Moreover, mangiferin inhibited ET-1 secretion and restored the loss of NO production when cells were exposed to high glucose. Mangiferin enhanced AMPK phosphorylation and AMPK inhibitor compound C diminished its beneficial effects, indicating the potential role of AMPK in its action. Our work showed the beneficial effects of mangiferin on the improvement of endothelial homeostasis and elucidated the molecular pathway through which mangiferin ameliorated endothelial dysfunction by inhibition of ER stress-associated TXNIP/NLRP3 inflammasome activation in endothelial cells. These findings demonstrated the beneficial effects of mangiferin on the regulation of endothelial homeostasis and indicated its potential application in the management of diabetic cardiovascular complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Endoplasmic reticulum stress regulates tumor growth and anti-tumor immunity: a promising opportunity for cancer immunotherapy.

PubMed

Mohamed, Eslam; Cao, Yu; Rodriguez, Paulo C

2017-08-01

The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes. In order to cope with TME-induced ER stress, tumor and stromal cells initiate an adaptive response process that aims to resolve ER stress and to restore cellular homeostasis, which is referred as the unfolded protein responses (UPR). Paradoxically, the UPR can also induce cell death under severe and/or permanent ER stress. The UPR is started through three mediators, the activation of the inositol-requiring enzyme-1α, the pancreatic ER kinase-like ER kinase, and the activating transcription factor 6. In this minireview, we will discuss the pro- and anti-tumorigenic role of the UPR in cancer cells. In addition, we will describe the effects of the TME-induced ER stress in the immunosuppressive activity of tumor-infiltrating myeloid cells. Also, we will review the results of emerging therapeutic interventions that target ER stress and the UPR mediators in cancer. We postulate that the inhibition of ER stress or the UPR-related elements could represent a significant approach to increase the efficacy of various forms of cancer immunotherapy.

Geological investigations and hydrogeologic model development in support of DoD and DOE environmental programs on Kirtland Air Force Base, New Mexico, U.S.A.

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

Gibson, J.D.; Pratt, G.; Davidson, H.

This paper presents results of preliminary geologic site characterization and hydrogeologic conceptual model development for the 250-km{sup 2} Kirtland Air Force Base (KAFB) and associated lands in central New Mexico. The research, development, and other operational activities of the Department of Defense (DoD) and Department of Energy (DOE) on KAFB over the last 50 years have resulted in diverse hazardous, radioactive, and mixed-waste environmental concerns. Because multiple federal, state, and local agencies are responsible for administrating the involved lands and because of the nature of many U.S. environmental regulations, individual contaminated and potentially contaminated DoD and DOE environmental restoration (ER)more » sites on KAFB are commonly handled as distinct entities with little consideration for the cumulative environmental and health risk from all sites. A site-wide characterization program has been undertaken at Sandia National Laboratories/New Mexico (SNL/NM), under the auspices of the DOE, to construct a conceptual hydrogeologic model for the base. This conceptual model serves as the basis for placing each ER site into a broader context for evaluating background (i.e., non-contaminated) conditions and for modeling of possible contaminant pathways and travel-times. Regional and local hydrogeologic investigations from KAFB can be used as models for characterizing and evaluating other sites around the world where combined civilian and military environmental programs must work together to resolve environmental problems that may present health risks to workers and the general public.« less

A Cluster of Exertional Rhabdomyolysis Cases in a ROTC Program Engaged in an Extreme Exercise Program.

PubMed

Raleigh, Meghan F; Barrett, John P; Jones, Brent D; Beutler, Anthony I; Deuster, Patricia A; O'Connor, Francis G

2018-03-01

Exertional rhabdomyolysis (ER) is on the rise among service members and high school and college athletes. Reported risk factors for ER include fitness level, sudden increase in exercise intensity and duration, and eccentric predominant exercise. This study examined an ER cluster among Reserve Officer Training Corps cadets who participated in a mandatory, timed, extreme conditioning program (ECP) workout. Forty-four cadets participated in this ECP; 11 were subsequently hospitalized with ER. Thirty-five cadets, including all who developed ER, completed a questionnaire to assess ECP times, prior fitness scores, and other ER risk factors. Cadets completed the ECP workout as individuals or in teams. Nine of 29 (31%) individual and two of 15 (13%) team participants were hospitalized with ER. Among the cadets, no associations were noted between hospitalization for ER and finish time, previous fitness scores, or dietary supplement use. The relative risk of developing ER was significantly increased in those who consumed alcohol in the week preceding the ECP (RR = 4.20; 95% CI 1.95, 9.03). In this cohort of Reserve Officer Training Corps cadets, an ECP resulted in a high rate of hospitalization for ER. Contrary to reported ER risk factors, higher baseline fitness was not protective. Rather, cadet knowledge that ECP performance was strongly linked to final cadet ranking greatly influenced intensity of effort.

38 CFR 58.13 - VA Form 10-10SH-State Home Program Application for Veteran Care Medical Certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false VA Form 10-10SH-State Home Program Application for Veteran Care Medical Certification. 58.13 Section 58.13 Pensions, Bonuses... Home Program Application for Veteran Care Medical Certification. ER29AP09.150 ER29AP09.151 ER29AP09.152...

Environmental Restoration (ER) Consolidated Quarterly Report_April to June 2017_ October 2017

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

Cochran, John R.

2017-10-01

This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented at Sandia National Laboratories, New Mexico (SNL/NM) during the April, May, and June 2017 quarterly reporting period. Table I-1 lists the Solid Waste Management Units (SWMUs) and Areas of Concern (AOCs) identified for corrective action at SNL/NM. Sections I.2.1 and I.2.2 summarize the work completed during this quarter. Section I.2.1 summarizes the quarterly activities at sites undergoing corrective action field activities. Field activities are conducted at the three groundwater AOCs (Burn Site Groundwater [BSG AOC], Technical Area [TA]-V Groundwatermore » [TAVG AOC], and Tijeras Arroyo Groundwater [TAG AOC]). Section I.2.2 summarizes quarterly activities at sites where the New Mexico Environment Department (NMED) Hazardous Waste Bureau (HWB) issued a certificate of completion and the sites are in the corrective action complete (CAC) regulatory process. Currently, SWMUs 8 and 58, 68, 149, 154, and 502 are in the CAC regulatory process. Corrective action activities are deferred at the Long Sled Track (SWMU 83), the Gun Facilities (SWMU 84), and the Short Sled Track (SWMU 240) because these three sites are active mission facilities. These three active mission sites are located in TA-III.« less

Nevada National Security Site Environmental Report 2010

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

C. Wills, ed.

2011-09-13

This NNSSER was prepared to satisfy DOE Order DOE O 231.1B, “Environment, Safety and Health Reporting.” Its purpose is to (1) report compliance status with environmental standards and requirements, (2) present results of environmental monitoring of radiological and nonradiological effluents, (3) report estimated radiological doses to the public from releases of radioactive material, (4) summarize environmental incidents of noncompliance and actions taken in response to them, (5) describe the NNSA/NSO Environmental Management System and characterize its performance, and (6) highlight significant environmental programs and efforts. This NNSSER summarizes data and compliance status for calendar year 2010 at the Nevada Nationalmore » Security Site (NNSS) (formerly the Nevada Test Site) and its two support facilities, the North Las Vegas Facility (NLVF) and the Remote Sensing Laboratory–Nellis (RSL-Nellis). It also addresses environmental restoration (ER) projects conducted at the Tonopah Test Range (TTR). Through a Memorandum of Agreement, NNSA/NSO is responsible for the oversight of TTR ER projects, and the Sandia Site Office of NNSA (NNSA/SSO) has oversight of all other TTR activities. NNSA/SSO produces the TTR annual environmental report available at http://www.sandia.gov/news/publications/environmental/index.html.« less

STIM1L traps and gates Orai1 channels without remodeling the cortical ER

PubMed Central

Saüc, Sophie; Bulla, Monica; Nunes, Paula; Orci, Lelio; Marchetti, Anna; Antigny, Fabrice; Bernheim, Laurent; Cosson, Pierre; Frieden, Maud; Demaurex, Nicolas

2015-01-01

STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca2+ entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca2+ influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca2+ imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1−/−/Stim2−/− fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca2+ elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides. PMID:25736291

ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis.

PubMed

DeZwaan-McCabe, Diane; Sheldon, Ryan D; Gorecki, Michelle C; Guo, Deng-Fu; Gansemer, Erica R; Kaufman, Randal J; Rahmouni, Kamal; Gillum, Matthew P; Taylor, Eric B; Teesch, Lynn M; Rutkowski, D Thomas

2017-05-30

The unfolded protein response (UPR), induced by endoplasmic reticulum (ER) stress, regulates the expression of factors that restore protein folding homeostasis. However, in the liver and kidney, ER stress also leads to lipid accumulation, accompanied at least in the liver by transcriptional suppression of metabolic genes. The mechanisms of this accumulation, including which pathways contribute to the phenotype in each organ, are unclear. We combined gene expression profiling, biochemical assays, and untargeted lipidomics to understand the basis of stress-dependent lipid accumulation, taking advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid accumulation in both organs. These findings provide evidence for both direct and indirect regulation of peripheral metabolism by ER stress. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes

PubMed Central

Cheng, Tsing; Orlow, Seth J.; Manga, Prashiela

2013-01-01

Summary Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of proapoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress. PMID:23962237

The influence of erbium:yttrium-aluminum-garnet laser ablation with variable pulse width on morphology and microleakage of composite restorations.

PubMed

Navarro, Ricardo Scarparo; Gouw-Soares, Sheila; Cassoni, Alessandra; Haypek, Patricia; Zezell, Denise Maria; de Paula Eduardo, Carlos

2010-11-01

The objective of this study was to evaluate the influence of various pulse widths with different energy parameters of erbium:yttrium-aluminum-garnet (Er:YAG) laser (2.94 mum) on the morphology and microleakage of cavities restored with composite resin. Identically sized class V cavities were prepared on the buccal surfaces of 54 bovine teeth by high-speed drill (n = 6, control, group 1) and prepared by Er:YAG laser (Fidelis 320A, Fotona, Slovenia) with irradiation parameters of 350 mJ/ 4 Hz or 400 mJ/2 Hz and pulse width: group 2, very short pulse (VSP); group 3, short pulse (SP); group 4, long pulse (LP); group 5, very long pulse (VLP). All cavities were filled with composite resin (Z-250-3 M), stored at 37 degrees C in distilled water, polished after 24 h, and thermally stressed (700 cycles/5-55 degrees C). The teeth were impermeabilized, immersed in 50% silver nitrate solution for 8 h, sectioned longitudinally, and exposed to Photoflood light for 10 min to reveal the stain. The leakage was evaluated under stereomicroscope by three different examiners, in a double-blind fashion, and scored (0-3). The results were analyzed by Kruskal-Wallis test (P > 0.05) and showed that there was no significant differences between the groups tested. Under scanning electron microscopy (SEM) the morphology of the cavities prepared by laser showed irregular enamel margins and dentin internal walls, and a more conservative pattern than that of conventional cavities. The different power settings and pulse widths of Er:YAG laser in cavity preparation had no influence on microleakage of composite resin restorations.

Influence of different conditioning methods on the shear bond strength of novel light-curing nano-ionomer restorative to enamel and dentin.

PubMed

Korkmaz, Yonca; Ozel, Emre; Attar, Nuray; Ozge Bicer, Ceren

2010-11-01

The purpose of this study was to investigate shear bond strength (SBS) between a light-curing nano-ionomer restorative and enamel or dentin after acid etching, after erbium:yttrium-aluminum-garnet (Er:YAG) laser etching, or after combined treatment. Forty third molars were selected, the crowns were sectioned, and 80 tooth slabs were obtained. The specimens were assigned to two groups, which were divided into four subgroups(n = 10). Group 1 [enamel (e)], treated with 37% phosphoric acid (A) + Ketac nano-primer (K); group 2 [dentin (d)], (A) + (K); group 3(e), Er:YAG laser etching (L) + (A) + (K); group 4(d), (L) + (A) + (K); group 5(e), (L) + (K); group 6(d), (L) + (K); group 7(e), (K); group 8(d), (K). The SBS of the specimens was measured with a universal test machine (1 mm/min). Data were analyzed by independent samples t-test, one-way analysis of variance (ANOVA) and a post-hoc Duncan test (p < 0.05). No difference was determined between groups 3 and 5 (p > 0.05). Group 7 exhibited higher SBS values than those of groups 3 and 5 (p < 0.05). Group 1 showed higher SBSs than those of groups 3, 5 and 7 (p < 0.05). There was no significant difference between groups 4 and 6 (p > 0.05). No difference was observed between groups 2 and 4 (p > 0.05). However, group 2 presented higher SBSs than did group 6 (p < 0.05). Group 8 exhibited the highest SBS values when compared with groups 2, 4 and 6 (p < 0.05). Er:YAG laser adversely affected the adhesion of the light-curing nano-ionomer restorative to both enamel and dentin.

ERK1/2 signalling protects against apoptosis following endoplasmic reticulum stress but cannot provide long-term protection against BAX/BAK-independent cell death.

PubMed

Darling, Nicola J; Balmanno, Kathryn; Cook, Simon J

2017-01-01

Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway. This is causally related to ER stress since reactivation of ERK1/2 can protect cells from ER stress-induced apoptosis whilst ERK1/2 pathway inhibition sensitises cells to ER stress. Furthermore, cancer cell lines harbouring constitutively active BRAFV600E are addicted to ERK1/2 signalling for protection against ER stress-induced cell death. ERK1/2 signalling normally represses the pro-death proteins BIM, BMF and PUMA and it has been proposed that ER stress induces BIM-dependent cell death. We found no evidence that ER stress increased the expression of these proteins; furthermore, BIM was not required for ER stress-induced death. Rather, ER stress caused the PERK-dependent inhibition of cap-dependent mRNA translation and the progressive loss of pro-survival proteins including BCL2, BCLXL and MCL1. Despite these observations, neither ERK1/2 activation nor loss of BAX/BAK could confer long-term clonogenic survival to cells exposed to ER stress. Thus, ER stress induces cell death by at least two biochemically and genetically distinct pathways: a classical BAX/BAK-dependent apoptotic response that can be inhibited by ERK1/2 signalling and an alternative ERK1/2- and BAX/BAK-independent cell death pathway.

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia.

PubMed

Fano, Diego; Vásquez-Velásquez, Cinthya; Gonzales-Castañeda, Cynthia; Guajardo-Correa, Emanuel; Orihuela, Pedro A; Gonzales, Gustavo F

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ER β , but only the aqueous fraction increased androgen receptors and ER α . In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ER β without affecting androgen receptors and ER α . This effect was not observed with aqueous fraction of methanolic extract of red maca.

Transmission of Er:YAG laser through different dental ceramics.

PubMed

Sari, Tugrul; Tuncel, Ilkin; Usumez, Aslihan; Gutknecht, Norbert

2014-01-01

The aim of this study was to determine the erbium-doped yttrium aluminum garnet (Er:YAG) laser transmission ratio through different dental ceramics with different thicknesses. Laser debonding procedure of adhesively luted all-ceramic restorations is based on the transmission of laser energy through the ceramic and the ablation of resin cement, because of the transmitted laser energy. Five different dental ceramics were evaluated in this study: sintered zirconium-oxide core ceramic, monolithic zirconium-oxide ceramic, feldspathic ceramic, leucite-reinforced glass ceramic, and lithium disilicate-reinforced glass ceramic. Two ceramic discs with different thicknesses (0.5 and 1 mm) were fabricated for each group. Ceramic discs were placed between the sensor membrane of the laser power meter and the tip of the contact handpiece of an Er:YAG laser device with the aid of a custom- made acrylic holder. The transmission ratio of Er:YAG laser energy (500 mJ, 2 Hz, 1 W, 1000 μs) through different ceramic discs was measured with the power meter. Ten measurements were made for each group and the results were analyzed with two way analysis of variance (ANOVA) and Tukey honestly significant difference (HSD) tests. The highest transmission ratio was determined for lithium disilicate-reinforced ceramic with 0.5 mm thickness (88%) and the lowest was determined for feldspathic ceramic with 1 mm thickness (44%). The differences among the different ceramics and between the different thicknesses were significant (p<0.05). Ceramic type and thickness should be taken into consideration to adjust the laser irradiation parameters during laser debonding of adhesively luted all-ceramic restorations.

Endoplasmic Reticulum Stress in Sepsis

PubMed Central

Khan, Mohammad Moshahid; Yang, Weng-Lang; Wang, Ping

2015-01-01

Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units (ICU). Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with the sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under the stress and inflammation condition, ER loses the homeostasis in its function, which is termed as ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once the stress is beyond the compensatory capacity of UPR or protracted, the apoptosis would be initiated by triggering cell injuries, even to cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidences that ER stress participate in the pathogenesis of sepsis. In this review, we summarize the current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma- hemorrhage, and ischemia/reperfusion (I/R) injury. We also discuss the potential implication of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis. PMID:26125088

Respiratory epithelial cell responses to cigarette smoke: the unfolded protein response.

PubMed

Kelsen, Steven G

2012-12-01

Cigarette smoking exposes the respiratory epithelium to highly toxic, reactive oxygen nitrogen species which damage lung proteins in the endoplasmic reticulum (ER), the cell organelle in which all secreted and membrane proteins are processed. Accumulation of damaged or misfolded proteins in the ER, a condition termed ER stress, activates a complex cellular process termed the unfolded protein responses (UPR). The UPR acts to restore cellular protein homeostasis by regulating all aspects of protein metabolism including: protein translation and syntheses; protein folding; and protein degradation. However, activation of the UPR may also induce signaling pathways which induce inflammation and cell apoptosis. This review discusses the role of UPR in the respiratory epithelial cell response to cigarette smoke and the pathogenesis of lung diseases like COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy

PubMed Central

Giuliano, Mario; Hu, Huizhong; Wang, Yen-Chao; Fu, Xiaoyong; Nardone, Agostina; Herrera, Sabrina; Mao, Sufeng; Contreras, Alejandro; Gutierrez, Carolina; Wang, Tao; Hilsenbeck, Susan G.; De Angelis, Carmine; Wang, Nicholas J.; Heiser, Laura M.; Gray, Joe W.; Lopez-Tarruella, Sara; Pavlick, Anne C.; Trivedi, Meghana V.; Chamness, Gary C.; Chang, Jenny C.; Osborne, C. Kent; Rimawi, Mothaffar F.; Schiff, Rachel

2015-01-01

Purpose To investigate the direct effect and therapeutic consequences of epidermal growth factor receptor 2 (HER2)-targeting therapy on expression of estrogen receptor (ER) and Bcl2 in preclinical models and clinical tumor samples. Experimental design Archived xenograft tumors from two preclinical models (UACC812 and MCF7/HER2-18) treated with ER and HER2-targeting therapies, and also HER2+ clinical breast cancer specimens collected in a lapatinib neoadjuvant trial (baseline and week 2 post treatment), were used. Expression levels of ER and Bcl2 were evaluated by immunohistochemistry and western blot. The effects of Bcl2 and ER inhibition, by ABT-737 and fulvestrant respectively, were tested in parental versus lapatinib-resistant UACC812 cells in vitro. Results Expression of ER and Bcl2 was significantly increased in xenograft tumors with acquired resistance to anti-HER2 therapy, compared with untreated tumors, in both preclinical models (UACC812: ER p=0.0014; Bcl2 p<0.001. MCF7/HER2-18: ER p=0.0007; Bcl2 p=0.0306). In the neoadjuvant clinical study, lapatinib treatment for two weeks was associated with parallel upregulation of ER and Bcl2 (Spearman’s coefficient: 0.70; p=0.0002). Importantly, 18% of tumors originally ER-negative (ER−) converted to ER+ upon anti-HER2 therapy. In ER−/HER2+ MCF7/HER2-18 xenografts, ER re-expression was primarily observed in tumors responding to potent combination of anti-HER2 drugs. Estrogen deprivation added to this anti-HER2 regimen significantly delayed tumor progression (p=0.018). In the UACC812 cells, fulvestrant, but not ABT-737, was able to completely inhibit anti-HER2-resistant growth (p<0.0001). Conclusion HER2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance. PMID:26015514

A Comparison of Hyporheic Transport at a Cross-Vane Structure and Natural Riffle.

PubMed

Smidt, Samuel J; Cullin, Joseph A; Ward, Adam S; Robinson, Jesse; Zimmer, Margaret A; Lautz, Laura K; Endreny, Theodore A

2015-01-01

While restoring hyporheic flowpaths has been cited as a benefit to stream restoration structures, little documentation exists confirming that constructed restoration structures induce comparable hyporheic exchange to natural stream features. This study compares a stream restoration structure (cross-vane) to a natural feature (riffle) concurrently in the same stream reach using time-lapsed electrical resistivity (ER) tomography. Using this hydrogeophysical approach, we were able to quantify hyporheic extent and transport beneath the cross-vane structure and the riffle. We interpret from the geophysical data that the cross-vane and the natural riffle induced spatially and temporally unique hyporheic extent and transport, and the cross-vane created both spatially larger and temporally longer hyporheic flowpaths than the natural riffle. Tracer from the 4.67-h injection was detected along flowpaths for 4.6 h at the cross-vane and 4.2 h at the riffle. The spatial extent of the hyporheic zone at the cross-vane was 12% larger than that at the riffle. We compare ER results of this study to vertical fluxes calculated from temperature profiles and conclude significant differences in the interpretation of hyporheic transport from these different field techniques. Results of this study demonstrate a high degree of heterogeneity in transport metrics at both the cross-vane and the riffle and differences between the hyporheic flowpath networks at the two different features. Our results suggest that restoration structures may be capable of creating sufficient exchange flux and timescales of transport to achieve the same ecological functions as natural features, but engineering of the physical and biogeochemical environment may be necessary to realize these benefits. © 2014, National Ground Water Association.

Moving from rhetoric to reality: adapting Housing First for homeless individuals with mental illness from ethno-racial groups.

PubMed

Stergiopoulos, Vicky; O'Campo, Patricia; Gozdzik, Agnes; Jeyaratnam, Jeyagobi; Corneau, Simon; Sarang, Aseefa; Hwang, Stephen W

2012-10-02

The literature on interventions addressing the intersection of homelessness, mental illness and race is scant. The At Home/Chez Soi research demonstration project is a pragmatic field trial investigating a Housing First intervention for homeless individuals with mental illness in five cities across Canada. A unique focus at the Toronto site has been the development and implementation of a Housing First Ethno-Racial Intensive Case Management (HF ER-ICM) arm of the trial serving 100 homeless individuals with mental illness from ethno-racial groups. The HF ER-ICM program combines the Housing First approach with an anti-racism/anti-oppression framework of practice. This paper presents the findings of an early implementation and fidelity evaluation of the HF ER-ICM program, supplemented by participant narrative interviews to inform our understanding of the HF ER-ICM program theory. Descriptive statistics are used to describe HF ER-ICM participant characteristics. Focus group interviews, key informant interviews and fidelity assessments were conducted between November 2010 and January 2011, as part of the program implementation evaluation. In-depth qualitative interviews with HF ER-ICM participants and control group members were conducted between March 2010 and June 2011. All qualitative data were analysed using grounded theory methodology. The target population had complex health and social service needs. The HF ER-ICM program enjoyed a high degree of fidelity to principles of both anti-racism/anti-oppression practice and Housing First and comprehensively addressed the housing, health and sociocultural needs of participants. Program providers reported congruence of these philosophies of practice, and program participants valued the program and its components. Adapting Housing First with anti-racism/anti-oppression principles offers a promising approach to serving the diverse needs of homeless people from ethno-racial groups and strengthening the service systems developed to support them. The use of fidelity and implementation evaluations can be helpful in supporting successful adaptations of programs and services.

Physical exercise alleviates ER stress in obese humans through reduction in the expression and release of GRP78 chaperone.

PubMed

Khadir, Abdelkrim; Kavalakatt, Sina; Abubaker, Jehad; Cherian, Preethi; Madhu, Dhanya; Al-Khairi, Irina; Abu-Farha, Mohamed; Warsame, Samia; Elkum, Naser; Dehbi, Mohammed; Tiss, Ali

2016-09-01

Perturbation of the endoplasmic reticulum (ER) homeostasis has emerged as one of the prominent features of obesity and diabetes. This occurs when the adaptive unfolded protein response (UPR) fails to restore ER function in key metabolic tissues. We previously reported increased inflammation and impaired heat shock response (HSR) in obese human subjects that were restored by physical exercise. Here, we investigated the status of ER stress chaperone; glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human obese, and their modulation by a supervised 3-month physical exercise. Subcutaneous adipose tissue (SAT) and blood samples were collected from non-diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months of physical exercise). Transcriptomic profiling was used as a primary screen to identify differentially expressed genes and it was carried out on SAT samples using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR, immunohistochemistry, immunofluorescence, Western blot and ELISA were used to validate the transcriptomic data. Correlation analyses with the physical, clinical and biochemical outcomes were performed using Pearson's rank correlation coefficient. Levels of GRP78 and its three downstream UPR arms; activating transcription factor-6 (ATF6), inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were increased in obese subjects. More interestingly, higher levels of circulating GRP78 protein were found in obese compared to lean subjects which correlated negatively with maximum oxygen uptake (VO2 Max) but positively with high-sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI, percentage body fat (PBF) and waist circumference. GRP78 increased secretion in obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER stress. Finally, we showed that physical exercise significantly attenuated the expression and release of GRP78 with a concomitant reduction in the phosphorylation of IRE1α and eukaryotic initiation factor-2α (eIF2α). Our results suggest that physical exercise alleviates ER stress in human obese through attenuation of GRP78 signaling network. Copyright © 2016 Elsevier Inc. All rights reserved.

EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum-associated degradation system in Arabidopsis

PubMed Central

Liu, Yidan; Zhang, Congcong; Wang, Dinghe; Su, Wei; Liu, Linchuan; Wang, Muyang; Li, Jianming

2015-01-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7) gene encodes an ER membrane-localized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMG-CoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant-specific component of a plant ERAD pathway and also suggest its likely biochemical function. PMID:26371323

The effect of erbium family laser on tensile bond strength of composite to dentin in comparison with conventional method.

PubMed

Shahabi, Sima; Chiniforush, Nasim; Bahramian, Hoda; Monzavi, Abbas; Baghalian, Ali; Kharazifard, Mohammad Javad

2013-01-01

The purpose of this study was to evaluate the effect of Er:YAG and Er,Cr:YSGG laser on tensile bond strength of composite resin to dentine in comparison with bur-prepared cavities. Fifteen extracted caries-free human third molars were selected. The teeth were cut at a level below the occlusal pit and fissure plan and randomly divided into three groups. Five cavities were prepared by diamond bur, five cavities prepared by Er:YAG laser, and the other group prepared by Er,Cr:YSGG laser. Then, all the cavities were restored by composite resin. The teeth were sectioned longitudinally with Isomet and the specimens prepared in dumbbelled shape (n = 36). The samples were attached to special jigs, and the tensile bond strength of the three groups was measured by universal testing machine at a speed of 0.5 mm/min. The results of the three groups were analyzed with one-way ANOVA and Tamhane test. The means and standard deviations of tensile bond strength of bur-cut, Er:YAG laser-ablated, and Er,Cr:YSGG laser-ablated dentine were 5.04 ± 0.93, 13.37 ± 3.87, and 4.85 ± 0.93 MPa, respectively. There is little difference in tensile bond strength of composite resin in Er,Cr:YSGG lased-prepared cavities in comparison with bur-prepared cavities, but the Er:YAG laser group showed higher bond strength than the other groups.

γ-Oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice.

PubMed

Kozuka, Chisayo; Sunagawa, Sumito; Ueda, Rei; Higa, Moritake; Tanaka, Hideaki; Shimizu-Okabe, Chigusa; Ishiuchi, Shogo; Takayama, Chitoshi; Matsushita, Masayuki; Tsutsui, Masato; Miyazaki, Jun-ichi; Oyadomari, Seiichi; Shimabukuro, Michio; Masuzaki, Hiroaki

2015-04-01

Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of β-cells under high-fat diet and hyperglycemia. Our recent study in mice showed that γ-oryzanol, a unique component of brown rice, acts as a chemical chaperone in the hypothalamus and improves feeding behavior and diet-induced dysmetabolism. However, the entire mechanism whereby γ-oryzanol improves glucose metabolism throughout the body still remains unclear. In this context, we tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells using murine β-cell line MIN6. In MIN6 cells with augmented ER stress by tunicamycin, γ-oryzanol decreased exaggerated expression of ER stress-related genes and phosphorylation of eukaryotic initiation factor-2α, resulting in restoration of glucose-stimulated insulin secretion and prevention of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration of γ-oryzanol improved glucose-stimulated insulin secretion on following reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the impact of γ-oryzanol on low-dose streptozotocin-induced diabetic mice, where exaggerated ER stress and resultant apoptosis in β-cells were observed. Also in this model, γ-oryzanol attenuated mRNA level of genes involved in ER stress and apoptotic signaling in islets, leading to amelioration of glucose dysmetabolism. Taken together, our findings demonstrate that γ-oryzanol directly ameliorates ER stress-induced β-cell dysfunction and subsequent apoptosis, highlighting usefulness of γ-oryzanol for the treatment of diabetes mellitus.

Adjustment of the evoked response sensitivity after hospital discharge in pacemaker patients with automatic ventricular threshold tracking activated.

PubMed

Schuchert, A; Ventura, R; Meinertz, T

2001-02-01

Automatic threshold tracking in cardiac pacemakers allows ventricular capture verification and self-adaptive pacing output regulation. The Autocapture algorithm detects the evoked response (ER) signal immediately after the pacing pulse to verify the efficacy of ventricular pacing. Before hospital delivery, the ER sensitivity must be programmed individually so that the pacemaker detects the ER signal adequately without sensing lead polarization. The aims of the study were to assess the frequency of patients in whom Autocapture could be activated and whether the ER sensitivity had to be adjusted after hospital discharge. The study included 44 patients who received the VVIR pacemaker Regency SR+ (St. Jude Medical) connected to the model 1450 T pacing lead. ER signal, lead polarization, and ER sensitivity were evaluated before hospital discharge and 1, 3, and 6 months after implantation. The system recommended activating Autocapture in 42 of 44 patients. The mean ER signal was 8.4+/-1.2 mV at discharge, 9.0+/-3.9 mV at month 1, 8.9+/-4.9 mV at month 3, and 9.3+/-4.5 mV at month 6. Polarization was 1.0+/-0.1 mV at discharge, 1.1+/-0.5 mV at month 1, 1.1+/-0.2 mV at month 3, and 1.1+/-0.5 mV at month 6. Mean ER sensitivity was 3.7+/-1.8 mV at discharge, 4.0+/-1.8 mV after 1, 4.1+/-2.2 mV after 3, and 4.1+/-1.8 mV after 6 months. ER sensitivity could remain unadjusted in 14 patients. Programming to a less sensitive ER setting from 2.9+/-1.2 mV to 4.3+/-1.5 mV was possible in 21 patients. Programming to a more sensitive ER setting from 4.1+/-1.1 mV to 2.5+/-0.9 mV was required in nine patients because of the decrease of the ER signal. The automatic threshold tracking algorithm Autocapture could be activated in 95% of patients. Programming to more sensitive ER settings was recommended in 21% of the patients after hospital discharge. Therefore, ER signal and polarization must be checked at each follow-up, as a decrease in ER signal amplitude can make reprogramming of the ER sensitivity necessary. There is no risk for the patient if the ER is not sensed, as high voltage backup stimulation is present.

Microprocessing of human hard tooth tissues surface by mid-infrared erbium lasers radiation

NASA Astrophysics Data System (ADS)

Belikov, Andrey V.; Shatilova, Ksenia V.; Skrypnik, Alexei V.

2015-03-01

A new method of hard tooth tissues laser treatment is described. The method consists in formation of regular microdefects on tissue surface by mid-infrared erbium laser radiation with propagation ratio M2<2 (Er-laser microprocessing). Proposed method was used for preparation of hard tooth tissues surface before filling for improvement of bond strength between tissues surface and restorative materials, microleakage reduction between tissues surface and restorative materials, and for caries prevention as a result of increasing microhardness and acid resistance of tooth enamel.

Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease

PubMed Central

Cao, Stewart Siyan

2014-01-01

Abstract Significance: The endoplasmic reticulum (ER) is a specialized organelle for the folding and trafficking of proteins, which is highly sensitive to changes in intracellular homeostasis and extracellular stimuli. Alterations in the protein-folding environment cause accumulation of misfolded proteins in the ER that profoundly affect a variety of cellular signaling processes, including reduction–oxidation (redox) homeostasis, energy production, inflammation, differentiation, and apoptosis. The unfolded protein response (UPR) is a collection of adaptive signaling pathways that evolved to resolve protein misfolding and restore an efficient protein-folding environment. Recent Advances: Production of reactive oxygen species (ROS) has been linked to ER stress and the UPR. ROS play a critical role in many cellular processes and can be produced in the cytosol and several organelles, including the ER and mitochondria. Studies suggest that altered redox homeostasis in the ER is sufficient to cause ER stress, which could, in turn, induce the production of ROS in the ER and mitochondria. Critical Issues: Although ER stress and oxidative stress coexist in many pathologic states, whether and how these stresses interact is unknown. It is also unclear how changes in the protein-folding environment in the ER cause oxidative stress. In addition, how ROS production and protein misfolding commit the cell to an apoptotic death and contribute to various degenerative diseases is unknown. Future Directions: A greater fundamental understanding of the mechanisms that preserve protein folding homeostasis and redox status will provide new information toward the development of novel therapeutics for many human diseases. Antioxid. Redox Signal. 21, 396–413. PMID:24702237

Coordination of Endoplasmic Reticulum (ER) Signaling During Maize Seed Development

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

Boston, Rebecca S.

2010-11-20

Seed storage reserves represent one of the most important sources of renewable fixed carbon and nitrogen found in nature. Seeds are well-adapted for diverting metabolic resources to synthesize storage proteins as well as enzymes and structural proteins needed for their transport and packaging into membrane bound storage protein bodies. Our underlying hypothesis is that the endoplasmic reticulum (ER) stress response provides the critical cellular control of metabolic flux required for optimal accumulation of storage reserves in seeds. This highly conserved response is a cellular mechanism to monitor the protein folding environment of the ER and restore homeostasis in the presencemore » of unfolded or misfolded proteins. In seeds, deposition of storage proteins in protein bodies is a highly specialized process that takes place even in the presence of mutant proteins that no longer fold and package properly. The capacity of the ER to deposit these aberrant proteins in protein bodies during a period that extends several weeks provides an excellent model for deconvoluting the ER stress response of plants. We have focused in this project on the means by which the ER senses and responds to functional perturbations and the underlying intracellular communication that occurs among biosynthetic, trafficking and degradative pathways for proteins during seed development.« less

Acetylcholine ameliorates endoplasmic reticulum stress in endothelial cells after hypoxia/reoxygenation via M3 AChR-AMPK signaling.

PubMed

Bi, Xueyuan; He, Xi; Xu, Man; Zhao, Ming; Yu, Xiaojiang; Lu, Xingzhu; Zang, Weijin

2015-08-03

Endoplasmic reticulum (ER) stress is associated with various cardiovascular diseases. However, its pathophysiological relevance and the underlying mechanisms in the context of hypoxia/reoxygenation (H/R) in endothelial cells are not fully understood. Previous findings have suggested that acetylcholine (ACh), the major vagal nerve neurotransmitter, protected against cardiomyocyte injury by activating AMP-activated protein kinase (AMPK). This study investigated the role of ER stress in endothelial cells during H/R and explored the beneficial effects of ACh. Our results showed that H/R triggered ER stress and apoptosis in endothelial cells, evidenced by the elevation of glucose-regulated protein 78, cleaved caspase-12 and C/EBP homologous protein expression. ACh significantly decreased ER stress and terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling positive cells and restored ER ultrastructural changes induced by H/R, possibly via protein kinase-like ER kinase and inositol-requiring kinase 1 pathways. Additionally, 4-diphenylacetoxy-N-methylpiperidine methiodide, a type-3 muscarinic ACh receptor (M3 AChR) inhibitor, abolished ACh-mediated increase in AMPK phosphorylation during H/R. Furthermore, M3 AChR or AMPK siRNA abrogated the ACh-elicited the attenuation of ER stress in endothelial cells, indicating that the salutary effects of ACh were likely mediated by M3 AChR-AMPK signaling. Overall, ACh activated AMPK through M3 AChR, thereby inhibited H/R-induced ER stress and apoptosis in endothelial cells. We have suggested for the first time that AMPK may function as an essential intermediate step between M3 AChR stimulation and inhibition of ER stress-associated apoptotic pathway during H/R, which may help to develop novel therapeutic approaches targeting ER stress to prevent or alleviate ischemia/reperfusion injury.

Functional activation of the estrogen receptor-α and aromatase by the HDAC inhibitor, entinostat, sensitizes of ER-negative tumors to letrozole

PubMed Central

Sabnis, Gauri J; Goloubeva, Olga; Chumsri, Saranya; Nguyen, Nguyen; Sukumar, Saraswati; Brodie, Angela MH

2011-01-01

Approximately 25% of breast cancers do not express the estrogen receptor (ERα) and consequently do not respond to endocrine therapy. In these tumors, ERα repression is often due to epigenetic modifications such as methylation and histone deacetylation. For this reason, we investigated the ability of the histone deacetylase inhibitor entinostat (ENT) to trigger re-expression of ERα and aromatase in breast cancer cells, with the notion that this treatment would restore sensitivity to the aromatase inhibitor letrozole. ENT treatment of tumor cells increased expression of ERα and aromatase along with the enzymatic activity of aromatase, in a dose-dependent manner both in vitro and in vivo. Notably, ERα and aromatase upregulation resulted in sensitization of breast cancer cells to estrogen and letrozole. Tumor growth rate was significantly lower in tumor xenografts following treatment with ENT alone and in combination with letrozole compared to control tumors (p >0.001). ENT plus letrozole also prevented lung colonization and growth of tumor cells with a significant reduction (p>0.03) in both visible and microscopic foci. Our results demonstrate that ENT treatment can be used to restore the letrozole responsiveness of ER-negative tumors. More generally, they provide a strong rationale for immediate clinical evaluation of combinations of histone deacetylase and aromatase inhibitors to treat ER-negative and endocrine-resistant breast cancers. PMID:21245100

Sealing ability of three root-end filling materials prepared using an erbium: Yttrium aluminium garnet laser and endosonic tip evaluated by confocal laser scanning microscopy

PubMed Central

Nanjappa, A Salin; Ponnappa, KC; Nanjamma, KK; Ponappa, MC; Girish, Sabari; Nitin, Anita

2015-01-01

Aims: (1) To compare the sealing ability of mineral trioxide aggregate (MTA), Biodentine, and Chitra-calcium phosphate cement (CPC) when used as root-end filling, evaluated under confocal laser scanning microscope using Rhodamine B dye. (2) To evaluate effect of ultrasonic retroprep tip and an erbium:yttrium aluminium garnet (Er:YAG) laser on the integrity of three different root-end filling materials. Materials and Methods: The root canals of 80 extracted teeth were instrumented and obturated with gutta-percha. The apical 3 mm of each tooth was resected and 3 mm root-end preparation was made using ultrasonic tip (n = 30) and Er:YAG laser (n = 30). MTA, Biodentine, and Chitra-CPC were used to restore 10 teeth each. The samples were coated with varnish and after drying, they were immersed in Rhodamine B dye for 24 h. The teeth were then rinsed, sectioned longitudinally, and observed under confocal laser scanning microscope. Statistical Analysis Used: Data were analyzed using one-way analysis of variance (ANOVA) and a post-hoc Tukey's test at P < 0.05 (R software version 3.1.0). Results: Comparison of microleakage showed maximum peak value of 0.45 mm for Biodentine, 0.85 mm for MTA, and 1.05 mm for Chitra-CPC. The amount of dye penetration was found to be lesser in root ends prepared using Er:YAG laser when compared with ultrasonics, the difference was found to be statistically significant (P < 0.05). Conclusions: Root-end cavities prepared with Er:YAG laser and restored with Biodentine showed superior sealing ability compared to those prepared with ultrasonics. PMID:26180420

Influence of Er:YAG laser irradiation distance on the bond strength of a restorative system to enamel.

PubMed

Chimello-Sousa, Daniela Thomazatti; de Souza, Aline Evangelista; Chinelatti, Michelle Alexandra; Pécora, Jesus Djalma; Palma-Dibb, Regina Guenka; Milori Corona, Silmara Aparecida

2006-03-01

The aim of the present study was to investigate in vitro the effect of Er:YAG laser on bonding to enamel, varying the irradiation distance. Tensile bond strength of an adhesive restorative system to non-irradiated and irradiated enamel surfaces was evaluated. Thirty caries-free human third molars were sectioned in mesio-distal direction and embedded in acrylic resin. Enamel was flattened, and a 3-mm-diameter bonding area was demarcated. Specimens were randomly assigned into six groups: groups I-V were treated with the Er:YAG laser (80 mJ/2 Hz), varying the irradiation distance (11, 12 mm-focused, 14, 16 and 17 mm, respectively), followed by 35% phosphoric acid etching. Control group (VI) received treatment with phosphoric acid alone. Single Bond adhesive system was applied on the conditioned enamel, and composite resin cones, bonded to enamel, were fabricated with Z250. After storage, samples were tested in tensile to failure (50 kgf and 0.5 mm/min). Means in MPa were: I-9.67 (+/-3.44); II-13.29 (+/-2.65); III-13.33 (+/-2.22); IV-14.87 (+/-3.58); V-16.43 (+/-4.52); VI-22.90 (+/-3.03). ANOVA and Tukey test revealed statistically significant decrease of bond strength in group I (P < 0.05). Groups II-IV presented similar results, as did groups IV and V. Control group (VI) yielded the best overall performance (P < 0.05). Er:YAG laser irradiation adversely affected adhesion to enamel. However, bond strength was influenced by the irradiation distance, thus being stronger with the increase of distance to the target tissue.

Shear bond strength of composite bonded with three adhesives to Er,Cr:YSGG laser-prepared enamel.

PubMed

Türkmen, Cafer; Sazak-Oveçoğlu, Hesna; Günday, Mahir; Güngör, Gülşad; Durkan, Meral; Oksüz, Mustafa

2010-06-01

To assess in vitro the shear bond strength of a nanohybrid composite resin bonded with three adhesive systems to enamel surfaces prepared with acid and Er,Cr:YSGG laser etching. Sixty extracted caries- and restoration-free human maxillary central incisors were used. The teeth were sectioned 2 mm below the cementoenamel junction. The crowns were embedded in autopolymerizing acrylic resin with the labial surfaces facing up. The labial surfaces were prepared with 0.5-mm reduction to receive composite veneers. Thirty specimens were etched with Er,Cr:YSGG laser. This group was also divided into three subgroups, and the following three bonding systems were then applied on the laser groups and the other three unlased groups: (1) 37% phosphoric acid etch + Bond 1 primer/adhesive (Pentron); (2) Nano-bond self-etch primer (Pentron) + Nano-bond adhesive (Pentron); and (3) all-in-one adhesive-single dose (Futurabond NR, Voco). All of the groups were restored with a nanohybrid composite resin (Smile, Pentron). Shear bond strength was measured with a Zwick universal test device with a knife-edge loading head. The data were analyzed with two-factor ANOVA. There were no significant differences in shear bond strength between self-etch primer + adhesive and all-in-one adhesive systems for nonetched and laser-etched enamel groups (P > .05). However, bond strength values for the laser-etched + Bond 1 primer/adhesive group (48.00 +/- 13.86 MPa) were significantly higher than the 37% phosphoric acid + Bond 1 primer/adhesive group (38.95 +/- 20.07 MPa) (P < .05). The Er,Cr:YSGG laser-powered hydrokinetic system etched the enamel surface more effectively than 37% phosphoric acid for subsequent attachment of composite material.

Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes.

PubMed

Cheng, Tsing; Orlow, Seth J; Manga, Prashiela

2013-11-01

Accumulation of proteins in the endoplasmic reticulum (ER) typically induces stress and initiates the unfolded protein response (UPR) to facilitate recovery. If homeostasis is not restored, apoptosis is induced. However, adaptation to chronic UPR activation can increase resistance to subsequent acute ER stress. We therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2 (Oca2)-null melanocytes where UPR signaling is arrested despite continued tyrosinase accumulation leading to resistance to the chemical ER stressor thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk-mediated phosphorylation of eIF2α, in Oca2-null melanocytes, eIF2α was rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the Gadd34-PP1α phosphatase complex. Gadd34-complex inhibition blocked eIF2α dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption of pro-apoptotic Perk signaling, which promotes cell survival. This is the first study to demonstrate rapid eIF2α dephosphorylation as an adaptive mechanism to ER stress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Restoration of shoulder biomechanics according to degree of repair completion in a cadaveric model of massive rotator cuff tear: importance of margin convergence and posterior cuff fixation.

PubMed

Oh, Joo Han; McGarry, Michelle H; Jun, Bong Jae; Gupta, Akash; Chung, Kyung Chil; Hwang, James; Lee, Thay Q

2012-11-01

Complete repair in massive rotator cuff tear may not be possible, allowing for only partial repair. However, the effect of partial repair on glenohumeral biomechanics has not been evaluated. Therefore, the purpose of this study was to compare the rotational range of motion (ROM), glenohumeral kinematics, and gap formation at the repaired tendon edge following massive cuff tear and repair according to the degree of repair completion. Posterior fixation will restore the altered biomechanics of massive rotator cuff tear. Controlled laboratory study. Eight cadaveric shoulders were tested at 0°, 30°, and 60° of abduction in the scapular plane. Muscle loading was applied based on physiological muscle cross-sectional area ratios. Maximum internal (MaxIR) and external rotations (MaxER) were measured. Humeral head apex (HHA) position and gap formation at the repaired tendon edge were measured using a MicroScribe from MaxIR to MaxER in 30° increments. Testing was performed for intact, massive cuff tear, complete repair, and 4 types of partial repair. A repeated-measures analysis of variance was used to determine significant differences. Massive tear significantly increased ROM and shifted HHA superiorly in MaxIR at all abduction angles (P < .05). The complete repair restored ROM to intact (P < .05), while all partial repairs did not. Abnormal HHA elevation due to massive tear was restored by all repairs (P < .05). Release of the anterior single row alone and release of the marginal convergence significantly increased gap formation at the anterior tendon edge (P < .05). This study emphasizes the importance of anterior fixation in massive cuff tear to restore rotational range of motion and decrease gap formation at the repaired tendon edge and of posterior fixation to restore abnormal glenohumeral kinematics due to massive cuff tear. If complete repair of massive cuff tear is not possible, posterior cuff (infraspinatus) repair is necessary to restore abnormal glenohumeral kinematics, and margin convergence anteriorly is recommended to decrease gap formation of the repaired tendon edge, which may provide a better biomechanical environment for healing.

Moving from rhetoric to reality: adapting Housing First for homeless individuals with mental illness from ethno-racial groups

PubMed Central

2012-01-01

Background The literature on interventions addressing the intersection of homelessness, mental illness and race is scant. The At Home/Chez Soi research demonstration project is a pragmatic field trial investigating a Housing First intervention for homeless individuals with mental illness in five cities across Canada. A unique focus at the Toronto site has been the development and implementation of a Housing First Ethno-Racial Intensive Case Management (HF ER-ICM) arm of the trial serving 100 homeless individuals with mental illness from ethno-racial groups. The HF ER-ICM program combines the Housing First approach with an anti-racism/anti-oppression framework of practice. This paper presents the findings of an early implementation and fidelity evaluation of the HF ER-ICM program, supplemented by participant narrative interviews to inform our understanding of the HF ER-ICM program theory. Methods Descriptive statistics are used to describe HF ER-ICM participant characteristics. Focus group interviews, key informant interviews and fidelity assessments were conducted between November 2010 and January 2011, as part of the program implementation evaluation. In-depth qualitative interviews with HF ER-ICM participants and control group members were conducted between March 2010 and June 2011. All qualitative data were analysed using grounded theory methodology. Results The target population had complex health and social service needs. The HF ER-ICM program enjoyed a high degree of fidelity to principles of both anti-racism/anti-oppression practice and Housing First and comprehensively addressed the housing, health and sociocultural needs of participants. Program providers reported congruence of these philosophies of practice, and program participants valued the program and its components. Conclusions Adapting Housing First with anti-racism/anti-oppression principles offers a promising approach to serving the diverse needs of homeless people from ethno-racial groups and strengthening the service systems developed to support them. The use of fidelity and implementation evaluations can be helpful in supporting successful adaptations of programs and services. Trial registration Current Controlled Trials ISRCTN42520374 PMID:23031406

Mesoscale Design of Magnetoelectric Nanocomposites

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

Viehland, Dwight; Priya, Shashank

This is a final report for a transient program that was issued to Virginia Tech as a new program (DE-SC0001450), rather than as a renewal to our existing program (DE-FG02-06ER46290). The renewal proposal was submitted in November 2014, but because of confusion in the negotiations got issued as a new program. Subsequently, a correction was made where the new program (DE-SC0001450) was terminated, and a renewal to the existing program (DE-FG02-06ER46290) issued. About $8,000 was expended on the new program before the mistake was discovered, and actions begun to correct it. The Department of Materials Science and Engineering at Virginiamore » Tech issued a ‘Letter of Guarantee’ to the University to continue work while the issues were sorted out. The renewal proposal (DE-FG02-06ER46290) that was eventually funded was the same one as the new proposal (DE-SC0001450) that was initially funded. The $8,000 expended on the new proposal was subtracted from the eventual amount given in the renewal proposal. Here, we submit the final report for this new program (DE-SC0001450) that was terminated. Since the Statement of Work was identical to the renewal proposal (DE-FG02-06ER46290), we submit to you as the final report for the new program (DE-SC0001450) the same information that we submitted as our annual report for DE-FG02-06ER46290 that was submitted to the program manager (Refik Kortan) in June 2016.« less

US Army Research Laboratory Directed Energy Internship Program 2014

DTIC Science & Technology

2015-11-01

7 1400–1800 nm. However, when making EDFs, the solubility of Er in traditional silica ( SiO2 )-based glass is low and the ions that successfully...Thus, either half or all of the energy in a pair of excited ions could be wasted. In traditional SiO2 -based Er-doped glass (Er-SD), Er is co-doped...upconversion, Er-doped SiO2 NPs (Er-NP) are doped into the glass core of a fiber. This process is thought to create a cage of Al and O ions around each Er

Bacteria, the endoplasmic reticulum and the unfolded protein response: friends or foes?

PubMed

Celli, Jean; Tsolis, Renée M

2015-02-01

The unfolded protein response (UPR) is a cytoprotective response that is aimed at restoring cellular homeostasis following physiological stress exerted on the endoplasmic reticulum (ER), which also invokes innate immune signalling in response to invading microorganisms. Although it has been known for some time that the UPR is modulated by various viruses, recent evidence indicates that it also has multiple roles during bacterial infections. In this Review, we describe how bacteria interact with the ER, including how bacteria induce the UPR, how subversion of the UPR promotes bacterial proliferation and how the UPR contributes to innate immune responses against invading bacteria.

Muscadine Grape Skin Extract Induces an Unfolded Protein Response-Mediated Autophagy in Prostate Cancer Cells: A TMT-Based Quantitative Proteomic Analysis

PubMed Central

Burton, Liza J.; Rivera, Mariela; Hawsawi, Ohuod; Zou, Jin; Hudson, Tamaro; Wang, Guangdi; Zhang, Qiang; Cubano, Luis; Boukli, Nawal; Odero-Marah, Valerie

2016-01-01

Muscadine grape skin extract (MSKE) is derived from muscadine grape (Vitis rotundifolia), a common red grape used to produce red wine. Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy. We hypothesized that MSKE may induce a severe ER stress response-mediated autophagy leading to apoptosis. As a model, we treated C4-2 prostate cancer cells with MSKE and performed a quantitative Tandem Mass Tag Isobaric Labeling proteomic analysis. ER stress response, autophagy and apoptosis were analyzed by western blot, acridine orange and TUNEL/Annexin V staining, respectively. Quantitative proteomics analysis indicated that ER stress response proteins, such as GRP78 were greatly elevated following treatment with MSKE. The up-regulation of pro-apoptotic markers PARP, caspase-12, cleaved caspase-3, -7, BAX and down-regulation of anti-apoptotic marker BCL2 was confirmed by Western blot analysis and apoptosis was visualized by increased TUNEL/Annexin V staining upon MSKE treatment. Moreover, increased acridine orange, and LC3B staining was detected in MSKE-treated cells, suggesting an ER stress/autophagy response. Finally, MSKE-mediated autophagy and apoptosis was antagonized by co-treatment with chloroquine, an autophagy inhibitor. Our results indicate that MSKE can elicit an UPR that can eventually lead to apoptosis in prostate cancer cells. PMID:27755556

Muscadine Grape Skin Extract Induces an Unfolded Protein Response-Mediated Autophagy in Prostate Cancer Cells: A TMT-Based Quantitative Proteomic Analysis.

PubMed

Burton, Liza J; Rivera, Mariela; Hawsawi, Ohuod; Zou, Jin; Hudson, Tamaro; Wang, Guangdi; Zhang, Qiang; Cubano, Luis; Boukli, Nawal; Odero-Marah, Valerie

2016-01-01

Muscadine grape skin extract (MSKE) is derived from muscadine grape (Vitis rotundifolia), a common red grape used to produce red wine. Endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) that serves as a survival mechanism to relieve ER stress and restore ER homeostasis. However, when persistent, ER stress can alter the cytoprotective functions of the UPR to promote autophagy and cell death. Although MSKE has been documented to induce apoptosis, it has not been linked to ER stress/UPR/autophagy. We hypothesized that MSKE may induce a severe ER stress response-mediated autophagy leading to apoptosis. As a model, we treated C4-2 prostate cancer cells with MSKE and performed a quantitative Tandem Mass Tag Isobaric Labeling proteomic analysis. ER stress response, autophagy and apoptosis were analyzed by western blot, acridine orange and TUNEL/Annexin V staining, respectively. Quantitative proteomics analysis indicated that ER stress response proteins, such as GRP78 were greatly elevated following treatment with MSKE. The up-regulation of pro-apoptotic markers PARP, caspase-12, cleaved caspase-3, -7, BAX and down-regulation of anti-apoptotic marker BCL2 was confirmed by Western blot analysis and apoptosis was visualized by increased TUNEL/Annexin V staining upon MSKE treatment. Moreover, increased acridine orange, and LC3B staining was detected in MSKE-treated cells, suggesting an ER stress/autophagy response. Finally, MSKE-mediated autophagy and apoptosis was antagonized by co-treatment with chloroquine, an autophagy inhibitor. Our results indicate that MSKE can elicit an UPR that can eventually lead to apoptosis in prostate cancer cells.

Evaluation of Access, a Primary Care Program for Indigent Patients: Inpatient and Emergency Room Utilization.

ERIC Educational Resources Information Center

Davidson, Richard A.; Giancola, Angela; Gast, Andrea; Ho, Janice; Waddell, Rhondda

2003-01-01

Evaluated the impact of Accessing Community Care through Eastside Social Services (ACCESS), a program that provided indigent patients with free primary care, on inpatient admissions, emergency room (ER) visits, and subsequent charges. Data on 19 people before and after program enrollment showed significant decreases in ER visits following…

Phase II DERP/ER Public Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story ¢Â€Â“ 7:00 PM Open House 7:00 – 9:00 PM Meeting and Public CommentStart Time: 18:00Date: 2012-11

20 CFR 222.21 - When marriage is terminated by final divorce.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false When marriage is terminated by final divorce... Widow(er) § 222.21 When marriage is terminated by final divorce. A final divorce, often referred to as an absolute divorce, completely dissolves the marriage relationship and restores the parties to the...

20 CFR 222.21 - When marriage is terminated by final divorce.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When marriage is terminated by final divorce... Widow(er) § 222.21 When marriage is terminated by final divorce. A final divorce, often referred to as an absolute divorce, completely dissolves the marriage relationship and restores the parties to the...

20 CFR 222.21 - When marriage is terminated by final divorce.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true When marriage is terminated by final divorce... Widow(er) § 222.21 When marriage is terminated by final divorce. A final divorce, often referred to as an absolute divorce, completely dissolves the marriage relationship and restores the parties to the...

20 CFR 222.21 - When marriage is terminated by final divorce.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false When marriage is terminated by final divorce... Widow(er) § 222.21 When marriage is terminated by final divorce. A final divorce, often referred to as an absolute divorce, completely dissolves the marriage relationship and restores the parties to the...

20 CFR 222.21 - When marriage is terminated by final divorce.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true When marriage is terminated by final divorce... Widow(er) § 222.21 When marriage is terminated by final divorce. A final divorce, often referred to as an absolute divorce, completely dissolves the marriage relationship and restores the parties to the...

Homeostatic Regulation of the PI(4,5)P2-Ca2+ Signaling System at ER-PM Junctions

PubMed Central

Chang, Chi-Lun; Liou, Jen

2016-01-01

The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca2+ signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca2+ from the endoplasmic reticulum (ER) store to the cytosol to activate Ca2+-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca2+ must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca2+. Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca2+ influx across the PM is required to refill the ER Ca2+ store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca2+ signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca2+ signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca2+ signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occurs, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca2+ signaling, including the ER Ca2+ sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This review is part of a Special Issue entitled The Cellular Lipid Landscape. PMID:26924250

Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration.

PubMed

Karthikeyan, Bose; Harini, Lakshminarasimhan; Krishnakumar, Vaithilingam; Kannan, Velu Rajesh; Sundar, Krishnan; Kathiresan, Thandavarayan

2017-01-01

Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H 2 O 2 ) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells. The oxidant molecules influenced MRPE cells showed an increased level of intracellular calcium [Ca 2+ ] i in ER and transferred to mitochondria through ER-mitochondrial tether site then increased ROS production. EGCG restores [Ca 2+ ] i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis. Effect of EGCG on ER stress-mediated apoptosis was elucidated by exploring the UPR signalling pathways. EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells. In addition to this, inhibition of apoptosis by EGCG was also confirmed with expression of proteins Akt, PTEN and GSK3β. MRPE cells with EGCG upregulates phosphorylation of Akt at ser473 and phospho ser380 of PTEN, but phosphorylation at ser9 of GSK3β was inhibited. Further, constitutively active (myristoylated) CA-Akt transfected in MRPE cells had an increased Akt activity in EGCG influenced cells. These findings strongly suggest that antioxidant molecules inhibit cell death through the proper balancing of [Ca 2+ ] i and ROS production in order to maintain UPR of ER in MRPE cells. Thus, modulation of UPR signalling may provide a potential target for the therapeutic approaches of AMD.

U.S. Department of Energy worker health risk evaluation methodology for assessing risks associated with environmental restoration and waste management

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

Blaylock, B.P.; Legg, J.; Travis, C.C.

1995-06-01

This document describes a worker health risk evaluation methodology for assessing risks associated with Environmental Restoration (ER) and Waste Management (WM). The methodology is appropriate for estimating worker risks across the Department of Energy (DOE) Complex at both programmatic and site-specific levels. This document supports the worker health risk methodology used to perform the human health risk assessment portion of the DOE Programmatic Environmental Impact Statement (PEIS) although it has applications beyond the PEIS, such as installation-wide worker risk assessments, screening-level assessments, and site-specific assessments.

Final Report on the Proposal to Provide Asian Science and Technology Information

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

Kahaner, David K.

2003-07-23

The Asian Technology Information Program (ATIP) conducted a seven-month Asian science and technology information program for the Office:of Energy Research (ER), U.S: Department of Energy (DOE.) The seven-month program consists of 1) monitoring, analyzing, and dissemiuating science and technology trends and developments associated with Asian high performance computing and communications (HPC), networking, and associated topics, 2) access to ATIP's annual series of Asian S&T reports for ER and HPC related personnel and, 3) supporting DOE and ER designated visits to Asia to study and assess Asian HPC.

Sub-ablative Er,Cr:YSGG laser irradiation under all-ceramic restorations: effects on demineralization and shear bond strength.

PubMed

Bağlar, Serdar

2018-01-01

This study evaluated the caries resistant effects of sub-ablative Er,Cr:YSGG laser irradiation alone and combined with fluoride in comparison with fluoride application alone on enamel prepared for veneer restorations. And also, evaluated these treatments' effects on the shear bond strength of all-ceramic veneer restorations. One hundred and thirty-five human maxillary central teeth were assigned to groups of 1a-control, 1b-laser treated, 1c-fluoride treated, 1d-laser + fluoride treated for shear bond testing and to groups of 2a-positive control(non-demineralised), 2b-laser treated, 2c-fluoride treated, 2d-laser + fluoride treated, 2e-negative control (demineralised) for microhardness testing (n = 15, N = 135). Demineralisation solutions of microhardness measurements were used for the ICP-OES elemental analysis. The parameters for laser irradiation were as follows: power output, 0.25 W; total energy density, 62.5 J/cm 2 and energy density per pulse, 4.48 J/cm 2 with an irradiation time of 20 s and with no water cooling. Five percent NaF varnish was used as fluoride preparate. ANOVA and Tukey HSD tests were performed (α = 5%). Surface treatments showed no significant effects on shear bond strength values (p = 0.579). However, significant differences were found in microhardness measurements and in elemental analysis of Ca and P amounts (p < 0.01). Surface-treated groups showed significantly high VNH values and significantly low ICP-OES values when compared with non-treated (-control) group while there were no significance among surface-treated groups regarding VHN and ICP-OES values. Sub-ablative Er,Cr:YSGG treatment alone or combined with fluoride is as an effective method as at least fluoride alone for preventing the prepared enamel to demineralization with no negative effect on shear bond strength.

Induction of endoplasmic reticulum stress under endotoxin tolerance increases inflammatory responses and decreases Pseudomonas aeruginosa pneumonia.

PubMed

Kim, Sena; Joe, Yeonsoo; Park, Se-Ung; Jeong, Sun Oh; Kim, Jin-Kyung; Park, Seong Hoon; Pae, Hyun-Ock; Surh, Young-Joon; Shin, Jaekyoon; Chung, Hun Taeg

2018-06-20

Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box-binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages. Animal and in vitro models of endotoxin tolerance were studied along with a model of LPS-induced endotoxin tolerance and a model of cecal ligation and puncture (CLP)-induced endotoxin tolerance. To detect the suppressed inflammatory response during endotoxin tolerance, inflammatory-cytokine expression levels were measured by quantitative real-time PCR and an ELISA. Our research revealed that induction of ER stress alleviated lung injury in a septic host infected with Pseudomonas aeruginosa via the activation of GSK-3β and XBP-1 in an IRE1α-mediated manner. Consequently, in the lungs of the septic host infected with P. aeruginosa, symptoms of pneumonia improved and the infecting bacteria were cleared. Thus, for septic patients, determination of immune status may guide the selection of appropriate immunomodulation, and ER stress can be a novel therapeutic strategy restoring the immune response in patients with endotoxin tolerance. ©2018 Society for Leukocyte Biology.

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

PubMed

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Analysis of ER Resident Proteins in S. cerevisiae: Implementation of H/KDEL Retrieval Sequences

PubMed Central

Young, Carissa L.; Raden, David L.; Robinson, Anne S.

2013-01-01

An elaborate quality control system regulates ER homeostasis by ensuring the fidelity of protein synthesis and maturation. In budding yeast, genomic analyses and high-throughput proteomic studies have identified ER resident proteins that restore homeostasis following local perturbations. Yet, how these folding factors modulate stress has been largely unexplored. In this study, we designed a series of PCR-based modules including codon-optimized epitopes and FP variants complete with C-terminal H/KDEL retrieval motifs. These conserved sequences are inherent to most soluble ER resident proteins. To monitor multiple proteins simultaneously, H/KDEL cassettes are available with six different selection markers, providing optimal flexibility for live-cell imaging and multicolor labeling in vivo. A single pair of PCR primers can be used for the amplification of these 26 modules, enabling numerous combinations of tags and selection markers. The versatility of pCY H/KDEL cassettes was demonstrated by labeling BiP/Kar2p, Pdi1p, and Scj1p with all novel tags, thus providing a direct comparison among FP variants. Furthermore, to advance in vitro studies of yeast ER proteins, Strep-tag II was engineered with a C-terminal retrieval sequence. Here, an efficient purification strategy was established for BiP under physiological conditions. PMID:23324027

77 FR 57074 - Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... Damage Assessment, Remediation, and Restoration Program for Fiscal Year 2011 AGENCY: National Oceanic and..., Remediation, and Restoration Program for Fiscal Year 2011. SUMMARY: The National Oceanic and Atmospheric Administration's (NOAA's) Damage Assessment, Remediation, and Restoration Program (DARRP) is announcing new...

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

PubMed Central

Chhunchha, Bhavana; Fatma, Nigar; Kubo, Eri; Rai, Prerana; Singh, Sanjay P.

2013-01-01

Oxidative stress and endoplasmic reticulum (ER) stress are emerging as crucial events in the etiopathology of many neurodegenerative diseases. While the neuroprotective contributions of the dietary compound curcumin has been recognized, the molecular mechanisms underlying curcumin's neuroprotection under oxidative and ER stresses remains elusive. Herein, we show that curcumin protects HT22 from oxidative and ER stresses evoked by the hypoxia (1% O2 or CoCl2 treatment) by enhancing peroxiredoxin 6 (Prdx6) expression. Cells exposed to CoCl2 displayed reduced expression of Prdx6 with higher reactive oxygen species (ROS) expression and activation of NF-κB with IκB phosphorylation. When NF-κB activity was blocked by using SN50, an inhibitor of NF-κB, or cells treated with curcumin, the repression of Prdx6 expression was restored, suggesting the involvement of NF-κB in modulating Prdx6 expression. These cells were enriched with an accumulation of ER stress proteins, C/EBP homologous protein (CHOP), GRP/78, and calreticulin, and had activated states of caspases 12, 9, and 3. Reinforced expression of Prdx6 in HT22 cells by curcumin reestablished survival signaling by reducing propagation of ROS and blunting ER stress signaling. Intriguingly, knockdown of Prdx6 by antisense revealed that loss of Prdx6 contributed to cell death by sustaining enhanced levels of ER stress-responsive proapoptotic proteins, which was due to elevated ROS production, suggesting that Prdx6 deficiency is a cause of initiation of ROS-mediated ER stress-induced apoptosis. We propose that using curcumin to reinforce the naturally occurring Prdx6 expression and attenuate ROS-based ER stress and NF-κB-mediated aberrant signaling improves cell survival and may provide an avenue to treat and/or postpone diseases associated with ROS or ER stress. PMID:23364261

Endoplasmic reticulum stress (ER-stress) by 2-deoxy-D-glucose (2DG) reduces cyclooxygenase-2 (COX-2) expression and N-glycosylation and induces a loss of COX-2 activity via a Src kinase-dependent pathway in rabbit articular chondrocytes.

PubMed

Yu, Seon-Mi; Kim, Song-Ja

2010-11-30

Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein, as determined by a Western blot analysis. In addition, induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66-70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficiently recovered 2DG- modified COX-2 molecular mass and COX-2 activity might be associated with COX-2 N-glycosylation. Also, treatment of 2DG increased phosphorylation of Src in chondrocytes. The inhibition of the Src signaling pathway with PP2 (Src tyrosine kinase inhibitor) suppressed grp94 expression and restored COX-2 expression, N-glycosylation, and PGE2 production, as determined by a Western blot analysis and PGE2 assay. Taken together, our results indicate that the ER stress induced by 2DG results in a decrease of the transcription level, the molecular mass, and the activity of COX-2 in rabbit articular chondrocytes via a Src kinase-dependent pathway.

Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia.

PubMed

Bohnert, Kyle R; Gallot, Yann S; Sato, Shuichi; Xiong, Guangyan; Hindi, Sajedah M; Kumar, Ashok

2016-09-01

Cachexia is a devastating syndrome that causes morbidity and mortality in a large number of patients with cancer. However, the mechanisms of cancer cachexia remain poorly understood. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes stress. The ER responds to this stress through activating certain pathways commonly known as the unfolding protein response (UPR). The main function of UPR is to restore homeostasis, but excessive or prolonged activation of UPR can lead to pathologic conditions. In this study, we examined the role of ER stress and UPR in regulation of skeletal muscle mass in naïve conditions and during cancer cachexia. Our results demonstrate that multiple markers of ER stress are highly activated in skeletal muscle of Lewis lung carcinoma (LLC) and Apc(Min/+) mouse models of cancer cachexia. Treatment of mice with 4-phenylbutyrate (4-PBA), a chemical chaperon and a potent inhibitor of ER stress, significantly reduced skeletal muscle strength and mass in both control and LLC-bearing mice. Blocking the UPR also increased the proportion of fast-type fibers in soleus muscle of both control and LLC-bearing mice. Inhibition of UPR reduced the activity of Akt/mTOR pathway and increased the expression of the components of the ubiquitin-proteasome system and autophagy in LLC-bearing mice. Moreover, we found that the inhibition of UPR causes severe atrophy in cultured myotubes. Our study provides initial evidence that ER stress and UPR pathways are essential for maintaining skeletal muscle mass and strength and for protection against cancer cachexia.-Bohnert, K. R., Gallot, Y. S., Sato, S., Xiong, G., Hindi, S. M., Kumar, A. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia. © FASEB.

Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

PubMed

Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

2017-08-01

Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.

Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.

PubMed

Bozi, Luiz H M; Jannig, Paulo R; Rolim, Natale; Voltarelli, Vanessa A; Dourado, Paulo M M; Wisløff, Ulrik; Brum, Patricia C

2016-11-01

Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate-intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN-1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin-like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI-induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post-MI heart failure rats. These results reinforce the importance of AET as primary non-pharmacological therapy to cardiovascular disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Effect of CO2, Nd:YAG and Er:YAG Lasers on Microtensile Bond Strength of Composite to Bleached-Enamel.

PubMed

Basir, Mahshid Mohammadi; Rezvani, Mohammad Bagher; Chiniforush, Nasim; Moradi, Zohreh

2016-01-01

Tooth restoration immediately after bleaching is challenging due to the potential problems in achieving adequate bond strength. The aim of this study was to evaluate the effect of surface treatment with ER:YAG, ND:YAG, CO2 lasers and 10% sodium ascorbate solution on immediate microtensile bond strength of composite resin to recently bleached enamel. Ninety sound molar teeth were randomly divided into three main groups (n:30) : NB (without bleaching), HB (bleached with 38% carbamide peroxide) and OB (bleached with Heydent bleaching gel assisted by diode laser). Each group was divided into five subgroups (n:6) : Si (without surface treatment), Er (Er:YAG laser), CO2 (CO2 laser), Nd (Nd:YAG laser) and As (Immersion in 10% sodium ascorbate solution). The bonding system was then applied and composite build-ups were constructed. The teeth were sectioned by low speed saw to obtain enamel- resin sticks and submitted to microtensile bond testing. Statistical analyses were done using two- way ANOVA, Tukey and Tamhane tests. µTBS of bleached teeth irradiated with ND:YAG laser was not significantly different from NB-Nd group. Microtensile bond strength of OB-Er group was higher than NB-Er and HB-Er groups. The mean µTBS of HB-CO2 group was higher than NB-CO2 group; the average µTBS of HB-As and OB-As groups was also higher than NB-As group. Use of Nd:YAG, CO2 lasers and 10% sodium ascorbate solution could improve the bond strength in home-bleached specimens. Application of ND:YAG laser on nonbleached specimens and Er:YAG laser on office-bleached specimens led to the highest µTBS in comparison to other surface treatments in each main group.

The Economic Value of Remote Sensing of Earth Resources from Space: An ERTS Overview and the Value of Continuity of Service. Volume 1: Summary

NASA Technical Reports Server (NTRS)

Hazelrigg, G. A., Jr.; Heiss, K. P.

1974-01-01

An overview of the ERTS program is given to determine the magnitude of the benefits that can be reasonably expected to flow from an Earth Resources Survey (ERS) Program, and to assess the benefits foregone in the event of a one or two-year gap in ERS services. An independent evaluation of the benefits attributable to ERS-derived information in key application areas is presented. These include two case studies in agriculture-distribution, production and import/export, and one study in water management. The cost-effectiveness of satellites in an ERS system is studied by means of a land cover case study. The annual benefits achieveable from an ERS system are measured by the in-depth case studies to be in the range of $430 to $746 million. Benefits foregone in the event of a one-year gap in ERS service are estimated to be $147 to $220 million and $274 to $420 million for a two-year gap in ERS service.

Oak restoration trials: Santa Catalina Island

Treesearch

Lisa Stratton

2002-01-01

Two restoration trials involving four oak species have been implemented as part of a larger restoration program for Catalina Island. In 1997 the Catalina Island Conservancy began an active program of restoration after 50 years of ranching and farming activities on the island. The restoration program includes removing feral goats and pigs island-wide and converting 80...

FY 2009 SERDP Annual Report

DTIC Science & Technology

2010-02-01

Focus Areas: Environmental Restoration - Phytoremediation for the Containment and Treatment of Energetic and Propellant Material Releases on Testing...and Training Ranges, and a second project, Sustainable Range Management of RDX and TNT by Phytoremediation with Engineered Plants; Munitions...and Engineering Laboratory  Sustainable Range Management of RDX and TNT by Phytoremediation with Engineered Plants (ER-1498), University of York

Low molecular weight fucoidan improves endoplasmic reticulum stress-reduced insulin sensitivity through AMP-activated protein kinase activation in L6 myotubes and restores lipid homeostasis in a mouse model of type 2 diabetes.

PubMed

Jeong, Yong-Tae; Kim, Yong Deuk; Jung, Young-Mi; Park, Dong-Chan; Lee, Dong-Sub; Ku, Sae-Kwang; Li, Xian; Lu, Yue; Chao, Guang Hsuan; Kim, Keuk-Jun; Lee, Jai-Youl; Baek, Moon-Chang; Kang, Wonku; Hwang, Seung-Lark; Chang, Hyeun Wook

2013-07-01

Low molecular weight fucoidan (LMWF) is widely used to treat metabolic disorders, but its physiologic effects have not been well determined. In the present study, we investigated the metabolic effects of LMWF in obese diabetic mice (leptin receptor-deficient db/db mice) and the underlying molecular mechanisms involved in endoplasmic reticulum (ER) stress-responsive L6 myotubes. The effect of LMWF-mediated AMP-activated protein kinase (AMPK) activation on insulin resistance via regulation of the ER stress-dependent pathway was examined in vitro and in vivo. In db/db mice, LMWF markedly reduced serum glucose, triglyceride, cholesterol, and low-density lipoprotein levels, and gradually reduced body weights by reducing lipid parameters. Furthermore, it effectively ameliorated glucose homeostasis by elevating glucose tolerance. In addition, the phosphorylation levels of AMPK and Akt were markedly reduced by ER stressor, and subsequently, glucose uptake and fatty acid oxidation were also reduced. However, these adverse effects of ER stress were significantly ameliorated by LMWF. Finally, in L6 myotubes, LMWF markedly reduced the ER stress-induced upregulation of the mammalian target of rapamycin-p70S61 kinase network and subsequently improved the action of insulin via AMPK stimulation. Our findings suggest that AMPK activation by LMWF could prevent metabolic diseases by controlling the ER stress-dependent pathway and that this beneficial effect of LMWF provides a potential therapeutic strategy for ameliorating ER stress-mediated metabolic dysfunctions.

The Grand Banks ERS-1 SAR wave spectra validation experiment

NASA Technical Reports Server (NTRS)

Vachon, P. W.; Dobson, F. W.; Smith, S. D.; Anderson, R. J.; Buckley, J. R.; Allingham, M.; Vandemark, D.; Walsh, E. J.; Khandekar, M.; Lalbeharry, R.

1993-01-01

As part of the ERS-1 validation program, the ERS-1 Synthetic Aperture Radar (SAR) wave spectra validation experiment was carried out over the Grand Banks of Newfoundland (Canada) in Nov. 1991. The principal objective of the experiment was to obtain complete sets of wind and wave data from a variety of calibrated instruments to validate SAR measurements of ocean wave spectra. The field program activities are described and the rather complex wind and wave conditions which were observed are summarized. Spectral comparisons with ERS-1 SAR image spectra are provided. The ERS-1 SAR is shown to have measured swell and range traveling wind seas, but did not measure azimuth traveling wind seas at any time during the experiment. Results of velocity bunching forward mapping and new measurements of the relationship between wind stress and sea state are also shown.

A New Vision for Integrated Breast Care

DTIC Science & Technology

2001-09-01

100%] Lumpectomy 3 day/ 5 day/ 7 day [ 40 %, 70%, 95%] Mastectomy 3day/ 5 day/7 day [ 30 %, 50%, 95%] ER/PR 7 day [100%] Her-2/neu 7 day/12 day [60%, 95...Cosmetic result [95%] Radiation after Lumpectomy < 50 years [95-100%] 50-69 years (ER+/ER-) [70/90%] > 70 years (ER+/ER-) [ 30 / 40 %] Program Satisfaction... vegetables , fruits and fiber can reduce recurrence rates for breast cancer, whether participation in support groups (and what kinds) can improve survival

Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

PubMed

Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

2017-09-01

An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.

Men's Experience with Penile Rehabilitation Following Radical Prostatectomy: A Qualitative Study with the Goal of Informing a Therapeutic Intervention

PubMed Central

Nelson, Christian J.; Lacey, Stephanie; Kenowitz, Joslyn; Pessin, Hayley; Shuk, Elyse; Mulhall, John P.

2016-01-01

Objectives Erectile rehabilitation (ER) following radical prostatectomy (RP) is considered an essential component to help men regain erectile functioning; however many men have difficulty adhering to this type of a program. This qualitative study explored men's experience with ER, erectile dysfunction (ED), and ED treatments to inform a psychological intervention designed to help men adhere to ER post-RP. Methods Thirty men, one to three years post-RP, who took part in an ER program, participated in one of four focus groups. Thematic analysis was used to identify the primary themes. Results Average age was 59 (SD=7); mean time since surgery was 26 months (SD=6). Six primary themes emerged: 1) frustration with the lack of information about post-surgery ED; 2) negative emotional impact of ED and avoidance of sexual situations; 3) negative emotional experience with penile injections and barriers leading to avoidance; 4) the benefit of focusing on the long-term advantage of ER versus short-term anxiety; 5) using humor to help cope; and 6) the benefit of support from partners and peers. Conclusions Men's frustration surrounding ED can lead to avoidance of sexual situations and ED treatments, which negatively impact men's adherence to an ER program. The theoretical construct of Acceptance and Commitment Therapy (ACT) was used to place the themes into a framework to conceptualize the mechanisms underlying both avoidance and adherence in this population. As such, ACT has the potential to serve as a conceptual underpinning of a psychological intervention to help men reduce avoidance to penile injections and adhere to an ER program. PMID:25707812

Fracture Forces of Dentin after Surface Treatment with High Speed Drill Compared to Er:YAG and Er,Cr:YSGG Laser Irradiation

PubMed Central

Franzen, Rene; Kianimanesh, Nasrin; Marx, Rudolf; Ahmed, Asma; Gutknecht, Norbert

2016-01-01

Dental tooth restorative procedures may weaken the structural integrity of the tooth, with the possibility of leading to fracture. In this study we present findings of coronal dentin strength after different techniques of surface modification. The fracture strength of dentin beams after superficial material removal with a fine diamond bur high speed drill hand piece, Er:YAG (2.94 μm, 8 J/cm2), and Er,Cr:YSGG (2.78 μm, 7.8 J/cm2) laser irradiation slightly above the ablation threshold was measured by a four-point bending apparatus. Untreated dentin beams served as a control. A total of 58 dentin beams were manufactured from sterilized human extracted molars using the coronal part of the available dentin. Mean values of fracture strength were calculated as 82.0 ± 27.3 MPa for the control group (n = 10), 104.5 ± 26.3 MPa for high speed drill treatment (n = 10), 96.1 ± 28.1 MPa for Er,Cr:YSGG laser irradiation (n = 20), and 89.1 ± 36.3 MPa for Er:YAG laser irradiation (n = 18). Independent Student's t-tests showed no significant difference between each two groups (p > 0.05). Within the parameter settings and the limits of the experimental setup used in this study, both lasers systems as well as the high speed drill do not significantly weaken coronal dentin after surface treatment. PMID:26962473

50 CFR 80.120 - What is program income?

Code of Federal Regulations, 2013 CFR

2013-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80...

50 CFR 80.120 - What is program income?

Code of Federal Regulations, 2014 CFR

2014-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80...

50 CFR 80.123 - How may an agency use program income?

Code of Federal Regulations, 2012 CFR

2012-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program...

50 CFR 80.123 - How may an agency use program income?

Code of Federal Regulations, 2011 CFR

2011-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program...

Effects of solvent evaporation time on immediate adhesive properties of universal adhesives to dentin.

PubMed

Luque-Martinez, Issis V; Perdigão, Jorge; Muñoz, Miguel A; Sezinando, Ana; Reis, Alessandra; Loguercio, Alessandro D

2014-10-01

To evaluate the microtensile bond strengths (μTBS) and nanoleakage (NL) of three universal or multi-mode adhesives, applied with increasing solvent evaporation times. One-hundred and forty caries-free extracted third molars were divided into 20 groups for bond strength testing, according to three factors: (1) Adhesive - All-Bond Universal (ABU, Bisco, Inc.), Prime&Bond Elect (PBE, Dentsply), and Scotchbond Universal Adhesive (SBU, 3M ESPE); (2) Bonding strategy - self-etch (SE) or etch-and-rinse (ER); and (3) Adhesive solvent evaporation time - 5s, 15s, and 25s. Two extra groups were prepared with ABU because the respective manufacturer recommends a solvent evaporation time of 10s. After restorations were constructed, specimens were stored in water (37°C/24h). Resin-dentin beams (0.8mm(2)) were tested at 0.5mm/min (μTBS). For NL, forty extracted molars were randomly assigned to each of the 20 groups. Dentin disks were restored, immersed in ammoniacal silver nitrate, sectioned and processed for evaluation under a FESEM in backscattered mode. Data from μTBS were analyzed using two-way ANOVA (adhesive vs. drying time) for each strategy, and Tukey's test (α=0.05). NL data were computed with non-parametric tests (Kruskal-Wallis and Mann-Whitney tests, α=0.05). Increasing solvent evaporation time from 5s to 25s resulted in statistically higher mean μTBS for all adhesives when used in ER mode. Regarding NL, ER resulted in greater NL than SE for each of the evaporation times regardless of the adhesive used. A solvent evaporation time of 25s resulted in the lowest NL for SBU-ER. Residual water and/or solvent may compromise the performance of universal adhesives, which may be improved with extended evaporation times. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

76 FR 61089 - Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-03

... Damage Assessment, Remediation, and Restoration Program for Fiscal Years 2009 and 2010 AGENCY: National... Damage Assessment, Remediation, and Restoration Program for Fiscal Years 2009 and 2010. SUMMARY: The National Oceanic and Atmospheric Administration's (NOAA's) Damage Assessment, Remediation, and Restoration...

50 CFR 80.120 - What is program income?

Code of Federal Regulations, 2012 CFR

2012-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80.120 What...

50 CFR 80.123 - How may an agency use program income?

Code of Federal Regulations, 2013 CFR

2013-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program...

50 CFR 80.123 - How may an agency use program income?

Code of Federal Regulations, 2014 CFR

2014-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program...

50 CFR 80.120 - What is program income?

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80.120 What...

Extensive Reading Program Which Changes Reluctant Engineering Students into Autonomous Learners of English

NASA Astrophysics Data System (ADS)

Nishizawa, Hitoshi; Yoshioka, Takayoshi; Itoh, Kazuaki

This article introduces extensive reading (ER) as an approach to improve fundamental communication skills in English of reluctant EFL learners : average Japanese engineering students. It is distinct from concurrent translation approach from a perspective that the learners use English instead of Japanese to grasp the meaning of what they read and enjoy reading. In the ER program at Toyota National College of Technology, many students developed more positive attitude toward English, increased their reading speed, and achieved higher TOEIC scores, which was compared to those of the students before this ER program was introduced. Comparison between three groups of the students showed strong correlation between their TOEIC scores and the reading amount.

Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase

PubMed Central

Babajani, Gholamreza; Kermode, Allison R

2014-01-01

Gaucher disease is a prevalent lysosomal storage disease characterized by a deficiency in the activity of lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent disease-causing mutations in humans is a L444P missense mutation in the GCase protein, which results in its disrupted folding in the endoplasmic reticulum (ER) and impaired post-ER trafficking. To determine whether the post-ER trafficking of this severely malfolded protein can be restored, we expressed the mutant L444P GCase as a recombinant protein in transgenic tobacco (Nicotiana tabacum L. cv Bright Yellow 2 [BY2]) cells, in which the GCase variant was equipped with a plant signal peptide to allow for secretion upon rescued trafficking out of the ER. The recombinant L444P mutant GCase was retained in the plant endoplasmic reticulum (ER). Kifunensine and Eeyarestatin I, both inhibitors of ER-associated degradation (ERAD), and the proteostasis regulators, celastrol and MG-132, increased the steady-state levels of the mutant protein inside the plant cells and further promoted the post-ER trafficking of L444P GCase, as indicated by endoglycosidase-H sensitivity- and secretion- analyses. Transcript profiling of genes encoding ER-molecular chaperones, ER stress responsive proteins, and cytoplasmic heat shock response proteins, revealed insignificant or only very modest changes in response to the ERAD inhibitors and proteostasis regulators. An exception was the marked response to celastrol which reduced the steady-state levels of cytoplasmic HSP90 transcripts and protein. As HSP90 participates in the targeting of misfolded proteins to the proteasome pathway, its down-modulation in response to celastrol may partly account for the mechanism of improved homeostasis of L444P GCase mediated by this triterpene. PMID:24713615

50 CFR 80.121 - May an agency earn program income?

Code of Federal Regulations, 2014 CFR

2014-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80...

50 CFR 80.121 - May an agency earn program income?

Code of Federal Regulations, 2013 CFR

2013-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80...

78 FR 53425 - Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

... DEPARTMENT OF COMMERCE Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration.... ACTION: Notice of Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for... Assessment, Remediation, and Restoration Program (DARRP) is announcing new indirect cost rates on the...

50 CFR 80.121 - May an agency earn program income?

Code of Federal Regulations, 2012 CFR

2012-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80.121 May...

50 CFR 80.121 - May an agency earn program income?

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Program Income § 80.121 May...

Making Long-Lasting Changes with the Environment Rating Scales

ERIC Educational Resources Information Center

Harms, Thelma

2010-01-01

An assessment with the Environment Rating Scales (ERS) is designed to give early childhood administrators and teaching staff much more than a set of quality scores. Appropriately used, an ERS assessment can provide a blueprint for planning and carrying out both immediate and long-range program improvements. Unfortunately, programs often complete…

78 FR 58526 - Strategic Environmental Research and Development Program, Scientific Advisory Board; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

..., Recontamination (FY14 New Start). Austin, TX. 1:45 p.m 14 ER03-028 (ER-2429): Combining Mass Balance Dr. Philip... DEPARTMENT OF DEFENSE Office of the Secretary Strategic Environmental Research and Development... following meeting of the Strategic Environmental Research and Development Program, Scientific Advisory Board...

Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans

PubMed Central

Levi-Ferber, Mor; Gian, Hai; Dudkevich, Reut; Henis-Korenblit, Sivan

2015-01-01

Deciphering effective ways to suppress tumor progression and to overcome acquired apoptosis resistance of tumor cells are major challenges in the tumor therapy field. We propose a new concept by which tumor progression can be suppressed by manipulating tumor cell identity. In this study, we examined the effect of ER stress on apoptosis resistant tumorous cells in a Caenorhabditis elegans germline tumor model. We discovered that ER stress suppressed the progression of the lethal germline tumor by activating the ER stress sensor IRE-1. This suppression was associated with the induction of germ cell transdifferentiation into ectopic somatic cells. Strikingly, transdifferentiation of the tumorous germ cells restored their ability to execute apoptosis and enabled their subsequent removal from the gonad. Our results indicate that tumor cell transdifferentiation has the potential to combat cancer and overcome the escape of tumor cells from the cell death machinery. DOI: http://dx.doi.org/10.7554/eLife.08005.001 PMID:26192965

An early shoulder repositioning program in birth-related brachial plexus injury: a pilot study of the Sup-ER protocol.

PubMed

Verchere, Cynthia; Durlacher, Kim; Bellows, Doria; Pike, Jeffrey; Bucevska, Marija

2014-06-01

Birth-related brachial plexus injury (BRBPI) occurs in 1.2/1,000 births in British Columbia. Even in children with "good" recovery, external rotation (ER) and supination (Sup) are often weaker, and permanent skeletal imbalance ensues. A preventive early infant shoulder passive repositioning program was created using primarily a novel custom splint holding the affected arm in full ER and Sup: the Sup-ER splint. The details of the splint and the shoulder repositioning program evolved with experience over several years. This study reviews the first 4 years. A retrospective review of BCCH patients managed with the Sup-ER protocol from 2008 to 2011 compared their recovery scores to matched historical controls selected from our database by two independent reviewers. The protocol was initiated in 18 children during the study period. Six were excluded due to the following: insufficient data points, non-compliance, late splint initiation, and loss to follow-up. Of the 12 matches, the Sup-ER group final score at 2 years was better than controls by 1.18 active movement scale (AMS) points (p = 0.036) in Sup and 0.96 AMS points in ER (but not statistically significant (p = 0.13)). Unexpectedly, but importantly, during the study period, zero subjects were assessed to have the active functional criteria to indicate brachial plexus reconstruction, where previously we operated on 13 %. Early application of passive shoulder repositioning into Sup and ER may improve outcomes in function of the arm in infants with BRBPI. A North American multi-site randomized control trial has been approved and has started recruitment.

Ticagrelor protects against AngII-induced endothelial dysfunction by alleviating endoplasmic reticulum stress.

PubMed

Wang, Xiaoyu; Han, Xuejie; Li, Minghui; Han, Yu; Zhang, Yun; Zhao, Shiqi; Li, Yue

2018-05-16

Ticagrelor has been reported to decrease cardiovascular mortality compared with clopidogrel. This benefit cannot be fully explained by the more efficient platelet inhibition. Many studies demonstrated that ticagrelor improved endothelial function, leaving the mechanism elusive though. The present study aims to investigate whether ticagrelor protects against endothelial dysfunction induced by angiotensinII (AngII) through alleviating endoplasmic reticulum (ER) stress. Male Sprague Dawley rats were infused with AngII or vehicle and administrated with ticagrelor or vehicle for 14 days. Reactive oxygen species (ROS) was detected. Aortas from normal mice were incubated with endoplasmic reticulum stress inducer tunicamycin with or without ticagrelor. Vasorecactivity was measured on wire myography. Rat aortic endothelial cells (RAECs) were pretreated with ticagrelor followed by AngII or tunicamycin. Endothelial nitric oxide synthase (eNOS) phosphorylation and ER stress markers were determined by western blotting. Impaired endothelial function, induction of ER stress, reduced eNOS phosphorylation and elevated ROS generation was restored by ticagrelor treatment in vivo. In addition, tunicamycin induced endothelial dysfunction was improved by ticagrelor. In vitro, the induction of ER stress and inhibited eNOS phosphorylation in REACs exposed to AngII as well as tunicamycin was reversed by co-culturing with ticagrelor. In conclusion, ticagrelor protects against AngII-induced endothelial dysfunction via alleviating ER stress. Copyright © 2017. Published by Elsevier Inc.

Treatment with Panax Ginseng Antagonizes the Estrogen Decline in Ovariectomized Mice

PubMed Central

Xu, Ying; Ding, Jie; Ma, Xiao-Ping; Ma, Ying-Hui; Liu, Zhi-Qiang; Lin, Na

2014-01-01

Ginseng is a popular herb for alleviating menopausal symptoms; however, no conclusive scientific data has shown ginseng as being efficient in such therapies. The present study was designed to evaluate the estrogenic efficacy of ginseng on reproductive target tissues of ovariectomized (OVX) mice. The OVX mice were treated with ginseng at doses of 12.0, 18.0 and 24.0 g/kg per day for four weeks. Ginseng treatments restored the estrus cycle and demonstrated significant estrogenic activity, as indicated by the reversal of the atrophy of the uterus and vagina, upregulation of estrogen receptor (ER) α and ER β expression at the protein and mRNA level in the reproductive tissues, where ER α upregulation was stronger than that of ER β. Meanwhile, treatment with ginseng significantly increased adrenal gland weight and serum estradiol and clearly decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in circulation. Notably, the largest changes in these parameters were found at the highest dose of 24.0 g/kg. Moreover, ginseng at 18.0 g/kg resulted in the greatest decrease in weight gain caused by ovariectomy. The data suggest that ginseng estrogenic responses show tissue variation that reflects different affinities of ERs for ginseng components. This study demonstrates that ginseng activity is mediated through estrogenic components and provides further evidence for ginseng treatment of postmenopausal symptoms. PMID:24806341

Temperature rises during application of Er:YAG laser under different primary dentin thicknesses.

PubMed

Hubbezoglu, Ihsan; Unal, Murat; Zan, Recai; Hurmuzlu, Feridun

2013-05-01

The present study investigated the effects of the Er:YAG laser's different pulse repetition rates on temperature rise under various primary dentin thicknesses. The Er:YAG laser can be used for restorative approaches in clinics and is used to treat dental caries. There are some reports that explain the temperature rise effect of the Er:YAG laser. Recently, the Er:YAG laser has been found to play an important role in temperature rises during the application on dentin. Caries-free primary mandibular molars were prepared to obtain dentin discs with 0.5, 1, 1.5, and 2 mm thicknesses (n=10). These discs were placed between the Teflon mold cylinders of a temperature test apparatus. We preferred three pulse repetition rates of 10, 15, and 20 Hz with an energy density of 12.7 J/cm2 and a 230 μs pulse duration. All dentin discs were irradiated for 30 sec by the Er:YAG laser. Temperature rises were recorded using an L-type thermocouple and universal data loggers/scanners (E-680, Elimko Co., Turkey). Data were analyzed by two-way ANOVA and Tukey tests. Whereas the lowest temperature rise (0.44±0.09 °C) was measured from a 10 Hz pulse repetition rate at a dentin thickness of 2 mm, the highest temperature rise (3.86±0.43 °C) was measured from a 20 Hz pulse repetition rate at a 0.5 mm dentin thickness. Temperature rise did not reach critical value for pulpal injury in any primary dentin thicknesses irradiated by a high repetition rate of the Er:YAG laser.

Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells.

PubMed

Kim, Boyun; Kim, Hee Seung; Jung, Eun-Ji; Lee, Jung Yun; K Tsang, Benjamin; Lim, Jeong Mook; Song, Yong Sang

2016-05-01

Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells. © 2015 Wiley Periodicals, Inc.

Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice

PubMed Central

Ai, Ding; Baez, Juan M.; Jiang, Hongfeng; Conlon, Donna M.; Hernandez-Ono, Antonio; Frank-Kamenetsky, Maria; Milstein, Stuart; Fitzgerald, Kevin; Murphy, Andrew J.; Woo, Connie W.; Strong, Alanna; Ginsberg, Henry N.; Tabas, Ira; Rader, Daniel J.; Tall, Alan R.

2012-01-01

Recent GWAS have identified SNPs at a human chromosom1 locus associated with coronary artery disease risk and LDL cholesterol levels. The SNPs are also associated with altered expression of hepatic sortilin-1 (SORT1), which encodes a protein thought to be involved in apoB trafficking and degradation. Here, we investigated the regulation of Sort1 expression in mouse models of obesity. Sort1 expression was markedly repressed in both genetic (ob/ob) and high-fat diet models of obesity; restoration of hepatic sortilin-1 levels resulted in reduced triglyceride and apoB secretion. Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Conversely, genetically increased hepatic mTORC1 activity was associated with repressed Sort1 and increased apoB secretion. Treating WT mice with the ER stressor tunicamycin led to marked repression of hepatic sortilin-1 expression, while administration of the chemical chaperone PBA to ob/ob mice led to amelioration of ER stress, increased sortilin-1 expression, and reduced apoB and triglyceride secretion. Moreover, the ER stress target Atf3 acted at the SORT1 promoter region as a transcriptional repressor, whereas knockdown of Atf3 mRNA in ob/ob mice led to increased hepatic sortilin-1 levels and decreased apoB and triglyceride secretion. Thus, in mouse models of obesity, induction of mTORC1 and ER stress led to repression of hepatic Sort1 and increased VLDL secretion via Atf3. This pathway may contribute to dyslipidemia in metabolic disease. PMID:22466652

75 FR 34656 - Energy Conservation Program for Consumer Products: Energy Conservation Standards for Certain...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... diameter, elliptical reflector (ER), and bulged reflector (BR) incandescent reflector lamps. In that... document or any other aspect of the rulemaking for certain small diameter, ER, and BR incandescent..., ER, and BR incandescent reflector lamps, and provide docket number EERE-2010- BT-STD-0005 and/or RIN...

Amalgam ablation with the Er:YAG laser

NASA Astrophysics Data System (ADS)

Wigdor, Harvey A.; Visuri, Steven R.; Walsh, Joseph T., Jr.

1995-04-01

Any laser that will be used by dentist to replace the dental drill (handpiece) must remove dental hard tissues safely. These lasers must also have the ability to ablate the restorative dental materials which are present in the teeth being treated. Prior to any laser being used to treat humans a thorough knowledge of the effects of the laser treatment on dental materials must be understood. Cores of dental amalgam were created and sliced into thin wafers for this experiment. Ablation efficiency and thermal changes were evaluated with and without water. It appears as if the Er:YAG laser can effectively ablate amalgam dental material with and without water. The water prevents the temperature from increasing much above baseline and does not reduce efficiency of ablation.

Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

PubMed Central

Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

2014-01-01

Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs).

PubMed

Wang, Li; Zhang, Yi; Wang, Weiguo; Zhu, Yunjie; Chen, Yang; Tian, Bole

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3'-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53-R273H. Upregulation of uPA abolished CP-31398-mediated restoration of mutant p53 transcriptional activity in panc-1 CSCs. Gemcitabine treatment induced ER stress and promoted mutant p53-R273H stabilization via transcriptionally activated uPA which may contribute to chemoresistance to gemcitabine. Notably, upregulation of uPA by gemcitabine treatment may lead to the failure of CP-31398; thus, a novel strategy for modulating mutant p53 function needs to be developed.

Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs)

PubMed Central

Wang, Weiguo; Zhu, Yunjie; Chen, Yang

2017-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. Methods We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3’-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Results Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53-R273H. Upregulation of uPA abolished CP-31398-mediated restoration of mutant p53 transcriptional activity in panc-1 CSCs. Conclusion Gemcitabine treatment induced ER stress and promoted mutant p53-R273H stabilization via transcriptionally activated uPA which may contribute to chemoresistance to gemcitabine. Notably, upregulation of uPA by gemcitabine treatment may lead to the failure of CP-31398; thus, a novel strategy for modulating mutant p53 function needs to be developed. PMID:28854261

A self-defeating anabolic program leads to β-cell apoptosis in endoplasmic reticulum stress-induced diabetes via regulation of amino acid flux.

PubMed

Krokowski, Dawid; Han, Jaeseok; Saikia, Mridusmita; Majumder, Mithu; Yuan, Celvie L; Guan, Bo-Jhih; Bevilacqua, Elena; Bussolati, Ovidio; Bröer, Stefan; Arvan, Peter; Tchórzewski, Marek; Snider, Martin D; Puchowicz, Michelle; Croniger, Colleen M; Kimball, Scot R; Pan, Tao; Koromilas, Antonis E; Kaufman, Randal J; Hatzoglou, Maria

2013-06-14

Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that are mediated via phosphorylation of the translation initiation factor eIF2α. It is reported here that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. This program included expression of amino acid transporter and aminoacyl-tRNA synthetase genes downstream of the stress-induced ATF4-mediated transcription program. The anabolic response was associated with increased amino acid flux and charging of tRNAs for branched chain and aromatic amino acids (e.g. leucine and tryptophan), the levels of which are early serum indicators of diabetes. We conclude that regulation of amino acid transport in β-cells during ER stress involves responses leading to increased protein synthesis, which can be protective during acute stress but can lead to apoptosis during chronic stress. These studies suggest that the increased expression of amino acid transporters in islets can serve as early diagnostic biomarkers for the development of diabetes.

A Self-defeating Anabolic Program Leads to β-Cell Apoptosis in Endoplasmic Reticulum Stress-induced Diabetes via Regulation of Amino Acid Flux*

PubMed Central

Krokowski, Dawid; Han, Jaeseok; Saikia, Mridusmita; Majumder, Mithu; Yuan, Celvie L.; Guan, Bo-Jhih; Bevilacqua, Elena; Bussolati, Ovidio; Bröer, Stefan; Arvan, Peter; Tchórzewski, Marek; Snider, Martin D.; Puchowicz, Michelle; Croniger, Colleen M.; Kimball, Scot R.; Pan, Tao; Koromilas, Antonis E.; Kaufman, Randal J.; Hatzoglou, Maria

2013-01-01

Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that are mediated via phosphorylation of the translation initiation factor eIF2α. It is reported here that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. This program included expression of amino acid transporter and aminoacyl-tRNA synthetase genes downstream of the stress-induced ATF4-mediated transcription program. The anabolic response was associated with increased amino acid flux and charging of tRNAs for branched chain and aromatic amino acids (e.g. leucine and tryptophan), the levels of which are early serum indicators of diabetes. We conclude that regulation of amino acid transport in β-cells during ER stress involves responses leading to increased protein synthesis, which can be protective during acute stress but can lead to apoptosis during chronic stress. These studies suggest that the increased expression of amino acid transporters in islets can serve as early diagnostic biomarkers for the development of diabetes. PMID:23645676

The Director's Discretionary Early Release Science Program for JWST

NASA Astrophysics Data System (ADS)

Levenson, Nancy A.; Sembach, Kenneth

2018-06-01

We will introduce the Director's Discretionary Early Release Science (DD-ERS) Program for the James Webb Space Telescope (JWST). These programs will educate and inform the community about JWST's instruments and capabilities, providing open access to early observations, and science-enabling products that the DD-ERS teams produce. During this session, we will provide updates on JWST status, and the 13 selected teams will give an overview of their planned observations and future work.

Nevada National Security Site Industrial Sites Project Closeout - 12498

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

Cabble, Kevin; Krauss, Mark; Matthews, Pat

The U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office is responsible for environmental restoration (ER) at the Nevada National Security Site (NNSS). This includes remediation at Industrial Sites where past nuclear testing activities and activities that supported nuclear testing may have or are known to have resulted in the release of contaminants into the environment. Industrial Sites at the NNSS have included nuclear facilities that supported the nuclear rocket/missile development programs, gas stations, landfills, spill sites, ordnance sites, and numerous other waste disposal and release sites. The NNSS Industrial Sites activities neared completion at the endmore » of fiscal year 2011 while other activities required under the Federal Facility Agreement and Consent Order (FFACO) and part of the same NNSS ER Project are forecasted to extend to 2027 or beyond. With the majority of Industrial Sites corrective action units (CAUs) completed (more than 250 CAUs and over 1,800 corrective action sites), it was determined that an activity closeout process should be implemented to ensure that the work completed over the past 15 years is well documented in a comprehensive and concise summary. While the process used to close each individual CAU is described in approved documents, no single document describes in summary fashion the work completed to close the many individual Industrial Sites. The activity closeout process will be used to develop an Industrial Sites closeout document that describes these years of work. This document will summarize the number of Industrial Sites closed under the FFACO and provide general descriptions of projects, contaminants removed, and sites closed in place with corresponding Use Restrictions. Other pertinent information related to Industrial Sites work such as the project history, closure decisions, historical declarations, remediation strategies, and final CAU status will be included in the closeout document, along with a table listing each CAU and corresponding corrective action sites within each CAU. Using this process of conducting the activity closeout and developing a closeout document may prove useful for other ER projects within the DOE complex in describing how a long period of ER can be summarized in a single document. The NNSS Industrial Sites activities were completed over the span of 15 years and involved the investigation, cleanup or Use Restriction, and closure of more than 260 CAUs and over 1,800 sites. These activities will conclude in FY 2012 (with the exception of one CAU). In order to capture the work completed over this length of time and document decisions made during the activities, a closeout effort was initiated. The closeout will review the work conducted during the Industrial Sites activities and produce a single document that summarizes Industrial Sites activities. This closeout is being conducted at an interim stage in the overall NNSA/NSO ER Project since the Soils and UGTA activities will continue for a number of years, but the completion of the Industrial Sites project warrants conducting a closeout now while personnel are available and information is still current. The process followed by NNSA/NSO in conducing project closeout for the Industrial Sites portion of the ER program may prove useful within the DOE complex in demonstrating how a large ER project can be summarized. (authors)« less

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

PubMed

Jeselsohn, Rinath; Bergholz, Johann S; Pun, Matthew; Cornwell, MacIntosh; Liu, Weihan; Nardone, Agostina; Xiao, Tengfei; Li, Wei; Qiu, Xintao; Buchwalter, Gilles; Feiglin, Ariel; Abell-Hart, Kayley; Fei, Teng; Rao, Prakash; Long, Henry; Kwiatkowski, Nicholas; Zhang, Tinghu; Gray, Nathanael; Melchers, Diane; Houtman, Rene; Liu, X Shirley; Cohen, Ofir; Wagle, Nikhil; Winer, Eric P; Zhao, Jean; Brown, Myles

2018-02-12

Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER + ) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties that promote a pro-metastatic phenotype. Analysis of the genome-wide ER binding sites identified mutant ER unique recruitment mediating the allele-specific transcriptional program. Genetic screens identified genes that are essential for the ligand-independent growth driven by the mutants. These studies provide insights into the mechanism of endocrine therapy resistance engendered by ER mutations and potential therapeutic targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Endoplasmic reticulum stress inhibits expression of genes involved in thyroid hormone synthesis and their key transcriptional regulators in FRTL-5 thyrocytes

PubMed Central

Wen, Gaiping; Eder, Klaus

2017-01-01

Endoplasmic reticulum (ER) stress is characterized by the accumulation of misfolded proteins due to an impairment of ER quality control pathways leading to the activation of a defense system, called unfolded protein response (UPR). While thyrocytes are supposed to be highly susceptible to environmental conditions that cause ER stress due to the synthesis of large amounts of secretory proteins required for thyroid hormone synthesis, systematic investigations on the effect of ER stress on expression of key genes of thyroid hormone synthesis and their transcriptional regulators are lacking. Since the aim of the ER stress-induced UPR is to restore ER homeostasis and to facilitate cell survival through transient shutdown of ribosomal protein translation, we hypothesized that the expression of genes involved in thyroid hormone synthesis and their transcriptional regulators, all of which are not essential for cell survival, are down-regulated in thyrocytes during ER stress, while sterol regulatory element-binding proteins (SREBPs) are activated during ER stress in thyrocytes. Treatment of FRTL-5 thyrocytes with the ER stress inducer tunicamycin (TM) dose-dependently increased the mRNA and/or protein levels of known UPR target genes, stimulated phosphorylation of the ER stress sensor protein kinase RNA-like ER kinase (PERK) and of the PERK target protein eukaryotic initiation factor 2α (eIF2α) and caused splicing of the ER stress-sensitive transcription factor X-box binding protein (XBP-1) (P < 0.05). The mRNA levels and/or protein levels of genes involved in thyroid hormone synthesis, sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), their transcriptional regulators and thyrotropin (TSH) receptor and the uptake of Na125I were reduced at the highest concentration of TM tested (0.1 μg/mL; P < 0.05). Proteolytic activation of the SREBP-1c pathway was not observed in FRTL-5 cells treated with TM, whereas TM reduced proteolytic activation of the SREBP-2 pathway at 0.1 μg TM/mL (P < 0.05). In conclusion, the expression of key genes involved in thyroid hormone synthesis and their critical regulators and of the TSH receptor as well as the uptake of iodide is attenuated in thyrocytes during mild ER stress. Down-regulation of NIS, TPO and TG during ER stress is likely the consequence of impaired TSH/TSHR signaling in concert with reduced expression of critical transcriptional regulators of these genes. PMID:29095946

Endoplasmic reticulum stress inhibits expression of genes involved in thyroid hormone synthesis and their key transcriptional regulators in FRTL-5 thyrocytes.

PubMed

Wen, Gaiping; Ringseis, Robert; Eder, Klaus

2017-01-01

Endoplasmic reticulum (ER) stress is characterized by the accumulation of misfolded proteins due to an impairment of ER quality control pathways leading to the activation of a defense system, called unfolded protein response (UPR). While thyrocytes are supposed to be highly susceptible to environmental conditions that cause ER stress due to the synthesis of large amounts of secretory proteins required for thyroid hormone synthesis, systematic investigations on the effect of ER stress on expression of key genes of thyroid hormone synthesis and their transcriptional regulators are lacking. Since the aim of the ER stress-induced UPR is to restore ER homeostasis and to facilitate cell survival through transient shutdown of ribosomal protein translation, we hypothesized that the expression of genes involved in thyroid hormone synthesis and their transcriptional regulators, all of which are not essential for cell survival, are down-regulated in thyrocytes during ER stress, while sterol regulatory element-binding proteins (SREBPs) are activated during ER stress in thyrocytes. Treatment of FRTL-5 thyrocytes with the ER stress inducer tunicamycin (TM) dose-dependently increased the mRNA and/or protein levels of known UPR target genes, stimulated phosphorylation of the ER stress sensor protein kinase RNA-like ER kinase (PERK) and of the PERK target protein eukaryotic initiation factor 2α (eIF2α) and caused splicing of the ER stress-sensitive transcription factor X-box binding protein (XBP-1) (P < 0.05). The mRNA levels and/or protein levels of genes involved in thyroid hormone synthesis, sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), their transcriptional regulators and thyrotropin (TSH) receptor and the uptake of Na125I were reduced at the highest concentration of TM tested (0.1 μg/mL; P < 0.05). Proteolytic activation of the SREBP-1c pathway was not observed in FRTL-5 cells treated with TM, whereas TM reduced proteolytic activation of the SREBP-2 pathway at 0.1 μg TM/mL (P < 0.05). In conclusion, the expression of key genes involved in thyroid hormone synthesis and their critical regulators and of the TSH receptor as well as the uptake of iodide is attenuated in thyrocytes during mild ER stress. Down-regulation of NIS, TPO and TG during ER stress is likely the consequence of impaired TSH/TSHR signaling in concert with reduced expression of critical transcriptional regulators of these genes.

RESTORATION PLUS: A COLLABORATIVE RESEARCH PROGRAM TO DEVELOP AND EVALUATE ECOSYSTEM RESTORATION AND MANAGEMENT OPTIONS TO ACHIEVE ECOLOGICALLY AND ECONOMICALLY SUSTAINABLE SOLUTIONS

EPA Science Inventory

EPA is evaluating ecosystem restoration and management techniques to ensure they create sustainable solutions for degraded watersheds. ORD NRMRL initiated the Restoration Plus (RePlus) program in 2002 to a) evaluate ecosystem restoration and management options, b) assess the non-...

50 CFR 80.11 - Submission of proposals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.11 Submission of...) authorized to sign the Wildlife and Sport Fish Restoration Program documents, and any changes in such...

48 CFR 228.102-70 - Defense Environmental Restoration Program construction contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Restoration Program construction contracts. 228.102-70 Section 228.102-70 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds 228.102-70 Defense Environmental Restoration Program construction contracts...

Improving Emotion Regulation and Sibling Relationship Quality: The More Fun with Sisters and Brothers Program

ERIC Educational Resources Information Center

Kennedy, Denise E.; Kramer, Laurie

2008-01-01

We examined the role of emotion regulation (ER) in improving sibling relationship quality (SRQ) by evaluating the More Fun With Sisters and Brothers Program where 4- to 8-year-old siblings from 95 families were taught emotional and social competencies. Parents reported on SRQ and ER, and sibling interactions were observed in homes. SRQ and ER…

Estuary ecosystem restoration: implementing and institutionalizing adaptive management: Institutionalizing adaptive management

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

Ebberts, Blaine D.; Zelinsky, Ben D.; Karnezis, Jason P.

We successfully implemented and institutionalized an adaptive management (AM) process for the Columbia Estuary Ecosystem Restoration Program, which is a large-scale restoration program focused on improving ecosystem conditions in the 234-km lower Columbia River and estuary. For our purpose, “institutionalized” means the AM process and restoration program are embedded in the work flow of the implementing agencies and affected parties. While plans outlining frameworks, processes, or approaches to AM of ecosystem restoration programs are commonplace, establishment for the long term is not. This paper presents the basic AM framework and explains how AM was implemented and institutionalized. Starting with amore » common goal, we pursued included a well-understood governance and decision-making structure, routine coordination and communication activities, data and information sharing, commitment from partners and upper agency management to the AM process, and meaningful cooperation among program managers and partners. The overall approach and steps to implement and institutionalize AM for ecosystem restoration explained here are applicable to situations where it has been less than successful or, as in our case, the restoration program is just getting started.« less

Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

PubMed

Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

2015-10-01

The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

76 FR 56678 - Energy Efficiency Program for Consumer Products: Public Meeting and Availability of the Framework...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... reflector (ER) and bulged reflector (BR) bulb shapes, and with diameters of 2.75 inches or less. Therefore....25 and 2.75 inches, as well as lamps with ER, BR, bulged parabolic aluminized reflector (BPAR), or... certain reflector (R), ER and BR IRLs. DOE has concluded, for the reasons that follow, that it has the...

Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance.

PubMed

Fregno, Ilaria; Molinari, Maurizio

2018-01-01

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied transcriptional/translational programs defined as "unfolded protein responses" that increase the ER volume and the expression of ER-resident proteins regulating the numerous ER functions. Less understood are the lysosomal catabolic processes that maintain ER size at steady state, that prevent excessive ER expansion during ER stresses, or that ensure return to physiologic ER size during recovery from ER stresses. These catabolic processes may also be activated to remove ER subdomains where proteasome-resistant misfolded proteins or damaged lipids have been segregated. Insights into these catabolic mechanisms have only recently emerged with the identification of so-called ER-phagy receptors, which label specific ER subdomains for selective lysosomal delivery for clearance. Here, in eight chapters and one addendum, we comment on recent advances in ER turnover pathways induced by ER stress, nutrient deprivation, misfolded proteins, and live bacteria. We highlight the role of yeast (Atg39 and Atg40) and mammalian (FAM134B, SEC62, RTN3, and CCPG1) ER-phagy receptors and of autophagy genes in selective and non-selective catabolic processes that regulate cellular proteostasis by controlling ER size, turnover, and function.

Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development.

PubMed

Tang, Qian; Zheng, Gang; Feng, Zhenhua; Chen, Yu; Lou, Yiting; Wang, Chenggui; Zhang, Xiaolei; Zhang, Yu; Xu, Huazi; Shang, Ping; Liu, Haixiao

2017-10-05

Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model. We found aberrant p62 accumulation and increased apoptosis in human OA cartilage and chondrocytes. Consistently, p62 and cleaved caspase-3 levels increased in mouse chondrocytes under oxidative stress. Furthermore, trehalose restored oxidative stress-induced autophagic flux disruption and targeted autophagy selectively by activating BCL2 interacting protein 3 (BNIP3) and Phosphoglycerate mutase family member 5 (PGAM5). Trehalose could ameliorate oxidative stress-mediated mitochondrial membrane potential collapse, ATP level decrease, dynamin-related protein 1 (drp-1) translocation into the mitochondria, and the upregulation of proteins involved in mitochondria and endoplasmic reticulum (ER) stress-related apoptosis pathway. In addition, trehalose suppressed the cleavage of caspase 3 and poly(ADP-ribose) polymerase (PARP) and prevented DNA damage under oxidative stress. However, the anti-apoptotic effects of trehalose in TBHP-treated chondrocytes were partially abolished by autophagic flux inhibitor chloroquine and BNIP3- siRNA. The protective effect of trehalose was also found in mouse OA model. Taken together, these results indicate that trehalose has anti-apoptotic effects through the suppression of oxidative stress-induced mitochondrial injury and ER stress which is dependent on the promotion of autophagic flux and the induction of selective autophagy. Thus, trehalose is a promising therapeutic agent for OA.

Comparison of tensile bond strengths of four one-bottle self-etching adhesive systems with Er:YAG laser-irradiated dentin.

PubMed

Jiang, Qianzhou; Chen, Minle; Ding, Jiangfeng

2013-12-01

This study aimed to investigate the interaction of current one-bottle self-etching adhesives and Er:YAG laser with dentin using a tensile bond strength (TBS) test and scanning electron microscopy (SEM) in vitro. Two hundred and thirteen dentin discs were randomly distributed to the Control Group using bur cutting and to the Laser Group using an Er:YAG laser (200 mJ, VSP, 20 Hz). The following adhesives were investigated: one two-step total-etch adhesive [Prime & Bond NT (Dentsply)] and four one-step self-etch adhesives [G-Bond plus (GC), XENO V (Dentsply), iBond Self Etch (Heraeus) and Adper Easy One (3 M ESPE)]. Samples were restored with composite resin, and after 24-hour storage in distilled water, subjected to the TBS test. For morphological analysis, 12 dentin specimens were prepared for SEM. No significant differences were found between the control group and laser group (p = 0.899); dentin subjected to Prime & Bond NT, XENOV and Adper Easy One produced higher TBS. In conclusion, this study indicates that Er:YAG laser-prepared dentin can perform as well as bur on TBS, and some of the one-step one-bottle adhesives are comparable to the total-etch adhesives in TBS on dentin.

Transcriptional Regulation of X-Box-binding Protein One (XBP1) by Hepatocyte Nuclear Factor 4α (HNF4Α) Is Vital to Beta-cell Function.

PubMed

Moore, Benjamin D; Jin, Ramon U; Lo, Heiyong; Jung, Min; Wang, Haiyan; Battle, Michele A; Wollheim, Claes B; Urano, Fumihiko; Mills, Jason C

2016-03-18

The transcription factor, X-box-binding protein-1 (XBP1), controls the development and maintenance of the endoplasmic reticulum (ER) in multiple secretory cell lineages. We show here that Hepatocyte Nuclear Factor 4α (HNF4α) directly induces XBP1 expression. Mutations in HNF4α cause Mature-Onset Diabetes of the Young I (MODYI), a subset of diabetes characterized by diminished GSIS. In mouse models, cell lines, and ex vivo islets, using dominant negative and human- disease-allele point mutants or knock-out and knockdown models, we show that disruption of HNF4α caused decreased expression of XBP1 and reduced cellular ER networks. GSIS depends on ER Ca(2+) signaling; we show that diminished XBP1 and/or HNF4α in β-cells led to impaired ER Ca(2+) homeostasis. Restoring XBP1 expression was sufficient to completely rescue GSIS in HNF4α-deficient β-cells. Our findings uncover a transcriptional relationship between HNF4α and Xbp1 with potentially broader implications about MODYI and the importance of transcription factor signaling in the regulation of secretion. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.

PubMed

Brookes, Steven J; Barron, Martin J; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J

2014-05-01

Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.

Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate

PubMed Central

Brookes, Steven J.; Barron, Martin J.; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J.

2014-01-01

Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease. PMID:24362885

Innate Sensing of Influenza A Virus Hemagglutinin Glycoproteins by the Host Endoplasmic Reticulum (ER) Stress Pathway Triggers a Potent Antiviral Response via ER-Associated Protein Degradation.

PubMed

Frabutt, Dylan A; Wang, Bin; Riaz, Sana; Schwartz, Richard C; Zheng, Yong-Hui

2018-01-01

Innate immunity provides an immediate defense against infection after host cells sense danger signals from microbes. Endoplasmic reticulum (ER) stress arises from accumulation of misfolded/unfolded proteins when protein load overwhelms the ER folding capacity, which activates the unfolded protein response (UPR) to restore ER homeostasis. Here, we show that a mechanism for antiviral innate immunity is triggered after the ER stress pathway senses viral glycoproteins. When hemagglutinin (HA) glycoproteins from influenza A virus (IAV) are expressed in cells, ER stress is induced, resulting in rapid HA degradation via proteasomes. The ER-associated protein degradation (ERAD) pathway, an important UPR function for destruction of aberrant proteins, mediates HA degradation. Three class I α-mannosidases were identified to play a critical role in the degradation process, including EDEM1, EDEM2, and ERManI. HA degradation requires either ERManI enzymatic activity or EDEM1/EDEM2 enzymatic activity when ERManI is not expressed, indicating that demannosylation is a critical step for HA degradation. Silencing of EDEM1, EDEM2, and ERManI strongly increases HA expression and promotes IAV replication. Thus, the ER stress pathway senses influenza HA as "nonself" or misfolded protein and sorts HA to ERAD for degradation, resulting in inhibition of IAV replication. IMPORTANCE Viral nucleic acids are recognized as important inducers of innate antiviral immune responses that are sensed by multiple classes of sensors, but other inducers and sensors of viral innate immunity need to be identified and characterized. Here, we used IAV to investigate how host innate immunity is activated. We found that IAV HA glycoproteins induce ER stress, resulting in HA degradation via ERAD and consequent inhibition of IAV replication. In addition, we have identified three class I α-mannosidases, EDEM1, EDEM2, and ERManI, which play a critical role in initiating HA degradation. Knockdown of these proteins substantially increases HA expression and IAV replication. The enzymatic activities and joint actions of these mannosidases are required for this antiviral activity. Our results suggest that viral glycoproteins induce a strong innate antiviral response through activating the ER stress pathway during viral infection. Copyright © 2017 American Society for Microbiology.

50 CFR 80.9 - Notice of desire to participate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.9 Notice of desire to... Federal Assistance which contains plans for the use of Wildlife and Sport Fish Restoration Program funds...

50 CFR 80.124 - How may an agency use unexpended program income?

Code of Federal Regulations, 2012 CFR

2012-10-01

... OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.124 - How may an agency use unexpended program income?

Code of Federal Regulations, 2011 CFR

2011-10-01

... OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

76 FR 14372 - New Mexico Collaborative Forest Restoration Program Technical Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... DEPARTMENT OF AGRICULTURE Forest Service New Mexico Collaborative Forest Restoration Program Technical Advisory Panel AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The New Mexico Collaborative Forest Restoration Program Technical Advisory Panel will meet in Albuquerque, New Mexico. The...

7 CFR 701.10 - Qualifying minimum cost of restoration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Qualifying minimum cost of restoration. 701.10 Section..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CONSERVATION PROGRAM EMERGENCY CONSERVATION PROGRAM AND CERTAIN RELATED PROGRAMS PREVIOUSLY ADMINISTERED UNDER THIS PART § 701.10 Qualifying minimum cost of restoration...

High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.

PubMed

Chen, Xi; Shen, Wei-Bin; Yang, Penghua; Dong, Daoyin; Sun, Winny; Yang, Peixin

2018-06-01

Maternal diabetes induces neural tube defects by suppressing neurogenesis in the developing neuroepithelium. Our recent study further revealed that high glucose inhibited embryonic stem cell differentiation into neural lineage cells. However, the mechanism whereby high glucose suppresses neural differentiation is unclear. To investigate whether high glucose-induced oxidative stress and endoplasmic reticulum (ER) stress lead to the inhibition of neural differentiation, the effect of high glucose on neural stem cell (the C17.2 cell line) differentiation was examined. Neural stem cells were cultured in normal glucose (5 mM) or high glucose (25 mM) differentiation medium for 3, 5, and 7 days. High glucose suppressed neural stem cell differentiation by significantly decreasing the expression of the neuron marker Tuj1 and the glial cell marker GFAP and the numbers of Tuj1 + and GFAP + cells. The antioxidant enzyme superoxide dismutase mimetic Tempol reversed high glucose-decreased Tuj1 and GFAP expression and restored the numbers of neurons and glial cells differentiated from neural stem cells. Hydrogen peroxide treatment imitated the inhibitory effect of high glucose on neural stem cell differentiation. Both high glucose and hydrogen peroxide triggered ER stress, whereas Tempol blocked high glucose-induced ER stress. The ER stress inhibitor, 4-phenylbutyrate, abolished the inhibition of high glucose or hydrogen peroxide on neural stem cell differentiation. Thus, oxidative stress and its resultant ER stress mediate the inhibitory effect of high glucose on neural stem cell differentiation.

Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosis in vivo and in vitro.

PubMed

Liu, Shing-Hwa; Yang, Ching-Chin; Chan, Ding-Cheng; Wu, Cheng-Tien; Chen, Li-Ping; Huang, Jenq-Wen; Hung, Kuan-Yu; Chiang, Chih-Kang

2016-04-19

Renal tubulointerstitial fibrosis is the common and final pathologic change of kidney in end-stage renal disease. Interesting, endoplasmic reticulum (ER) stress is known to contribute to the pathophysiological mechanisms during the development of renal fibrosis. Here, we investigated the effects of chemical chaperon sodium 4-phenylbutyrate (4-PBA) on renal fibrosis in vivo and in vitro. In a rat unilateral ureteral obstruction (UUO) model, 4-PBA mimicked endogenous ER chaperon in the kidneys and significantly reduced glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), activating transcription factor 4 (ATF4), and phosphorylated JNK protein expressions as well as restored spliced X-box-binding protein 1 (XBP1) expressions in the kidneys of UUO rats. 4-PBA also attenuated the increases of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) protein expressions, tubulointerstitial fibrosis, and apoptosis in the kidneys of UUO rats. Moreover, transforming growth factor (TGF)-β markedly increased ER stress-associated molecules, profibrotic factors, and apoptotic markers in the renal tubular cells (NRK-52E), all of which could be significantly counteracted by 4-PBA treatment. 4-PBA also diminished TGF-β-increased CTGF promoter activity and CTGF mRNA expression in NRK-52E cells. Taken together, our results indicated that 4-PBA acts as an ER chaperone to ameliorate ER stress-induced renal tubular cell apoptosis and renal fibrosis.

Oestrogen receptor negativity in breast cancer: a cause or consequence?

PubMed Central

Gajulapalli, Vijaya Narasihma Reddy; Malisetty, Vijaya Lakshmi; Chitta, Suresh Kumar; Manavathi, Bramanandam

2016-01-01

Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of oestrogen receptor α (ERα) expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate oestrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable. To answer that, two important approaches are considered: (1) understanding the cellular origin of heterogeneity and ER negativity in breast cancers and (2) characterization of molecular regulators of endocrine resistance. Breast tumours are heterogeneous in nature, having distinct molecular, cellular, histological and clinical behaviour. Recent advancements in perception of the heterogeneity of breast cancer revealed that the origin of a particular mammary tumour phenotype depends on the interactions between the cell of origin and driver genetic hits. On the other hand, histone deacetylases (HDACs), DNA methyltransferases (DNMTs), miRNAs and ubiquitin ligases emerged as vital molecular regulators of ER negativity in breast cancers. Restoring response to endocrine therapy through re-expression of ERα by modulating the expression of these molecular regulators is therefore considered as a relevant concept that can be implemented in treating ER-negative breast cancers. In this review, we will thoroughly discuss the underlying mechanisms for the loss of ERα expression and provide the future prospects for implementing the strategies to negate ER negativity in breast cancers. PMID:27884978

Statistical analyses of the background distribution of groundwater solutes, Los Alamos National Laboratory, New Mexico.

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

Longmire, Patrick A.; Goff, Fraser; Counce, D. A.

2004-01-01

Background or baseline water chemistry data and information are required to distingu ish between contaminated and non-contaminated waters for environmental investigations conducted at Los Alamos National Laboratory (referred to as the Laboratory). The term 'background' refers to natural waters discharged by springs or penetrated by wells that have not been contaminated by LANL or other municipal or industrial activities, and that are representative of groundwater discharging from their respective aquifer material. These investigations are conducted as part of the Environmental Restoration (ER) Project, Groundwater Protection Program (GWPP), Laboratory Surveillance Program, the Hydrogeologic Workplan, and the Site-Wide Environmental Impact Statement (SWEIS).more » This poster provides a comprehensive, validated database of inorganic, organic, stable isotope, and radionuclide analyses of up to 136 groundwater samples collected from 15 baseline springs and wells located in and around Los Alamos National Laboratory, New Mexico. The region considered in this investigation extends from the western edge of the Jemez Mountains eastward to the Rio Grande and from Frijoles Canyon northward to Garcia Canyon. Figure 1 shows the fifteen stations sampled for this investigation. The sampling stations and associated aquifer types are summarized in Table 1.« less

Calendar Year 2016 Annual Groundwater Monitoring Report.

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

Copland, John R.; Jackson, Timmie Okchumpulla; Li, Jun

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned/contractoroperated laboratory. National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., manages and operates SNL/NM for the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA). The DOE/NNSA Sandia Field Office administers the contract and oversees contractor operations at the site. Two types of groundwater surveillance monitoring are conducted at SNL/NM: (1) on a site-wide basis as part of the SNL/NM Long-Term Stewardship (LTS) Program’s Groundwater Monitoring Program (GMP) Groundwater Surveillance Task and (2) on a site-specific groundwater monitoring at LTS/Environmental Restoration (ER) Operationsmore » sites with ongoing groundwater investigations. This Annual Groundwater Monitoring Report summarizes data collected during groundwater monitoring events conducted at GMP locations and at the following SNL/NM sites through December 31, 2016: Burn Site Groundwater Area of Concern (AOC); Chemical Waste Landfill; Mixed Waste Landfill; Technical Area-V Groundwater AOC; and the Tijeras Arroyo Groundwater AOC. Environmental monitoring and surveillance programs are required by the New Mexico Environment Department (NMED) and DOE Order 436.1, Departmental Sustainability, and DOE Order 231.1B, Environment, Safety, and Health Reporting.« less

50 CFR 80.124 - How may an agency use unexpended program income?

Code of Federal Regulations, 2013 CFR

2013-10-01

... OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.124 - How may an agency use unexpended program income?

Code of Federal Regulations, 2014 CFR

2014-10-01

... OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

Demonstration and Commercialization of the Sediment Ecosystem Assessment Protocol: Project ER-201130 Environmental Restoration Project

DTIC Science & Technology

2017-01-01

65 5-15. Dissolved oxygen and temperature data from T = 34 month (2015) post-remedy...Continuous measurements of dissolved oxygen and temperature in SEA Ring chambers placed at 3-meter depth at Chollas Creek mouth (CC1-B) and adjacent to...which the organisms would be exposed, such as salinity and temperature . This action provided valuable data to determine if any effects observed were

Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

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

Pan, Mu-Yun; Shen, Yuh-Chiang; National Research Institute of Chinese Medicine, Taipei, Taiwan

Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ERmore » stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified as an endoplasmic reticulum (ER) stress inducer. ► Prodigiosin-induced cytotoxicity involves ER stress-mediated cell death. ► Prodigiosin transcriptionally induces CHOP to suppress BCL2 for evoking cell death. ► Prodigiosin engages the IRE1–JNK and PERK–eIF2α pathways to up-regulate CHOP.« less

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

PubMed

Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

2017-03-01

Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

50 CFR 80.30 - Why must an agency certify the number of paid license holders?

Code of Federal Regulations, 2013 CFR

2013-10-01

... SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH... apportion funds in the Wildlife Restoration and Sport Fish Restoration programs among the States. ...

50 CFR 80.30 - Why must an agency certify the number of paid license holders?

Code of Federal Regulations, 2014 CFR

2014-10-01

... SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH... apportion funds in the Wildlife Restoration and Sport Fish Restoration programs among the States. ...

Calendar Year 2001 Annual Site Environmental Report, Sandia National Laboratories, Albuquerque, New Mexico

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

VIGIL, FRANCINE S.; SANCHEZ, REBECCA D.; WAGNER, KATRINA

2002-09-01

Sandia National Laboratories, New Mexico (SNL/NM) is a government-owned, contractor-operated facility overseen by the U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA) through the Albuquerque Operations Office (AL), Office of Kirtland Site Operations (OKSO). Sandia Corporation, a wholly-owned subsidiary of Lockheed Martin Corporation, operates SNL/NM. Work performed at SNL/NM is in support of the DOE and Sandia Corporation's mission to provide weapon component technology and hardware for the needs of the nation's security. Sandia Corporation also conducts fundamental research and development (R&D) to advance technology in energy research, computer science, waste management, microelectronics, materials science, and transportation safetymore » for hazardous and nuclear components. In support of Sandia Corporation's mission, the Integrated Safety and Security (ISS) Center and the Environmental Restoration (ER) Project at SNL/NM have established extensive environmental programs to assist Sandia Corporation's line organizations in meeting all applicable local, state, and federal environmental regulations and DOE requirements. This annual report summarizes data and the compliance status of Sandia Corporation's environmental protection and monitoring programs through December 31, 2001. Major environmental programs include air quality, water quality, groundwater protection, terrestrial surveillance, waste management, pollution prevention (P2), environmental remediation, oil and chemical spill prevention, and the National Environmental Policy Act (NEPA). Environmental monitoring and surveillance programs are required by DOE Order 5400.1, General Environmental Protection Program (DOE 1990) and DOE Order 231.1, Environment, Safety, and Health Reporting (DOE 1996).« less

50 CFR 86.94 - What crediting language should I use?

Code of Federal Regulations, 2012 CFR

2012-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.94 What crediting...: (a) Example 1: The Federal Aid in Sport Fish Restoration Program funded this facility thanks to your...

50 CFR 86.94 - What crediting language should I use?

Code of Federal Regulations, 2010 CFR

2010-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.94 What crediting...: (a) Example 1: The Federal Aid in Sport Fish Restoration Program funded this facility thanks to your...

50 CFR 86.94 - What crediting language should I use?

Code of Federal Regulations, 2011 CFR

2011-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.94 What crediting...: (a) Example 1: The Federal Aid in Sport Fish Restoration Program funded this facility thanks to your...

76 FR 65182 - Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal Years 2009 and 2010 AGENCY: National... Atmospheric Administration's (NOAA's) Damage Assessment, Remediation, and Restoration Program (DARRP) is...

Restoring and rehabilitating sagebrush habitats

USGS Publications Warehouse

Pyke, David A.; Knick, S.T.; Connelly, J.W.

2011-01-01

Less than half of the original habitat of the Greater Sage-Grouse (Centrocercus uropha-sianus) currently exists. Some has been perma-nently lost to farms and urban areas, but the remaining varies in condition from high quality to no longer adequate. Restoration of sagebrush (Artemisia spp.) grassland ecosystems may be pos-sible for resilient lands. However, Greater Sage-Grouse require a wide variety of habitats over large areas to complete their life cycle. Effective restoration will require a regional approach for prioritizing and identifying appropriate options across the landscape. A landscape triage method is recommended for prioritizing lands for restora-tion. Spatial models can indicate where to protect and connect intact quality habitat with other simi-lar habitat via restoration. The ecological site con-cept of land classification is recommended for characterizing potential habitat across the region along with their accompanying state and transi-tion models of plant community dynamics. These models assist in identifying if passive, manage-ment-based or active, vegetation manipulation?based restoration might accomplish the goals of improved Greater Sage-Grouse habitat. A series of guidelines help formulate questions that manag-ers might consider when developing restoration plans: (1) site prioritization through a landscape triage; (2) soil verification and the implications of soil features on plant establishment success; (3) a comparison of the existing plant community to the potential for the site using ecological site descriptions; (4) a determination of the current successional status of the site using state and transition models to aid in predicting if passive or active restoration is necessary; and (5) implemen-tation of post-treatment monitoring to evaluate restoration effectiveness and post-treatment man-agement implications to restoration success.

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS

PubMed Central

Cardoso, Rodolfo C.; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C.

2016-01-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype. PMID:27792406

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS.

PubMed

Cardoso, Rodolfo C; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C; Padmanabhan, Vasantha

2016-12-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype.

Sandia National Laboratories site-wide hydrogeologic characterization project calendar year 1992 annual report

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

Crowson, D.; Gibson, J.D.; Haase, C.S.

1993-10-01

The Sandia National Laboratories, New Mexico (SNL/NM) Site-Wide Hydrogeologic Characterization (SWHC) project has been implemented as part of the SNL/NM Environmental Restoration (ER) Program to develop the regional hydrogeologic framework and baseline for the approximately 100 mi of Kirtland Air Force Base (KAFB) and adjacent withdrawn public lands upon which SNL/NM has performed research and development activities. Additionally, the SWHC project will investigate and characterize generic hydrogeologic issues associated with the 172 ER sites owned by SNL/NM across its facilities on KAFB. As called for in the Hazardous and Solid Waste Amendments (HSWA) to the Resource Conservation and Recovery Actmore » (RCRA) Part B permit agreement between the U.S. Environmental Protection Agency (EPA) as the permitter and the U.S. Department of Energy (DOE) and SNL/NM as the permittees, an annual report is to be prepared by the SWHC project team. This document serves two primary purposes: (1) to identify and describe the conceptual framework for the hydrogeologic system underlying SNL/NM and (2) to describe characterization activities undertaken in the preceding year that add to our understanding (reduce our uncertainties) regarding the conceptual and quantitative hydrogeologic framework. This SWHC project annual report focuses primarily on purpose 1, providing a summary description of the current {open_quotes}state of knowledge{close_quotes} of the Sandia National Laboratories/Kirtland Air Force Base (SNL/KAFB) hydrogeologic setting.« less

Analysis of G-Protein Coupled Receptor 30 (GPR30) on Endothelial Inflammation.

PubMed

Chakrabarti, Subhadeep; Davidge, Sandra T

2016-01-01

The female sex hormone estrogen (the most common form 17-β-estradiol or E2) is known to have both anti-inflammatory and pro-inflammatory effects. Given the diversity of estrogen responses mediated through its three distinct receptors, namely, estrogen receptor α (ERα), ERβ, and the G-protein coupled receptor 30 (GPR30), it is plausible that different receptors have specific modulatory effects on inflammation in different tissues. We have shown that activation of GPR30 exerted anti-inflammatory effects as demonstrated by significant attenuation of tumor necrosis factor (TNF)-mediated upregulation of adhesion molecules in isolated human umbilical vein endothelial cells. Interestingly, estrogen alone had no such effect and blockade of classical ERs restored the anti-inflammatory effect, suggesting that this effect was dependent on GPR30 and opposed to classical ERs. These findings were further validated by the negation of anti-inflammatory GPR30 effects by classical ER agonists. This chapter focuses on multiple pharmacological options to activate GPR30 and the use of TNF activated endothelial cells as a model system for inflammatory response as assessed by adhesion molecule detection through western blotting.

Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage.

PubMed

Ji, Cheng

2015-06-03

Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.

A chemical chaperone improves muscle function in mice with a RyR1 mutation.

PubMed

Lee, Chang Seok; Hanna, Amy D; Wang, Hui; Dagnino-Acosta, Adan; Joshi, Aditya D; Knoblauch, Mark; Xia, Yan; Georgiou, Dimitra K; Xu, Jianjun; Long, Cheng; Amano, Hisayuki; Reynolds, Corey; Dong, Keke; Martin, John C; Lagor, William R; Rodney, George G; Sahin, Ergun; Sewry, Caroline; Hamilton, Susan L

2017-03-24

Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca 2+ release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca 2+ transient, resting cytosolic Ca 2+ levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production. Treatment of mice carrying the I4895T mutation with a chemical chaperone, sodium 4-phenylbutyrate (4PBA), reduces ER stress/UPR and improves muscle function, but does not restore SR Ca 2+ transients in I4895T fibres to wild type levels, suggesting that decreased SR Ca 2+ release is not the major driver of the myopathy. These findings suggest that 4PBA, an FDA-approved drug, has potential as a therapeutic intervention for RyR1 myopathies that are associated with ER stress.

A chemical chaperone improves muscle function in mice with a RyR1 mutation

PubMed Central

Lee, Chang Seok; Hanna, Amy D.; Wang, Hui; Dagnino-Acosta, Adan; Joshi, Aditya D.; Knoblauch, Mark; Xia, Yan; Georgiou, Dimitra K.; Xu, Jianjun; Long, Cheng; Amano, Hisayuki; Reynolds, Corey; Dong, Keke; Martin, John C.; Lagor, William R.; Rodney, George G.; Sahin, Ergun; Sewry, Caroline; Hamilton, Susan L.

2017-01-01

Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca2+ release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca2+ transient, resting cytosolic Ca2+ levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production. Treatment of mice carrying the I4895T mutation with a chemical chaperone, sodium 4-phenylbutyrate (4PBA), reduces ER stress/UPR and improves muscle function, but does not restore SR Ca2+ transients in I4895T fibres to wild type levels, suggesting that decreased SR Ca2+ release is not the major driver of the myopathy. These findings suggest that 4PBA, an FDA-approved drug, has potential as a therapeutic intervention for RyR1 myopathies that are associated with ER stress. PMID:28337975

Saturated fatty acid palmitate negatively regulates autophagy by promoting ATG5 protein degradation in meniscus cells.

PubMed

Mallik, Aritra; Yammani, Raghunatha R

2018-07-20

Obesity and associated metabolic factors are major risk factors for the development of osteoarthritis. Previously, we have shown that the free fatty acid palmitate induces endoplasmic reticulum (ER) stress and induces apoptosis in meniscus cells. However, the molecular mechanisms involved in these effects are not clearly understood. In our current study, we found that palmitate inhibits autophagy by modulating the protein levels of autophagy-related genes-5 (ATG5) that is associated with decreased lipidation of LC3 and increased activation of cleaved caspase 3. Pretreatment of meniscus cells with 4-phenyl butyric acid, a small molecule chemical chaperone that alleviates ER stress, or with MG-132, a proteasome inhibitor, restored normal levels of ATG5 and autophagosome formation, and decreased expression of cleaved caspase 3. Thus, our data suggest that palmitate downregulates autophagy in meniscus cells by degrading ATG5 protein via ER-associated protein degradation, and thus promotes apoptosis. This is the first study to demonstrate that palmitate-induced endoplasmic reticulum stress negatively regulates autophagy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Defective interplay between mTORC1 activity and endoplasmic reticulum stress-unfolded protein response in uremic vascular calcification.

PubMed

Panda, Dibyendu K; Bai, Xiuying; Sabbagh, Yves; Zhang, Yan; Zaun, Hans-Christian; Karellis, Angeliki; Koromilas, Antonis E; Lipman, Mark L; Karaplis, Andrew C

2018-06-01

Vascular calcification increases the risk of cardiovascular disease and death in patients with chronic kidney disease (CKD). Increased activity of mammalian target of rapamycin complex 1 (mTORC1) and endoplasmic reticulum (ER) stress-unfolded protein response (UPR) are independently reported to partake in the pathogenesis of vascular calcification in CKD. However, the association between mTORC1 activity and ER stress-UPR remains unknown. We report here that components of the uremic state [activation of the receptor for advanced glycation end products (RAGE) and hyperphosphatemia] potentiate vascular smooth muscle cell (VSMC) calcification by inducing persistent and exaggerated activity of mTORC1. This gives rise to prolonged and excessive ER stress-UPR as well as attenuated levels of sestrin 1 ( Sesn1) and Sesn3 feeding back to inhibit mTORC1 activity. Activating transcription factor 4 arising from the UPR mediates cell death via expression of CCAAT/enhancer-binding protein (c/EBP) homologous protein (CHOP), impairs the generation of pyrophosphate, a potent inhibitor of mineralization, and potentiates VSMC transdifferentiation to the osteochondrocytic phenotype. Short-term treatment of CKD mice with rapamycin, an inhibitor of mTORC1, or tauroursodeoxycholic acid, a bile acid that restores ER homeostasis, normalized mTORC1 activity, molecular markers of UPR, and calcium content of aortas. Collectively, these data highlight that increased and/or protracted mTORC1 activity arising from the uremic state leads to dysregulated ER stress-UPR and VSMC calcification. Manipulation of the mTORC1-ER stress-UPR pathway opens up new therapeutic strategies for the prevention and treatment of vascular calcification in CKD.

Modulation of Pancreatic Islets' Function and Survival During Aging Involves the Differential Regulation of Endoplasmic Reticulum Stress by p21 and CHOP

PubMed Central

Mihailidou, Chrysovalantou; Chatzistamou, Ioulia; Papavassiliou, Athanasios G.

2017-01-01

Abstract Aims: Although endoplasmic reticulum (ER) stress is recognized as a major mechanism causing pancreatic dysfunction in diabetes, little is known on how aging modulates the process. Here, we compared the response with ER stress, viability, and insulin release from pancreatic islets of young (6 weeks) or aged (14 months) mice. Results: Islets from aged mice were more sensitive to ER stress than their younger counterparts; they exhibited more pronounced unfolded protein response (UPR) and caspase activation and displayed compromised insulin release after high-glucose stimulation. Genetic ablation of p21 sensitized the islets to ER stress, especially in the aged group, whereas CHOP ablation was protective for islets from both aged and younger animals. Ciclopirox (CPX), an iron chelator that stimulates p21 expression, protected islets from glucotoxicity and mice from diet-induced diabetes, especially in the aged group in a manner that was both p21 and CHOP dependent. Innovation: For the first time, the study shows that age-dependent susceptibility to diet-induced diabetes is associated with the activity of p21 and CHOP in pancreatic islets and that CPX protects islets from glucotoxicity and mice from diabetes in an age-dependent manner. Conclusions: Our results identify ER stress as an age-dependent modifier of islet survival and function by mechanisms implicating enhancement of CHOP activity and inhibition of the protective activity of p21. These findings suggest that interventions restoring the homeostatic activity of ER stress, by agents such as CPX, may be particularly beneficial for the management of diabetes in the elderly. Antioxid. Redox Signal. 27, 185–200. PMID:27931122

Mechanical properties and molecular structure analysis of subsurface dentin after Er:YAG laser irradiation.

PubMed

He, Zhengdi; Chen, Lingling; Hu, Xuejuan; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Ruan, Shuangchen

2017-10-01

The purpose of this study was to evaluate the chemical and mechanical modifications in subsurface dentin layer after Er: YAG (Erbium-Yttrium Aluminium Garnet) laser irradiation, as the guidance of new dental restorative materials specific for laser irradiated dentin. Dentin disks obtained from extracted human molars were prepared and exposed to a single pulse Er:YAG laser irradiation at 80mJ/pulse. After laser irradiation the mechanical and chemical characteristics of intertubular dentin in subsurface layer were studied using nanoindentation tester and micro-Raman spectromy (μ-RS). The dentin 5-50µm depth beneath the lased surface was determined as testing area. Two-way analysis of variance (ANOVA) were used to compare the mechanical values between lased and untreated subsurface dentin (P = 0.05). A laser affected subsurface dentin layer after Er:YAG laser treatment is present. The laser irradiation is considered to decrease the mechanical properties in the superficial subsurface layer (<15µm deep). There was no significant difference in nanohardness and Young's modulus between lased subsurface dentin and untreated dentin (p > 0.05) under the depth of 15µm. However, the dentin at 5µm and 10µm depth beneath the lased surface exhibited significantly lower (~ 47.8% and ~ 33.6% respectively) hardness (p < 0.05). Er:YAG laser irradiation affected both mineral and organic components in subsurface dentin layer, a higher degree of crystallinity and reduced organic compounds occurred in the lased subsurface dentin. Under the tested laser parameters, Er:YAG laser irradiation causes lower mechanical values and reduction of organic components in subsurface dentin, which has deleterious effects on resin adhesion to this area. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis.

PubMed

Yam, Gary Hin-Fai; Gaplovska-Kysela, Katarina; Zuber, Christian; Roth, Jürgen

2007-04-01

To evaluate the effect of chemical chaperones on the trafficking of secretion-incompetent primary open-angle glaucoma-associated mutant myocilin and the possibility to rescue cells coexpressing mutant and wild-type myocilin from endoplasmic reticulum (ER) stress and apoptosis. CHO-K1, HEK293 and human trabecular meshwork cells were transfected to express wild-type or mutant (C245Y, G364V, P370L, Y437H) myocilin-green fluorescent protein fusion protein and were treated or not with various chemical chaperones (glycerol, dimethylsulfoxide, or sodium 4-phenylbutyrate) for different time periods. The secretion, Triton X-100 solubility, and intracellular distribution of wild-type and mutant myocilin were analyzed by immunoprecipitation, Western blotting, and confocal double immunofluorescence. The effect of sodium 4-phenylbutyrate on ER stress proteins and apoptosis was examined in cells coexpressing mutant and wild-type myocilin. Treatment with sodium 4-phenylbutyrate, but not with glycerol or dimethylsulfoxide, reduced the amount of detergent-insoluble myocilin aggregates, diminished myocilin interaction with calreticulin, and restored the secretion of mutant myocilin. Heteromeric complexes formed by mutant and wild-type myocilin induced the ER stress-associated phosphorylated form of ER-localized eukaryotic initiation factor (eIF)-2alpha kinase and the active form of caspase 3, which resulted in an increased rate of apoptosis. Sodium 4-phenylbutyrate treatment of cells coexpressing mutant and wild-type myocilin relieved ER stress and significantly reduced the rate of apoptosis. These findings indicate that sodium 4-phenylbutyrate protects cells from the deleterious effects of ER-retained aggregated mutant myocilin. These data point to the possibility of a chemical chaperone treatment for myocilin-caused primary open-angle glaucoma.

Modulation of Pancreatic Islets' Function and Survival During Aging Involves the Differential Regulation of Endoplasmic Reticulum Stress by p21 and CHOP.

PubMed

Mihailidou, Chrysovalantou; Chatzistamou, Ioulia; Papavassiliou, Athanasios G; Kiaris, Hippokratis

2017-08-01

Although endoplasmic reticulum (ER) stress is recognized as a major mechanism causing pancreatic dysfunction in diabetes, little is known on how aging modulates the process. Here, we compared the response with ER stress, viability, and insulin release from pancreatic islets of young (6 weeks) or aged (14 months) mice. Islets from aged mice were more sensitive to ER stress than their younger counterparts; they exhibited more pronounced unfolded protein response (UPR) and caspase activation and displayed compromised insulin release after high-glucose stimulation. Genetic ablation of p21 sensitized the islets to ER stress, especially in the aged group, whereas CHOP ablation was protective for islets from both aged and younger animals. Ciclopirox (CPX), an iron chelator that stimulates p21 expression, protected islets from glucotoxicity and mice from diet-induced diabetes, especially in the aged group in a manner that was both p21 and CHOP dependent. For the first time, the study shows that age-dependent susceptibility to diet-induced diabetes is associated with the activity of p21 and CHOP in pancreatic islets and that CPX protects islets from glucotoxicity and mice from diabetes in an age-dependent manner. Our results identify ER stress as an age-dependent modifier of islet survival and function by mechanisms implicating enhancement of CHOP activity and inhibition of the protective activity of p21. These findings suggest that interventions restoring the homeostatic activity of ER stress, by agents such as CPX, may be particularly beneficial for the management of diabetes in the elderly. Antioxid. Redox Signal. 27, 185-200.

50 CFR 80.25 - Multiyear financing under the Dingell-Johnson Sport Fish Restoration Program.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-Johnson Sport Fish Restoration Program. 80.25 Section 80.25 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH... SPORT FISH RESTORATION ACTS § 80.25 Multiyear financing under the Dingell-Johnson Sport Fish Restoration...

Eat it right: ER-phagy and recovER-phagy.

PubMed

Loi, Marisa; Fregno, Ilaria; Guerra, Concetta; Molinari, Maurizio

2018-05-25

The endoplasmic reticulum (ER) is the site of protein, lipid, phospholipid, steroid and oligosaccharide synthesis and modification, calcium ion storage, and detoxification of endogenous and exogenous products. Its volume (and activity) must be maintained under normal growth conditions, must be expanded in a controlled manner on activation of ER stress programs and must be reduced to pre-stress size during the recovery phase that follows ER stress termination. ER-phagy is the constitutive or regulated fragmentation and delivery of ER fragments to lysosomal compartments for clearance. It gives essential contribution to the maintenance of cellular homeostasis, proteostasis, lipidostasis and oligosaccharidostasis (i.e. the capacity to produce the proteome, lipidome and oligosaccharidome in appropriate quality and quantity). ER turnover is activated on ER stress, nutrient deprivation, accumulation of misfolded polypeptides, pathogen attack and by activators of macroautophagy. The selectivity of these poorly characterized catabolic pathways is ensured by proteins displayed at the limiting membrane of the ER subdomain to be removed from cells. These proteins are defined as ER-phagy receptors and engage the cytosolic macroautophagy machinery via specific modules that associate with ubiquitin-like, cytosolic proteins of the Atg8/LC3/GABARAP family. In this review, we give an overview on selective ER turnover and on the yeast and mammalian ER-phagy receptors identified so far. © 2018 The Author(s).

50 CFR 86.94 - What crediting language should I use?

Code of Federal Regulations, 2013 CFR

2013-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.94 What crediting...: (a) Example 1: The Federal Aid in Sport Fish Restoration Program funded this facility thanks to your...

50 CFR 86.94 - What crediting language should I use?

Code of Federal Regulations, 2014 CFR

2014-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.94 What crediting...: (a) Example 1: The Federal Aid in Sport Fish Restoration Program funded this facility thanks to your...

Reducing errors benefits the field-based learning of a fundamental movement skill in children.

PubMed

Capio, C M; Poolton, J M; Sit, C H P; Holmstrom, M; Masters, R S W

2013-03-01

Proficient fundamental movement skills (FMS) are believed to form the basis of more complex movement patterns in sports. This study examined the development of the FMS of overhand throwing in children through either an error-reduced (ER) or error-strewn (ES) training program. Students (n = 216), aged 8-12 years (M = 9.16, SD = 0.96), practiced overhand throwing in either a program that reduced errors during practice (ER) or one that was ES. ER program reduced errors by incrementally raising the task difficulty, while the ES program had an incremental lowering of task difficulty. Process-oriented assessment of throwing movement form (Test of Gross Motor Development-2) and product-oriented assessment of throwing accuracy (absolute error) were performed. Changes in performance were examined among children in the upper and lower quartiles of the pretest throwing accuracy scores. ER training participants showed greater gains in movement form and accuracy, and performed throwing more effectively with a concurrent secondary cognitive task. Movement form improved among girls, while throwing accuracy improved among children with low ability. Reduced performance errors in FMS training resulted in greater learning than a program that did not restrict errors. Reduced cognitive processing costs (effective dual-task performance) associated with such approach suggest its potential benefits for children with developmental conditions. © 2011 John Wiley & Sons A/S.

The endoplasmic reticulum in plant immunity and cell death

PubMed Central

Eichmann, Ruth; Schäfer, Patrick

2012-01-01

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells and a major production site of proteins destined for vacuoles, the plasma membrane, or apoplast in plants. At the ER, these secreted proteins undergo multiple processing steps, which are supervised and conducted by the ER quality control system. Notably, processing of secreted proteins can considerably elevate under stress conditions and exceed ER folding capacities. The resulting accumulation of unfolded proteins is defined as ER stress. The efficiency of cells to re-establish proper ER function is crucial for stress adaptation. Besides delivering proteins directly antagonizing and resolving stress conditions, the ER monitors synthesis of immune receptors. This indicates the significance of the ER for the establishment and function of the plant immune system. Recent studies point out the fragility of the entire system and highlight the ER as initiator of programed cell death (PCD) in plants as was reported for vertebrates. This review summarizes current knowledge on the impact of the ER on immune and PCD signaling. Understanding the integration of stress signals by the ER bears a considerable potential to optimize development and to enhance stress resistance of plants. PMID:22936941

The endoplasmic reticulum in plant immunity and cell death.

PubMed

Eichmann, Ruth; Schäfer, Patrick

2012-01-01

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells and a major production site of proteins destined for vacuoles, the plasma membrane, or apoplast in plants. At the ER, these secreted proteins undergo multiple processing steps, which are supervised and conducted by the ER quality control system. Notably, processing of secreted proteins can considerably elevate under stress conditions and exceed ER folding capacities. The resulting accumulation of unfolded proteins is defined as ER stress. The efficiency of cells to re-establish proper ER function is crucial for stress adaptation. Besides delivering proteins directly antagonizing and resolving stress conditions, the ER monitors synthesis of immune receptors. This indicates the significance of the ER for the establishment and function of the plant immune system. Recent studies point out the fragility of the entire system and highlight the ER as initiator of programed cell death (PCD) in plants as was reported for vertebrates. This review summarizes current knowledge on the impact of the ER on immune and PCD signaling. Understanding the integration of stress signals by the ER bears a considerable potential to optimize development and to enhance stress resistance of plants.

Neutron Scattering Studies of Classical and Quantum Fluids in Porous Media

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

Glyde, Henry R.

This is an annual and the final report on DE-FG02-03ER46038 (ER46680) following a no cost extension of DE-FG02-03ER46038 from February 16, 2016 to November 15, 2016. The report period is February 16, 2016 to November 15, 2016. The contract DE-FG02-03ER46038 (ER46680) was closed on November 15, 2016. The contract institution is the University of Delaware, address: Room 210, Hullihen %%@ Hall, University of Delaware, Newark, DE 19716. The Principal Investigator is Henry R. Glyde, Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (email: glyde@udel.edu). The Administrative Point of Contact is Dale S. Weiss Tel: 302 831 3634more » dsweiss@udel.edu. The DOE Program is the Office of Basic Energy %%@ Sciences, U.S. Department of Energy, Germantown Building, 1000 Independence Ave., SW Washington, DC 20585. The program manager is Dr. P. Thiyagarajan, Neutron Scattering SC-22.2/ Germantown Bldg., Tel: 301-903-9706, email: P. Thiyagarajan@Science.DOE.GOV.« less

Modulation of Endoplasmic Reticulum Stress Controls CD4+ T-cell Activation and Antitumor Function.

PubMed

Thaxton, Jessica E; Wallace, Caroline; Riesenberg, Brian; Zhang, Yongliang; Paulos, Chrystal M; Beeson, Craig C; Liu, Bei; Li, Zihai

2017-08-01

The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca 2+ stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca 2+ buffering protein. We hypothesized that the ER stress response may be important for CD4 + T-cell activation and that gp96 may be integral to this process. To test our hypothesis, we utilized genetic deletion of the gp96 gene Hsp90b1 in a CD4 + T cell-specific manner. We show that gp96-deficient CD4 + T cells cannot undergo activation-induced glycolysis due to defective Ca 2+ mobilization upon TCR engagement. We found that activating naïve CD4 + T cells while inhibiting ER Ca 2+ exchange, through pharmacological blockade of the ER Ca 2+ channel inositol trisphosphate receptor (IP 3 R), led to a reduction in cytosolic Ca 2+ content and generated a pool of CD62L high /CD44 low CD4 + T cells compared with wild-type (WT) matched controls. In vivo IP 3 R-inhibited CD4 + T cells exhibited elevated tumor control above WT T cells. Together, these data show that ER-modulated cytosolic Ca 2+ plays a role in defining CD4 + T-cell phenotype and function. Factors associated with the ER stress response are suitable targets for T cell-based immunotherapies. Cancer Immunol Res; 5(8); 666-75. ©2017 AACR . ©2017 American Association for Cancer Research.

Performance of the BG1Luc ER TA method in a qHTS format.

PubMed

Ceger, Patricia; Allen, David; Huang, Ruili; Xia, Menghang; Casey, Warren

2015-01-01

In 2012, the BG1Luc4E2 estrogen receptor (ER) transactivation (TA) method (BG1Luc ER TA) was accepted by U.S. regulatory agencies and the Organisation for Economic Co-operation and Development to detect substances with ER agonist activity. The method is now part of the Tier 1 testing battery in the Environmental Protection Agency's Endocrine Disruptor Screening Program. The BG1Luc ER TA method uses the BG1 ovarian cell line that endogenously expresses full-length ER (α and β) and is stably transfected with a plasmid containing four estrogen responsive elements upstream of a luciferase reporter gene. To allow increased throughput and testing efficiency, the BG1Luc ER TA ("BG1 manual") method was adapted for quantitative high-throughput screening (BG1 qHTS) in the U.S. Tox21 testing program. The BG1 qHTS test method was used to test approximately 10,000 chemicals three times each, and concentration-response data (n=15) were analyzed to evaluate test method performance. The balanced accuracy of the BG1 qHTS test method (97% [32/33]) was determined by comparing results to ER TA performance standards for the BG1 manual method. Concordance between the BG1 manual and qHTS methods was 92% (57/62) when calculated for a larger set of non-reference chemicals tested in both methods. These data demonstrate that the performance of the BG1 qHTS is similar to the currently accepted BG1 manual method, thereby establishing the utility of the BG1 qHTS method for identifying ER active environmental chemicals.

Neuro Emotional Literacy Program: Does Teaching the Function of Affect and Affect Regulation Strategies Improve Affect Management and Well-Being?

ERIC Educational Resources Information Center

Patten, Kathryn E.; Campbell, Stephen R.

2016-01-01

Although research on Emotion Regulation (ER) is developing at a rapid rate, much of it lacks a clear theoretical framework and most focuses on a narrow set of ER strategies. This work presents the details of a pilot project, the Neuro Emotional Literacy Program (NELP), designed for parents and based on the Somatic Appraisal Model of Affect (SAMA).…

50 CFR 80.14 - Application of Wildlife and Sport Fish Restoration Program funds.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Application of Wildlife and Sport Fish Restoration Program funds. 80.14 Section 80.14 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM...

The Next Generation of Ground Operations Command and Control; Scripting in C Sharp and Visual Basic

NASA Technical Reports Server (NTRS)

Ritter, George; Pedoto, Ramon

2010-01-01

This slide presentation reviews the use of scripting languages in Ground Operations Command and Control. It describes the use of scripting languages in a historical context, the advantages and disadvantages of scripts. It describes the Enhanced and Redesigned Scripting (ERS) language, that was designed to combine the features of a scripting language and the graphical and IDE richness of a programming language with the utility of scripting languages. ERS uses the Microsoft Visual Studio programming environment and offers custom controls that enable an ERS developer to extend the Visual Basic and C sharp language interface with the Payload Operations Integration Center (POIC) telemetry and command system.

pyres: a Python wrapper for electrical resistivity modeling with R2

NASA Astrophysics Data System (ADS)

Befus, Kevin M.

2018-04-01

A Python package, pyres, was written to handle common as well as specialized input and output tasks for the R2 electrical resistivity (ER) modeling program. Input steps including handling field data, creating quadrilateral or triangular meshes, and data filtering allow repeatable and flexible ER modeling within a programming environment. pyres includes non-trivial routines and functions for locating and constraining specific known or separately-parameterized regions in both quadrilateral and triangular meshes. Three basic examples of how to run forward and inverse models with pyres are provided. The importance of testing mesh convergence and model sensitivity are also addressed with higher-level examples that show how pyres can facilitate future research-grade ER analyses.

The Error Reporting in the ATLAS TDAQ System

NASA Astrophysics Data System (ADS)

Kolos, Serguei; Kazarov, Andrei; Papaevgeniou, Lykourgos

2015-05-01

The ATLAS Error Reporting provides a service that allows experts and shift crew to track and address errors relating to the data taking components and applications. This service, called the Error Reporting Service (ERS), gives to software applications the opportunity to collect and send comprehensive data about run-time errors, to a place where it can be intercepted in real-time by any other system component. Other ATLAS online control and monitoring tools use the ERS as one of their main inputs to address system problems in a timely manner and to improve the quality of acquired data. The actual destination of the error messages depends solely on the run-time environment, in which the online applications are operating. When an application sends information to ERS, depending on the configuration, it may end up in a local file, a database, distributed middleware which can transport it to an expert system or display it to users. Thanks to the open framework design of ERS, new information destinations can be added at any moment without touching the reporting and receiving applications. The ERS Application Program Interface (API) is provided in three programming languages used in the ATLAS online environment: C++, Java and Python. All APIs use exceptions for error reporting but each of them exploits advanced features of a given language to simplify the end-user program writing. For example, as C++ lacks language support for exceptions, a number of macros have been designed to generate hierarchies of C++ exception classes at compile time. Using this approach a software developer can write a single line of code to generate a boilerplate code for a fully qualified C++ exception class declaration with arbitrary number of parameters and multiple constructors, which encapsulates all relevant static information about the given type of issues. When a corresponding error occurs at run time, the program just need to create an instance of that class passing relevant values to one of the available class constructors and send this instance to ERS. This paper presents the original design solutions exploited for the ERS implementation and describes how it was used during the first ATLAS run period. The cross-system error reporting standardization introduced by ERS was one of the key points for the successful implementation of automated mechanisms for online error recovery.

Expanding a community's justice response to sex crimes through advocacy, prosecutorial, and public health collaboration: introducing the RESTORE program.

PubMed

Koss, Mary P; Bachar, Karen J; Hopkins, C Quince; Carlson, Carolyn

2004-12-01

Problems in criminal justice system response to date-acquaintance rape and nonpenetration sexual offenses include (a) they are markers of a sexual offending career, yet are viewed as minor; (b) perpetrators are not held accountable in ways that reduce reoffense; and (c) criminal justice response disappoints and traumatizes victims. To address these problems, a collaboration of victim services, prosecutors, legal scholars, and public health professionals are implementing and evaluating RESTORE, a victim-driven, community-based restorative justice program for selected sex crimes. RESTORE prepares survivors, responsible persons (offenders), and both parties' families and friends for face-to-face dialogue to identify the harm and develop a redress plan. The program then monitors the offender's compliance for 12 months. The article summarizes empirical data on problems in criminal justice response, defines restorative justice models, and examines outcome. Then the RESTORE program processes and goals are described. The article highlights community collaboration in building and sustaining this program.

Cell biology. ER-to-Golgi traffic--this bud's for you.

PubMed

Brittle, E E; Waters, M G

2000-07-21

How do protein-transporting vesicles, which bud from the endoplasmic reticulum (ER), specifically dock to, and fuse with, the Golgi apparatus? In their Perspective, Brittle and Waters discuss new work (Allan et al.) suggesting that some vesicle-associated docking and fusion proteins are "programmed" during vesicle budding from the ER and direct downstream events that occur during fusion of these transport vesicles with the membranes of the Golgi.

Assessment of interim flow water-quality data of the San Joaquin River restoration program and implications for fishes, California, 2009-11

USGS Publications Warehouse

Wulff, Marissa L.; Brown, Larry R.

2015-01-01

After more than 50 years of extensive water diversion for urban and agriculture use, a major settlement was reached among the U.S. Departments of the Interior and Commerce, the Natural Resources Defense Council, and the Friant Water Users Authority in an effort to restore the San Joaquin River. The settlement received Federal court approval in October 2006 and established the San Joaquin River Restoration Program, a multi-agency collaboration between State and Federal agencies to restore and maintain fish populations, including Chinook salmon, in the main stem of the river between Friant Dam and the confluence with the Merced River. This is to be done while avoiding or minimizing adverse water supply effects to all of the Friant Division contractors that could result from restoration flows required by the settlement. The settlement stipulates that water- and sediment-quality data be collected to help assess the restoration goals. This report summarizes and evaluates water-quality data collected in the main stem of the San Joaquin River between Friant Dam and the Merced River by the U.S. Bureau of Reclamation for the San Joaquin River Restoration Program during 2009-11. This summary and assessment consider sampling frequency for adequate characterization of variability, sampling locations for sufficient characterization of the San Joaquin River Restoration Program restoration reach, sampling methods for appropriate media (water and sediment), and constituent reporting limits. After reviewing the water- and sediment-quality results for the San Joaquin River Restoration Program, several suggestions were made to the Fisheries Management Work Group, a division of the San Joaquin River Restoration Program that focuses solely on the reintroduction strategies and health of salmon and other native fishes in the river. Water-quality results for lead and total organic carbon exceeded the Surface Water Ambient Monitoring Program Basin Plan Objectives for the San Joaquin Basin, and results for copper exceeded the U.S. Environmental Protection Agency Office of Pesticide Programs' aquatic-life chronic and acute benchmarks for invertebrates. One sediment sample contained detections of pyrethroid pesticides bifenthrin, lambda-cyhalothrin, and total permethrin at concentrations above published chronic toxicity thresholds.

Adaptive Long-Term Monitoring at Environmental Restoration Sites (ER-0629)

DTIC Science & Technology

2009-05-01

Figures Figure 2-1 General Flowchart of Software Application Figure 2-2 Overview of the Genetic Algorithm Approach Figure 2-3 Example of a...and Model Builder) are highlighted on Figure 2-1, which is a general flowchart illustrating the application of the software. The software is applied...monitoring event (e.g., contaminant mass based on interpolation) that modeling is provided by Model Builder. 4 Figure 2-1. General Flowchart of Software

Bearing restoration by grinding

NASA Technical Reports Server (NTRS)

Hanau, H.; Parker, R. J.; Zaretsky, E. V.; Chen, S. M.; Bull, H. L.

1976-01-01

A joint program was undertaken by the NASA Lewis Research Center and the Army Aviation Systems Command to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. No bearing failures occurred related to the restoration by grinding process. The risk and cost of a bearing restoration by grinding programs was analyzed. A microeconomic impact analysis was performed.

Ablation by-products of dental materials from the Er:YAG laser and the dental handpiece

NASA Astrophysics Data System (ADS)

Wigdor, Harvey A.; Visuri, Steven R.; Walsh, Joseph T., Jr.

1995-05-01

Recently there has been much interest in lasers and their potential use to replace the dental drill. The research has been directed towards vital dental tissues. It must be understood that any laser to be used in dentistry which will replace the dental drill must also ablate and remove existing dental materials. Some concern exists about the ablation products when the Er:YAG laser is used to ablate dental materials. It is incumbent on the professionals using these lasers to understand the materials being produced by these lasers and protect themselves and their patients from possible toxic products. It is the intent of this paper to evaluate the products produced by the ablation of both dental amalgam and composite dental restorative materials and compare them with those produced by the traditional dental handpiece (drill).

Access to Ribosomal Protein Rpl25p by the Signal Recognition Particle Is Required for Efficient Cotranslational Translocation

PubMed Central

Dalley, Jane A.; Selkirk, Alexander

2008-01-01

Targeting of proteins to the endoplasmic reticulum (ER) occurs cotranslationally necessitating the interaction of the signal recognition particle (SRP) and the translocon with the ribosome. Biochemical and structural studies implicate ribosomal protein Rpl25p as a major ribosome interaction site for both these factors. Here we characterize an RPL25GFP fusion, which behaves as a dominant mutant leading to defects in co- but not posttranslational translocation in vivo. In these cells, ribosomes still interact with ER membrane and the translocon, but are defective in binding SRP. Overexpression of SRP can restore ribosome binding of SRP, but only partially rescues growth and translocation defects. Our results indicate that Rpl25p plays a critical role in the recruitment of SRP to the ribosome. PMID:18448667

RESTORATION PLUS: A COLLABORATIVE ENVIRONMENTAL PROTECTION AGENCY RESEARCH PROGRAM TO DEVELOP AND EVALUATE ECOSYSTEM RESTORATION AND MANAGEMENT OPTIONS TO ACHIEVE ECOLOGICALLY AND ECONOMICALLY SUSTAINABLE SOLUTIONS

EPA Science Inventory

The U.S. Environmental Protection Agency (U.S. EPA) is evaluating ecosystem restoration and management techniques to ensure they create sustainable solutions for degraded watersheds. The ORD/NRMRL initiated the Restoration Plus (RePlus) program in 2002, which emphasizes collabora...

Power and Authority in the Student-Instructor Relationship in a Restorative Practices-Based Graduate Program

ERIC Educational Resources Information Center

Bailie, John W., III

2012-01-01

This study examined power and authority in the student-instructor relationship in a restorative practices-based graduate program. This qualitative investigation utilized a narrative approach. Ten alumni of the International Institute for Restorative Practices master's degree programs were engaged in a one-time face-to-face interview and document…

Restorative Justice at Work: Examining the Impact of Restorative Justice Resolutions on Juvenile Recidivism

ERIC Educational Resources Information Center

Rodriguez, Nancy

2007-01-01

Programs with restorative justice ideals attempt to incorporate victims and community members into the administration of justice. Although these programs have become increasingly popular, only a few programs in the United States have been the focus of prior studies. Using official juvenile court data from an urban, metropolitan area, this study…

GSD Update: Restoration on the range: Healing America's iconic landscapes

Treesearch

Christie Aschwanden

2011-01-01

Restoration is one of five focal areas of the Grassland, Shrubland and Desert Ecosystems Science Program (GSD). Our program mission is to develop and deliver knowledge and tools that will help to sustain and restore grasslands, shrublands and deserts threatened by invasive species, disturbances, urban pressures and climate change. Scientists in our program develop...

Review of Ice-Induced Scour Impacts to Navigation and Structures

DTIC Science & Technology

2017-07-17

ER D C SR -1 7- 3 Navigation Systems Research Program Review of Ice-Induced Scour Impacts to Navigation and Structures En gi ne er R...unlimited. The U.S. Army Engineer Research and Development Center (ERDC) solves the nation’s toughest engineering and environmental challenges...reports published by ERDC, visit the ERDC online library at http://acwc.sdp.sirsi.net/client/default. Navigation Systems Research Program ERDC SR-17

A crosstalk between p21 and UPR-induced transcription factor C/EBP homologous protein (CHOP) linked to type 2 diabetes.

PubMed

Mihailidou, Chrysovalantou; Papavassiliou, Athanasios G; Kiaris, Hippokratis

2014-04-01

Type 2 diabetes (T2D) is a disease that is characterized by raised levels of glucose in the blood combined with insulin resistance and relative insulin deficiency. The pathogenesis of type 2 diabetes is associated with the induction of the unfolded protein response (UPR). While UPR aims to restore tissue homeostasis following stress of the endoplasmic reticulum (ER), prolonged ER stress triggers apoptosis at least in part through the unfolded protein response (UPR)-activated transcription factor C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP). CHOP has elevated as a critical mediator connecting accumulation and aggregation of unfolded proteins in the ER and oxidative stress and also contributes to the induction of apoptosis in β-cell (beta-cell) - cells under conditions of increased insulin demand. p21 is a cell cycle regulator that is implicated in the regulation of the UPR by various mechanisms involving inhibition of apoptosis and facilitation of the regeneration capacity of the β cells. In this review we summarize the role of ER stress in the pathogenesis of type 2 diabetes which is associated with the induction of the unfolded protein response (UPR). We also review recent evidence associating p21 activity with β cell health and regenerative capacity by mechanisms that may interfere with the effects of p21 in the UPR or operate independently of ER stress. Most likely understanding the molecular details of the pathogenesis of type 2 diabetes will be beneficial for the management of the disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Nordihydroguaiaretic acid blocks protein transport in the secretory pathway causing redistribution of Golgi proteins into the endoplasmic reticulum.

PubMed

Fujiwara, T; Takami, N; Misumi, Y; Ikehara, Y

1998-01-30

We have investigated the effect of nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, on the intracellular protein transport and the structure of the Golgi complex. Pulse-chase experiments and immunoelectron microscopy showed that NDGA strongly inhibits the transport of newly synthesized secretory proteins to the Golgi complex resulting in their accumulation in the endoplasmic reticulum (ER). Despite their retention in the ER, oligosaccharides of secretory and ER-resident proteins were processed to endoglycosidase H-resistant forms, raising the possibility that oligosaccharide-processing enzymes are redistributed from the Golgi to the ER. Morphological observations further revealed that alpha-mannosidase II (a cis/medial-Golgi marker), but not TGN38 (a trans-Golgi network marker), rapidly redistributes to the ER in the presence of NDGA, resulting in the disappearance of the characteristic Golgi structure. Upon removal of the drug, the Golgi complex was reassembled into the normal structure as judged by perinuclear staining of alpha-mannosidase II and by restoration of the secretion. These effects of NDGA are quite similar to those of brefeldin A. However, unlike brefeldin A, NDGA did not cause a dissociation of beta-coatomer protein, a subunit of coatomer, from the Golgi membrane. On the contrary, NDGA exerted the stabilizing effect on beta-coatomer protein/membrane interaction against the dissociation caused by brefeldin A and ATP depletion. Taken together, these results indicate that NDGA is a potent agent disrupting the structure and function of the Golgi complex with a mechanism different from those known for other drugs reported so far.

Mechanisms of disordered neurodegenerative function: concepts and facts about the different roles of the protein kinase RNA-like endoplasmic reticulum kinase (PERK).

PubMed

Taalab, Yasmeen M; Ibrahim, Nour; Maher, Ahmed; Hassan, Mubashir; Mohamed, Wael; Moustafa, Ahmed A; Salama, Mohamed; Johar, Dina; Bernstein, Larry

2018-06-27

Neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, prion disease, and amyotrophic lateral sclerosis, are a dissimilar group of disorders that share a hallmark feature of accumulation of abnormal intraneuronal or extraneuronal misfolded/unfolded protein and are classified as protein misfolding disorders. Cellular and endoplasmic reticulum (ER) stress activates multiple signaling cascades of the unfolded protein response (UPR). Consequently, translational and transcriptional alterations in target gene expression occur in response directed toward restoring the ER capacity of proteostasis and reestablishing the cellular homeostasis. Evidences from in vitro and in vivo disease models indicate that disruption of ER homeostasis causes abnormal protein aggregation that leads to synaptic and neuronal dysfunction. However, the exact mechanism by which it contributes to disease progression and pathophysiological changes remains vague. Downstream signaling pathways of UPR are fully integrated, yet with diverse unexpected outcomes in different disease models. Three well-identified ER stress sensors have been implicated in UPR, namely, inositol requiring enzyme 1, protein kinase RNA-activated-like ER kinase (PERK), and activating transcription factor 6. Although it cannot be denied that each of the involved stress sensor initiates a distinct downstream signaling pathway, it becomes increasingly clear that shared pathways are crucial in determining whether or not the UPR will guide the cells toward adaptive prosurvival or proapoptotic responses. We review a body of work on the mechanism of neurodegenerative diseases based on oxidative stress and cell death pathways with emphasis on the role of PERK.

Disrupted carbon cycling in restored and unrestored urban streams: Critical timescales and controls

USGS Publications Warehouse

Larsen, L. G.; Harvey, Judson

2017-01-01

Carbon fixation and respiration in flowing waterways play significant roles in global and regional carbon budgets, yet how land use and watershed management interact with temporal disturbances (storms) to influence metabolism remains poorly understood. Here, we combine long-term with synoptic sampling of metabolism and its variable controls in neighboring watersheds of the Chesapeake Bay to resolve limiting factors and critical timescales associated with recovery from disturbance. We found that, relative to predictions of the river continuum concept, focal streams have “disrupted” carbon cycles, with carbon balances closer to zero, and, in some cases, tighter coupling between gross primary production (GPP) and ecosystem respiration (ER), attributable to carbon limitation. Carbon became limiting to ER where flashy storm hydrographs and simplified channel geomorphology inhibited accumulation of fine sediment. Shannon entropy analysis of timescales revealed that fine sediment served as a time-release capsule for nutrients and carbon over 4–6 months, fueling biogeochemical transformations. Loss of fines through hydraulic disturbance had up to 30-d impacts on GPP and 50-d impacts on ER in the stream with carbon limitation. In contrast, where GPP and ER were not tightly coupled, recovery occurred within 1 d. Results suggest that a complex interplay between nutrient and carbon limitation and mechanical and chemical disturbance governs patterns and consequences of disrupted carbon cycling in urban streams. Carbon limitation and tight GPP/ER coupling enhance the vulnerability of stream ecosystem functions, but best management practices that target stormflow reduction and channel geomorphic diversity can break that coupling and minimize carbon cycle disruptions.

hCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in Leydig cells of the testis

PubMed Central

Park, Sun-Ji; Kim, Tae-Shin; Park, Choon-Keun; Lee, Sang-Hee; Kim, Jin-Man; Lee, Kyu-Sun; Lee, In-kyu; Park, Jeen-Woo; Lawson, Mark A; Lee, Dong-Seok

2014-01-01

Endoplasmic reticulum (ER) stress generally occurs in secretory cell types. It has been reported that Leydig cells, which produce testosterone in response to human chorionic gonadotropin (hCG), express key steroidogenic enzymes for the regulation of testosterone synthesis. In this study, we analyzed whether hCG induces ER stress via three unfolded protein response (UPR) pathways in mouse Leydig tumor (mLTC-1) cells and the testis. Treatment with hCG induced ER stress in mLTC-1 cells via the ATF6, IRE1a/XBP1, and eIF2α/GADD34/ATF4 UPR pathways, and transient expression of 50 kDa protein activating transcription factor 6 (p50ATF6) reduced the expression level of steroidogenic 3β-hydroxy-steroid dehydrogenase Δ5-Δ4-isomerase (3β-HSD) enzyme. In an in vivo model, high-level hCG treatment induced expression of p50ATF6 while that of steroidogenic enzymes, especially 3β-HSD, 17α-hydroxylase/C17–20 lyase (CYP17), and 17β-hydrozysteroid dehydrogenase (17β-HSD), was reduced. Expression levels of steroidogenic enzymes were restored by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Furthermore, lentivirus-mediated transient expression of p50ATF6 reduced the expression level of 3β-HSD in the testis. Protein expression levels of phospho-JNK, CHOP, and cleaved caspases-12 and -3 as markers of ER stress-mediated apoptosis markedly increased in response to high-level hCG treatment in mLTC-1 cells and the testis. Based on transmission electron microscopy and H&E staining of the testis, it was shown that abnormal ER morphology and destruction of testicular histology induced by high-level hCG treatment were reversed by the addition of TUDCA. These findings suggest that hCG-induced ER stress plays important roles in steroidogenic enzyme expression via modulation of the ATF6 pathway as well as ER stress-mediated apoptosis in Leydig cells. PMID:23256993

Participation of Water in the Binding of Estrogen Receptor with Estrogen Responsive Element in vitro.

PubMed

Zhu, Guo-Zhang; Tang, Guo-Qing; Ruan, Kang-Cheng; Gong, Yue-Ting; Zhang, Yong-Lian

1998-01-01

Many reports have showed that bound water was involved in the interaction between/among the macromolecules. However, it has not been reported whether bound water is also involved in the binding of trans-factors and cis-elements in the regulation of the eukaryotic gene trans-cription or not. Preliminary studies have been made on the effect of bound water on the binding of estrogen receptor with estrogen responsive element in vitro. In the gel retardation assay using the cytosol extract of rat uterus as the supplier of estrogen receptor and 32 bp oligonucleotide containing a concensus vitellogenin A(2) ERE as the probe, various cosolvents, such as glycerol, sucrose, N-dimethylformamide and dimethylsulfoxide, were added respectively to the reaction mixture in varying concentrations to regulate the osmotic pressure. The results indicated that the binding of ER-ERE was enhanced with the increase in the final concentration of these individual cosolvents. On the other hand, when the reaction was carried out under an increasing hydrostatic pressure, the ER-ERE binding was decreased sharply. After decompression the binding of ER-ERE was gradually restored to the normal level with the lapse of time. These results suggested that bound water was directly involved in the binding of ER-ERE and may play an important role in the regulation of the eukaryotic gene transcription.

Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells

PubMed Central

Nayak, Ramesh C.; Trump, Lisa R.; Aronow, Bruce J.; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M.; Valencia, C. Alexander; Paddison, Patrick J.; Horwitz, Marshall S.; Grimes, H. Leighton; Lutzko, Carolyn; Cancelas, Jose A.

2015-01-01

Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN patient–derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues the dysgranulopoietic defect in SCN patient–derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to correct NE mislocalization. PMID:26193632

Mangiferin suppresses endoplasmic reticulum stress in perivascular adipose tissue and prevents insulin resistance in the endothelium.

PubMed

Xu, Xiaoshan; Chen, Yupeng; Song, Junna; Hou, Fangjie; Ma, Xuelian; Liu, Baolin; Huang, Fang

2018-06-01

Mangiferin is a naturally occurring glucosylxanthone with beneficial effects on glucose and lipid homeostasis. This study investigates the potential therapeutic effect of Mangiferin in perivascular adipose tissue (PVAT) and whether it contributes to regulating insulin action in the endothelium. Palmitate challenge evoked ROS-associated endoplasmic reticulum stress (ER stress) and NLRP3 inflammasome activation in PVAT. The conditioned medium from PA-stimulated PVAT was prepared to induce endothelial insulin resistance, and improved endothelium-dependent vasodilation in response to insulin was detected in vitro and in vivo. Mangiferin treatment enhanced LKB1-dependent AMPK activity and suppressed ER stress with downregulation of TXNIP induction, leading to the inhibition of NLRP3 inflammasome activation evidenced by attenuated NLRP3 and cleaved caspase-1 expression as well as reduced IL-1β secretion. Moreover, Mangiferin restored insulin-mediated Akt and eNOS phosphorylations with increased NO production, immunohistochemistry examination of adipocytes, and endothelial tissue in high-fat diet-fed mice also showed that oral administration of Mangiferin inhibited ER stress and NLRP3 induction in PVAT, and then effectively prevented insulin resistance in the vessel endothelium. Taken together, these results revealed that Mangiferin suppressed ER stress-associated NLRP3 inflammasome activation in PVAT through regulation of AMPK activity, which prevented endothelial insulin resistance. These findings suggested that the amelioration of PVAT dysfunction may be a therapeutic strategy for the prevention of endothelial insulin resistance.

Community Targets for JWST's Early Release Science Program: Evaluation of Transiting Exoplanet WASP-63b.

NASA Astrophysics Data System (ADS)

Kilpatrick, Brian; Cubillos, Patricio; Bruno, Giovanni; Lewis, Nikole K.; Stevenson, Kevin B.; Wakeford, Hannah; Blecic, Jasmina; Burrows, Adam Seth; Deming, Drake; Heng, Kevin; Line, Michael R.; Madhusudhan, Nikku; Morley, Caroline; Waldmann, Ingo P.; Transiting Exoplanet Early Release Science Community

2017-06-01

We present observations of the Hubble Space Telescope (HST) ``A Preparatory Program to Identify the Single Best Transiting Exoplanet for JWST Early Release Science" for WASP-63b, one of the community targets proposed for the James Webb Space Telescope (JWST) Early Release Science (ERS) program. A large collaboration of transiting exoplanet scientists identified a set of ``community targets" which meet a certain set of criteria for ecliptic latitude, period, host star brightness, well constrained orbital parameters, and strength of spectroscopic features. WASP-63b was one of the targets identified as a potential candidate for the ERS program. It is presented as an inflated planet with a large signal. It will be accessible to JWST approximately six months after the planned start of Cycle 1/ERS in April 2019 making it an ideal candidate should there be any delays in the JWST timetable. Here, we observe WASP-63b to evaluate its suitability as the best target to test the capabilities of JWST. Ideally, a clear atmosphere will be best suited for bench marking the instruments ability to detect spectroscopic features. We can use the strength of the water absorption feature at 1.4 μm as a way to determine the presence of obscuring clouds/hazes. The results of atmospheric retrieval are presented along with a discussion on the suitability of WASP-63b as the best target to be observed during the ERS Program.

A spatial database for restoration management capability on national forests in the Pacific Northwest USA

Treesearch

Chris Ringo; Alan A. Ager; Michelle A. Day; Sarah Crim

2016-01-01

Understanding the capacity to reduce wildfire risk and restore dry forests on Western national forests is a key part of prioritizing new accelerated restoration programs initiated by the Forest Service. Although a number of social and biophysical factors influence the ability to implement restoration programs, one key driver is the suite of forest plan land...

Social factors and private benefits influence landholders' riverine restoration priorities in tropical Australia.

PubMed

Januchowski-Hartley, Stephanie Renee; Moon, Katie; Stoeckl, Natalie; Gray, Sally

2012-11-15

Private land conservation is an essential component of conservation that requires organizing both protection and restoration actions accordingly. Yet private land conservation programs are often formulated to generate public benefits, with inadequate consideration of costs or benefits to private landholders. Landholders' willingness to participate in conservation programs depends on a complex set of social factors, and the benefits they expect from participation. However, these two attributes are commonly evaluated independent of one another. We addressed this limitation through interviews aimed at determining landholders': 1) willingness to participate in restoration programs; 2) barriers to participation; 3) prioritization of proposed riverine restoration actions; 4) expected public or private benefits for undertaking proposed riverine restoration actions; and 5) most preferred incentive for undertaking proposed restoration actions on their land. Our results revealed four main findings. First, landholders stated that biases towards ecological rather than production outcomes, impractical programs, and government mistrust (structural factors) were the major barriers that prevented them from participating in riverine restoration on their land. Second, private benefits influenced landholders' willingness to engage riverine restoration. Third, 'a sense of stewardship and improved landscape aesthetics' (an internal factor) was the most commonly reported private benefit. Fourth, the most preferred incentives for high priority restoration actions were cash for on-ground works, extension and community recognition. We highlight the importance of designing private land conservation programs that align with landholders' priorities and deliver public benefits. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pilot James Barrilleaux with ER-2 aircraft on ramp

NASA Image and Video Library

1998-03-18

James Barrilleaux is the assistant chief pilot for ER-2s in the Flight Crew Branch of NASA's Dryden Flight Research Center, Edwards, California. The ER-2s--civilian variants of the military U-2S reconnaissance aircraft--are part of NASA's Airborne Science program. The ER-2s can carry airborne scientific payloads of up to 2,600 pounds to altitudes of about 70,000 feet to investigate such matters as earth resources, celestial phenomena, atmospheric chemistry and dynamics, and oceanic processes. Barrilleaux has held his current position since February 1998. Barrilleaux joined NASA in 1986 as a U-2/ER-2 pilot with NASA's Airborne Science program at Ames Research Center, Moffett Field, California. He flew both the U-2C (until 1989) and the ER-2 on a wide variety of missions both domestic and international. Barrilleaux flew high-altitude operations over Antarctica in which scientific instruments aboard the ER-2 defined the cause of ozone depletion over the continent, known as the ozone hole. He has also flown the ER-2 over the North Pole. Barrilleaux served for 20 years in the U.S. Air Force before he joined NASA. He completed pilot training at Reese Air Force Base, Lubbock, Texas, in 1966. He flew 120 combat missions as a F-4 fighter pilot over Laos and North Vietnam in 1970 and 1971. He joined the U-2 program in 1974, becoming the commander of an overseas U-2 operation in 1982. In 1983, he became commander of the squadron responsible for training all U-2 pilots and SR-71 crews located at Beale Air Force Base, Marysville, California. He retired from the Air Force as a lieutenant colonel in 1986. On active duty, he flew the U-2, F-4 Phantom, the T-38, T-37, and the T-33. His decorations included two Distinguished Flying Crosses, 12 Air Medals, two Meritorious Service Medals, and other Air Force and South Vietnamese awards. Barrilleaux earned a bachelor of science degree in chemical engineering from Texas A&M University, College Station, in 1964 and a master of science

Pilot James Barrilleaux with ER-2 aircraft on ramp

NASA Technical Reports Server (NTRS)

1998-01-01

James Barrilleaux is the assistant chief pilot for ER-2s in the Flight Crew Branch of NASA's Dryden Flight Research Center, Edwards, California. The ER-2s--civilian variants of the military U-2S reconnaissance aircraft--are part of NASA's Airborne Science program. The ER-2s can carry airborne scientific payloads of up to 2,600 pounds to altitudes of about 70,000 feet to investigate such matters as earth resources, celestial phenomena, atmospheric chemistry and dynamics, and oceanic processes. Barrilleaux has held his current position since February 1998. Barrilleaux joined NASA in 1986 as a U-2/ER-2 pilot with NASA's Airborne Science program at Ames Research Center, Moffett Field, California. He flew both the U-2C (until 1989) and the ER-2 on a wide variety of missions both domestic and international. Barrilleaux flew high-altitude operations over Antarctica in which scientific instruments aboard the ER-2 defined the cause of ozone depletion over the continent, known as the ozone hole. He has also flown the ER-2 over the North Pole. Barrilleaux served for 20 years in the U.S. Air Force before he joined NASA. He completed pilot training at Reese Air Force Base, Lubbock, Texas, in 1966. He flew 120 combat missions as a F-4 fighter pilot over Laos and North Vietnam in 1970 and 1971. He joined the U-2 program in 1974, becoming the commander of an overseas U-2 operation in 1982. In 1983, he became commander of the squadron responsible for training all U-2 pilots and SR-71 crews located at Beale Air Force Base, Marysville, California. He retired from the Air Force as a lieutenant colonel in 1986. On active duty, he flew the U-2, F-4 Phantom, the T-38, T-37, and the T-33. His decorations included two Distinguished Flying Crosses, 12 Air Medals, two Meritorious Service Medals, and other Air Force and South Vietnamese awards. Barrilleaux earned a bachelor of science degree in chemical engineering from Texas A&M University, College Station, in 1964 and a master of science degree in systems management from the University of Southern California in 1979. He has accumulated more than 5,800 hours of flying time over a period of 33 years and is currently the oldest active U-2/ER-2 pilot.

50 CFR 84.20 - What are the grant eligibility requirements?

Code of Federal Regulations, 2011 CFR

2011-10-01

... restoration, enhancement, or management of coastal wetlands ecosystems, providing restoration, enhancement, or... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM NATIONAL COASTAL WETLANDS CONSERVATION GRANT PROGRAM Applying for Grants § 84.20 What are the grant eligibility requirements...

78 FR 68825 - Strategic Environmental Research and Development Program, Scientific Advisory Board; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... (RC-2434)--FY14 Re-Brief, Dr. Jeffrey Foster, Northern Seed Dispersal Networks and Novel Arizona.... Sediments, and Biological Receptors. 1:25 p.m 14 ER03-025 (ER-2428)--FY14 New Start, Dr. Danny Reible, Texas...

Mediators of Mindfulness-Based Stress Reduction (MBSR): assessing the timing and sequence of change in cancer patients.

PubMed

Labelle, Laura E; Campbell, Tavis S; Faris, Peter; Carlson, Linda E

2015-01-01

This waitlist-controlled study examined the timing of changes during Mindfulness-Based Cancer Recovery (MBCR), and explored sequential mediated effects through enhanced mindfulness and emotion regulation (ER) in a cancer population. Patients were recruited from the MBCR program waitlist and were either registered for immediate participation (n = 135) or waiting for the next program to begin (n = 76). Participants completed self-report measures of stress symptoms, mood disturbance, mindfulness, and ER (rumination, worry, and experiential avoidance) pre-, mid- and post-MBCR or waiting period. There was a relatively early effect of MBCR on observing, nonjudging, rumination, and worry. All other measures changed later. Early changes in present-focused nonjudgmental awareness, rumination, and worry mediated the effect of MBCR on mindfulness skills such as nonreactivity later on. The constructs of mindfulness and ER may overlap and changes may be mutually facilitative during MBCR. The study informs our understanding of mindfulness and ER as mechanisms of mindfulness-based interventions. © 2014 Wiley Periodicals, Inc.

Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

PubMed Central

Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

2016-01-01

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

Metformin Restores Parkin-Mediated Mitophagy, Suppressed by Cytosolic p53

PubMed Central

Song, Young Mi; Lee, Woo Kyung; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Byung-Wan

2016-01-01

Metformin is known to alleviate hepatosteatosis by inducing 5’ adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy. Dysfunctional mitophagy in response to glucolipotoxicities might play an important role in hepatosteatosis. Here, we investigated the mechanism by which metformin induces mitophagy through restoration of the suppressed Parkin-mediated mitophagy. To this end, our ob/ob mice were divided into three groups: (1) ad libitum feeding of a standard chow diet; (2) intraperitoneal injections of metformin 300 mg/kg; and (3) 3 g/day caloric restriction (CR). HepG2 cells were treated with palmitate (PA) plus high glucose in the absence or presence of metformin. We detected enhanced mitophagy in ob/ob mice treated with metformin or CR, whereas mitochondrial spheroids were observed in mice fed ad libitum. Metabolically stressed ob/ob mice and PA-treated HepG2 cells showed an increase in expression of endoplasmic reticulum (ER) stress markers and cytosolic p53. Cytosolic p53 inhibited mitophagy by disturbing the mitochondrial translocation of Parkin, as demonstrated by immunoprecipitation. However, metformin decreased ER stress and p53 expression, resulting in induction of Parkin-mediated mitophagy. Furthermore, pifithrin-α, a specific inhibitor of p53, increased mitochondrial incorporation into autophagosomes. Taken together, these results indicate that metformin treatment facilitates Parkin-mediated mitophagy rather than mitochondrial spheroid formation by decreasing the inhibitory interaction with cytosolic p53 and increasing degradation of mitofusins. PMID:26784190

The Next Generation of Ground Operations Command and Control; Scripting in C no. and Visual Basic

NASA Technical Reports Server (NTRS)

Ritter, George; Pedoto, Ramon

2010-01-01

Scripting languages have become a common method for implementing command and control solutions in space ground operations. The Systems Test and Operations Language (STOL), the Huntsville Operations Support Center (HOSC) Scripting Language Processor (SLP), and the Spacecraft Control Language (SCL) offer script-commands that wrap tedious operations tasks into single calls. Since script-commands are interpreted, they also offer a certain amount of hands-on control that is highly valued in space ground operations. Although compiled programs seem to be unsuited for interactive user control and are more complex to develop, Marshall Space flight Center (MSFC) has developed a product called the Enhanced and Redesign Scripting (ERS) that makes use of the graphical and logical richness of a programming language while offering the hands-on and ease of control of a scripting language. ERS is currently used by the International Space Station (ISS) Payload Operations Integration Center (POIC) Cadre team members. ERS integrates spacecraft command mnemonics, telemetry measurements, and command and telemetry control procedures into a standard programming language, while making use of Microsoft's Visual Studio for developing Visual Basic (VB) or C# ground operations procedures. ERS also allows for script-style user control during procedure execution using a robust graphical user input and output feature. The availability of VB and C# programmers, and the richness of the languages and their development environment, has allowed ERS to lower our "script" development time and maintenance costs at the Marshall POIC.

Bird monitoring as an aid to riparian restoration: Findings from the Trinity River in northwestern California

Treesearch

C. Klamath Bird Observatory and USFS Pacific Southwest Research Station

2013-01-01

The Trinity River Restoration Program began in 2000 with the goal of restoring the Trinity River's salmon and steelhead fisheries, which were severely degraded during the last half-century as a result of dams, water diversions under the Central Valley Project, and land-use practices such as gold mining. The restoration program, as outlined in the U.S. Department...

Wide area restoration following biological contamination

NASA Astrophysics Data System (ADS)

Yang, Lynn; Hibbard, Wilthea; Edwards, Donna; Franco, David; Fruetel, Julie; Tucker, Mark; Einfeld, Wayne; Knowlton, Robert; Brown, Gary; Brockmann, John; Greenwalt, Robert; Miles, Robin; Raber, Ellen; Carlsen, Tina; Krauter, Paula; Dillon, Michael; MacQueen, Don; Intrepido, Tony; Hoppes, Bill; Wilson, Wendy; Mancieri, Sav

2008-04-01

Current understanding of how to restore a wide area that has been contaminated following a large biological attack is limited. The Department of Homeland Security and Department of Defense are executing a four-year collaborative program named the Interagency Biological Restoration Demonstration (IBRD) program. This program is aimed at developing technologies, methods, plans and policies necessary to restore a wide area, including military installations and critical infrastructures, in the event of a large outdoor aerosol release of anthrax. The IBRD program partner pilot city is the Seattle Urban Area to include Fort Lewis, WA and McChord Air Force Base. A front-end systems analysis was conducted as part of IBRD, to: 1) assess existing technologies and processes for wide area restoration; from this, 2) develop an "as-is" decision framework for wide area restoration; and 3) identify and prioritize capability gaps. Qualitative assessments and quantitative analyses, including sensitivity, timeline and case study analyses, were conducted to evaluate existing processes and rank capability gaps. This paper describes the approach and results from this front-end systems analysis.

The RESTORE program of restorative justice for sex crimes: vision, process, and outcomes.

PubMed

Koss, Mary P

2014-06-01

The article reports empirical evaluation of RESTORE, a restorative justice (RJ) conferencing program adapted to prosecutor-referred adult misdemeanor and felony sexual assaults. RESTORE conferences included voluntary enrollment, preparation, and a face-to-face meeting where primary and secondary victims voice impacts, and responsible persons acknowledge their acts and together develop a re-dress plan that is supervised for 1 year. Process data included referral and consent rates, participant characteristics, observational ratings of conferences compared with program design, services delivered, and safety monitoring. Outcome evaluation used 22 cases to assess (a) pre-post reasons for choosing RESTORE, (b) preparation and conference experiences, (c) overall program and justice satisfaction, and (d) completion rates. This is the first peer-reviewed quantitative evaluation of RJ conferencing for adult sexual assault. Although the data have limitations, the results support cautious optimism regarding feasibility, safety, and satisfactory outcomes. They help envision how conferencing could expand and individualize justice options for sexual assault.

How economics can further the success of ecological restoration.

PubMed

Iftekhar, Md Sayed; Polyakov, Maksym; Ansell, Dean; Gibson, Fiona; Kay, Geoffrey M

2017-04-01

Restoration scientists and practitioners have recently begun to include economic and social aspects in the design and investment decisions for restoration projects. With few exceptions, ecological restoration studies that include economics focus solely on evaluating costs of restoration projects. However, economic principles, tools, and instruments can be applied to a range of other factors that affect project success. We considered the relevance of applying economics to address 4 key challenges of ecological restoration: assessing social and economic benefits, estimating overall costs, project prioritization and selection, and long-term financing of restoration programs. We found it is uncommon to consider all types of benefits (such as nonmarket values) and costs (such as transaction costs) in restoration programs. Total benefit of a restoration project can be estimated using market prices and various nonmarket valuation techniques. Total cost of a project can be estimated using methods based on property or land-sale prices, such as hedonic pricing method and organizational surveys. Securing continuous (or long-term) funding is also vital to accomplishing restoration goals and can be achieved by establishing synergy with existing programs, public-private partnerships, and financing through taxation. © 2016 Society for Conservation Biology.

Talking Circles for Adolescent Girls in an Urban High School: A Restorative Practices Program for Building Friendships and Developing Emotional Literacy Skills

ERIC Educational Resources Information Center

Schumacher, Martha Ann

2012-01-01

Restorative Practices and Restorative Justice programs in schools are a new and emerging field. Meeting in Circles to build community, resolve conflict, and learn interactively are core components of these programs. This ethnographic study, which took place February 2010 to December 2011, evaluates 12 small, out-of-classroom Talking Circles for 60…

Survey of users of earth resources remote sensing data

NASA Technical Reports Server (NTRS)

Wukelic, G. E.; Stephan, J. G.; Smail, H. E.; Landis, L.; Ebbert, T. F.

1976-01-01

A user survey was conducted to determine current earth resources survey (ERS) data use/user status and recommendations for strengthening use. Only high-altitude aircraft and satellite (primarily LANDSAT) data were included. Emphasis was placed on the private sector/industrial user. Objectives of the survey included: who is using ERS data, how they are using the data, the relative value of current data use as well as obtaining user views as to possible ways of strengthening future ERS data use. The survey results are documented and should provide relevant decision making information for developing future programs of maximum benefit to all end users of satellite ERS data.

Interfaces in La2NiO4- La2CuO4 superlattices

NASA Astrophysics Data System (ADS)

Smadici, S.; Lee, J. C. T.; Wang, S.; Abbamonte, P.; Logvenov, G.; Gozar, A.; Bozovic, I.

2009-03-01

Ni substitution on Cu sites in underdoped La2-xSrxCuO4 quickly restores Neel order. This was attributed to strong interaction between the Ni and doped holes. An open question was whether the additional Ni empty orbital or the different spin on Ni sites was at the origin of this strong interaction. We have addressed this problem with resonant soft x-ray scattering on a La2NiO4- La2CuO4 heterostructure. La2NiO4 and La2CuO4 have close lattice structures and electronic configurations. However, the x-ray scattering contrast between superlattice layers is greatly enhanced at soft x-ray resonant energies. Based on our measurements at the O K, La M, Cu L and Ni L edges a model of the charge, orbital and spin structures in these superlattices will be presented with a special emphasis on the interface region. This work was supported by Grants. DE-FG02- 06ER46285, DE-AC02-98CH10886, MA-509-MACA, DE-FG02-07ER46453 and DE-FG02-07ER46471.

ER Consolidated Qtrly Rpt_July-September 2015_January 2016

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

Cochran, John R.

2016-01-01

This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) for the July, August, and September 2015 quarterly reporting period. The Solid Waste Management Units (SWMUs) and Areas of Concern (AOCs) identified for corrective action at SNL/NM are listed in Table I-1. The work completed during this quarter is reported below in Sections I.2.1 and I.2.2. Section I.2.1 summarizes the quarterly activities at sites undergoing corrective action field activities (SWMUs 8 and 58, 68, 149, 154, and 502, and three groundwater AOCs).more » Section I.2.2 summarizes quarterly activities at sites where the New Mexico Environment Department (NMED) has issued a certificate of completion and the site is in the corrective action complete (CAC) regulatory process. Currently, the Mixed Waste Landfill (MWL, SWMU 76) is the only site in the CAC regulatory process. Corrective action activities have been deferred at the Long Sled Track (SWMU 83), the Gun Facilities (SWMU 84), and the Short Sled Track (SWMU 240) because these are active mission facilities.« less

Multi-omics analysis reveals that ornithine decarboxylase contributes to erlotinib resistance in pancreatic cancer cells

PubMed Central

Song, Sang-Hoon; Lee, Naeun; Kim, Dong-Joon; Lee, Sooyeun; Jeong, Chul-Ho

2017-01-01

Molecular and metabolic alterations in cancer cells are one of the leading causes of acquired resistance to chemotherapeutics. In this study, we explored an experimental strategy to identify which of these alterations can induce erlotinib resistance in human pancreatic cancer. Using genetically matched erlotinib-sensitive (BxPC-3) and erlotinib-resistant (BxPC-3ER) pancreatic cancer cells, we conducted a multi-omics analysis of metabolomes and transcriptomes in these cells. Untargeted and targeted metabolomic analyses revealed significant changes in metabolic pathways involved in the regulation of polyamines, amino acids, and fatty acids. Further transcriptomic analysis identified that ornithine decarboxylase (ODC) and its major metabolite, putrescine, contribute to the acquisition of erlotinib resistance in BxPC-3ER cells. Notably, either pharmacological or genetic blockage of ODC was able to restore erlotinib sensitivity, and this could be rescued by treatment with exogenous putrescine in erlotinib-resistant BxPC-3ER cells. Moreover, using a panel of cancer cells we demonstrated that ODC expression levels in cancer cells are inversely correlated with sensitivity to chemotherapeutics. Taken together, our findings will begin to uncover mechanisms of acquired drug resistance and ultimately help to identify potential therapeutic markers in cancer. PMID:29190951

Flow Restoration in the Columbia River Basin: An Evaluation of a Flow Restoration Accounting Framework

NASA Astrophysics Data System (ADS)

McCoy, Amy L.; Holmes, S. Rankin; Boisjolie, Brett A.

2018-03-01

Securing environmental flows in support of freshwater biodiversity is an evolving field of practice. An example of a large-scale program dedicated to restoring environmental flows is the Columbia Basin Water Transactions Program in the Pacific Northwest region of North America, which has been restoring flows in dewatered tributary habitats for imperiled salmon species over the past decade. This paper discusses a four-tiered flow restoration accounting framework for tracking the implementation and impacts of water transactions as an effective tool for adaptive management. The flow restoration accounting framework provides compliance and flow accounting information to monitor transaction efficacy. We review the implementation of the flow restoration accounting framework monitoring framework to demonstrate (a) the extent of water transactions that have been implemented over the past decade, (b) the volumes of restored flow in meeting flow targets for restoring habitat for anadromous fish species, and (c) an example of aquatic habitat enhancement that resulted from Columbia Basin Water Transactions Program investments. Project results show that from 2002 to 2015, the Columbia Basin Water Transactions Program has completed more than 450 water rights transactions, restoring approximately 1.59 million megaliters to date, with an additional 10.98 million megaliters of flow protected for use over the next 100 years. This has resulted in the watering of over 2414 stream kilometers within the Columbia Basin. We conclude with a discussion of the insights gained through the implementation of the flow restoration accounting framework. Understanding the approach and efficacy of a monitoring framework applied across a large river basin can be informative to emerging flow-restoration and adaptive management efforts in areas of conservation concern.

Flow Restoration in the Columbia River Basin: An Evaluation of a Flow Restoration Accounting Framework.

PubMed

McCoy, Amy L; Holmes, S Rankin; Boisjolie, Brett A

2018-03-01

Securing environmental flows in support of freshwater biodiversity is an evolving field of practice. An example of a large-scale program dedicated to restoring environmental flows is the Columbia Basin Water Transactions Program in the Pacific Northwest region of North America, which has been restoring flows in dewatered tributary habitats for imperiled salmon species over the past decade. This paper discusses a four-tiered flow restoration accounting framework for tracking the implementation and impacts of water transactions as an effective tool for adaptive management. The flow restoration accounting framework provides compliance and flow accounting information to monitor transaction efficacy. We review the implementation of the flow restoration accounting framework monitoring framework to demonstrate (a) the extent of water transactions that have been implemented over the past decade, (b) the volumes of restored flow in meeting flow targets for restoring habitat for anadromous fish species, and (c) an example of aquatic habitat enhancement that resulted from Columbia Basin Water Transactions Program investments. Project results show that from 2002 to 2015, the Columbia Basin Water Transactions Program has completed more than 450 water rights transactions, restoring approximately 1.59 million megaliters to date, with an additional 10.98 million megaliters of flow protected for use over the next 100 years. This has resulted in the watering of over 2414 stream kilometers within the Columbia Basin. We conclude with a discussion of the insights gained through the implementation of the flow restoration accounting framework. Understanding the approach and efficacy of a monitoring framework applied across a large river basin can be informative to emerging flow-restoration and adaptive management efforts in areas of conservation concern.

Umatilla River Subbasin Fish Habitat Improvement Program, 2004-2005 Annual Report.

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

St. Hilaire, Danny R.

This annual report is in fulfillment of contractual obligations with Bonneville Power Administration (BPA), which is the funding source for the Oregon Department of Fish and Wildlife's (ODFW), Umatilla River Subbasin Fish Habitat Improvement Program (Program). The Program works cooperatively with private landowners to develop long-term restoration, under which, passive and active Habitat Improvement Projects are conducted. Historically, projects have included livestock exclusion fencing (passive restoration) to protect riparian habitats, along with the installation of instream structures (active restoration) to address erosion and improve fish habitat. In recent years, the focus of active restoration has shifted to bioengineering treatments and,more » more recently, to channel re-design and reconstruction aimed at improving fish habitat, by restoring stable channel function. This report provides a summary of Program activities for the 2004 calendar year (January 1 through December 31, 2004), within each of the four main project phases, including: (1) Implementation--Pre-Work, (2) Implementation--On Site Development, (3) Operation and Maintenance, and (4) Monitoring and Evaluation. This report also summarizes Program Administrative, Interagency Coordination, and Public Education activities.« less

EPA Awards Restore America's Estuaries with nearly $4 million to manage Southeast New England grant program

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency today announced a major grant to Restore America’s Estuaries under the Southeast New England Program (SNEP) of $3,945,172. With this grant, Restore America’s Estuaries will manage a competitive sub-award gr

7 CFR 623.4 - Eligible land.

Code of Federal Regulations, 2011 CFR

2011-01-01

... restored on the land under a CRP contract, or under a Federal or State wetland restoration program with an... AGRICULTURE WATER RESOURCES EMERGENCY WETLANDS RESERVE PROGRAM § 623.4 Eligible land. (a) Except as otherwise... condition and repairing related floodwater control systems; (3) Is likely to have its wetland value restored...

Immediate adhesive properties to dentin and enamel of a universal adhesive associated with a hydrophobic resin coat.

PubMed

Perdigão, J; Muñoz, M A; Sezinando, A; Luque-Martinez, I V; Staichak, R; Reis, A; Loguercio, A D

2014-01-01

To evaluate the effect of acid etching and application of a hydrophobic resin coat on the enamel/dentin bond strengths and degree of conversion (DC) within the hybrid layer of a universal adhesive system (G-Bond Plus [GB]). A total of 60 extracted third molars were divided into four groups for bond-strength testing, according to the adhesive strategy: GB applied as a one-step self-etch adhesive (1-stepSE); GB applied as in 1-stepSE followed by one coat of the hydrophobic resin Heliobond (2-stepSE); GB applied as a two-step etch-and-rinse adhesive (2-stepER); GB applied as in 2-stepER followed by one coat of the hydrophobic resin Heliobond (3-stepER). There were 40 teeth used for enamel microshear bond strength (μSBS) and DC; and 20 teeth used for dentin microtensile bond strength (μTBS) and DC. After restorations were constructed, specimens were stored in water (37°C/24 h) and then tested at 0.5 mm/min (μTBS) or 1.0 mm/min (μSBS). Enamel-resin and dentin-resin interfaces from each group were evaluated for DC using micro-Raman spectroscopy. Data were analyzed with two-way analysis of variance for each substrate and the Tukey test (α=0.05). For enamel, the use of a hydrophobic resin coat resulted in statistically significant higher mean enamel μSBS only for the ER strategy (3-stepER vs 2-stepER, p<0.0002). DC was significantly improved for the SE strategy (p<0.00002). For dentin, the use of a hydrophobic resin coat resulted in significantly higher dentin mean μTBS only for the SE strategy (2-stepSE vs 1-stepSE, p<0.0007). DC was significantly improved in groups 2-stepSE and 3-stepER when compared with 1-stepSE and 2-stepER, respectively (p<0.0009). The use of a hydrophobic resin coat may be beneficial for the selective enamel etching technique, because it improves bond strengths to enamel when applied with the ER strategy and to dentin when used with the SE adhesion strategy. The application of a hydrophobic resin coat may improve DC in resin-dentin interfaces formed with either the SE or the ER strategy. On enamel, DC may benefit from the application of a hydrophobic resin coat over 1-stepSE adhesives.

Drought offset ecological restoration program-induced increase in vegetation activity in the Beijing-Tianjin Sand Source Region, China.

PubMed

Wu, Zhitao; Wu, Jianjun; He, Bin; Liu, Jinghui; Wang, Qianfeng; Zhang, Hong; Liu, Yong

2014-10-21

To improve the ecological conditions, the Chinese government adopted six large-scale ecological restoration programs including 'Three-North Shelterbelt Project', "Grain for Green Project" and "Beijing-Tianjin Sand Source Control Project". Meanwhile, these ecologically vulnerable areas have experienced frequent droughts. However, little attention has been paid to the impact of drought on the effectiveness of these programs. Taking Beijing-Tianjin Sand Source Region (BTSSR) as study area, we investigated the role of droughts and ecological restoration program on trends of vegetation activities and to address the question of a possible "drought signal" in assessing effectiveness of ecological restoration program. The results demonstrate the following: (1) Vegetation activity increased in the BTSSR during 2000-2010, with 58.44% of the study area showing an increased NDVI, of which 11.80% had a significant increase at 0.95 confidential level. The decreasing NDVI trends were mainly concentrated in a southwest-to-northeast strip in the study area. (2) Drought was the main driving force for a decreasing trend of vegetation activity in the southwest-to-northeast regions of the BTSSR at the regional and spatial scales. Summer droughts in 2007 and 2009 contributed to the decreasing trend in NDVI. The severe and extreme droughts in summer reduced the NDVI by approximately 13.06% and 23.55%, respectively. (3) The residual analysis result showed that human activities, particularly the ecological restoration programs, have a positive impact on vegetation change. Hence, the decreasing trends in the southwest-to-northeast regions of the BTSSR cannot be explained by the improper ecological restoration program and is partly explained by droughts, especially summer droughts. Therefore, drought offset the ecological restoration program-induced increase in vegetation activity in the BTSSR.

Columbia Estuary Ecosystem Restoration Program: Restoration Design Challenges for Topographic Mounds, Channel Outlets, and Reed Canarygrass

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

Diefenderfer, Heida L.; Borde, Amy B.; Sinks, Ian A.

The purpose of this study was to provide science-based information to practitioners and managers of restoration projects in the Columbia Estuary Ecosystem Restoration Program (CEERP) regarding aspects of restoration techniques that currently pose known challenges and uncertainties. The CEERP is a program of the Bonneville Power Administration (BPA) and the U.S. Army Corps of Engineers (Corps), Portland District, in collaboration with the National Marine Fisheries Service and five estuary sponsors implementing restoration. The estuary sponsors are Columbia Land Trust, Columbia River Estuary Study Taskforce, Cowlitz Tribe, Lower Columbia Estuary Partnership, and Washington Department of Fish and Wildlife. The scope ofmore » the research conducted during federal fiscal year 2015 included three aspects of hydrologic reconnection that were selected based on available scientific information and feedback from restoration practitioners during project reviews: the design of mounds (also called hummocks, peninsulas, or berms); the control of reed canarygrass (Phalaris arundinaceae); and aspects of channel network design related to habitat connectivity for juvenile salmonids.« less

Shear Bond Strength of Self-etching Adhesives to Cavities Prepared by Diamond Bur or Er,Cr:YSGG Laser and Effect of Prior Acid Etching.

PubMed

Jhingan, Pulkit; Sachdev, Vinod; Sandhu, Meera; Sharma, Karan

2015-12-01

To compare and evaluate shear bond strength of self-etching adhesives bonded to cavities prepared by diamond bur or Er,Cr:YSGG laser and the effect of prior acid etching on shear bond strength. Ninety-six caries-free human premolars were selected and divided into 2 groups depending on mode of cavity preparation (48 teeth each). Cavities were prepared with Er,Cr:YSGG laser in group 1 and diamond burs in an air-turbine handpiece in group 2. Groups 1 and 2 were further subdivided into three subgroups of 8 teeth each, which were bonded with sixth- or seventh-generation adhesives with or without prior acid etching, followed by restoration of all samples with APX Flow. These samples were subjected to shear bond strength testing. In addition, the surface morphology of 24 samples each from groups 1 and 2 was evaluated using SEM. Data were analyzed using the Shapiro-Wilk test, one- and two-way ANOVA, the t-test, and the least significant difference test, which showed that the data were normally distributed (p > 0.05). The shear bond strength of adhesives in cavities prepared by Er,Cr:YSGG laser was significantly higher than in diamond bur-prepared cavities (p < 0.05). SEM analysis showed a smear-layer-free anfractuous surface on laser-ablated teeth, in contrast to conventional bur-prepared teeth. The Er,Cr:YSGG laser-ablated surface proved to be more receptive for adhesion than those prepared by diamond bur irrespective of the bonding agent used. Seventh-generation adhesives yielded higher shear bond strength than did sixth-generation adhesives. Prior acid etching decreased the shear bond strength of self-etching adhesives.

Intermittent injections of osteocalcin reverse autophagic dysfunction and endoplasmic reticulum stress resulting from diet-induced obesity in the vascular tissue via the NFκB-p65-dependent mechanism.

PubMed

Zhou, Bo; Li, Huixia; Liu, Jiali; Xu, Lin; Zang, Weijin; Wu, Shufang; Sun, Hongzhi

2013-06-15

The osteoblast-specific secreted molecule osteocalcin behaves as a hormone-regulating glucose and lipid metabolism, but the role of osteocalcin in cardiovascular disease (CVD) is not fully understood. In the present study, we investigated the effect of osteocalcin on autophagy and endoplasmic reticulum (ER) stress secondary to diet-induced obesity in the vascular tissue of mice and in vascular cell models and clarified the intracellular events responsible for osteocalcin-mediated effects. The evidences showed that intermittent injections of osteocalcin in mice fed the high-fat diet were associated with a reduced body weight gain, decreased blood glucose and improved insulin sensitivity compared with mice fed the high-fat diet receiving vehicle. Simultaneously, the administration of osteocalcin not only attenuated autophagy and ER stress but also rescued impaired insulin signaling in vascular tissues of mice fed a high-fat diet. Consistent with these results in vivo, the addition of osteocalcin reversed autophagy and ER stress and restored defective insulin sensitivity in vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in the presence of tunicamycin or in knockout XBP-1 (a transcription factor which mediates ER stress response) cells or in Atg7(-/-) cells. The protective effects of osteocalcin were nullified by suppression of Akt, mammalian target of rapamycin (mTOR) or nuclear factor kappa B (NFκB), suggesting that osteocalcin inhibits autophagy, ER stress and improves insulin signaling in the vascular tissue and cells under insulin resistance in a NFκB-dependent manner, which may be a promising therapeutic strategies of cardiovascular dysfunction secondary to obesity.

Effect of Various Laser Surface Treatments on Repair Shear Bond Strength of Aged Silorane-Based Composite

PubMed Central

Alizadeh Oskoee, Parnian; Savadi Oskoee, Siavash; Rikhtegaran, Sahand; Pournaghi-Azar, Fatemeh; Gholizadeh, Sarah; Aleyasin, Yasaman; Kasrae, Shahin

2017-01-01

Introduction: Successful repair of composite restorations depends on a strong bond between the old composite and the repair composite. This study sought to assess the repair shear bond strength of aged silorane-based composite following surface treatment with Nd:YAG, Er,Cr:YSGG and CO2 lasers. Methods: Seventy-six Filtek silorane composite cylinders were fabricated and aged by 2 months of water storage at 37°C. The samples were randomly divided into 4 groups (n=19) of no surface treatment (group 1) and surface treatment with Er,Cr:YSGG (group 2), Nd:YAG (group 3) and CO2 (group 4) lasers. The repair composite was applied and the shear bond strength was measured. The data were analyzed using one-way analysis of variance (ANOVA) and Tukey posthoc test. Prior to the application of the repair composite, 2 samples were randomly selected from each group and topographic changes on their surfaces following laser irradiation were studied using a scanning electron microscope (SEM). Seventeen other samples were also fabricated for assessment of cohesive strength of composite. Results: The highest and the lowest mean bond strength values were 8.99 MPa and 6.69 MPa for Er,Cr:YSGG and control groups, respectively. The difference in the repair bond strength was statistically significant between the Er,Cr:YSGG and other groups. Bond strength of the control, Nd:YAG and CO2 groups was not significantly different. The SEM micrographs revealed variable degrees of ablation and surface roughness in laser-treated groups. Conclusion: Surface treatment with Er,Cr:YSGG laser significantly increase the repair bond strength of aged silorane-based composite resin. PMID:29071025

Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress.

PubMed

Kim, Da Hye; Kim, Soochan; Lee, Jin Ha; Kim, Jae Hyeon; Che, Xiumei; Ma, Hyun Woo; Seo, Dong Hyuk; Kim, Tae Il; Kim, Won Ho; Kim, Seung Won; Cheon, Jae Hee

2018-06-22

Nuclear factor kappa B (NF-κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we evaluated whether new therapeutic probiotics have anti-colitic effects and we investigated their mechanisms related to NF-κB and ER-stress pathways. Luciferase, nitric oxide (NO), and cytokine assays using HT-29 or RAW264.7 cells were conducted. Mouse colitis was induced using dextran sulfate sodium (DSS) and confirmed by disease activity index and histology. Macrophages and T-cell subsets in isolated peritoneal cavity cells (PCCs) and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using RT-PCR. Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited NO production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the life span of DSS-treated mice and attenuated the severity of colitis by inducing M2 macrophages in PCCs and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of proinflammatory cytokines. Additionally, we found that LA1 exerts an anti-colitic effect by improving ER stress in HT-29 cells as well as in vivo. We showed that LA1 significantly interferes with ER stress and suppresses NF-κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment and the regulation of ER stress may have significant implications in treating IBD. This article is protected by copyright. All rights reserved.

Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

PubMed

Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

2016-05-23

The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms regulating food consumption through loss of anorexigenic endocrine signaling. The correlative therapeutic paradigm suggests that, in the context of hormone insufficiency with preservation of receptor sensitivity, obesity may be prevented or treated by GUCY2C hormone replacement.

Immediate bonding properties of universal adhesives to dentine.

PubMed

Muñoz, Miguel Angel; Luque, Issis; Hass, Viviane; Reis, Alessandra; Loguercio, Alessandro Dourado; Bombarda, Nara Hellen Campanha

2013-05-01

To evaluate the dentine microtensile bond strength (μTBS), nanoleakage (NL), degree of conversion (DC) within the hybrid layer for etch-and-rinse and self-etch strategies of universal simplified adhesive systems. forty caries free extracted third molars were divided into 8 groups for μTBS (n=5), according to the adhesive and etching strategy: Clearfil SE Bond [CSE] and Adper Single Bond 2 [SB], as controls; Peak Universal Adhesive System, self-etch [PkSe] and etch-and-rinse [PkEr]; Scotchbond Universal Adhesive, self-etch [ScSe] and etch-and-rinse [ScEr]; All Bond Universal, self-etch [AlSe] and etch-and-rinse [AlEr]. After restorations were constructed, specimens were stored in water (37°C/24h) and then resin-dentine sticks were prepared (0.8mm(2)). The sticks were tested under tension at 0.5mm/min. Some sticks from each tooth group were used for DC determination by micro-Raman spectroscopy or nanoleakage evaluation (NL). The pH for each solution was evaluated using a pH metre. Data were analyzed with one-way ANOVA and Tukey's test (α=0.05). For μTBS, only PkSe and PkEr were similar to the respective control groups (p>0.05). AlSe showed the lowest μTBS mean (p<0.05). For NL, ScEr, ScSe, AlSe, and AlEr showed the lowest NL similar to control groups (p<0.05). For DC, only ScSe showed lower DC than the other materials (p<0.05). Performance of universal adhesives was shown to be material-dependent. The results indicate that this new category of universal adhesives used on dentine as either etch-and-rinse or self-etch strategies were inferior as regards at least one of the properties evaluated (μTBS, NL and DC) in comparison with the control adhesives (CSE for self-etch and SB for etch-and-rinse). Copyright © 2013 Elsevier Ltd. All rights reserved.

In vitro longevity of bonding properties of universal adhesives to dentin.

PubMed

Muñoz, M A; Luque-Martinez, I; Malaquias, P; Hass, V; Reis, A; Campanha, N H; Loguercio, A D

2015-01-01

To evaluate the immediate and 6-month resin-dentin bond strength (μTBS) and nanoleakage (NL) of universal adhesives that contain or do not contain methacryloyloxydecyl dihydrogen phosphate (MDP) and are used in the etch-and-rinse and self-etch strategies. Forty caries-free extracted third molars were divided into eight groups for μTBS (n=5). The groups were bonded with the Clearfil SE Bond (CSE) and Adper Single Bond 2 (SB) as controls; Peak Universal, self-etch (PkSe) and etch-and rinse (PkEr); Scotchbond Universal Adhesive, self-etch (ScSe) and etch-and-rinse (ScEr); and All Bond Universal, self-etch (AlSe) and etch-and-rinse (AlEr). After composite restorations, specimens were longitudinally sectioned to obtain resin-dentin bonded sticks (0.8 mm(2)). The μTBS of the specimens was tested immediately (IM) or after 6 months of water storage (6M) at 0.5 mm/min. Some sticks at each storage period were immersed in silver nitrate and photo developed, and the NL was evaluated with scanning electron microscopy. Data were analyzed with two-way repeated-measures analysis of variance and Tukey test (α=0.05). At the IM period, PkSe and PkEr showed μTBS similar to the control adhesives (p>0.05) but increased NL pattern and lower μTBS after 6M (p<0.05). ScSe and ScEr showed intermediary μTBS values at the IM period but remained stable after 6 months (p>0.05). AlSe showed the lowest μTBS (p<0.05), but μTBS and NL remained stable after 6M (p>0.05). AlEr showed higher IM μTBS but showed higher degradation after 6M (p<0.05). Universal adhesives that contain MDP showed higher and more stable μTBS with reduced NL at the interfaces after 6 months of water storage.

Pancreatic and Duodenal Homeobox Protein 1 (Pdx-1) Maintains Endoplasmic Reticulum Calcium Levels through Transcriptional Regulation of Sarco-endoplasmic Reticulum Calcium ATPase 2b (SERCA2b) in the Islet β Cell*

PubMed Central

Johnson, Justin S.; Kono, Tatsuyoshi; Tong, Xin; Yamamoto, Wataru R.; Zarain-Herzberg, Angel; Merrins, Matthew J.; Satin, Leslie S.; Gilon, Patrick; Evans-Molina, Carmella

2014-01-01

Although the pancreatic duodenal homeobox 1 (Pdx-1) transcription factor is known to play an indispensable role in β cell development and secretory function, recent data also implicate Pdx-1 in the maintenance of endoplasmic reticulum (ER) health. The sarco-endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) pump maintains a steep Ca2+ gradient between the cytosol and ER lumen. In models of diabetes, our data demonstrated loss of β cell Pdx-1 that occurs in parallel with altered SERCA2b expression, whereas in silico analysis of the SERCA2b promoter revealed multiple putative Pdx-1 binding sites. We hypothesized that Pdx-1 loss under inflammatory and diabetic conditions leads to decreased SERCA2b levels and activity with concomitant alterations in ER health. To test this, siRNA-mediated knockdown of Pdx-1 was performed in INS-1 cells. The results revealed reduced SERCA2b expression and decreased ER Ca2+, which was measured using fluorescence lifetime imaging microscopy. Cotransfection of human Pdx-1 with a reporter fused to the human SERCA2 promoter increased luciferase activity 3- to 4-fold relative to an empty vector control, and direct binding of Pdx-1 to the proximal SERCA2 promoter was confirmed by chromatin immunoprecipitation. To determine whether restoration of SERCA2b could rescue ER stress induced by Pdx-1 loss, Pdx1+/− mice were fed a high-fat diet. Isolated islets demonstrated an increased spliced-to-total Xbp1 ratio, whereas SERCA2b overexpression reduced the Xbp1 ratio to that of wild-type controls. Together, these results identify SERCA2b as a novel transcriptional target of Pdx-1 and define a role for altered ER Ca2+ regulation in Pdx-1-deficient states. PMID:25271154

Resveratrol prevents doxorubicin-induced cardiotoxicity in H9c2 cells through the inhibition of endoplasmic reticulum stress and the activation of the Sirt1 pathway.

PubMed

Lou, Yu; Wang, Zhen; Xu, Yi; Zhou, Ping; Cao, Junxian; Li, Yuanshi; Chen, Yeping; Sun, Junfeng; Fu, Lu

2015-09-01

Treatment with doxorubicin (DOX) is one of the major causes of chemotherapy-induced cardiotoxicity and is therefore, the principal limiting factor in the effectiveness of chemotherapy for cancer patients. DOX‑induced heart failure is thought to result from endoplasmic reticulum (ER) stress and cardiomyocyte apoptosis. Resveratrol (RV), a polyphenol antioxidant found in red wine, has been shown to play a cardioprotective role. The aim of the present study was to examine the effects of RV on DOX‑induced cardiotoxicity in H9c2 cells. We hypothesized that RV would protect H9c2 cells against DOX‑induced ER stress and subsequent cell death through the activation of the Sirt1 pathway. Our results demonstrated that the decrease observed in the viability of the H9c2 cells following exposure to DOX was accompanied by a significant increase in the expression of the ER stress‑related proteins, glucose‑regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). However, we found that RV downregulated the expression of ER stress marker protein in the presence of DOX and restored the viability of the H9c2 cells. Exposure to RV or DOX alone only slightly increased the protein expression of Sirt1, whereas a significant increase in Sirt1 protein levels was observed in the cells treated with both RV and DOX. The Sirt1 inhibitor, nicotinamide (NIC), partially neutralized the effects of RV on the expression of Sirt1 in the DOX‑treated cells and completely abolished the effects of RV on the expression of GRP78 and CHOP. The findings of our study suggest that RV protects H9c2 cells against DOX‑induced ER stress through ER stabilization, and more specifically through the activation of the Sirt1 pathway, thereby leading to cardiac cell survival.

50 CFR 86.91 - What are my program crediting responsibilities?

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.91 What are my program crediting responsibilities? You should give public credit to the Federal Aid in Sport Fish...

50 CFR 86.91 - What are my program crediting responsibilities?

Code of Federal Regulations, 2011 CFR

2011-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.91 What are my program crediting responsibilities? You should give public credit to the Federal Aid in Sport Fish...

50 CFR 86.91 - What are my program crediting responsibilities?

Code of Federal Regulations, 2010 CFR

2010-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.91 What are my program crediting responsibilities? You should give public credit to the Federal Aid in Sport Fish...

Inflammation Fuels Tumor Progress and Metastasis

PubMed Central

Liu, Jingyi; Lin, Pengnian Charles; Zhou, Binhua P.

2017-01-01

Inflammation is a beneficial response that can remove pathogens, repair injured tissue and restore homeostasis to damaged tissues and organs. However, increasing evidence indicate that chronic inflammation plays a pivotal role in tumor development, as well as progression, metastasis, and resistance to chemotherapy. We will review the current knowledge regarding the contribution of inflammation to epithelial mesenchymal transition. We will also provide some perspectives on the relationship between ER-stress signals and metabolism, and the role of these processes in the development of inflammation. PMID:26004407

Idaho National Engineering Laboratory Waste Management Operations Roadmap Document

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

Bullock, M.

1992-04-01

At the direction of the Department of Energy-Headquarters (DOE-HQ), the DOE Idaho Field Office (DOE-ID) is developing roadmaps for Environmental Restoration and Waste Management (ER&WM) activities at Idaho National Engineering Laboratory (INEL). DOE-ID has convened a select group of contractor personnel from EG&G Idaho, Inc. to assist DOE-ID personnel with the roadmapping project. This document is a report on the initial stages of the first phase of the INEL`s roadmapping efforts.

7 CFR 625.4 - Program requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... activities that promote the restoration, protection, enhancement, maintenance, and management of forest... of successful restoration, enhancement, and protection of forest ecosystem functions and values when... AGRICULTURE WATER RESOURCES HEALTHY FORESTS RESERVE PROGRAM § 625.4 Program requirements. (a) General. Under...

Improving strength and postural control in young skiers: whole-body vibration versus equivalent resistance training.

PubMed

Mahieu, Nele N; Witvrouw, Erik; Van de Voorde, Danny; Michilsens, Diny; Arbyn, Valérie; Van den Broecke, Wouter

2006-01-01

Several groups have undertaken studies to evaluate the physiologic effects of whole-body vibration (WBV). However, the value of WBV in a training program remains unknown. To investigate whether a WBV program results in a better strength and postural control performance than an equivalent exercise program performed without vibration. Randomized, controlled trial. Laboratory. Thirty-three Belgian competitive skiers (ages = 9-15 years). Subjects were assigned to either the WBV group or the equivalent resistance (ER) group for 6 weeks of training at 3 times per week. Isokinetic plantar and dorsiflexion peak torque, isokinetic knee flexion and extension peak torque, explosive strength (high box test), and postural control were assessed before and after the training period. Both training programs significantly improved isokinetic ankle and knee muscle strength and explosive strength. Moreover, the increases in explosive strength and in plantar-flexor strength at low speed were significantly higher in the WBV group than in the ER group after 6 weeks. However, neither WBV training nor ER training seemed to have an effect on postural control. A strength training program that includes WBV appears to have additive effects in young skiers compared with an equivalent program that does not include WBV. Therefore, our findings support the hypothesis that WBV training may be a beneficial supplementary training technique in strength programs for young athletes.

Restoration of physical performance capacity of athletes after prolonged restriction of their motor activity

NASA Technical Reports Server (NTRS)

Soldatov, A. D.; Finogeyev, V. I.

1980-01-01

The effects of different regimens of treatment following prolonged hypokinesia were studied in order to determine the most effective program. The types of programs considered were passive means, consisting of physical therapy; active means, consisting of athletic training; and a combined program. In the first stage of the experiment, the effects of a 10 day period of hypokinesia were studied. It was determined that the restoration programs must address the problems of: (1) increasing defense function and general tone of the body; (2) restore orthostatic stability; and (3) increase general endurance. In later stages, groups of athletes and nonathletes underwent 30 day periods of hypokinesia. Restoration was carefully monitored for groups treated with the various regimens. It was determined that the most effective treatment was a comprehensive program of passive and active therapy.

Motivation and Outcomes for University Students in a Restorative Justice Program

ERIC Educational Resources Information Center

Gallagher Dahl, Meghan; Meagher, Peter; Vander Velde, Stacy

2014-01-01

A restorative justice program (RJP) was developed at a large university in the housing student conduct office. Students accused of misconduct who participated in a restorative justice (RJ) conference completed surveys regarding their motivations and perceived outcomes. Results showed that students who were motivated to make reparations to others…

Guanine nucleotide dissociation inhibitor is essential for Rab1 function in budding from the endoplasmic reticulum and transport through the Golgi stack

PubMed Central

1994-01-01

The small GTPase Rab1 is required for vesicular traffic from the ER to the cis-Golgi compartment, and for transport between the cis and medial compartments of the Golgi stack. In the present study, we examine the role of guanine nucleotide dissociation inhibitor (GDI) in regulating the function of Rab1 in the transport of vesicular stomatitis virus glycoprotein (VSV-G) in vitro. Incubation in the presence of excess GDI rapidly (t1/2 < 30 s) extracted Rab1 from membranes, inhibiting vesicle budding from the ER and sequential transport between the cis-, medial-, and trans-Golgi cisternae. These results demonstrate a direct role for GDI in the recycling of Rab proteins. Analysis of rat liver cytosol by gel filtration revealed that a major pool of Rab1 fractionates with a molecular mass of approximately 80 kD in the form of a GDI-Rab1 complex. When the GDI-Rab1 complex was depleted from cytosol by use of a Rab1-specific antibody, VSV-G failed to exit the ER. However, supplementation of depleted cytosol with a GDI-Rab1 complex prepared in vitro from recombinant forms of Rab1 and GDI efficiently restored export from the ER, and transport through the Golgi stack. These results provide evidence that a cytosolic GDI-Rab1 complex is required for the formation of non-clathrin-coated vesicles mediating transport through the secretory pathway. PMID:8089173

MEL-18 loss mediates estrogen receptor–α downregulation and hormone independence

PubMed Central

Lee, Jeong-Yeon; Won, Hee-Young; Park, Ji-Hye; Kim, Hye-Yeon; Choi, Hee-Joo; Shin, Dong-Hui; Kang, Ju-Hee; Woo, Jong-Kyu; Oh, Seung-Hyun; Son, Taekwon; Choi, Jin-Woo; Kim, Sehwan; Kim, Hyung-Yong; Yi, Kijong; Jang, Ki-Seok; Oh, Young-Ha; Kong, Gu

2015-01-01

The polycomb protein MEL-18 has been proposed as a tumor suppressor in breast cancer; however, its functional relevance to the hormonal regulation of breast cancer remains unknown. Here, we demonstrated that MEL-18 loss contributes to the hormone-independent phenotype of breast cancer by modulating hormone receptor expression. In multiple breast cancer cohorts, MEL-18 was markedly downregulated in triple-negative breast cancer (TNBC). MEL-18 expression positively correlated with the expression of luminal markers, including estrogen receptor–α (ER-α, encoded by ESR1). MEL-18 loss was also associated with poor response to antihormonal therapy in ER-α–positive breast cancer. Furthermore, whereas MEL-18 loss in luminal breast cancer cells resulted in the downregulation of expression and activity of ER-α and the progesterone receptor (PR), MEL-18 overexpression restored ER-α expression in TNBC. Consistently, in vivo xenograft experiments demonstrated that MEL-18 loss induces estrogen-independent growth and tamoxifen resistance in luminal breast cancer, and that MEL-18 overexpression confers tamoxifen sensitivity in TNBC. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1, thereby driving ESR1 transcription. MEL-18 facilitated the deSUMOylation process by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). These findings demonstrate that MEL-18 is a SUMO-dependent regulator of hormone receptors and suggest MEL-18 expression as a marker for determining the antihormonal therapy response in patients with breast cancer. PMID:25822021

50 CFR 86.91 - What are my program crediting responsibilities?

Code of Federal Regulations, 2014 CFR

2014-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.91 What are my program crediting responsibilities? You should give public credit to the Federal Aid in Sport Fish...

50 CFR 86.91 - What are my program crediting responsibilities?

Code of Federal Regulations, 2013 CFR

2013-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.91 What are my program crediting responsibilities? You should give public credit to the Federal Aid in Sport Fish...

Liganded and unliganded activation of estrogen receptor and hormone replacement therapies

PubMed Central

Maggi, Adriana

2011-01-01

Over the past two decades, our understanding of estrogen receptor physiology in mammals widened considerably as we acquired a deeper appreciation of the roles of estrogen receptor alpha and beta (ERα and ERβ) in reproduction as well as in bone and metabolic homeostasis, depression, vascular disorders, neurodegenerative diseases and cancer. In addition, our insights on ER transcriptional functions in cells increased considerably with the demonstration that ER activity is not strictly dependent on ligand availability. Indeed, unliganded ERs may be transcriptionally active and post-translational modifications play a major role in this context. The finding that several intracellular transduction molecules may regulate ER transcriptional programs indicates that ERs may act as a hub where several molecular pathways converge: this allows to maintain ER transcriptional activity in tune with all cell functions. Likely, the biological relevant role of ER was favored by evolution as a mean of integration between reproductive and metabolic functions. We here review the post-translational modifications modulating ER transcriptional activity in the presence or in the absence of estrogens and underline their potential role for ER tissue-specific activities. In our opinion, a better comprehension of the variety of molecular events that control ER activity in reproductive and non-reproductive organs is the foundation for the design of safer and more efficacious hormone-based therapies, particularly for menopause. PMID:21605666

Generation of signaling specificity in Arabidopsis by spatially restricted buffering of ligand-receptor interactions.

PubMed

Abrash, Emily B; Davies, Kelli A; Bergmann, Dominique C

2011-08-01

Core signaling pathways function in multiple programs during multicellular development. The mechanisms that compartmentalize pathway function or confer process specificity, however, remain largely unknown. In Arabidopsis thaliana, ERECTA (ER) family receptors have major roles in many growth and cell fate decisions. The ER family acts with receptor TOO MANY MOUTHS (TMM) and several ligands of the EPIDERMAL PATTERNING FACTOR LIKE (EPFL) family, which play distinct yet overlapping roles in patterning of epidermal stomata. Here, our examination of EPFL genes EPFL6/CHALLAH (CHAL), EPFL5/CHALLAH-LIKE1, and EPFL4/CHALLAH-LIKE2 (CLL2) reveals that this family may mediate additional ER-dependent processes. chal cll2 mutants display growth phenotypes characteristic of er mutants, and genetic interactions are consistent with CHAL family molecules acting as ER family ligands. We propose that different classes of EPFL genes regulate different aspects of ER family function and introduce a TMM-based discriminatory mechanism that permits simultaneous, yet compartmentalized and distinct, function of the ER family receptors in growth and epidermal patterning.

Effectiveness of a lifestyle exercise program for older people receiving a restorative home care service: a pragmatic randomized controlled trial.

PubMed

Burton, Elissa; Lewin, Gill; Clemson, Lindy; Boldy, Duncan

2013-01-01

Restorative home care services are short-term and aimed at maximizing a person's ability to live independently. They are multidimensional and often include an exercise program to improve strength, mobility, and balance. The aim of this study was to determine whether a lifestyle exercise program would be undertaken more often and result in greater functional gains than the current structured exercise program delivered as part of a restorative home care service for older adults. A pragmatic randomized controlled trial was conducted in an organization with an established restorative home care service. Individuals who were to have an exercise program as part of their service were randomized to receive either a lifestyle and functional exercise program called LiFE (as this was a new program, the intervention) or the structured exercise program currently being used in the service (control). Exercise data collected by the individuals throughout and pre and post intervention testing was used to measure balance, strength, mobility, falls efficacy, vitality, function, and disability. There was no difference between the groups in the amounts of exercise undertaken during the 8-week intervention period. Outcome measurement indicated that the LiFE program was as effective, and on 40% of the measures, more effective, than the structured exercise program. Organizations delivering restorative home care services that include an exercise component should consider whether LiFE rather than the exercise program they are currently using could help their clients achieve better outcomes.

Surface debris inventory at White Wing Scrap Yard, Oak Ridge Reservation, Oak Ridge, Tennessee

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

Rodriguez, R.E.; Tiner, P.F.; Williams, J.K.

1992-08-01

An inventory of surface debris in designated grid blocks at the White Wing Scrap Yard [Waste Area Grouping 11 (WAG 11)] was conducted intermittently from February through June 1992 by members of the Measurement Applications and Development Group, Health and Safety Research Division, Oak Ridge National Laboratory (ORNL) at the request of ORNL Environmental Restoration (ER) Program personnel. The objectives of this project are outlined in the following four phases: (1) estimate the amount (volume) and type (e.g., glass, metal and plastics) of surface waste material in 30 designated grid blocks (100- by 100-ft grids); (2) conduct limited air samplingmore » for organic chemical pollutants at selected locations (e.g., near drums, in holes, or other potentially contaminated areas); (3) conduct a walkover gamma radiation scan extending outward (approximately 50 ft) beyond the proposed location of the WAG 11 perimeter fence; and (4) recommend one grid block as a waste staging area. This recommendation is based on location and accessibility for debris staging/transport activities and on low levels of gamma radiation in the grid block.« less

1996 Site environmental report Sandia National Laboratories Albuquerque, New Mexico

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

Fink, C.H.; Duncan, D.; Sanchez, R.

1997-08-01

Sandia National Laboratories/New Mexico (SNL/NM) is operated in support of the U.S. Department of Energy (DOE) mission to provide weapon component technology and hardware for national security needs, and to conduct fundamental research and development (R&D) to advance technology in energy research, computer science, waste management, electronics, materials science, and transportation safety for hazardous and nuclear components. In support of this mission, the Environmental Safety and Health (ES&H) Center at SNL/NM conducts extensive environmental monitoring, surveillance, and compliance activities to assist SNL`s line organizations in meeting all applicable environmental regulations applicable to the site including those regulating radiological and nonradiologicalmore » effluents and emissions. Also herein are included, the status of environmental programs that direct and manage activities such as terrestrial surveillance; ambient air and meteorological monitoring; hazardous, radioactive, and solid waste management; pollution prevention and waste minimization; environmental restoration (ER); oil and chemical spill prevention; and National Environmental Policy Act (NEPA) documentation. This report has been prepared in compliance with DOE order 5400.1, General Environmental Protection.« less

Cost-benefit analysis of childhood asthma management through school-based clinic programs.

PubMed

Tai, Teresa; Bame, Sherry I

2011-04-01

Asthma is a leading chronic illness among American children. School-based health clinics (SBHCs) reduced expensive ER visits and hospitalizations through better healthcare access and monitoring in select case studies. The purpose of this study was to examine the cost-benefit of SBHC programs in managing childhood asthma nationwide for reduction in medical costs of ER, hospital and outpatient physician care and savings in opportunity social costs of lowing absenteeism and work loss and of future earnings due to premature deaths. Eight public data sources were used to compare costs of delivering primary and preventive care for childhood asthma in the US via SBHC programs, including direct medical and indirect opportunity costs for children and their parents. The costs of nurse staffing for a nationwide SBHC program were estimated at $4.55 billion compared to the estimated medical savings of $1.69 billion, including ER, hospital, and outpatient care. In contrast, estimated total savings for opportunity costs of work loss and premature death were $23.13 billion. Medical savings alone would not offset the expense of implementing a SBHC program for prevention and monitoring childhood asthma. However, even modest estimates of reducing opportunity costs of parents' work loss would be far greater than the expense of this program. Although SBHC programs would not be expected to affect the increasing prevalence of childhood asthma, these programs would be designed to reduce the severity of asthma condition with ongoing monitoring, disease prevention and patient compliance.

Plant ERD2-like proteins function as endoplasmic reticulum luminal protein receptors and participate in programmed cell death during innate immunity.

PubMed

Xu, Guoyong; Li, Sizhun; Xie, Ke; Zhang, Qiang; Wang, Yan; Tang, Yang; Liu, Dong; Hong, Yiguo; He, Chenyang; Liu, Yule

2012-10-01

The hypersensitive response (HR), a form of programmed cell death (PCD), is a tightly regulated innate immune response in plants that is hypothesized to restrict pathogen growth and disease development. Although considerable efforts have been made to understand HR PCD, it remains unknown whether the retrograde pathway from the Golgi to the endoplasmic reticulum (ER) is involved. Here we provide direct genetic evidence that two Nicotiana benthamiana homologs, ERD2a and ERD2b, function as ER luminal protein receptors and participate in HR PCD. Virus-induced gene silencing (VIGS) of ERD2a and/or ERD2b caused escape of ER-resident proteins from the ER, and resulted in plants that were more sensitive to ER stress. Silencing of ERD2b delayed HR PCD induced by the non-host pathogens Xanthomonas oryzae pv. oryzae and Pseudomonas syringae pv. tomato DC3000. However, both silencing of ERD2a and co-silencing of ERD2a and ERD2b exacerbated HR PCD. Individual and combined suppression of ERD2a and ERD2b exaggerated R gene-mediated cell death. Nevertheless, silencing of ERD2a and/or ERD2b had no detectable effects on bacterial growth. Furthermore, VIGS of several putative ligands of ERD2a/2b, including the ER quality control (ERQC) component genes BiP, CRT3 and UGGT, had different effects on HR PCD induced by different pathogens. This indicates that immunity-related cell death pathways are separate with respect to the genetic requirements for these ERQC components. These results suggest that ERD2a and ERD2b function as ER luminal protein receptors to ensure ERQC and alleviate ER stress, thus affecting HR PCD during the plant innate immune response. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

50 CFR 80.22 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.22 [Reserved] ...

50 CFR 80.19 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.19 [Reserved] ...

ER-2 in flight

NASA Technical Reports Server (NTRS)

1996-01-01

In this film clip, we see an ER-2 on its take off roll and climb as it departs from runway 22 at Edwards AFB, California. In 1981, NASA acquired its first ER-2 aircraft. The agency obtained a second ER-2 in 1989. These airplanes replaced two Lockheed U-2 aircraft, which NASA had used to collect scientific data since 1971. The U-2, and later the ER-2, were based at the Ames Research Center, Moffett Field, California, until 1997. In 1997, the ER-2 aircraft and their operations moved to NASA Dryden Flight Research Center, Edwards, California. Since the inaugural flight for this program, August 31, 1971, NASA U-2 and ER-2 aircraft have flown more than 4,000 data missions and test flights in support of scientific research conducted by scientists from NASA, other federal agencies, states, universities, and the private sector. NASA is currently using two ER-2 Airborne Science aircraft as flying laboratories. The aircraft, based at NASA Dryden, collect information about our surroundings, including Earth resources, celestial observations, atmospheric chemistry and dynamics, and oceanic processes. The aircraft also are used for electronic sensor research and development, satellite calibration, and satellite data validation. The ER-2 is a versatile aircraft well-suited to perform multiple mission tasks. It is 30 percent larger than the U-2 with a 20 feet longer wingspan and a considerably increased payload over the older airframe. The aircraft has four large pressurized experiment compartments and a high-capacity AC/DC electrical system, permitting it to carry a variety of payloads on a single mission. The modular design of the aircraft permits rapid installation or removal of payloads to meet changing mission requirements. The ER-2 has a range beyond 3,000 miles (4800 kilometers); is capable of long flight duration and can operate at altitudes up to 70,000 feet (21.3 kilometers) if required. Operating at an altitude of 65,000 feet (19.8 kilometers) the ER-2 acquires data above 95 percent of the Earth's atmosphere. At this altitude the aircraft provides a stable platform for Earth imagery, atmospheric research, and electronic sensor development. Because the ER-2 can fly so high, its sensors 'mimic' sensors carried aboard orbiting satellites. For most missions the ER-2 operates at altitudes between 65,000 feet and 70,000 feet. Depending on aircraft weight, the ER-2 reaches a cruise altitude of 65,000 feet within 20 minutes. Typical cruise speed is 410 knots. The range for a normal 6-hour mission is 2,200 nautical miles (4,070 kilometers), which yields 5 hours of data collection at high altitude. The aircraft is capable of longer missions of up to 8 hours and ranges of up to 3,000 nautical miles (5,500 kilometers). The ER-2 can carry a maximum payload of 2,600 pounds (1,179 kilograms) distributed in the equipment bay, nose area, and wing pods. In 1991, NASA launched a comprehensive program to study the Earth as an environmental system, now called the Earth Science Enterprise. By using satellites and other tools like the ER-2 to intensively study the Earth, NASA hopes to expand human understanding of how natural processes affect people and how people might be affecting them. Such studies will yield improved weather forecasts, tools for managing agriculture and forests, information for fishermen and local planners, and, eventually, the ability to predict how the climate will change in the future. NASA ER-2 aircraft have played an important role in Earth Science research, like studying ozone depletion over Antarctica and the Arctic. In August and September 1987 an ER-2 traveled to Punta Arenas, Chile, to conduct overflights of the Antarctic. Results from this study provided information suggesting that human-made chemical compounds, specifically chloro-fluorocarbons, caused enormous ozone depletion over the Antarctic region. Subsequent deployments have continued the study of the production and loss of ozone in the polar stratosphere. Atmospheric experiments were flown from Stavanger, Norway in January and February 1989 north of the Arctic Circle to investigate ozone loss in the stratosphere. From October 1991 through October 1994 a series of ER-2 flights were flown out of Fairbanks, Alaska; Bangor, Maine; and Christchurch, New Zealand to study the winter polar stratosphere. During these polar campaigns the ER-2 acquired atmospheric data with an array of up to 18 sampling instruments onboard the aircraft. Other atmospheric experiments provided more information about clouds and radiation that will help improve climate models. These experiments coordinated satellite, airborne, and surface observations to investigate how cloud formation affects global temperatures. Recently the ER-2, team conducted missions to help determine the effects of a proposed fleet of high-altitude, high-speed transport aircraft. Background measurements of chemistry at high altitudes have been compared to measurements of exhaust plumes of high altitude aircraft like the Concorde and the ER-2. A series of flights from April to September 1997 originating in Fairbanks, Alaska, resulted in the first in situ study of summer ozone conditions in a polar region. Since the program's inception, the NASA U-2's and ER-2's assisted in developing satellite sensors by testing sensor prototypes or by simulating proposed configurations with existing systems. In the early years of the program the U-2 flew prototypes of the Thematic Mapper and the Multispectral Scanner now operating on Landsats 4 and 5.

The widow(er)'s limit provision of Social Security.

PubMed

Weaver, D A

Widow benefits have been a part of the Social Security program since the 1939 amendments to the Social Security Act (widower benefits were added later). For many years, the Social Security law called for paying a widow(er) a fraction of the deceased worker's primary insurance amount (PIA). However, the worker--while alive--may have received the full PIA as his or her retirement benefit. Over time, arguments were made that a widow(er) should be treated as generously as his or her spouse was. The 1972 amendments to the Social Security Act allowed for a widow(er) to receive a full PIA, subject to actuarial reductions if the widow(er) benefit was claimed before the normal retirement age (NRA) and subject to a new provision of the law commonly referred to as the widow(er)'s limit. Generally, the widow(er)'s limit specifies that if a worker received reduced retirement benefits (because the worker claimed benefits before the NRA), then the worker's widow(er) cannot receive a monthly benefit equal to the full PIA. Rather, the widow(er)'s benefit is generally limited to the amount the worker would receive if he or she was still alive. The limit provision appears to be motivated by the overall intent of the 1972 Congress to pay a benefit to a widow(er) that was comparable with what the worker received. A number of changes to the limit provision have been discussed. This article looks at the following options: Abolishing the limit, Raising the limit by requiring that it never be set below the average PIA among all retired-worker beneficiaries. Adjusting the limit for some widow(er)s--that is, only persons who are widowed before the NRA (the ARLA option), Making a simpler adjustment to the limit by abolishing it for persons who are widowed before age 62 (the SARLA option), and A proposal by Robert J. Myers that would make modest adjustments to the limit for cases in which the worker died before the NRA. The most fundamental change--abolishing the limit--would increase benefits for about 2.8 million widow(er)s and would cost about $3.1 billion a year. Most of the additional government expenditures would not go to the poor and the near poor. Another change would be more successful in aiding low-income widow(er)s: requiring that the limit amount never be set below the average PIA among all retired-worker beneficiaries. About 58 percent of the government expenditures from that option would be received by the poor and the near poor. Overall, 1.2 million widow(er)s would be helped, and the cost would be about $816 million a year. Although the limit provision is consistent with the overall intent of the 1972 Congress, it can have effects that may have been unintended and that some policymakers might consider unusual. Persons who delay receipt of Social Security benefits usually receive higher monthly benefit amounts, but a widow(er) who faces a limit cannot increase his or her monthly benefit through delayed receipt of benefits. Thus, many persons who are widowed before the NRA face strong incentives to claim benefits early. That is somewhat unusual because the actuarial adjustments under Social Security are approximately fair, so there are no cost savings to the Social Security program from "forcing" a widow(er) to claim early benefits as opposed to allowing him or her to delay receipt of benefits in exchange for a higher monthly amount. And many widow(er)s would be better off if they could use the Social Security program to, in effect, save (that is, delay receipt of benefits in exchange for a higher amount later). This article analyzes two other options that would provide widow(er)s with additional filing options under Social Security. The ARLA option would ultimately help about 229,000 widow(er)s, and the cost would be small (about $69 million a year). The SARLA option would help about 117,000 widow(er)s, and the cost would be about $41 million a year. Robert J. Myers, a former Chief Actuary of Social Security, has offered a proposal that would provide relief from the widow(er)'s limit in cases in which the worker dies shortly after retirement. That proposal would help about 115,000 widow(er)s, and the cost would be low (about $57 million a year).

50 CFR 80.18 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.18 Responsibilities. In the...

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

Johnson, G.; Thom, R.; Whiting, A.

Habitat restoration in the Columbia River estuary (CRE) is an important off-site mitigation action in the 2000 Biological Opinion (BiOp), an operation of the Federal Columbia River Power System. The CRE, defined as the tidally influenced stretch of river from the mouth to Bonneville Dam 146 miles upstream, is part of the migration pathway for anadromous fish in the Columbia Basin, including salmon listed under the Endangered Species Act (ESA). Salmon in various stages of life, from fry to adults, use tidal channels and wetlands in the CRE to feed, find refuge from predators, and transition physiologically from freshwater tomore » saltwater. Over the last 100 years, however, the area of some wetland habitats has decreased by as much as 70% because of dike and levee building, flow regulation, and other activities. In response to the decline in available habitat, the BiOp's Reasonable and Prudent Alternative (RPA) included mandates to 'develop a plan addressing the habitat needs of juvenile salmon and steelhead in the estuary' (RPA Action 159) and 'develop and implement an estuary restoration program with a goal of protecting and enhancing 10,000 acres of tidal wetlands and other key habitats' (RPA Action 160). To meet Action 159 and support Action 160, this document develops a science-based approach designed to improve ecosystem functions through habitat restoration activities in the CRE. The CRE habitat restoration program's goal and principles focus on habitat restoration projects in an ecosystem context. Since restoration of an entire ecosystem is not generally practical, individual habitat restoration projects have the greatest likelihood of success when they are implemented with an ecosystem perspective. The program's goal is: Implementation of well-coordinated, scientifically sound projects designed to enhance, protect, conserve, restore, and create 10,000 acres of tidal wetlands and other key habitats to aid rebuilding of ESA-listed salmon populations and native species using the CRE. The program's underlying principles are: (1) projects are founded on the best available ecological restoration science, implemented in an ecosystem context, and developed with the intent to restore relevant ecological processes; (2) projects incorporate adaptive management practices with testable hypotheses to track ecological responses to a given restoration effort; and (3) projects are implemented in a coordinated, open process and scientific results from monitoring and evaluation are communicated widely and readily accessible. With this goal and these principles in mind, we developed an approach for CRE habitat restoration. The intent of this document is to provide a scientific basis and implementation guidelines for a habitat restoration program designed to improve ecosystem functions and enhance juvenile salmonid survival in the CRE. The stepwise approach to CRE habitat restoration outlined is somewhat general and broad because the available scientific information is incomplete, e.g., juvenile salmon usage of various CRE wetland habitats. As new data become available, a more specific, detailed plan than was possible here can be produced as an outgrowth of this document. In conclusion, this document provides a scientific basis and implementation guidelines for a habitat restoration program designed to improve ecosystem functions and enhance juvenile salmonid survival in the CRE. As more experience is gained with CRE habitat restoration and scientific uncertainties are resolved, this document should be used as a basis for a detailed habitat restoration plan that specifically addresses (1) which habitat types offer the greatest ecological benefit to salmon, (2) the location of potential sites that if restored would likely provide these habitat types, and (3) how and when the restoration work should be done. This document supports the use of adaptive management so that all elements of salmonid habitat restoration actions in the CRE are under continual evaluation and revision at both the project and program levels. Lessons learned from current and proposed habitat restoration projects need to be applied to all future work, such as the Estuary Partnership's habitat restoration program and the U.S. Army Corps of Engineers General Investigation Study for the CRE, to ensure the most effective use of resources and the best possible long term environment for salmonid growth and survival in the CRE.« less

42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

Short-term ecological consequences of collaborative restoration treatments in ponderosa pine forests of Colorado

Treesearch

Jennifer S. Briggs; Paula J. Fornwalt; Jonas A. Feinstein

2017-01-01

Ecological restoration treatments are being implemented at an increasing rate in ponderosa pine and other dry conifer forests across the western United States, via the USDA Forest Service’s Collaborative Forest Landscape Restoration (CFLR) program. In this program, collaborative stakeholder groups work with National Forests (NFs) to adaptively implement and monitor...

Collaborative restoration effects on forest structure in ponderosa pine-dominated forests of Colorado

Treesearch

Jeffery B. Cannon; Kevin J. Barrett; Benjamin M. Gannon; Robert N. Addington; Mike A. Battaglia; Paula J. Fornwalt; Gregory H. Aplet; Antony S. Cheng; Jeffrey L. Underhill; Jennifer S. Briggs; Peter M. Brown

2018-01-01

In response to large, severe wildfires in historically fire-adapted forests in the western US, policy initiatives, such as the USDA Forest Service’s Collaborative Forest Landscape Restoration Program (CFLRP), seek to increase the pace and scale of ecological restoration. One required component of this program is collaborative adaptive management, in which monitoring...

Liganded and unliganded activation of estrogen receptor and hormone replacement therapies.

PubMed

Maggi, Adriana

2011-08-01

Over the past two decades, our understanding of estrogen receptor physiology in mammals widened considerably as we acquired a deeper appreciation of the roles of estrogen receptor alpha and beta (ERα and ERβ) in reproduction as well as in bone and metabolic homeostasis, depression, vascular disorders, neurodegenerative diseases and cancer. In addition, our insights on ER transcriptional functions in cells increased considerably with the demonstration that ER activity is not strictly dependent on ligand availability. Indeed, unliganded ERs may be transcriptionally active and post-translational modifications play a major role in this context. The finding that several intracellular transduction molecules may regulate ER transcriptional programs indicates that ERs may act as a hub where several molecular pathways converge: this allows to maintain ER transcriptional activity in tune with all cell functions. Likely, the biological relevant role of ER was favored by evolution as a mean of integration between reproductive and metabolic functions. We here review the post-translational modifications modulating ER transcriptional activity in the presence or in the absence of estrogens and underline their potential role for ER tissue-specific activities. In our opinion, a better comprehension of the variety of molecular events that control ER activity in reproductive and non-reproductive organs is the foundation for the design of safer and more efficacious hormone-based therapies, particularly for menopause. This article is part of a Special Issue entitled: Translating Nuclear receptors from health to disease. Copyright © 2011 Elsevier B.V. All rights reserved.

50 CFR 80.90 - What are the grantee's responsibilities?

Code of Federal Regulations, 2012 CFR

2012-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.6 - Prohibited activities.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.6 Prohibited activities. The...

50 CFR 80.12 - Cost sharing.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.12 Cost sharing. Federal...

50 CFR 80.90 - What are the grantee's responsibilities?

Code of Federal Regulations, 2011 CFR

2011-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.21 - Assurances.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.21 Assurances. The State must...

50 CFR 80.24 - Recreational boating access facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.24... the Dingell-Johnson Sport Fish Restoration Act for recreational boating access facilities. However, a...

Hospitalizations for asthma: impact of a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil.

PubMed

Brandão, Heli Vieira; Cruz, Constança Margarida Sampaio; Santos, Ivan da Silva; Ponte, Eduardo Vieira; Guimarães, Armênio; Augusto Filho, Alvaro

2009-08-01

To evaluate the impact of the Programa de Controle da Asma e Rinite Alérgica em Feira de Santana (ProAR-FS, Program for the Control of Asthma and Allergic Rhinitis in Feira de Santana) on the frequency of hospitalizations for asthma in patients monitored at a referral center for one year. This was a historical control study involving 253 consecutive patients with asthma, ages ranging from 4 to 76 years. We compared the frequency of hospital admissions and visits to the emergency room (ER) in the 12 months prior to and after their admission to the ProAR-FS. During the program, patients received free treatment, including inhaled medications and education on asthma. Demographic and socioeconomic aspects were also assessed. There was a significant reduction in the number of hospitalizations (465 vs. 21) and of visits to the ER (2,473 vs. 184) after their admission to ProAR-FS (p < 0.001 for both). Of the 253 patients who had been hospitalized and had had ER visits within the year prior to the admission to ProAR-FS, only 16 were hospitalized and 92 visited the ER during the follow-up year, representing a reduction of 94% and 64%, respectively. Implementing a referral center for the treatment of asthma and rhinitis in the Unified Health Care System, with the free distribution of inhaled corticosteroids and the support of an education program, is a highly effective strategy for the control of asthma.

Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model.

PubMed

Browne, Patience; Judson, Richard S; Casey, Warren M; Kleinstreuer, Nicole C; Thomas, Russell S

2015-07-21

The U.S. Environmental Protection Agency (EPA) is considering high-throughput and computational methods to evaluate the endocrine bioactivity of environmental chemicals. Here we describe a multistep, performance-based validation of new methods and demonstrate that these new tools are sufficiently robust to be used in the Endocrine Disruptor Screening Program (EDSP). Results from 18 estrogen receptor (ER) ToxCast high-throughput screening assays were integrated into a computational model that can discriminate bioactivity from assay-specific interference and cytotoxicity. Model scores range from 0 (no activity) to 1 (bioactivity of 17β-estradiol). ToxCast ER model performance was evaluated for reference chemicals, as well as results of EDSP Tier 1 screening assays in current practice. The ToxCast ER model accuracy was 86% to 93% when compared to reference chemicals and predicted results of EDSP Tier 1 guideline and other uterotrophic studies with 84% to 100% accuracy. The performance of high-throughput assays and ToxCast ER model predictions demonstrates that these methods correctly identify active and inactive reference chemicals, provide a measure of relative ER bioactivity, and rapidly identify chemicals with potential endocrine bioactivities for additional screening and testing. EPA is accepting ToxCast ER model data for 1812 chemicals as alternatives for EDSP Tier 1 ER binding, ER transactivation, and uterotrophic assays.

Effect of analgesic nerve block electrical stimulation in a patient with adhesive capsulitis.

PubMed

Gulick, Dawn T; Borger, Amy; McNamee, Lauren

2007-01-01

Although the pathophysiology of adhesive capsulitis is poorly understood, the primary goal of therapeutic intervention is to restore pain-free, functional range of motion (ROM) of the shoulder. Pain and muscle guarding, particularly of the subscapularis muscle, are common impairments that occur with adhesive capsulitis. The purpose of this case report is to describe a novel approach to help the pain-muscle guarding-pain cycle associated with pain and limited shoulder motion in a patient with a medical diagnosis of adhesive capsulitis. The patient was a 64-year-old female with adhesive capsulitis. Outcome variables were the Shoulder Pain and Disability Index (SPADI), internal rotation (IR) and external rotation (ER) ROM, and rotational lack. Twelve treatments of moist heat, analgesic nerve block electrical stimulation, contract/relax exercises for shoulder IR/ER, and Pendulum/Codman exercises were administered. After both 2 and 4 weeks of treatment, the patient demonstrated marked improvements in all areas. Overall, there was a 78-106% increase in ROM (IR and ER) and a 50-83% improvement in functional mobility (rotational lack & SPADI). It appears that analgesic electrical stimulation may have helped decrease the pain-muscle guarding cycle associated with adhesive capsulitis to enhance functional outcomes in a timely manner.

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

PubMed

Yang, Seoyeon; Lee, Ji-Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

2018-05-28

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

Endodontic Treatment of an Autogenous Transplanted Tooth Using an Er,Cr:YSGG Laser and Radial Firing Tips: Case Report.

PubMed

Martins, Miguel Rodrigues; Lima, Rita C; Pina-Vaz, Irene; Carvalho, Manuel Fontes; Gutknecht, Norbert

2016-10-01

Although several surgical techniques have been reported, no study has yet reported alternative strategies for endodontic treatment of autogenous transplanted teeth. Therefore, the aim of this clinical report is to present the long-term endodontic outcome of a nonvital autogenously transplanted third molar treated with an Er,Cr:YSGG laser and radial firing tips (RFTs). Autogenous tooth transplantation can be considered an alternative to restore edentulous areas and, in donor's teeth with complete root formation, root canal treatment should be performed up to 14 days following transplantation. In the present case report, the patient returned only after 6 months, with clinical and radiological signs of apical periodontitis (AP) associated with the transplanted tooth. Instead of traditional endodontic chemical irrigants or medications, the protocol for smear-layer removal and root canal disinfection was based on intracanal irradiation with an Er,Cr:YSGG laser and RFTs. After 3-years' follow-up, the complete reestablishment of the periodontal ligament and the arrest of the resorptive process could be noticed. This protocol has shown to be effective for the endodontic treatment of a transplanted multi-rooted tooth with AP. Further randomized clinical trials should be conducted to clearly demonstrate the effectiveness of this laser-assisted endodontic protocol.

50 CFR 86.90 - What are my responsibilities for information signs?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.90...

50 CFR 86.90 - What are my responsibilities for information signs?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.90...

An emergency room decision-support program that increased physician office visits, decreased emergency room visits, and saved money.

PubMed

Navratil-Strawn, Jessica L; Hawkins, Kevin; Wells, Timothy S; Ozminkowski, Ronald J; Hartley, Stephen K; Migliori, Richard J; Yeh, Charlotte S

2014-10-01

The objective of this study was to evaluate an Emergency Room having a Decision-Support (ERDS) program designed to appropriately reduce ER use among frequent users, defined as 3 or more visits within a 12-month period. To achieve this, adults with an AARP Medicare Supplement Insurance plan insured by UnitedHealthcare Insurance Company (for New York residents, UnitedHealthcare Insurance Company of New York) were eligible to participate in the program. These included 7070 individuals who elected to enroll in the ERDS program and an equal number of matched nonparticipants who were eligible but either declined or were unreachable. Program-related benefits were estimated by comparing the difference in downstream health care utilization and expenditures between engaged and not engaged individuals after using propensity score matching to adjust for case mix differences between these groups. As a result, compared with the not engaged, engaged individuals experienced better care coordination, evidenced by a greater reduction in ER visits (P=0.033) and hospital admissions (P=0.002) and an increase in office visits (P<0.001). The program was cost-effective, with a return on investment (ROI) of 1.24, which was calculated by dividing the total program savings ($3.41 million) by the total program costs ($2.75 million). The ROI implies that for every dollar invested in this program, $1.24 was saved, most of which was for the federal Medicare program. In conclusion, the decrease in ER visits and hospital admissions and the increase in office visits may indicate the program helped individuals to seek the appropriate levels of care.

50 CFR 80.54 - What activities are ineligible for funding?

Code of Federal Regulations, 2012 CFR

2012-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Eligible...

50 CFR 80.32 - What is the certification period?

Code of Federal Regulations, 2013 CFR

2013-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Certification of...

50 CFR 80.54 - What activities are ineligible for funding?

Code of Federal Regulations, 2011 CFR

2011-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Eligible...

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology.

PubMed

Guzel, Elif; Arlier, Sefa; Guzeloglu-Kayisli, Ozlem; Tabak, Mehmet Selcuk; Ekiz, Tugba; Semerci, Nihan; Larsen, Kellie; Schatz, Frederick; Lockwood, Charles Joseph; Kayisli, Umit Ali

2017-04-08

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis.

Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology

PubMed Central

Guzel, Elif; Arlier, Sefa; Guzeloglu-Kayisli, Ozlem; Tabak, Mehmet Selcuk; Ekiz, Tugba; Semerci, Nihan; Larsen, Kellie; Schatz, Frederick; Lockwood, Charles Joseph; Kayisli, Umit Ali

2017-01-01

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis. PMID:28397763

A role for post-transcriptional control of endoplasmic reticulum dynamics and function in C. elegans germline stem cell maintenance.

PubMed

Maheshwari, Richa; Pushpa, Kumari; Subramaniam, Kuppuswamy

2016-09-01

Membrane-bound receptors, which are crucial for mediating several key developmental signals, are synthesized on endoplasmic reticulum (ER). The functional integrity of ER must therefore be important for the regulation of at least some developmental programs. However, the developmental control of ER function is not well understood. Here, we identify the C. elegans protein FARL-11, an ortholog of the mammalian STRIPAK complex component STRIP1/2 (FAM40A/B), as an ER protein. In the C. elegans embryo, we find that FARL-11 is essential for the cell cycle-dependent morphological changes of ER and for embryonic viability. In the germline, FARL-11 is required for normal ER morphology and for membrane localization of the GLP-1/Notch receptor involved in germline stem cell (GSC) maintenance. Furthermore, we provide evidence that PUF-8, a key translational regulator in the germline, promotes the translation of farl-11 mRNA. These findings reveal that ER form and function in the C. elegans germline are post-transcriptionally regulated and essential for the niche-GSC signaling mediated by GLP-1. © 2016. Published by The Company of Biologists Ltd.

50 CFR 80.5 - Eligible undertakings.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.5 Eligible undertakings. The... necessary to be a responsible hunter or archer. (b) Dingell-Johnson Sport Fish Restoration Act. (1) Projects...

50 CFR 80.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.1 Definitions. As used in this... administration and execution of the Wildlife and Sport Fish Restoration Acts. Project. One or more related...

50 CFR 80.54 - What activities are ineligible for funding?

Code of Federal Regulations, 2014 CFR

2014-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Eligible...

50 CFR 80.54 - What activities are ineligible for funding?

Code of Federal Regulations, 2013 CFR

2013-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Eligible...

50 CFR 80.8 - Availability of funds.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.8 Availability of funds. Funds...

50 CFR 80.13 - Substantiality in character and design.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.13...

50 CFR 80.16 - Payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.16 Payments. Payments must be made for the...

50 CFR 80.134 - How must an agency use real property?

Code of Federal Regulations, 2011 CFR

2011-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Real...

50 CFR 80.7 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.7 Appeals. Any difference of opinion over the...

Quartermaster Reach Restoration Project

EPA Pesticide Factsheets

Information about the SFBWQP Quartermaster Reach Restoration Project, part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources.

Thirty-year solid waste generation forecast for facilities at SRS

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

Not Available

1994-07-01

The information supplied by this 30-year solid waste forecast has been compiled as a source document to the Waste Management Environmental Impact Statement (WMEIS). The WMEIS will help to select a sitewide strategic approach to managing present and future Savannah River Site (SRS) waste generated from ongoing operations, environmental restoration (ER) activities, transition from nuclear production to other missions, and decontamination and decommissioning (D&D) programs. The EIS will support project-level decisions on the operation of specific treatment, storage, and disposal facilities within the near term (10 years or less). In addition, the EIS will provide a baseline for analysis ofmore » future waste management activities and a basis for the evaluation of the specific waste management alternatives. This 30-year solid waste forecast will be used as the initial basis for the EIS decision-making process. The Site generates and manages many types and categories of waste. With a few exceptions, waste types are divided into two broad groups-high-level waste and solid waste. High-level waste consists primarily of liquid radioactive waste, which is addressed in a separate forecast and is not discussed further in this document. The waste types discussed in this solid waste forecast are sanitary waste, hazardous waste, low-level mixed waste, low-level radioactive waste, and transuranic waste. As activities at SRS change from primarily production to primarily decontamination and decommissioning and environmental restoration, the volume of each waste s being managed will change significantly. This report acknowledges the changes in Site Missions when developing the 30-year solid waste forecast.« less

Bridges to life: evaluation of an in-prison restorative justice intervention.

PubMed

Armour, Marilyn Peterson; Sage, John; Rubin, Allen; Windsor, Liliane C

2005-12-01

Restorative justice initiatives have been identified as primarily, if not exclusively, useful as a "front-end" diversionary option reserved for non violent property crimes and minor assaults. In-prison restorative justice programs are rare and have not been examined for their impact on recidivism. Bridges to Life (BTL) is a voluntary, manualized, ecumenical faith-based restorative justice program offered to incarcerated offenders who are within nine months of their release. A survey of BTL graduates (n=1021) found an appreciatively lower recidivism rate than the general population of released inmates. Quantitative and qualitative analyses suggest that BTL helps break through offenders' denial and self-centeredness, exposing them to the impact of their actions and helping them feel the pain their crimes created. Possible reasons for the positive nature of participants' responses are advanced. The use of in-prison restorative justice programs to facilitate offender re-entry is also discussed.

Completion Report for Well ER-EC-5

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

Bechtel Nevada

2004-10-01

Well ER-EC-5 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of the Nevada Environmental Restoration Project at the Nevada Test Site, Nye County, Nevada. This well was drilled in the summer of 1999 as part of the U.S. Department of Energy's hydrogeologic investigation program in the Western Pahute Mesa - Oasis Valley region just west of the Nevada Test Site. A 44.5-centimeter surface hole was drilled and cased off to a depth of 342.6 meters below ground surface. The borehole diameter was then decreased to 31.1 centimeters for drilling to amore » total depth of 762.0 meters. One completion string with three isolated slotted intervals was installed in the well. A preliminary composite, static water level was measured at the depth of 309.9 meters, 40 days after installation of the completion string. Detailed lithologic descriptions with stratigraphic assignments are included in the report. These are based on composite drill cuttings collected every 3 meters, and 18 sidewall samples taken at various depths below 349.6 meters, supplemented by geophysical log data and results from detailed chemical and mineralogical analyses of rock samples. The well penetrated Tertiary-age tuffs of the Thirsty Canyon Group, caldera moat-filling sedimentary deposits, lava of the Beatty Wash Formation, and landslide breccia and tuffs of the Timber Mountain Group. The well reached total depth in welded ashflow tuff of the Ammonia Tanks Tuff after penetrating 440.1 meters of this unit, which is also the main water-producing unit in the well. The geologic interpretation of data from this well constrains the western margin of the Ammonia Tanks caldera to the west of the well location.« less

Nevada National Security Site Environmental Report 2011

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

Cathy Wills, ed

2012-09-12

This report was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This and previous years reports, called Annual Site Environmental Reports (ASERs), Nevada Test Site Environmental Reports (NTSERs), and, beginning in 2010, Nevada National Security Site Environmental Reports (NNSSERs), are posted on the NNSA/NSO website at http://www.nv.energy.gov/library/publications/aser.aspx. This NNSSER was prepared to satisfy DOE Order DOE O 231.1B, 'Environment,more » Safety and Health Reporting.' Its purpose is to (1) report compliance status with environmental standards and requirements, (2) present results of environmental monitoring of radiological and nonradiological effluents, (3) report estimated radiological doses to the public from releases of radioactive material, (4) summarize environmental incidents of noncompliance and actions taken in response to them, (5) describe the NNSA/NSO Environmental Management System and characterize its performance, and (6) highlight significant environmental programs and efforts. This NNSSER summarizes data and compliance status for calendar year 2011 at the Nevada National Security Site (NNSS) (formerly the Nevada Test Site) and its two support facilities, the North Las Vegas Facility (NLVF) and the Remote Sensing Laboratory-Nellis (RSL-Nellis). It also addresses environmental restoration (ER) projects conducted at the Tonopah Test Range (TTR). Through a Memorandum of Agreement, NNSA/NSO is responsible for the oversight of TTR ER projects, and the Sandia Site Office of NNSA (NNSA/SSO) has oversight of all other TTR activities. NNSA/SSO produces the TTR annual environmental report available at http://www.sandia.gov/news/publications/environmental/index.html.« less

Nevada Test Site Environmental Report 2009

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

Cathy Wills, ed.

2010-09-13

The Nevada Test Site Environmental Report 2009 was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This and previous years’ Nevada Test Site Environmental Reports (NTSERs) are posted on the NNSA/NSO website at http://www.nv.doe.gov/library/publications/aser.aspx. This NTSER was prepared to satisfy DOE Order DOE O 231.1A, “Environment, Safety and Health Reporting.” Its purpose is to (1) report compliance status withmore » environmental standards and requirements, (2) present results of environmental monitoring of radiological and nonradiological effluents, (3) report estimated radiological doses to the public from releases of radioactive material, (4) summarize environmental incidents of noncompliance and actions taken in response to them, (5) describe the NNSA/NSO Environmental Management System and characterize its performance, and (6) highlight significant environmental programs and efforts. This NTSER summarizes data and compliance status for calendar year 2009 at the Nevada Test Site (NTS) and its two support facilities, the North Las Vegas Facility (NLVF) and the Remote Sensing Laboratory (RSL)-Nellis. It also addresses environmental restoration (ER) projects conducted at the Tonopah Test Range (TTR). Through a Memorandum of Agreement, NNSA/NSO is responsible for the oversight of TTR ER projects, and the Sandia Site Office of NNSA (NNSA/SSO) has oversight of all other TTR activities. NNSA/SSO produces the TTR annual environmental report available at http://www.sandia.gov/news/publications/environmental/index.html.« less

50 CFR 86.93 - Where should I use the SFR logo?

Code of Federal Regulations, 2013 CFR

2013-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.93 Where should I use the SFR...

50 CFR 86.92 - Who can use the SFR logo?

Code of Federal Regulations, 2012 CFR

2012-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.92 Who can use the SFR logo? The States...

50 CFR 86.93 - Where should I use the SFR logo?

Code of Federal Regulations, 2014 CFR

2014-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.93 Where should I use the SFR...

50 CFR 86.92 - Who can use the SFR logo?

Code of Federal Regulations, 2014 CFR

2014-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.92 Who can use the SFR logo...

50 CFR 86.92 - Who can use the SFR logo?

Code of Federal Regulations, 2013 CFR

2013-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.92 Who can use the SFR logo...

50 CFR 86.90 - What are my responsibilities for information signs?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.90 What are my...

50 CFR 86.92 - Who can use the SFR logo?

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.92 Who can use the SFR logo? The States...

50 CFR 86.90 - What are my responsibilities for information signs?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.90 What are my...

50 CFR 86.90 - What are my responsibilities for information signs?

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.90 What are my...

50 CFR 86.92 - Who can use the SFR logo?

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.92 Who can use the SFR logo? The States...

50 CFR 80.98 - How must an agency report barter transactions?

Code of Federal Regulations, 2011 CFR

2011-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

California partners for fish and wildlife program: conserving birds through private partnerships

Treesearch

Debra Schlafmann; Philip Morrison

2005-01-01

The Partners for Fish and Wildlife Program, the U.S. Fish and Wildlife Service's (Service) habitat restoration assistance program for private landowners, was created primarily to improve habitat for waterfowl. Since its inception in 1987, however, the program has grown to include the restoration of all types of habitat. The purpose of this paper is to explain how...

The Impact of Early Involvement in a Postdischarge Support Program for Ostomy Surgery Patients on Preventable Healthcare Utilization

PubMed Central

2018-01-01

PURPOSE: To evaluate the impact of a postdischarge ostomy support program as an adjunct to nurse-led ostomy care on preventable healthcare utilization. DESIGN: A cross-sectional study. SUBJECTS AND SETTING: A postdischarge support program offered by an ostomy product's manufacturer provides persons living with an ostomy with patient-centered and easily accessible assistance. Individuals who underwent ostomy surgery within 18 months prior to the survey date were selected from an ostomy patient database maintained by the ostomy patient support program provider. Of 7026 surveys sent to program enrollees, 493 (7%) responded, compared with 225 (5%) out of 4149 surveys sent to individuals in a comparison group. The 2 groups were similar in demographics. A majority of the survey respondents were female (60% of program enrollees vs 55% of respondents in the comparison group). Among the program enrollees, 44% had colostomy, 43% had ileostomy, 10% had urostomy, and 4% had at least 2 types of ostomy surgery compared with 52%, 32%, 12%, and 4% of the respondents in a comparison group, respectively. METHODS: The study compared hospital readmission and emergency room (ER) visit rates attributable to ostomy complications between program enrollees and respondents in the comparison group. The event rates were measured in 2 study periods: within the first month of discharge and after the first month of discharge. Eligible individuals received an online survey that included the following domains: characteristics of ostomy surgery; readmissions and ER visits within the first month or after the first month of discharge, including reasons for preventable events; and level of health care access. Multivariate logistic regressions controlling for covariates were applied to investigate associations between program enrollment and ostomy-related readmission or ER visit rates. RESULTS: Logistic regression analyses showed that, when compared with respondents in the comparison group, program enrollees had a significantly lower likelihood of being readmitted and visiting the ER due to ostomy complications after the first month of hospital discharge and up to 18 months postdischarge (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.27-0.73; and OR = 0.37; 95% CI, 0.22-0.64, respectively). CONCLUSIONS: Findings suggest that enrolling patients in the postdischarge ostomy support program provides an effective approach to reducing preventable healthcare utilization. PMID:29189646

The Impact of Early Involvement in a Postdischarge Support Program for Ostomy Surgery Patients on Preventable Healthcare Utilization.

PubMed

Rojanasarot, Sirikan

To evaluate the impact of a postdischarge ostomy support program as an adjunct to nurse-led ostomy care on preventable healthcare utilization. A cross-sectional study. A postdischarge support program offered by an ostomy product's manufacturer provides persons living with an ostomy with patient-centered and easily accessible assistance. Individuals who underwent ostomy surgery within 18 months prior to the survey date were selected from an ostomy patient database maintained by the ostomy patient support program provider. Of 7026 surveys sent to program enrollees, 493 (7%) responded, compared with 225 (5%) out of 4149 surveys sent to individuals in a comparison group. The 2 groups were similar in demographics. A majority of the survey respondents were female (60% of program enrollees vs 55% of respondents in the comparison group). Among the program enrollees, 44% had colostomy, 43% had ileostomy, 10% had urostomy, and 4% had at least 2 types of ostomy surgery compared with 52%, 32%, 12%, and 4% of the respondents in a comparison group, respectively. The study compared hospital readmission and emergency room (ER) visit rates attributable to ostomy complications between program enrollees and respondents in the comparison group. The event rates were measured in 2 study periods: within the first month of discharge and after the first month of discharge. Eligible individuals received an online survey that included the following domains: characteristics of ostomy surgery; readmissions and ER visits within the first month or after the first month of discharge, including reasons for preventable events; and level of health care access. Multivariate logistic regressions controlling for covariates were applied to investigate associations between program enrollment and ostomy-related readmission or ER visit rates. Logistic regression analyses showed that, when compared with respondents in the comparison group, program enrollees had a significantly lower likelihood of being readmitted and visiting the ER due to ostomy complications after the first month of hospital discharge and up to 18 months postdischarge (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.27-0.73; and OR = 0.37; 95% CI, 0.22-0.64, respectively). Findings suggest that enrolling patients in the postdischarge ostomy support program provides an effective approach to reducing preventable healthcare utilization.

Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

PubMed

Park, Jun Won; Lee, Su Hyung; Woo, Gye-Hyung; Kwon, Hyo-Jung; Kim, Dae-Yong

2018-04-06

TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

A methodological study of genome-wide DNA methylation analyses using matched archival formalin-fixed paraffin embedded and fresh frozen breast tumors.

PubMed

Espinal, Allyson C; Wang, Dan; Yan, Li; Liu, Song; Tang, Li; Hu, Qiang; Morrison, Carl D; Ambrosone, Christine B; Higgins, Michael J; Sucheston-Campbell, Lara E

2017-02-28

DNA from archival formalin-fixed and paraffin embedded (FFPE) tissue is an invaluable resource for genome-wide methylation studies although concerns about poor quality may limit its use. In this study, we compared DNA methylation profiles of breast tumors using DNA from fresh-frozen (FF) tissues and three types of matched FFPE samples. For 9/10 patients, correlation and unsupervised clustering analysis revealed that the FF and FFPE samples were consistently correlated with each other and clustered into distinct subgroups. Greater than 84% of the top 100 loci previously shown to differentiate ER+ and ER- tumors in FF tissues were also FFPE DML. Weighted Correlation Gene Network Analyses (WCGNA) grouped the DML loci into 16 modules in FF tissue, with ~85% of the module membership preserved across tissue types. Restored FFPE and matched FF samples were profiled using the Illumina Infinium HumanMethylation450K platform. Methylation levels (β-values) across all loci and the top 100 loci previously shown to differentiate tumors by estrogen receptor status (ER+ or ER-) in a larger FF study, were compared between matched FF and FFPE samples using Pearson's correlation, hierarchical clustering and WCGNA. Positive predictive values and sensitivity levels for detecting differentially methylated loci (DML) in FF samples were calculated in an independent FFPE cohort. FFPE breast tumors samples show lower overall detection of DMLs versus FF, however FFPE and FF DMLs compare favorably. These results support the emerging consensus that the 450K platform can be employed to investigate epigenetics in large sets of archival FFPE tissues.

50 CFR 80.26 - Symbols.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.26 Symbols. We have prescribed distinctive...-Johnson Sport Fish Restoration Act and items on which taxes and duties have been collected to support the...

50 CFR 80.27 - Information collection requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.27 Information... under the Dingell-Johnson Sport Fish Restoration Act (16 U.S.C. 777-777n) and the Pittman-Robertson...

Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury

PubMed Central

Folch-Puy, Emma; Panisello, Arnau; Oliva, Joan; Lopez, Alexandre; Castro Benítez, Carlos; Adam, René; Roselló-Catafau, Joan

2016-01-01

The endoplasmic reticulum (ER) is involved in calcium homeostasis, protein folding and lipid biosynthesis. Perturbations in its normal functions lead to a condition called endoplasmic reticulum stress (ERS). This can be triggered by many physiopathological conditions such as alcoholic steatohepatitis, insulin resistance or ischemia-reperfusion injury. The cell reacts to ERS by initiating a defensive process known as the unfolded protein response (UPR), which comprises cellular mechanisms for adaptation and the safeguarding of cell survival or, in cases of excessively severe stress, for the initiation of the cell death program. Recent experimental data suggest the involvement of ERS in ischemia/reperfusion injury (IRI) of the liver graft, which has been considered as one of major problems influencing outcome after liver transplantation. The purpose of this review is to summarize updated data on the molecular mechanisms of ERS/UPR and the consequences of this pathology, focusing specifically on solid organ preservation and liver transplantation models. We will also discuss the potential role of ERS, beyond the simple adaptive response and the regulation of cell death, in the modification of cell functional properties and phenotypic changes. PMID:27231901

50 CFR 80.35 - What additional requirements apply to multiyear licenses?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.151 - May an agency appeal a decision?

Code of Federal Regulations, 2012 CFR

2012-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Revisions and Appeals § 80...

50 CFR 80.95 - How does an agency receive Federal grant funds?

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.95 - How does an agency receive Federal grant funds?

Code of Federal Regulations, 2011 CFR

2011-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.151 - May an agency appeal a decision?

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Revisions and Appeals § 80...

Evaluation of ball and roller bearings restored by grinding

NASA Technical Reports Server (NTRS)

Parker, R. J.; Zaretsky, E. V.; Chen, S. M.

1976-01-01

A joint program was undertaken to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. Groups of each of these bearings were visually and dimensionally inspected for suitability for restoration. A total of 250 bearings were restored by grinding. Of this number, 30 bearings from each type were endurance tested to a TBO of 1600 hours. No bearing failures occurred related to the restoration by grinding process. The two bearing failures which occurred were due to defective rolling elements and were typical of those which may occur in new bearings. The restorable component yield to the three groups was in excess of 90 percent.

The Influence of Translation on Reading Amount, Proficiency, and Speed in Extensive Reading

ERIC Educational Resources Information Center

Sakurai, Nobuko

2015-01-01

This study attempted to examine the influence of a decrease in translation on the number of words read, reading comprehension, and reading rate in an extensive reading (ER) program. The participants were 70 first-year university students who experienced ER both in and outside the classroom for 15 weeks. The results of regression analyses confirmed…

Precise orbit computation and sea surface modeling

NASA Technical Reports Server (NTRS)

Wakker, Karel F.; Ambrosius, B. A. C.; Rummel, R.; Vermaat, E.; Deruijter, W. P. M.; Vandermade, J. W.; Zimmerman, J. T. F.

1991-01-01

The research project described below is part of a long-term program at Delft University of Technology aiming at the application of European Remote Sensing satellite (ERS-1) and TOPEX/POSEIDON altimeter measurements for geophysical purposes. This program started in 1980 with the processing of Seasat laser range and altimeter height measurements and concentrates today on the analysis of Geosat altimeter data. The objectives of the TOPEX/POSEIDON research project are the tracking of the satellite by the Dutch mobile laser tracking system MTLRS-2, the computation of precise TOPEX/POSEIDON orbits, the analysis of the spatial and temporal distribution of the orbit errors, the improvement of ERS-1 orbits through the information obtained from the altimeter crossover difference residuals for crossing ERS-1 and TOPEX/POSEIDON tracks, the combination of ERS-1 and TOPEX/POSEIDON altimeter data into a single high-precision data set, and the application of this data set to model the sea surface. The latter application will focus on the determination of detailed regional mean sea surfaces, sea surface variability, ocean topography, and ocean currents in the North Atlantic, the North Sea, the seas around Indonesia, the West Pacific, and the oceans around South Africa.

A survey of environmental needs and innovative technologies in Germany

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

Voss, C.F.; Roberds, W.J.

1995-05-01

The International Technology Program (IT?), formerly the international Technology Exchange Program (ITEP), of the Department of Energy`s (DOE`s) Office of Environmental Restoration and Waste Management (EM) is responsible for promoting: (1) the import of innovative technologies to better address EM`s needs; and (2) the export of US services into foreign markets to enhance US competitiveness. Under this program: (1) the environmental restoration market in Germany was evaluated, including the description of the general types of environmental problems, the environmental regulations, and specific selected contaminated sites; and (2) potentially innovative environmental restoration technologies, either commercially available or under development in Germany,more » were identified, described and evaluated. It was found that: (1) the environmental restoration market in Germany is very large, on the order of several billion US dollars per year, with a significant portion possibly available to US businesses; and (2) a large number (54) of innovative environmental restoration technologies, which are either commercially available or under development in Germany, may have some benefit to the DOE EM program and should be considered for transfer to the US.« less

50 CFR 86.93 - Where should I use the SFR logo?

Code of Federal Regulations, 2012 CFR

2012-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.93 Where should I use the SFR logo? You...

50 CFR 84.12 - What are the information collection, record keeping, and reporting requirements?

Code of Federal Regulations, 2010 CFR

2010-10-01

... RESTORATION PROGRAM NATIONAL COASTAL WETLANDS CONSERVATION GRANT PROGRAM General Background § 84.12 What are... conserved, with a breakdown by conservation method (for example, acquired, restored, or both) and type of...

50 CFR 86.93 - Where should I use the SFR logo?

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.93 Where should I use the SFR logo? You...

50 CFR 86.93 - Where should I use the SFR logo?

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM BOATING INFRASTRUCTURE GRANT (BIG) PROGRAM State Use of Signs and Sport Fish Restoration Symbols § 86.93 Where should I use the SFR logo? You...

50 CFR 80.93 - When may an agency incur costs under a grant?

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.96 - May an agency use Federal funds without using match?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.92 - How long are funds available for a Federal obligation?

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.20 - What does revenue from hunting and fishing licenses include?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.160 - What are the information collection requirements of this part?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.53 - Are costs of State central services eligible for funding?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.160 - What are the information collection requirements of this part?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.20 - What does revenue from hunting and fishing licenses include?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.92 - How long are funds available for a Federal obligation?

Code of Federal Regulations, 2011 CFR

2011-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.96 - May an agency use Federal funds without using match?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.93 - When may an agency incur costs under a grant?

Code of Federal Regulations, 2011 CFR

2011-10-01

... THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General...

50 CFR 80.53 - Are costs of State central services eligible for funding?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.150 - How does an agency ask for revision of a grant?

Code of Federal Regulations, 2011 CFR

2011-10-01

... OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

Science driven restoration: A candle in a demon haunted world—response to cabin

Treesearch

Christian P. Giardina; Creighton M. Litton; Jarrod M. Thaxton; Susan Cordell; Lisa J. Hadway; Darren R. Sandquist

2007-01-01

Cabin (2007) asks whether formal science is an effective framework and methodology for designing and implementing ecological restoration programs. He argues that beyond certain ancillary benefits, restoration science has little of practical value to offer the practice of restoration. He goes on to suggest that restoration science most often represents an impediment to...

50 CFR 80.52 - May an activity be eligible for funding if it is not explicitly eligible in this part?

Code of Federal Regulations, 2014 CFR

2014-10-01

... SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Eligible Activities § 80.52 May an activity be eligible for... Pittman-Robertson Wildlife Restoration Act or the Dingell-Johnson Sport Fish Restoration Act; and (b) The...

50 CFR 80.52 - May an activity be eligible for funding if it is not explicitly eligible in this part?

Code of Federal Regulations, 2013 CFR

2013-10-01

... SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS Eligible Activities § 80.52 May an activity be eligible for... Pittman-Robertson Wildlife Restoration Act or the Dingell-Johnson Sport Fish Restoration Act; and (b) The...

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

NONE

The High Ranking Facilities Deactivation Project (HRFDP), commissioned by the US Department of Energy Nuclear Materials and Facility Stabilization Program, is to place four primary high-risk surplus facilities with 28 associated ancillary facilities at Oak Ridge National Laboratory in a safe, stable, and environmentally sound condition as rapidly and economically as possible. The facilities will be deactivated and left in a condition suitable for an extended period of minimized surveillance and maintenance (S and M) prior to decontaminating and decommissioning (D and D). These four facilities include two reactor facilities containing spent fuel. One of these reactor facilities also containsmore » 55 tons of sodium with approximately 34 tons containing activated sodium-22, 2.5 tons of lithium hydride, approximately 100 tons of potentially contaminated lead, and several other hazardous materials as well as bulk quantities of contaminated scrap metals. The other two facilities to be transferred include a facility with a bank of hot cells containing high levels of transferable contamination and also a facility containing significant quantities of uranyl nitrate and quantities of transferable contamination. This work plan documents the objectives, technical requirements, and detailed work plans--including preliminary schedules, milestones, and conceptual FY 1996 cost estimates--for the Oak Ridge National Laboratory (ORNL). This plan has been developed by the Environmental Restoration (ER) Program of Lockheed Martin Energy Systems (Energy Systems) for the US Department of Energy (DOE) Oak Ridge Operations Office (ORO).« less

Forest restoration at Redwood National Park: a case study of an emerging program

Treesearch

Jason R. Teraoka

2012-01-01

For more than 30 years, Redwood National Park has been working to establish a Forest Restoration Program to rehabilitate its impaired, second-growth forests. This case study outlines the Park’s history of using silviculture as a restoration tool, which began in 1978 after the Park's expansion. The most recent effort was the 1,700 acre South Fork of Lost Man Creek...

50 CFR 80.53 - Are costs of State central services eligible for funding?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.53 - Are costs of State central services eligible for funding?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.160 - What are the information collection requirements of this part?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.160 - What are the information collection requirements of this part?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.20 - What does revenue from hunting and fishing licenses include?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.20 - What does revenue from hunting and fishing licenses include?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

Cullinan Ranch Tidal Marsh Restoration Project

EPA Pesticide Factsheets

Information about the SFBWQP Cullinan Ranch Tidal Marsh Restoration Project, part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources.

Restoration of Apollo Data by the NSSDC and the PDS Lunar Data Node

NASA Technical Reports Server (NTRS)

Williams, David R.; Hills, H. Kent; Lowman, Paul D.; Taylor, Patrick T.; Guinness, Edward A.

2011-01-01

The Lunar Data Node (LDN), under the auspices of the Geosciences Node of the Planetary Data System (PDS), is restoring Apollo data archived at the National Space Science Data Center. The Apollo data were arch ived on older media (7 -track tapes. microfilm, microfiche) and in ob solete digital formats, which limits use of the data. The LDN is maki ng these data accessible by restoring them to standard formats and archiving them through PDS. The restoration involves reading the older m edia, collecting supporting data (metadata), deciphering and understa nding the data, and organizing into a data set. The data undergo a pe er review before archive at PDS. We will give an update on last year' s work. We have scanned notebooks from Otto Berg, P.1. for the Lunar Ejecta and Meteorites Experiment. These notebooks contain information on the data and calibration coefficients which we hope to be able to use to restore the raw data into a usable archive. We have scanned Ap ollo 14 and 15 Dust Detector data from microfilm and are in the proce ss of archiving thc scans with PDS. We are also restoring raw dust de tector data from magnetic tape supplied by Yosio Nakamura (UT Austin) . Seiichi Nagihara (Texas Tech Univ.) and others in cooperation with NSSDC are recovering ARCSAV tapes (tapes containing raw data streams from all the ALSEP instruments). We will be preparing these data for archive with PDS. We are also in the process of recovering and archivi ng data not previously archived, from the Apollo 16 Gamma Ray Spectro meter and the Apollo 17 Infrared Spectrometer.

Verification and Improvement of ERS-1/2 Altimeter Geophysical Data Records for Global Change Studies

NASA Technical Reports Server (NTRS)

Shum, C. K.

2000-01-01

This Final Technical Report summarizes the research work conducted under NASA's Physical Oceanography Program entitled, Verification And Improvement Of ERS-112 Altimeter Geophysical Data Recorders For Global Change Studies, for the time period from January 1, 2000 through June 30, 2000. This report also provides a summary of the investigation from July 1, 1997 - June 30, 2000. The primary objectives of this investigation include verification and improvement of the ERS-1 and ERS-2 radar altimeter geophysical data records for distribution of the data to the ESA-approved U.S. ERS-1/-2 investigators for global climate change studies. Specifically, the investigation is to verify and improve the ERS geophysical data record products by calibrating the instrument and assessing accuracy for the ERS-1/-2 orbital, geophysical, media, and instrument corrections. The purpose is to ensure that the consistency of constants, standards and algorithms with TOPEX/POSEIDON radar altimeter for global climate change studies such as the monitoring and interpretation of long-term sea level change. This investigation has provided the current best precise orbits, with the radial orbit accuracy for ERS-1 (Phases C-G) and ERS-2 estimated at the 3-5 cm rms level, an 30-fold improvement compared to the 1993 accuracy. We have finalized the production and verification of the value-added ERS-1 mission (Phases A, B, C, D, E, F, and G), in collaboration with JPL PODAAC and the University of Texas. Orbit and data verification and improvement of algorithms led to the best data product available to-date. ERS-2 altimeter data have been improved and we have been active on Envisat (2001 launch) GDR algorithm review and improvement. The data improvement of ERS-1 and ERS-2 led to improvement in the global mean sea surface, marine gravity anomaly and bathymetry models, and a study of Antarctica mass balance, which was published in Science in 1998.

Role of Adult Asthma Education in Improving Asthma Control and Reducing Emergency Room Utilization and Hospital Admissions in an Inner City Hospital

PubMed Central

Mishra, Rashmi; Venkatram, Sindhaghatta; George, Teresa; Luo, Kristina; Diaz-Fuentes, Gilda

2017-01-01

Objective. Asthma education programs have been shown to decrease healthcare utilization and improve disease control and management. The purpose of our study was to evaluate the impact of an outpatient adult asthma education program in an inner city hospital caring for patients with low socioeconomic and educational status. Methods. An asthma education program was implemented in September 2014. Patients who received education from September 2014 to July 2015 were evaluated. Outcomes were compared for the same group of patients before and after education. Primary outcomes were emergency room (ER) visits and hospital admissions. Secondary outcomes were change in Asthma Control Test (ACT) score and number of pulmonary clinic visits. Results. Asthma education significantly decreased number of patients requiring ER visits and hospital admissions (p = 0.0005 and p = 0.0015, resp.). Asthma control as per ACT score ≥ 20 improved with education (p = 0.0001) with an increase in clinic visits (p = 0.0185). Conclusions. Our study suggests that implementation of a structured asthma education program in an inner city community hospital has a positive impact on reduction of ER visits and hospital admissions with improvement in asthma control. Institutional Review Board Clinical Study registration number is 01081507. PMID:28546781

Lessons Learned from the Everglades Collaborative Adaptive Management Program

EPA Science Inventory

Recent technical papers explore whether adaptive management (AM) is useful for environmental management and restoration efforts and discuss the many challenges to overcome for successful implementation, especially for large-scale restoration programs (McLain and Lee 1996; Levine ...

Identifying Metabolically Active Chemicals Using a Consensus ...

EPA Pesticide Factsheets

Endocrine disrupting chemicals (EDCs) are abundant throughout the environment and can alter neurodevelopment, behavior, and reproductive success of humans and other species by perturbing signaling pathways related to the estrogen receptor (ER). A recent study compared results across 18 ER-related assays in the ToxCast™ in vitro screening program to predict the likelihood of a chemical exhibiting in vivo estrogenic activity, with the purpose of eliminating chemicals that may produce a false signal by interfering with the technological attributes of an individual assay. However, flaws in in vitro assay design can also prevent induction of signal activity by EDCs. Another reason for not observing activity for some EDCs in in vitro assays is that metabolic activation is required to perturb ER-related pathways. In the current study, 1,024 chemicals were identified as lacking ER activity after establishing a consensus across each of the 18 ER-related in vitro assays, and nearly 2,000 primary and 3,700 secondary unique metabolites were predicted for these chemicals. The ER binding activity for each metabolite was then predicted using an existing ER activity quantitative structure activity relationship (QSAR) consensus model. Binding activity was predicted for 2-3% of the metabolites within each generation. Of the inactive parent compounds generating at least one metabolite predicted to have ER-binding activity, nearly 30% were found to have metabolites from both gene

Transformative Graduate Education through the Use of Restorative Practices

ERIC Educational Resources Information Center

Bailie, John W.; Adamson, Craig W.

2016-01-01

This chapter discusses key findings from two recent studies that examine transformative learning experiences in a restorative practices-based graduate program at the International Institute for Restorative Practices (IIRP). Restorative practices is a new interdisciplinary social science that studies the development and maintenance of relationships…

15 CFR 923.22 - Areas for preservation or restoration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Areas for preservation or restoration... preservation or restoration. The management program must include procedures whereby specific areas may be designated for the purpose of preserving or restoring them for their conservation, recreational, ecological...

The Soil Program of the Restoration Seedbank Initiative: addressing knowledge gaps in degraded soils for use in dryland restoration

NASA Astrophysics Data System (ADS)

Muñoz-Rojas, Miriam; Bateman, Amber; Erickson, Todd E.; Turner, Shane; Merritt, David J.

2017-04-01

Global environmental changes and other anthropogenic impacts are rapidly transforming the structure and functioning of ecosystems worldwide. These changes are leading to land degradation with an estimated 25 % of the global land surface being affected. Landscape-scale restoration of these degraded ecosystems has therefore been recognised globally as an international priority. In the resource-rich biodiverse semi-arid Pilbara region of north-west Western Australia hundreds of thousands of hectares are disturbed due to established and emerging iron-ore mine operations. At this scale, the need to develop cost-effective large-scale solutions to restore these landscapes becomes imperative to preserve biodiversity and achieve functionality and sustainability of these ecosystems. The Restoration Seedbank Initiative (RSB) (http://www.plants.uwa.edu.au/ research/restoration-seedbank-initiative) is a five-year multidisciplinary research project that aims to build knowledge and design strategies to restore mine-impacted landscapes in the Pilbara and other arid and semi-arid landscapes worldwide (Kildiseheva et al., 2016). The RSB comprises four research programs that focus on seedbank management and curation, seed storage, seed enhancement, and the use of alternative soil substrates (soil or growing medium program) respectively. These multi-disciplinary programs address the significant challenges of landscape scale restoration in arid systems. In the soil program we follow an integrated approach that includes the characterization of undisturbed ecosystems, assessment of restored soils with the use of soil quality indicators, and design of alternative soil substrates to support the establishment of native plant communities. A series of glasshouse studies and field trials have been conducted in the last three years to advance our knowledge on soil limitations and to provide solutions to effectively overcome these challenges in arid ecosystem restoration. These studies include (i) the determination of ecophysiological indicators influencing drought responses of arid native plants in reconstructed soils (Bateman et al, 2016), ii) the analysis of the influence of climate and edaphic factors in the recruitment of arid zone seedlings (Muñoz-Rojas et al., 2016a) and (ii) the evaluation of soil physicochemical and microbiological indicators to assess functionality of restored soils in degraded semiarid ecosystems (Muñoz-Rojas et al., 2016b). Here, we summarize our latest results in the soil program of the RSB, and propose recommendations for integrating soil science in cost-effective landscape-scale restoration practices in ecosystems worldwide. References Bateman A, Lewandrowski W, Stevens J, Muñoz-Rojas M (2016b) Ecophysiological indicators to assess drought responses of arid zone native seedlings in reconstructed soils. Land Degradation & Development, in press, DOI: 10.1002/ldr.2660. Kildisheva OA, Erickson TE, Merritt DJ, Dixon KW (2016), Setting the scene for dryland recovery: an overview and key findings from a workshop targeting seed-based restoration. Restoration Ecology 24, S36-S42. Muñoz-Rojas M, Erickson TE, Dixon KW, Merritt DJ (2016) Soil quality indicators to assess functionality of restored soils in degraded semiarid ecosystems. Restoration Ecology 24, S43-S52. DOI: 10.1111/rec.12368 Muñoz-Rojas M, Erickson TE, Martini DC, Dixon KW, Merritt DJ (2016a) Climate and soil factors influencing seedling recruitment of plant species used for dryland restoration. SOIL 2, 287-298. DOI: 10.5194/soil-2016-25

Frequency and reliability of oestrogen receptor, progesterone receptor and HER2 in breast carcinoma determined by immunohistochemistry in Australasia: results of the RCPA Quality Assurance Program.

PubMed

Francis, Glenn D; Dimech, Margaret; Giles, Leanne; Hopkins, Alison

2007-11-01

Immunohistochemistry (IHC) has replaced radioligand binding assay for the determination of oestrogen receptor (ER) status in breast carcinoma. IHC is also used for assessment of progesterone receptor (PR) and HER2. The Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) introduced a breast markers module in 2003 to evaluate the performance of laboratories with IHC for ER, PR and HER2. An audit of laboratories reporting breast carcinomas was performed in 2005 and 2006 to evaluate in-house results. Laboratories were asked to submit the hormone receptor and HER2 status on each invasive breast carcinoma for the previous 6 month period up to a maximum of 100 cases. The time periods were 1 July 2004 to 31 December 2004, and 1 July 2005 to 31 December 2005. A total of 55 laboratories returned information for 2004 and 67 for 2005. Complete data on 8128 patients was returned for both surveys, 3353 cases for 2004 and 4775 for 2005. The results were similar for both surveys. Of the 8128 cases, 59.0% were ER+/PR+, 15.9% ER+/PR-, 2.4% ER-/PR+ and 22.7% ER-/PR-. HER2 data were submitted for a total of 6512 patients (excludes 52 patients with incomplete data sets); 17.1% were reported as 3+ positive on IHC, 12.5% as 2+ and 70.4% as negative. A laboratory audit was introduced into the RCPA QAP for breast markers due to concerns raised by participating laboratories about technical differences in supplied tissues for testing. This audit indicates that overall the results for ER, PR and HER2 fall inside established parameters. However, a number of individual laboratories do not meet the target values and variation in results would impact on patient treatment decisions.

50 CFR 80.10 - Who is eligible to receive the benefits of the Acts?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.10 - Who is eligible to receive the benefits of the Acts?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.34 - How does an agency calculate net revenue from a license?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.22 - What must a State do to resolve a declaration of diversion?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

5 Star Wetland and Urban Waters Restoration Grants

EPA Pesticide Factsheets

The Five Star Restoration Program brings together students, conservation corps, other youth groups, citizen groups, corporations, landowners and government agencies to provide environmental education and training through projects that restore wetlands

Imaging the secretory compartments involved in the intracellular traffic of CHS-4, a class IV chitin synthase, in Neurospora crassa.

PubMed

Rico-Ramírez, Adriana M; Roberson, Robert W; Riquelme, Meritxell

2018-03-27

In Neurospora crassa hyphae the localization of all seven chitin synthases (CHSs) at the Spitzenkörper (Spk) and at developing septa has been well analyzed. Hitherto, the mechanisms of CHSs traffic and sorting from synthesis to delivery sites remain largely unexplored. In Saccharomyces cerevisiae exit of Chs3p from the endoplasmic reticulum (ER) requires chaperone Chs7p. Here, we analyzed the role of CSE-7, N. crassa Chs7p orthologue in the biogenesis of CHS-4 (orthologue of Chs3p). In a N. crassa Δcse-7 mutant, CHS-4-GFP no longer accumulated at the Spk and septa. Instead, fluorescence was retained in hyphal subapical regions in an extensive network of elongated cisternae (NEC) referred to previously as tubular vacuoles. In a complemented strain expressing a copy of cse-7 the localization of CHS-4-GFP at the Spk and septa was restored, providing evidence that CSE-7 is necessary for the localization of CHS-4 at hyphal tips and septa. CSE-7 was revealed at delimited regions of the ER at the immediacies of nuclei, at the NEC, and remarkably also at septa and the Spk. The organization of the NEC was dependent on the cytoskeleton. SEC-63, an extensively used ER marker, and NCA-1, a SERCA-type ATPase previously localized at the nuclear envelope, were used as markers to discern the nature of the membranes containing CSE-7. Both SEC-63 and NCA-1 were found at the nuclear envelope, but also at regions of the NEC. However, at the NEC only NCA-1 co-localized extensively with CSE-7. Observations by transmission electron microscopy revealed abundant rough ER sheets and distinct electron translucent smooth flattened cisternae, which could correspond collectively to the NEC, thorough the subapical cytoplasm. This study identifies CSE-7 as the putative ER receptor for its cognate cargo, the polytopic membrane protein CHS-4, and elucidates the complexity of the ER system in filamentous fungi. Copyright © 2018. Published by Elsevier Inc.

Precise satellite orbit determination with particular application to ERS-1

NASA Astrophysics Data System (ADS)

Fernandes, Maria Joana Afonso Pereira

The motivation behind this study is twofold. First to assess the accuracy of ERS-1 long arc ephemerides using state of the art models. Second, to develop improved methods for determining precise ERS-1 orbits using either short or long arc techniques. The SATAN programs, for the computation of satellite orbits using laser data were used. Several facilities were added to the original programs: the processing of PRARE range and altimeter data, and a number of algorithms that allow more flexible solutions by adjusting a number of additional parameters. The first part of this study, before the launch of ERS-1, was done with SEAS AT data. The accuracy of SEASAT orbits computed with PRARE simulated data has been determined. The effect of temporal distribution of tracking data along the arc and the extent to which altimetry can replace range data have been investigated. The second part starts with the computation of ERS-1 long arc solutions using laser data. Some aspects of modelling the two main forces affecting ERS-l's orbit are investigated. With regard to the gravitational forces, the adjustment of a set of geopotential coefficients has been considered. With respect to atmospheric drag, extensive research has been carried out on determining the influence on orbit accuracy of the measurements of solar fluxes (P10.7 indices) and geomagnetic activity (Kp indices) used by the atmospheric model in the computation of atmospheric density at satellite height. Two new short arc methods have been developed: the Constrained and the Bayesian method. Both methods are dynamic and consist of solving for the 6 osculating elements. Using different techniques, both methods overcome the problem of normal matrix ill- conditioning by constraining the solution. The accuracy and applicability of these methods are discussed and compared with the traditional non-dynamic TAR method.

TWRS vadose zone contamination issue expert panel report

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

Shafer, D.S.

1997-05-01

When members were first canvassed for participation in the Vadose Zone Expert Panel the stated purpose for convening the Panel was to review a controversial draft report, the SX Tank Farm Report. This report was produced by a DOE Grand Junction Project Office (GJPO) contractor, RUST Geotech, now MACTEC-ERS, for the DOE Richland Office (DOERL). Three meetings were planned for June, July and August, 1995 to review the draft report and to complete a Panel report by mid-September. The Expert Panel has found its efforts confounded by various non-technical issues. The Expert Panel has chosen to address some of themore » non-technical issues in this Preface rather than to dilute the technical discussion that follows in the body of this independent expert panel status report (Panel Report). Rather than performing a straightforward manuscript review, the Panel was asked to resolve conflicting interpretations of gamma-ray logging measurements performed in vadose zone boreholes (drywells) surrounding the high-level radioactive wastes of the SX tank farm. There are numerous and complex technical issues that must be evaluated before the vertical and radial extent of contaminant migration at the SX tank farm can be accurately assessed. When the Panel first met in early June, 1996, it quickly became apparent that the scientific and technical issues were obscured by policy and institutional affairs which have polarized discussion among various segments of the Hanford organization. This situation reflects the kinds of institutional problems described separately in reports by the National Research Council of the National Academy of Sciences (NAS/NRC), The Hanford Tanks Environmental Impacts and Policy Choices and BmTiers to Science: Technical Management of the Department of Energy Environmental Remediation Program. The Vadose Zone Characterization Program, appears to be caught between conflicting pressures and organizational mandates, some imposed from outside DOE-RL and some self-imposed. The institutional problems they encountered include having both Tank Waste Remediation System (TWRS), the parent organization of the Vadose Zone Characterization Program and Environmental Restoration (ER), each under different regulatory controls and different organizational units, seeking to defend the status quo and discount many of the Panel`s conclusions and recommendations. The results presented in the SX Tank Farm Report, especially the visualizations, have created concern in the public sector, both on a local, personal level and on a national political level.« less

50 CFR 80.91 - What is a Federal obligation of funds and how does it occur?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

50 CFR 80.91 - What is a Federal obligation of funds and how does it occur?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION...

Impact of patient-centered medical home assignment on emergency room visits among uninsured patients in a county health system.

PubMed

Roby, Dylan H; Pourat, Nadereh; Pirritano, Matthew J; Vrungos, Shelley M; Dajee, Himmet; Castillo, Dan; Kominski, Gerald F

2010-08-01

The Medical Services Initiative program--a safety net-based system of care--in Orange County included assignment of uninsured, low-income residents to a patient-centered medical home. The medical home provided case management, a team-based approach for treating disease, and increased access to primary and specialty care among other elements of a patient-centered medical home. Providers were paid an enhanced fee and pay-for-performance incentives to ensure delivery of comprehensive treatment. Medical Services Initiative enrollees who were assigned to a medical home for longer time periods were less likely to have any emergency room (ER) visits or multiple ER visits. Switching medical homes three or more times was associated with enrollees being more likely to have any ER visits or multiple ER visits. The findings provide evidence that successful implementation of the patient-centered medical home model in a county-based safety net system is possible and can reduce unnecessary ER use.

Red Wolf (Canis rufus) Recovery: A Review with Suggestions for Future Research

PubMed Central

Hinton, Joseph W.; Chamberlain, Michael J.; Rabon, David R.

2013-01-01

Simple Summary Once widespread in the Eastern United States, early 20th century predator-control programs reduced red wolves to a remnant population by the 1970s. The U.S. Fish and Wildlife Service, through the Red Wolf Recovery Program, restored red wolves to northeastern North Carolina in 1987. After 25 years of restoration efforts, issues of hybridization with coyotes, inbreeding, and human-caused mortality continue to hamper red wolf recovery. To understand how these issues influence recovery efforts, we examine the history of red wolf restoration and its challenges. We then formulate areas of research that are of direct relevance to the restoration of red wolves. Abstract By the 1970s, government-supported eradication campaigns reduced red wolves to a remnant population of less than 100 individuals on the southern border of Texas and Louisiana. Restoration efforts in the region were deemed unpromising because of predator-control programs and hybridization with coyotes. The U.S. Fish and Wildlife Service (USFWS) removed the last remaining red wolves from the wild and placed them in a captive-breeding program. In 1980, the USFWS declared red wolves extinct in the wild. During 1987, the USFWS, through the Red Wolf Recovery Program, reintroduced red wolves into northeastern North Carolina. Although restoration efforts have established a population of approximately 70–80 red wolves in the wild, issues of hybridization with coyotes, inbreeding, and human-caused mortality continue to hamper red wolf recovery. We explore these three challenges and, within each challenge, we illustrate how research can be used to resolve problems associated with red wolf-coyote interactions, effects of inbreeding, and demographic responses to human-caused mortality. We hope this illustrates the utility of research to advance restoration of red wolves. PMID:26479530

L-type Calcium Channel Blockers Enhance Trafficking and Function of Epilepsy-associated α1(D219N) Subunits of GABA(A) Receptors.

PubMed

Han, Dong-Yun; Guan, Bo-Jhih; Wang, Ya-Juan; Hatzoglou, Maria; Mu, Ting-Wei

2015-09-18

Gamma-aminobutyric acid type A (GABAA) receptors are the primary inhibitory ion channels in the mammalian central nervous system and play an essential role in regulating inhibition-excitation balance in neural circuits. The α1 subunit harboring the D219N mutation of GABAA receptors was reported to be retained in the endoplasmic reticulum (ER) and traffic inefficiently to the plasma membrane, leading to a loss of function of α1(D219N) subunits and thus idiopathic generalized epilepsy (IGE). We present the use of small molecule proteostasis regulators to enhance the forward trafficking of α1(D219N) subunits to restore their function. We showed that treatment with verapamil (4 μM, 24 h), an L-type calcium channel blocker, substantially increases the α1(D219N) subunit cell surface level in both HEK293 cells and neuronal SH-SY5Y cells and remarkably restores the GABA-induced maximal chloride current in HEK293 cells expressing α1(D219N)β2γ2 receptors to a level that is comparable to wild type receptors. Our drug mechanism study revealed that verapamil treatment promotes the ER to Golgi trafficking of the α1(D219N) subunits post-translationally. To achieve that, verapamil treatment enhances the interaction between the α1(D219N) subunit and β2 subunit and prevents the aggregation of the mutant protein by shifting the protein from the detergent-insoluble fractions to detergent-soluble fractions. By combining (35)S pulse-chase labeling and MG-132 inhibition experiments, we demonstrated that verapamil treatment does not inhibit the ER-associated degradation of the α1(D219N) subunit. In addition, its effect does not involve a dynamin-1 dependent endocytosis. To gain further mechanistic insight, we showed that verapamil increases the interaction between the mutant protein and calnexin and calreticulin, two major lectin chaperones in the ER. Moreover, calnexin binding promotes the forward trafficking of the mutant subunit. Taken together, our data indicate that verapamil treatment enhances the calnexin-assisted forward trafficking and subunit assembly, which leads to substantially enhanced functional surface expression of the mutant receptors. Since verapamil is an FDA-approved drug that crosses blood-brain barrier and has been used as an additional medication for some epilepsies, our findings suggest that verapamil holds great promise to be developed to ameliorate IGE resulting from α1(D219N) subunit trafficking deficiency.

Brief Counseling and Exercise Referral Scheme: A Pragmatic Trial in Mexico.

PubMed

Gallegos-Carrillo, Katia; García-Peña, Carmen; Salmerón, Jorge; Salgado-de-Snyder, Nelly; Lobelo, Felipe

2017-02-01

The effectiveness of clinical-community linkages for promotion of physical activity (PA) has not been explored in low- and middle-income countries. This study assessed the effectiveness of a primary care-based, 16-week intervention rooted in behavioral theory approaches to increase compliance with aerobic PA recommendations. Pragmatic cluster randomized trial. Patients had diagnosed (<5 years) hypertension, were aged 35-70 years, self-reported as physically inactive, had a stated intention to engage in PA, and attended Primary Healthcare Centers in the Social Security health system in Cuernavaca, Mexico. Of 23 Primary Healthcare Centers, four were selected based on proximity (5 km radius) to a center. Each center was randomized to a brief PA counseling (BC, n=2) or an exercise referral (ER, n=2) intervention. The study was conducted between 2011 and 2012. Change in objectively measured PA levels (ActiGraph GT3X accelerometers) at baseline, 16, and 24 weeks. Intention-to-treat analyses were used to assess the effectiveness of the intervention overall and according to ER intervention attendance. Longitudinal multilevel mixed-effects analyses considering the interaction (time by intervention) were conducted. Each model was also adjusted by baseline value of the outcome measure, demographic and health variables, social support, PA self-efficacy, and barriers. Minutes/week of objectively measured moderate to vigorous PA increased by 40 and 53 minutes in the ER and BC groups, respectively (p=0.59). Participants attending >50% of ER program sessions increased their moderate to vigorous PA by 104 minutes/week and compliance with aerobic PA recommendations by 23.8%, versus the BC group (both p<0.05). Both BC and ER led to modest improvements in PA levels, with no significant differences between groups. Adequate adherence with the ER program sessions led to significant improvements in compliance with aerobic PA recommendations versus BC. These results can help guide development and implementation of programs integrating standardized PA assessment, counseling, and referrals via clinical-community linkages in Mexico and other low- and middle-income countries in the region. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Production possibility frontiers and socioecological tradeoffs for restoration of fire adapted forests

Treesearch

Alan A. Ager; Michelle A. Day; Kevin Vogler

2016-01-01

We used spatial optimization to analyze alternative restoration scenarios and quantify tradeoffs for a large, multifaceted restoration program to restore resiliency to forest landscapes in the western US. We specifically examined tradeoffs between provisional ecosystem services, fire protection, and the amelioration of key ecological stressors. The results...

50 CFR 80.1 - What does this part do?

Code of Federal Regulations, 2014 CFR

2014-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General § 80.1 What does this... apportionments from the Federal Aid to Wildlife Restoration Fund (16 U.S.C. 669(b)), if authorized, and the Sport...

50 CFR 80.1 - What does this part do?

Code of Federal Regulations, 2012 CFR

2012-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General § 80.1 What does this part do... the Federal Aid to Wildlife Restoration Fund (16 U.S.C. 669(b)), if authorized, and the Sport Fish...

50 CFR 80.1 - What does this part do?

Code of Federal Regulations, 2013 CFR

2013-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE AND SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General § 80.1 What does this... apportionments from the Federal Aid to Wildlife Restoration Fund (16 U.S.C. 669(b)), if authorized, and the Sport...

7 CFR 625.12 - The HFRP restoration plan development.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false The HFRP restoration plan development. 625.12 Section... CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE WATER RESOURCES HEALTHY FORESTS RESERVE PROGRAM § 625.12 The HFRP restoration plan development. (a) The development of the HFRP restoration plan shall be made...

50 CFR 80.1 - What does this part do?

Code of Federal Regulations, 2011 CFR

2011-10-01

...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS General § 80.1 What does this part do... the Federal Aid to Wildlife Restoration Fund (16 U.S.C. 669(b)), if authorized, and the Sport Fish...