A Comparison of Visual Outcomes and Patient Satisfaction Between Photorefractive Keratectomy and Femtosecond Laser-Assisted In Situ Keratomileusis

PubMed Central

Hashmani, Nauman; Hashmani, Sharif; Ramesh, Priyanka; Ahmed, Junaid; Kumar, Jaish; Kumar, Arun; Jamali, Munira

2017-01-01

Purpose To compare visual outcomes and satisfaction among patients of photorefractive keratectomy (PRK; Wavelight EX 500, Alcon, Ft Worth, TX, USA) and femtosecond laser-assisted in situ keratomileusis (FAL; Wavelight FS 200 laser and Wavelight EX 500, Alcon, Ft Worth, TX, USA). Methods We performed a retrospective study of 409 eyes in 207 patients that underwent either PRK (n=90) or FAL (n=117) at the two centers of Hashmanis Hospital, Karachi, Pakistan. The included refractive outcomes were sphere diopters (D), cylinder D, and spherical equivalent D. Additionally, visual acuities were included. All of these were assessed preoperatively and at the one-month postoperative check-up. Patient satisfaction was gauged at the time of chart review by contacting the patient. Results When looking at the postoperative outcomes, we found all values to be statistically significant (p<0.001) with superior outcomes in the FAL cohort. Additionally, 90% and 15% of eyes achieved a postoperative uncorrected visual acuity (UCVA) of 20/20 in FAL and PRK, respectively. Furthermore, the efficacy indexes of the FAL and PRK arms were 1.00 and 0.82, respectively. The predictability of the procedures were 92.1% and 64.9%, respectively. Lastly, 93.3% of patients were satisfied with FAL and 95.7% with PRK. Conclusion Our study shows superior visual outcomes in patients undergoing FAL. However, we found a higher satisfaction rate in those that underwent PRK, perhaps due to the higher cost of FAL. PMID:29119072

Corrective Action Decision Document/Closure Report for Corrective Action Unit 482: Area 15 U15a/e Muckpiles and Ponds Nevada Test Site

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

NSTec Environmental Restoration

This Corrective Action Decision Document /Closure Report (CADD/CR) was prepared by the Defense Threat Reduction Agency (DTRA) for Corrective Action Unit (CAU) 482 U15a/e Muckpiles and Ponds. This CADD/CR is consistent with the requirements of the Federal Facility Agreement and Consent Order agreed to by the State of Nevada, the U.S. Department of Energy, and the U.S. Department of Defense. Corrective Action Unit 482 is comprised of three Corrective Action Sites (CASs) and one adjacent area: CAS 15-06-01, U15e Muckpile; CAS 15-06-02, U15a Muckpile; CAS 15-38-01, Area 15 U15a/e Ponds; and Drainage below the U15a Muckpile. The purpose of thismore » CADD/CR is to provide justification and documentation supporting the recommendation for closure with no further corrective action, by placing use restrictions on the three CASs and the adjacent area of CAU 482. To support this recommendation, a corrective action investigation (CAI) was performed in September 2002. The purpose of the CAI was to fulfill the following data needs as defined during the Data Quality Objective (DQO) process: (1) Determine whether contaminants of concern (COCs) are present. (2) If COCs are present, determine their nature and extent. (3) Provide sufficient information and data to determine appropriate corrective actions. The CAU 482 dataset from the CAI was evaluated based on the data quality indicator parameters. This evaluation demonstrated the quality and acceptability of the dataset for use in fulfilling the DQO data needs. Analytes detected during the CAI were evaluated against final action levels (FALs) established in this document. Tier 2 FALS were determined for the hazardous constituents of total petroleum hydrocarbons (TPH)-diesel-range organics (DRO) and the radionuclides americium (Am)-241, cesium (Cs)-137, plutonium (Pu)-238, and Pu-239. The Tier 2 FALs were calculated for the radionuclides using site-specific information. The hazardous constituents of TPH-DRO were compared to the PALs defined in the CAIP, and because none of the preliminary action levels (PALs) were exceeded, the PALs became the FALs. The radionuclide FALs were calculated using the Residual Radioactive (RESRAD) code (version 6.21). The RESRAD calculation determined the activities of all radionuclides that together would sum to an exposure dose of 25 millirem per year to a site receptor (based on their relative abundances at each CAS). Based on the field investigation, the following contaminants were determined to be present at concentrations exceeding their corresponding FALs: (1) CAS 15-06-01 - None. (2) CAS 15-06-02 - Cs-137 and Pu-239. (3) CAS 15-38-01 - Am-241, Cs-137, Pu-238, and Pu-239. (4) Drainage below CAS 15-06-02 - Cs-137 and Pu-239. Based on the data and risk evaluations, the DQO data needs presented in the Corrective Action Investigation Plan were met, and the data accurately represent the radiological and chemical risk present at CAU 482. Based on the results of the CAI data evaluation, it was determined that closure in place with use restrictions is the appropriate corrective action for CAU 482 and that use restrictions will effectively control exposure to future land users. This is based on the fact that even though the FALs were exceeded in a few samples, this remote, controlled access site poses only limited risk overall to public health and the environment. Given the relatively low levels of contamination present, it would create a greater hazard to worker safety, public health, and the environment to remove the contamination, transport it, and bury it at another location. Therefore, DTRA provides the following recommendations: (1) Close COCs in place at CAS 15-06-02, CAS 15-38-01, and the drainage below CAS 15-06-02 with use restrictions. (2) No further action for CAU 482. (3) A Notice of Completion be issued to DTRA by the Nevada Division of Environmental Protection for closure of CAU 482. (4) Move CAU 482 from Appendix III to Appendix IV of the Federal Facility Agreement and Consent Order.« less

Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis.

PubMed

Zou, Zhang-Yu; Zhou, Zhi-Rui; Che, Chun-Hui; Liu, Chang-Yun; He, Rao-Li; Huang, Hua-Pin

2017-07-01

Genetic studies have shown that C9orf72 , SOD1 , TARDBP and FUS are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS. We performed an extensive literature research to identify all original articles reporting frequencies of C9orf72 , SOD1 , TARDBP and FUS mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis. 111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the C9orf72 repeat expansions (FALS 33.7%, SALS 5.1%), followed by SOD1 (FALS 14.8%, SALS 1.2%), TARDBP (FALS 4.2%, SALS 0.8%) and FUS mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were SOD1 mutations (FALS 30.0%, SALS 1.5%), followed by FUS (FALS 6.4%, SALS 0.9%), C9orf72 (FALS 2.3%, SALS 0.3%) and TARDBP (FALS 1.5%, SALS 0.2%) mutations. These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Closure Report for Corrective Action Unit 574: Neptune, Nevada National Security Site, Nevada

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

NSTec Environmental Restoration

Corrective Action Unit (CAU) 574 is identified in the Federal Facility Agreement and Consent Order (FFACO) as 'Neptune' and consists of the following two Corrective Action Sites (CASs), located in Area 12 of the Nevada National Security Site: (1) CAS 12-23-10, U12c.03 Crater (Neptune); and (2) CAS 12-45-01, U12e.05 Crater (Blanca). This Closure Report presents information supporting closure of CAU 574 according to the FFACO (FFACO, 1996 [as amended March 2010]) and the Streamlined Approach for Environmental Restoration Plan for CAU 574 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office [NNSA/NSO], 2011). The following activities were performedmore » to support closure of CAU 574: (1) In situ external dose rate measurements were collected using thermoluminescent dosimeters at CAS 12-45-01, U12e.05 Crater (Blanca). (2) Total effective dose rates were determined at both sites by summing the internal and external dose rate components. (3) A use restriction (UR) was implemented at CAS 12-23-10, U12c.03 Crater (Neptune). Areas that exceed the final action level (FAL) of 25 millirems per year (mrem/yr) based on the Occasional Use Area exposure scenario are within the existing use restricted area for CAU 551. The 25-mrem/yr FAL is not exceeded outside the existing CAU 551 UR for any of the exposure scenarios (Industrial Area, Remote Work Area, and Occasional Use Area). Therefore, the existing UR for CAU 551 is sufficient to bound contamination that exceeds the FAL. (4) An administrative UR was implemented at CAS 12-45-01, U12e.05 Crater (Blanca) as a best management practice (BMP). The 25-mrem/yr FAL was not exceeded for the Remote Work Area or Occasional Use Area exposure scenarios; therefore, a UR is not required. However, because the 25-mrem/yr FAL was exceeded for the Industrial Area exposure scenario, an administrative UR was established as a BMP. UR documentation is included as Appendix B. The UR at CAS 12-23-10, U12c.03 Crater (Neptune), is within the existing UR for CAU 551. Additional postings were not installed, and annual post-closure inspections will be performed in conjunction with the inspections performed for CAU 551. At CAS 12-45-01, U12e.05 Crater (Blanca), the administrative UR does not require postings or inspections. NNSA/NSO requests the following: (1) A Notice of Completion from the Nevada Division of Environmental Protection to NNSA/NSO for closure of CAU 574; and (2) The transfer of CAU 574 from Appendix III to Appendix IV, Closed Corrective Action Units, of the FFACO« less

In-cell NMR reveals potential precursor of toxic species from SOD1 fALS mutants

NASA Astrophysics Data System (ADS)

Luchinat, Enrico; Barbieri, Letizia; Rubino, Jeffrey T.; Kozyreva, Tatiana; Cantini, Francesca; Banci, Lucia

2014-11-01

Mutations in the superoxide dismutase 1 (SOD1) gene are related to familial cases of amyotrophic lateral sclerosis (fALS). Here we exploit in-cell NMR to characterize the protein folding and maturation of a series of fALS-linked SOD1 mutants in human cells and to obtain insight into their behaviour in the cellular context, at the molecular level. The effect of various mutations on SOD1 maturation are investigated by changing the availability of metal ions in the cells, and by coexpressing the copper chaperone for SOD1, hCCS. We observe for most of the mutants the occurrence of an unstructured SOD1 species, unable to bind zinc. This species may be a common precursor of potentially toxic oligomeric species, that are associated with fALS. Coexpression of hCCS in the presence of copper restores the correct maturation of the SOD1 mutants and prevents the formation of the unstructured species, confirming that hCCS also acts as a molecular chaperone.

Corrective Action Decision Document/Closure Report for Corrective Action Unit 561: Waste Disposal Areas, Nevada National Security Site, Nevada, Revision 0

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

Mark Krauss

2011-08-01

CAU 561 comprises 10 CASs: (1) 01-19-01, Waste Dump; (2) 02-08-02, Waste Dump and Burn Area; (3) 03-19-02, Debris Pile; (4) 05-62-01, Radioactive Gravel Pile; (5) 12-23-09, Radioactive Waste Dump; (6) 22-19-06, Buried Waste Disposal Site; (7) 23-21-04, Waste Disposal Trenches ; (8) 25-08-02, Waste Dump; (9) 25-23-21, Radioactive Waste Dump; and (10) 25-25-19, Hydrocarbon Stains and Trench. The purpose of this CADD/CR is to provide justification and documentation supporting the recommendation for closure of CAU 561 with no further corrective action. The purpose of the CAI was to fulfill the following data needs as defined during the DQO process:more » (1) Determine whether COCs are present; (2) If COCs are present, determine their nature and extent; and (3) Provide sufficient information and data to complete appropriate corrective actions. The following contaminants were determined to be present at concentrations exceeding their corresponding FALs: (1) No contamination exceeding FALs was identified at CASs 01-19-01, 03-19-02, 05-62-01, 12-23-09, and 22-19-06. (2) The surface and subsurface soil within the burn area at CAS 02-08-02 contains arsenic and lead above the FALs of 23 milligrams per kilogram (mg/kg) and 800 mg/kg, respectively. The surface and subsurface soil within the burn area also contains melted lead slag (potential source material [PSM]). The soil within the waste piles contains polyaromatic hydrocarbons (PAHs) above the FALs. The contamination within the burn area is spread throughout the area, as it was not feasible to remove all the PSM (melted lead), while at the waste piles, the contamination is confined to the piles. (3) The surface and subsurface soils within Trenches 3 and 5 at CAS 23-21-04 contain arsenic and polychlorinated biphenyls (PCBs) above the FALs of 23 mg/kg and 0.74 mg/kg, respectively. The soil was removed from both trenches, and the soil that remains at this CAS does not contain contamination exceeding the FALs. Lead bricks and counterweights were also removed, and the soil below these items does not contain contamination that exceeds the FAL for lead. (4) The concrete-like material at CAS 25-08-02 contains arsenic above the FAL of 23 mg/kg. This concrete-like material was removed, and the soil that remains at this CAS does not contain contamination exceeding the FALs. Lead-acid batteries were also removed, and the soil below the batteries does not contain contamination that exceeds the FAL for lead. (5) The surface soils within the main waste dump at the posted southern radioactive material area (RMA) at CAS 25-23-21 contain cesium (Cs)-137 and PCBs above the FALs of 72.9 picocuries per gram (pCi/g) and 0.74 mg/kg, respectively. The soil was removed from the RMA, and the soil that remains at this CAS does not contain contamination exceeding the FALs. (6) The surface and subsurface soils at CAS 25-25-19 do not contain contamination exceeding the FALs. In addition, lead bricks were removed, and the soil below these items does not contain contamination that exceeds the FAL for lead. The following best management practices were implemented: (1) Housekeeping debris at CASs 02-08-02, 23-21-04, 25-08-02, 25-23-21, and 25-25-19 was removed and disposed of; (2) The open trenches at CAS 23-21-04 were backfilled; (3) The waste piles at CAS 25-08-02 were removed and the area leveled to ground surface; and (4) The remaining waste piles at the main waste dump at CAS 25-23-21 were leveled to ground surface. Therefore, NNSA/NSO provides the following recommendations: (1) No further action for CASs 01-19-01, 03-19-02, 05-62-01, 12-23-09, and 22-19-06; (2) Closure in place with an FFACO use restriction (UR) at CAS 02-08-02 for the remaining PAH-, arsenic-, and lead-contaminated soil, and the melted lead PSM. The UR form and map have been filed in the NNSA/NSO Facility Information Management System, the FFACO database, and the NNSA/NSO CAU/CAS files; (3) No further corrective action at CAS 23-21-04, as the lead bricks and counterweights (PSM) have been removed, and the COCs of arsenic and PCBs in soil have been removed; (4) No further corrective action at CAS 25-08-02, as the COC of arsenic in soil has been removed, and the lead-acid batteries have been removed; (5) No further corrective action at CAS 25-23-21, as the COCs of Cs-137 and PCBs in soil have been removed, and the cast-iron pipes have been removed and disposed of; (6) No further corrective action at CAS 25-25-19, as the lead bricks (PSM) been removed; (7) A Notice of Completion to the NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 561; and (8) Corrective Action Unit 561 should be moved from Appendix III to Appendix IV of the FFACO.« less

Addendum to the Closure Report for Corrective Action Unit 326: Areas 6 and 27 Release Sites, Nevada Test Site, Nevada, Revision 1

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

Grant Evenson

This document constitutes an addendum to the Closure Report for Corrective Action Unit 326: Areas 6 and 27 Release Sites, Nevada Test Site, Nevada (Revision 1), December 2002 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • Themore » cover, title, and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 06-25-01, CP-1 Heating Oil Release. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 403: Second Gas Station, Tonopah Test Range, Nevada, Revision 0

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

Grant Evenson

This document constitutes an addendum to the Closure Report for Corrective Action Unit 403: Second Gas Station, Tonopah Test Range, Nevada, September 1998 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title, and signature pagesmore » of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 03-02-004-0360, Underground Storage Tanks. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 339: Area 12 Fleet Operations Steam Cleaning Discharge Area, Nevada Test Site, Revision 0

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

Grant Evenson

This document constitutes an addendum to the Closure Report for CAU 339: Area 12 Fleet Operations Steam Cleaning Discharge Area Nevada Test Site, December 1997 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title, andmore » signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 12-19-01, A12 Fleet Ops Steam Cleaning Efflu. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum 2 to the Closure Report for Corrective Action Unit 358: Areas 18, 19, 20 Cellars/Mud Pits, Nevada Test Site, Nevada, Revison 0

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

Grant Evenson

This document constitutes an addendum to the Closure Report for Corrective Action Unit 358: Areas 18, 19, 20 Cellars/Mud Pits, Nevada Test Site, Nevada, January 2004 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title,more » and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 19-09-05, Mud Pit. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Corrective Action Plan for Corrective Action Unit 366: Area 11 Plutonium Valley Dispersion Sites, Nevada National Security Site, Nevada

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

None

This Corrective Action Plan has been prepared for Corrective Action Unit (CAU) 366, Area 11 Plutonium Valley Dispersion Sites, in accordance with the Federal Facility Agreement and Consent Order (FFACO, 1996 as amended). CAU 366 consists of the following six Corrective Action Sites (CASs) located in Area 11 of the Nevada National Security Site: · CAS 11-08-01, Contaminated Waste Dump #1 · CAS 11-08-02, Contaminated Waste Dump #2 · CAS 11-23-01, Radioactively Contaminated Area A · CAS 11-23-02, Radioactively Contaminated Area B · CAS 11-23-03, Radioactively Contaminated Area C · CAS 11-23-04, Radioactively Contaminated Area D Site characterization activities weremore » performed in 2011 and 2012, and the results are presented in Appendix A of the Corrective Action Decision Document (CADD) for CAU 366 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office [NNSA/NSO], 2012a). The following closure alternatives were recommended in the CADD: · No further action for CAS 11-23-01 · Closure in place for CASs 11-08-01, 11-08-02, 11-23-02, 11-23-03, and 11-23-04 The scope of work required to implement the recommended closure alternatives includes the following: · Non-engineered soil covers approximately 3 feet thick will be constructed at CAS 11-08-01 over contaminated waste dump (CWD) #1 and at CAS 11-08-02 over CWD #2. · FFACO use restrictions (URs) will be implemented for the areas where the total effective dose (TED) exceeds the final action level (FAL) of 25 millirems per Occasional Use Area year (mrem/OU-yr). The FAL is based on an assumption that the future use of the site includes occasional work activities and that workers will not be assigned to the area on a regular basis. A site worker under this scenario is assumed to be on site for a maximum of 80 hours per year for 5 years. The FFACO UR boundaries will encompass the areas where a worker would be exposed to 25 millirems of radioactivity per year if they are present for 80 hours per year. These boundaries will be defined as follows: – It is assumed that radiological contaminants are present at CAS 11-08-01 and CAS 11-08-02 within CWDs #1 and #2 at levels exceeding the FAL. Therefore, UR boundaries will be established around the perimeters of the soil covers that will be constructed at CWD #1 and CWD #2. A geophysical survey revealed buried metallic debris outside the fence and adjacent to CWD #1. Therefore, the UR boundary for CWD #1 will be expanded to include the mound containing buried material. – It is assumed that radiological contaminants are present at CAS 11-23-02, CAS 11-23-03, and CAS 11-23-04, within the three High Contamination Area (HCA) boundaries associated with the 11b, 11c, and 11d test areas at levels exceeding the FAL. Therefore, the UR boundaries will be established around the perimeters of the HCAs. The TED at an area of soil impacted by radiological debris outside the fence and adjacent to the 11c test area HCA exceeds the FAL of 25 mrem/OU-yr. Because the radiological impact from the debris at this location is visible on the aerial flyover radiological survey, all other areas within this isopleth of the flyover survey are conservatively also assumed to exceed the FAL. Therefore, the UR boundaries for the 11b, 11c, and 11d test areas will be expanded to include the areas within this isopleth. · The FFACO URs will all be located within the large Contamination Area (CA) that encompasses Plutonium Valley. Because access to the CA is limited and entry into the CA for post-closure inspections and maintenance would be impractical, UR warning signs will be posted along the existing CA fence. In accordance with the Soils Risk-Based Corrective Action Evaluation Process (NNSA/NSO, 2012b), an administrative UR will be implemented as a best management practice for the areas where the TED exceeds 25 millirems per Industrial Area year. This limit is based on continuous industrial use of the site and addresses exposure to industrial workers who would regularly be assigned to the work area for an entire career (250 days per year, 8 hours per day, for 25 years). Establishing an administrative UR will prevent inadvertent exposure of workers to radioactivity if a more intensive use of the site were to be considered in the future. As a precautionary measure, the administrative UR boundary will be expanded to include the areas where removable contamination is present that exceeds the criterion for a CA. This will further ensure that workers will not perform future activities within this area without being notified of the presence of site contaminants. Therefore, the administrative UR boundary will be established around the perimeters of the large CA that encompasses the site and the CAs associated with the decontamination station and hot park.« less

Valorization of lignite combustion residues and ferroalumina in the production of aggregates.

PubMed

Anagnostopoulos, I M; Stivanakis, V E; Angelopoulos, G N; Papamantellos, D C

2010-02-15

The present research study investigates the synergy of industrial solid by-products from lignite combustion (fly ash and bottom ash) and aluminum production (ferroalumina) in the production of lightweight aggregates (LWA). The process consists of two stages, pelletization and sintering. Bottom ash (BA) is used as the principal raw material in mixtures while ferroalumina (FAL) is added in lower percentages (5-30 wt%). BA carbon content is used as the fuel of sintering process in high temperatures, around 1250 degrees C, and gas generation is responsible for porous structure formation. Physical properties such as porosity, water absorption and bulk density, of sintering products are measured. Increase of FAL percentage in sintering mixtures results in decrease of porosity from 61% to 35% and of water absorption from 61% to 21% and in increase of bulk density from 1.02 g/cm(3) to 1.80 g/cm(3) of the produced aggregates. Aggregates produced by FAL addition up to 20 wt% are characterized as LWA. Aggregates formed are used in the production of concrete specimens. Compressive strength of concrete increases by increasing FAL addition in aggregates from 5 wt% to 15 wt% (highest strength value), while decrease by increasing FAL addition from 20 wt% to 30 wt%. FAL addition in lignite ashes sintering mixtures (up to 15 wt%) is considered as an important parameter for enhancing aggregates strength.

Addendum to the Closure Report for Corrective Action Unit 427: Area 3 Septic Waste Systems 2, 6, Tonopah Test Range, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the April 1999, Closure Report for Corrective Action Unit 427: Area 3 Septic Waste Systems 2, 6, Tonopah Test Range, Nevada as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modificationmore » document, this addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 03-05-002-SW02, Septic Waste System • CAS 03-05-002-SW06, Septic Waste System These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Streamlined Approach for Environmental Restoration Closure Report for Corrective Action Unit 454: Historical Undrground Storage Tank Release Sites, Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the April 1998, Streamlined Approach for Environmental Restoration Closure Report for Corrective Action Unit 454: Historical Underground Storage Tank Release Sites as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modificationmore » document, this addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 12-25-09, Spill 960722-02 (from UST 12-B-3). This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 335: Area 6 Injection Well and Drain Pit Nevada Test Site, Nevada, Revison 0

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

Lynn Kidman

This document constitutes an addendum to the June 2003, Closure Report for Corrective Action Unit 335: Area 6 Injection Well and Drain Pit as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consistsmore » of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 06-20-02, 20-inch Cased Hole • CAS 06-23-03, Drain Pit These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Closure Report for Corrective Action Unit 356: Mud Pits and Disposal Sites Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the November 2002, Closure Report for Corrective Action Unit 356: Mud Pits and Disposal Sites as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: •more » This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 03-04-01, Area 3 Change House Septic System • CAS 03-09-04, Mud Pit These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Corrective Action Decision Document/Closure Report for Corrective Action Unit 321: Area 22 Weather Station Fuel Storage Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the August 2001, Corrective Action Decision Document / Closure Report for Corrective Action Unit 321: Area 22 Weather Station Fuel Storage as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modificationmore » document, this addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 22-99-05, Fuel Storage Area. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 398: Area 25 Spill Sites, Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the April 2003, Closure Report for Corrective Action Unit 398: Area 25 Spill Sites as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • Thismore » cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 25-25-17, Subsurface Hydraulic Oil Spill. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 423: Area 3 Building 03-60 Underground Discharge Point, Tonopah Test Range, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the July 1999, Closure Report for Corrective Action Unit 423: Area 3 Building 0360 Underground Discharge Point, Tonopah Test Range, Nevada as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modificationmore » document, this addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 03-02-002-0308, Underground Discharge Point. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 214: Bunkers and Storage Areas Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the September 2006, Closure Report for Corrective Action Unit 214: Bunkers and Storage Areas as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • Thismore » cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 25-23-01, Contaminated Materials • CAS 25-23-19, Radioactive Material Storage These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Closure Report for Corrective Action Unit 342: Area 23 Mercury Fire Training Pit Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the April 2000, Closure Report for Corrective Action Unit 342: Area 23 Mercury Fire Training Pit as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of:more » • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 23-56-01, Former Mercury Fire Training Pit. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 322: Areas 1 & 3 Release Sites and Injection Wells Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the June 2006, Closure Report for Corrective Action Unit 322: Areas 1 & 3 Release Sites and Injection Wells as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, thismore » addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 01-25-01, AST Release • CAS 03-25-03, Mud Plant AST Diesel Release These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

PubMed Central

Kenna, Kevin P; van Doormaal, Perry T C; Dekker, Annelot M; Ticozzi, Nicola; Kenna, Brendan J; Diekstra, Frank P; van Rheenen, Wouter; van Eijk, Kristel R; Jones, Ashley R; Keagle, Pamela; Shatunov, Aleksey; Sproviero, William; Smith, Bradley N; van Es, Michael A; Topp, Simon D; Kenna, Aoife; Miller, Jack W; Fallini, Claudia; Tiloca, Cinzia; McLaughlin, Russell L; Vance, Caroline; Troakes, Claire; Colombrita, Claudia; Mora, Gabriele; Calvo, Andrea; Verde, Federico; Al-Sarraj, Safa; King, Andrew; Calini, Daniela; de Belleroche, Jacqueline; Baas, Frank; van der Kooi, Anneke J; de Visser, Marianne; Asbroek, Anneloor L M A ten; Sapp, Peter C; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Muñoz-Blanco, José Luis; Strom, Tim M; Meitinger, Thomas; Morrison, Karen E; Lauria, Giuseppe; Williams, Kelly L; Leigh, P Nigel; Nicholson, Garth A; Blair, Ian P; Leblond, Claire S; Dion, Patrick A; Rouleau, Guy A; Pall, Hardev; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Taroni, Franco; Boylan, Kevin B; Van Blitterswijk, Marka; Rademakers, Rosa; Esteban-Pérez, Jesús; García-Redondo, Alberto; Van Damme, Phillip; Robberecht, Wim; Chio, Adriano; Gellera, Cinzia; Drepper, Carsten; Sendtner, Michael; Ratti, Antonia; Glass, Jonathan D; Mora, Jesús S; Basak, Nazli A; Hardiman, Orla; Ludolph, Albert C; Andersen, Peter M; Weishaupt, Jochen H; Brown, Robert H; Al-Chalabi, Ammar; Silani, Vincenzo; Shaw, Christopher E; van den Berg, Leonard H; Veldink, Jan H; Landers, John E

2017-01-01

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology. PMID:27455347

Effect of CCS on the Accumulation of FALS SOD1 Mutant-containing Aggregates and on Mitochondrial Translocation of SOD1 Mutants: Implication of a Free Radical Hypothesis

PubMed Central

Kim, Ha Kun; Chung, Youn Wook; Chock, P. Boon; Yim, Moon B.

2011-01-01

Missense mutations of SOD1 are linked to familial amyotrophic lateral sclerosis (FALS) through a yet-to-be identified toxic-gain-of-function. One of the proposed mechanisms involves enhanced aggregate formation. However, a recent study showed that dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated FALS symptoms with enhanced mitochondrial pathology compared to G93A mice. Using a dicistronic mRNA to simultaneously generate hSOD1 mutants, G93A, A4V and G85R, and hCCS in AAV293 cells, we revealed: (i) CCS is degraded primarily via a macroautophagy pathway. It forms a stable heterodimer with inactive G85R, and via its novel copper chaperone-independent molecular chaperone activity facilitates G85R degradation via a macroautophagy-mediated pathway. For active G93A and A4V, CCS catalyzes their maturation to form active and soluble homodimers. (ii) CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H2O2, mitochondrial translocation of inactive SOD1 mutants. These results, together with previous reports showing FALS SOD1 mutants enhanced free radical-generating activity, provide a mechanistic explanation for the observations with G93A/CCS dual transgenic mice and suggest that free radical generation by FALS SOD1, enhanced by CCS, may, in part, be responsible for the FALS SOD1 mutant-linked aggregation, mitochondrial translocation, and degradation. PMID:21354101

Corrective Action Decision Document/Closure Report for Corrective Action Unit 374: Area 20 Schooner Unit Crater, Nevada National Security Site, Nevada with ROTC 1 and 2, Revision 0

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

Matthews, Patrick

Corrective Action Unit 374 comprises five corrective action sites (CASs): • 18-22-05, Drum • 18-22-06, Drums (20) • 18-22-08, Drum • 18-23-01, Danny Boy Contamination Area • 20-45-03, U-20u Crater (Schooner) The purpose of this Corrective Action Decision Document/Closure Report is to provide justification and documentation supporting the recommendation that no further corrective action is needed for CAU 374 based on the implementation of corrective actions. The corrective action of closure in place with administrative controls was implemented at CASs 18-23-01 and 20-45-03, and a corrective action of removing potential source material (PSM) was conducted at CAS 20-45-03. The othermore » CASs require no further action; however, best management practices of removing PSM and drums at CAS 18-22-06, and removing drums at CAS 18-22-08 were performed. Corrective action investigation (CAI) activities were performed from May 4 through October 6, 2010, as set forth in the Corrective Action Investigation Plan for Corrective Action Unit 374: Area 20 Schooner Unit Crater, Nevada Test Site, Nevada. The approach for the CAI was divided into two facets: investigating the primary release of radionuclides and investigating other releases (migration in washes and chemical releases). The purpose of the CAI was to fulfill data needs as defined during the data quality objective (DQO) process. The CAU 374 dataset of investigation results was evaluated based on the data quality indicator parameters. This evaluation demonstrated the dataset is acceptable for use in fulfilling the DQO data needs. Analytes detected during the CAI were evaluated against final action levels (FALs) established in this document. Radiological doses exceeding the FAL of 25 millirem per year were found to be present in the surface soil that was sampled. It is assumed that radionuclide levels present in subsurface media within the craters and ejecta fields (default contamination boundaries) at the Danny Boy and Schooner sites exceed the FAL. It is also assumed that PSM in the form of lead-acid batteries at Schooner exceeds the FAL. Therefore, corrective actions were undertaken that consist of removing PSM, where present, and implementing a use restriction and posting warning signs at the Danny Boy and Schooner sites. These use restrictions were recorded in the FFACO database; the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Facility Information Management System; and the NNSA/NSO CAU/CAS files. Therefore, NNSA/NSO provides the following recommendations: • No further corrective actions are necessary for CAU 374. • A Notice of Completion to NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 374. • Corrective Action Unit 374 should be moved from Appendix III to Appendix IV of the FFACO.« less

Addendum to the Streamlined Approach for Environmental Restoration Closure Report for Corrective Action Unit 452: Historical Underground Storage Tank Release Sites, Nevada Test Site, Nevada, Revision 0

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

Grant Evenson

This document constitutes an addendum to the Streamlined Approach for Environmental Restoration Closure Report for Corrective Action Unit 452: Historical Underground Storage Tank Release Sites, Nevada Test Site, Nevada, April 1998 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additionalmore » information • The cover, title, and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the URs for CASs: • 25-25-09, Spill H940825C (from UST 25-3101-1) • 25-25-14, Spill H940314E (from UST 25-3102-3) • 25-25-15, Spill H941020E (from UST 25-3152-1) These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum 2 to the Streamlined Approach for Environmental Restoration Closure Report for Corrective Action Unit 454: Historical Underground Storage Tank Release Sites, Nevada Test Site, Nevada, Revision 0

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

Grant Evenson

This document constitutes an addendum to the Streamlined Approach for Environmental Restoration Closure Report for Corrective Action Unit 454: Historical Underground Storage Tank Release Sites, Nevada Test Site, Nevada, April 1998 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additionalmore » information • The cover, title, and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the URs for CASs: • 12-25-08, Spill H950524F (from UST 12-B-1) • 12-25-10, Spill H950919A (from UST 12-COMM-1) These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Strategies for the Construction of Supramolecular Dimers versus Homoleptic 1D Coordination Polymers Starting from the Diphosphorus [Cp2Mo2(CO)4(η2‐P2)] Complex and Silver(I) Salts

PubMed Central

Elsayed Moussa, Mehdi; Fleischmann, Martin; Peresypkina, Eugenia V.; Dütsch, Luis; Seidl, Michael; Balázs, Gabor

2017-01-01

The reactions of the tetrahedral diphosphorus [Cp2Mo2(CO)4(η2‐P2)] (1; Cp = C5H5) complex with Ag[Al{OC(CF3)3}4] (AgTEF) (A) and Ag[FAl{OC(C6F5)(C6F10)}3] (AgFAl) (B) were studied. The first reaction led to the formation of the [Ag2(η2‐1)2(η1:η1‐1)2][TEF]2 (2) dimer and the [Ag2(η1:η1‐1)3]n[TEF]2n (3) coordination polymer, whereas the second reaction afforded the [Ag2(η1:η1‐1)2(η1‐CH2Cl2)2(η2‐C7H8)2][FAl]2 (4) or the [Ag2(η2‐1)2(η1:η1‐1)2][FAl]2 (5) dimer and the [Ag2(η1:η1‐1)4]n[FAl]2n (6) coordination polymer. In each case, the products obtained depended on the ratio of the reactants and/or the synthetic procedure. PMID:28943780

Effect of CCS on the accumulation of FALS SOD1 mutant-containing aggregates and on mitochondrial translocation of SOD1 mutants: implication of a free radical hypothesis.

PubMed

Kim, Ha Kun; Chung, Youn Wook; Chock, P Boon; Yim, Moon B

2011-05-15

Missense mutations of SOD1 are linked to familial amyotrophic lateral sclerosis (FALS) through a yet-to-be identified toxic-gain-of-function. One of the proposed mechanisms involves enhanced aggregate formation. However, a recent study showed that dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated FALS symptoms with enhanced mitochondrial pathology compared to G93A mice. Using a dicistronic mRNA to simultaneously generate hSOD1 mutants, G93A, A4V and G85R, and hCCS in AAV293 cells, we revealed: (i) CCS is degraded primarily via a macroautophagy pathway. It forms a stable heterodimer with inactive G85R, and via its novel copper chaperone-independent molecular chaperone activity facilitates G85R degradation via a macroautophagy-mediated pathway. For active G93A and A4V, CCS catalyzes their maturation to form active and soluble homodimers. (ii) CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H(2)O(2), mitochondrial translocation of inactive SOD1 mutants. These results, together with previous reports showing FALS SOD1 mutants enhanced free radical-generating activity, provide a mechanistic explanation for the observations with G93A/CCS dual transgenic mice and suggest that free radical generation by FALS SOD1, enhanced by CCS, may, in part, be responsible for the FALS SOD1 mutant-linked aggregation, mitochondrial translocation, and degradation. Published by Elsevier Inc.

Influence of the Atmospheric Model on Hanle Diagnostics

NASA Astrophysics Data System (ADS)

Ishikawa, Ryohko; Uitenbroek, Han; Goto, Motoshi; Iida, Yusuke; Tsuneta, Saku

2018-05-01

We clarify the uncertainty in the inferred magnetic field vector via the Hanle diagnostics of the hydrogen Lyman-α line when the stratification of the underlying atmosphere is unknown. We calculate the anisotropy of the radiation field with plane-parallel semi-empirical models under the nonlocal thermal equilibrium condition and derive linear polarization signals for all possible parameters of magnetic field vectors based on an analytical solution of the atomic polarization and Hanle effect. We find that the semi-empirical models of the inter-network region (FAL-A) and network region (FAL-F) show similar degrees of anisotropy in the radiation field, and this similarity results in an acceptable inversion error ( e.g., {˜} 40 G instead of 50 G in field strength and {˜} 100° instead of 90° in inclination) when FAL-A and FAL-F are swapped. However, the semi-empirical models of FAL-C (averaged quiet-Sun model including both inter-network and network regions) and FAL-P (plage regions) yield an atomic polarization that deviates from all other models, which makes it difficult to precisely determine the magnetic field vector if the correct atmospheric model is not known ( e.g., the inversion error is much larger than 40% of the field strength; {>} 70 G instead of 50 G). These results clearly demonstrate that the choice of model atmosphere is important for Hanle diagnostics. As is well known, one way to constrain the average atmospheric stratification is to measure the center-to-limb variation of the linear polarization signals. The dependence of the center-to-limb variations on the atmospheric model is also presented in this paper.

FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis

PubMed Central

Deng, Han-Xiang; Zhai, Hong; Bigio, Eileen H.; Yan, Jianhua; Fecto, Faisal; Ajroud, Kaouther; Mishra, Manjari; Ajroud-Driss, Senda; Heller, Scott; Sufit, Robert; Siddique, Nailah; Mugnaini, Enrico; Siddique, Teepu

2014-01-01

Objective Amyotrophic lateral sclerosis (ALS) is a fatal disorder of motor neuron degeneration. Most cases of ALS are sporadic (SALS), but about 5-10% of ALS cases are familial (FALS). Recent studies have shown that mutations in FUS are causal in approximately 4-5% of FALS and some apparent SALS cases. The pathogenic mechanism of the mutant FUS-mediated ALS and potential roles of FUS in non-FUS ALS remain to be investigated. Methods Immunostaining was performed on postmortem spinal cords from 78 ALS cases, including SALS (n=52), ALS with dementia (ALS/dementia, n=10) and FALS (n=16). In addition, postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration (FTLD) were also studied. In total, 100 cases were studied. Results FUS-immunoreactive inclusions were observed in spinal anterior horn neurons in all sporadic and familial ALS cases, except for those with SOD1 mutations. The FUS-containing inclusions were also immunoreactive with antibodies to TDP43, p62 and ubiquitin. A fraction of tested FUS antibodies recognized FUS inclusions and an unusual antigen retrieval appeared to be important for detection of the skein-like FUS inclusions. Interpretation Although mutations in FUS account for only a small fraction of FALS and SALS, our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying SALS, non-SOD1 FALS, ALS/dementia and related disorders. Our data also indicate that SOD1-linked ALS may have a distinct pathogenic pathway from SALS and other types of FALS. PMID:20517935

A Novel Locus for Familial Amyotrophic Lateral Sclerosis, on Chromosome 18q

PubMed Central

Hand, Collette K.; Khoris, Jawad; Salachas, François; Gros-Louis, François; Lopes, Ana Amélia Simões; Mayeux-Portas, Veronique; Brown, Jr., Robert H.; Meininger, Vincent; Camu, William; Rouleau, Guy A.

2002-01-01

Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by the death of motor neurons in the cortex, brain stem, and spinal cord. Despite intensive research the basic pathophysiology of ALS remains unclear. Although most cases are sporadic, ∼10% of ALS cases are familial (FALS). Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause ∼20% of FALS. The gene(s) responsible for the remaining 80% of FALS remain to be found. Using a large European kindred without SOD1 mutation and with classic autosomal dominant adult-onset ALS, we have identified a novel locus by performing a genome scan and linkage analysis. The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus. PMID:11706389

FUS GENE MUTATIONS IN FAMILIAL AND SPORADIC AMYOTROPHIC LATERAL SCLEROSIS

PubMed Central

Rademakers, Rosa; Stewart, Heather; DeJesus-Hernandez, Mariely; Krieger, Charles; Graff-Radford, Neill; Fabros, Marife; Briemberg, Hannah; Cashman, Neil; Eisen, Andrew; Mackenzie, Ian R. A.

2010-01-01

Introduction Mutations in the fused in sarcoma (FUS) gene have recently been found to cause familial amyotrophic lateral sclerosis (FALS). Methods We screened FUS in a cohort of 200 ALS patients [32 FALS and 168 sporadic ALS (SALS)]. Results In one FALS proband, we identified a mutation (p.R521C) that was also present in her affected daughter. Their clinical phenotype was remarkably similar and atypical of classic ALS, with symmetric proximal pelvic and pectoral weakness. Distal weakness and upper motor neuron features only developed late. Neuropathological examination demonstrated FUS-immunoreactive neuronal and glial inclusions in the spinal cord and many extramotor regions, but no TDP-43 pathology. We also identified a novel mutation (p.G187S) in one SALS patient. Overall, FUS mutations accounted for 3% of our non-SOD1, non-TARDBP FALS cases and 0.6% of SALS. Discussion This study demonstrates that the phenotype with FUS mutations extends beyond classical ALS. It suggests there are specific clinicogenetic correlations and provides the first detailed neuropathological description. PMID:20544928

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 573: Alpha Contaminated Sites Nevada National Security Site, Nevada, Revision 0

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

Matthews, Patrick

CAU 573 comprises the following corrective action sites (CASs): • 05-23-02, GMX Alpha Contaminated Area • 05-45-01, Atmospheric Test Site - Hamilton These two CASs include the release at the Hamilton weapons-related tower test and a series of 29 atmospheric experiments conducted at GMX. The two CASs are located in two distinctly separate areas within Area 5. To facilitate site investigation and data quality objective (DQO) decisions, all identified releases (i.e., CAS components) were organized into study groups. The reporting of investigation results and the evaluation of DQO decisions are at the release level. The corrective action alternatives (CAAs) weremore » evaluated at the FFACO CAS level. The purpose of this CADD/CAP is to evaluate potential CAAs, provide the rationale for the selection of recommended CAAs, and provide the plan for implementation of the recommended CAA for CAU 573. Corrective action investigation (CAI) activities were performed from January 2015 through November 2015, as set forth in the CAU 573 Corrective Action Investigation Plan (CAIP). Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the contaminants of concern. Assessment of the data generated from investigation activities conducted at CAU 573 revealed the following: • Radiological contamination within CAU 573 does not exceed the FALs (based on the Occasional Use Area exposure scenario). • Chemical contamination within CAU 573 does not exceed the FALs. • Potential source material—including lead plates, lead bricks, and lead-shielded cables—was removed during the investigation and requires no additional corrective action.« less

Addendum to the Closure Report for Corrective Action Unit 358: Areas 18, 19, 20 Cellars/Mud Pits Nevada Test Site, Nevada

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

Lynn Kidman

This document constitutes an addendum to the January 2004, Closure Report for Corrective Action Unit 358: Areas 18, 19, 20 Cellars/Mud Pits as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of:more » • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 20-23-02, Postshot Cellar • CAS 20-23-03, Cellar • CAS 20-23-04, Postshot Cellar • CAS 20-23-05, Postshot Cellar • CAS 20-23-06, Cellar • CAS 20-37-01, Cellar & Mud Pit • CAS 20-37-05, Cellar These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Closure Report for Corrective Action Unit 394: Areas 12, 18, and 29 Spill/Release Sites Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the September 2003, Closure Report for Corrective Action Unit 394: Areas 12, 18, and 29 Spill/Release Sites as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consistsmore » of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 12-25-04, UST 12-16-2 Waste Oil Release • CAS 18-25-01, Oil Spills • CAS 18-25-02, Oil Spills • CAS 18-25-03, Oil Spill • CAS 29-44-01, Fuel Spill These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Recent progress in the genetics of motor neuron disease.

PubMed

Finsterer, Josef; Burgunder, Jean-Marc

2014-02-01

Genetic background and pathogenesis of motor neuron diseases (MNDs) have been increasingly elucidated over recent years. To give an overview about publications during the last year concerning the genetic background and phenotypic manifestations of MNDs, such as familial or sporadic amyotrophic lateral sclerosis (fALS, sALS), spinal muscular atrophies (SMA), bulbospinal muscular atrophy (BSMA), and unclassified MNDs. Pubmed search for literature about ALS, SMA, and BSMA for the period 10/2012 to 9/2013. An increasing number of mutated genes is recognised in fALS but also sALS patients. Genes mutated in sALS include C9orf72, SOD1, TARDBP, FUS, UBQL2, SQSTM1, DCTN1, and UNC13A. Juvenile (onset <20y) and adult ALS (early onset 20-60y, late onset >60y) are differentiated. Juvenile fALS is most frequently caused by mutations in ALS2, SETX, spatacsin, or Sigmar1 and adult fALS by mutations in C9orf72, SOD1, TARDBP, and FUS. Onset, phenotype, progression, and outcome of ALS are variable between different mutations, different genes, and different countries. Differentiation between sALS and fALS cases becomes artificial. Further progress has been made over the last year in the clarification and understanding of the aetiology and pathogenesis of MNDs. However, further effort is needed to answer the many remaining questions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Development of resting membrane potentials in differentiating murine neuroblastoma cells (N1E-115) evaluated by flow cytometry.

PubMed

Kisaalita, W S; Bowen, J M

1997-09-01

With the aid of a voltage-sensitive oxonol dye, flow cytometry was used to measure relative changes in resting membrane potential (V(m)) and forward angle light scatter (FALS) profiles of a differentiating/differentiated murine neuroblastoma cell line (N1E-115). Electrophysiological differentiation was characterized by V(m) establishment. The (V(m))-time profile was found to be seed cell concentration-dependent for cell densities of less than 2 × 10(4) cells/cm(2). At higher initial cell densities, under differentiating culture conditions, V(m) development commenced on day 2 and reached a steady-state on day 12. The relative distribution of differentiated cells between low and high FALS has been proposed as a potential culture electrophysiological differentiation state index. These experiments offer a general methodology to characterize cultured excitable cells of nervous system origin, with respect to electrophysiological differentiation. This information is valuable in studies employing neuroblastoma cells as in vitro screening models for safety/hazard evaluation and/or risk assessment of therapeutical and industrial chemicals under development.

Genetic Heterogeneity in Streptococcus mutans1

PubMed Central

Coykendall, Alan L.

1971-01-01

The genetic homogeneity among eight cariogenic strains of Streptococcus mutans was assessed by deoxyribonucleic acid (DNA)-DNA reassociation experiments. DNA species were extracted from strains GS5, Ingbritt, 10449, FAl, BHT, E49, SLl, and KlR. Labeled DNA (14C-DNA) was extracted from strains 10449, FAl, and SLl. Denatured 14C-DNA fragments were allowed to reassociate, i.e., form hybrid duplexes, with denatured DNA immobilized on membrane filters incubated in 0.45 m NaCl-0.045 m sodium citrate at 67 or 75 C. At 67 C, 10449 14C-DNA reassociated extensively only with GS5 and Ingbritt DNA. FAl 14C-DNA hybridized extensively only with BHT DNA, and SLl 14C-DNA reassociated with KlR and E49 DNA. DNA which hybridized extensively at 67 C also reassociated to a high degree at 75 C. Thermal elution of 14C-FAl-BHT duplexes showed that the hybrid duplexes were thermostable. The results indicate that S. mutans is a genetically heterogeneous species. The strains studied can be divided into three (possibly four) genetic groups, and these groups closely parallel antigenic groups. PMID:5551636

Effect of Thermal Maturation on n-alkanes and Kerogen in Preserved Organic Matter: Implications for Paleoenvironment Biomarkers

NASA Astrophysics Data System (ADS)

Craven, O. D.; Longbottom, T. L.; Hockaday, W. C.; Blackaby, E.

2017-12-01

Understanding the effects of maturity on biomarkers is vital in assessing biomarker reliability in mature sediments. It is well known for n-alkanes that increased maturity shortens chain lengths and decreases the odd over even preference however, the amount of change in these variables has not been determined for different maturities and types of preserved organic matter. For this reason, it is difficult to judge the trustworthiness of even lightly matured samples for paleoenvironment reconstruction. Another complication is the difficulty of accurately determining maturity as many maturity indicators are error-prone or not appropriate at low maturities. Using hydrous pyrolysis, we artificially matured black shale samples with type I (lacustrine) and type II (marine) kerogen to measure changes in n-alkane length and odd over even preference. Whole rock samples underwent hydrous pyrolysis for 72 hours, at 250 °C, 300 °C, 325 °C, 350 °C, and 375 °C to cover a wide maturity range. From the immature and artificially matured samples, the bitumen was extracted and the saturate fraction was separated using column chromatography. The saturate fraction was analyzed for n-alkanes using gas chromatography-mass spectroscopy. Kerogen structural changes were also measured using solid-state 13C NMR to relate changes in n-alkane biomarkers to changes in kerogen structure. Results show that for type I bitumen the n-alkanes did not change at low maturities considered premature in terms of oil generation (<325 °C). The NMR spectra of the type I kerogen support the lack of change, at low maturities no changes in the aliphatic portion (Fal) were observed, however, after 325 °C Fal decreased with increasing maturity. The loss of Fal indicates kerogen contributing hydrocarbons to bitumen that cause changes in n-alkane measurements. The type II kerogen's Fal also decreased with increasing maturity, but unlike the type I kerogen Fal loss started at low maturities. The differences between the matured type I and II organic matter indicate that organic matter type affects when n-alkane measurements change due to maturity. Additionally, the kerogen carbonyl functional group (FaC) decreases greatly from immature to low maturities, leveling off between 300 °C and 325 °C, allowing FaC to be a tool for determining low maturities.

Competitive adsorption of Cd2+, Pb2+ and Ni2+ onto Fe3+-modified argillaceous limestone: Influence of pH, ionic strength and natural organic matters.

PubMed

He, Shuran; Li, Yongtao; Weng, Liping; Wang, Jinjin; He, Jinxian; Liu, Yonglin; Zhang, Kun; Wu, Qihong; Zhang, Yulong; Zhang, Zhen

2018-10-01

In present study, the feasibility of applying a natural adsorbent with Fe 3+ modification (Fe 3+ -modified argillaceous limestone, FAL) on the competitive adsorption of heavy metals (i.e., Cd 2+ , Pb 2+ and Ni 2+ ) was evaluated. The current results revealed an efficient adsorption on Cd 2+ , Pb 2+ and Ni 2+ in mono-metal system. Further experiments demonstrated a high selectivity of Pb 2+ during the competitive adsorption of Cd 2+ , Pb 2+ and Ni 2+ . The adsorption selectivity of the metal ions followed the order of Pb ≫ Cd > Ni. In addition, both pH and ionic strength are important factors affecting the metal adsorptions. It is interestingly that various NOMs (i.e., humic acid (HA) and glycine (Gly)) exerted different effects on the adsorption behaviors, probably due to the different affinities for Pb 2+ , Cd 2+ and Ni 2+ and the redistribution of newly-formed metal-DOM complexes. X-ray photoelectron spectroscopy (XPS) analysis together with X-ray diffraction (XRD) and energy dispersive spectrometer (EDS) analysis revealed that the metal adsorptions were mainly regulated via the synergistic mechanisms of ion exchange by Na + , Ca 2+ , and Al 3+ , precipitation to form CdCO 3 and Pb 2 (OH) 2 (CO 3 ) 2 , as well as complexes of FAL-OPb and FAL-ONi by hydroxyl groups on the surface of FAL. The application of FAL would be a promising option in leading to an efficient heavy metal removal. Copyright © 2018 Elsevier B.V. All rights reserved.

Integrated Defense: Lessons Learned from Joint Base Balad

DTIC Science & Technology

2013-01-01

Fall 2004): 65–74. http://www.airpower.au.af.mil/airchronicles /apj/apj04/fal04/Fal04.pdf. Butterfield, SSgt Phillip . “Iraqi Army Returns to Joint...PhD Air University Press Team Chief Editor Jerry L. Gantt Copy Editor Sherry Terrell Cover Art and Book Design Daniel Armstrong Composition and Prepress Production Nedra Looney Print Preparation and Distribution Diane Clark

Functional Adult Literacy: An Alternative Gateway to Grassroots Women's Improved Income Generation in Lango Subregion, Northern Uganda

ERIC Educational Resources Information Center

Akello, Judith Abal; Lutwama-Rukundo, Evelyn; Musiimenta, Peace

2017-01-01

This article presents findings of study on women's experiences of Functional Adult Literacy (FAL) as a gateway to their financial progress and welfare in Lango region, Northern Uganda. The qualitative study of 45 participants aimed at examining women's live changes resulting from using their acquired FAL knowledge and skills to participate in…

Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1.

PubMed

Ghadge, Ghanashyam D; Pavlovic, John D; Koduvayur, Sujatha P; Kay, Brian K; Roos, Raymond P

2013-08-01

Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Corrective Action Decision Document/Closure Report for Corrective Action Unit 375: Area 30 Buggy Unit Craters, Nevada National Security Site, Nevada, Revision 0

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

Patrick Matthews

2011-08-01

Corrective Action Unit 375 comprises three corrective action sites (CASs): (1) 25-23-22, Contaminated Soils Site; (2) 25-34-06, Test Cell A Bunker; and (3) 30-45-01, U-30a, b, c, d, e Craters. The purpose of this CADD/CR is to provide justification and documentation supporting the recommendation that no further corrective action is needed for CAU 375 based on the implementation of corrective action of closure in place with administrative controls at CAS 25-23-22, no further action at CAS 25-34-06, and closure in place with administrative controls and removal of potential source material (PSM) at CAS 30-45-01. Corrective action investigation (CAI) activities weremore » performed from July 28, 2010, through April 4, 2011, as set forth in the Corrective Action Investigation Plan for Corrective Action Unit 375: Area 30 Buggy Unit Craters. The approach for the CAI was divided into two facets: investigation of the primary release of radionuclides, and investigation of other releases (migration in washes and chemical releases). The purpose of the CAI was to fulfill data needs as defined during the data quality objective (DQO) process. The CAU 375 dataset of investigation results was evaluated based on the data quality assessment. This assessment demonstrated the dataset is acceptable for use in fulfilling the DQO data needs. Investigation results were evaluated against final action levels (FALs) established in this document. A radiological dose FAL of 25 millirem per year was established based on the Remote Work Area exposure scenario (336 hours of annual exposure). Radiological doses exceeding the FAL were assumed to be present within the default contamination boundaries at CASs 25-23-22 and 30-45-01. No contaminants were identified at CAS 25-34-06, and no corrective action is necessary. Potential source material in the form of lead plate, lead-acid batteries, and oil within an abandoned transformer were identified at CAS 30-45-01, and corrective actions were undertaken that consisted of removing the PSM. Use restrictions and warning signs were implemented for the remaining radiological contamination at CASs 25-23-22 and 30-45-01. These use restrictions were recorded in the FFACO database; the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Facility Information Management System; and the NNSA/NSO CAU/CAS files. Therefore, NNSA/NSO provides the following recommendations: (1) No further corrective actions are necessary for CAU 375; (2) A Notice of Completion to NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 375; and (3) Move CAU 375 from Appendix III to Appendix IV of the FFACO.« less

Addendum to the Corrective Action Decision Document/Closure Report for Corrective Action Unit 406: Area 3 Building 03-74 & Building 03-58 Underground Discharge Points and Corrective Action Unit 429: Area 3 Building 03-55 & Area 9 Building 09-52 Underground Discharge Points, Tonopah Test Range, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the March 2000, Corrective Action Decision Document / Closure Report for Corrective Action Unit 406: Area 3 Building 03-74 & 03-58 Underground Discharge Points and Corrective Action Unit 429: Area 3 Building 03-55 & Area 9 Building 09-52 Underground Discharge Points (TTR) as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. Themore » approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 03-51-001-0355 – Photo Shop UDP, Drains in CAU 429. It should be noted that there are no changes to CAU 406. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 413: Clean Slate II Plutonium Dispersion (TTR) Tonopah Test Range, Nevada. Revision 0

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

Matthews, Patrick

This Corrective Action Decision Document/Corrective Action Plan provides the rationale and supporting information for the selection and implementation of corrective actions at Corrective Action Unit (CAU) 413, Clean Slate II Plutonium Dispersion (TTR). CAU 413 is located on the Tonopah Test Range and includes one corrective action site, TA-23-02CS. CAU 413 consists of the release of radionuclides to the surface and shallow subsurface from the Clean Slate II (CSII) storage–transportation test conducted on May 31, 1963. The CSII test was a non-nuclear detonation of a nuclear device located inside a concrete bunker covered with 2 feet of soil. To facilitatemore » site investigation and the evaluation of data quality objectives decisions, the releases at CAU 413 were divided into seven study groups: 1 Undisturbed Areas 2 Disturbed Areas 3 Sedimentation Areas 4 Former Staging Area 5 Buried Debris 6 Potential Source Material 7 Soil Mounds Corrective action investigation (CAI) activities, as set forth in the CAU 413 Corrective Action Investigation Plan, were performed from June 2015 through May 2016. Radionuclides detected in samples collected during the CAI were used to estimate total effective dose using the Construction Worker exposure scenario. Corrective action was required for areas where total effective dose exceeded, or was assumed to exceed, the radiological final action level (FAL) of 25 millirem per year. The results of the CAI and the assumptions made in the data quality objectives resulted in the following conclusions: The FAL is exceeded in surface soil in SG1, Undisturbed Areas; The FAL is assumed to be exceeded in SG5, Buried Debris, where contaminated debris and soil were buried after the CSII test; The FAL is not exceeded at SG2, SG3, SG4, SG6, or SG7. Because the FAL is exceeded at CAU 413, corrective action is required and corrective action alternatives (CAAs) must be evaluated. For CAU 413, three CAAs were evaluated: no further action, clean closure, and closure in place. The CAAs were evaluated on technical merit focusing on performance, reliability, feasibility, safety, and cost. Based on the evaluation of analytical data from the CAI, review of future and current operations at CAU 413, and the detailed and comparative analysis of CAAs, clean closure was selected as the preferred CAA for CAU 413 by the U.S. Air Force, Nevada Division of Environmental Protection, and U.S. Department of Energy at the CAA meeting held on August 24, 2016.« less

Familial Amyotrophic Lateral Sclerosis-linked Mutations in Profilin 1 Exacerbate TDP-43-induced Degeneration in the Retina of Drosophila melanogaster through an Increase in the Cytoplasmic Localization of TDP-43.

PubMed

Matsukawa, Koji; Hashimoto, Tadafumi; Matsumoto, Taisei; Ihara, Ryoko; Chihara, Takahiro; Miura, Masayuki; Wakabayashi, Tomoko; Iwatsubo, Takeshi

2016-11-04

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons. Causative genes for familial ALS (fALS), e.g. TARDBP or FUS/TLS, have been found, among which mutations within the profilin 1 (PFN1) gene have recently been identified in ALS18. To elucidate the mechanism whereby PFN1 mutations lead to neuronal death, we generated transgenic Drosophila melanogaster overexpressing human PFN1 in the retinal photoreceptor neurons. Overexpression of wild-type or fALS mutant PFN1 caused no degenerative phenotypes in the retina. Double overexpression of fALS mutant PFN1 and human TDP-43 markedly exacerbated the TDP-43-induced retinal degeneration, i.e. vacuolation and thinning of the retina, whereas co-expression of wild-type PFN1 did not aggravate the degenerative phenotype. Notably, co-expression of TDP-43 with fALS mutant PFN1 increased the cytoplasmic localization of TDP-43, the latter remaining in nuclei upon co-expression with wild-type PFN1, whereas co-expression of TDP-43 lacking the nuclear localization signal with the fALS mutant PFN1 did not aggravate the retinal degeneration. Knockdown of endogenous Drosophila PFN1 did not alter the degenerative phenotypes of the retina in flies overexpressing wild-type TDP-43 These data suggest that ALS-linked PFN1 mutations exacerbate TDP-43-induced neurodegeneration in a gain-of-function manner, possibly by shifting the localization of TDP-43 from nuclei to cytoplasm. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The unfolded protein response in familial amyotrophic lateral sclerosis.

PubMed

Wang, Lijun; Popko, Brian; Roos, Raymond P

2011-03-01

Mutant superoxide dismutase type 1 (MTSOD1) is thought to cause ∼20% of cases of familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Previous studies have shown that MTSOD1 accumulates inside the endoplasmic reticulum (ER) and activates the unfolded protein response (UPR), suggesting that ER stress is involved in the pathogenesis of FALS. We used a genetic approach to investigate the role of the UPR in FALS. We crossed G85RSOD1 transgenic mice with pancreatic ER kinase haploinsufficient (PERK(+/-)) mice to obtain G85R/PERK(+/-) mice. PERK(+/-) mice carry a loss of function mutation of PERK, which is the most rapidly activated UPR pathway, but have no abnormal phenotype. Compared with G85R transgenic mice, G85R/PERK(+/-) mice had a dramatically accelerated disease onset as well as shortened disease duration and lifespan. There was also acceleration of the pathology and earlier MTSOD1 aggregation. A diminished PERK response accelerated disease and pathology in G85R transgenic mice presumably because the mice had a reduced capacity to turn down synthesis of misfolded SOD1, leading to an early overloading of the UPR. The results indicate that the UPR has a significant influence on FALS, and suggest that enhancing the UPR may be effective in treating ALS.

Soils Project Risk-Based Corrective Action Evaluation Process with ROTC 1 and ROTC 2, Revision 0

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

Matthews, Patrick; Sloop, Christina

2012-04-01

This document formally defines and clarifies the NDEP-approved process the NNSA/NSO Soils Activity uses to fulfill the requirements of the FFACO and state regulations. This process is used to establish FALs in accordance with the risk-based corrective action (RBCA) process stipulated in Chapter 445 of the Nevada Administrative Code (NAC) as described in the ASTM International (ASTM) Method E1739-95 (NAC, 2008; ASTM, 1995). It is designed to provide a set of consistent standards for chemical and radiological corrective actions.

cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.

PubMed

Choi, Jin Sun; Kim, Kidae; Lee, Do Hee; Cho, Sayeon; Ha, Jae Du; Park, Byoung Chul; Kim, Sunhong; Park, Sung Goo; Kim, Jeong-Hoon

2016-11-18

Although the ubiquitin-proteasome system is believed to play an important role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS), caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1), the mechanism of how mutant SOD1 protein is regulated in cells is still poorly understood. Here we have demonstrated that cellular inhibitor of apoptosis proteins (cIAPs) are specifically associated with FALS-linked mutant SOD1 (mSOD1) and that this interaction promotes the ubiquitin-dependent proteasomal degradation of mutant SOD1. By utilizing cumate inducible SOD1 cells, we also showed that knock-down or pharmacologic depletion of cIAPs leads to H 2 O 2 induced cytotoxicity in mSOD1 expressing cells. Altogether, our results reveal a novel role of cIAPs in FALS-associated mutant SOD1 regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluoride or/and aluminum induced toxicity in guinea pig teeth with the low expression of dentine phosphoprotein.

PubMed

Han, Tianlong; Wang, Min; Cao, Chunfang; Chen, Huacheng; Zhang, Guanghe; Wang, Liping; Wang, Jundong

2017-08-01

This study investigated the damage and expression of dentine phosphoprotein (DPP) in guinea pig teeth by the administration of fluoride (F) or/and aluminum (Al). Fifty-two guinea pigs were divided randomly into four groups (control, F, Al, and F+Al). F (150 mg NaF/L) or/and Al (300 mg AlCl 3 /L) were added in their drinking water for 90 days. The levels of F ion, dentine sialophosphoprotein (DSPP) gene, and DPP protein in incisor and molar were determined, respectively. The results showed that the concentrations of F ion in F and F+Al groups were increased significantly. F induced the mottled enamel and irregular abrasion of teeth, which might occur as a consequence of depressed DSPP mRNA and DPP protein expression. Both the gene and protein expressions showed obvious decrease induced by Al, especially by F. There were no synergistic effects between F and Al, instead, Al inhibited the toxicity of F. © 2017 Wiley Periodicals, Inc.

Solid-state NMR studies of metal-free SOD1 fibrillar structures.

PubMed

Banci, Lucia; Blaževitš, Olga; Cantini, Francesca; Danielsson, Jens; Lang, Lisa; Luchinat, Claudio; Mao, Jiafei; Oliveberg, Mikael; Ravera, Enrico

2014-06-01

Copper-zinc superoxide dismutase 1 (SOD1) is present in the protein aggregates deposited in motor neurons of amyotrophic lateral sclerosis (ALS) patients. ALS is a neurodegenerative disease that can be either sporadic (ca. 90%) or familial (fALS). The most widely studied forms of fALS are caused by mutations in the sequence of SOD1. Ex mortuo SOD1 aggregates are usually found to be amorphous. In vitro SOD1, in its immature reduced and apo state, forms fibrillar aggregates. Previous literature data have suggested that a monomeric SOD1 construct, lacking loops IV and VII, (apoSODΔIV-VII), shares the same fibrillization properties of apoSOD1, both proteins having the common structural feature of the central β-barrel. In this work, we show that structural information can be obtained at a site-specific level from solid-state NMR. The residues that are sequentially assignable are found to be located at the putative nucleation site for fibrillar species formation in apoSOD, as detected by other experimental techniques.

Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia.

PubMed

Wu, Weiqing; Liu, Yang; Zhou, Qinghua; Wang, Qin; Luo, Fuwei; Xu, Zhiyong; Geng, Qian; Li, Peining; Zhang, Hui Z; Xie, Jiansheng

2017-07-01

Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known complement groups caused by mutations in different genes. FA complementation group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant variants in the FANCL gene were documented. Phenotype and genotype correlation in FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in the FANCL gene. The patient's clinical course was typical for FA with progression to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at 9 years of age. Mutation analysis also detected a likely somatic c.2608G > A (p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and gains of 3q and 21q and accumulated non-clonal single cell chromosomal abnormalities were detected in blood leukocytes as her FA progressed. This is the first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene mutation and copy number aberrations could be used to monitor disease progression and the clinical findings provide further information for genotype-phenotype correlation for FA-L. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

FUS/TLS-immunoreactive neuronal and glial cell inclusions increase with disease duration in familial amyotrophic lateral sclerosis with an R521C FUS/TLS mutation.

PubMed

Suzuki, Naoki; Kato, Shinsuke; Kato, Masako; Warita, Hitoshi; Mizuno, Hideki; Kato, Masaaki; Shimakura, Naoko; Akiyama, Haruhiko; Kobayashi, Zen; Konno, Hidehiko; Aoki, Masashi

2012-09-01

Basophilic inclusions (BIs) are pathological features of a subset of frontotemporal lobar degeneration disorders, including sporadic amyotrophic lateral sclerosis (ALS) and familial ALS (FALS). Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have recently been identified as a cause of FALS. The FUS/TLS-immunoreactive inclusions are consistently found in cases of frontotemporal lobar degeneration with BIs; however, the association between ALS cases with BIs and FUS/TLS accumulation is not well understood. We used immunohistochemistry to analyze 3 autopsy cases of FALS with the FUS/TLS mutation and with BIs using anti-FUS/TLS antibodies. The disease durations were 1, 3, and 9 years. As the disease duration becomes longer, there were broader distributions of neuronal and glial FUS/TLS-immunoreactive inclusions. As early as 1 year after the onset, BIs, neuronal cytoplasmic inclusions and glial cytoplasmic inclusions were found in the substantia nigra in addition to the anterior horn of the spinal cord. Glial cytoplasmic inclusions are found earlier and in a wider distribution than neuronal cytoplasmic inclusions. The distribution of FUS/TLS-immunoreactive inclusions in FUS/TLS-mutated FALS with BIs was broader than that of BIs alone, suggesting that the pathogenetic mechanism may have originated from the FUS/TLS proteinopathy.

Addendum to the Closure Report for Corrective Action Unit 355: Area 2 Cellars/Mud Pits Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the November 2003, Closure Report for Corrective Action Unit 355: Area 2 Cellars/Mud Pits as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • Thismore » cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 02-37-01, Cellar & Mud Pit • CAS 02-37-03, Cellar & Mud Pit • CAS 02-37-04, Cellar & Mud Pit • CAS 02-37-05, Cellar & Mud Pit • CAS 02-37-06, Cellar & Mud Pit • CAS 02-37-07, Cellar & Mud Pit • CAS 02-37-10, Cellar & Mud Pit • CAS 02-37-11, Cellar & Mud Pit • CAS 02-37-12, Cellar & Mud Pit • CAS 02-37-13, Cellar & Mud Pit • CAS 02-37-14, Cellar & Mud Pit • CAS 02-37-15, Cellar & Mud Pit • CAS 02-37-16, Cellar & Mud Pit • CAS 02-37-17, Cellar • CAS 02-37-18, Cellar & Tanks These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

The fission yeast MTREC and EJC orthologs ensure the maturation of meiotic transcripts during meiosis.

PubMed

Marayati, Bahjat Fadi; Hoskins, Victoria; Boger, Robert W; Tucker, James F; Fishman, Emily S; Bray, Andrew S; Zhang, Ke

2016-09-01

Meiosis is a highly regulated process by which genetic information is transmitted through sexual reproduction. It encompasses unique mechanisms that do not occur in vegetative cells, producing a distinct, well-regulated meiotic transcriptome. During vegetative growth, many meiotic genes are constitutively transcribed, but most of the resulting mRNAs are rapidly eliminated by the Mmi1-MTREC (Mtl1-Red1 core) complex. While Mmi1-MTREC targets premature meiotic RNAs for degradation by the nuclear 3'-5' exoribonuclease exosome during mitotic growth, its role in meiotic gene expression during meiosis is not known. Here, we report that Red5, an essential MTREC component, interacts with pFal1, an ortholog of eukaryotic translation initiation factor eIF4aIII in the fission yeast Schizosaccharomyces pombe In mammals, together with MAGO (Mnh1), Rnps1, and Y14, elF4AIII (pFal1) forms the core of the exon junction complex (EJC), which is essential for transcriptional surveillance and localization of mature mRNAs. In fission yeast, two EJC orthologs, pFal1 and Mnh1, are functionally connected with MTREC, specifically in the process of meiotic gene expression during meiosis. Although pFal1 interacts with Mnh1, Y14, and Rnps1, its association with Mnh1 is not disrupted upon loss of Y14 or Rnps1. Mutations of Red1, Red5, pFal1, or Mnh1 produce severe meiotic defects; the abundance of meiotic transcripts during meiosis decreases; and mRNA maturation processes such as splicing are impaired. Since studying meiosis in mammalian germline cells is difficult, our findings in fission yeast may help to define the general mechanisms involved in accurate meiotic gene expression in higher eukaryotes. © 2016 Marayati et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Palmitoylation of superoxide dismutase 1 (SOD1) is increased for familial amyotrophic lateral sclerosis-linked SOD1 mutants.

PubMed

Antinone, Sarah E; Ghadge, Ghanashyam D; Lam, Tukiet T; Wang, Lijun; Roos, Raymond P; Green, William N

2013-07-26

Mutations in Cu,Zn-superoxide dismutase (mtSOD1) cause familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease resulting from motor neuron degeneration. Here, we demonstrate that wild type SOD1 (wtSOD1) undergoes palmitoylation, a reversible post-translational modification that can regulate protein structure, function, and localization. SOD1 palmitoylation was confirmed by multiple techniques, including acyl-biotin exchange, click chemistry, cysteine mutagenesis, and mass spectrometry. Mass spectrometry and cysteine mutagenesis demonstrated that cysteine residue 6 was the primary site of palmitoylation. The palmitoylation of FALS-linked mtSOD1s (A4V and G93A) was significantly increased relative to that of wtSOD1 expressed in HEK cells and a motor neuron cell line. The palmitoylation of FALS-linked mtSOD1s (G93A and G85R) was also increased relative to that of wtSOD1 when assayed from transgenic mouse spinal cords. We found that the level of SOD1 palmitoylation correlated with the level of membrane-associated SOD1, suggesting a role for palmitoylation in targeting SOD1 to membranes. We further observed that palmitoylation occurred predominantly on disulfide-reduced as opposed to disulfide-bonded SOD1, suggesting that immature SOD1 is the primarily palmitoylated species. Increases in SOD1 disulfide bonding and maturation with increased copper chaperone for SOD1 expression caused a decrease in wtSOD1 palmitoylation. Copper chaperone for SOD1 overexpression decreased A4V palmitoylation less than wtSOD1 and had little effect on G93A mtSOD1 palmitoylation. These findings suggest that SOD1 palmitoylation occurs prior to disulfide bonding during SOD1 maturation and that palmitoylation is increased when disulfide bonding is delayed or decreased as observed for several mtSOD1s.

Validation of minicams for measuring concentrations of chemical agent in environmental air

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

Menton, R.G.; Hayes, T.L.; Chou, Y.L.

1993-05-13

Environmental monitoring for chemical agents is necessary to ensure that notification and appropriate action will be taken in the, event that there is a release exceeding control limits of such agents into the workplace outside of engineering controls. Prior to implementing new analytical procedures for environmental monitoring, precision and accuracy (PA) tests are conducted to ensure that an agent monitoring system performs according to specified accuracy, precision, and sensitivity requirements. This testing not only establishes the accuracy and precision of the method, but also determines what factors can affect the method's performance. Performance measures that are particularly important in agentmore » monitoring include the Detection Limit (DL), Decision Limit (DC), Found Action Level (FAL), and the Target Action Level (TAL). PA experiments were performed at Battelle's Medical Research and Evaluation Facility (MREF) to validate the use of the miniature chemical agent monitoring system (MINICAMs) for measuring environmental air concentrations of sulfur mustard (HD). This presentation discusses the experimental and statistical approaches for characterizing the performance of MINICAMS for measuring HD in air.« less

Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS

PubMed Central

Bosco, Daryl A.; Morfini, Gerardo; Karabacak, N. Murat; Song, Yuyu; Gros-Louis, Francois; Pasinelli, Piera; Goolsby, Holly; Fontaine, Benjamin A.; Lemay, Nathan; McKenna-Yasek, Diane; Frosch, Matthew P.; Agar, Jeffery N.; Julien, Jean-Pierre; Brady, Scott T.; Brown, Robert H.

2010-01-01

Many mutations confer upon copper/zinc superoxide dismutase-1 (SOD1) one or more toxic function(s) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we demonstrate that oxidized WT-SOD1 and mutant-SOD1 share a conformational epitope that is not present in normal WT-SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord displayed striking C4F6 immunoreactivity, denoting the presence of aberrant WT-SOD1 species. Recombinant, oxidized WT-SOD1 and WT-SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to FALS-linked mutant SOD1. Studies here suggest that WT-SOD1 can be pathogenic in SALS and identifies an SOD1-dependent pathogenic mechanism common to FALS and SALS. PMID:20953194

U.S. Navy Fault-Tolerant Microcomputer.

DTIC Science & Technology

1982-07-01

105 8929 SEPULVEDA BLVD. LOS ANGELES, CALIFORNIA 90045 To: DEFENSE TECHNICAL INFORMATION CENTER Fal-ae Technoog Corporation MILITARY STANDARD FAULT...maintainability. Com- puter errors at any significant level can be disastrous in terms of human injury, aborted missions, loss of critical information and...employed to resolve the question "who checks the checker?" The IOC votes on information received from the bus and outputs the maiority decision. Thus no

Magneto-Elastic behaviour of Steels for Naval Applications

DTIC Science & Technology

1991-02-01

test specimens to be inserted. The specimens are preferably long and thin to avoid demagnetization effects, but are also preferably short and squat ...jr.".-.IC’’" ?!o w:.I ,,od ntt’pcrtJ B15 q12 fA-l spc +icob are as ’l . The stress level was -200l MIa for the Dt l((Td) ’ process, and ranged from 0

Demonstration of a Cylinder-Fill System Based on Solid Electrolyte Oxygen Separator (SEOS) Technology: One Year Early Field Assessment at a USAF Maintenance Facility

DTIC Science & Technology

2011-02-01

vacuum swing adsorption (VSA). This system would also be extremely quiet while operating. In applications where a pressurized air feed is available...review of the latest data set. 02 Apr 10, Friday - Status: OK. Tinker AFB reported a FAL alarm occurs when the compressor isn’t pumping oxygen. The...FAL alarm terminates when the compressor starts pumping oxygen. APCI/Ceramatec confirmed this occurrence is normal operation, however, it isn’t

[History of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P)].

PubMed

Takashima, Hiroshi

2013-01-01

We established a new disease autosomal dominant hereditary motor and sensory neuropathy with proximal dominant involvement (HMSNP) in 1997, in Okinawa, Japan. This disease is characterized by proximal dominant neurogenic atrophy with fasciculations, painful muscle cramp, obvious sensory nerve involvement, areflexia, high incidence of elevated creatine kinase levels, hyperlipidemia and hyperglycemia. (MIM %604484). HMSNP is so called or HMSNO (HMSN OKINAWA type),. These clinical features resembled those of Kennedy-Alter-Sung syndrome. Most HMSNP patients have severe muscle atrophy and finally the tracheostomy and artificial ventilation are required. Therefore, we initially thought to classify HMSNP into a subtype of motor neuron disease (MND) like familial amyotrophic lateral sclerosis (FALS) or spinal muscular atrophy (SMA). However, the general consensus for MND was no sensory involvement. Therefore, as the disease showed severe sensory involvement, we categorized HMSNP in subtype of HMSN at that time. We also reported the pathology of HMSNP, showing severely decreased anterior horn cells, decreased posterior horn cells, and loss of posterior funiculus in the spinal cord.

Summary Report for the Environmental Protection Agency MERL/FRMAC Mission Alignment Exercise held at the Environmental Protection Agency Facility on June 24-26 2014

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

Allen, Mark B.; Shanks, Sonoya Toyoko; Fournier, Sean Donovan

From June 24th thru June 26th 2014, members of the Federal Radiological Monitoring and Assessment Center (FRMAC), FRMAC Fly Away Laboratory, and the Environmental Protection Agency (EPA) participated in a joint nuclear incident emergency response/round robin exercise at the EPA facility in Las Vegas, Nevada. The purpose of this exercise was to strengthen the interoperability relationship between the FRMAC Fly Away Laboratory (FAL) and the EPA Mobile Environmental Radiation Laboratory (MERL) stationed in Las Vegas, Nevada. The exercise was designed to allow for immediate delivery of pre-staged, spiked samples to the EPA MERL and the FAL for sample preparation andmore » radiological analysis. Upon completion of laboratory analysis, data was reviewed and submitted back to the FRMAC via an electronic data deliverable (EDD). In order to conduct a laboratory inter-comparison study, samples were then traded between the two laboratories and re-counted. As part of the exercise, an evaluation was conducted to identify gaps and potential areas for improvements for FRMAC, FAL and EPA operations. Additionally, noteworthy practices and potential future areas of interoperability opportunities between the FRMAC, FAL and EPA were acknowledged. The exercise also provided a unique opportunity for FRMAC personnel to observe EPA sample receipt and sample preparation processes and to gain familiarity with the MERL laboratory instrumentation and radiation detection capabilities. The areas for potential improvements and interoperability from this exercise will be critical for developing a more efficient, integrated response for future interactions between the FRMAC and EPA MERL assets.« less

Differential dopamine function in fibromyalgia.

PubMed

Albrecht, Daniel S; MacKie, Palmer J; Kareken, David A; Hutchins, Gary D; Chumin, Evgeny J; Christian, Bradley T; Yoder, Karmen K

2016-09-01

Approximately 30 % of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [(18)F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and 11 female controls completed study procedures. Subjects received one FAL PET scan while performing a "2-back" task, and one while performing a "0-back" (attentional control, "baseline") task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.

Use of global assays to understand clinical phenotype in congenital factor VII deficiency.

PubMed

Greene, L A; Goldenberg, N A; Simpson, M L; Villalobos-Menuey, E; Bombardier, C; Acharya, S S; Santiago-Borrero, P J; Cambara, A; DiMichele, D M

2013-09-01

Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored. © 2013 John Wiley & Sons Ltd.

A molecular chaperone activity of CCS restores the maturation of SOD1 fALS mutants.

PubMed

Luchinat, Enrico; Barbieri, Letizia; Banci, Lucia

2017-12-12

Superoxide dismutase 1 (SOD1) is an important metalloprotein for cellular oxidative stress defence, that is mutated in familiar variants of Amyotrophic Lateral Sclerosis (fALS). Some mutations destabilize the apo protein, leading to the formation of misfolded, toxic species. The Copper Chaperone for SOD1 (CCS) transiently interacts with SOD1 and promotes its correct maturation by transferring copper and catalyzing disulfide bond formation. By in vitro and in-cell NMR, we investigated the role of the SOD-like domain of CCS (CCS-D2). We showed that CCS-D2 forms a stable complex with zinc-bound SOD1 in human cells, that has a twofold stabilizing effect: it both prevents the accumulation of unstructured mutant SOD1 and promotes zinc binding. We further showed that CCS-D2 interacts with apo-SOD1 in vitro, suggesting that in cells CCS stabilizes mutant apo-SOD1 prior to zinc binding. Such molecular chaperone function of CCS-D2 is novel and its implications in SOD-linked fALS deserve further investigation.

Hazard Assessment Computer System HACS/UIM Users’ Operation Manual. Volume II.

DTIC Science & Technology

1981-09-01

AMMONIUM OXALATE FAS FERROUS AMMONIUM SULFATE FCL FERRIC CHLORIDE FCP FERRIC GLYCEROPHOSPHATE FEC FERROUS CHLORIDE FFA FURFURAL FFB FERROUS FLUOROBORATE...FAL FFA FFBi FMA FNS FSA FSL FXX BAK GAT SAY SCM GCR GCS SOC SOS SPL SRF GSR STA J-2 HAC HAI HAL HEIR HCC HCL HCN HDC HE’S HDZ HFA HFX HMD HMI HPA...ENP EOEI EOP EOT EPC ETA ETC ETD ETf3 ETI FAL FFA FFB FMA FMS VSL OCR GOS GIA MAC HAI HCL Ht’Z HFA HMD HMI HPA HPdkt HPO HSS HXG IAA IAC IAL IAN IBR

Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

2004-06-01

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Flow Direction Reversal

PubMed Central

Heuslein, Joshua L.; Meisner, Joshua K.; Li, Xuanyue; Song, Ji; Vincentelli, Helena; Leiphart, Ryan J.; Ames, Elizabeth G.; Price, Richard J.

2015-01-01

Objective Collateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of flow direction reversal, occurring in numerous collateral artery segments after femoral artery ligation (FAL), is unknown. Our objective was to determine if flow direction reversal in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis. Approach and Results Collateral segments experiencing flow reversal after FAL in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post-FAL) remodeling. Genome-wide transcriptional analyses on HUVECs exposed to flow reversal conditions mimicking those occurring in-vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (NFκB, VEGF, FGF2, TGFβ) and arteriogenic canonical pathways (PKA, PDE, MAPK). Augmented expression of key pro-arteriogenic molecules (KLF2, ICAM-1, eNOS) was also verified by qRT-PCR, leading us to test whether ICAM-1 and/or eNOS regulate amplified arteriogenesis in flow-reversed collateral segments in-vivo. Interestingly, enhanced pericollateral macrophage recruitment and amplified arteriogenesis was attenuated in flow-reversed collateral segments after FAL in ICAM-1−/− mice; however, eNOS−/− mice showed no such differences. Conclusions Flow reversal leads to a broad amplification of pro-arteriogenic endothelial signaling and a sustained ICAM-1-dependent augmentation of arteriogenesis. Further investigation of the endothelial mechanotransduction pathways activated by flow reversal may lead to more effective and durable therapeutic options for arterial occlusive diseases. PMID:26338297

Complexes of monocationic Group 13 elements with pentaphospha- and pentaarsaferrocene.

PubMed

Fleischmann, Martin; Welsch, Stefan; Krauss, Hannes; Schmidt, Monika; Bodensteiner, Michael; Peresypkina, Eugenia V; Sierka, Marek; Gröger, Christian; Scheer, Manfred

2014-03-24

Reactions of the sandwich complexes [Cp*Fe(η(5)-E5)] (Cp*=η(5)-C5Me5; E=P (1), As (2)) with the monovalent Group 13 metals Tl(+), In(+), and Ga(+) containing the weakly coordinating anion [TEF] ([TEF]=[Al{OC(CF3)3}4](-)) are described. Here, the one-dimensional coordination polymers [M(μ,η(5):η(1 -E5 FeCp*)3]n [TEF]n (E=P, M=Tl (3 a), In (3 b), Ga (3 c); E=As, M=Tl (4 a), In (4 b)) are obtained as sole products in good yields. All products were analyzed by single-crystal X-ray diffraction, revealing a similar assembly of the products with η(5)-bound E5 ligands and very weak σ-interactions between one P or As atom of the ring to the neighbored Group 13 metal cation. By exchanging the [TEF] anion of 4 a for the larger [FAl] anion ([FAl]=[FAl{OC6F10(C6F5)}3](-)), the coordination compound [Tl{(η(5)-As5)FeCp*}3][FAl] (5) without any σ-interactions of the As5-ring is obtained. All products are readily soluble in CH2 Cl2 and exhibit a dynamic coordination behavior in solution, which is supported by NMR spectroscopy and ESI-MS spectrometry as well as by osmometric molecular-weight determination. For a better understanding of the proceeding equilibrium DFT calculations of the cationic complexes were performed for the gas phase and in solution. Furthermore, the (31)P{(1)H} magic-angle spinning (MAS) NMR spectra of 3 a-c are presented and the first crystal structure of the starting material 2 was determined. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison study of [18F]FAl-NOTA-PRGD2, [18F]FPPRGD2, and [68Ga]Ga-NOTA-PRGD2 for PET imaging of U87MG tumors in mice.

PubMed

Lang, Lixin; Li, Weihua; Guo, Ning; Ma, Ying; Zhu, Lei; Kiesewetter, Dale O; Shen, Baozhong; Niu, Gang; Chen, Xiaoyuan

2011-12-21

[(18)F]FPPRGD2, an F-18 labeled dimeric cyclic RGDyK peptide, has favorable properties for PET imaging of angiogenesis by targeting the α(v)β(3) integrin receptor. This radiotracer has been approved by the FDA for use in clinical trials. However, the time-consuming multiple-step synthetic procedure required for its preparation may hinder the widespread usage of this tracer. The recent development of a method using an F-18 fluoride-aluminum complex to radiolabel peptides provides a strategy for simplifying the labeling procedure. On the other hand, the easy-to-prepare [(68)Ga]-labeled NOTA-RGD derivatives have also been reported to have promising properties for imaging α(v)β(3) integrin receptors. The purpose of this study was to prepare [(18)F]FPPRGD2 [corrected] , [(18)F]FAl-NOTA-PRGD2, and [(68)Ga]Ga-NOTA-PRGD2 and to compare their pharmacokinetics and tumor imaging properties using small animal PET. All three compounds showed rapid and high tracer uptake in U87MG tumors with high target-to-background ratios. The uptake in the liver, kidneys, and muscle were similar for all three tracers, and they all showed predominant renal clearance. In conclusion, [(18)F]FAl-NOTA-PRGD2 and [(68)Ga]Ga-NOTA-PRGD2 have imaging properties and pharmacokinetics comparable to those of [(18)F]FPPRGD2. Considering their ease of preparation and good imaging qualities, [(18)F]FAl-NOTA-PRGD2 and [(68)Ga]NOTA-PRGD2 are promising alternatives to [(18)F]FPPRGD2 for PET imaging of tumor α(v)β(3) integrin expression.

Corrective Action Decision Document/Closure Report for Corrective Action Unit 371: Johnnie Boy Crater and Pin Stripe Nevada Test Site, Nevada, Revision 0

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

Patrick Matthews

This Corrective Action Decision Document/Closure Report has been prepared for Corrective Action Unit 371, Johnnie Boy Crater and Pin Stripe, located within Areas 11 and 18 at the Nevada Test Site, Nevada, in accordance with the Federal Facility Agreement and Consent Order (FFACO). Corrective Action Unit (CAU) 371 comprises two corrective action sites (CASs): • 11-23-05, Pin Stripe Contamination Area • 18-45-01, U-18j-2 Crater (Johnnie Boy) The purpose of this Corrective Action Decision Document/Closure Report is to provide justification and documentation supporting the recommendation that no further corrective action is needed for CAU 371 based on the implementation of correctivemore » actions. The corrective action of closure in place with administrative controls was implemented at both CASs. Corrective action investigation (CAI) activities were performed from January 8, 2009, through February 16, 2010, as set forth in the Corrective Action Investigation Plan for Corrective Action Unit 371: Johnnie Boy Crater and Pin Stripe. The approach for the CAI was divided into two facets: investigation of the primary release of radionuclides and investigation of other releases (migration in washes and chemical releases). The purpose of the CAI was to fulfill data needs as defined during the data quality objective (DQO) process. The CAU 371 dataset of investigation results was evaluated based on the data quality indicator parameters. This evaluation demonstrated the dataset is acceptable for use in fulfilling the DQO data needs. Analytes detected during the CAI were evaluated against final action levels (FALs) established in this document. Radiological doses exceeding the FAL of 25 millirem per year were not found to be present in the surface soil. However, it was assumed that radionuclides are present in subsurface media within the Johnnie Boy crater and the fissure at Pin Stripe. Due to the assumption of radiological dose exceeding the FAL, corrective actions were undertaken that consist of implementing a use restriction and posting warning signs at each site. These use restrictions were recorded in the FFACO database; the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Facility Information Management System; and the NNSA/NSO CAU/CAS files. Therefore, NNSA/NSO provides the following recommendations: • No further corrective actions are necessary for CAU 371. • A Notice of Completion to NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 371. • Corrective Action Unit 371 should be moved from Appendix III to Appendix IV of the FFACO.« less

Revascularization and Muscle Adaptation to Limb Demand Ischemia in Diet Induced Obese Mice

PubMed Central

Albadawi, Hassan; Tzika, Aria; Rask-Madsen, Christian; Crowley, Lindsey M.; Koulopoulos, Michael W.; Yoo, Hyung-Jin; Watkins, Michael T.

2016-01-01

Background Obesity and type 2 diabetes are major risk factors for peripheral arterial disease (PAD) in humans which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularization, fiber size, and signaling pathways in the ischemic hind limb muscles of mice with diet-induced obesity (DIO). Materials and Methods DIO mice (n=7) underwent unilateral femoral artery ligation (FAL) and recovered for 2-weeks followed by 4-weeks with daily treadmill exercise to induce demand ischemia. A parallel sedentary ischemia group (n=7) had FAL without exercise. The contralateral limb muscles of sedentary ischemia served as control. Muscles were examined for capillary density, myofiber cross-sectional area (CSA), cytokine levels, and phosphorylation of STAT3 and ERK1/2. Results Exercise significantly enhanced capillary density (p<0.01) and markedly lowered CSA (p<0.001) in demand ischemia compared to sedentary ischemia. These findings coincided with a significant increase in G-CSF (p<0.001) and IL-7 (p<0.01) levels. In addition, phosphorylation of STAT3 and ERK1/2 (p<0.01) were increased while UCP-1 and MCP-1 protein levels were lower (p<0.05) without altering VEGF and TNFα protein levels. Demand ischemia increased the PGC1α mRNA (p<0.001) without augmenting PGC1α protein levels. Conclusions Exercise induced limb demands ischemia in the setting of DIO causes myofiber atrophy despite an increase in muscle capillary density. The combination of persistent increase in TNFα, lower VEGF and failure to increase PGC1α protein may reflect a deficient adaption to demand ischemia in DIO. PMID:27620999

Corrective Action Decision Document for Corrective Action Unit 563: Septic Systems, Nevada Test Site, Nevada, Revision 0

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

Grant Evenson

2008-02-01

This Corrective Action Decision Document has been prepared for Corrective Action Unit (CAU) 563, Septic Systems, in accordance with the Federal Facility Agreement and Consent Order (FFACO, 1996; as amended January 2007). The corrective action sites (CASs) for CAU 563 are located in Areas 3 and 12 of the Nevada Test Site, Nevada, and are comprised of the following four sites: •03-04-02, Area 3 Subdock Septic Tank •03-59-05, Area 3 Subdock Cesspool •12-59-01, Drilling/Welding Shop Septic Tanks •12-60-01, Drilling/Welding Shop Outfalls The purpose of this Corrective Action Decision Document is to identify and provide the rationale for the recommendation of a correctivemore » action alternative (CAA) for the four CASs within CAU 563. Corrective action investigation (CAI) activities were performed from July 17 through November 19, 2007, as set forth in the CAU 563 Corrective Action Investigation Plan (NNSA/NSO, 2007). Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the contaminants of concern (COCs) for each CAS. The results of the CAI identified COCs at one of the four CASs in CAU 563 and required the evaluation of CAAs. Assessment of the data generated from investigation activities conducted at CAU 563 revealed the following: •CASs 03-04-02, 03-59-05, and 12-60-01 do not contain contamination at concentrations exceeding the FALs. •CAS 12-59-01 contains arsenic and chromium contamination above FALs in surface and near-surface soils surrounding a stained location within the site. Based on the evaluation of analytical data from the CAI, review of future and current operations at CAS 12-59-01, and the detailed and comparative analysis of the potential CAAs, the following corrective actions are recommended for CAU 563.« less

High frequency of C9orf72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis patients from two founder populations sharing the same risk haplotype.

PubMed

Goldstein, Orly; Gana-Weisz, Mali; Nefussy, Beatrice; Vainer, Batel; Nayshool, Omri; Bar-Shira, Anat; Traynor, Bryan J; Drory, Vivian E; Orr-Urtreger, Avi

2018-04-01

We characterized the C9orf72 hexanucleotide repeat expansion (RE) mutation in amyotrophic lateral sclerosis (ALS) patients of 2 distinct origins, Ashkenazi and North Africa Jews (AJ, NAJ), its frequency, and genotype-phenotype correlations. In AJ, 80% of familial ALS (fALS) and 11% of sporadic ALS carried the RE, a total of 12.9% of all AJ-ALS compared to 0.3% in AJ controls (odds ratio [OR] = 44.3, p < 0.0001). In NAJ, 10% of fALS and 9% of sporadic ALS carried the RE, a total of 9.1% of all NAJ-ALS compared to 1% in controls (OR = 9.9, p = 0.0006). We identified a risk haplotype shared among all ALS patients, although an association with age at disease onset, fALS, and dementia were observed only in AJ. Variations were identified downstream the repeats. The risk haplotype and these polymorphisms were at high frequencies in alleles with 8 repeats or more, suggesting sequence instability. The different genotype-phenotype correlations and OR, together with the large range in age at onset, suggest that other modifiers and risk factors may affect penetrance and phenotype in ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential screening of mutated SOD1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons.

PubMed

Dupuis, L; de Tapia, M; René, F; Lutz-Bucher, B; Gordon, J W; Mercken, L; Pradier, L; Loeffler, J P

2000-08-01

In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of human FALS. Using an optimized suppression subtractive hybridization method, a cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal cord of G86R mice was identified by sequence analysis as the KIF3-associated protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed that KAP3 induction was an early event arising long before axonal degeneration. Immunohistochemical studies further revealed that KAP3 protein predominantly accumulates in large motor neurons of the ventral spinal cord. We further demonstrated that KAP3 up-regulation occurs independent of any change in the other components of the kinesin II complex. However, since the ubiquitous KIF1A motor is up-regulated, our results show an early and complex rearrangement of the fast axonal transport machinery in the course of FALS pathology. Copyright 2000 Academic Press.

Modeling fission product vapor transport in the Falcon facility

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

Shepherd, I.M.; Drossinos, Y.; Benson, C.G.

1995-05-01

An extensive database of aerosol Experiments exists and has been used for checking aerosol transport codes. Data for fission product vapor transport are harder to find. Some qualitative data are available, but the Falcon thermal gradient tube tests carried out at AEA Technology`s laboratories in Winfrith, England, mark the first serious attempt to provide a set of experiments suitable for the validation of codes that predict the transport and condensation of realistic mixtures of fission product vapors. Four of these have been analyzed to check how well the computer code VICTORIA can predict the most important phenomena. Of the fourmore » experiments studied, two are reference cases (FAL-17 and FAL-19), one is a case without boric acid (FAL-18), and the other is run in a reducing atmosphere (FAL-20). The results show that once the vapors condense onto aerosols, VICTORIA can predict their deposition rather well. The dominant mechanism is thermophoresis, and each element deposits with more or less the same deposition velocity. The behavior of the vapors is harder to interpret. Essentially, it is important to know the temperature at which each element condenses. It is clear from the measurements that this temperature changed from test to test-caused mostly by the different speciation as the composition of the carrier gas and the relative concentration of other fission products changed. Only in the test with a steam atmosphere and without boric acid was the assumption valid that most of the iodine is cesium iodide and most of the cesium is cesium hydroxide. In general, VICTORIA predicts that, with the exception of cesium, there will be less variation in the speciation-and, hence, variation in the deposition-between tests than is in fact observed. VICTORIA underpredicts the volatility of most elements, and this is partly a consequence of the ideal solution assumption and partly an overestimation of vapor/aerosol interactions.« less

Compositional effects on the chemorheological properties and forming behavior of aqueous alumina-poly(vinyl alcohol) gelcasting suspensions

NASA Astrophysics Data System (ADS)

Morissette, Sherry L.

A new gelcasting system based on aqueous, alumina-poly(vinyl alcohol) (PVA) suspensions cross-linked by an organotitanate coupling agent has been developed. Both the chemorheological properties and forming behavior of this system exhibited a strong compositional dependence. A sol- gel phase diagram was established, which yielded the critical titanium concentration [Ti] c required for gelation at a given PVA volume fraction, as well as the minimum PVA volume fraction ( fminPVA = 0.0245) and titanium PVA concentration ([Ti]min = 9.984 x 10--4 g Ti/ml) below which gelation was not observed irrespective of solution composition. The gelation time of suspensions of constant PVA volume fraction ( fsolnPVA ) decreased with increasing cross-linking agent concentration, PVA temperature, and solids volume fraction. The steady-state viscosity and elastic modulus of polymer solutions ( fsolnPVA = 0.05) of varying [Ti] were well described by the PVA percolation model, giving scaling exponents of 0.84 and 1.79, respectively. The steady-state elastic modulus of gel casting suspensions, which provides a measure of their handling strength in the as-gelled state, increased with increasing solids volume fraction. Gelcasting suspensions were used as feedstock for solid free-form fabrication (SFF) of ceramic components. The influence of processing conditions (e.g., tip diameter, mixing rate, table speed, etc.) and suspension rheology on deposition behavior was investigated. Continuous printablity was achieved for tip diameters ranging from dt = 0.254 -- 1.370 mm for all mixing rates (Rmix 5 -- 300 rpm) and suspension compositions (i.e., fAl2O3 = 0.45, φPVA = 0.275, [Ti] 0 -- 6.30 x 10--3 g Ti/ml) probed, where the minimum tip diameter for continuous printing was 0.203 mm. Printed lines were uniform with good edge definition. Line dimensions were independent of mixing rate for the given process conditions. The as-cast alumina volume fraction ( fAl2O3 ) depended on casting conditions and cross-linking agent concentration, where fAl2O3 decreased with increasing tip diameter and increased with increasing cross-linking agent concentration. Free-fomied Al2O3 components exhibited uniform particle packing and had minimal macro-defects (e.g., slumping or stair casing) and no detectable micro-defects (e.g., bubbles or cracking).

Vascular growth responses to chronic arterial occlusion are unaffected by myeloid specific focal adhesion kinase (FAK) deletion

NASA Astrophysics Data System (ADS)

Heuslein, Joshua L.; Murrell, Kelsey P.; Leiphart, Ryan J.; Llewellyn, Ryan A.; Meisner, Joshua K.; Price, Richard J.

2016-05-01

Arteriogenesis, or the lumenal expansion of pre-existing arterioles in the presence of an upstream occlusion, is a fundamental vascular growth response. Though alterations in shear stress stimulate arteriogenesis, the migration of monocytes into the perivascular space surrounding collateral arteries and their differentiation into macrophages is critical for this vascular growth response to occur. Focal adhesion kinase’s (FAK) role in regulating cell migration has recently been expanded to primary macrophages. We therefore investigated the effect of the myeloid-specific conditional deletion of FAK on vascular remodeling in the mouse femoral arterial ligation (FAL) model. Using laser Doppler perfusion imaging, whole mount imaging of vascular casted gracilis muscles, and immunostaining for CD31 in gastrocnemius muscles cross-sections, we found that there were no statistical differences in perfusion recovery, arteriogenesis, or angiogenesis 28 days after FAL. We therefore sought to determine FAK expression in different myeloid cell populations. We found that FAK is expressed at equally low levels in Ly6Chi and Ly6Clo blood monocytes, however expression is increased over 2-fold in bone marrow derived macrophages. Ultimately, these results suggest that FAK is not required for monocyte migration to the perivascular space and that vascular remodeling following arterial occlusion occurs independently of myeloid specific FAK.

Corrective Action Investigation Plan for Corrective Action Unit 371: Johnnie Boy Crater and Pin Stripe Nevada Test Site, Nevada, Revision 0

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

Patrick Matthews

Corrective Action Unit (CAU) 371 is located in Areas 11 and 18 of the Nevada Test Site, which is approximately 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 371 is comprised of the two corrective action sites (CASs) listed below: • 11-23-05, Pin Stripe Contamination Area • 18-45-01, U-18j-2 Crater (Johnnie Boy) These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives. Additional information will be obtained by conducting a corrective action investigation before evaluating corrective action alternatives and selecting the appropriate correctivemore » action for each CAS. The results of the field investigation will support a defensible evaluation of viable corrective action alternatives that will be presented in the Corrective Action Decision Document. The sites will be investigated based on the data quality objectives (DQOs) developed on November 19, 2008, by representatives of the Nevada Division of Environmental Protection; U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office; Stoller-Navarro Joint Venture; and National Security Technologies, LLC. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective actions for CAU 371. Appendix A provides a detailed discussion of the DQO methodology and the DQOs specific to each CAS. The scope of the corrective action investigation for CAU 371 includes the following activities: • Move surface debris and/or materials, as needed, to facilitate sampling. • Conduct radiological surveys. • Measure in situ external dose rates using thermoluminescent dosimeters or other dose measurement devices. • Collect and submit environmental samples for laboratory analysis to determine internal dose rates. • Combine internal and external dose rates to determine whether total dose rates exceed final action levels (FALs). • Collect and submit environmental samples for laboratory analysis to determine whether chemical contaminants are present at concentrations exceeding FALs. • If contamination exceeds FALs, define the extent of the contamination exceeding FALs. • Investigate waste to determine whether potential source material is present. This Corrective Action Investigation Plan has been developed in accordance with the Federal Facility Agreement and Consent Order that was agreed to by the State of Nevada; U.S. Department of Energy; and U.S. Department of Defense. Under the Federal Facility Agreement and Consent Order, this Corrective Action Investigation Plan will be submitted to the Nevada Division of Environmental Protection for approval. Fieldwork will be conducted following approval of the plan.« less

DNA strand breaks and TDP-43 mislocation are absent in the murine hSOD1G93A model of amyotrophic lateral sclerosis in vivo and in vitro

PubMed Central

Witte, Otto W.; Grosskreutz, Julian

2017-01-01

Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g., organelle dysfunction, RNA metabolism and oxidative DNA damage conferred by SOD1 malfunction. However, apart from metabolically evoked DNA oxidation, it is unclear whether severe genotoxicity including DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), originates from loss of function of nuclear SOD1 enzyme. Factors that endogenously interfere with DNA integrity and repair complexes in hSOD1-mediated fALS remain similarly unexplored. In this regard, uncontrolled activation of transposable elements (TEs) might contribute to DNA disintegration and neurodegeneration. The aim of this study was to elucidate the role of the fALS-causing hSOD1G93A mutation in the generation of severe DNA damage beyond well-characterized DNA base oxidation. Therefore, DNA damage was assessed in spinal tissue of hSOD1G93A-overexpressing mice and in corresponding motor neuron-enriched cell cultures in vitro. Overexpression of the hSOD1G93A locus did not change the threshold for severe DNA damage per se. We found that levels of SSBs and DSBs were unaltered between hSOD1G93A and control conditions, as demonstrated in post-mitotic motor neurons and in astrocytes susceptible to replication-dependent DNA breakage. Analogously, parameters indicative of DNA damage response processes were not activated in vivo or in vitro. Evidence for a mutation-related elevation in TE activation was not detected, in accordance with the absence of TAR DNA binding protein 43 (TDP-43) proteinopathy in terms of cytoplasmic mislocation or nuclear loss, as nuclear TDP-43 is supposed to silence TEs physiologically. Conclusively, the superoxide dismutase function of SOD1 might not be required to preserve DNA integrity in motor neurons, at least when the function of TDP-43 is unaltered. Our data establish a foundation for further investigations addressing functional TDP-43 interaction with ALS-relevant genetic mutations. PMID:28832631

Reduction in hSOD1 copy number significantly impacts ALS phenotype presentation in G37R (line 29) mice: implications for the assessment of putative therapeutic agents.

PubMed

Zwiegers, Pierre; Lee, Grace; Shaw, Christopher A

2014-08-08

In vivo animal models of familial amyotrophic lateral sclerosis (fALS) are widely used to delineate the potential role that genetic mutations play in the neurodegenerative process. While these models are extensively used for establishing the safety and efficacy of putative therapeutics during pre-clinical development, effective clinical translation of pharmacological interventions has been largely unsuccessful. In this report we compare a recent cohort of G37R (line 29) mice generated from mating wild-type females with transgenic males obtained commercially to a previous set of offspring produced with transgenic male breeders from a colony established at a local collaborator's facility. Commercially derived progeny presented with a tightly clustered genomic signature for the mutant human superoxide dismutase1 transgene (hSOD1) locus, and exhibited a greater than two-fold reduction in the number of transgene copies present in the genome compared to offspring derived locally. Decrease in transgene levels corresponded with delayed ALS progression and a significant increase in overall lifespan (146%). These results highlight some key challenges inherent to the use of G37R (line 29) animals in pre-clinical studies for the development of ALS therapeutics. Without stringent assessment of mutant SOD1 copy number/protein levels, heterogeneity of transgene levels within cohorts may influence the behavioural and pathological presentation of disease and thus calls to question the validity of any detected therapeutic effects. Nuanced changes in mutant SOD1 copy number that currently remain unreported may undermine research endeavours, delay efforts for clinical translation, and compromise the rigor of animal studies by limiting reproducibility amongst research groups.

Treatment and resource recovery from inorganic fluoride-containing waste produced by the pesticide industry.

PubMed

Li, Yang; Zhang, Hua; Zhang, Zhiqi; Shao, Liming; He, Pinjing

2015-05-01

The rapid development of the fluorinated pesticide industry has produced a large amount of fluorine-containing hazardous waste, especially inorganic fluoride-containing waste (IFCW). A two-step process, including extraction and recovery, was developed to recover fluorine as synthetic cryolite from IFCW produced by the pesticide industry. The optimum conditions for extraction were found to be a temperature of 75°C, an initial pH (pHi) of 12, a 4-hr incubation time and a liquid-to-solid ratio of 40mL/g; these conditions resulted in a fluorine extraction ratio of 99.0%. The effects of pH and the F/Al molar ratio on fluorine recovery and the compositional, mineralogical and morphological characteristics of the cryolite products were investigated. Field-emission scanning electron microscopy of recovered precipitates showed changes in morphology with the F/Al molar ratio. Coupling Fourier transform and infrared spectroscopy, X-ray diffraction indicated that the formation of AlF6(3-) was restricted as increasing pH. Both the amount of fluorine recovered and the quality of the cryolite were optimized at initial pH=3 and a F/Al molar ratio 5.75. This study proposed a reliable and environmentally friendly method for the treatment of fluoride-containing wastes, which could be suitable for industrial applications. Copyright © 2015. Published by Elsevier B.V.

Magnetic Resonance Spectroscopy of Regional Brain Metabolite Markers in FALS Mice and the Effects of Dietary Creatine Supplementation

PubMed Central

Choi, JiKyung; Kustermann, Ekkehard; Dedeoglu, Alpaslan; Jenkins, Bruce G.

2010-01-01

We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased NAA, decreased glutamate and increased glutamine, taurine and myo-inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild-type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%) reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on NAA loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention leading to a 13% increase in weight between 120-130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models. PMID:19930399

A comprehensive review of amyotrophic lateral sclerosis

PubMed Central

Zarei, Sara; Carr, Karen; Reiley, Luz; Diaz, Kelvin; Guerra, Orleiquis; Altamirano, Pablo Fernandez; Pagani, Wilfredo; Lodin, Daud; Orozco, Gloria; Chinea, Angel

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease affecting motor neurons with an incidence of about 1/100,000. Most ALS cases are sporadic, but 5–10% of the cases are familial ALS. Both sporadic and familial ALS (FALS) are associated with degeneration of cortical and spinal motor neurons. The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, genetic factors, symptoms, diagnostic, treatment, and even the available supplement and management of ALS. This will provide the reader with an advantage of receiving a broad range of information about the disease. PMID:26629397

Ethical considerations in the management of amyotrophic lateral sclerosis.

PubMed

Eisen, Andrew; Krieger, Charles

2013-11-01

This article examines some of the ethical concerns relevant for the management of amyotrophic lateral sclerosis (ALS). We emphasize the importance for providing a competent assessment of the clinical deficit to correctly identify the disease and to avoid incorrect diagnoses. Conveying the diagnosis to the patient and their family requires empathy and it is important to remain supportive and positive, even in the face of this incurable disease. The essence of care in ALS is to permit the patient to have optimal function for their level of ability. This may require the use of gastrostomy and non-invasive or permanent ventilation. Employment of a multi-disciplinary team will permit optimization of patient care to achieve a good quality of life for as long as possible. The patient should also be informed of the risks associated with unproven therapies and the risks and potential benefits of therapeutic trials. The wishes of patients in regard to gastrostomy, long-term ventilation and end-of life decisions must be considered in an unbiased fashion. Recent advances in the genetics of familial ALS (FALS) have demonstrated some overlap between FALS, sporadic ALS and fronto-temporal lobar dementia (FTLD). The interpretation and dissemination of the results of genetic testing although important can induce confusion, considerable anxiety and guilt in patients and their families and proper counseling is imperative. Copyright © 2013 Elsevier Ltd. All rights reserved.

A revisit to model the Cr i triplet at 5204-5208 Å and the Ba ii D2 line at 4554 Å in the Second Solar Spectrum

NASA Astrophysics Data System (ADS)

Smitha, H. N.; Nagendra, K. N.; Stenflo, J. O.; Bianda, M.; Sampoorna, M.; Ramelli, R.

2015-10-01

In our previous attempt to model the Stokes profiles of the Cr i triplet at 5204-5208 Å and the Ba ii D2 at 4554 Å, we found it necessary to slightly modify the standard FAL model atmospheres to fit the observed polarization profiles. In the case of Cr i triplet, this modification was done to reduce the theoretical continuum polarization, and in the case of Ba ii D2, it was needed to reproduce the central peak in Q/I. In this work, we revisit both these cases using different standard model atmospheres whose temperature structures closely resemble those of the modified FAL models, and explore the possibility of synthesizing the line profiles without the need for small modifications of the model atmosphere.

Observation of c.260A > G mutation in superoxide dismutase 1 that causes p.Asn86Ser in Iranian amyotrophic lateral sclerosis patient and absence of genotype/phenotype correlation.

PubMed

Khani, Marzieh; Alavi, Afagh; Nafissi, Shahriar; Elahi, Elahe

2015-07-06

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder in European populations. ALS can be sporadic ALS (SALS) or familial ALS (FALS). Among 20 known ALS genes, mutations in C9orf72 and superoxide dismutase 1 (SOD1) are the most common genetic causes of the disease. Whereas C9orf72 mutations are more common in Western populations, the contribution of SOD1 to ALS in Iran is more than C9orf72. At present, a clear genotype/phenotype correlation for ALS has not been identified. We aimed to perform mutation screening of SOD1 in a newly identified Iranian FALS patient and to assess whether a genotype/phenotype correlation for the identified mutation exists. The five exons of SOD1 and flanking intronic sequences of a FALS proband were screened for mutations by direct sequencing. The clinical features of the proband were assessed by a neuromuscular specialist (SN). The phenotypic presentations were compared to previously reported patients with the same mutation. Heterozygous c.260A > G mutation in SOD1 that causes Asn86Ser was identified in the proband. Age at onset was 34 years and site of the first presentation was in the lower extremities. Comparisons of clinical features of different ALS patients with the same mutation evidenced variable presentations. The c.260A > G mutation in SOD1 that causes Asn86Ser appears to cause ALS with variable clinical presentations.

Student perceptions of independent versus facilitated small group learning approaches to compressed medical anatomy education.

PubMed

Whelan, Alexander; Leddy, John J; Mindra, Sean; Matthew Hughes, J D; El-Bialy, Safaa; Ramnanan, Christopher J

2016-01-01

The purpose of this study was to compare student perceptions regarding two, small group learning approaches to compressed (46.5 prosection-based laboratory hours), integrated anatomy education at the University of Ottawa medical program. In the facilitated active learning (FAL) approach, tutors engage students and are expected to enable and balance both active learning and progression through laboratory objectives. In contrast, the emphasized independent learning (EIL) approach stresses elements from the "flipped classroom" educational model: prelaboratory preparation, independent laboratory learning, and limited tutor involvement. Quantitative (Likert-style questions) and qualitative data (independent thematic analysis of open-ended commentary) from a survey of students who had completed the preclerkship curriculum identified strengths from the EIL (promoting student collaboration and communication) and FAL (successful progression through objectives) approaches. However, EIL led to student frustration related to a lack of direction and impaired completion of objectives, whereas active learning opportunities in FAL were highly variable and dependent on tutor teaching style. A "hidden curriculum" was also identified, where students (particularly EIL and clerkship students) commonly compared their compressed anatomy education or their anatomy learning environment with other approaches. Finally, while both groups highly regarded the efficiency of prosection-based learning and expressed value for cadaveric-based learning, student commentary noted that the lack of grade value dedicated to anatomy assessment limited student accountability. This study revealed critical insights into small group learning in compressed anatomy education, including the need to balance student active learning opportunities with appropriate direction and feedback (including assessment). © 2015 American Association of Anatomists.

Benthic foraminifera (Protista) as indicators of metal pollution in areas of historic mining: examples from southwest England

NASA Astrophysics Data System (ADS)

Hart, Malcolm; Smart, Christopher

2016-04-01

Southwest England has been, from Roman times, an important mining area supplying a range of important metals, including copper, tin, tungsten, arsenic, zinc, silver, etc. This mining activity virtually disappeared in the twentieth century, although one tungsten mine near Plymouth has recently re-opened. Large areas of Cornwall and West Devon are now inscribed as the 'Cornish Mining World Heritage Site' on the cultural list of UNESCO. Many of the old mines with their spoil heaps and tailings dams are now protected and, together with the mineral-rich local geology, provide many catchments with on-going metal pollution. In January 1992, after a period of prolonged, heavy rainfall Wheal Jane mine flooded and discharged heavily polluted, acidic, water into Restonguet Creek and the Fal Estuary. This event provided the setting for a detailed investigation of the immediate impact of the pollution and the resulting environmental improvements caused by engineering interventions and natural re-adjustment. Benthic foraminifera disappeared from Restronguet Creek for a number of years and while there is now an abundant, though low diversity, estuarine assemblage of foraminifera living in the creek there are still high levels (<15% in 2004) of test deformity recorded (Olugbode et al., 2005). In other parts of the Fal Estuary (a Special Area of Conservation under the EU Habitats Directive, 2000), deformed foraminifera are very rare and the measured levels of pollution can be used to compare with the test deformity data. In other estuarine systems in southwest England, such as the River Fowey and the River Tamar, levels of deformity are less, though still significant for areas no longer being actively mined. This demonstrates that polluted sediments in all these estuaries, which can be disturbed during floods or times of stormy weather, and the background levels of metal elements in the catchments that supply these estuaries, are sufficient to maintain these levels of deformity in the long term. OLUGBODE, O.I., HART, M.B. & STUBBLES, S.J. 2005. Foraminifera from Restronguet Creek: monitoring recovery from the Wheal Jane pollution incident. Geoscience in south-west England, 11, 82-92.

Evaluation of cement treated base courses : technical assistance report.

DOT National Transportation Integrated Search

2000-12-01

The objectives of this project are to determine the strength characteristics of soil cement bases that were constructed under stabilized procedures (DOTD TR 432M/432-99) and the cement treated design philosophy. This was accomplished by using the Fal...

Comparison of "saw and seal" procedure and performance grade binder to minimize thermal cracking.

DOT National Transportation Integrated Search

2001-04-01

In an effort to compare performance and cost effectiveness of the Saw and : Seal procedure and Performance Grade (PG) binders, the Maine Department Of : Transportation (MDOT) constructed an experimental project in Weston, Maine : during the fal...

Flower morphology and development in Artemisia annua, a medicinal plant used as a treatment against malaria

USDA-ARS?s Scientific Manuscript database

Artemisia annua produces a wide spectrum of bioactive phytochemicals that possess pharmacological properties including antimalarial, antitumor, anti-inflammatory, and anthelmintic activities. The main active ingredient, artemisinin, is extremely effective against multi-drug resistant Plasmodium fal...

Hepatic carcinosarcoma: evidence of polyclonal origin based on microsatellite analysis.

PubMed

Gu, Yi-Jin; Zhu, Yu-Yao; Lu, Xin-Yuan; Zhao, Qian; Cong, Wen-Ming

2015-12-01

Hepatic carcinosarcoma (HCS) is an aggressive tumor for which a consensus regarding the clonal origin has not yet been reached. The aim of the study was to identify the origin of the hepatocellular carcinoma (HCC) and sarcoma components in HCS. We chose microsatellite technique containing loss of heterozygosity (LOH) and microsatellite instability (MSI) on three HCS patients who underwent curative resection confirmed by pathological examination. Tumors were firstly analyzed for Hep Par 1, CK18, CD10, CD117, SMA and vimentin expression by immunohistochemistry. LOH and MSI were then investigated. The incidence rate of LOH/MSI in all nine MS was calculated as the fractional allelic loss (FAL) index, which was internationally recognized standard. A FAL<30% was representative of a monoclonal origin and a FAL≥30% indicated a polyclonal origin. All patients were positive for HBsAg. Microscopic examination showed HCS containing two different cell types: a fibrosarcoma component with spindle cells and an HCC population of cells with a trabecular pattern. In the HCC tumor portions, Hep Par 1, CK18, CD10 were expressed while vimentin was not. In contrast, the spindle cell populations were positive for vimentin and negative for Hep Par 1, CK18, CD10. The highest frequencies of LOH and MSI were at the D16S505 (2/3; 66.7%), D17S831 (2/3; 66.7%) and D17S938 MS (2/3; 66.7%). The FALs for the three cases of HCS were 50% (4/8), 55.6% (5/9) and 33.3% (3/9), suggesting a polyclonal origin. Immunohistochemistry and analysis of LOH and MSI strongly demonstrated that the three HCS samples were consistent with a polyclonal origin for all three cases. Copyright © 2015 Elsevier GmbH. All rights reserved.

Mitochondrial dynamics and bioenergetic dysfunction is associated with synaptic alterations in mutant SOD1 motor neurons

PubMed Central

Magrané, Jordi; Sahawneh, Mary Anne; Przedborski, Serge; Estévez, Álvaro G.; Manfredi, Giovanni

2012-01-01

Mutations in Cu,Zn superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (FALS), a rapidly fatal motor neuron disease. Mutant SOD1 has pleiotropic toxic effects on motor neurons, among which mitochondrial dysfunction has been proposed as one of the contributing factors in motor neuron demise. Mitochondria are highly dynamic in neurons; they are constantly reshaped by fusion and move along neurites to localize at sites of high-energy utilization, such as synapses. The finding of abnormal mitochondria accumulation in neuromuscular junctions, where the SOD1-FALS degenerative process is though to initiate, suggests that impaired mitochondrial dynamics in motor neurons may be involved in pathogenesis. We addressed this hypothesis by live imaging microscopy of photo-switchable fluorescent mitoDendra in transgenic rat motor neurons expressing mutant or wild type human SOD1. We demonstrate that mutant SOD1 motor neurons have impaired mitochondrial fusion in axons and cell bodies. Mitochondria also display selective impairment of retrograde axonal transport, with reduced frequency and velocity of movements. Fusion and transport defects are associated with smaller mitochondrial size, decreased mitochondrial density, and defective mitochondrial membrane potential. Furthermore, mislocalization of mitochondria at synapses among motor neurons, in vitro, correlates with abnormal synaptic number, structure, and function. Dynamics abnormalities are specific to mutant SOD1 motor neuron mitochondria, since they are absent in wild type SOD1 motor neurons, they do not involve other organelles, and they are not found in cortical neurons. Taken together, these results suggest that impaired mitochondrial dynamics may contribute to the selective degeneration of motor neurons in SOD1-FALS. PMID:22219285

Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with (18)F-Al labeled Cys(39)-exendin-4.

PubMed

Mi, Baoming; Xu, Yuping; Pan, Donghui; Wang, Lizhen; Yang, Runlin; Yu, Chunjing; Wan, Weixing; Wu, Yiwei; Yang, Min

2016-02-26

Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with (18)F-Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells. Copyright © 2016 Elsevier Inc. All rights reserved.

ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia.

PubMed

Zhang, Kang; Liu, Qing; Liu, Keqiang; Shen, Dongchao; Tai, Hongfei; Shu, Shi; Ding, Qingyun; Fu, Hanhui; Liu, Shuangwu; Wang, Zhili; Li, Xiaoguang; Liu, Mingsheng; Zhang, Xue; Cui, Liying

2018-06-01

To investigate the genetic contribution of ANXA11 , a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia. Sequencing all the coding exons of ANXA11 and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in peripheral blood generated from a splicing mutation were examined by reverse transcriptase PCR. We identified 6 nonsynonymous heterozygous mutations (5 novel and 1 recurrent), 1 splice site mutation, and 1 deletion of 10 amino acids (not accounted in the mutant frequency) in 11 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS, and 8.3% (1/12) in ALS-FTD. The deletion of 10 amino acids was detected in 1 clinically undetermined male with an ALS family history who had atrophy in hand muscles and myotonic discharges revealed by EMG. The novel p. P36R mutation was identified in 1 FALS index, 1 patient with SALS, and 1 ALS-FTD. The splicing mutation (c.174-2A>G) caused in-frame skipping of the entire exon 6. The rest missense mutations including p.D40G, p.V128M, p.S229R, p.R302C and p.G491R were found in 6 unrelated patients with SALS. The ANXA11 gene is one of the most frequently mutated genes in Chinese patients with SALS. A canonical splice site mutation leading to skipping of the entire exon 6 further supports the loss-of-function mechanism. In addition, the study findings further expand the ANXA11 phenotype, first highlighting its pathogenic role in ALS-FTD.

ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19

PubMed Central

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V.; Dion, Patrick A.; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A.; Williams, Kelly L.; Blair, Ian P.; Nicholson, Garth A.; Gonzalez-Perez, Paloma; Brown, Robert H.; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A.; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3–5 years from onset. Familial ALS (FALS) comprises 5%–10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. PMID:24119685

Indole-3-Carbonitriles as DYRK1A Inhibitors by Fragment-Based Drug Design.

PubMed

Meine, Rosanna; Becker, Walter; Falke, Hannes; Preu, Lutz; Loaëc, Nadège; Meijer, Laurent; Kunick, Conrad

2018-01-24

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a potential drug target because of its role in the development of Down syndrome and Alzheimer's disease. The selective DYRK1A inhibitor 10-iodo-11 H -indolo[3,2- c ]quinoline-6-carboxylic acid (KuFal194), a large, flat and lipophilic molecule, suffers from poor water solubility, limiting its use as chemical probe in cellular assays and animal models. Based on the structure of KuFal194, 7-chloro-1 H -indole-3-carbonitrile was selected as fragment template for the development of smaller and less lipophilic DYRK1A inhibitors. By modification of this fragment, a series of indole-3-carbonitriles was designed and evaluated as potential DYRK1A ligands by molecular docking studies. Synthesis and in vitro assays on DYRK1A and related protein kinases identified novel double-digit nanomolar inhibitors with submicromolar activity in cell culture assays.

Structure-Based Prediction of Unstable Regions in Proteins: Applications to Protein Misfolding Diseases

NASA Astrophysics Data System (ADS)

Guest, Will; Cashman, Neil; Plotkin, Steven

2009-03-01

Protein misfolding is a necessary step in the pathogenesis of many diseases, including Creutzfeldt-Jakob disease (CJD) and familial amyotrophic lateral sclerosis (fALS). Identifying unstable structural elements in their causative proteins elucidates the early events of misfolding and presents targets for inhibition of the disease process. An algorithm was developed to calculate the Gibbs free energy of unfolding for all sequence-contiguous regions of a protein using three methods to parameterize energy changes: a modified G=o model, changes in solvent-accessible surface area, and solution of the Poisson-Boltzmann equation. The entropic effects of disulfide bonds and post-translational modifications are treated analytically. It incorporates a novel method for finding local dielectric constants inside a protein to accurately handle charge effects. We have predicted the unstable parts of prion protein and superoxide dismutase 1, the proteins involved in CJD and fALS respectively, and have used these regions as epitopes to prepare antibodies that are specific to the misfolded conformation and show promise as therapeutic agents.

Identifying Unstable Regions of Proteins Involved in Misfolding Diseases

NASA Astrophysics Data System (ADS)

Guest, Will; Cashman, Neil; Plotkin, Steven

2009-05-01

Protein misfolding is a necessary step in the pathogenesis of many diseases, including Creutzfeldt-Jakob disease (CJD) and familial amyotrophic lateral sclerosis (fALS). Identifying unstable structural elements in their causative proteins elucidates the early events of misfolding and presents targets for inhibition of the disease process. An algorithm was developed to calculate the Gibbs free energy of unfolding for all sequence-contiguous regions of a protein using three methods to parameterize energy changes: a modified G=o model, changes in solvent-accessible surface area, and all-atoms molecular dynamics. The entropic effects of disulfide bonds and post-translational modifications are treated analytically. It incorporates a novel method for finding local dielectric constants inside a protein to accurately handle charge effects. We have predicted the unstable parts of prion protein and superoxide dismutase 1, the proteins involved in CJD and fALS respectively, and have used these regions as epitopes to prepare antibodies that are specific to the misfolded conformation and show promise as therapeutic agents.

Corrective Action Decision Document for Corrective Action Unit 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada, Rev. No.: 0

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

Grant Evenson

2006-05-01

This Corrective Action Decision Document has been prepared for Corrective Action Unit (CAU) 151, Septic Systems and Discharge Area, at the Nevada Test Site, Nevada, according to the ''Federal Facility Agreement and Consent Order'' (FFACO) (1996). Corrective Action Unit 151 is comprised of eight corrective action sites (CASs): (1) CAS 02-05-01, UE-2ce Pond; (2) CAS 12-03-01, Sewage Lagoons (6); (3) CAS 12-04-01, Septic Tanks; (4) CAS 12-04-02, Septic Tanks; (5) CAS 12-04-03, Septic Tank; (6) CAS 12-47-01, Wastewater Pond; (7) CAS 18-03-01, Sewage Lagoon; and (8) CAS 18-99-09, Sewer Line (Exposed). The purpose of this Corrective Action Decision Document ismore » to identify and provide the rationale for the recommendation of corrective action alternatives (CAAs) for each of the eight CASs within CAU 151. Corrective action investigation (CAI) activities were performed from September 12 through November 18, 2005, as set forth in the CAU 151 Corrective Action Investigation Plan and Record of Technical Change No. 1. Additional confirmation sampling was performed on December 9, 2005; January 10, 2006; and February 13, 2006. Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the contaminants of concern for each CAS. The results of the CAI identified contaminants of concern at two of the eight CASs in CAU 151 and required the evaluation of CAAs. Assessment of the data generated from investigation activities conducted at CAU 151 revealed the following: (1) Soils at CASs 02-05-01, 12-04-01, 12-04-02, 12-04-03, 12-47-01, 18-03-01, 18-99-09, and Lagoons B through G of CAS 12-03-01 do not contain contamination at concentrations exceeding the FALs. (2) Lagoon A of CAS 12-03-01 has arsenic above FALs in shallow subsurface soils. (3) One of the two tanks of CAS 12-04-01, System No.1, has polychlorinated biphenyls (aroclor-1254), trichloroethane, and cesium-137 above FALs in the sludge. Both CAS 12-04-01, System No.1 tanks contain trichloroethane and 1,4-dichlorobenzene above ''Resource Conservation and Recovery Act'' toxicity characteristic limits. Based on the evaluation of analytical data from the CAI, review of future and current operations at the eight CASs, and the detailed and comparative analysis of the potential CAAs, the following corrective actions are recommended for CAU 151. No Further Action is the recommended corrective action for soils at CASs 02-05-01, 12-04-01, 12-04-02, 12-04-03, 18-03-01, and 18-99-09; and Lagoons C, D, F, and G of CAS 12-03-01. No Further Action with implementation of a best management practice (BMP) is recommended for soils at CAS 12-47-01 and Lagoons B and E of CAS 12-03-01. To be protective of future workers should the present scenario used to calculate FALs change, an administrative use restriction will be recorded per the FFACO agreement as a BMP. Close in Place with Administrative Controls is the recommended corrective action for Lagoon A of CAS 12-03-01. Based on the evaluation of analytical data from the CAI; review of future and current operations at CASs 12-04-01, 12-04-02, and 12-04-03; and the detailed and comparative analysis of the potential CAAs, the following corrective actions are recommended for the septic tanks at these CASs. No Further Action with implementation of BMPs is the recommended corrective action for septic tanks that do not contain potential source material from CAS 12-04-01, System No.4 (four tanks); CAS 12-04-02, System No.5 (six tanks); and CAS 12-04-03, System No.3 (four tanks). Clean Closure with implementation of BMPs is the recommended corrective action for the septic tanks from CAS 12-04-01, System No.1 (two tanks). The preferred CAAs were evaluated on technical merit focusing on performance, reliability, feasibility, safety, and cost. The alternatives were judged to meet all requirements for the technical components evaluated. The alternatives meet all applicable federal and state regulations for closure of the site and will reduce potential exposure pathways to the contaminated media to an acceptable level at CAU 151.« less

Effect of simulated sanitizer carryover on recovery of salmonella from broiler carcass rinsates

USDA-ARS?s Scientific Manuscript database

Numerous antimicrobial chemicals are currently utilized as processing aids with the aim of reducing pathogenic bacteria on processed poultry carcasses. Carry-over of active sanitizer to a carcass rinse solution intended for detection of viable pathogenic bacteria by regulatory agencies may cause fal...

Closure Report for Corrective Action Unit 539: Areas 25 and 26 Railroad Tracks Nevada National Security Site, Nevada with ROTC-1, Revision 0

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

Mark Kauss

2011-06-01

This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 539: Areas 25 and 26 Railroad Tracks, Nevada National Security Site, Nevada. This CR complies with the requirements of the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. The corrective action sites (CASs) within CAU 539 are located within Areas 25 and 26 of the Nevada National Security Site. Corrective Action Unit 539 comprises the following CASs: • 25-99-21, Area 25 Railroad Tracksmore » • 26-99-05, Area 26 Railroad Tracks The purpose of this CR is to provide documentation supporting the completed corrective actions and provide data confirming that the closure objectives for CASs within CAU 539 were met. To achieve this, the following actions were performed: • Reviewed documentation on historical and current site conditions, including the concentration and extent of contamination. • Conducted radiological walkover surveys of railroad tracks in both Areas 25 and 26. • Collected ballast and soil samples and calculated internal dose estimates for radiological releases. • Collected in situ thermoluminescent dosimeter measurements and calculated external dose estimates for radiological releases. • Removed lead bricks as potential source material (PSM) and collected verification samples. • Implemented corrective actions as necessary to protect human health and the environment. • Properly disposed of corrective action and investigation wastes. • Implemented an FFACO use restriction (UR) for radiological contamination at CAS 25-99-21. The approved UR form and map are provided in Appendix F and will be filed in the DOE, National Nuclear Security Administration Nevada Site Office (NNSA/NSO), Facility Information Management System; the FFACO database; and the NNSA/NSO CAU/CAS files. From November 29, 2010, through May 2, 2011, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 539: Areas 25 and 26 Railroad Tracks, Nevada Test Site, Nevada. The purposes of the activities as defined during the data quality objectives process were as follows: • Determine whether contaminants of concern (COCs) are present. • If COCs are present, determine their nature and extent, implement appropriate corrective actions, and properly dispose of wastes. Analytes detected during the closure activities were evaluated against final action levels (FALs) to determine COCs for CAU 539. Assessment of the data generated from closure activities revealed the following: • At CAS 26-99-05, the total effective dose for radiological releases did not exceed the FAL of 25 millirem per Industrial Area year. Potential source material in the form of lead bricks was found at three locations. A corrective action of clean closure was implemented at these locations, and verification samples indicated that no further action is necessary. • At CAS 25-99-21, the total effective dose for radiological releases exceeds the FAL of 25 millirem per Industrial Area year. Potential source material in the form of lead bricks was found at eight locations. A corrective action was implemented by removing the lead bricks and soil above FALs at these locations, and verification samples indicated that no further action is necessary. Pieces of debris with high radioactivity were identified as PSM and remain within the CAS boundary. A corrective action of closure in place with a UR was implemented at this CAS because closure activities showed evidence of remaining soil contamination and radioactive PSM. Future land use will be restricted from surface and intrusive activities. Closure activities generated waste streams consisting of industrial solid waste, recyclable materials, low-level radioactive waste, and mixed low-level radioactive waste. Wastes were disposed of in the appropriate onsite landfills. The NNSA/NSO provides the following recommendations: • Clean closure is required at CAS 26-99-05. • Closure in place is required at CAS 25-99-21. • A UR is required at CAS 25-99-21. • A Notice of Completion to the NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 539. • Corrective Action Unit 539 should be moved from Appendix III to Appendix IV of the FFACO.« less

Free-to-Roll Investigation of Uncommanded Lateral Motions for an Aircraft with Vented Strakes

NASA Technical Reports Server (NTRS)

Owens, Elaine M.; Bryant, Elaine M.; Barlow, Jewel B.

2005-01-01

A free-to-roll study of the low-speed lateral characteristics of the pre-production F/A-l8E was conducted in the NASA Langley 12-Foot Low-Speed Tunnel. In developmental flight tests the F/A-18E unexpectedly experienced uncommanded lateral motions in the power approach configuration. The objective of this study was to determine the feasibility of using the free-to-roll technique for the detection of uncommanded lateral motions for the pre-production F/A-l8E in the power approach configuration. The data revealed that this technique in conjunction with static data revealed insight into the cause of the lateral motions. The free-to-roll technique identified uncommanded lateral motions at the same angle-of-attack range as experienced in flight tests. The cause of the uncommanded lateral motions was unsteady asymmetric wing stall. The paper also shows that free-to-roll data or static force and moment data alone are not enough to accurately capture the potential for an aircraft to experience uncommanded lateral motion.

Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning.

PubMed

de la Torre, M Lourdes; Escarabajal, M Dolores; Agüero, Ángeles

2015-10-01

Vulnerability to ethanol abuse may be a function of the balance between the opposing (aversive and rewarding) motivational effects of the drug. The study of these effects is particularly important for understanding alcohol addiction. Research in this field seems to point out that ethanol effects are determined by a set of internal factors (sex, ethanol intake history, etc.), as well as by environmental conditions surrounding the individual (i.e., stress) and, of course, the interactions between all these factors. This work explores sex differences in sensitivity to aversive effects of ethanol using the procedure of flavor avoidance learning (FAL), as well as the effect of this learning experience on subsequent voluntary ethanol consumption, in adult rats. The results obtained indicated a slight sex based difference in the amount of FAL acquired in that females acquisition was weaker (experiment 1), and a differing influence of previous experience with the aversive effects of ethanol on the voluntary consumption of the drug for each sex (experiment 2). In particular, it was observed that female ethanol-naive rats showed a higher intake level and preference for ethanol than both ethanol-experienced female rats and ethanol-naive male rats. In contrast, the ethanol-experienced male rats showed a greater consumption of and preference for ethanol than ethanol-naive male rats and ethanol-experienced female rats. These data are discussed noting a range of possible explicative factors (sex hormones, hedonic processing, etc.), but further studies are warranted to elucidate the mechanisms by which ethanol pre-exposure influences the subsequent intake of ethanol differently by sex. Copyright © 2015 Elsevier Inc. All rights reserved.

ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19.

PubMed

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V; Dion, Patrick A; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A; Williams, Kelly L; Blair, Ian P; Nicholson, Garth A; Gonzalez-Perez, Paloma; Brown, Robert H; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-11-07

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genetic and Pathological Assessment of hnRNPA1, hnRNPA2/B1, and hnRNPA3 in Familial and Sporadic Amyotrophic Lateral Sclerosis.

PubMed

Fifita, Jennifer A; Zhang, Katharine Y; Galper, Jasmin; Williams, Kelly L; McCann, Emily P; Hogan, Alison L; Saunders, Neil; Bauer, Denis; Tarr, Ingrid S; Pamphlett, Roger; Nicholson, Garth A; Rowe, Dominic; Yang, Shu; Blair, Ian P

2017-01-01

Mutations in the genes encoding the heterogeneous nuclear ribonucleoproteins hnRNPA1 and hnRNPA2/B1 have been reported in a multisystem proteinopathy that includes amyotrophic lateral sclerosis (ALS) and inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia. Mutations were also described in the prion-like domain of hnRNPA1 in patients with classic ALS. Another hnRNP protein, hnRNPA3, has been found to be associated with the ALS/frontotemporal dementia protein C9orf72. To further assess their role in ALS, we examined these hnRNPs in spinal cord tissue from sporadic (SALS) and familial ALS (FALS) patients, including C9orf72 repeat expansion-positive patients, and controls. We also sought to determine the prevalence of HNRNPA1, HNRNPA2B1, and HNRNPA3 mutations in Australian ALS patients. Immunostaining was used to assess hnRNPs in ALS patient spinal cords. Mutation analysis of the HNRNPA1, HNRNPA2B1, and HNRNPA3 genes was performed in FALS and of their prion-like domains in SALS patients. Immunostaining of spinal motor neurons of ALS patients with the C9orf72 repeat expansion showed significant mislocalisation of hnRNPA3, and no differences in hnRNPA1 or A2/B1 localisation, compared to controls. No novel or known mutations were identified in HNRNPA1, HNRNPA2B1, or HNRNPA3 in Australian ALS patients. hnRNPA3 pathology was identified in motor neurons of ALS patients with C9orf72 repeat expansions, implicating hnRNPA3 in the pathogenesis of C9orf72-linked ALS. hnRNPA3 warrants further investigation into the pathogenesis of ALS linked to C9orf72. This study also determined that HNRNP mutations are not a common cause of FALS and SALS in Australia. © 2017 S. Karger AG, Basel.

The anabolic/androgenic steroid nandrolone exacerbates gene expression modifications induced by mutant SOD1 in muscles of mice models of amyotrophic lateral sclerosis

PubMed Central

Galbiati, Mariarita; Onesto, Elisa; Zito, Arianna; Crippa, Valeria; Rusmini, Paola; Mariotti, Raffaella; Bentivoglio, Marina; Bendotti, Caterina; Poletti, Angelo

2012-01-01

Anabolic/androgenic steroids (AAS) are drugs that enhance muscle mass, and are often illegally utilized in athletes to improve their performances. Recent data suggest that the increased risk for amyotrophic lateral sclerosis (ALS) in male soccer and football players could be linked to AAS abuse. ALS is a motor neuron disease mainly occurring in sporadic (sALS) forms, but some familial forms (fALS) exist and have been linked to mutations in different genes. Some of these, in their wild type (wt) form, have been proposed as risk factors for sALS, i.e. superoxide dismutase 1 (SOD1) gene, whose mutations are causative of about 20% of fALS. Notably, SOD1 toxicity might occur both in motor neurons and in muscle cells. Using gastrocnemius muscles of mice overexpressing human mutant SOD1 (mutSOD1) at different disease stages, we found that the expression of a selected set of genes associated to muscle atrophy, MyoD, myogenin, atrogin-1, and transforming growth factor (TGF)β1, is up-regulated already at the presymptomatic stage. Atrogin-1 gene expression was increased also in mice overexpressing human wtSOD1. Similar alterations were found in axotomized mouse muscles and in cultured ALS myoblast models. In these ALS models, we then evaluated the pharmacological effects of the synthetic AAS nandrolone on the expression of the genes modified in ALS muscle. Nandrolone administration had no effects on MyoD, myogenin, and atrogin-1 expression, but it significantly increased TGFβ1 expression at disease onset. Altogether, these data suggest that, in fALS, muscle gene expression is altered at early stages, and AAS may exacerbate some of the alterations induced by SOD1 possibly acting as a contributing factor also in sALS. PMID:22178654

The anabolic/androgenic steroid nandrolone exacerbates gene expression modifications induced by mutant SOD1 in muscles of mice models of amyotrophic lateral sclerosis.

PubMed

Galbiati, Mariarita; Onesto, Elisa; Zito, Arianna; Crippa, Valeria; Rusmini, Paola; Mariotti, Raffaella; Bentivoglio, Marina; Bendotti, Caterina; Poletti, Angelo

2012-02-01

Anabolic/androgenic steroids (AAS) are drugs that enhance muscle mass, and are often illegally utilized in athletes to improve their performances. Recent data suggest that the increased risk for amyotrophic lateral sclerosis (ALS) in male soccer and football players could be linked to AAS abuse. ALS is a motor neuron disease mainly occurring in sporadic (sALS) forms, but some familial forms (fALS) exist and have been linked to mutations in different genes. Some of these, in their wild type (wt) form, have been proposed as risk factors for sALS, i.e. superoxide dismutase 1 (SOD1) gene, whose mutations are causative of about 20% of fALS. Notably, SOD1 toxicity might occur both in motor neurons and in muscle cells. Using gastrocnemius muscles of mice overexpressing human mutant SOD1 (mutSOD1) at different disease stages, we found that the expression of a selected set of genes associated to muscle atrophy, MyoD, myogenin, atrogin-1, and transforming growth factor (TGF)β1, is up-regulated already at the presymptomatic stage. Atrogin-1 gene expression was increased also in mice overexpressing human wtSOD1. Similar alterations were found in axotomized mouse muscles and in cultured ALS myoblast models. In these ALS models, we then evaluated the pharmacological effects of the synthetic AAS nandrolone on the expression of the genes modified in ALS muscle. Nandrolone administration had no effects on MyoD, myogenin, and atrogin-1 expression, but it significantly increased TGFβ1 expression at disease onset. Altogether, these data suggest that, in fALS, muscle gene expression is altered at early stages, and AAS may exacerbate some of the alterations induced by SOD1 possibly acting as a contributing factor also in sALS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with {sup 18}F-Al labeled Cys{sup 39}-exendin-4

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

Mi, Baoming; Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University; Xu, Yuping

Purpose: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, {sup 18}F-Al labeled exendin-4 analog, {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. Methods: The targeting of {sup 18}F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined throughmore » post mortern examinations. Results: The pancreas of healthy rats was readily visualized after administration of {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. Conclusion: The favorable preclinical data indicated that {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.« less

Student Perceptions of Independent versus Facilitated Small Group Learning Approaches to Compressed Medical Anatomy Education

ERIC Educational Resources Information Center

Whelan, Alexander; Leddy, John J.; Mindra, Sean; Matthew Hughes, J. D.; El-Bialy, Safaa; Ramnanan, Christopher J.

2016-01-01

The purpose of this study was to compare student perceptions regarding two, small group learning approaches to compressed (46.5 prosection-based laboratory hours), integrated anatomy education at the University of Ottawa medical program. In the facilitated active learning (FAL) approach, tutors engage students and are expected to enable and…

77 FR 32060 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... currently requires revising the Airworthiness Limitations Section (ALS) of the Instructions for Continued... limitations are currently published in the Airbus A318/A319/A320/A321 Airworthiness Limitations Section (ALS... Airbus A318/A319/A320/A321 ALS Part 5. The issue 4 of Airbus A318/A319/A320/A321 FAL Document introduces...

Macroeconomics and Public Policy. Revision.

DTIC Science & Technology

1984-04-01

Brown & Co., 1981. Polakoff, M. E., et al, Financial Institutions and Markets , Boston: Houghton Mifflin Co., 1970. Robinson, R. I. & Wrightman, F...al, Financial Institutions and Markets , M. D. Ketchum, ed., New York: Houghton Mifflin Co., 1970. Samuelson, P. A., "Interactions Between the...The Brookings Institution , 1960. Polakoff, M. E., et al, Financial Institutions and Markets , Boston: Houghton Mifflin Co., 1970. Ritter, L. S. & Sibler

Non-Reciprocal on Wafer Microwave Devices

DTIC Science & Technology

2015-05-27

filter uses a barium hexagonal ferrite film incorporated into the dielectric layer of a microstrip transmission line. The zero-field operational...Fal,, Robert E. Camley. Millimeter wave phase shifter based on ferromagnetic resonancein a hexagonal barium ferrite thin film, Applied Physics...materials for on-wafer microwave devices concentrated on barium hexagonal ferrite (BaM) films grown on Si because these material is a good candidate

Reframing Alice's Restaurant: Reflections on Globalisation, Adult Education, and Transformative Learning

ERIC Educational Resources Information Center

Etmanski, Catherine

2005-01-01

In the mid-1960s, the foundations of Participatory Research were being laid in Tanzania and around the world through the work of muckraking adult educators--President Julius Nyerere, Marja-Liisa Swantz, Orlando Fals Borda, Rajesh Tandon, Budd Hall and many more of their friends and colleagues. At the same time, a bunch of American kids were over…

Aircraft Maintenance Experience Design Handbook

DTIC Science & Technology

1978-09-11

RlOM A JOB P iiLPAhATIL)N MINOR MAINTFNANCF DELAYS • ACCESS SF Fit L ING OUr FORMS FAL ISLAI11N ’ FAULT COIRNNCTION M4N[. FANCE 6 AOJUSIMUNT CALIBRATION...Washington , D).(. Auglsit. 19t4. "A*SC Dh 1-9, Maintainability (for Ground Electronics Syste.ms)", A1LS L _sigil handbook. Series -- 0. Gene •ai

Chromosphere Active Region Plasma Diagnostics Based On Observations Of Millimeter Radiation

NASA Astrophysics Data System (ADS)

Loukitcheva, M.; Nagnibeda, V.

1999-10-01

In this paper we present the results of millimeter radiation calculations for different elements of chromospheric and transition region structures of the quiet Sun and S-component - elements of chromosphere network, sunspot groups and plages. The calculations were done on the basis of standard optical and UV models ( models by Vernazza et al. (1981,VAL), their modifications by Fontenla et al. (1993,FAL)). We also considered the sunspot model by Lites and Skumanich (1982,LS), S-component model by Staude et al.(1984) and modification of VAL and FAL models by Bocchialini and Vial - models NET and CELL. We compare these model calculations with observed characteristics of components of millimeter Solar radiation for the quiet Sun and S-component obtained with the radiotelescope RT-7.5 MGTU (wavelength 3.4 mm) and radioheliograph Nobeyama (wavelength 17.6 mm). From observations we derived spectral characteristics of millimeter sources and active region source structure. The comparison has shown that observed radio data are clearly in dissagrement with all the considered models. Finally, we propose further improvement of chromospheric and transition region models based on optical and UV observations in order to use for modelling information obtained from radio data.

Corrective Action Decision Document/Closure Report for Corrective Action Unit 367: Area 10 Sedan, Ess and Uncle Unit Craters Nevada National Security Site, Nevada, Revision 0

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

Patrick Matthews

2011-06-01

Corrective Action Unit 367 comprises four corrective action sites (CASs): • 10-09-03, Mud Pit • 10-45-01, U-10h Crater (Sedan) • 10-45-02, Ess Crater Site • 10-45-03, Uncle Crater Site The purpose of this Corrective Action Decision Document/Closure Report is to provide justification and documentation of the corrective actions and site closure activities implemented at CAU 367. A corrective action of closure in place with use restrictions was completed at each of the three crater CASs (10-45-01, 10-45-02, and 10-45-03); corrective actions were not required at CAS 10-09-03. In addition, a limited soil removal corrective action was conducted at the locationmore » of a potential source material release. Based on completion of these correction actions, no additional corrective action is required at CAU 367, and site closure is considered complete. Corrective action investigation (CAI) activities were performed from February 2010 through March 2011, as set forth in the Corrective Action Investigation Plan for Corrective Action Unit 367: Area 10 Sedan, Ess and Uncle Unit Craters, Nevada Test Site, Nevada. The approach for the CAI was divided into two facets: investigation of the primary release of radionuclides, and investigation of non-test or other releases (e.g., migration in washes and potential source material). Based on the proximity of the Uncle, Ess, and Sedan craters, the impact of the Sedan test on the fallout deposited from the two earlier tests, and aerial radiological surveys, the CAU 367 investigation was designed to study the releases from the three crater CASs as one combined release (primary release). Corrective Action Site 10-09-03, Mud Pit, consists of two mud pits identified at CAU 367. The mud pits are considered non-test releases or other releases and were investigated independent of the three crater CASs. The purpose of the CAI was to fulfill data needs as defined during the data quality objective (DQO) process. The CAU 367 dataset of investigation results was evaluated based on a data quality assessment. This assessment demonstrated the dataset is complete and acceptable for use in fulfilling the DQO data needs. Analytes detected during the CAI were evaluated against final action levels (FALs) established in this document. For the primary release, radiological doses exceeding the FAL of 25 millirem per year were not found to be present in the surface or shallow subsurface soil outside the default contamination boundary. However, it was assumed that radionuclides are present in subsurface media within each of the three craters (Sedan, Ess, and Uncle) due to prompt injection of radionuclides from the tests. Based on the assumption of radiological dose exceeding the FAL, corrective actions were undertaken that consisted of implementing a use restriction and posting warning signs at each crater CAS. These use restrictions were recorded in the FFACO database; the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Facility Information Management System; and the NNSA/NSO CAU/CAS files. With regard to other releases, no contaminants of concern were identified at the mud pits or any of the other release locations, with one exception. Potential source material in the form of lead was found at one location. A corrective action of clean closure was implemented at this location, and verification samples indicated that no further action is necessary. Therefore, NNSA/NSO provides the following recommendations: • A Notice of Completion to NNSA/NSO is requested from the Nevada Division of Environmental Protection for closure of CAU 367. • Corrective Action Unit 367 should be promoted from Appendix III to Appendix IV of the FFACO.« less

Man-Machine Impact of Technology on Coast Guard Missions and Systems

DTIC Science & Technology

1979-12-01

t Cost of Rar~dom, Acce~ss eoy~mAlr 97 f-Al 1000 MOS RAM-(409 BITS/CHIP) . 100 _ I• z LLJ 10 (I) UI 1.04 I.-I- ’ YEAR ii A .. I. FiueA-.oecs pedo ...of these advances will iTOSt likely be accomplished through focal plane arrays of detectors, charge coupled device readout techniques for the video

Development of Probabilistic and Possebilistic Approaches to Approximate Reasoning and Its Applications

DTIC Science & Technology

1989-10-31

fo tmaa OmfuogeM ara Mmi. fal in fM?05V~ ~ ~ ~ ~ ~ A D A 2 4 0409"~ n ugt Psoo,@’ oducbof Proton (07044 136M. WagaWapN. DC 20141 T1 3. REPORT TYPE...Al (circumscription, non- monotonic reasoning, and default reasoning), our approach is based on fuzzy logic and, more specifically, on the theory of

Uranium and Its Decay Products in Floodplain Sediments from the River Fal

NASA Astrophysics Data System (ADS)

Millward, G. E.; Blake, W. H.; Little, R.; Couldrick, L.

2012-04-01

European river basins are subject to longer-term storage of legacy contaminants in sedimentary sinks and their potential release presents a credible risk to achieving water quality targets required by the EU Water Framework Directive. The catchment of the River Fal, south west England, is extensively mineralised and has been greatly impacted by heavy metal mining. Uranium and radium were extracted and processed between 1870 and 1930 and spoil tips along the channel banks are assumed to have been a source of radionuclides into the river. Radionuclides were determined in five cores obtained from the river floodplain, including a reference core positioned upstream of the uranium mine enabling evaluation of its impact on past and contemporary sediment quality. The core was sectioned into 1 cm thick slices and they were analysed by gamma spectrometry for products of the U-238 decay series, i.e. Th-234 (a surrogate for U-238), Pb-214 (a surrogate for Ra-226), Pb-210 and fallout Am-241 and Cs-137. Peak Cs-137 concentrations at mid-depth were associated with fallout after atmospheric nuclear tests in 1963 and were used to estimate sedimentation rates. However, the activity concentrations of Pb-210 were elevated at all depths and the result indicated a significant input of unsupported Pb-210 (linked to processed spoil material) throughout the period of deposition. At some sites, peak activity concentrations of Th-234 suggested inputs from mining activity during major release and/or flood events. The cores downstream of the mine all had higher radionuclide inventories, of the order 105 Bq m-2, compared to the reference core due to the presences of products from the U-238 decay series. In addition, the inventories did not decrease systematically downstream indicating storage regions within the river channel. Storage of such legacy contaminants at levels in excess of contemporary environmental quality guidelines raises important questions and challenges for floodplain use and management.

Historical Review of Uncommanded Lateral-Directional Motions at Transonic Conditions

NASA Technical Reports Server (NTRS)

Chambers, Joseph R.; Hall, Robert M.

2003-01-01

This paper presents the results of a survey of past experiences with uncommanded lateral-directional motions at transonic speeds during specific military aircraft programs. The effort was undertaken to provide qualitative and quantitative information on past airplane programs that might be of use to the participants in the joint NASA/Navy/Air Force Abrupt Wing Stall (AWS) Program. The AWS Program was initiated because of the experiences of the F/A-l8E/F development program, during which unexpected, severe wing-drop motions were encountered by preproduction aircraft at transonic conditions. These motions were judged to be significantly degrading to the primary mission requirements of the aircraft. Although the problem was subsequently solved for the production version of the F/A-l8E/F, a high-level review panel emphasized the poor understanding of such phenomena and issued a strong recommendation to: "Initiate a national research effort to thoroughly and systematically study the wing drop phenomena." A comprehensive, cooperative NASA/Navy/Air Force AWS Program was designed to respond to provide the required technology requirements. As part of the AWS Program, a work element was directed at a historical review of wing-drop experiences in past aircraft development programs at high subsonic and transonic speeds. In particular, information was requested regarding: specific aircraft configurations that exhibited uncommanded motions and the nature of the motions; geometric characteristics of the air- planes; flight conditions involved in occurrences; relevant data, including wind-tunnel, computational, and flight sources; figures of merit used for analyses; and approaches used to alleviate the problem. An attempt was also made to summarize some of the more important lessons learned from past experiences, and to recommend specific research efforts. In addition to providing technical information to assist the AWS research objectives, the study produced fundamental information regarding the historical challenge of uncommanded lateral-directional motions at transonic conditions and the associated aerodynamic phenomena.

SOD1 oxidation and formation of soluble aggregates in yeast: Relevance to sporadic ALS development

PubMed Central

Martins, Dorival; English, Ann M.

2014-01-01

Misfolding and aggregation of copper–zinc superoxide dismutase (Sod1) are observed in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Mutations in Sod1 lead to familial ALS (FALS), which is a late-onset disease. Since oxidative damage to proteins increases with age, it had been proposed that oxidation of Sod1 mutants may trigger their misfolding and aggregation in FALS. However, over 90% of ALS cases are sporadic (SALS) with no obvious genetic component. We hypothesized that oxidation could also trigger the misfolding and aggregation of wild-type Sod1 and sought to confirm this in a cellular environment. Using quiescent, stationary-phase yeast cells as a model for non-dividing motor neurons, we probed for post-translational modification (PTM) and aggregation of wild-type Sod1 extracted from these cells. By size-exclusion chromatography (SEC), we isolated two populations of Sod1 from yeast: a low-molecular weight (LMW) fraction that is catalytically active and a catalytically inactive, high-molecular weight (HMW) fraction. High-resolution mass spectrometric analysis revealed that LMW Sod1 displays no PTMs but HMW Sod1 is oxidized at Cys146 and His71, two critical residues for the stability and folding of the enzyme. HMW Sod1 is also oxidized at His120, a copper ligand, which will promote loss of this catalytic metal cofactor essential for SOD activity. Monitoring the fluorescence of a Sod1-green-fluorescent-protein fusion (Sod1-GFP) extracted from yeast chromosomally expressing this fusion, we find that HMW Sod1-GFP levels increase up to 40-fold in old cells. Thus, we speculate that increased misfolding and inclusion into soluble aggregates is a consequence of elevated oxidative modifications of wild-type Sod1 as cells age. Our observations argue that oxidative damage to wild-type Sod1 initiates the protein misfolding mechanisms that give rise to SALS. PMID:24936435

Similarities between the discovery and regulation of pharmaceuticals and pesticides: in support of a better understanding of the risks and benefits of each

USDA-ARS?s Scientific Manuscript database

An argument by analogy is presented as a logical basis from which the role of pharmaceuticals and pesticides can be viewed in terms of contributing to human health. We will argue that what is true for pharmaceuticals (A) is also true for pesticides (B) and that logically if A=B then B cannot be fal...

Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwide.

PubMed

García-Redondo, Alberto; Dols-Icardo, Oriol; Rojas-García, Ricard; Esteban-Pérez, Jesús; Cordero-Vázquez, Pilar; Muñoz-Blanco, José Luis; Catalina, Irene; González-Muñoz, Miguel; Varona, Luis; Sarasola, Esther; Povedano, Monica; Sevilla, Teresa; Guerrero, Antonio; Pardo, Julio; López de Munain, Adolfo; Márquez-Infante, Celedonio; de Rivera, Francisco Javier Rodríguez; Pastor, Pau; Jericó, Ivonne; de Arcaya, Amaya Álvarez; Mora, Jesús S; Clarimón, Jordi; Gonzalo-Martínez, Juan Francisco; Juárez-Rufián, Alexandra; Atencia, Gabriela; Jiménez-Bautista, Rosario; Morán, Yolanda; Mascías, Javier; Hernández-Barral, María; Kapetanovic, Solange; García-Barcina, María; Alcalá, Carmen; Vela, Alvaro; Ramírez-Ramos, Concepción; Galán, Lucía; Pérez-Tur, Jordi; Quintáns, Beatriz; Sobrido, M Jesús; Fernández-Torrón, Roberto; Poza, Juan José; Gorostidi, Ana; Paradas, Carmen; Villoslada, Pablo; Larrodé, Pilar; Capablo, José Luis; Pascual-Calvet, Jordi; Goñi, Miguel; Morgado, Yolanda; Guitart, Miriam; Moreno-Laguna, Sira; Rueda, Almudena; Martín-Estefanía, Carlos; Cemillán, Carlos; Blesa, Rafael; Lleó, Alberto

2013-01-01

A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) can cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). We assessed its frequency in 781 sporadic ALS (sALS) and 155 familial ALS (fALS) cases, and in 248 Spanish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 Ceph Europeans from Utah (CEU), 170 Yoruba Africans, 81 Han Chinese, and 85 Japanese subjects. The C9orf72 expansion was present in 27.1% of fALS and 3.2% of sALS. Mutation carriers showed lower age at onset (P = 0.04), shorter survival (P = 0.02), greater co-occurrence of FTD (P = 8.2 × 10(-5)), and more family history of ALS (P = 1.4 × 10(-20)), than noncarriers. No association between alleles within the normal range and the risk of ALS was found (P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Yoruba Africans, 8.9% CEU, 3.9% Japanese, and 1.6% Han Chinese chromosomes. © 2012 Wiley Periodicals, Inc.

Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS.

PubMed

Suzuki, Masatoshi; McHugh, Jacalyn; Tork, Craig; Shelley, Brandon; Hayes, Antonio; Bellantuono, Ilaria; Aebischer, Patrick; Svendsen, Clive N

2008-12-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which there is a progressive loss of motor neurons and their connections to muscle, leading to paralysis. In order to maintain muscle connections in a rat model of familial ALS (FALS), we performed intramuscular transplantation with human mesenchymal stem cells (hMSCs) used as "Trojan horses" to deliver growth factors to the terminals of motor neurons and to the skeletal muscles. hMSCs engineered to secrete glial cell line-derived neurotrophic factor (hMSC-GDNF) were transplanted bilaterally into three muscle groups. The cells survived within the muscle, released GDNF, and significantly increased the number of neuromuscular connections and motor neuron cell bodies in the spinal cord at mid-stages of the disease. Further, intramuscular transplantation with hMSC-GDNF was found to ameliorate motor neuron loss within the spinal cord where it connects with the limb muscles receiving transplants. While disease onset was similar in all the animals, hMSC-GDNF significantly delayed disease progression, increasing overall lifespan by up to 28 days, which is one of the largest effects on survival noted for this rat model of FALS. This preclinical data provides a novel and practical approach toward ex vivo gene therapy for ALS.

Calculated and Observed Speeds of Cavitation About Two- and Three- Dimensional Bodies in Water

DTIC Science & Technology

1942-11-01

yE1l0.044po ellipse of - 36 (1 - Y) 6 0 .l.Olxx 0(y) L . 6.54 Porabolo Elipe em - Cicl Y ,11p f. 2 1 - fal: Figure 1 ScinofCylinders and Bodies of...Propellers,* by E.Z. Stowell and A.F. Deming , BACA Report 526, 1935. (2) "Flow about a Pair of Adjacent, Parallel Cylinders Normal to a Stream, Theoretical

AGARD Flight Test Instrumentation Series. Volume 11. Pressure and Flow Measurement

DTIC Science & Technology

1980-07-01

Unempfindlichkeit gegen Schrdg- anstr~ mung . Luftfo-ahrtforschung V (1935), S.75-79. 35. Winternitz, F.A.L. Cantilevered pitot cylinder. The Engineer 199 (1955), pp...cur Str ~mungsmessung. Z.far Instrumentenkunde 71 (1963) 7, 187-197. 42. Davies, P.O.A.L. The behavior of a pitot tube in transverse shear. J. Fluid...Ober den Einflug der Kompressibilitit auf die Druckan-eige eines Prandtl-Rohres bei Str ~mungen mit Unterschallgeschwin- digkeit. Jahrbuch der

The Development of a Portable Modular Component Building System for the Armed Forces

DTIC Science & Technology

1985-11-08

environment and provide optimum thermal comfort and energy performance throughout a wide climatic range. Finally, such a system would provide optimum user...I I I I I l i 56. ind thermal comfort . The low humidity of the atmosphere allows temperatures to fal. deeply at night so buildings constructed of hig...site topographies. Extensive support equipment is also required for their transport, erection and sustained thermal comfort for the occupants. Off the

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Spiegelman, Dan; McConkey, Brendan J; Vande Velde, Christine; Bouchard, Jean-Pierre; Lacomblez, Lucette; Pochigaeva, Ksenia; Salachas, Francois; Pradat, Pierre-Francois; Camu, William; Meininger, Vincent; Dupre, Nicolas; Rouleau, Guy A

2008-05-01

Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.

A Study of Mechanisms Producing Astrophysical Jets.

DTIC Science & Technology

1988-03-01

REPORT NUMBER(S) IS0001f A FAL- T R-88-007 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION (if applicable...entire rest energy by some , ,, . , , , - , . , . ,4 . ,... .- t . mechanism or other. If matter is in-falling in this fashion, conservation of angular...they are still enveloped in the dense gas and dust from which they are condensing. Associated with a class of these stars, the T Tauri stars, are

US Army Medical Bioengineering Research and Development Laboratory Annual Progress Report FY1981.

DTIC Science & Technology

1981-10-01

8217 AND 0 LTPAVIOt.ET LIGHT WERE ANALYZED. TH;- OFC~ THr HE SPO ’fl 𔃻 ’’ T,_ Tfi FAl’ ARMY W~ORM SPODOPTERA FRUGIPERDA BY I)CT N. N0 𔄁 1’ .. 7 -, U...a.-~’ -J control r)o,% Aedes aegypti n experi- ipathogen. has heat, T he ’h ., Spodoptera . ’’ri spores . The ’I>r .. -. . A itus, Ae. .5 .~x .1i

First evidence of anisotropy of GPS phase slips caused by the mid-latitude field-aligned ionospheric irregularities

NASA Astrophysics Data System (ADS)

Afraimovich, E. L.; Ishin, A. B.; Tinin, M. V.; Yasyukevich, Yu. V.; Jin, S. G.

2011-05-01

The mid-latitude field-aligned irregularity (FAI) along the magnetic field line is a common phenomenon in the ionosphere. However, few data reveal the field-aligned ionospheric irregularities. They are insufficient to identify FAIs effects so far, particularly effect on global positioning system (GPS) signals. In this paper, the mid-latitude FAIs by line-of-sight angular scanning relative to the local magnetic field vector are investigated using the denser GPS network observations in Japan. It has been the first found that total GPS L2 phase slips over Japan, during the recovery phase of the 12 Feb 2000 geomagnetic storm were caused by GPS signal scattering on FAIs both for the lines-of-sight aligned to the magnetic field line (the field of aligned scattering, FALS) and across the magnetic field line (the field of across scattering, FACS). The FALS results are also in a good agreement with the data of the magnetic field orientation control of GPS occultation observations of equatorial scintillation during thorough low earth orbit (LEO) satellites measurements, e.g. Challenging Minisatellite Payload (CHAMP) and Satellite de Aplicaciones Cientificas-C (SAC-C). The role of large-angle scattering almost along the normal to the magnetic field line in GPS scintillation is determined by attenuation of the irregularity anisotropy factor as compared with the other factors.

TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update.

PubMed

Lattante, Serena; Rouleau, Guy A; Kabashi, Edor

2013-06-01

Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP-43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP-43 positive inclusion bodies were first discovered in ubiquitin-positive, tau-negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C-terminus of the proteins. The molecular mechanisms through which mutant TDP-43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS. © 2013 Wiley Periodicals, Inc.

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

Olthoff, Edward

The Municipal Electric Utility of the City of Cedar Falls (dba Cedar Fals Utilities or CFU) received a congressionally directed grant funded through DOE-EERE to run three short (4 hour) duration test burns and one long (10 days) duration test burn to test the viability of renewable fuels in Streeter Station Boiler #6, a stoker coal fired electric generation unit. The long test burn was intended to test supply chain assumptions, optimize boiler combustion and assess the effects of a longer duration burn of biomass on the boiler.

Preclinical Testing of a Translocator Protein Ligand for the Treatment of Amyotrophic Lateral Sclerosis

DTIC Science & Technology

2017-03-01

Accessed October 26, 2015]. Barneoud, P. et al., 1997. Quantitative motor assessment in FALS mice: a longitudinal study . Neuroreport, 8, pp.2861–2865...cell study , we found that PK acts directly on motor neurons to prevent their death, not via the astrocytes. Then, we evidenced that PK protects not...in TSPO content may protect motor neurons against ALS. Second, in our preclinical study in ALS mice, we have determined that the best route to

Carbon-embedded Ni nanocatalysts derived from MOFs by a sacrificial template method for efficient hydrogenation of furfural to tetrahydrofurfuryl alcohol.

PubMed

Su, Yanping; Chen, Chun; Zhu, Xiaoguang; Zhang, Yong; Gong, Wanbing; Zhang, Haimin; Zhao, Huijun; Wang, Guozhong

2017-05-16

We report a fast and simple method for the synthesis of Ni-based metal-organic-frameworks (Ni-MOFs). Due to the existence of nickel ions and an organic ligand, the MOFs are employed as a sacrificial template for the facile preparation of carbon-embedded Ni (Ni/C) catalysts by a direct thermal decomposition method. The obtained Ni/C catalysts exhibit excellent catalytic activity for selectively transforming furfural (FAL) to tetrahydrofurfuryl alcohol (THFOL) due to the Ni nanoparticles (NPs) embedded uniformly in the ligand-derived carbon. The exemplified results illustrate that the catalytic performance of the Ni/C catalyst is greatly affected by the calcination conditions (temperature and time), composition of the Ni-MOF precursor and the catalysis conditions. The conversion of FAL and selectivity of THFOL both reached 100% under the conditions of 120 °C, 1 MPa H 2 pressure and 120 min of hydrogenation over the Ni/C-500 catalyst, derived from the pyrolysis of Ni-MOFs (Ni : BTC mole ratio of 1.0) at 500 °C for 120 min, which exhibits an average nanoparticle size of ∼14 nm and uniform dispersion, and the highest BET surface area (∼92 m 2 g -1 ) among all investigated Ni/C catalysts. This facilely prepared heterogeneous catalyst would be very promising for the replacement of noble metal catalysts for the efficient catalytic conversion of biomass-derived feedstocks into value-added chemicals.

The Two-On-One Stochastic Duel

DTIC Science & Technology

1983-12-01

ACN 67500 TRASANA-TR-43-83 (.0 (v THE TWO-ON-ONE STOCHASTIC DUEL I • Prepared By A.V. Gafarian C.J. Ancker, Jr. DECEMBER 19833D I°"’" " TIC ELECTE...83 M A IL / _ _ 4. TITLE (and Subtitle) TYPE OF REPORT & PERIOD CO\\,ERED The Two-On-One Stochastic Duel Final Report 6. PERFORMING ORG. REPORT NUMBER...Stochastic Duels , Stochastic Processed, and Attrition. 5-14cIa~c fal roLCS-e ss 120. ABSTRACT (C’ntfMte am reverse Ed& if necesemay and idemtitf by block

Corrective Action Investigation Plan for Corrective Action Unit 104: Area 7 Yucca Flat Atmospheric Test Sites, Nevada National Security Site, Nevada, Revision 0

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

Patrick Matthews

2011-08-01

CAU 104 comprises the 15 CASs listed below: (1) 07-23-03, Atmospheric Test Site T-7C; (2) 07-23-04, Atmospheric Test Site T7-1; (3) 07-23-05, Atmospheric Test Site; (4) 07-23-06, Atmospheric Test Site T7-5a; (5) 07-23-07, Atmospheric Test Site - Dog (T-S); (6) 07-23-08, Atmospheric Test Site - Baker (T-S); (7) 07-23-09, Atmospheric Test Site - Charlie (T-S); (8) 07-23-10, Atmospheric Test Site - Dixie; (9) 07-23-11, Atmospheric Test Site - Dixie; (10) 07-23-12, Atmospheric Test Site - Charlie (Bus); (11) 07-23-13, Atmospheric Test Site - Baker (Buster); (12) 07-23-14, Atmospheric Test Site - Ruth; (13) 07-23-15, Atmospheric Test Site T7-4; (14) 07-23-16,more » Atmospheric Test Site B7-b; (15) 07-23-17, Atmospheric Test Site - Climax These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives (CAAs). Additional information will be obtained by conducting a corrective action investigation before evaluating CAAs and selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible evaluation of viable CAAs that will be presented in the Corrective Action Decision Document. The sites will be investigated based on the data quality objectives (DQOs) developed on April 28, 2011, by representatives of the Nevada Division of Environmental Protection and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective actions for CAU 104. The releases at CAU 104 consist of surface-deposited radionuclides from 30 atmospheric nuclear tests. The presence and nature of contamination at CAU 104 will be evaluated based on information collected from a field investigation. Radiological contamination will be evaluated based on a comparison of the total effective dose (TED) to the dose-based final action level (FAL). The presence of TED exceeding the FAL is considered a radiological contaminant of concern (COC). Anything identified as a COC will require corrective action. The TED will be calculated as the total of separate estimates of internal and external dose. Results from the analysis of soil samples will be used to calculate internal radiological dose. Thermoluminescent dosimeters will be used to measure external radiological dose. Based on process knowledge of the releases associated with the nuclear tests and radiological survey information about the location and shape of the resulting contamination plume, it was determined that the releases from the nuclear tests are co-located and will be investigated concurrently. A field investigation will be performed to define areas where TED exceeds the FAL and to determine whether other COCs are present at the site. The investigation will also collect information to determine the presence and nature of contamination associated with migration and excavation, as well as any potential releases discovered during the investigation. Appendix A provides a detailed discussion of the DQO methodology and the DQOs specific to each CAS.« less

Nutrient Intakes and Work Performance of Soldiers during Seven Days of Exercise at 7,200 Feet Ready-to-Eat Ration

DTIC Science & Technology

1986-09-19

100.000 *4 • D " ",4.. .4.’-’ FrteiuEncy of M1aE Fouds Consumed CLASS=khJlTS FCOOD NAM~E FOOD FREQUENCY CUM? FaL1 £EjcENlI CUM PER~CENT APPLESAUCE ...4 1/2 3/4 all JELLY 1/4 1/2 3/4 all PEANUT BUTTER 1/4 1/2 3/4 all FRUIT APPLESAUCE 1/4 1/2 3/4 all MIXED FRUITS 1/4 1/2 3/4 all PEACHES 1/4 1/2 3/4

[An early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development].

PubMed

Abe, Koji

2018-03-28

The present review focuses an early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development. In relation to foreign previous reports, five topics are introduced and discussed on ALS with dementia, ALS/Parkinsonism dementia complex (ALS/PDC), familial ALS (FALS), spinal bulbar muscular atrophy (SBMA), and multisystem involvement especially in cerebellar system of ALS including ALS/SCA (spinocerebellar ataxia) crossroad mutation Asidan. This review found the great contribution of Japanese reports on the above five topics, and confirmed the great development of ALS-related diseases over the past 120 years.

Is Innate Immunity and Inflammasomes Involved in Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)?

PubMed

Volpe, Caroline M O; Nogueira-Machado, Jose A

2015-01-01

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease is an axonopathy with adultonset, progressive and irreversible degeneration of upper and lower motor neurons. Around 90% of ALS is considered as sporadic ALS (sALS) without apparent genetic cause while in the familial type of ALS (fALS) at least one affected blood relative needs to be identified. Both sALS and fALS show similar progression and pathological profile. Biochemical and immunological roles have been reported for both types of ALS. It has been suggested that mutation in SOD1 gene would be responsible for the oxidative stress and neurotoxicity. Besides, oxidative stress, protein aggregation, altered cholinergic synapse, neuro-inflammation and production of pro-inflammatory cytokines have also been reported. Thus, the focus of the present review was on biochemical and immunological biomarkers and pathogenic mechanism. Regulatory T cells, pro-inflammatory cytokines and activation of pro-inflammatory signaling pathway are discussed. The activation of NRL inflammasomes in ALS and the involvement of IL-18, IL-1β and caspases-1 are also suggested. The presence and importance of HMGB-1 (DAMP) and activation of Tolllike receptors and/or RAGE also are envisaged. The patents US20140212508, WO2014145776, WO2014145118, US20140255371, US20140194427, US20140243400, WO2014128254, WO2014076702, WO2014071449, WO2014043696, WO2014001742, and WO2013082299 are summarized. This review intends to evaluate the biochemical and immunological responses and the involvement of inflammasomes in the pathogenesis of ALS. In the present review, we suggest hypothetical model for ALS pathogenesis and we discuss some patents that suggest new treatment and/or therapeutic targets. Due to a large number of patents covering therapy and control of neurodegenerative diseases, our focus was restricted only to discuss the latest registered patents in 2014.

Catalysts for selective hydrogenation of furfural derived from the double complex salt [Pd(NH 3 ) 4 ](ReO 4 ) 2 on γ-Al 2 O 3

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

Thompson, Simon T.; Lamb, H. Henry

The double complex salt [Pd(NH3)4](ReO4)2 was employed as precursor of supported bimetallic catalysts for selective hydrogenation of furfural. Direct reduction of [Pd(NH3)4](ReO4)2 on γ-Al2O3 in flowing H2 at 400 °C yields bimetallic nanoparticles 1–2 nm in size that exhibit significant interaction between the metals, as evidenced by temperature-programmed hydride decomposition (complete suppression of β-PdHx formation), extended X-ray absorption fine structure spectroscopy at the Pd K and Re LIII edges (PdRe distance = 2.72 Å), and scanning transmission electron microscopy with energy dispersive X-ray analysis. In contrast, calcination of [Pd(NH3)4](ReO4)2 on γ-Al2O3 at 350 °C in air and subsequent reduction inmore » H2 at 400 °C results in metal segregation and formation of large (>50 nm) supported Pd particles; Re species cover the Pd particles and γ-Al2O3 support. A PdRe 1:2 catalyst prepared by sequential impregnation and calcination using HReO4 and [Pd(NH3)4](NO3)2 has a similar morphology. The catalyst derived by direct reduction of [Pd(NH3)4](ReO4)2 on γ-Al2O3 exhibits remarkably high activity for selective hydrogenation of furfural to furfuryl alcohol (FAL) at 150 °C and 1 atm. Suppression of H2 chemisorption via elimination of Pd threefold sites, as evidenced by CO diffuse-reflectance infrared Fourier transform spectroscopy, correlates with increased FAL selectivity.« less

High-affinity dopamine D2/D3 PET radioligands 18F-fallypride and 11C-FLB457: A comparison of kinetics in extrastriatal regions using a multiple-injection protocol

PubMed Central

Vandehey, Nicholas T; Moirano, Jeffrey M; Converse, Alexander K; Holden, James E; Mukherjee, Jogesh; Murali, Dhanabalan; Nickles, R Jerry; Davidson, Richard J; Schneider, Mary L; Christian, Bradley T

2010-01-01

18F-Fallypride and 11C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D2/D3 receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of 18F-fallypride and 11C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K1, k2, fNDkon, Bmax, and koff in the midbrain and cortical regions of the rhesus monkey. 11C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume (K1/k2) that is three times higher than 18F-fallypride, primarily due to a slower k2 (FAL:FLB; k2=0.54 min−1:0.18 min−1). The dissociation rate constant, koff, was slower for 11C-FLB457, resulting in a lower KDapp than 18F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D2/D3 binding could be detected in the cerebellum for 11C-FLB457 but not 18F-fallypride. Both radioligands can be used to image extrastriatal D2/D3 receptors, with 11C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and 18F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D2/D3 binding in the cerebellum, reference region analysis methods will give a greater bias in BPND with 11C-FLB457 than with 18F-fallypride. PMID:20040928

Aqueous corrosion and corrosion-sensitive embrittlement of Fe{sub 3}Al-based and lean-aluminum iron aluminides

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

Kim, J.G.; Buchanan, R.A.

Aqueous corrosion and corrosion-sensitive embrittlement of iron aluminides were characterized as functions of environment, alloying content, notch sensitivity, and strain rate. Polarization resistance and cyclic anodic polarization evaluations were performed in 3.5 wt % NaCl, 200 ppM Cl{sup {minus}} (pH = 4), and 1 N NaOH solutions. In the mild acid-chloride solution [200 ppM Cl{sup {minus}} (pH = 4)], the pitting-corrosion resistance of the new lean-aluminum iron aluminides (FAP-Y and CM-Mo) was comparable to that of the Fe{sub 3}Al-based FAL-Mo. In the higher-chloride 3.5 wt % NaCl, the resistance of CM-Mo was slightly less but FAP-Y showed quite similar behaviormore » to FAL-Mo. In 1 N NaOH solution, all materials exhibited ideal passive behavior. Under slow-strain-rate test conditions in the mild acid-chloride electrolyte, prior work had shown the ductilities (% elongations) of Fe{sub 3}Al-based materials to be {approximately}7% and {approximately}1% at the freely-corroding and hydrogen-charging potentials, respectively. Present studied on the lean-aluminum materials have shown the ductilities to be {approximately}17% and {approximately}5%, respectively. Thus, the present results indicate that these new materials have reasonably-good aqueous-corrosion properties in chloride environments and significantly-enhanced ductilities under aqueous corrosion conditions. The strain rate and notch sensitivities of high-aluminum iron aluminide (FA-129) were investigated by performing slow-strain-rate tests. The notch sensitivity was independent of strain rate and the notch sensitivity in the aqueous environment was similar to that in air.« less

Computational investigation of the human SOD1 mutant, Cys146Arg, that directs familial amyotrophic lateral sclerosis.

PubMed

Srinivasan, E; Rajasekaran, R

2017-07-25

The genetic substitution mutation of Cys146Arg in the SOD1 protein is predominantly found in the Japanese population suffering from familial amyotrophic lateral sclerosis (FALS). A complete study of the biophysical aspects of this particular missense mutation through conformational analysis and producing free energy landscapes could provide an insight into the pathogenic mechanism of ALS disease. In this study, we utilized general molecular dynamics simulations along with computational predictions to assess the structural characterization of the protein as well as the conformational preferences of monomeric wild type and mutant SOD1. Our static analysis, accomplished through multiple programs, predicted the deleterious and destabilizing effect of mutant SOD1. Subsequently, comparative molecular dynamic studies performed on the wild type and mutant SOD1 indicated a loss in the protein conformational stability and flexibility. We observed the mutational consequences not only in local but also in long-range variations in the structural properties of the SOD1 protein. Long-range intramolecular protein interactions decrease upon mutation, resulting in less compact structures in the mutant protein rather than in the wild type, suggesting that the mutant structures are less stable than the wild type SOD1. We also presented the free energy landscape to study the collective motion of protein conformations through principal component analysis for the wild type and mutant SOD1. Overall, the study assisted in revealing the cause of the structural destabilization and protein misfolding via structural characterization, secondary structure composition and free energy landscapes. Hence, the computational framework in our study provides a valuable direction for the search for the cure against fatal FALS.

Automatic Relocation of Ground Control Points in Landsat Imagery

DTIC Science & Technology

1981-06-01

This progras mtes use of a method of relocating in.jviiU.u1 S-p. this beini, done by Ott s~brosotir.. UXICCPF klocali-t gzp ). which is des.:ritrJ in t...dAil in se zt ’n ’. Erk t falJmit sec:tikrns dtscr-"be thv all gzps in ar. image ar.e iocate~.ý 3.2 CrýUnd c.Yntr,ýl pinat’cpu The tasýk or t~~IS...using the purpose-written progrn Ifl.CMI!P IX. The prc-blea cf rwltccating gzps is madle nic-h easier than the general pattern iecugnitior pmt.aleu

FAL Clowes, 1921-2016: a Memoir.

PubMed

Barlow, Peter W

2018-03-04

With the death of Frederick Albert Lionel Clowes on 21 September 2016, plant sciences lost a member of that lineage of experimental morphologists which reaches back to Johann Wolfgang von Goethe. In 1949, he discovered a group of cells at the tip of the beech root apex which were metabolically inert. In 1954, he confirmed generality of this root apex feature and coined the term 'quiescent center'. He continued to study these unique cells throughout next decades up to his last papers published in 1980s. Concept of the quiescent centre of plant roots is one of the milestones in plant cell biology and plant physiology.

Glucose and Fructose to Platform Chemicals: Understanding the Thermodynamic Landscapes of Acid-Catalysed Reactions Using High-Level ab Initio Methods

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

Assary, Rajeev S.; Kim, Taijin; Low, John

Molecular level understanding of acid-catalysed conversion of sugar molecules to platform chemicals such as hydroxy-methyl furfural (HMF), furfuryl alcohol (FAL), and levulinic acid (LA) is essential for efficient biomass conversion. In this paper, the high-level G4MP2 method along with the SMD solvation model is employed to understand detailed reaction energetics of the acid-catalysed decomposition of glucose and fructose to HMF. Based on protonation free energies of various hydroxyl groups of the sugar molecule, the relative reactivity of gluco-pyranose, fructo-pyranose and fructo-furanose are predicted. Calculations suggest that, in addition to the protonated intermediates, a solvent assisted dehydration of one of themore » fructo-furanosyl intermediates is a competing mechanism, indicating the possibility of multiple reaction pathways for fructose to HMF conversion in aqueous acidic medium. Two reaction pathways were explored to understand the thermodynamics of glucose to HMF; the first one is initiated by the protonation of a C2–OH group and the second one through an enolate intermediate involving acyclic intermediates. Additionally, a pathway is proposed for the formation of furfuryl alcohol from glucose initiated by the protonation of a C2–OH position, which includes a C–C bond cleavage, and the formation of formic acid. The detailed free energy landscapes predicted in this study can be used as benchmarks for further exploring the sugar decomposition reactions, prediction of possible intermediates, and finally designing improved catalysts for biomass conversion chemistry in the future.« less

Glucose and fructose to platform chemicals: understanding the thermodynamic landscapes of acid-catalysed reactions using high-level ab initio methods.

PubMed

Assary, Rajeev S; Kim, Taejin; Low, John J; Greeley, Jeff; Curtiss, Larry A

2012-12-28

Molecular level understanding of acid-catalysed conversion of sugar molecules to platform chemicals such as hydroxy-methyl furfural (HMF), furfuryl alcohol (FAL), and levulinic acid (LA) is essential for efficient biomass conversion. In this paper, the high-level G4MP2 method along with the SMD solvation model is employed to understand detailed reaction energetics of the acid-catalysed decomposition of glucose and fructose to HMF. Based on protonation free energies of various hydroxyl groups of the sugar molecule, the relative reactivity of gluco-pyranose, fructo-pyranose and fructo-furanose are predicted. Calculations suggest that, in addition to the protonated intermediates, a solvent assisted dehydration of one of the fructo-furanosyl intermediates is a competing mechanism, indicating the possibility of multiple reaction pathways for fructose to HMF conversion in aqueous acidic medium. Two reaction pathways were explored to understand the thermodynamics of glucose to HMF; the first one is initiated by the protonation of a C2-OH group and the second one through an enolate intermediate involving acyclic intermediates. Additionally, a pathway is proposed for the formation of furfuryl alcohol from glucose initiated by the protonation of a C2-OH position, which includes a C-C bond cleavage, and the formation of formic acid. The detailed free energy landscapes predicted in this study can be used as benchmarks for further exploring the sugar decomposition reactions, prediction of possible intermediates, and finally designing improved catalysts for biomass conversion chemistry in the future.

Modeling of boron species in the Falcon 17 and ISP-34 integral tests

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

Lazaridis, M.; Capitao, J.A.; Drossinos, Y.

1996-09-01

The RAFT computer code for aerosol formation and transport was modified to include boron species in its chemical database. The modification was necessary to calculate fission product transport and deposition in the FAL-17 and ISP-34 Falcon tests, where boric acid was injected. The experimental results suggest that the transport of cesium is modified in the presence of boron. The results obtained with the modified RAFT code are presented; they show good agreement with experimental results for cesium and partial agreement for boron deposition in the Falcon silica tube. The new version of the RAFT code predicts the same behavior formore » iodine deposition as the previous version, where boron species were not included.« less

Energy Transfer between Post-Transition Elements & Rare Earths in Oxide & Chalcogenide Glasses.

DTIC Science & Technology

1979-08-27

Caird [13]. A calculation of reduced matrix elements of Pr3 in 20 Na O • 80 TeO2 glass [14] showed that they differ slightly from data of ref. [121... glasses Transition (lass 35 ZnO 65 TeO2 20 Na2 O 80 TeO 2 fX 106 fX 106 l.,eas 3a, a) Ia’l. faI f.me.s f al f+ I fal 3 H4 - 3 H6 1.56 1.65 1.12...Rare-Earth Doped Glasses 20. jIST HAEV CCnFn~m ,i cn,on ra e sideit If c."*Ar’ -- ~ 14-r by t?-h.c .: r Intensity parameters, radiative transition

Prime Contract Awards Alphabetically by Contractor, State or Country, and Place. Part 2 (American Management Systems Inc, Arlington, Virginia - Basil & Trataros JV, Loring AFB, Maine), FY1991

DTIC Science & Technology

1991-01-01

m 00 -4w( I N0 >14 *C600 U a I4 co N0 p-~tq. 0MM)cx l o WO I -(( 1r (A U oo 2 6~ 000 UC x p 4N4 )-UL6000m U. 0 q c N10 00 fanC fal 06 000 U * q*I r...0) I -4"(. C. 00 0 0 0 0 0 0 0 00 0 0 0 0 Z00 0 0. U 0)-NO IIS WWOWaLJ WWWW WW OOOWWWOOOOW00000 D40 W >C 0 0 0a<>cU U I Mm -4N0 gen H -4 -4 4-4 -4 -4

The Lewis superacid Al[N(C6F5)2]3 and its higher homolog Ga[N(C6F5)2]3 – structural features, theoretical investigation and reactions of a metal amide with higher fluoride ion affinity than SbF5† †Electronic supplementary information (ESI) available. CCDC 1557072–1557076. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc03988c

PubMed Central

Kögel, J. F.; Sorokin, D. A.; Khvorost, A.; Scott, M.; Harms, K.; Himmel, D.; Krossing, I.

2017-01-01

Herein we present the synthesis of the two Lewis acids Al[N(C6F5)2]3 (ALTA) and Ga[N(C6F5)2]3 (GATA) via salt elimination reactions. The metal complexes were characterized by NMR-spectroscopic methods and X-ray diffraction analysis revealing the stabilization of the highly Lewis acidic metal centers by secondary metal–fluorine contacts. The Lewis acidic properties of Al[N(C6F5)2]3 and Ga[N(C6F5)2]3 are demonstrated by reactions with Lewis bases resulting in the formation of metallates accompanied by crucial structural changes. The two metallates [Cs(Tol)3]+[FAl(N(C6F5)2)3]– and [AsPh4]+[ClGa(N(C6F5)2)3]– contain interesting weakly coordinating anions. The reaction of Al[N(C6F5)2]3 with trityl fluoride yielded [CPh3]+[FAl(N(C6F5)2)3]– which could find application in the activation of metallocene polymerization catalysts. The qualitative Lewis acidity of Al[N(C6F5)2]3 and Ga[N(C6F5)2]3 was investigated by means of competition experiments for chloride ions in solution. DFT calculations yielded fluoride ion affinities in the gas phase (FIA) of 555 kJ mol–1 for Al[N(C6F5)2]3 and 472 kJ mol–1 for Ga[N(C6F5)2]3. Thus, Al[N(C6F5)2]3 can be considered a Lewis superacid with a fluoride affinity higher than SbF5 (493 kJ mol–1) whereas the FIA of the corresponding gallium complex is slightly below the threshold to Lewis superacidity. PMID:29629094

Delayed Disease Onset and Extended Survival in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis after Suppression of Mutant SOD1 in the Motor Cortex

PubMed Central

Thomsen, Gretchen M.; Gowing, Genevieve; Latter, Jessica; Chen, Maximus; Vit, Jean-Philippe; Staggenborg, Kevin; Avalos, Pablo; Alkaslasi, Mor; Ferraiuolo, Laura; Likhite, Shibi; Kaspar, Brian K.

2014-01-01

Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by a progressive loss of motor neurons leading to paralysis and death typically within 3–5 years of onset. Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1G93A rats through targeted delivery of AAV9–SOD1–shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease. PMID:25411487

The fused in sarcoma protein forms cytoplasmic aggregates in motor neurons derived from integration-free induced pluripotent stem cells generated from a patient with familial amyotrophic lateral sclerosis carrying the FUS-P525L mutation.

PubMed

Liu, Xinxiu; Chen, Jiayu; Liu, Wenchao; Li, Xiaogang; Chen, Qi; Liu, Tao; Gao, Shaorong; Deng, Min

2015-07-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons (MNs) and has no effective treatment. Mutations in the fused in sarcoma (FUS) gene and abnormal aggregation of FUS protein have been reported in ALS. However, the mechanisms involved in ALS are poorly understood. Clinical drug trails have failed due to a lack of appropriate disease models, including a lack of access to MNs from ALS patients. Induced pluripotent stem (iPS) cells derived from patients with ALS provide an indispensable resource for in vitro mechanistic studies and for future patient-specific cell-based therapies. Previous reports demonstrated that viral-based ALS-iPS cells generated from fibroblasts harvested from Caucasian populations are ideal for basic research; however, ALS-iPS cells are precluded from cell-based therapeutic applications because of the risks associated with the integration of viral sequences into the genome and inconvenience associated with dermal biopsies. To establish a model for use in clinical applications, using episomal vectors, we generated an integration-free iPS cell line from peripheral blood mononuclear cells (PBMCs) harvested from a familial ALS (FALS) patient carrying the FUS-P525L mutation and a healthy control. Furthermore, we successfully differentiated ALS patient-specific iPS cells into MNs and subsequently detected cytoplasmic mislocalization and formation of FUS protein aggregates in MNs due to the FUS-P525L mutation. Our findings offer a cell-based disease model for use in further elucidating ALS pathogenesis and provide a tool for exploring gene repair coupled with cell replacement therapy.

Corrective Action Investigation Plan for Corrective Action Unit 569: Area 3 Yucca Flat Atmospheric Test Sites Nevada National Security Site, Nevada, Revision 0

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

Patrick Matthews; Christy Sloop

2012-02-01

Corrective Action Unit (CAU) 569 is located in Area 3 of the Nevada National Security Site, which is approximately 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 569 comprises the nine numbered corrective action sites (CASs) and one newly identified site listed below: (1) 03-23-09, T-3 Contamination Area (hereafter referred to as Annie, Franklin, George, and Moth); (2) 03-23-10, T-3A Contamination Area (hereafter referred to as Harry and Hornet); (3) 03-23-11, T-3B Contamination Area (hereafter referred to as Fizeau); (4) 03-23-12, T-3S Contamination Area (hereafter referred to as Rio Arriba); (5) 03-23-13, T-3T Contamination Area (hereafter referred tomore » as Catron); (6) 03-23-14, T-3V Contamination Area (hereafter referred to as Humboldt); (7) 03-23-15, S-3G Contamination Area (hereafter referred to as Coulomb-B); (8) 03-23-16, S-3H Contamination Area (hereafter referred to as Coulomb-A); (9) 03-23-21, Pike Contamination Area (hereafter referred to as Pike); and (10) Waste Consolidation Site 3A. Because CAU 569 is a complicated site containing many types of releases, it was agreed during the data quality objectives (DQO) process that these sites will be grouped. These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives (CAAs). Additional information will be obtained by conducting a corrective action investigation before evaluating CAAs and selecting the appropriate corrective action for each study group. The results of the field investigation will support a defensible evaluation of viable CAAs that will be presented in the Corrective Action Decision Document. The sites will be investigated based on the DQOs developed on September 26, 2011, by representatives of the Nevada Division of Environmental Protection and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective actions for CAU 569. The presence and nature of contamination at CAU 569 will be evaluated based on information collected from a field investigation. Radiological contamination will be evaluated based on a comparison of the total effective dose (TED) at sample locations to the dose-based final action level (FAL). The TED will be calculated as the total of separate estimates of internal and external dose. Results from the analysis of soil samples will be used to calculate internal radiological dose. Thermoluminescent dosimeters placed at the center of each sample location will be used to measure external radiological dose. A field investigation will be performed to define any areas where TED exceeds the FAL and to determine whether contaminants of concern are present at the site from other potential releases. The presence and nature of contamination from other types of releases (e.g., excavation, migration, and any potential releases discovered during the investigation) will be evaluated using soil samples collected from biased locations indicating the highest levels of contamination. Appendix A provides a detailed discussion of the DQO methodology and the objectives specific to each study group.« less

Alcoholysis: A Promising Technology for Conversion of Lignocellulose and Platform Chemicals.

PubMed

Zhu, Shanhui; Guo, Jing; Wang, Xun; Wang, Jianguo; Fan, Weibin

2017-06-22

In the catalytic conversion of lignocellulose to valuable products, the first entry point is to break down these biopolymers to sugar units or aromatic monomers, which is conventionally achieved by hydrolysis in water medium. Recent years have seen tremendous progress in the alcoholysis process, which has remarkable advantages, such as the avoidance of treating waste water, suppression of humins or chars, and enhancement of reaction rate and product yield. Advances have been focused on the alcoholysis of cellulose, hemicellulose, and lignin to alkyl glucosides, xylosides, and aromatic monomers, respectively. Alcoholysis of the platform molecule furfuryl alcohol (FAL) to alkyl levulinate (AL) and integrated alcoholysis of cellulose and furfural into AL are also summarized. This Minireview highlights the comparisons between alcoholysis and hydrolysis, the reaction mechanism of alcoholysis, and future challenges for industrial applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of FFM accumulation and skeletal muscle architecture in powerlifting performance.

PubMed

Brechue, William F; Abe, Takashi

2002-02-01

The purpose of this study was to determine the distribution and architectural characteristics of skeletal muscle in elite powerlifters, and to investigate their relationship to fat-free mat (FFM) accumulation and powerlifting performance. Twenty elite male powerlifters (including four world and three US national champions) volunteered for this study. FFM, skeletal muscle distribution (muscle thickness at 13 anatomical sites), and isolated muscle thickness and fascicle pennation angle (PAN) of the triceps long-head (TL), vastus lateralis, and gastrocnemius medialis (MG) muscles were measured with B-mode ultrasound. Fascicle length (FAL) was calculated. Best lifting performance in the bench press (BP), squat lift (SQT), and dead lift (DL) was recorded from competition performance. Significant correlations (P < or = 0.01) were observed between muscle distribution (individual muscle thickness from 13 sites) and performance of the SQT (r = 0.79 to r = 0.91), BP (r = 0.63 to r = 0.85) and DL (r = 0.70 to r = 0.90). Subscapular muscle thickness was the single best predictor of powerlifting performance in each lift. Performance of the SQT, BP, and DL was strongly correlated with FFM and FFM relative to standing height (r = 0.86 to 0.95, P < or = 0.001). FAL of the triceps long head and vastus lateralis were significantly correlated with FFM (r = 0.59, P < or = 0.01; 0.63, P < or = 0.01, respectively) and performance of the SQT (r = 0.45; r = 0.50, respectively; P < or = 0.05), BP (r = 0.52; r = 0.56, respectively; P < or = 0.05), and DL (r = 0.56; r = 0.54, respectively; P < or = 0.01). A significant positive correlation was observed between isolated muscle thickness and PAN for triceps long-head (r = 0.64, P < or = 0.01) and gastrocnemius medialis (r = 0.48, P < or = 0.05) muscles, but not for vastus lateralis (r = 0.35). PAN was negatively correlated with powerlifting performance. Our results indicate that powerlifting performance is a function of FFM and, therefore, may be limited by the ability to accumulate FFM. Additionally, muscle architecture appears to play an important role in powerlifting performance in that greater fascicle lengths are associated with greater FFM accumulation and powerlifting performance.

Sample-ready multiplex qPCR assay for detection of malaria

PubMed Central

2014-01-01

Background Microscopy and antigen detecting rapid diagnostic tests are the diagnostic tests of choice in management of clinical malaria. However, due to their limitations, the need to utilize more sensitive methods such as real-time PCR (qPCR) is evident as more studies are now utilizing molecular methods in detection of malaria. Some of the challenges that continue to limit the widespread utilization of qPCR include lack of assay standardization, assay variability, risk of contamination, and the need for cold-chain. Lyophilization of molecular assays can overcome some of these limitations and potentially enable widespread qPCR utilization. Methods A recently published multiplex malaria qPCR assay was lyophilized by freezing drying into Sample-Ready™ format (MMSR). MMSR assay contained all the required reagents for qPCR including primers and probes, requiring only the addition of water and sample to perform qPCR. The performance of the MMSR assay was compared to the non-freeze dried, “wet” assay. Stability studies were done by maintaining the MMSR assays at four different ambient temperatures of 4°C, room temperature (RT), 37°C and 42°C over a period of 42 days, tested at seven-day intervals. Plasmodium falciparum and Plasmodium vivax DNAs were used for analysis of the MMSR assay either as single or mixed parasites, at two different concentrations. The CT values and the standard deviations (SD) were used in the analysis of the assay performance. Results The limit of detection for the MMSR assay was 0.244 parasites/μL for Plasmodium spp. (PLU) and P. falciparum (FAL) assay targets compared to “wet” assay which was 0.39 and 3.13 parasites/μL for PLU and FAL assay targets, respectively. The MMSR assay performed with high efficiencies similar to those of the “wet” assay and was stable at 37°C for 42 days, with estimated shelf-life of 5 months. When used to analyse field clinical samples, MMSR assay performed with 100% sensitivity and specificity compared to the “wet” assay. Conclusion The MMSR assay has the same robust performance characteristics as the “wet” assay and is highly stable. Availability of MMSR assay allows flexibility and provides an option in choosing assay for malaria diagnostics depending on the application, needs and budget. PMID:24767409

Sample-ready multiplex qPCR assay for detection of malaria.

PubMed

Kamau, Edwin; Alemayehu, Saba; Feghali, Karla C; Juma, Dennis W; Blackstone, George M; Marion, William R; Obare, Peter; Ogutu, Bernhards; Ockenhouse, Christian F

2014-04-25

Microscopy and antigen detecting rapid diagnostic tests are the diagnostic tests of choice in management of clinical malaria. However, due to their limitations, the need to utilize more sensitive methods such as real-time PCR (qPCR) is evident as more studies are now utilizing molecular methods in detection of malaria. Some of the challenges that continue to limit the widespread utilization of qPCR include lack of assay standardization, assay variability, risk of contamination, and the need for cold-chain. Lyophilization of molecular assays can overcome some of these limitations and potentially enable widespread qPCR utilization. A recently published multiplex malaria qPCR assay was lyophilized by freezing drying into Sample-Ready™ format (MMSR). MMSR assay contained all the required reagents for qPCR including primers and probes, requiring only the addition of water and sample to perform qPCR. The performance of the MMSR assay was compared to the non-freeze dried, "wet" assay. Stability studies were done by maintaining the MMSR assays at four different ambient temperatures of 4°C, room temperature (RT), 37°C and 42°C over a period of 42 days, tested at seven-day intervals. Plasmodium falciparum and Plasmodium vivax DNAs were used for analysis of the MMSR assay either as single or mixed parasites, at two different concentrations. The CT values and the standard deviations (SD) were used in the analysis of the assay performance. The limit of detection for the MMSR assay was 0.244 parasites/μL for Plasmodium spp. (PLU) and P. falciparum (FAL) assay targets compared to "wet" assay which was 0.39 and 3.13 parasites/μL for PLU and FAL assay targets, respectively. The MMSR assay performed with high efficiencies similar to those of the "wet" assay and was stable at 37°C for 42 days, with estimated shelf-life of 5 months. When used to analyse field clinical samples, MMSR assay performed with 100% sensitivity and specificity compared to the "wet" assay. The MMSR assay has the same robust performance characteristics as the "wet" assay and is highly stable. Availability of MMSR assay allows flexibility and provides an option in choosing assay for malaria diagnostics depending on the application, needs and budget.

A Yeast Model of FUS/TLS-Dependent Cytotoxicity

PubMed Central

Ju, Shulin; Tardiff, Daniel F.; Han, Haesun; Divya, Kanneganti; Zhong, Quan; Maquat, Lynne E.; Bosco, Daryl A.; Hayward, Lawrence J.; Brown, Robert H.; Lindquist, Susan; Ringe, Dagmar; Petsko, Gregory A.

2011-01-01

FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). Although FUS/TLS is normally located predominantly in the nucleus, the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression. PMID:21541368

SUNQUAKE GENERATION BY CORONAL MAGNETIC RESTRUCTURING

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

Russell, A. J. B.; Mooney, M. K.; Leake, J. E.

2016-11-01

Sunquakes are the surface signatures of acoustic waves in the Sun’s interior that are produced by some but not all flares and coronal mass ejections (CMEs). This paper explores a mechanism for sunquake generation by the changes in magnetic field that occur during flares and CMEs, using MHD simulations with a semiempirical FAL-C atmosphere to demonstrate the generation of acoustic waves in the interior in response to changing magnetic tilt in the corona. We find that Alfvén–sound resonance combined with the ponderomotive force produces acoustic waves in the interior with sufficient energy to match sunquake observations when the magnetic fieldmore » angle changes of the order of 10° in a region where the coronal field strength is a few hundred gauss or more. The most energetic sunquakes are produced when the coronal field is strong, while the variation of magnetic field strength with height and the timescale of the change in tilt are of secondary importance.« less

Synthesis, characterization, and application of two Al(OR(F))3 Lewis superacids.

PubMed

Kraft, Anne; Trapp, Nils; Himmel, Daniel; Böhrer, Hannes; Schlüter, Peter; Scherer, Harald; Krossing, Ingo

2012-07-23

We report herein the synthesis and full characterization of the donor-free Lewis superacids Al(OR(F))(3) with OR(F) = OC(CF(3))(3) (1) and OC(C(5)F(10))C(6)F(5) (2), the stabilization of 1 as adducts with the very weak Lewis bases PhF, 1,2-F(2)C(6)H(4), and SO(2), as well as the internal C-F activation pathway of 1 leading to Al(2)(F)(OR(F))(5) (4) and trimeric [FAl(OR(F))(2)](3) (5, OR(F) = OC(CF(3))(3)). Insights have been gained from NMR studies, single-crystal structure determinations, and DFT calculations. The usefulness of these Lewis acids for halide abstractions has been demonstrated by reactions with trityl chloride (NMR; crystal structures). The trityl salts allow the introduction of new, heteroleptic weakly coordinating [Cl-Al(OR(F))(3)](-) anions, for example, by hydride or alkyl abstraction reactions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mutations in FUS cause FALS and SALS in French and French Canadian populations

PubMed Central

Belzil, V. V.; Valdmanis, P. N.; Dion, P. A.; Daoud, H.; Kabashi, E.; Noreau, A.; Gauthier, J.; Hince, P.; Desjarlais, A.; Bouchard, J. -P.; Lacomblez, L.; Salachas, F.; Pradat, P. -F.; Camu, W.; Meininger, V.; Dupré, N.; Rouleau, G. A.

2009-01-01

Background: The identification of mutations in the TARDBP and more recently the identification of mutations in the FUS gene as the cause of amyotrophic lateral sclerosis (ALS) is providing the field with new insight about the mechanisms involved in this severe neurodegenerative disease. Methods: To extend these recent genetic reports, we screened the entire gene in a cohort of 200 patients with ALS. An additional 285 patients with sporadic ALS were screened for variants in exon 15 for which mutations were previously reported. Results: In total, 3 different mutations were identified in 4 different patients, including 1 3-bp deletion in exon 3 of a patient with sporadic ALS and 2 missense mutations in exon 15 of 1 patient with familial ALS and 2 patients with sporadic ALS. Conclusions: Our study identified sporadic patients with mutations in the FUS gene. The accumulation and description of different genes and mutations helps to develop a more comprehensive picture of the genetic events underlying amyotrophic lateral sclerosis. PMID:19741216

Mutations in FUS cause FALS and SALS in French and French Canadian populations.

PubMed

Belzil, V V; Valdmanis, P N; Dion, P A; Daoud, H; Kabashi, E; Noreau, A; Gauthier, J; Hince, P; Desjarlais, A; Bouchard, J-P; Lacomblez, L; Salachas, F; Pradat, P-F; Camu, W; Meininger, V; Dupré, N; Rouleau, G A

2009-10-13

The identification of mutations in the TARDBP and more recently the identification of mutations in the FUS gene as the cause of amyotrophic lateral sclerosis (ALS) is providing the field with new insight about the mechanisms involved in this severe neurodegenerative disease. To extend these recent genetic reports, we screened the entire gene in a cohort of 200 patients with ALS. An additional 285 patients with sporadic ALS were screened for variants in exon 15 for which mutations were previously reported. In total, 3 different mutations were identified in 4 different patients, including 1 3-bp deletion in exon 3 of a patient with sporadic ALS and 2 missense mutations in exon 15 of 1 patient with familial ALS and 2 patients with sporadic ALS. Our study identified sporadic patients with mutations in the FUS gene. The accumulation and description of different genes and mutations helps to develop a more comprehensive picture of the genetic events underlying amyotrophic lateral sclerosis.

Recovery from TBT pollution in English Channel environments: A problem solved?

PubMed

Langston, W J; Pope, N D; Davey, M; Langston, K M; O' Hara, S C M; Gibbs, P E; Pascoe, P L

2015-06-30

Following recognition of effects in the 1980s, tributyltin (TBT) has been monitored at sites in the English Channel to evaluate the prognosis for biota - spanning the introduction of restrictions on TBT use on small boats and the recent phase-out on the global fleet. We describe how persistence and impact of TBT in clams Scrobicularia plana has changed during this period in Southampton Water and Poole Harbour. TBT contamination (and loss) in water, sediment and clams reflects the abundance and type of vessel activity: half-times in sediment (up to 8y in Poole, 33y in Southampton) are longest near commercial shipping. Recovery of clam populations - slowest in TBT-contaminated deposits - provides a useful biological measure of legislative efficacy in estuaries. On rocky shores, recovery from imposex in Nucella lapillus is evident at many sites but, near ports, is prolonged by shipping impacts, including sediment legacy, for example, in the Fal. Copyright © 2014 Elsevier Ltd. All rights reserved.

New Technological Interventions in Conservation Conflicts: Countering Emotions and Contested Knowledge.

PubMed

Verma, Audrey; van der Wal, René; Fischer, Anke

2017-01-01

New technologies have increasingly featured in environmental conservation conflicts. We examined the deployment of imaging devices such as sonar equipment and cameras to survey the Fal estuary in Cornwall, UK. Due to heavy use of these waters, there have been several disputes coalescing around protected marine features, including the estuary's rare maerl beds. A comparison of two cases, scallop dredging and docks development, showed technical instruments being deployed to produce information about the marine environment as evidence to inform decision-making. The use of imaging devices stimulated political action and was regarded as a move away from emotion-based decision-making towards desired objectivity. Simultaneously, however, the process of deploying these devices was challenged and there was recognition that the resultant information could be used to construct the estuary as a politically charged space. Thus, rather than clarifying and resolving contentious issues, technological interventions generated new baselines for knowledge contestation and amplified ongoing battles for credibility and authority.

Impact of ammonia and sulphate concentration on thermophilic anaerobic digestion.

PubMed

Siles, J A; Brekelmans, J; Martín, M A; Chica, A F; Martín, A

2010-12-01

The effect of increasing concentrations of ammonia and sulphate on thermophilic anaerobic digestion (52 degrees C) was studied at laboratory-scale. The substrate consisted of a synthetic solution supplemented with ammonia and sodium sulphate. In terms of biogas production, the results showed that the C/N and C/SO(4)(2-) thresholds were 4.40 and 1.60, respectively, corresponding to 620 mg FA (free ammonia)/L and 1400 mg SO(4)(2-)/L. No reduction in biogas production was observed until reaching the above concentration of sulphate in the sulphate toxicity test. However, when the concentration of ammonia was increased to 620 mg FA/L in the ammonia toxicity test, a gradual decrease of 21% was observed for the biogas. In order to characterise each set of experiments kinetically, a biogas production first-order kinetic model was used to fit the experimental data. The proposed model accurately predicted the behaviour of the microorganisms affecting the thermophilic anaerobic digestion, allowing its evolution to be predicted. 2010 Elsevier Ltd. All rights reserved.

Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography

PubMed Central

Chen, Haojun; Tong, Xiao; Lang, Lixin; Jacobson, Orit; Yung, Bryant C.; Yang, Xiangyu; Bai, Ruiliang; Kiesewetter, Dale O.; Ma, Ying; Wu, Hua; Niu, Gang; Chen, Xiaoyuan

2017-01-01

Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Pswere overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis. PMID:28744320

Delayed disease onset and extended survival in the SOD1G93A rat model of amyotrophic lateral sclerosis after suppression of mutant SOD1 in the motor cortex.

PubMed

Thomsen, Gretchen M; Gowing, Genevieve; Latter, Jessica; Chen, Maximus; Vit, Jean-Philippe; Staggenborg, Kevin; Avalos, Pablo; Alkaslasi, Mor; Ferraiuolo, Laura; Likhite, Shibi; Kaspar, Brian K; Svendsen, Clive N

2014-11-19

Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by a progressive loss of motor neurons leading to paralysis and death typically within 3-5 years of onset. Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1(G93A) rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1(G93A) rats through targeted delivery of AAV9-SOD1-shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease. Copyright © 2014 the authors 0270-6474/14/3415587-14$15.00/0.

A Mouse Model of Familial ALS Has Increased CNS Levels of Endogenous Ubiquinol9/10 and Does Not Benefit from Exogenous Administration of Ubiquinol10

PubMed Central

Lucchetti, Jacopo; Marino, Marianna; Papa, Simonetta; Tortarolo, Massimo; Guiso, Giovanna; Pozzi, Silvia; Bonetto, Valentina; Caccia, Silvio; Beghi, Ettore; Bendotti, Caterina; Gobbi, Marco

2013-01-01

Oxidative stress and mitochondrial impairment are the main pathogenic mechanisms of Amyotrophic Lateral Sclerosis (ALS), a severe neurodegenerative disease still lacking of effective therapy. Recently, the coenzyme-Q (CoQ) complex, a key component of mitochondrial function and redox-state modulator, has raised interest for ALS treatment. However, while the oxidized form ubiquinone10 was ineffective in ALS patients and modestly effective in mouse models of ALS, no evidence was reported on the effect of the reduced form ubiquinol10, which has better bioavailability and antioxidant properties. In this study we compared the effects of ubiquinone10 and a new stabilized formulation of ubiquinol10 on the disease course of SOD1G93A transgenic mice, an experimental model of fALS. Chronic treatments (800 mg/kg/day orally) started from the onset of disease until death, to mimic the clinical trials that only include patients with definite ALS symptoms. Although the plasma levels of CoQ10 were significantly increased by both treatments (from <0.20 to 3.0–3.4 µg/mL), no effect was found on the disease progression and survival of SOD1G93A mice. The levels of CoQ10 in the brain and spinal cord of ubiquinone10- or ubiquinol10-treated mice were only slightly higher (≤10%) than the endogenous levels in vehicle-treated mice, indicating poor CNS availability after oral dosing and possibly explaining the lack of pharmacological effects. To further examine this issue, we measured the oxidized and reduced forms of CoQ9/10 in the plasma, brain and spinal cord of symptomatic SOD1G93A mice, in comparison with age-matched SOD1WT. Levels of ubiquinol9/10, but not ubiquinone9/10, were significantly higher in the CNS, but not in plasma, of SOD1G93A mice, suggesting that CoQ redox system might participate in the mechanisms trying to counteract the pathology progression. Therefore, the very low increases of CoQ10 induced by oral treatments in CNS might be not sufficient to provide significant neuroprotection in SOD1G93A mice. PMID:23936040

Applying the creating lasting family connections marriage enhancement program to marriages affected by prison reentry.

PubMed

Shamblen, Stephen R; Arnold, Brooke B; McKiernan, Patrick; Collins, David A; Strader, Ted N

2013-09-01

Divorce proportions are currently high in the US and they are even higher among those who are incarcerated with substance abuse problems. Although much research has examined marital interventions, only two studies have examined marital interventions with prison populations. There is some empirical evidence that incarcerated couples benefit from traditional marital therapy (O'Farrell and Fals-Stewart, 1999, Addictions: A comprehensive guidebook, New York, Oxford University Press). An adaptation of the evidence-based Creating Lasting Family Connections program was implemented with 144 married couples, where one spouse was incarcerated, in a southern state with particularly high divorce and incarceration proportions. Results suggested that married men exposed to the program had larger improvements in some relationship skills relative to a convenience sample of men not so exposed. Both husbands and wives exposed to the program exhibited similar and significant increases in relationship skills. The results were comparable to a Prevention and Relationship Enhancement Program adaptation for inmates. The implications of the findings for prevention practitioners are discussed. © FPI, Inc.

Rare case of nephrotic syndrome: Schimke syndrome.

PubMed

Pedrosa, Anna Kelly Krislane de Vasconcelos; Torres, Luiz Fernando Oliveira; Silva, Ana Corina Brainer Amorim da; Dantas, Adrianna Barros Leal; Zuntini, Káthia Liliane da Cunha Ribeiro; Aguiar, Lia Cordeiro Bastos

2016-01-01

Schimke syndrome corresponds to dysplasia of bone and immunity, associated with progressive renal disease secondary to nephrotic syndrome cortico-resistant, with possible other abnormalities such as hypothyroidism and blond marrow aplasia. It is a rare genetic disorder, with few reports in the literature. The most frequent renal involvement is nephrotic syndrome with focal segmental glomerulosclerosis and progressive renal failure. The objective of this study was to report a case of Schimke syndrome, diagnostic investigation and management of the case. Resumo A síndrome Schimke corresponde à displasia imuno-óssea, associada à doença renal progressiva secundária à síndrome nefrótica córtico-resistente, podendo haver outras anormalidades como hipotireoidismo e aplasia de medula óssea. Trata-se de uma patologia genética rara, com poucos relatos na literatura. O acometimento renal mais frequente é uma síndrome nefrótica por glomeruloesclerose segmentar e focal e falência renal progressiva. O objetivo deste estudo foi relatar um caso de síndrome de Schimke, investigação diagnóstica e condução do caso.

Summary Report for the Evaluation of Current QA Processes Within the FRMAC FAL and EPA MERL.

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

Shanks, Sonoya T.; Redding, Ted; Jaussi, Lynn

The Federal Radiological Monitoring and Assessment Center (FRMAC) relies on accurate and defensible analytical laboratory data to support its mission. Therefore, FRMAC must ensure that the environmental analytical laboratories providing analytical services maintain an ongoing capability to provide accurate analytical results to DOE. It is undeniable that the more Quality Assurance (QA) and Quality Control (QC) measures required of the laboratory, the less resources that are available for analysis of response samples. Being that QA and QC measures in general are understood to comprise a major effort related to a laboratory’s operations, requirements should only be considered if they aremore » deemed “value-added” for the FRMAC mission. This report provides observations of areas for improvement and potential interoperability opportunities in the areas of Batch Quality Control Requirements, Written Communications, Data Review Processes, Data Reporting Processes, along with the lessons learned as they apply to items in the early phase of a response that will be critical for developing a more efficient, integrated response for future interactions between the FRMAC and EPA assets.« less

Geographic List of Prime Contract Awards. Oct 1992-Sep 1993. FY 1993. (Acton (Sta), Mass.-Wayne County, Missouri). Part 7

DTIC Science & Technology

1994-03-01

ED00LEI00ED00 0D 00C ( o DE O 1 c’m mmlmmm am mm~ mII MeO ds~)(4 - -4,.4-I4 .-4 ’ 4 -4 -4 4 No v0 to M (V) 110 1 0 4’) If I (i9tot i 0 (20) D(1...ooIm~0o Uom4-( el.W it I W00 II’a4- 00 W4al 000 0al0al)04fal -n U )-4 as W IfI cacao IIZN.-4 V-4 &A-4 v -4 to CO-E..4-4 " .*-E4 4 -4 -4U1r -44-v .4 -40...n E 44V4.*4 x Cn 11 cacao MI mn -4.E W CON Off 0 00050 If >- 11 01 cooG it -4 _a LLa 11 c 1 0000 1 N4cr 11 100 0 W 1 11 1 E for 10 -4- -4 -.4 -4- ý4

An Analysis of Interactions between Fluorescently-Tagged Mutant and Wild-Type SOD1 in Intracellular Inclusions

PubMed Central

Qualls, David A.; Crosby, Keith; Brown, Hilda; Borchelt, David R.

2013-01-01

Background By mechanisms yet to be discerned, the co-expression of high levels of wild-type human superoxide dismutase 1 (hSOD1) with variants of hSOD1 encoding mutations linked familial amyotrophic lateral sclerosis (fALS) hastens the onset of motor neuron degeneration in transgenic mice. Although it is known that spinal cords of paralyzed mice accumulate detergent insoluble forms of WT hSOD1 along with mutant hSOD1, it has been difficult to determine whether there is co-deposition of the proteins in inclusion structures. Methodology/Principal Findings In the present study, we use cell culture models of mutant SOD1 aggregation, focusing on the A4V, G37R, and G85R variants, to examine interactions between WT-hSOD1 and misfolded mutant SOD1. In these studies, we fuse WT and mutant proteins to either yellow or red fluorescent protein so that the two proteins can be distinguished within inclusions structures. Conclusions/Significance Although the interpretation of the data is not entirely straightforward because we have strong evidence that the nature of the fused fluorophores affects the organization of the inclusions that form, our data are most consistent with the idea that normal dimeric WT-hSOD1 does not readily interact with misfolded forms of mutant hSOD1. We also demonstrate the monomerization of WT-hSOD1 by experimental mutation does induce the protein to aggregate, although such monomerization may enable interactions with misfolded mutant SOD1. Our data suggest that WT-hSOD1 is not prone to become intimately associated with misfolded mutant hSOD1 within intracellular inclusions that can be generated in cultured cells. PMID:24391857

12 CFR 263.82 - Establishment of minimum capital levels.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Establishment of minimum capital levels. 263.82... Maintain Adequate Capital § 263.82 Establishment of minimum capital levels. The Board has established minimum capital levels for state member banks and bank holding companies in its Capital Adequacy...

First-principles study of alloying effects on fluorine incorporation in Al x Ga1-x N alloys

NASA Astrophysics Data System (ADS)

Wang, Rong; Tan, Wei; Zhang, Jian; Chen, Feng-Xiang; Wei, Su-Huai

2018-02-01

Incorporation of fluorine (F) into the AlGaN layer is crucial to the fabrication of enhancement-mode (E-mode) AlGaN/GaN high electron mobility transistors (HEMTs). However, the understanding of properties of F doping in AlGaN alloys is rather limited. Using first-principles calculations and the special quasirandom structure (SQS) approach, we investigate the alloying effects on the doping properties of F-incorporated Al x Ga1-x N alloys. We find that substitutional F on N sites (FN) and interstitial F (Fi) are dominant defects for F in Al x Ga1-x N alloys. For these two types of defects, both the global composition x and the local motif surrounding the dopant play important roles. On contrary, the incorporation of substitutional F on Ga sites (FGa) or Al sites (FAl) are affected only by the composition x. We also find that there exists a large asymmetric bowing for the effective formation energies of FN and Fi. These results are explained in terms of local structural distortion and electronic effects. The mechanism discussed in this paper can also be used in understanding doping in other semiconductor alloys.

Actuator and aerodynamic modeling for high-angle-of-attack aeroservoelasticity

NASA Technical Reports Server (NTRS)

Brenner, Martin J.

1993-01-01

Accurate prediction of airframe/actuation coupling is required by the imposing demands of modern flight control systems. In particular, for agility enhancement at high angle of attack and low dynamic pressure, structural integration characteristics such as hinge moments, effective actuator stiffness, and airframe/control surface damping can have a significant effect on stability predictions. Actuator responses are customarily represented with low-order transfer functions matched to actuator test data, and control surface stiffness is often modeled as a linear spring. The inclusion of the physical properties of actuation and its installation on the airframe is therefore addressed using detailed actuator models which consider the physical, electrical, and mechanical elements of actuation. The aeroservoelastic analysis procedure is described in which the actuators are modeled as detailed high-order transfer functions and as approximate low-order transfer functions. The impacts of unsteady aerodynamic modeling on aeroservoelastic stability are also investigated by varying the order of approximation, or number of aerodynamic lag states, in the analysis. Test data from a thrust-vectoring configuration of an F/A-l8 aircraft are compared to predictions to determine the effects on accuracy as a function of modeling complexity.

Historical Review of Uncommanded Lateral-Directional Motions At Transonic Conditions (Invited)

NASA Technical Reports Server (NTRS)

Chambers, Joseph R.; Hall, Robert M.

2003-01-01

This paper presents the results of a survey of past experiences with uncommanded lateral-directional motions at transonic speeds during specific military aircraft programs. The effort was undertaken to provide qualitative and quantitative information on past airplane programs that might be of use to the participants in the joint NASA/Navy/Air Force Abrupt Wing Stall (AWS) Program. The AWS Program was initiated because of the experiences of the F/A-18E/F development program, during which unexpected, severe wing-drop motions were encountered by preproduction aircraft at transonic conditions. These motions were judged to be significantly degrading to the primary mission requirements of the aircraft. Although the problem was subsequently solved for the production version of the F/A-l8E/F, a high-level review panel emphasized the poor understanding of such phenomena and issued a strong recommendation to: Initiate a national research effort to thoroughly and systematically study the wing drop phenomena. A comprehensive, cooperative NASA/Navy/Air Force AWS Program was designed to respond to provide the required technology requirements. As part of the AWS Program, a work element was directed at a historical review of wing-drop experiences in past aircraft development programs at high subsonic and transonic speeds. In particular, information was requested regarding: specific aircraft configurations that exhibited uncommanded motions and the nature of the motions; geometric characteristics of the air- planes; flight conditions involved in occurrences; relevant data, including wind-tunnel, computational, and flight sources; figures of merit used for analyses; and approaches used to alleviate the problem. An attempt was also made to summarize some of the more important lessons learned from past experiences, and to recommend specific research efforts. In addition to providing technical information to assist the AWS research objectives, the study produced fundamental information regarding the historical challenge of uncommanded lateral-directional motions at transonic conditions and the associated aerodynamic phenomena.

New insights into the gene expression associated to amyotrophic lateral sclerosis.

PubMed

Recabarren-Leiva, Daniela; Alarcón, Marcelo

2018-01-15

Amyotrophic lateral sclerosis (ALS) is the most prevalent neuromuscular disease worldwide. It is a lethal and progressive neurodegenerative disease, principally affecting motor neurons; patient clinical characteristics are muscle weakness, dysphagia and respiratory failure. The mean age is related to family history (40years, familial ALS or FALS) or with no family history (50years), but it is more common in people aged 60-69years. The cause of ALS is not known and it is not known yet why it affects some people and not others. However expert consensus is that molecular alterations in different cells are involved in the development and progression of the disease. For example, motor neuron death is caused by a variety of cellular defects, including the processing of RNA molecules, water channels, and calcium levels, increasing evidence that these alterations of cells in the nervous system play an important role in ALS. Here we will systematically examine different genes (AQP1, SLC14A1, MT1X, DSCR1L1, PCP4, UCHL1, GABRA1, EGR1, OLFM1 and VSNL1) that are "up or down" regulated in the motor cortex and spinal cord and their association with ALS risk. These could be novel biomarkers associated with ALS risk. We built an interaction Network with Cytoscape, this was used to identify pathways, miRNA and drugs associated to ALS. The most important affected pathway is PI3K-Akt signaling. Thirteen microRNAs (miRNA-19B1, miRNA-107, miRNA-124-1, miRNA-124-2, miRNA-9-2, miRNA-29A, miRNA-9-3, miRNA-328, miRNA-19B2, miRNA-29B2, miRNA-124-3, miRNA-15A and miRNA-9-1) and four drugs (Estradiol, Acetaminophen, Progesterone and resveratrol) for new possible treatments were identified. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of disulfide cross-linking of mutant SOD1 in the formation of inclusion-body-like structures.

PubMed

Roberts, Brittany L T; Patel, Kinaree; Brown, Hilda H; Borchelt, David R

2012-01-01

Pathologic aggregates of superoxide dismutase 1 (SOD1) harboring mutations linked to familial amyotrophic lateral sclerosis (fALS) have been shown to contain aberrant intermolecular disulfide cross-links. In prior studies, we observed that intermolecular bonding was not necessary in the formation of detergent- insoluble SOD1 complexes by mutant SOD1, but we were unable to assess whether this type of bonding may be important for pathologic inclusion formation. In the present study, we visually assess the formation of large inclusions by fusing mutant SOD1 to yellow fluorescent protein (YFP). Experimental constructs possessing mutations at all cysteine residues in SOD1 (sites 6, 57, 111, and 146 to F,S,Y,R or G,S,Y,R, respectively) were shown to maintain a high propensity of inclusion formation despite the inability to form disulfide cross-links. Interestingly, although aggregates form when all cysteines were mutated, double mutants of the ALS mutation C6G with an experimental mutation C111S exhibited low aggregation propensity. Overall, this study is an extension of previous work demonstrating that cysteine residues in mutant SOD1 play a role in modulating aggregation and that intermolecular disulfide bonds are not required to produce large intracellular inclusion-like structures.

An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation.

PubMed

Okamoto, Koichi; Fujita, Yukio; Hoshino, Eri; Tamura, Yuhji; Fukuda, Toshio; Hasegawa, Masato; Takatama, Masamitsu

2015-10-01

We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked-in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation-dependent transactivation response DNA-binding protein of 43 kDa (pTDP-43)-positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin- and p62-positive inclusions was markedly lower than that of pTDP-43-positive inclusions. NCIs and many fine dot-like pTDP-43-positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti-pTDP-43 antibody was slightly different from previous TDP-43 pathological subtypes. © 2015 Japanese Society of Neuropathology.

Burden of rare variants in ALS genes influences survival in familial and sporadic ALS.

PubMed

Pang, Shirley Yin-Yu; Hsu, Jacob Shujui; Teo, Kay-Cheong; Li, Yan; Kung, Michelle H W; Cheah, Kathryn S E; Chan, Danny; Cheung, Kenneth M C; Li, Miaoxin; Sham, Pak-Chung; Ho, Shu-Leong

2017-10-01

Genetic variants are implicated in the development of amyotrophic lateral sclerosis (ALS), but it is unclear whether the burden of rare variants in ALS genes has an effect on survival. We performed whole genome sequencing on 8 familial ALS (FALS) patients with superoxide dismutase 1 (SOD1) mutation and whole exome sequencing on 46 sporadic ALS (SALS) patients living in Hong Kong and found that 67% had at least 1 rare variant in the exons of 40 ALS genes; 22% had 2 or more. Patients with 2 or more rare variants had lower probability of survival than patients with 0 or 1 variant (p = 0.001). After adjusting for other factors, each additional rare variant increased the risk of respiratory failure or death by 60% (p = 0.0098). The presence of the rare variant was associated with the risk of ALS (Odds ratio 1.91, 95% confidence interval 1.03-3.61, p = 0.03), and ALS patients had higher rare variant burden than controls (MB, p = 0.004). Our findings support an oligogenic basis with the burden of rare variants affecting the development and survival of ALS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases?

USGS Publications Warehouse

Bradley, Walter G.; Borenstein, Amy R.; Nelson, Lorene M.; Codd, Geoffrey A.; Rosen, Barry H.; Stommel, Elijah W.; Cox, Paul Alan

2013-01-01

There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5–10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the syndrome of ALS, although exposure to chemicals including lead and pesticides, and to agricultural environments, smoking, certain sports, and trauma have all been identified with an increased risk of ALS. There is a need for research to quantify the relative roles of each of the identified risk factors for ALS. Recent evidence has strengthened the theory that chronic environmental exposure to the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) produced by cyanobacteria may be an environmental risk factor for ALS. Here we describe methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems. Rigorous epidemiologic studies could determine the risks associated with exposure to cyanobacteria, and if combined with genetic analysis of ALS cases and controls could reveal etiologically important gene-environment interactions in genetically vulnerable individuals.

Next Generation Sequencing and ALS: known genes, different phenotyphes.

PubMed

Campopiano, Rosa; Ryskalin, Larisa; Giardina, Emiliano; Zampatti, Stefania; Busceti, Carla L; Biagioni, Francesca; Ferese, Rosangela; Storto, Marianna; Gambardella, Stefano; Fornai, Francesco

2017-12-01

Amyotrophic lateral sclerosis (ALS) is fatal neurodegenerative disease clinically characterized by upper and lower motor neuron dysfunction resulting in rapidly progressive paralysis and death from respiratory failure. Most cases appear to be sporadic, but 5-10 % of cases have a family history of the disease, and over the last decade, identification of mutations in about 20 genes predisposing to these disorders has provided the means to better understand their pathogenesis. Next Generation sequencing (NGS) is an advanced high-throughput DNA sequencing technology which have rapidly contributed to an acceleration in the discovery of genetic risk factors for both familial and sporadic neurological and neurodegenerative diseases. These strategies allowed to rapidly identify disease-associated variants and genetic risk factors for both familial (fALS) and sporadic ALS (sALS), strongly contributing to the knowledge of the genetic architecture of ALS. Moreover, as the number of ALS genes grows, many of the proteins they encode are in intracellular processes shared with other known diseases, suggesting an overlapping of clinical and phatological features between different diseases. To emphasize this concept, the review focuses on genes coding for Valosin-containing protein (VPC) and two Heterogeneous nuclear RNA-binding proteins (HNRNPA1 and hnRNPA2B1), recently idefied through NGS, where different mutations have been associated in both ALS and other neurological and neurodegenerative diseases.

75 FR 28643 - Pine Island, Matlacha Pass, Island Bay, and Caloosahatchee National Wildlife Refuges, Lee and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... would work with the partners to establish benchmarks to record sea level rise and beach profiles and... partners to establish benchmarks to record sea level rise and beach profiles and shoreline changes, which... establish benchmarks to record sea level rise and beach profiles and shoreline changes, which could...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

40 CFR 180.33 - Fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (b) Each petition for the establishment of a tolerance at a lower numerical level or levels than a... additional raw agricultural commodities at the same numerical level as a tolerance already established for... has a tolerance for other uses at the same numerical level or a higher numerical level shall be...

Hydrology of Indiana lakes

USGS Publications Warehouse

Perrey, Joseph Irving; Corbett, Don Melvin

1956-01-01

The stabilization of lake levels often requires the construction of outlet control structures. A detailed study of past lake-level elevations and other hydologic date is necessary to establish a level that can be maintained and to determine the means necessary for maintaining the established level. Detailed lake-level records for 28 lakes are included in the report, and records for over 100 other lakes data are available in the U.S. Geological Survey Office, Indianapolis, Ind. Evaporation data from the four Class A evaporation station of the U. S. Weather Bureau have been compiled in this report. A table showing the established legal lake level and related data is included.

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2011 CFR

2011-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2014 CFR

2014-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2013 CFR

2013-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2012 CFR

2012-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

Precipitation of impurities in 9-32-0 grade fluid fertilizers

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

Dillard, E.F.; Scheib, R.M.; Greenwell, B.E.

1986-01-01

For several years TVA has been studying production of 9-32-0 ammonium polyphosphate suspension produced from ammoniated merchant-grade wet-process orthophosphoric acid. Suspensions containing polyphosphate have an advantage over those that contain only orthophosphate in that they can be stored satisfactorily at much lower temperature. However, the introduction of polyphosphate (pyrophosphate anion) complicates the precipitation of impurities and has yielded inconsistent storage characteristics in 9-32-0 fluid fertilizers. Fluorine also has been shown to affect suspension fertilizer properties. The viscosity of 13-38-0 orthophosphate suspension fertilizers is affected by the atomic ratios F:(Al + Fe + Mg). Addition of fluorine prevents sludges and precipitatesmore » in ammonium polyphosphate fertilizer solutions - the proper amount of fluorine is related to the amount of each of the metallic impurities present and also to the fraction of the phosphate present as pyrophosphate. Incorporation of polyphosphate or fluorine or both has been shown to have positive effects on ammoniated wet-process phosphoric acid (WPPA), but they do not report the solubility relationships of the cation impurities (Fe, Al, Mg, and Ca) with respect to the anion constituents (PO/sub 4/, P/sub 2/O/sub 7/, and F). Therefore, a factorial study was developed to determine the solubility relationships of the precipitated metal impurities encountered in 9-32-0 fluid fertilizers. 10 refs., 1 fig., 20 tabs.« less

Phenotypic and genotypic studies of ALS cases in ALS-SMA families.

PubMed

Corcia, Philippe; Vourc'h, Patrick; Blasco, Helene; Couratier, Philippe; Dangoumau, Audrey; Bellance, Remi; Desnuelle, Claude; Viader, Fausto; Pautot, Vivien; Millecamps, Stephanie; Bakkouche, Salah; Salachas, FranÇois; Andres, Christian R; Meininger, Vincent; Camu, William

2018-08-01

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most frequent motor neuron disorders in adulthood and infancy, respectively. There is a growing literature supporting common pathophysiological patterns between those disorders. One important clinical issue for that is the co-occurrence of both diseases within a family. To collect families in which ALS and SMA patients co-exist and describe the phenotype and the genotype of ALS patients. Nine families with co-occurrence of SMA and ALS have been gathered over the last 15 years. Epidemiological, phenotype and genetic status were collected. Out of the nine families, six corresponded to the criteria of familial ALS (FALS). Clinical data were available for 11 patients out of the 15 ALS cases. Mean age of onset was 58.5 years, site of onset was lower limbs in nine cases (81.8%), median duration was 22 months. Four ALS patients carried a mutation: three mutations in SOD1 gene (G147N in two cases and one with E121G) and one repeat expansion in the C9ORF72 gene. Three patients had abnormal SMN1 copy numbers. While the high proportion of familial history of ALS cases in these ALS-SMA pedigrees could have suggested that these familial clusters of the two most frequent MND rely on a genetic background, we failed to exclude that this occurred by chance.

Use of probability analysis to establish routine bioassay screening levels

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

Carbaugh, E.H.; Sula, M.J.; McFadden, K.M.

1990-09-01

Probability analysis was used by the Hanford Internal Dosimetry Program to establish bioassay screening levels for tritium and uranium in urine. Background environmental levels of these two radionuclides are generally detectable by the highly sensitive urine analysis procedures routinely used at Hanford. Establishing screening levels requires balancing the impact of false detection with the consequence of potentially undetectable occupation dose. To establish the screening levels, tritium and uranium analyses were performed on urine samples collected from workers exposed only to environmental sources. All samples were collected at home using a simulated 12-hour protocol for tritium and a simulated 24-hour collectionmore » protocol for uranium. Results of the analyses of these samples were ranked according to tritium concentration or total sample uranium. The cumulative percentile was calculated and plotted using log-probability coordinates. Geometric means and screening levels corresponding to various percentiles were estimated by graphical interpolation and standard calculations. The potentially annual internal dose associated with a screening level was calculated. Screening levels were selected corresponding to the 99.9 percentile, implying that, on the average, 1 out of 1000 samples collected from an unexposed worker population would be expected to exceed the screening level. 4 refs., 2 figs.« less

Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache

PubMed Central

Simpson, David M.; Hallett, Mark; Ashman, Eric J.; Comella, Cynthia L.; Green, Mark W.; Gronseth, Gary S.; Armstrong, Melissa J.; Gloss, David; Potrebic, Sonja; Jankovic, Joseph; Karp, Barbara P.; Naumann, Markus; So, Yuen T.; Yablon, Stuart A.

2016-01-01

Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria. Results and recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B). PMID:27164716

21 CFR 530.22 - Safe levels and analytical methods for food-producing animals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... analytical method; or (3) Establish a safe level based on other appropriate scientific, technical, or... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Safe levels and analytical methods for food... § 530.22 Safe levels and analytical methods for food-producing animals. (a) FDA may establish a safe...

21 CFR 530.22 - Safe levels and analytical methods for food-producing animals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... analytical method; or (3) Establish a safe level based on other appropriate scientific, technical, or... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Safe levels and analytical methods for food... § 530.22 Safe levels and analytical methods for food-producing animals. (a) FDA may establish a safe...

21 CFR 530.22 - Safe levels and analytical methods for food-producing animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... analytical method; or (3) Establish a safe level based on other appropriate scientific, technical, or... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Safe levels and analytical methods for food... § 530.22 Safe levels and analytical methods for food-producing animals. (a) FDA may establish a safe...

21 CFR 530.22 - Safe levels and analytical methods for food-producing animals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... analytical method; or (3) Establish a safe level based on other appropriate scientific, technical, or... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Safe levels and analytical methods for food... § 530.22 Safe levels and analytical methods for food-producing animals. (a) FDA may establish a safe...

Communication Apprehension and Maths Anxiety as Barriers to Communication and Numeracy Skills Development in Accounting and Business Education

ERIC Educational Resources Information Center

Joyce, John; Hassall, Trevor; Montano, Jose Luis Arquero; Anes, Jose Antonio Donoso

2006-01-01

Purpose: To establish the existence of barriers to communication and numeracy skills development and to establish the levels of these exhibited by accounting and business students at the commencement of their courses in higher education. Design/methodology/approach: Uses questionnaires to establish the levels of communication apprehension (CA) and…

Memorandum of the Establishment of Cleanup Levels for CERCLA Sites with Radioactive Contamination

EPA Pesticide Factsheets

This memorandum presents clarifying guidance for establishing protective cleanup levels for radioactive contamination at Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) sites.

Fluctuations of ground-water levels in Lee County, Florida, in 1975 water year

USGS Publications Warehouse

O'Donnell, T. H.

1977-01-01

During the 1975 water year, rainfall was about average at Page Field, Florida, and from 20-25 percent below average at Lehigh Acres and Sanibel Island. Water levels were monitored in 57 observation wells in Lee County, Florida. Of the 23 wells that tap the water-table aquifer, one record high and 5 record low water levels were established. Record low water levels were established in 5 of 20 wells that tap the sandstone aquifer and in 1 of 10 wells that tap the upper Hawthorn aquifer. A record high water level was established in 1 of 3 wells that tap the lower Hawthorn aquifer. (Woodard-USGS)

Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration

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

Sheard, Michael A., E-mail: msheard@chla.usc.edu; Ghent, Matthew V., E-mail: mattghent@gmail.com; Cabral, Daniel J., E-mail: dcabral14@gmail.com

2015-05-15

Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival,more » expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. - Highlights: • Establishing new ALL cell lines in 5% oxygen resulted in higher glycolytic expression and function. • Establishing new ALL cell lines in 5% oxygen resulted in higher proliferation and lower cell death. • The divergent metabolic phenotypes selected in 5% and 20% oxygen are semi-permanent.« less

40 CFR Appendix Ix to Part 261 - Wastes Excluded Under §§ 260.20 and 260.22

Code of Federal Regulations, 2010 CFR

2010-07-01

... delisting level established in Condition (1), or is at a level in the ground water or soil higher than the... violation of the delisting petition and a possible revocation of the decision. American Steel Cord... established in Condition (1), or is at a level in the ground water or soil higher than the health based level...

45 CFR 400.101 - Financial eligibility standards.

Code of Federal Regulations, 2014 CFR

2014-10-01

... established at up to 200% of the national poverty level; and (b) In States without a medically needy program... eligibility standard established at up to 200% of the national poverty level. [54 FR 5480, Feb. 3, 1989, as...

45 CFR 400.101 - Financial eligibility standards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... established at up to 200% of the national poverty level; and (b) In States without a medically needy program... eligibility standard established at up to 200% of the national poverty level. [54 FR 5480, Feb. 3, 1989, as...

45 CFR 400.101 - Financial eligibility standards.

Code of Federal Regulations, 2013 CFR

2013-10-01

... established at up to 200% of the national poverty level; and (b) In States without a medically needy program... eligibility standard established at up to 200% of the national poverty level. [54 FR 5480, Feb. 3, 1989, as...

45 CFR 400.101 - Financial eligibility standards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... established at up to 200% of the national poverty level; and (b) In States without a medically needy program... eligibility standard established at up to 200% of the national poverty level. [54 FR 5480, Feb. 3, 1989, as...

45 CFR 400.101 - Financial eligibility standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... established at up to 200% of the national poverty level; and (b) In States without a medically needy program... eligibility standard established at up to 200% of the national poverty level. [54 FR 5480, Feb. 3, 1989, as...

[Establishment of oxygen and glucose deprive model of in vitro cultured hippocampal neuron and effect of ligustrazine on intracellular Ca+ level in model neurons].

PubMed

Wan, Hai-tong; Wang, Yu; Yang, Jie-hong

2007-03-01

To establish the oxygen and glucose deprive (OGD) model in cultured hippocampal neuron and study the effect of ligustrazine on intracellular Ca2+ level in the model neurons. The OGD model was established in cultured hippocampal neuron, and the intracellular Ca2+ level in it was detected by laser scanning confocal microscope (LSCM). The OGD model was successfully established in cultured hippocampal neurons; the intracellular Ca2+ level in the OGD model group was significantly higher than that in the blank control group (P < 0.05), and that in the nemodipine and high and medium dosage of ligustrazine treated groups was lower than that in the OGD model group (P < 0.05). Intracellular Ca2+ overload occurs in OGD model neuron, which could be antagonized by ligustrazine, indicating that ligustrazine has a protective effect on hippocampal neuron from hypoxic-ischemic injury.

Provisional standards of radiation safety during flights

NASA Technical Reports Server (NTRS)

1977-01-01

Radiation effects during space flights are discussed in the context of the sources and dangers of such radiation and the radiobiological prerequisites for establishing safe levels of radiation dosage. Standard safe levels of radiation during space flight are established.

Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration.

PubMed

Sheard, Michael A; Ghent, Matthew V; Cabral, Daniel J; Lee, Joanne C; Khankaldyyan, Vazgen; Ji, Lingyun; Wu, Samuel Q; Kang, Min H; Sposto, Richard; Asgharzadeh, Shahab; Reynolds, C Patrick

2015-05-15

Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. Copyright © 2015. Published by Elsevier Inc.

40 CFR 434.71 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... determines that it is not feasible for a remining operator to re-establish baseline pollutant levels in accordance with the statistical procedures contained in Appendix B of this part, pre-existing discharge limitations at existing remining operations shall remain subject to baseline pollutant levels established...

EVALUATION OF LITERATURE ESTABLISHING SCREENING LEVELS FOR TERRESTRIAL PLANTS/INVERTEBRATES

EPA Science Inventory

Scientific publications often lack key information on experimental design or do not follow appropriate test methods and therefore cannot be used in deriving reliable benchmarks. Risk based soil screening levels (Eco-SSLs) are being established for chemicals of concern to terrestr...

Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

PubMed

Sonobe, Yoshifumi; Ghadge, Ghanashyam; Masaki, Katsuhisa; Sendoel, Ataman; Fuchs, Elaine; Roos, Raymond P

2018-08-01

Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G 4 C 2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G 4 C 2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. Copyright © 2018 Elsevier Inc. All rights reserved.

ALS-linked mutant SOD1 proteins promote Aβ aggregates in ALS through direct interaction with Aβ.

PubMed

Jang, Ja-Young; Cho, Hyungmin; Park, Hye-Yoon; Rhim, Hyangshuk; Kang, Seongman

2017-11-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons. Aggregation of ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) is a hallmark of a subset of familial ALS (fALS). Recently, intracellular amyloid-β (Aβ) is detected in motor neurons of both sporadic and familial ALS. We have previously shown that intracellular Aβ specifically interacts with G93A, an ALS-linked SOD1 mutant. However, little is known about the pathological and biological effect of this interaction in neurons. In this study, we have demonstrated that the Aβ-binding region is exposed on the SOD1 surface through the conformational changes due to misfolding of SOD1. Interestingly, we found that the intracellular aggregation of Aβ is enhanced through the direct interaction of Aβ with the Aβ-binding region exposed to misfolded SOD1. Ultimately, increased Aβ aggregation by this interaction promotes neuronal cell death. Consistent with this result, Aβ aggregates was three-fold higher in the brains of G93A transgenic mice than those of non Tg. Our study provides the first direct evidence that Aβ, an AD-linked factor, is associated to the pathogenesis of ALS and provides molecular clues to understand common aggregation mechanisms in the pathogenesis of neurodegenerative diseases. Furthermore, it will provide new insights into the development of therapeutic approaches for ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

7 CFR 760.633 - 2008 SURE guarantee calculation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... percent of the NAP established price for the crop; (2) Coverage level in § 760.631(a)(1)(iv) is 70 percent... the NAP established price for the crop; and (ii) Coverage level in §§ 760.631(a)(1)(iv) and 760.634(a...

41 CFR 102-80.115 - Is there more than one option for establishing that an equivalent level of safety exists?

Code of Federal Regulations, 2010 CFR

2010-07-01

... equivalent level of safety. (c) As a third option, other technical analysis procedures, as approved by the... Equivalent Level of Safety Analysis § 102-80.115 Is there more than one option for establishing that an... areas of safety. Available safe egress times would be developed based on analysis of a number of assumed...

Systems Security Engineering Capability Maturity Model SSE-CMM Model Description Document

DTIC Science & Technology

1999-04-01

management is the process of accessing and quantifying risk , and establishing an acceptable level of risk for the organization. Managing risk is an...Process of assessing and quantifying risk and establishing acceptable level of risk for the organization. [IEEE 13335-1:1996] Security Engineering

Characteristics of Knowledge Interconnectedness in Teaching

ERIC Educational Resources Information Center

Antonijevic, Radovan

2006-01-01

The subject of the paper presents establishing basic characteristics, forms and levels of knowledge interconnectedness in teaching, especially in mathematics and biology teaching. The analysis was realized by considering basic theoretical views in this field, as well as by establishing features and levels of knowledge interconnectedness in the…

7 CFR 1450.213 - Levels and rates for establishment payments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Levels and rates for establishment payments. 1450.213 Section 1450.213 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM...

7 CFR 1450.213 - Levels and rates for establishment payments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Levels and rates for establishment payments. 1450.213 Section 1450.213 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE PROGRAM...

USING RESPONSES OF OYSTERS IN ESTABLISHING MINIMUM FLOWS AND LEVELS IN THE CALOOSAHATCHEE ESTUARY, FLORIDA

EPA Science Inventory

Volety, Aswani K., S. Gregory Tolley and James T. Winstead. 2002. Using Responses of Oysters in Establishing Minimum Flows and Levels in the Caloosahatchee Estuary, Florida (Abstract). Presented at the 6th International Conference on Shellfish Restoration, 20-24 November 2002, Ch...

40 CFR 60.102a - Emissions limitations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the initial performance test, required by § 60.8, is completed, but not later than 60 days after... fall below the level established during the most recent performance test; and (ii) The daily average exhaust coke burn-off rate must not exceed the level established during the most recent performance test...

40 CFR 60.102a - Emissions limitations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the initial performance test, required by § 60.8, is completed, but not later than 60 days after... fall below the level established during the most recent performance test; and (ii) The daily average exhaust coke burn-off rate must not exceed the level established during the most recent performance test...

77 FR 25721 - Small Entity Compliance Guide: Bottled Water: Quality Standard: Establishing an Allowable Level...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

...] Small Entity Compliance Guide: Bottled Water: Quality Standard: Establishing an Allowable Level for di(2-ethylhexyl)phthalate; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled...

20 CFR 416.1337 - Exceptions to the continuation of previously established payment level.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Exceptions to the continuation of previously established payment level. 416.1337 Section 416.1337 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Suspensions and Terminations § 416.1337...

Attending surgeon burnout and satisfaction with the establishment of a regional acute care surgical service

PubMed Central

Helewa, Ramzi M.; Kholdebarin, Ramin; Hochman, David J.

2012-01-01

Background Establishment of the Acute Care Surgical Service (ACSS) has dramatically changed the management of acute, nontrauma surgical patients in Winnipeg, Manitoba. Its formation was partially driven by increasing strain on surgeons and surgical services. We sought to determine surgeon level of burnout and satisfaction with the ACSS. Methods All Winnipeg ACSS surgeons were mailed surveys. Burnout was established using the Maslach Burnout Inventory Human Services Survey. Satisfaction was ascertained with a series of questions. Results We attained a response rate of 76%. Most surgeons were married men with children. A burnout level of 61% was determined. Although most surgeons felt the ACSS was a positive change in their careers, they felt that operating room accessibility and teaching opportunities were lacking. Conclusion Although a high level of burnout exists among ACSS surgeons, most are satisfied with its establishment. Factors such as operating room accessibility and teaching opportunities must be addressed. PMID:22854111

Business establishment survival and transportation level of service.

DOT National Transportation Integrated Search

2016-06-15

In this project we seek to fill a gap in empirically supported knowledge linking the survival and : economic success of business establishments to local land use and access to the transportation : system that serves these establishments. We investiga...

5 CFR 319.203 - Establishment of positions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Establishment of positions. 319.203 Section 319.203 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment...

The Feasibility of Establishing Highway Safety Manpower Development and Research Centers at University-Level Institutions. Final Report, Volume I: Study Report.

ERIC Educational Resources Information Center

Chorness, Maury H.; And Others

To examine the feasibility of establishing Highway Safety Manpower Development and Research (HSMDR) Centers at university-level institutions which would produce three types of manpower--safety specialists, safety professionals, and research manpower, previous National Highway Safety Bureau research studies and approximately 50 federally funded…

Doing the right thing without being told: joint effects of initiative climate and general self-efficacy on employee proactive customer service performance.

PubMed

Raub, Steffen; Liao, Hui

2012-05-01

We developed and tested a cross-level model of the antecedents and outcomes of proactive customer service performance. Results from a field study of 900 frontline service employees and their supervisors in 74 establishments of a multinational hotel chain located in Europe, the Middle East, Africa, and Asia demonstrated measurement equivalence and suggested that, after controlling for service climate, initiative climate at the establishment level and general self-efficacy at the individual level predicted employee proactive customer service performance and interacted in a synergistic way. Results also showed that at the establishment level, controlling for service climate and collective general service performance, initiative climate was positively and indirectly associated with customer service satisfaction through the mediation of aggregated proactive customer service performance. We discuss important theoretical and practical implications of these findings. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Clinical correlates of vitamin D deficiency in established psychosis.

PubMed

Lally, J; Gardner-Sood, P; Firdosi, M; Iyegbe, C; Stubbs, B; Greenwood, K; Murray, R; Smith, S; Howes, O; Gaughran, F

2016-03-22

Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L). The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p < 0.002), triglycerides (r = -0.160, p = 0.024), total cholesterol (r = -0.144, p = 0.043), fasting glucose (r = -0.191, p = 0.007), HbA1c (r = -0.183, p = 0.01), and serum CRP levels (r = -0.211, p = 0.003) and were linked to the presence of metabolic syndrome. This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010.

Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 544: Cellars, Mud Pits, and Oil Spills, Nevada Test Site, Nevada, Revision 0

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

Mark Krauss

2010-07-01

This Streamlined Approach for Environmental Restoration (SAFER) Plan addresses the actions needed to achieve closure for Corrective Action Unit (CAU) 544, Cellars, Mud Pits, and Oil Spills, identified in the Federal Facility Agreement and Consent Order (FFACO). Corrective Action Unit 544 comprises the following 20 corrective action sites (CASs) located in Areas 2, 7, 9, 10, 12, 19, and 20 of the Nevada Test Site (NTS): • 02-37-08, Cellar & Mud Pit • 02-37-09, Cellar & Mud Pit • 07-09-01, Mud Pit • 09-09-46, U-9itsx20 PS #1A Mud Pit • 10-09-01, Mud Pit • 12-09-03, Mud Pit • 19-09-01, Mudmore » Pits (2) • 19-09-03, Mud Pit • 19-09-04, Mud Pit • 19-25-01, Oil Spill • 19-99-06, Waste Spill • 20-09-01, Mud Pits (2) • 20-09-02, Mud Pit • 20-09-03, Mud Pit • 20-09-04, Mud Pits (2) • 20-09-06, Mud Pit • 20-09-07, Mud Pit • 20-09-10, Mud Pit • 20-25-04, Oil Spills • 20-25-05, Oil Spills This plan provides the methodology for field activities needed to gather the necessary information for closing each CAS. There is sufficient information and process knowledge from historical documentation and investigations of similar sites regarding the expected nature and extent of potential contaminants to recommend closure of CAU 544 using the SAFER process. Using the approach approved for previous mud pit investigations (CAUs 530–535), 14 mud pits have been identified that • are either a single mud pit or a system of mud pits, • are not located in a radiologically posted area, and • have no evident biasing factors based on visual inspections. These 14 mud pits are recommended for no further action (NFA), and further field investigations will not be conducted. For the sites that do not meet the previously approved closure criteria, additional information will be obtained by conducting a field investigation before selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible recommendation for closure of the remaining CASs in CAU 544. This will be presented in a closure report (CR) that will be prepared and submitted to the Nevada Division of Environmental Protection (NDEP) for review and approval. The sites will be investigated based on the data quality objectives (DQOs) developed on April 27, 2010, by representatives of NDEP and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO). The DQO process was used to identify and define the type, amount, and quality of data needed to determine and implement appropriate corrective actions for each CAS in CAU 544. The DQO process developed for this CAU identified the following expected closure options: (1) investigation and confirmation that no contamination exists above the final action levels (FALs) leading to an NFA declaration, (2) characterization of the nature and extent of contamination leading to closure in place with use restrictions, (3) clean closure by remediation and verification, (4) closure in place with use restrictions with no investigation if CASs are in crater areas that have been determined to be unsafe to enter, or (5) NFA if the mud pit CAS meets the criteria established during the CAUs 530–535 SAFER investigation. The following summarizes the SAFER activities that will support the closure of CAU 544: • Perform visual inspection of all CASs. • Perform site preparation activities (e.g., utilities clearances, construction of temporary site exclusion zones). • Removal of easily managed, nonhazardous, and nonradioactive debris, including vegetation (e.g., tumbleweeds), at various CASs that interfere with sampling, if required to inspect soil surface or collect soil sample. • Collect environmental samples from designated target populations (e.g., mud pits, cellars, stained soil) to confirm or disprove the presence of contaminants of concern (COCs) as necessary to supplement existing information. • If no COCs are present at a CAS, establish NFA as the corrective action. • If COCs exist, collect environmental samples from designated target populations (e.g., clean soil adjacent to contaminated soil) and submit for laboratory analyses to define the extent of COC contamination. • If a COC is present at a CAS, either - Establish clean closure as the corrective action. The material to be remediated will be removed, disposed of as waste, and verification samples will be collected from remaining soil, or - Establish closure in place as the corrective action and implement the appropriate use restrictions. • Confirm the preferred closure option is sufficient to protect human health and the environment.« less

76 FR 8768 - Establishment of the Wildland Fire Executive Council

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

... DEPARTMENT OF THE INTERIOR Office of the Secretary Establishment of the Wildland Fire Executive... are announcing the establishment of the Wildland Fire Executive Council (WFEC). The purpose of the WFEC is to provide advice on the coordinated national level wildland fire policy leadership, direction...

A Framework for an Institutional High Level Security Policy for the Processing of Medical Data and their Transmission through the Internet

PubMed Central

Pangalos, George

2001-01-01

Background The Internet provides many advantages when used for interaction and data sharing among health care providers, patients, and researchers. However, the advantages provided by the Internet come with a significantly greater element of risk to the confidentiality, integrity, and availability of information. It is therefore essential that Health Care Establishments processing and exchanging medical data use an appropriate security policy. Objective To develop a High Level Security Policy for the processing of medical data and their transmission through the Internet, which is a set of high-level statements intended to guide Health Care Establishment personnel who process and manage sensitive health care information. Methods We developed the policy based on a detailed study of the existing framework in the EU countries, USA, and Canada, and on consultations with users in the context of the Intranet Health Clinic project. More specifically, this paper has taken into account the major directives, technical reports, law, and recommendations that are related to the protection of individuals with regard to the processing of personal data, and the protection of privacy and medical data on the Internet. Results We present a High Level Security Policy for Health Care Establishments, which includes a set of 7 principles and 45 guidelines detailed in this paper. The proposed principles and guidelines have been made as generic and open to specific implementations as possible, to provide for maximum flexibility and adaptability to local environments. The High Level Security Policy establishes the basic security requirements that must be addressed to use the Internet to safely transmit patient and other sensitive health care information. Conclusions The High Level Security Policy is primarily intended for large Health Care Establishments in Europe, USA, and Canada. It is clear however that the general framework presented here can only serve as reference material for developing an appropriate High Level Security Policy in a specific implementation environment. When implemented in specific environments, these principles and guidelines must also be complemented by measures, which are more specific. Even when a High Level Security Policy already exists in an institution, it is advisable that the management of the Health Care Establishment periodically revisits it to see whether it should be modified or augmented. PMID:11720956

A framework for an institutional high level security policy for the processing of medical data and their transmission through the Internet.

PubMed

Ilioudis, C; Pangalos, G

2001-01-01

The Internet provides many advantages when used for interaction and data sharing among health care providers, patients, and researchers. However, the advantages provided by the Internet come with a significantly greater element of risk to the confidentiality, integrity, and availability of information. It is therefore essential that Health Care Establishments processing and exchanging medical data use an appropriate security policy. To develop a High Level Security Policy for the processing of medical data and their transmission through the Internet, which is a set of high-level statements intended to guide Health Care Establishment personnel who process and manage sensitive health care information. We developed the policy based on a detailed study of the existing framework in the EU countries, USA, and Canada, and on consultations with users in the context of the Intranet Health Clinic project. More specifically, this paper has taken into account the major directives, technical reports, law, and recommendations that are related to the protection of individuals with regard to the processing of personal data, and the protection of privacy and medical data on the Internet. We present a High Level Security Policy for Health Care Establishments, which includes a set of 7 principles and 45 guidelines detailed in this paper. The proposed principles and guidelines have been made as generic and open to specific implementations as possible, to provide for maximum flexibility and adaptability to local environments. The High Level Security Policy establishes the basic security requirements that must be addressed to use the Internet to safely transmit patient and other sensitive health care information. The High Level Security Policy is primarily intended for large Health Care Establishments in Europe, USA, and Canada. It is clear however that the general framework presented here can only serve as reference material for developing an appropriate High Level Security Policy in a specific implementation environment. When implemented in specific environments, these principles and guidelines must also be complemented by measures, which are more specific. Even when a High Level Security Policy already exists in an institution, it is advisable that the management of the Health Care Establishment periodically revisits it to see whether it should be modified or augmented.

Effective Utilization of Carbohydrate in Corncob to Synthesize Furfuralcohol by Chemical-Enzymatic Catalysis in Toluene-Water Media.

PubMed

Xue, Xin-Xia; Di, Jun-Hua; He, Yu-Cai; Wang, Bing-Qian; Ma, Cui-Luan

2018-05-01

In this study, carbohydrates (cellulose plus hemicellulose) in corncob were effectively converted furfuralcohol (FOL) via chemical-enzymatic catalysis in a one-pot manner. After corncob (2.5 g, dry weight) was pretreated with 0.5 wt% oxalic acid, the obtained corncob-derived xylose (19.8 g/L xylose) could be converted to furfural at 60.1% yield with solid acid catalyst SO 4 2- /SnO 2 -attapulgite (3.6 wt% catalyst loading) in the water-toluene (3:1, v/v) at 170 °C for 20 min. Moreover, the oxalic acid-pretreated corncob residue (1.152 g, dry weight) was enzymatically hydrolyzed to 0.902 g glucose and 0.202 g arabinose. Using the corncob-derived glucose (1.0 mM glucose/mM furfural) as cosubstrate, the furfural liquor (48.3 mM furfural) was successfully biotransformed to FOL by recombinant Escherichia coli CCZU-A13 cells harboring an NADH-dependent reductase (SsCR) in the water-toluene (4:1, v/v) under the optimum conditions (50 mM PEG-6000, 0.2 mM Zn 2+ , 0.1 g wet cells/mL, 30 °C, pH 6.5). After the bioreduction for 2 h, FAL was completely converted to FOL. The FOL yield was obtained at 0.11 g FOL/g corncob. Clearly, this one-pot synthesis strategy shows high potential application for the effective synthesis of FOL.

Fractionation of fulvic acid by iron and aluminum oxides: influence on copper toxicity to Ceriodaphnia dubia

USGS Publications Warehouse

Smith, Kathleen S.; Ranville, James F.; Lesher, Emily K.; Diedrich, Daniel J.; McKnight, Diane M.; Sofield, Ruth M.

2014-01-01

This study examines the effect on aquatic copper toxicity of the chemical fractionation of fulvic acid (FA) that results from its association with iron and aluminum oxyhydroxide precipitates. Fractionated and unfractionated FAs obtained from streamwater and suspended sediment were utilized in acute Cu toxicity tests on ,i>Ceriodaphnia dubia. Toxicity test results with equal FA concentrations (6 mg FA/L) show that the fractionated dissolved FA was 3 times less effective at reducing Cu toxicity (EC50 13 ± 0.6 μg Cu/L) than were the unfractionated dissolved FAs (EC50 39 ± 0.4 and 41 ± 1.2 μg Cu/L). The fractionation is a consequence of preferential sorption of molecules having strong metal-binding (more aromatic) moieties to precipitating Fe- and Al-rich oxyhydroxides, causing the remaining dissolved FA to be depleted in these functional groups. As a result, there is more bioavailable dissolved Cu in the water and hence greater potential for Cu toxicity to aquatic organisms. In predicting Cu toxicity, biotic ligand models (BLMs) take into account dissolved organic carbon (DOC) concentration; however, unless DOC characteristics are accounted for, model predictions can underestimate acute Cu toxicity for water containing fractionated dissolved FA. This may have implications for water-quality criteria in systems containing Fe- and Al-rich sediment, and in mined and mineralized areas in particular. Optical measurements, such as specific ultraviolet absorbance at 254 nm (SUVA254), show promise for use as spectral indicators of DOC chemical fractionation and inferred increased Cu toxicity.

Deciphering amyotrophic lateral sclerosis: what phenotype, neuropathology and genetics are telling us about pathogenesis.

PubMed

Ravits, John; Appel, Stanley; Baloh, Robert H; Barohn, Richard; Brooks, Benjamin Rix; Elman, Lauren; Floeter, Mary Kay; Henderson, Christopher; Lomen-Hoerth, Catherine; Macklis, Jeffrey D; McCluskey, Leo; Mitsumoto, Hiroshi; Przedborski, Serge; Rothstein, Jeffrey; Trojanowski, John Q; van den Berg, Leonard H; Ringel, Steven

2013-05-01

Amyotrophic lateral sclerosis (ALS) is characterized phenotypically by progressive weakness and neuropathologically by loss of motor neurons. Phenotypically, there is marked heterogeneity. Typical ALS has mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Primary lateral sclerosis has predominant UMN involvement. Progressive muscular atrophy has predominant LMN involvement. Bulbar and limb ALS have predominant regional involvement. Frontotemporal dementia has significant cognitive and behavioral involvement. These phenotypes can be so distinctive that they would seem to have differing biology. However, they cannot be distinguished, at least neuropathologically or genetically. In sporadic ALS (SALS), they are mostly characterized by ubiquitinated cytoplasmic inclusions of TDP-43. In familial ALS (FALS), where phenotypes are indistinguishable from SALS and similarly heterogeneous, each mutated gene has its own genetic and molecular signature. Overall, since the same phenotypes can have multiple causes including different gene mutations, there must be multiple molecular mechanisms causing ALS - and ALS is a syndrome. Since, however, multiple phenotypes can be caused by one single gene mutation, a single molecular mechanism can cause heterogeneity. What the mechanisms are remain unknown, but active propagation of the pathology neuroanatomically seems to be a principal component. Leading candidate mechanisms include RNA processing, cell-cell interactions between neurons and non-neuronal neighbors, focal seeding from a misfolded protein that has prion-like propagation, and fatal errors introduced during neurodevelopment of the motor system. If fundamental mechanisms could be identified and understood, ALS therapy could rationally target progression and stop the disease - a goal that seems increasingly achievable.

Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis?

PubMed

Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Rouleau, Guy A

2007-12-01

The identification in 1993 of superoxide dismutase-1 (SOD1) mutations as the cause of 10 to 20% of familial amyotrophic lateral sclerosis cases, which represents 1 to 2% of all amyotrophic lateral sclerosis (ALS) cases, prompted a substantial amount of research into the mechanisms of SOD1-mediated toxicity. Recent experiments have demonstrated that oxidation of wild-type SOD1 leads to its misfolding, causing it to gain many of the same toxic properties as mutant SOD1. In vitro studies of oxidized/misfolded SOD1 and in vivo studies of misfolded SOD1 have indicated that these protein species are selectively toxic to motor neurons, suggesting that oxidized/misfolded SOD1 could lead to ALS even in individuals who do not carry an SOD1 mutation. It has also been reported that glial cells secrete oxidized/misfolded mutant SOD1 to the extracellular environment, where it can trigger the selective death of motor neurons, offering a possible explanation for the noncell autonomous nature of mutant SOD1 toxicity and the rapid progression of disease once the first symptoms develop. Therefore, considering that sporadic (SALS) and familial ALS (FALS) cases are clinically indistinguishable, the toxic properties of mutated SOD1 are similar to that of oxidized/misfolded wild-type SOD1 (wtSOD1), and secreted/extracellular misfolded SOD1 is selectively toxic to motor neurons, we propose that oxidized/misfolded SOD1 is the cause of most forms of classic ALS and should be a prime target for the design of ALS treatments.

Trailblazers: An Examination of Community College Black Women in Senior Level Administrator Roles--Their Stories through Their Eyes

ERIC Educational Resources Information Center

Williams-Bruce, Tameka Lazette

2013-01-01

This paper explores how Black women who work in senior level administrative positions at community colleges were able to establish successful career paths. The literature review draws from the theoretical framework of critical race theory, the Black feminist thought, and critical race feminism. The use of counter-stories establishes a platform for…

49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

Code of Federal Regulations, 2013 CFR

2013-10-01

... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not....410. (7) Establish a continuing public education program in compliance with § 195.440 before...

49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

Code of Federal Regulations, 2014 CFR

2014-10-01

... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not....410. (7) Establish a continuing public education program in compliance with § 195.440 before...

49 CFR 195.11 - What is a regulated rural gathering line and what requirements apply?

Code of Federal Regulations, 2012 CFR

2012-10-01

... established under § 195.406 corresponding to— (i) A stress level greater than 20-percent of the specified minimum yield strength of the line pipe; or (ii) If the stress level is unknown or the pipeline is not....410. (7) Establish a continuing public education program in compliance with § 195.440 before...

Over-Education, Under-Education and Credentialism in the Australian Labour Market. NCVER Monograph Series 10/2012

ERIC Educational Resources Information Center

Dockery, Alfred Michael; Miller, Paul W.

2012-01-01

It is well established that workers with more years of education earn higher wages. By establishing a reference or "required" level of education for a worker's occupation, it is possible to decompose an individual's actual level of education into years of required education and years of over-education or under-education relative to that…

25 CFR 1000.106 - Once a Tribe/Consortium establishes a base budget, are funding amounts renegotiated each year?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Bureau of Indian Affairs Programs Establishing Self-Governance Base Budgets § 1000.106 Once a Tribe... renegotiates funding levels: (a) It must negotiate all funding levels in the AFA using the process for determining residuals and funding amounts on the same basis as other Tribes; and (b) It is eligible for...

Iranian Special Library Standards.

ERIC Educational Resources Information Center

Harvey, John F.

The purposes of these standards are: (1) to suggest the steps necessary for the establishment of special libraries; (2) for those recently established, to suggest the steps necessary to achieve satisfactory performance levels in all areas, and finally, (3) for well established libraries, to suggest the steps necessary to achieve excellence. These…

Is Set Shifting Really Impaired in Trait Anxiety? Only When Switching Away from an Effortfully Established Task Set

PubMed Central

Gustavson, Daniel E.; Altamirano, Lee J.; Johnson, Daniel P.; Whisman, Mark A.; Miyake, Akira

2016-01-01

The current study investigated whether trait anxiety was systematically related to task-set shifting performance, using a task-switching paradigm in which one task was more attentionally demanding than the other. Specifically, taking advantage of a well-established phenomenon known as asymmetric switch costs, we tested the hypothesis that the association between trait anxiety and task-set shifting is most clearly observed when individuals must switch away from a more attentionally demanding task for which it was necessary to effortfully establish an appropriate task set. Ninety-one young adults completed an asymmetric switching task and trait-level mood questionnaires. Results indicated that higher levels of trait anxiety were systematically associated with greater asymmetry in reaction-time (RT) switch costs. Specifically, the RT costs for switching from the more attentionally demanding task to the less demanding task were significantly greater with higher levels of trait anxiety, whereas the RT costs for switching in the opposite direction were not significantly associated with trait anxiety levels. Further analyses indicated that these associations were not attributable to comorbid dysphoria or worry. These results suggest that levels of trait anxiety may not be related to general set-shifting ability per se, but, rather, that anxiety-specific effects may primarily be restricted to when one must efficiently switch away from (or let go of) an effortfully established task set. PMID:27429194

40 CFR Table 3 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Mercury Emission Limits and Boilers and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... minimum pressure drop and liquid flow-rate at or above the operating levels established during the... leak detection system alarm does not sound more than 5 percent of the operating time during a 6-month... control Maintain the minimum sorbent or carbon injection rate at or above the operating levels established...

40 CFR Table 3 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Mercury Emission Limits and Boilers and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... minimum pressure drop and liquid flow-rate at or above the operating levels established during the... leak detection system alarm does not sound more than 5 percent of the operating time during a 6-month... control Maintain the minimum sorbent or carbon injection rate at or above the operating levels established...

Clinical and epidemiological aspects of cornea transplant patients of a reference hospital.

PubMed

Cruz, Giovanna Karinny Pereira; Azevedo, Isabelle Campos de; Carvalho, Diana Paula de Souza Rego Pinto; Vitor, Allyne Fortes; Santos, Viviane Euzébia Pereira; Ferreira, Marcos Antonio

2017-06-08

clinically characterizing cornea transplant patients and their distribution according to indicated and post-operative conditions of cornea transplantation, as well as estimating the average waiting time. a cross-sectional, descriptive and analytical study performed for all cornea transplants performed at a reference service (n=258). Data were analyzed using Statistical Package for the Social Sciences, version 20.0. the main indicator for cornea transplant was keratoconus. The mean waiting time for the transplant was approximately 5 months and 3 weeks for elective transplants and 9 days for urgent cases. An association between the type of corneal disorder with gender, age, previous surgery, eye classification, glaucoma and anterior graft failure were found. keratoconus was the main indicator for cornea transplant. Factors such as age, previous corneal graft failure (retransplantation), glaucoma, cases of surgeries prior to cornea transplant (especially cataract surgery) may be related to the onset corneal endothelium disorders. caracterizar clínicamente los pacientes trasplantados y su distribución, con descripción de las condiciones indicadoras y posoperatorias de los trasplantes de córneas, así como estimar el tiempo promedio en la fila de espera. estudio epidemiológico, transversal, descriptivo y analítico, realizado con todos los trasplantes de córnea realizados en un servicio de referencia (n=258). Los datos fueron analizados con el software Statistical Package for the Social Sciences, versión 20.0. la principal condición indicadora para el trasplante de córnea fue el queratocono. El tiempo promedio en fila de espera para realización del trasplante fue de aproximadamente 5 meses y tres semanas, para trasplantes electivos y de 9 días para los casos de urgencia. Existió asociación entre el tipo de disturbio de la córnea con: sexo, intervalo etario, cirugía previa, clasificación del ojo, glaucoma y rechazo del injerto anterior. el queratocono fue la principal condición indicadora para el trasplante de córnea. Factores como: edad; rechazo de injerto de córnea anterior (retrasplante); glaucoma; y casos de cirugías previas al trasplante de córnea, destacando la cirugía de catarata, pueden estar relacionados con el aparecimiento de disturbios de la córnea de tipo endotelial. caracterizar clinicamente os pacientes transplantados e sua distribuição com descrição das condições indicadoras e pós-operatórias dos transplantes de córneas, bem como estimar o tempo médio em fila de espera. estudo epidemiológico, transversal, descritivo e analítico, realizado com todos os transplantes de córnea realizados em um serviço de referência (n= 258). Os dados foram analisados com uso do software Statistical Package for the Social Sciences, versão 20.0. a principal condição indicadora para o transplante de córnea foi o ceratocone. O tempo médio em fila de espera para realização do transplante foi de aproximadamente 5 meses e três semanas para o transplantes eletivos e 9 dias para os casos de urgência. Existiu associação entre o tipo de distúrbio da córnea com sexo, faixa etária, cirurgia prévia, classificação do olho, glaucoma e falência do enxerto anterior. o ceratocone foi a principal condição indicadora para o transplante de córnea. Fatores como idade, falência de enxerto corneano anterior (retransplante), glaucoma, casos de cirurgias prévias ao transplante de córnea, com destaque para a cirurgia de catarata, podem estar relacionados com o aparecimento de distúrbios da córnea do tipo endotelial.

Superfund record of decision (EPA Region 3): Stanley Kessler Superfund Site, King of Prussia, PA, September 1994

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

Not Available

1994-09-29

This decision document presents the final selected remedial action for the Stanley Kessler Superfund Site (the Site). The selected remedy for the Site will restore contaminated ground water to its beneficial use by cleaning up the ground water to background levels as established by EPA or the appropriate Maximum Contaminant Levels or non-zero Maximum Contaminant Level Goals established under the Federal Safe Drinking Water Act whichever is more stringent. The selected remedy is the only planned action for the Site.

A Method to Establish Stimulus Control and Compliance with Instructions

ERIC Educational Resources Information Center

Borgen, John G.; Mace, F. Charles; Cavanaugh, Brenna M.; Shamlian, Kenneth; Lit, Keith R.; Wilson, Jillian B.; Trauschke, Stephanie L.

2017-01-01

We evaluated a unique procedure to establish compliance with instructions in four young children diagnosed with autism spectrum disorder (ASD) who had low levels of compliance. Our procedure included methods to establish a novel therapist as a source of positive reinforcement, reliably evoke orienting responses to the therapist, increase the…

Experimental evidence of human recreational disturbance effects on bird-territory establishment.

PubMed

Bötsch, Yves; Tablado, Zulima; Jenni, Lukas

2017-07-12

The worldwide increase in human outdoor activities raises concerns for wildlife. Human disturbances, even at low levels, are likely to impact species during sensitive periods of the annual cycle. However, experimental studies during the putative sensitive period of territory establishment of birds which not only investigate low disturbance levels, but which also exclude the effect of habitat modification (e.g. walking trails) are lacking. Here, we experimentally disturbed birds in forest plots by walking through twice a day during territory establishment. Later we compared the breeding bird community of experimentally disturbed plots with that of undisturbed control plots. We discovered that the number of territories (-15.0%) and species richness (-15.2%) in disturbed plots were substantially reduced compared with control plots. Species most affected included those sensitive to human presence (assessed by flight-initiation distances), open-cup nesters and above-ground foragers. Long-distance migrants, however, were unaffected due to their arrival after experimental disturbance took place. These findings highlight how territory establishment is a sensitive period for birds, when even low levels of human recreation may be perceived as threatening, and alter settlement decisions. This can have important implications for the conservation of species, which might go unnoticed when focusing only on already established birds. © 2017 The Author(s).

Impact of Prematurity and Perinatal Antibiotics on the Developing Intestinal Microbiota: A Functional Inference Study.

PubMed

Arboleya, Silvia; Sánchez, Borja; Solís, Gonzalo; Fernández, Nuria; Suárez, Marta; Hernández-Barranco, Ana M; Milani, Christian; Margolles, Abelardo; de Los Reyes-Gavilán, Clara G; Ventura, Marco; Gueimonde, Miguel

2016-04-29

The microbial colonization of the neonatal gut provides a critical stimulus for normal maturation and development. This process of early microbiota establishment, known to be affected by several factors, constitutes an important determinant for later health. We studied the establishment of the microbiota in preterm and full-term infants and the impact of perinatal antibiotics upon this process in premature babies. To this end, 16S rRNA gene sequence-based microbiota assessment was performed at phylum level and functional inference analyses were conducted. Moreover, the levels of the main intestinal microbial metabolites, the short-chain fatty acids (SCFA) acetate, propionate and butyrate, were measured by Gas-Chromatography Flame ionization/Mass spectrometry detection. Prematurity affects microbiota composition at phylum level, leading to increases of Proteobacteria and reduction of other intestinal microorganisms. Perinatal antibiotic use further affected the microbiota of the preterm infant. These changes involved a concomitant alteration in the levels of intestinal SCFA. Moreover, functional inference analyses allowed for identifying metabolic pathways potentially affected by prematurity and perinatal antibiotics use. A deficiency or delay in the establishment of normal microbiota function seems to be present in preterm infants. Perinatal antibiotic use, such as intrapartum prophylaxis, affected the early life microbiota establishment in preterm newborns, which may have consequences for later health.

SU-E-P-10: Establishment of Local Diagnostic Reference Levels of Routine Exam in Computed Tomography

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

Yeh, M; Wang, Y; Weng, H

Introduction National diagnostic reference levels (NDRLs) can be used as a reference dose of radiological examination can provide radiation dose as the basis of patient dose optimization. Local diagnostic reference levels (LDRLs) by periodically view and check doses, more efficiency to improve the way of examination. Therefore, the important first step is establishing a diagnostic reference level. Computed Tomography in Taiwan had been built up the radiation dose limit value,in addition, many studies report shows that CT scan contributed most of the radiation dose in different medical. Therefore, this study was mainly to let everyone understand DRL’s international status. Formore » computed tomography in our hospital to establish diagnostic reference levels. Methods and Materials: There are two clinical CT scanners (a Toshiba Aquilion and a Siemens Sensation) were performed in this study. For CT examinations the basic recommended dosimetric quantity is the Computed Tomography Dose Index (CTDI). Each exam each different body part, we collect 10 patients at least. Carried out the routine examinations, and all exposure parameters have been collected and the corresponding CTDIv and DLP values have been determined. Results: The majority of patients (75%) were between 60–70 Kg of body weight. There are 25 examinations in this study. Table 1 shows the LDRL of each CT routine examination. Conclusions: Therefore, this study would like to let everyone know DRL’s international status, but also establishment of computed tomography of the local reference levels for our hospital, and providing radiation reference, as a basis for optimizing patient dose.« less

Tendency towards stigmatization of families of a person with autistic spectrum disorders.

PubMed

Milačić-Vidojević, Ivona; Gligorović, Milica; Dragojević, Nada

2014-02-01

Family members experience stigma via their connection with the affected member. Family stigma contains stereotypes of blame, shame and contamination. To establish the tendency towards stigmatization of family members of a person with autistic spectrum disorders (ASD) by a sample of the general public of Belgrade. The sample encompassed 181 participants, of various ages and levels of education, and of different, self-assessed levels of knowledge about autism. The structure of stigmatization of family members of a person with ASD was explored applying the Family Stigma Questionnaire (FSQ) and the Level of Familiarity Questionnaire (LFQ). Analysis of the obtained results established that scores indicating the tendency towards stigmatization were most pronounced for variables connected to blame for deterioration of the condition of the person with autism, contamination of the individual family members by the condition, and to feeling pity for family members of a person with ASD. Statistically significant differences were established when the FSQ scores stigmatizing parents and siblings were compared. Significant differences in stigmatizing stereotypes were established according to gender and level of education, and according to the self-assessment of knowledge about autism and the level of previous contact to persons with mental disorders. Anti-stigma programmes are important especially bearing in mind that participants who self-evaluated as having the least knowledge about ASD demonstrated the highest tendency towards stigmatizing the parents of a person suffering from ASD, and those of lower education demonstrated the highest tendency towards stigmatizing the family members.

Is set shifting really impaired in trait anxiety? Only when switching away from an effortfully established task set.

PubMed

Gustavson, Daniel E; Altamirano, Lee J; Johnson, Daniel P; Whisman, Mark A; Miyake, Akira

2017-02-01

The current study investigated whether trait anxiety was systematically related to task-set shifting performance, using a task-switching paradigm in which 1 task was more attentionally demanding than the other. Specifically, taking advantage of a well-established phenomenon known as asymmetric switch costs, we tested the hypothesis that the association between trait anxiety and task-set shifting is most clearly observed when individuals must switch away from a more attentionally demanding task for which it was necessary to effortfully establish an appropriate task set. Ninety-one young adults completed an asymmetric switching task and trait-level mood questionnaires. Results indicated that higher levels of trait anxiety were systematically associated with greater asymmetry in reaction time (RT) switch costs. Specifically, the RT costs for switching from the more attentionally demanding task to the less demanding task were significantly greater with higher levels of trait anxiety, whereas the RT costs for switching in the opposite direction were not significantly associated with trait anxiety levels. Further analyses indicated that these associations were not attributable to comorbid dysphoria or worry. These results suggest that levels of trait anxiety may not be related to general set-shifting ability per se, but, rather, that anxiety-specific effects may primarily be restricted to when one must efficiently switch away from (or let go of) an effortfully established task set. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Evidence-based psychosocial treatments for children and adolescents with attention-deficit/hyperactivity disorder.

PubMed

Evans, Steven W; Owens, Julie Sarno; Bunford, Nora

2014-01-01

The purpose of this research was to update the Pelham and Fabiano ( 2008 ) review of evidence-based practices for children and adolescents with attention-deficit/hyperactivity disorder. We completed a systematic review of the literature published between 2007 and 2013 to establish levels of evidence for psychosocial treatments for these youth. Our review included the identification of relevant articles using criteria established by the Society of Clinical Child and Adolescent Psychology (see Southam-Gerow & Prinstein, in press ) using keyword searches and a review of tables of contents. We extend the conceptualization of treatment research by differentiating training interventions from behavior management and by reviewing the growing literature on training interventions. Consistent with the results of the previous review we conclude that behavioral parent training, behavioral classroom management, and behavioral peer interventions are well-established treatments. In addition, organization training met the criteria for a well-established treatment. Combined training programs met criteria for Level 2 (Probably Efficacious), neurofeedback training met criteria for Level 3 (Possibly Efficacious), and cognitive training met criteria for Level 4 (Experimental Treatments). The distinction between behavior management and training interventions provides a method for considering meaningful differences in the methods and possible mechanisms of action for treatments for these youth. Characteristics of treatments, participants, and measures, as well as the variability in methods for classifying levels of evidence for treatments, are reviewed in relation to their potential effect on outcomes and conclusions about treatments. Implications of these findings for future science and practice are discussed.

7 CFR 1450.213 - Levels and rates for establishment payments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... establishing non-woody perennial crops and woody perennial crops specified in the conservation plan, forest stewardship plan, or equivalent plan. (b) The average cost of performing a practice may be determined by CCC...

They fight because we let them! Applying a situational crime prevention model to barroom violence.

PubMed

Graham, Kathryn

2009-03-01

This paper draws on situational crime prevention and social interactionist theories to develop a theoretical model for preventing aggression and injury in licensed drinking establishments. The model includes six components: (i) the presence of willing participants; (ii) the role of guardians, handlers and place managers; (iii) environmental deterrents of aggression; (iv) environmental precipitators of aggression; (v) theories regarding the effects of alcohol that contribute to increased risk of aggression; and (vi) social interaction theory relevant to the process of aggressive incidents in drinking establishments. The model provides a basis for developing a range of strategies to reduce barroom aggression that includes but is not restricted to addressing the role of alcohol. The paper discusses how these strategies can be developed and implemented through interventions, programs, policies or regulations at the level of the drinking establishment, the community level or the state/national level.

Analysis of moisture content, acidity and contamination by yeast and molds in Apis mellifera L. honey from central Brazil

PubMed Central

Ananias, Karla Rubia; de Melo, Adriane Alexandre Machado; de Moura, Celso José

2013-01-01

The development of mold of environmental origin in honey affects its quality and leads to its deterioration, so yeasts and molds counts have been used as an important indicator of hygiene levels during its processing, transportation and storage. The aim of this study was to evaluate the levels of yeasts and molds contamination and their correlation with moisture and acidity levels in Apis mellifera L. honey from central Brazil. In 20% of the samples, the yeasts and molds counts exceeded the limit established by legislation for the marketing of honey in the MERCOSUR, while 42.8% and 5.7% presented above-standard acidity and moisture levels, respectively. Although samples showed yeasts and molds counts over 1.0 × 102 UFC.g−1, there was no correlation between moisture content and the number of microorganisms, since, in part of the samples with above-standard counts, the moisture level was below 20%. In some samples the acidity level was higher than that established by legislation, but only one sample presented a yeasts and molds count above the limit established by MERCOSUR, which would suggest the influence of the floral source on this parameter. In general, of the 35 samples analyzed, the quality was considered inadequate in 45.7% of cases. PMID:24516434

Analysis of moisture content, acidity and contamination by yeast and molds in Apis mellifera L. honey from central Brazil.

PubMed

Ananias, Karla Rubia; de Melo, Adriane Alexandre Machado; de Moura, Celso José

2013-01-01

The development of mold of environmental origin in honey affects its quality and leads to its deterioration, so yeasts and molds counts have been used as an important indicator of hygiene levels during its processing, transportation and storage. The aim of this study was to evaluate the levels of yeasts and molds contamination and their correlation with moisture and acidity levels in Apis mellifera L. honey from central Brazil. In 20% of the samples, the yeasts and molds counts exceeded the limit established by legislation for the marketing of honey in the MERCOSUR, while 42.8% and 5.7% presented above-standard acidity and moisture levels, respectively. Although samples showed yeasts and molds counts over 1.0 × 10(2) UFC.g(-1), there was no correlation between moisture content and the number of microorganisms, since, in part of the samples with above-standard counts, the moisture level was below 20%. In some samples the acidity level was higher than that established by legislation, but only one sample presented a yeasts and molds count above the limit established by MERCOSUR, which would suggest the influence of the floral source on this parameter. In general, of the 35 samples analyzed, the quality was considered inadequate in 45.7% of cases.

Intelligent Learning System using cognitive science theory and artificial intelligence methods

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

Cristensen, D.L.

1986-01-01

This dissertation is a presentation of a theoretical model of an intelligent Learning System (ILS). The approach view intelligent computer-based instruction on a curricular-level and educational-theory base, instead of the conventional instructional-only level. The ILS is divided into two components: (1) macro-level, curricular; and (2) micro-level (MAIS), instructional. The primary purpose of the ILS macro level is to establish the initial conditions of learning by considering individual difference variables within specification of the curriculum content domain. Second, the ILS macro-level will iteratively update the conditions of learning as the individual student progresses through the given curriculum. The term dynamic ismore » used to describe the expert tutor that establishes and monitors the conditions of instruction between the ILS macro level and the micro level. As the student progresses through the instruction, appropriate information is sent back continuously to the macro level to constantly improve decision making for succeeding conditions of instruction.« less

Partial Cutting and Establishment of Artificial Nuttall Oak Regeneration in the Mississippi Alluvial Plain

Treesearch

Benjamin P. Ware; Emile S. Gardiner

2004-01-01

In the fall of 1998, we harvested a mixed bottomland hardwood stand in Sharkey County, MS, to establish two replicates of three residual stocking levels (0, 25, and 50 percent). We compared the various stand densities for suitability in establishment and growth of artificial oak regeneration. Following the overstory harvest, treatment plots received chain saw site...

[THE POSSIBILITY OF APPLICATION OF COLORIMETRY TECHNIQUE OF DETECTION OF LEVELS OF OXIDATIVE STRESS AND ANTIOXIDANT CAPACITY OF SERUM].

PubMed

Sapojnikova, M A; Strakhova, L A; Blinova, T V; Makarov, I A; Rakhmanov, R S; Umniagina, I A

2015-11-01

The analysis was implemented concerning indicators of oxidative status and antioxidant capacity of serum. The indicators were received by colorimetry technique based on detection of peroxides in blood serum in examined patients of different categories: healthy persons aged from 17 to 20 years and from 30 to 60 years and patients with bronchopulmonary pathology. The low level of oxidative stress and high antioxidant capacity of serum were established in individuals ofyounger age. With increasing of age, degree of expression of oxidative stress augmented and level of antioxidant defense lowered. Almost all patients with bronchopulmonary pathology had high level of oxidative stress and low level of antioxidant defense. The analysis of quantitative data of examined indicators their conformity with health condition was established

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

PubMed

Higgins, J R; Papayianni, A; Brady, H R; Darling, M R; Walshe, J J

1998-08-01

Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Regional Educational Laboratory Electronic Network Phase 2 System

NASA Technical Reports Server (NTRS)

Cradler, John

1995-01-01

The Far West Laboratory in collaboration with the other regional educational laboratories is establishing a regionally coordinated telecommunication network to electronically interconnect each of the ten regional laboratories with educators and education stakeholders from the school to the state level. For the national distributed information database, each lab is working with mid-level networks to establish a common interface for networking throughout the country and include topics of importance to education reform as assessment and technology planning.

Center-to-limb observations and modeling of the Ca I 4227 Å line

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

Supriya, H. D.; Smitha, H. N.; Nagendra, K. N.

2014-09-20

The observed center-to-limb variation (CLV) of the scattering polarization in different lines of the Second Solar Spectrum can be used to constrain the height variation of various atmospheric parameters, in particular the magnetic fields, via the Hanle effect. Here we attempt to model the nonmagnetic CLV observations of the Q/I profiles of the Ca I 4227 Å line recorded with the Zurich Imaging Polarimeter-3 at IRSOL. For modeling, we use the polarized radiative transfer with partial frequency redistribution with a number of realistic one-dimensional (1D) model atmospheres. We find that all the standard Fontenla-Avrett-Loeser (FAL) model atmospheres, which we used,more » fail to simultaneously fit the observed (I, Q/I) at all the limb distances (μ). However, an attempt is made to find a single model which can provide a fit to at least the CLV of the observed Q/I instead of a simultaneous fit to the (I, Q/I) at all μ. To this end we construct a new 1D model by combining two of the standard models after modifying their temperature structures in the appropriate height ranges. This new combined model closely reproduces the observed Q/I at all μ but fails to reproduce the observed rest intensity at different μ. Hence we find that no single 1D model atmosphere succeeds in providing a good representation of the real Sun. This failure of 1D models does not, however, cause an impediment to the magnetic field diagnostic potential of the Ca I 4227 Å line. To demonstrate this we deduce the field strength at various μ positions without invoking the use of radiative transfer.« less

Voronoi-based spatial analysis reveals selective interneuron changes in the cortex of FALS mice.

PubMed

Minciacchi, Diego; Kassa, Roman M; Del Tongo, Claudia; Mariotti, Raffaella; Bentivoglio, Marina

2009-01-01

The neurodegenerative disease amyotrophic lateral sclerosis affects lower motoneurons and corticospinal cells. Mice expressing human mutant superoxide dismutase (SOD)1 provide widely investigated models of the familial form of disease, but information on cortical changes in these mice is still limited. We here analyzed the spatial organization of interneurons characterized by parvalbumin immunoreactivity in the motor, somatosensory, and visual cortical areas of SOD1(G93A) mice. Cell number and sociological spatial behavior were assessed by digital charts of cell location in cortical samples, cell counts, and generation of two-dimensional Voronoi diagrams. In end-stage SOD1-mutant mice, an increase of parvalbumin-containing cortical interneurons was found in the motor and somatosensory areas (about 35% and 20%, respectively) with respect to wild-type littermates. Changes in cell spatial distribution, as documented by Voronoi-derived coefficients of variation, indicated increased tendency of parvalbumin cells to aggregate into clusters in the same areas of the SOD1-mutant cortex. Counts and coefficients of variation of parvalbumin cells in the visual cortex gave instead similar results in SOD1-mutant and wild-type mice. Analyses of motor and somatosensory areas in presymptomatic SOD1-mutant mice provided findings very similar to those obtained at end-stage, indicating early changes of interneurons in these cortical areas during the pathology. Altogether the data reveal in the SOD1-mutant mouse cortex an altered architectonic pattern of interneurons, which selectively affects areas involved in motor control. The findings, which can be interpreted as pathogenic factors or early disease-related adaptations, point to changes in the cortical regulation and modulation of the motor circuit during motoneuron disease.

Multispectral signature analysis measurements of selected sniper rifles and small arms

NASA Astrophysics Data System (ADS)

Law, David B.; Carapezza, Edward M.; Csanadi, Christina J.; Edwards, Gerald D.; Hintz, Todd M.; Tong, Ronald M.

1997-02-01

During October 1995 - June 1996, the Naval Command, Control and Ocean Surveillance Center RDT&E Division (NRaD), under sponsorship from Defense Advanced Research Projects Agency (DARPA), conducted an intensive series of multi-spectral signature analyses of typical sniper weapons. Multi-spectral signatures of the muzzle flashes from rifles and pistols and some imagery of the bullets in flight were collected. Multi- spectral signatures of the muzzle flash were collected in the infrared (2.5 - 14.5 microns), visible -- near-IR (400 - 1200 nanometers), and the ultra-violet (185 - 400 nanometers) wavelength regions. These measurements consisted of high spectral resolution (0.0159 micron) measurements of the spectral radiance of the muzzle flash. A time history plot of the muzzle flash as it evolves just forward of the end of the muzzle is provided. These measurements were performed with a CI Systems Model SR5000 IR/Visible spectroradiometer and an Ocean Optics Model PC1000 UV spectroradiometer. Muzzle flash infrared imagery is provided to show the effect that specific muzzle breaks have on the resulting muzzle flash. The following set of sniper weapons were included in this test: AK-47, SKS, M16A2, M-14, FN-FAL, SMLE IIa, 03 Springfield, SVD Dragunov, 50 caliber McMillan, and a 45 caliber ACP pistol. The results of this signature analysis show that important measurable electro-optical differences do exist between all these weapons in terms of spectral radiance of the flash, spectral content of the gun powders, and spectral shapes/geometries of the muzzle flashes. These differences were sufficient such that, after a more complete data base is collected, it will be possible to develop a passive electro-optical weapon and ammunition identifier.

Bee venom effects on ubiquitin proteasome system in hSOD1(G85R)-expressing NSC34 motor neuron cells.

PubMed

Kim, Seon Hwy; Jung, So Young; Lee, Kang-Woo; Lee, Sun Hwa; Cai, MuDan; Choi, Sun-Mi; Yang, Eun Jin

2013-07-18

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model. NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 μg/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies. We found that GFP-hSOD1G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells. Our findings suggest that BV may rescue the impairment of the UPS in ALS models.

Mutations of Profilin-1 Associated with Amyotrophic Lateral Sclerosis Promote Aggregation Due to Structural Changes of Its Native State.

PubMed

Del Poggetto, Edoardo; Bemporad, Francesco; Tatini, Francesca; Chiti, Fabrizio

2015-11-20

The PFN1 gene, coding for profilin-1, has recently been associated with familial amyotrophic lateral sclerosis (fALS), as three mutations, namely C71G, M114T, and G118V, have been found in patients with familial forms of the disease and another, E117G, has been proposed to be a moderate risk factor for disease onset. In this work, we have purified the four profilin-1 variants along with the wild-type protein. The resulting aggregates appear to be fibrillar, to have a weak binding to ThT, and to possess a significant amount of intermolecular β-sheet structure. Using ThT fluorescence assays, far-UV circular dichroism, and dynamic light scattering, we found that all four variants have an aggregation propensity higher than that of the wild-type counterpart. In particular, the C71G mutation was found to induce the most dramatic change in aggregation, followed by the G118V and M114T substitutions and then the E117G mutation. Such a propensity was found not to strictly correlate with the conformational stability in this group of profilin-1 variants, determined using both urea-induced denaturation at equilibrium and folding/unfolding kinetics. However, it correlated with structural changes of the folded states, as monitored with far-UV circular dichroism, intrinsic fluorescence spectroscopy, ANS binding, acrylamide quenching, and dynamic light scattering. Overall, the results suggest that all four mutations increase the tendency of profilin-1 to aggregate and that such aggregation behavior is largely determined by the mutation-induced structural changes occurring in the folded state of the protein.

A general strategy for the chemical aspects of the safety assessment of extractables and leachables in pharmaceutical drug products: the chemical assessment triad.

PubMed

Jenke, Dennis

2012-01-01

During the course of their manufacturing, storage, and administration, pharmaceutical drug products come in contact with materials, components, and systems. Such contact may result in an interaction between the drug product and these entities. One such interaction is the migration of substances from these entities and into the drug product, which is of concern due to the potential toxicity of the migrating substances. In order to properly assess the risk and manage the hazard posed by migratory substances, it is necessary to establish the identities of the migratory substances and the levels to which they will accumulate in the finished drug product, as these two pieces of information establish the hazard posed by an individual substance and the magnitude of the patient exposure (dose). The process by which migrating compounds are discovered and identified, and by which their accumulation levels in a finished drug product are established, is termed chemical assessment. Because the development of a finished drug product is a long and complicated process, chemical assessment is most typically not a single action but rather a series of actions that together establish a process of risk management. It is the purpose of this manuscript to establish a high-level strategy, illustrated in the chemical assessment triad, which can be applied to such a risk management process. During the course of their manufacturing, storage, and administration, pharmaceutical drug products come in contact with materials, components, and systems. Such contact may result in an interaction between the drug product and these entities. One such interaction is the migration of substances from these entities and into the drug product, which is of concern due to the potential toxicity of the migrating substances. It is the purpose of this manuscript to outline a high-level strategy, illustrated in the chemical assessment triad, to chemically establish the safety risk related to the migrating substances.

Measles virus induces persistent infection by autoregulation of viral replication.

PubMed

Doi, Tomomitsu; Kwon, Hyun-Jeong; Honda, Tomoyuki; Sato, Hiroki; Yoneda, Misako; Kai, Chieko

2016-11-24

Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.

[How to establish a good acupuncture-moxibustion standard?].

PubMed

Wu, Xiao-dong; Xiao, Hui

2014-10-01

At the beginning of a standard item, the standardized objects and involved contents should be demonstrated thoroughly, which is the precondition of establishing a good standard. After the proposal of this standard, a high-level drafting group should be built, led by top specialists who also draft the standard, which is essential to guarantee the quality of the standard. Before drafting the standard, literature regarding this standard should be searched completely, and Directives for Standardization should be learned to understand the basic requirements of establishing a standard; in the meanwhile, selections on standardized contents and quantitative boundaries of technical indices should be comprehensively and deeply studied. At the stage of consultation, focus should be paid on the scope of the consultation departments, level and personnel quality. As for standard review, it should be precise and truth-seeking. At the stage of submitting and authorization, it is necessary to have timely communication. Only by full cooperations of all parties, and by strictly following the procedure, method and rule of standard establishment, can a high-quality acupuncture-moxibustion standard be established.

Application of local policy to prevent alcohol problems: experiences from a community trial.

PubMed

Holder, H D; Reynolds, R I

1997-06-01

Alcohol policy conventionally has been established at the national or regional, state and provincial levels. Alcohol policy at any level is not actually limited to the regulation and control of alcohol production, wholesale distribution, and retail sales. There are a number of alternatives for setting alcohol policies within a local community. Building upon existing national and state/provincial laws, policy makers at the community level can set priorities for allocating resources and enforcing laws related to drinking and driving, underage alcohol sales, alcohol serving practices of bars and restaurants and geographical density of alcohol outlets in the community. This paper concludes from the Community Trials Project that policies established at the local level can reduce alcohol problems.

Food hygiene and safety measures among food handlers in street food shops and food establishments of Dessie town, Ethiopia: A community-based cross-sectional study.

PubMed

Adane, Metadel; Teka, Brhanu; Gismu, Yirga; Halefom, Goitom; Ademe, Muluneh

2018-01-01

In sub-Saharan Africa foodborne disease and foodborne disease outbreaks are frequently ascribed to poor personal hygiene of street food vendors and food handlers in food establishments. Evidence on the level of food hygiene practices and food safety measures among food handlers is required for proper planning and implementation of targeted interventions. In this study, we aimed to determine the level of food hygiene and safety measures among street food vendors and food handlers in food establishments of Dessie Town, Ethiopia. A community-based cross-sectional study was performed in Dessie town, Ethiopia from December 2013 to June 2014. Data were collected using a pre-tested structured questionnaire and an observational checklist by a trained data collector among 116 food handlers from 116 food establishments and 19 food handlers from 19 street food vendors. Multivariable logistic regression analysis with 95% confidence interval (CI) was used to identify the factors significantly associated with good level of food hygiene and safety practices. Almost three-quarter (72%; 84/116) of food handlers in food establishments had a good level of food hygiene and safety practices compared to nearly half (53%; 10/19) of street food vendors. However, this difference was not statistically significant. Average monthly income of >$21 US (adjusted odds ratio [AOR] = 3.2; 95%CI: 1.3-7.7), availability of service training (AOR = 6.7; 95%CI: 1.8-25), wearing a gown during food handling (AOR = 19; 95%CI: 6.8-51) and medical checkup (AOR = 5.2; 95%CI: 2.1-13) were significantly associated with good levels of food hygiene and safety measures. Comprehensive health education and promotion programs through continuous training on food hygiene and safety, with promotion of wearing gown during food handling, regular medical checkups of food handlers and programs that enhance the monthly income of food handlers are promising strategies for promoting proper food handling practices in Dessie town, Ethiopia.

Anti-Cyclic Citrullinated Peptide Assays Differ in Subjects at Elevated Risk for Rheumatoid Arthritis and Subjects with Established Disease

PubMed Central

Demoruelle, M. Kristen; Parish, Mark C.; Derber, Lezlie A.; Kolfenbach, Jason R.; Hughes-Austin, Jan M.; Weisman, Michael H.; Gilliland, William; Edison, Jess D.; Buckner, Jane H.; Mikuls, Ted R.; O’Dell, James R.; Keating, Richard M.; Gregersen, Peter K.; Norris, Jill M.; Holers, V. Michael; Deane, Kevin D.

2013-01-01

Objective To compare commonly-available tests for antibodies to citrullinated protein antigens (ACPAs) for diagnostic accuracy and assay agreement in established rheumatoid arthritis (RA) and subjects at elevated risk for RA. Methods ELISA testing for anti-cyclic citrullinated peptide (anti-CCP) antibodies was performed using CCP2 (Axis-Shield) and CCP3.1 (IgA/IgG INOVA) in the following subjects: 1) probands with established RA (N=340) from the Studies of the Etiology of RA (SERA), 2) first degree relatives (FDRs) without RA (family members of SERA RA probands; N=681), 3) Department of Defense Serum Repository (DoDSR) RA cases with pre-diagnosis samples (N=83; 47/83 also had post-diagnosis samples), and 4) blood-donor and DoDSR controls (N=283). Results In established RA, CCP2 was more specific (99.2% vs. 93.1%, p<0.01), but less sensitive (58.7% vs. 67.4%, p=0.01) than CCP3.1, with specificity of CCP3.1 increasing to 97.2% if levels ≥3 times the standard cut-off level were considered. In all subjects, at standard cut-off levels, CCP3.1 positivity was more prevalent. In DoDSR cases, CCP2 was more specific than CCP3.1 for a future diagnosis of RA, and higher CCP levels trended towards greater specificity for disease onset within 2 years. At standard cut-off levels, assay agreement was good in established RA (kappa=0.76), but poor in FDRs without inflammatory arthritis (kappa=0.25). Conclusion Anti-CCP assays differ to an extent that may be meaningful in diagnosing RA in patients with inflammatory arthritis, and in evaluating the natural history of RA development in subjects at-risk for future RA. Mechanisms underlying these differences in test performance need further investigation. PMID:23686569

Differential Secretion of Satiety Hormones With Progression of Obesity in JCR: LA-corpulent Rats

PubMed Central

Parnell, Jill A.; Reimer, Raylene A.

2013-01-01

Objective To characterize the gastrointestinal tract at the onset and in well-established obesity. Methods and Procedures Lean (+/?) and obese (cp/cp) male JCR:LA-cp rats lacking a functional leptin receptor were killed at 3.5 weeks and 9 months of age and plasma concentrations of satiety hormones determined. The small intestine, colon, and stomach were measured, weighed, and mRNA levels of satiety genes quantified. Results At the onset of obesity, obese rats had greater intestine, colon, and liver mass when adjusted for body weight compared to lean rats. Conversely, adult rats with established obesity had lower intestine and colon mass and length after adjustment for body weight. Early changes in gene expression included decreased ghrelin mRNA levels in stomach and increased peptide YY (PYY) mRNA levels in duodenum of young obese rats. After massive accumulation of adipose tissue had occurred, adult obese rats had increased proglucagon and ghrelin mRNA expression in the proximal intestine. In the distal small intestine, obese rats had lower proglucagon, ghrelin, and PYY mRNA levels. Finally, at the onset and in well-established obesity, obese rats had higher plasma insulin, amylin, glucagon like peptide-1 (GLP-1), and PYY, a finding, with the exception of insulin, unique to this model. Plasma total ghrelin levels were significantly lower at the onset of obesity and established obesity compared to the lean rats. Discussion Several defects are manifested in the obese gut early on in the disease before the accumulation of large excesses of body fat and represent potential targets for early intervention in obesity. PMID:18239578

Evidence-Based Psychosocial Treatments for Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Evans, Steven W; Owens, Julie; Bunford, Miss Nora

2014-01-01

Objective The purpose of this research was to update the Pelham and Fabiano (2008) review of evidence-based practices for children and adolescents with Attention-Deficit/ Hyperactivity Disorder. Method We completed a systematic review of the literature published between 2008 and 2013 to establish levels of evidence for psychosocial treatments for these youth. The review included the identification of relevant articles using criteria established by the Society of Clinical Child and Adolescent Psychology (see Southam-Gerow & Prinstein, in press) using keyword searches and a review of tables of contents. Results We extend the conceptualization of treatment research by differentiating training interventions from behavior management and by reviewing the growing literature on training interventions. Consistent with the results of the previous review we concluded that behavioral parent training, behavioral classroom management and behavioral peer interventions were well-established treatments. In addition, organization training met the criteria for a well-established treatment. Combined training programs met criteria for Level 2 (Probably Efficacious), neurofeedback training met criteria for Level 3 (Possibly Efficacious), and cognitive training met criteria for Level 4 (Experimental Treatments). Conclusions The distinction between behavior management and training interventions provides a method for considering meaningful differences in the methods and possible mechanisms of action for treatments for these youth. Characteristics of treatments, participants, and measures, as well as the variability in methods for classifying levels of evidence for treatments, are reviewed in relation to their potential effect on outcomes and conclusions about treatments. Implications of these findings for future science and practice are discussed. PMID:24245813

Access to Community Living Infrastructure and Its Impact on the Establishment of Community-Based Day Care Centres for Seniors in Rural China.

PubMed

Li, Man; Zhong, Renyao; Zhu, Shanwen; Ramsay, Lauren C; Li, Fen; Coyte, Peter C

2018-06-06

Community-based day care centres play an important role in service delivery for Chinese seniors. Little research has examined how community living infrastructure has influenced the establishment of these day care centres in rural communities. The purposes of this study were: (1) explore regional differences in community living infrastructure; and (2) to examine the impact of such infrastructure on the establishment of day care centres for Chinese seniors in rural communities. The data were derived from “The Fourth Sample Survey on the Living Conditions of Elderly People in Urban and Rural China (2015)”. The establishment of at least one day care centre was the outcome of interest, which was dichotomized at the community level into the establishment of at least one day care centre or the absence of any day care centres. Logistic regression analysis was employed to examine the impact of various community living infrastructural characteristics on the establishment of day care centres. The results showed that of the 4522 rural communities surveyed in 2015, only 10.1% had established at least one day care centre. Community living infrastructural characteristics that were significantly associated with the establishment of day care centres were the availability of cement/asphalt roads, natural gas, tap drinking water, sewage systems, and centralized garbage disposal. Our findings suggest that the significant association between community-level characteristics, especially community living infrastructure, and the establishment of rural day care centre for seniors may inform policy decision making.

48 CFR 970.1504-1-3 - Special considerations: Laboratory management and operation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... appropriate for laboratories (science/technology and support) is rated at less than the target level of... established for the life of the contract. It will be established at time of award, as part of the extend...

48 CFR 970.1504-1-3 - Special considerations: Laboratory management and operation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... appropriate for laboratories (science/technology and support) is rated at less than the target level of... established for the life of the contract. It will be established at time of award, as part of the extend...

48 CFR 970.1504-1-3 - Special considerations: Laboratory management and operation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... appropriate for laboratories (science/technology and support) is rated at less than the target level of... established for the life of the contract. It will be established at time of award, as part of the extend...

48 CFR 970.1504-1-3 - Special considerations: Laboratory management and operation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... appropriate for laboratories (science/technology and support) is rated at less than the target level of... established for the life of the contract. It will be established at time of award, as part of the extend...

Panel-touch behavior of horses established by an autoshaping procedure.

PubMed

Miyashita, Y; Nakajima, S; Imada, H

1999-12-01

Panel-touch behavior of 3 geldings was successfully established by a response-termination type of autoshaping procedure. An omission or negative contingency introduced after the training of an animal, however, decreased the response rate to a near-zero level.

Rationales for regulatory activity

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

Perhac, R.M.

1997-02-01

The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

34 CFR 361.86 - Performance levels.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Performance levels. 361.86 Section 361.86 Education... Standards and Performance Indicators § 361.86 Performance levels. (a) General. (1) Paragraph (b) of this section establishes performance levels for— (i) General or combined DSUs; and (ii) DSUs serving...

34 CFR 361.86 - Performance levels.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 2 2012-07-01 2012-07-01 false Performance levels. 361.86 Section 361.86 Education... Standards and Performance Indicators § 361.86 Performance levels. (a) General. (1) Paragraph (b) of this section establishes performance levels for— (i) General or combined DSUs; and (ii) DSUs serving...

Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

PubMed

Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

2015-01-01

Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

Evaluation of the effectiveness of child safety restraints

DOT National Transportation Integrated Search

1987-03-01

The goals of the study were to better establish the relationsips between proper and improper usage of safety seats in crashes and the resulting injury levels and mechanisms and to establish measures of the distance from home that the children were wh...

A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages.

PubMed

Radzisheuskaya, Aliaksandra; Chia, Gloryn Le Bin; dos Santos, Rodrigo L; Theunissen, Thorold W; Castro, L Filipe C; Nichols, Jennifer; Silva, José C R

2013-06-01

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated the role of Oct4 using the process of induced pluripotency. We found that a defined embryonic stem cell (ESC) level of Oct4 is required for pluripotency entry. However, once pluripotency is established, the Oct4 level can be decreased up to sevenfold without loss of self-renewal. Unexpectedly, cells constitutively expressing Oct4 at an ESC level robustly differentiated into all embryonic lineages and germline. In contrast, cells with low Oct4 levels were deficient in differentiation, exhibiting expression of naive pluripotency genes in the absence of pluripotency culture requisites. The restoration of Oct4 expression to an ESC level rescued the ability of these to restrict naive pluripotent gene expression and to differentiate. In conclusion, a defined Oct4 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages.

48 CFR 2801.601 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

... directly to specific persons without regard for intermediate organizational levels only establishes... organizational relationship between the contracting officers and higher administrative and supervisory levels in the performance of their duties. ...

48 CFR 2801.601 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... directly to specific persons without regard for intermediate organizational levels only establishes... organizational relationship between the contracting officers and higher administrative and supervisory levels in the performance of their duties. ...

34 CFR 300.814 - Other State-level activities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Other State-level activities. 300.814 Section 300.814...) For activities at the State and local levels to meet the performance goals established by the State... CHILDREN WITH DISABILITIES Preschool Grants for Children with Disabilities § 300.814 Other State-level...

42 CFR 412.348 - Exception payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... beginning on or after October 1, 1991 and before October 1, 2001. (c) Minimum payment level by class of hospital. (1) CMS establishes a minimum payment level by class of hospital. The minimum payment level for a hospital will equal a fixed percentage of the hospital's capital-related costs. The minimum payment levels...

Rough wave-like heaped overburden promotes establishment of woody vegetation while leveling promotes grasses during unassisted post mining site development.

PubMed

Frouz, Jan; Mudrák, Ondřej; Reitschmiedová, Erika; Walmsley, Alena; Vachová, Pavla; Šimáčková, Hana; Albrechtová, Jana; Moradi, Jabbar; Kučera, Jiří

2018-01-01

Geodiversity plays an important role in species establishment during spontaneous succession. At post-mining sites in the Czech Republic in 2003, we established plots in which the surface of the heaped overburden was either kept wave-like or leveled. Based on surveys conducted from 2006 to 2015, leveled plots were increasingly dominated by grasses and herbs (and especially by the grass Calamagrostis epigejos) while the wave-like plots were increasingly dominated by the trees Salix caprea and Betula pendula. In 2015, a detailed survey was conducted of the dominant species. Both S. caprea and B. pendula occurred more often in wave-like plots than in leveled plots; this was particularly true for trees taller than 1 m, which were absent in leveled plots. In wave-like plots, leaf and root biomasses of both woody species were higher on the wave slopes than on the wave depressions. Nitrogen content was higher but content stress indicating proline in leaves of S. caprea was lower in wave-like plots than in leveled plots. In wave-like plots, both woody species occurred mainly on wave slopes but C. epigejos occurred mainly in the depressions. We speculate that trees were more abundant in wave-like plots than in leveled plots because the waves trapped tree seeds and snow and because the soil porosity was greater in wave-like than in leveled plots. Grasses may have preferred the leveled plots because soil porosity was lower and clay content was higher in leveled than in wave-like plots. Copyright © 2017 Elsevier Ltd. All rights reserved.

Macular pigment and lens optical density measurements-evaluating a flicker machine with novel features

NASA Astrophysics Data System (ADS)

Mukherjee, Anirbaan

Age related macular degeneration (AMD) is one of the leading causes of blindness amongst the elderly. Macular pigment (MP) in the retina has been established to protect individuals against AMD. Improving levels of MP by diet or supplements is the constant quest of clinical practitioners and researchers, thus necessitating development of instruments capable of repeatable and reliable MP measurement. Cataract, a consequence of the rising opacity levels of the lens with age is one of the other major causes of blindness in the world. Mapcatsf, a LED-based microprocessor-controlled heterochromatic flicker photometer (HFP) using photopic vision is capable of measuring the levels of MP and the opacity of the lens in terms of optical density. Test-retest measurements conducted on 83 subjects were analyzed for repeatability in macular pigment optical density (MPOD) measurements. Reliability of the lens optical density (LOD) measurements were tested and compared with those obtained at absolute scotopic thresholds for 25 individuals. A supplement study with 32 individuals both in the young (50) age groups for 6 months further established Mapcatsf's capacity to monitor changing levels of MP in individuals. As an overall outcome, high levels of repeatability and reliability were obtained in MPOD and LOD measurements establishing Mapcatsf as an instrument for use in clinical settings in the future.

Mercury pollution in Malaysia.

PubMed

Hajeb, Parvaneh; Jinap, S; Ismail, Ahmad; Mahyudin, Nor Ainy

2012-01-01

Although several studies have been published on levels of mercury contamination of the environment, and of food and human tissues in Peninsular Malaysia, there is a serious dearth of research that has been performed in East Malaysia (Sabah and Sarawak). Industry is rapidly developing in East Malaysia, and, hence, there is a need for establishing baseline levels of mercury contamination in environmental media in that part of the country by performing monitoring studies. Residues of total mercury and inorganic in food samples have been determined in nearly all previous studies that have been conducted; however, few researchers have analyzed samples for the presence of methlymercury residues. Because methylmercury is the most toxic form of mercury, and because there is a growing public awareness of the risk posed by methylmercury exposure that is associated with fish and seafood consumption, further monitoring studies on methylmercury in food are also essential. From the results of previous studies, it is obvious that the economic development in Malaysia, in recent years, has affected the aquatic environment of the country. Primary areas of environmental concern are centered on the rivers of the west Peninsular Malaysian coast, and the coastal waters of the Straits of Malacca, wherein industrial activities are rapidly expanding. The sources of existing mercury input to both of these areas of Malaysia should be studied and identified. Considering the high levels of mercury that now exists in human tissues, efforts should be continued, and accelerated in the future, if possible, to monitor mercury contamination levels in the coastal states, and particularly along the west Peninsular Malaysian coast. Most studies that have been carried out on mercury residues in environmental samples are dated, having been conducted 20-30 years ago; therefore, the need to collect much more and more current data is urgent. Furthermore, establishing baseline levels of mercury exposure to humans in Malaysia will be useful in establishing the levels at which detrimental effects in both humans and marine life may occur, and therefore the levels at which warning should be raised or limits established. In particular, we believe that two or three monitoring centers should be established in Peninsular Malaysia, and one in East Malaysia for the specific purpose of monitoring for the presence of hazardous environmental chemicals, and particularly monitoring for heavy metals such as mercury that reach food that is subject to consistent human consumption.

Aluminium content of foods originating from aluminium-containing food additives.

PubMed

Ogimoto, Mami; Suzuki, Kumi; Haneishi, Nahoko; Kikuchi, Yuu; Takanashi, Mayu; Tomioka, Naoko; Uematsu, Yoko; Monma, Kimio

2016-09-01

Aluminium (Al) levels of 90 food samples were investigated. Nineteen samples contained Al levels exceeding the tolerable weekly intake (TWI) for young children [body weight (bw): 16 kg] when consuming two servings/week. These samples were purchased multiple times at specific intervals and were evaluated for Al levels. Al was detected in 27 of the 90 samples at levels ranging from 0.01 (limit of quantitation) to 1.06 mg/g. Of these, the Al intake levels in two samples (cookie and scone mix, 1.3 and 2 mg/kg bw/week, respectively) exceeded the TWI as established by European Food Safety Authority, although the level in the scone mix was equivalent to the provisional TWI (PTWI) as established by Joint Food and Agriculture Organization of the United Nations/World Health Organization Expert Committee on Food Additives. The Al levels markedly decreased in 14 of the 19 samples with initially high Al levels. These results indicated reductions in the Al levels to below the PTWI limits in all but two previously identified food samples.

12 CFR 5.39 - Financial subsidiaries.

Code of Federal Regulations, 2011 CFR

2011-01-01

... indexing mechanism jointly established by regulation by the Secretary of the Treasury and the Board of... indexing mechanism); and (F) If applicable, certify that the bank meets the eligible debt requirement in... billion (or the increased level established by the indexing mechanism); and (vi) If applicable, certify...

12 CFR 5.39 - Financial subsidiaries.

Code of Federal Regulations, 2012 CFR

2012-01-01

... indexing mechanism jointly established by regulation by the Secretary of the Treasury and the Board of... indexing mechanism); and (F) If applicable, certify that the bank meets the eligible debt requirement in... billion (or the increased level established by the indexing mechanism); and (vi) If applicable, certify...

12 CFR 5.39 - Financial subsidiaries.

Code of Federal Regulations, 2014 CFR

2014-01-01

... indexing mechanism jointly established by regulation by the Secretary of the Treasury and the Board of... $50 billion (or the increased level established by the indexing mechanism); and (F) If applicable... indexing mechanism); and (vi) If applicable, certify that the bank meets the eligible debt requirement in...

12 CFR 5.39 - Financial subsidiaries.

Code of Federal Regulations, 2010 CFR

2010-01-01

... indexing mechanism jointly established by regulation by the Secretary of the Treasury and the Board of... indexing mechanism); and (F) If applicable, certify that the bank meets the eligible debt requirement in... billion (or the increased level established by the indexing mechanism); and (vi) If applicable, certify...

12 CFR 5.39 - Financial subsidiaries.

Code of Federal Regulations, 2013 CFR

2013-01-01

... indexing mechanism jointly established by regulation by the Secretary of the Treasury and the Board of... $50 billion (or the increased level established by the indexing mechanism); and (F) If applicable... indexing mechanism); and (vi) If applicable, certify that the bank meets the eligible debt requirement in...

Why We Should Establish a National System of Standards.

ERIC Educational Resources Information Center

Hennen, Thomas J., Jr.

2000-01-01

Explains the need to establish a national system of standards for public libraries. Discusses local standards, state standards, and international standards, and suggests adopting a tiered approach including three levels: minimum standards; target standards; and benchmarking standards, as found in total quality management. (LRW)

HANDBOOK: GUIDANCE ON SETTING PERMIT CONDITIONS AND REPORTING TRIAL BURN RESULTS

EPA Science Inventory

This Handbook provides guidance for establishing operational conditions for incinerators. he document provides a means for state and local agencies to achieve a level of consistency in setting permit conditions that will result in establishment of more uniform permit conditions n...

A Reevaluation of Needs Analysis in ESP.

ERIC Educational Resources Information Center

Chambers, F.

1980-01-01

Proposes use of target situation analysis (TSA) as means of removing superfluous terminology and establishing different levels of need in order to realize value of needs analysis in ESP. TSA goes into situations, collects and analyzes data to establish the communication that occurs. (Author/BK)

Venezuela: from doctrine to dialogue to participation in the processes of regional development.

PubMed

Allor, D J

1984-01-01

The growing toward decentralization and democratization of development planning in Venezuela was discussed. Venezuela has a long tradition of rule by a strong centralized authority. Currently, the Office of the President is vested with considerable power, despite the existence of an elected legislator and an independent judiciary. The president rules by decree. State legislatures are elected, but governors of the states are appointed by the president. There are also elected municipal councils. Both state and municipal governments are almost fully dependent on the federal government for both their operating and capital investment budgets. Development programs are administered through 2 systems. Specific programs are administered by almost 100 different institutes and enterprises. The activities of these various programs are coordinated by administrative bodies at the state and federal level. The 2nd administrative system operates at the regional and federal levels. The administrative body at the federal level is the Central Office for Coordination and Planning and was established by Presidential Decree in 1958. This body prepares and coordinates all national development plans. The administrative bodies at the regional level are the Regional Organizations for Development. These bodies were created in specific regions through a series of legislative acts commencing in 1969 and continuing into the present. The development of these regional bodies represented a 1st step toward decentralization. Decree 478, promulgated in 1980, further promoted the decentalization of developmental planning. The decree established a series of assemblies and councils at various levels. A National Council of Regional Development was created at the federal level, and a Regional Council of Development was established at the regional level. At the state level an Assembly of Participation was organized, and at the municipal level a Committee of Citizen Participation was established. Neighborhood associations were mentioned in the decree, but their role was not formalized. This series of newly established bodies plays a role in both advisory and administrative processes. The advisory process begins at the lowest level, and local concerns are expressed upward through the hierarchy. The administrative process flows in the opposite direction. Participation remains highly formalized and is restricted to the participation of recognized leaders and organizations. For example, members of the Assembly of Participation include the state governor, representatives of municipal councils, and representatives of various industrial and commercial organizations. Despite the formal nature of the participation, the 1980 Decree clearly exhibited the trend toward decentralization predicted by John Freeman in his analysis of Venezuelan political structure and published in a book entitled "venezuela: From doctrine to Dialogue." Increased pressure will now be exerted for broader community participation in the development process, and eventually development planning will focus on the equitable distribution of development benefits rather than on the maximization of economic growth.

New optical engineering and instrument design programs at the University of California, Irvine Extension

NASA Astrophysics Data System (ADS)

Silberman, Donn M.; Doushkina, Valentina V.

2010-08-01

Three years ago we reported on a new optics education program established at the Irvine Center for Applied Competitive Technologies (CACT) at the Advanced Technology and Education Park (ATEP) operated by the South Orange County Community College District (SOCCCD). This paper reports on new Optical Engineering and Instrument Design Programs now being offered through the University of California, Irvine Extension. While there are some similarities between the two programs, the differences are mainly the students' level. The community college level programs were targeted primarily at technicians and junior level engineers. The university level programs are targeted at senior level engineering and physical sciences university students, graduate and post graduate students and designers in industry. This paper reviews the reasons for establishing these certificate programs and their content, the students' motivations for taking them and their employers' incentives for encouraging the students.

Chloride in diet

MedlinePlus

... level based on scientific research evidence. Adequate Intake (AI): This level is established when there is not ... that is thought to ensure enough nutrition. Infants (AI) 0 to 6 months old: 0.18 grams ...

5 CFR 351.403 - Competitive level.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Competitive level. 351.403 Section 351.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.403 Competitive level. (a)(1) Each agency shall establish competitive...

5 CFR 351.403 - Competitive level.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Competitive level. 351.403 Section 351.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.403 Competitive level. (a)(1) Each agency shall establish competitive...

5 CFR 351.403 - Competitive level.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Competitive level. 351.403 Section 351.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.403 Competitive level. (a)(1) Each agency shall establish competitive...

5 CFR 351.403 - Competitive level.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Competitive level. 351.403 Section 351.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.403 Competitive level. (a)(1) Each agency shall establish competitive...

5 CFR 351.403 - Competitive level.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Competitive level. 351.403 Section 351.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Scope of Competition § 351.403 Competitive level. (a)(1) Each agency shall establish competitive...

The establishment of cow's milk protein allergy in infants is related with a deficit of regulatory T cells (Treg) and vitamin D.

PubMed

Perezabad, Laura; López-Abente, Jacobo; Alonso-Lebrero, Elena; Seoane, Elena; Pion, Marjorie; Correa-Rocha, Rafael

2017-05-01

Cow's milk protein allergy (CMPA) is the most common food allergy in infants. However, little is known about which specific immune mechanisms are related with the CMPA onset. The objective was to investigate which immune alterations constitute differential factors between allergy and tolerance, and hence could be implicated in the CMPA establishment in infants. An extensive analysis of immune subsets, including Treg and cytokine-secreting cells was performed in blood samples from 28 infants younger than 9 mo obtained 1-4 d after the first adverse reaction to milk. Less than 4 d after first allergic reaction, infants who developed CMPA had decreased Treg counts and increased frequency of IL4-secreting CD4 T cells compared to controls. The deficit of Tregs was correlated with decreased serum levels of vitamin D. Values of Tregs, IL4-secreting cells and vitamin D were good predictors of CMPA diagnosis. Basal vitamin D levels in CMPA infants also predicted those CMPA patients developing spontaneous tolerance in the first year. Establishment of CMPA in infants was related with lower Treg and vitamin D levels. These immune alterations would be crucial factors behind the CMPA establishment and they could constitute a therapeutic target for treatment of CMPA.

[Establishment of enzyme-linked immunosorbent assay (ELISA) for measuring human urinary uromodulin and application of the method in patients with IgA nephropathy].

PubMed

Liu, Ying; Chen, Yu-qing; Zhou, Jing-jing; Han, Jia; Liang, Yu; Li, Xue-ying; Zhang, Hong

2012-04-18

To establish a method of enzyme-linked immunosorbent assay (ELISA) to measure urinary uromodulin and explore the urinary uromudulin level in IgA nephropathy. The rabbit anti-human uromodulin polyclonal antibodies were coated on plates to capture uromodulin and the mouse anti-human uromodulin monoclonal antibody was used as detecting antibody to set up ELISA procedure. The precision and repeatability of this ELISA method were evaluated, and then this method was compared with the commercialized Tamm-Horsfall Glycoprotein ELISA Kit by examining urinary uromodulin levels in 55 individuals. Finally, the urinary uromodulin level in 166 IgA nephropathy patients were detected as well as 48 normal controls with this established method. The detecting range of uromodulin was 0.78-12.5 μg/L by this method. The coefficient of variation within-run was 7.5%, and between-run of coefficient of variation was 7.9%. Correlation of this method and comercialized kit was good (r=0.615, P<0.001). The urinary uromodulin/urinary creatinine ratio in IgA nephropathy was significantly lower than that in normal controls. The established ELISA method is sensitive and repeatable, and can be used in further studies.

Factors associated with over-serving at drinking establishments.

PubMed

Buvik, Kristin; Rossow, Ingeborg

2015-04-01

To address characteristics of drinking establishments, bartenders and patrons that may affect the likelihood of over-serving. A systematic examination of 425 purchase attempts with pseudo-intoxicated patrons enacting scripts that, according to the law, should lead to the denial of alcohol sales. Drinking establishments in the three largest cities in Norway (Trondheim, Bergen and Oslo) were visited by male and female actors aged 20-30 years on weekend nights, with a total of 425 purchase items. Over-serving was recorded when the pseudo-intoxicated patron was served alcohol. Characteristics of the drinking establishment, the bartender and the pseudo-intoxicated patron were recorded systematically. Pseudo-intoxicated patrons were served in 347 of 425 purchase attempts (82%). In bivariate analyses, the over-serving rate increased with venue characteristics, music/noise level and intoxication level among patrons. These factors were intercorrelated and correlated with poor lighting. The over-serving rate was also higher when the pseudo-intoxicated patron was female and when the purchase attempt occurred after midnight. In multi-variate analyses, two factors increased the likelihood of over-serving significantly: a high problematic bar indicator score (poor lighting, high music/noise level and high intoxication level among patrons) [adjusted odds ratio (OR) = 3.5, 95% confidence interval (CI) = 1.9, 6.4] and female gender of pseudo-intoxicated patrons (adjusted OR = 2.6, 95% CI = 1.4, 4.7). The rate of over-serving was 95% when both risk factors were present and 67% when both factors were absent. In urban settings in Norway, it is likely that over-serving occurs frequently, and is increased by the risk factors of poor lighting, loud music and high intoxication level among patrons. © 2015 Society for the Study of Addiction.

Pollutant levels in discarded fish species by Spanish trawlers operating in the Great Sole Bank and the Atlantic coast of the Iberian Peninsula.

PubMed

Antelo, Luis T; Ordóñez-Del Pazo, Tatiana; Lopes, Carla; Franco-Uría, Amaya; Pérez-Martín, Ricardo I; Alonso, Antonio A

2016-07-15

Organic and inorganic pollutant levels were determined for the most discarded species from trawlers operating in Great Sole and Spanish coastal fishing grounds. Results for heavy metals indicated that Cd can reach values higher than legal limits for some species and tissues, while Hg and Pb concentrations are below established values. No significant variation was noticed with fishing grounds, but both season influences in the case of Pb and interspecies variation for Hg and Cd have been detected. Valorization recommendations could be therefore established according to the levels found in the different species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Energy efficient engine: High pressure turbine uncooled rig technology report

NASA Technical Reports Server (NTRS)

Gardner, W. B.

1979-01-01

Results obtained from testing five performance builds (three vane cascades and two rotating rigs of the Energy Efficient Engine uncooled rig have established the uncooled aerodynamic efficiency of the high-pressure turbine at 91.1 percent. This efficiency level was attained by increasing the rim speed and annulus area (AN(2)), and by increasing the turbine reaction level. The increase in AN(2) resulted in a performance improvement of 1.15 percent. At the design point pressure ratio, the increased reaction level rig demonstrated an efficiency of 91.1 percent. The results of this program have verified the aerodynamic design assumptions established for the Energy Efficient Engine high-pressure turbine component.

High-level waste tank farm set point document

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

Anthony, J.A. III

1995-01-15

Setpoints for nuclear safety-related instrumentation are required for actions determined by the design authorization basis. Minimum requirements need to be established for assuring that setpoints are established and held within specified limits. This document establishes the controlling methodology for changing setpoints of all classifications. The instrumentation under consideration involve the transfer, storage, and volume reduction of radioactive liquid waste in the F- and H-Area High-Level Radioactive Waste Tank Farms. The setpoint document will encompass the PROCESS AREA listed in the Safety Analysis Report (SAR) (DPSTSA-200-10 Sup 18) which includes the diversion box HDB-8 facility. In addition to the PROCESS AREASmore » listed in the SAR, Building 299-H and the Effluent Transfer Facility (ETF) are also included in the scope.« less

A critical assessment of antipsychotic drug monitoring.

PubMed

Waraska, J; Nagle, J D

1987-06-01

Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

Teacher Research at the Middle Level: Strengthening the Essential Attributes of Education for Young Adolescents

ERIC Educational Resources Information Center

DiLucchio, Connie; Leaman, Heather; Elicker, Kathleen; Mathisen, Denise

2014-01-01

Teacher research (practitioner inquiry) is an effective form of professional development for middle level teachers. Through teacher research, classroom teachers develop the skills needed to demonstrate mastery of the performance standards for middle level master teacher candidates. Using well-established research methods, middle level educators…

Who Studies Religion at Advanced Level: Why and to What Effect?

ERIC Educational Resources Information Center

Francis, Leslie J.; Astley, Jeff; Parker, Stephen G.

2016-01-01

This study was established to profile students currently studying religion at Advanced level (A level) in terms of their demography, motivation, experience and attitudes. Eight specific areas were identified for examination: their personal motivation to study religion at A level, the personal challenges posed by the subject, their personal…

Genetic predictors of exercise adherence in the Tiger study

USDA-ARS?s Scientific Manuscript database

Obesity established in adolescence strongly predicts obesity for the remainder of adult life, suggesting this is a critical time in which to establish healthy diet and physical activity behaviors. Many studies have reported low levels of habitual activity among this age group, however. We hypothesiz...

Preventing youth access to alcohol: outcomes from a multi-community time-series trial*.

PubMed

Wagenaar, Alexander C; Toomey, Traci L; Erickson, Darin J

2005-03-01

AIMS/INTERVENTION: The Complying with the Minimum Drinking Age project (CMDA) is a community trial designed to test effects of two interventions designed to reduce alcohol sales to minors: (1) training for management of retail alcohol establishments and (2) enforcement checks of alcohol establishments. CMDA is a multi-community time-series quasi-experimental trial with a nested cohort design. CMDA was implemented in 20 cities in four geographic areas in the US Midwest. The core outcome, propensity for alcohol sales to minors, was directly tested with research staff who attempted to purchase alcohol without showing age identification using a standardized protocol in 602 on-premise and 340 off-premise alcohol establishments. Data were collected every other week in all communities over 4 years. Mixed-model regression and Box-Jenkins time-series analyses were used to assess short- and long-term establishment-specific and general community-level effects of the two interventions. Effects of the training intervention were mixed. Specific deterrent effects were observed for enforcement checks, with an immediate 17% reduction in likelihood of sales to minors. These effects decayed entirely within 3 months in off-premise establishments and to an 8.2% reduction in on-premise establishments. Enforcement checks prevent alcohol sales to minors. At the intensity levels tested, enforcement primarily affected specific establishments checked, with limited diffusion to the whole community. Finally, most of the enforcement effect decayed within 3 months, suggesting that a regular schedule of enforcement is necessary to maintain deterrence.

Establishing treatment protocols for clinical mastitis.

PubMed

Roberson, Jerry R

2003-03-01

Each farm has a unique mix of mastitis pathogens and management procedures that have evolved over time. The herd veterinarian should work with the manager/owner to systematically develop treatment protocols that meet the needs and management of the farm. To establish a mastitis treatment protocol, it is necessary to develop a system to routinely identify clinical mastitis cases, develop a herd-specific severity level assessment system, manage the clinical mastitis cases based on severity level and culture result (when available), avoid antibiotic residues, and monitor the success of the system and alter the protocol as necessary.

Relation between the Hurst Exponent and the Efficiency of Self-organization of a Deformable System

NASA Astrophysics Data System (ADS)

Alfyorova, E. A.; Lychagin, D. V.

2018-04-01

We have established the degree of self-organization of a system under plastic deformation at different scale levels. Using fractal analysis, we have determined the Hurst exponent and correlation lengths in the region of formation of a corrugated (wrinkled) structure in [111] nickel single crystals under compression. This has made it possible to single out two (micro-and meso-) levels of self-organization in the deformable system. A qualitative relation between the values of the Hurst exponent and the stages of the stress-strain curve has been established.

Seismic response of reinforced concrete frames at different damage levels

NASA Astrophysics Data System (ADS)

Morales-González, Merangeli; Vidot-Vega, Aidcer L.

2017-03-01

Performance-based seismic engineering is focused on the definition of limit states to represent different levels of damage, which can be described by material strains, drifts, displacements or even changes in dissipating properties and stiffness of the structure. This study presents a research plan to evaluate the behavior of reinforced concrete (RC) moment resistant frames at different performance levels established by the ASCE 41-06 seismic rehabilitation code. Sixteen RC plane moment frames with different span-to-depth ratios and three 3D RC frames were analyzed to evaluate their seismic behavior at different damage levels established by the ASCE 41-06. For each span-to-depth ratio, four different beam longitudinal reinforcement steel ratios were used that varied from 0.85 to 2.5% for the 2D frames. Nonlinear time history analyses of the frames were performed using scaled ground motions. The impact of different span-to-depth and reinforcement ratios on the damage levels was evaluated. Material strains, rotations and seismic hysteretic energy changes at different damage levels were studied.

Determining Normal-Distribution Tolerance Bounds Graphically

NASA Technical Reports Server (NTRS)

Mezzacappa, M. A.

1983-01-01

Graphical method requires calculations and table lookup. Distribution established from only three points: mean upper and lower confidence bounds and lower confidence bound of standard deviation. Method requires only few calculations with simple equations. Graphical procedure establishes best-fit line for measured data and bounds for selected confidence level and any distribution percentile.

7 CFR 457.133 - Prune crop insurance provisions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Provisions that allow optional units by irrigated and non-irrigated practices are not applicable. Instead of establishing optional units by section, section equivalent, or FSA farm serial number optional units may be established if each optional unit is located on non-contiguous land. 3. Insurance Guarantees, Coverage Levels...

7 CFR 457.133 - Prune crop insurance provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Provisions that allow optional units by irrigated and non-irrigated practices are not applicable. Instead of establishing optional units by section, section equivalent, or FSA farm serial number optional units may be established if each optional unit is located on non-contiguous land. 3. Insurance Guarantees, Coverage Levels...

77 FR 24730 - Submission of Information Collection Under the Paperwork Reduction Act; Reinstatement

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

... regulatory authorities to establish and implement tribal internal control standards that provide a level of... system that, at a minimum, complies with the tribal internal control standards established by the tribal... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission Submission of Information Collection...

77 FR 9261 - Submission of Information Collection Under the Paperwork Reduction Act; Reinstatement

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... regulatory authorities to establish and implement tribal internal control standards that provide a level of... system that, at a minimum, complies with the tribal internal control standards established by the tribal... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission Submission of Information Collection...

Establishing Adaptive Sports Programs for Youth with Moderate to Severe Disabilities

ERIC Educational Resources Information Center

Ryan, Joseph B.; Katsiyannis, Antonis; Cadorette, Deborah; Hodge, Janie; Markham, Michelle

2014-01-01

Children with disabilities are at increased risk of health risk factors including obesity, often because of low levels of physical activity and limited participation in sports. However, organized adaptive sports programs are increasingly available for individuals with disabilities. This article provides recommendations for establishing successful…

Acoustic attenuation design requirements established through EPNL parametric trades

NASA Technical Reports Server (NTRS)

Veldman, H. F.

1972-01-01

An optimization procedure for the provision of an acoustic lining configuration that is balanced with respect to engine performance losses and lining attenuation characteristics was established using a method which determined acoustic attenuation design requirements through parametric trade studies using the subjective noise unit of effective perceived noise level (EPNL).

Update on the Condition of Vocational Education 1985.

ERIC Educational Resources Information Center

Worthington, Robert M.

The U.S. Department of Education has shown support for vocational education through a number of initiatives. Task forces on, for example, defense preparedness and entrepreneurship education have been established at the national level. Two new programs--corrections education and rural education--have been established and have had a significant…

Considerations and Strategies for Teaching Online Counseling Skills: Establishing Relationships in Cyberspace

ERIC Educational Resources Information Center

Trepal, Heather; Haberstroh, Shane; Duffey, Thelma; Evans, Marcheta

2007-01-01

As technology advances and the use of online counseling becomes more routine, attention must be paid to instruction regarding online counseling skills. The authors present considerations for teaching basic online counseling skills to master's-level counseling students. Recommendations are made for helping students to establish and maintain…

Community-Based Eco-Education: Sound Ecology and Effective Education.

ERIC Educational Resources Information Center

Niesenbaum, Richard A.; Gorka, Barbara

2001-01-01

Reports on the development of a college-level eco-educational course that attempts to capitalize on the ecological and educational strengths of ecotourism by establishing a partnership with a local community. Makes suggestions for establishing community partnerships for effective international eco-educational program development. (Contains 15…

Civilian Radioactive Waste Management System Requirements Document

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

C.A. Kouts

2006-05-10

The CRD addresses the requirements of Department of Energy (DOE) Order 413.3-Change 1, ''Program and Project Management for the Acquisition of Capital Assets'', by providing the Secretarial Acquisition Executive (Level 0) scope baseline and the Program-level (Level 1) technical baseline. The Secretarial Acquisition Executive approves the Office of Civilian Radioactive Waste Management's (OCRWM) critical decisions and changes against the Level 0 baseline; and in turn, the OCRWM Director approves all changes against the Level 1 baseline. This baseline establishes the top-level technical scope of the CRMWS and its three system elements, as described in section 1.3.2. The organizations responsible formore » design, development, and operation of system elements described in this document must therefore prepare subordinate project-level documents that are consistent with the CRD. Changes to requirements will be managed in accordance with established change and configuration control procedures. The CRD establishes requirements for the design, development, and operation of the CRWMS. It specifically addresses the top-level governing laws and regulations (e.g., ''Nuclear Waste Policy Act'' (NWPA), 10 Code of Federal Regulations (CFR) Part 63, 10 CFR Part 71, etc.) along with specific policy, performance requirements, interface requirements, and system architecture. The CRD shall be used as a vehicle to incorporate specific changes in technical scope or performance requirements that may have significant program implications. Such may include changes to the program mission, changes to operational capability, and high visibility stakeholder issues. The CRD uses a systems approach to: (1) identify key functions that the CRWMS must perform, (2) allocate top-level requirements derived from statutory, regulatory, and programmatic sources, and (3) define the basic elements of the system architecture and operational concept. Project-level documents address CRD requirements by further defining system element functions, decomposing requirements into significantly greater detail, and developing designs of system components, facilities, and equipment. The CRD addresses the identification and control of functional, physical, and operational boundaries between and within CRWMS elements. The CRD establishes requirements regarding key interfaces between the CRWMS and elements external to the CRWMS. Project elements define interfaces between CRWMS program elements. The Program has developed a change management process consistent with DOE Order 413.3-Change 1. Changes to the Secretarial Acquisition Executive and Program-level baselines must be approved by a Program Baseline Change Control Board. Specific thresholds have been established for identifying technical, cost, and schedule changes that require approval. The CRWMS continually evaluates system design and operational concepts to optimize performance and/or cost. The Program has developed systems analysis tools to assess potential enhancements to the physical system and to determine the impacts from cost saving initiatives, scientific and technological improvements, and engineering developments. The results of systems analyses, if appropriate, are factored into revisions to the CRD as revised Programmatic Requirements.« less

The risks of injury in public ice skating.

PubMed Central

Radford, P J; Williamson, D M; Lowdon, I M

1988-01-01

A prospective survey has been made of the injuries to members of the public attending a well established ice rink in a major city. Comparison is made with series in the literature reporting high levels of injuries, with corresponding demands on local hospital services, from newly established ice rinks. The main conclusion is that demands on hospital services have been markedly reduced for the well established rink, with corresponding savings in health service resources. PMID:3167509

Food hygiene and safety measures among food handlers in street food shops and food establishments of Dessie town, Ethiopia: A community-based cross-sectional study

PubMed Central

Adane, Metadel; Teka, Brhanu; Gismu, Yirga; Halefom, Goitom

2018-01-01

Introduction In sub-Saharan Africa foodborne disease and foodborne disease outbreaks are frequently ascribed to poor personal hygiene of street food vendors and food handlers in food establishments. Evidence on the level of food hygiene practices and food safety measures among food handlers is required for proper planning and implementation of targeted interventions. In this study, we aimed to determine the level of food hygiene and safety measures among street food vendors and food handlers in food establishments of Dessie Town, Ethiopia. Method A community-based cross-sectional study was performed in Dessie town, Ethiopia from December 2013 to June 2014. Data were collected using a pre-tested structured questionnaire and an observational checklist by a trained data collector among 116 food handlers from 116 food establishments and 19 food handlers from 19 street food vendors. Multivariable logistic regression analysis with 95% confidence interval (CI) was used to identify the factors significantly associated with good level of food hygiene and safety practices. Result Almost three-quarter (72%; 84/116) of food handlers in food establishments had a good level of food hygiene and safety practices compared to nearly half (53%; 10/19) of street food vendors. However, this difference was not statistically significant. Average monthly income of >$21 US (adjusted odds ratio [AOR] = 3.2; 95%CI: 1.3–7.7), availability of service training (AOR = 6.7; 95%CI: 1.8–25), wearing a gown during food handling (AOR = 19; 95%CI: 6.8–51) and medical checkup (AOR = 5.2; 95%CI: 2.1–13) were significantly associated with good levels of food hygiene and safety measures. Conclusion Comprehensive health education and promotion programs through continuous training on food hygiene and safety, with promotion of wearing gown during food handling, regular medical checkups of food handlers and programs that enhance the monthly income of food handlers are promising strategies for promoting proper food handling practices in Dessie town, Ethiopia. PMID:29723288

The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/- -SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels.

PubMed

Leckngam, Prapapun; Limweeraprajak, Ektong; Kiewkarnkha, Tiemjan; Tatu, Thanusak

2017-01-01

Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- - SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - - SEA and -α 3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- - SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma.

PubMed

Agarwal, Ashok; Sharma, Rakesh; Roychoudhury, Shubhadeep; Du Plessis, Stefan; Sabanegh, Edmund

2016-09-01

To measure oxidative reduction potential (ORP) in semen and seminal plasma and to establish their reference levels. ORP levels were measured in semen and seminal plasma. Tertiary hospital. Twenty-six controls and 33 infertile men. None. Static ORP (sORP) and capacitance ORP (cORP) were measured in semen and seminal plasma at time 0 and 120 minutes. Correlation of ORP was assessed between [1] semen and seminal plasma and [2] time 0 and 120 minutes. The association with sperm parameters was studied in (a) controls and (b) infertile patients, and a receiver operating characteristic curve was generated to establish the sORP cutoff. Semen sORP and cORP levels were associated with seminal plasma levels at time 0 and time 120 minutes. In controls and infertile patients, an inverse relationship of sORP levels was established with concentration and total sperm count in semen as well as seminal plasma at time 0 and 120 minutes. Classification of subjects based on sperm motility showed that subjects with abnormal motility present with poor concentration, total count, morphology, and elevated levels of semen and seminal plasma sORP at time 120 minutes. The sORP cutoff of 1.48 in semen and 2.09 in seminal plasma based on motility was able to distinguish subjects with normal semen quality from those with abnormal semen quality. The MiOXSYS System can reliably measure ORP levels in semen and seminal plasma. ORP levels are not affected by semen age, making this new technology easy to employ in a clinical setting. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A Task-Dependent Causal Role for Low-Level Visual Processes in Spoken Word Comprehension

ERIC Educational Resources Information Center

Ostarek, Markus; Huettig, Falk

2017-01-01

It is well established that the comprehension of spoken words referring to object concepts relies on high-level visual areas in the ventral stream that build increasingly abstract representations. It is much less clear whether basic low-level visual representations are also involved. Here we asked in what task situations low-level visual…

Linking Comparisons of Absolute Gravimeters: A Proof of Concept for a new Global Absolute Gravity Reference System.

NASA Astrophysics Data System (ADS)

Wziontek, H.; Palinkas, V.; Falk, R.; Vaľko, M.

2016-12-01

Since decades, absolute gravimeters are compared on a regular basis on an international level, starting at the International Bureau for Weights and Measures (BIPM) in 1981. Usually, these comparisons are based on constant reference values deduced from all accepted measurements acquired during the comparison period. Temporal changes between comparison epochs are usually not considered. Resolution No. 2, adopted by IAG during the IUGG General Assembly in Prague 2015, initiates the establishment of a Global Absolute Gravity Reference System based on key comparisons of absolute gravimeters (AG) under the International Committee for Weights and Measures (CIPM) in order to establish a common level in the microGal range. A stable and unique reference frame can only be achieved, if different AG are taking part in different kind of comparisons. Systematic deviations between the respective comparison reference values can be detected, if the AG can be considered stable over time. The continuous operation of superconducting gravimeters (SG) on selected stations further supports the temporal link of comparison reference values by establishing a reference function over time. By a homogenous reprocessing of different comparison epochs and including AG and SG time series at selected stations, links between several comparisons will be established and temporal comparison reference functions will be derived. By this, comparisons on a regional level can be traced to back to the level of key comparisons, providing a reference for other absolute gravimeters. It will be proved and discussed, how such a concept can be used to support the future absolute gravity reference system.

Food safety objective approach for controlling Clostridium botulinum growth and toxin production in commercially sterile foods.

PubMed

Anderson, N M; Larkin, J W; Cole, M B; Skinner, G E; Whiting, R C; Gorris, L G M; Rodriguez, A; Buchanan, R; Stewart, C M; Hanlin, J H; Keener, L; Hall, P A

2011-11-01

As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (ΣR), and preventing an increase in levels (ΣI) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods.

A national project to evaluate and reduce high sound pressure levels from music.

PubMed

Ryberg, Johanna Bengtsson

2009-01-01

The highest recommended sound pressure levels for leisure sounds (music) in Sweden are 100 dB LAeq and 115 dB LAFmax for adults, and 97 dB LAeq and 110 dB LAFmax where children under the age of 13 have access. For arrangements intended for children, levels should be consistently less than 90 dB LAeq. In 2005, a national project was carried out with the aim of improving environments with high sound pressure levels from music, such as concert halls, restaurants, and cinemas. The project covered both live and recorded music. Of Sweden's 290 municipalities, 134 took part in the project, and 93 of these carried out sound measurements. Four hundred and seventy one establishments were investigated, 24% of which exceeded the highest recommended sound pressure levels for leisure sounds in Sweden. Of festival and concert events, 42% exceeded the recommended levels. Those who visit music events/establishments thus run a relatively high risk of exposure to harmful sound levels. Continued supervision in this field is therefore crucial.

Design, innovation, and rural creative places: Are the arts the cherry on top, or the secret sauce?

PubMed

Wojan, Timothy R; Nichols, Bonnie

2018-01-01

Creative class theory explains the positive relationship between the arts and commercial innovation as the mutual attraction of artists and other creative workers by an unobserved creative milieu. This study explores alternative theories for rural settings, by analyzing establishment-level survey data combined with data on the local arts scene. The study identifies the local contextual factors associated with a strong design orientation, and estimates the impact that a strong design orientation has on the local economy. Data on innovation and design come from a nationally representative sample of establishments in tradable industries. Latent class analysis allows identifying unobserved subpopulations comprised of establishments with different design and innovation orientations. Logistic regression allows estimating the association between an establishment's design orientation and local contextual factors. A quantile instrumental variable regression allows assessing the robustness of the logistic regression results with respect to endogeneity. An estimate of design orientation at the local level derived from the survey is used to examine variation in economic performance during the period of recovery from the Great Recession (2010-2014). Three distinct innovation (substantive, nominal, and non-innovators) and design orientations (design-integrated, "design last finish," and no systematic approach to design) are identified. Innovation- and design-intensive establishments were identified in both rural and urban areas. Rural design-integrated establishments tended to locate in counties with more highly educated workforces and containing at least one performing arts organization. A quantile instrumental variable regression confirmed that the logistic regression result is robust to endogeneity concerns. Finally, rural areas characterized by design-integrated establishments experienced faster growth in wages relative to rural areas characterized by establishments using no systematic approach to design.

Propellant Readiness Level: A Methodological Approach to Propellant Characterization

NASA Technical Reports Server (NTRS)

Bossard, John A.; Rhys, Noah O.

2010-01-01

A methodological approach to defining propellant characterization is presented. The method is based on the well-established Technology Readiness Level nomenclature. This approach establishes the Propellant Readiness Level as a metric for ascertaining the readiness of a propellant or a propellant combination by evaluating the following set of propellant characteristics: thermodynamic data, toxicity, applications, combustion data, heat transfer data, material compatibility, analytical prediction modeling, injector/chamber geometry, pressurization, ignition, combustion stability, system storability, qualification testing, and flight capability. The methodology is meant to be applicable to all propellants or propellant combinations; liquid, solid, and gaseous propellants as well as monopropellants and propellant combinations are equally served. The functionality of the proposed approach is tested through the evaluation and comparison of an example set of hydrocarbon fuels.

Food Safety Legislation Regarding Of Aflatoxins Contamination

NASA Astrophysics Data System (ADS)

Ketney, Otto

2015-09-01

The main objective of the European Union (EU) is to reduce certain contaminants in foodstuffs to acceptable levels. The occurrence of aflatoxin B1 in food was considered to be one of the most important issues of global food security to protect the health of humans and animals, over 100 nations have established maximum tolerable levels for aflatoxin in food. Although EU legislation covers many aspects of food safety was not legally establish an integrated framework that could effectively combat and cover all sectors of the food chain. Monitoring and reporting levels of aflatoxins after controls are essential actions that assist to identify potential risks to human health. The review process for aflatoxin regulations is a complex activity involving many factors and stakeholders.

Financial responsibility requirements for commercial motor vehicles.

DOT National Transportation Integrated Search

2013-01-01

Minimum liability insurance levels and related requirements for motor carriers to demonstrate financial responsibility in case of damages from crashes were established in the 1980s by Congressional legislation. These levels have not been changed s...

Drinkable, But. . . Much to be Done

ERIC Educational Resources Information Center

Sterrett, Frances S.

1977-01-01

Maximum levels of the principle water contaminants are discussed in this article. Difficulties related to establishing standards for contaminants in drinking water are identified and the possible results of high levels of these contaminants included. (MA)

Country-Level Correlates of Educational Achievement: Evidence from Large-Scale Surveys

ERIC Educational Resources Information Center

He, Jia; Van de Vijver, Fons J. R.; Kulikova, Alena

2017-01-01

Linking country-level educational achievement with other country-level indicators has the potential to drive systemic educational changes, as these correlates may reflect characteristics relevant for policy-making decisions to improve educational effectiveness. This study establishes a nomological network of educational achievement at the country…

40 CFR 63.1438 - Parameter monitoring levels and excursions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... required to submit Periodic Reports semiannually or quarterly. The first semiannual period is the 6-month... excursions. (5) For the fifth semiannual period—two excused excursions. (6) For the sixth and all subsequent... during the entire test period. The monitoring level(s) shall be those established during from the...

40 CFR 63.1438 - Parameter monitoring levels and excursions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... required to submit Periodic Reports semiannually or quarterly. The first semiannual period is the 6-month... excursions. (5) For the fifth semiannual period—two excused excursions. (6) For the sixth and all subsequent... during the entire test period. The monitoring level(s) shall be those established during from the...

40 CFR 63.1438 - Parameter monitoring levels and excursions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... required to submit Periodic Reports semiannually or quarterly. The first semiannual period is the 6-month... excursions. (5) For the fifth semiannual period—two excused excursions. (6) For the sixth and all subsequent... during the entire test period. The monitoring level(s) shall be those established during from the...

40 CFR 63.1438 - Parameter monitoring levels and excursions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... required to submit Periodic Reports semiannually or quarterly. The first semiannual period is the 6-month... excursions. (5) For the fifth semiannual period—two excused excursions. (6) For the sixth and all subsequent... during the entire test period. The monitoring level(s) shall be those established during from the...

Section summary: Institutional context, drivers and detectability in REDD+ implementation

Treesearch

Patricia Manley

2013-01-01

REDD+ and Forest DegradationREDD+ implementation requires two key steps: (1) establish a reference emission level or reference level (RL); and (2) monitor performance against the reference level (RL). A monitoring system must be able to monitor the performance of implementing action plans to reduce emissions....

32 CFR 174.14 - Maintenance and repair.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and protect those facilities and items of equipment needed for reuse in an economical manner that... consultation with the LRA, will establish initial levels of maintenance and repair needed to aid redevelopment... levels of maintenance and repair and its duration. In no case will these initial levels of maintenance...

32 CFR 174.14 - Maintenance and repair.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and protect those facilities and items of equipment needed for reuse in an economical manner that... consultation with the LRA, will establish initial levels of maintenance and repair needed to aid redevelopment... levels of maintenance and repair and its duration. In no case will these initial levels of maintenance...

15 CFR 4a.3 - Classification levels.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION... E.O. 12958. The levels established by E.O. 12958 (Top Secret, Secret, and Confidential) are the only...

15 CFR 4a.3 - Classification levels.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION... E.O. 12958. The levels established by E.O. 12958 (Top Secret, Secret, and Confidential) are the only...

15 CFR 4a.3 - Classification levels.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION... E.O. 12958. The levels established by E.O. 12958 (Top Secret, Secret, and Confidential) are the only...

15 CFR 4a.3 - Classification levels.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION... E.O. 12958. The levels established by E.O. 12958 (Top Secret, Secret, and Confidential) are the only...

15 CFR 4a.3 - Classification levels.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION... E.O. 12958. The levels established by E.O. 12958 (Top Secret, Secret, and Confidential) are the only...

Polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like PCBs in commercialized food products from Colombia.

PubMed

Pemberthy, D; Quintero, A; Martrat, M G; Parera, J; Ábalos, M; Abad, E; Villa, A L

2016-10-15

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) are commonly known as dioxins and are the most toxic members of persistent organic pollutants (POPs) because present a variety of health effects especially as promoting agent of growing and transformation of cancer cells. They are bio-accumulate in humans primarily via the diet, specifically by ingestion of foods that have high lipid content which are generally associated with foods of animal origin such as oils and fats and with fishery and dairy products. In Colombia the Ministry of Health and Social Protection which is the entity responsible for surveillance food conditions, has established maximum levels for dioxins and dl-PCBs in oils from animal and vegetable origins. Oils of vegetable and animal origin represent an appreciable intake in the country thus the presence of dioxins and dl-PCBs in these materials is a matter of concern because they can bioaccumulate in fat. In this contribution the levels of PCDD/Fs and dl-PCBs in olive, soybean, fish oil, butter and shrimp consumed in Colombia were determined using HRGC-HRMS and were compared with the maximum levels permitted in oil samples according to both the Colombian and European regulations. WHO-TEQ concentrations for PCDD/Fs and dioxin like PCBs ranged from 0.24 to 1.710pgWHO-TEQ PCDD/Fg(-1) of fat and from 0.050 to 3.000pgWHO-TEQ PCBg(-1) of fat, respectively. As expected, fish oils and shrimp present the highest WHO-TEQ PCDD/Fs and dl-PCBs values followed by butter and soybean oil sample, while the olive oil shows the lowest levels. In general, the vegetable oils show levels below the limits established by both the Colombian and European regulations. The levels from soybean oil found in this study were slightly higher than the threshold established both by the Commission Regulation European Union (EU) and the Colombian legislation, while fish oils showed concentrations above the European regulations. Furthermore, shrimp exhibited values below the maximum concentration levels established by the EU and Colombian regulation. Copyright © 2016. Published by Elsevier B.V.

Establishment of woody riparian species from natural seedfall at a former gravel pit

USGS Publications Warehouse

Roelle, J.E.; Gladwin, D.N.

1999-01-01

Establishment of native riparian communities through natural seedfall may be a viable reclamation alternative at some alluvial sand and gravel mines where water level can be controlled in the abandoned pit. We experimented with this approach at a pit in Fort Collins, Colorado, where a drain culvert equipped with a screw gate allows water levels to be manipulated. From 1994 to 1996 we conducted a series of annual drawdowns during the period of natural seedfall of Populus deltoides subsp. monilifera (plains cottonwood), Salix amygdaloides (peachleaf willow), and S. exigua (sand-bar willow), thus providing the bare, moist substrate conducive to establishment of these species. Establishment was highly variable from year to year; in the fall following establishment, frequency of occurrence on 0.5-m2 sample plots ranged from 8.6% to 50.6% for cottonwood, 15.9% to 22.0% for peachleaf willow, and 21.7% to 50.0% for sandbar willow. Mean densities, however, were comparable to those reported for other locations. Concurrent establishment of the undesirable exotic Tamarix ramosissima (saltcedar) was a problem, but we were able to eradicate most saltcedar seedlings by reflooding the lower elevations of the annual drawdown zones each fall. At the end of the 3-year period, at least one of the three native woody species survived on 41.1% of the plots, while saltcedar was present on only 6.1%. In addition to the potential for establishing valuable native habitats, adaptations of the techniques described may require less earth moving than other reclamation approaches.

THE IMPACT OF HEXAMETAPHOSPHATE ON COPPER CORROSION AND RELEASE

EPA Science Inventory

In 1991, U.S. Environmental Protection Agency (U.S. EPA) promulgated the Lead and Copper Rule, which established a copper action level of 1.3 mg/L in a 1-liter, first-draw sample collected from the consumer’s tap (Federal Register, 1991a, 1991b, 1992). The rule was established d...

Establishing and Maintaining Organizational Trust in the 21st Century

ERIC Educational Resources Information Center

Hunt, Matt; Lara, Tracy M.; Hughey, Aaron W.

2009-01-01

Recent corporate and academic scandals have led to decreasing levels of trust and confidence in many organizations. Whether the organization is a college or university, a government agency, a private company or a public corporation, the establishment and maintenance of trust is essential to both short-term success and long-term efficacy. This…

50 CFR 14.53 - Detention and refusal of clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... origin of the wildlife has not been established (in such cases, the burden is upon the owner, importer, exporter, consignor, or consignee to establish such identity by scientific name to the species level or, if any subspecies is protected by the laws of this country or the country of origin to the subspecies...

50 CFR 14.53 - Detention and refusal of clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... origin of the wildlife has not been established (in such cases, the burden is upon the owner, importer, exporter, consignor, or consignee to establish such identity by scientific name to the species level or, if any subspecies is protected by the laws of this country or the country of origin to the subspecies...

50 CFR 14.53 - Detention and refusal of clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... origin of the wildlife has not been established (in such cases, the burden is upon the owner, importer, exporter, consignor, or consignee to establish such identity by scientific name to the species level or, if any subspecies is protected by the laws of this country or the country of origin to the subspecies...

50 CFR 14.53 - Detention and refusal of clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... origin of the wildlife has not been established (in such cases, the burden is upon the owner, importer, exporter, consignor, or consignee to establish such identity by scientific name to the species level or, if any subspecies is protected by the laws of this country or the country of origin to the subspecies...

40 CFR 129.7 - Requirement and procedure for establishing a more stringent effluent limitation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS TOXIC POLLUTANT EFFLUENT STANDARDS Toxic Pollutant Effluent...) determines that the ambient water criterion established in these standards is not being met or will not be met in the receiving water as a result of one or more discharges at levels allowed by these standards...

20 CFR 658.410 - Establishment of State agency JS complaint system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... system. At the local office level, the local office manager shall be responsible for the management of... related), the local office manager shall transmit a copy of that portion of the log containing the... established for the handling of complaints and files relating to the handling of complaints. The Manager or...

75 FR 45584 - Planning and Establishment of State-Level Exchanges; Request for Comments Regarding Exchange...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... Act): (1) Facilitate the purchase of qualified health plans (QHPs); (2) provide for the establishment... Federal government for their State? When will this decision be made? Can planning grants assist in identifying and assessing relevant factors and making this decision? 2. To what extent have States already...

Using an Experience Documentation Opportunity to Certify Advanced-Level Health Education Specialists

ERIC Educational Resources Information Center

Wilson, Kelly L.; Dennis, Dixie L.; Gambescia, Stephen F.; Chen, W. William; Lysoby, Linda

2012-01-01

The worldwide burden of diseases, environmental threats, and injuries help establish the global context and need for credentialing in health education and promotion. To ensure effective practice by certified or credentialed individuals, it is critical that the global health education and promotion workforce identify, agree on, and establish core…

Corporate Establishments' Preferences and the Quest for Overseas' Qualifications by Nigerian University Students

ERIC Educational Resources Information Center

Okunola, Rashidi Akanji; Ikuomola, Adediran Daniel

2009-01-01

This study examines corporate establishment demand as the quest for foreign education in Nigeria and seeks to expose the motivation behind the rush abroad for foreign education; explicated by the increasing level of university seekers within and outside Nigeria. A combination of quantitative and qualitative research methodology was adopted for…

77 FR 75066 - Special Conditions: Airbus, A350-900 Series Airplane; Flight Envelope Protection (Icing and Non...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

... Protection (Icing and Non-Icing Conditions); High Incidence Protection and Alpha-Floor Systems AGENCY... or unusual design features associated with flight envelope protection in icing and non- icing... establish a level of safety equivalent to that established by the existing airworthiness standards. DATES...

Establishment of an Off-Campus Baccalaureate Nursing Program.

ERIC Educational Resources Information Center

Ostmoe, Patricia M.

In an effort to prepare more baccalaureate level nurses for the rural areas of central Wisconsin and to accommodate the educational needs of geographically bound nontraditional students, a basic baccalaureate nursing program was established at an off-campus site. This University of Wisconsin-Eau Claire program is offered in cooperation with two…

78 FR 31838 - Special Conditions: Embraer S.A., Model EMB-550 Airplanes; Flight Envelope Protection: General...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-28

... new control architecture and a full digital flight control system which provides flight envelope... Administrator considers necessary to establish a level of safety equivalent to that established by the existing... metal with composite empennage and control surfaces. The Model EMB-550 airplane is designed for 8...

Cosmetics or Radical Surgery? What’s Right For the Top Levels of the U.S Defense Establishment as it Downsizes?

DTIC Science & Technology

1993-04-15

1992. Thompson, W. Scott, and Donaldson D. Frizzell, ed. The Lessons of Viet Nam . New York: Crane, Russak & Company, 1977. Thurman, General Maxwell R...Depuftt .f Deawss. w SOY Or qifMade Thk 4amest may wt be IS-ýi ft 1W 0Mp•"s u ftbwsbee.demadby lbs appespdAdks Of enls COSMETICS OR RADICAL SURGERY...Classification) Cosmetics or Radical Surgery? What’s Right for the Top Levels of the U.S. Defense Establishment as It Downsizes? 12. PERSONAL AUTHOR(S) LTC

Preliminary measurement of the airframe noise from an F-106B delta wing aircraft at low flyover speeds. [establishment of lower limit for noise level of supersonic transport aircraft

NASA Technical Reports Server (NTRS)

Burley, R. R.

1974-01-01

To establish a realistic lower limit for the noise level of advanced supersonic transport aircraft will require knowledge concerning the amount of noise generated by the airframe itself as it moves through the air. The airframe noise level of an F-106B aircraft was determined and was compared to that predicted from an existing empirical relationship. The data were obtained from flyover and static tests conducted to determine the background noise level of the F-106B aircraft. Preliminary results indicate that the spectrum associated with airframe noise was broadband and peaked at a frequency of about 570 hertz. An existing empirical method successfully predicted the frequency where the spectrum peaked. However, the predicted OASPL value of 105 db was considerably greater than the measures value of 83 db.

Eighteenth annual report of the United States Geological Survey to the Secretary of the Interior, 1896-1897: Part I - Director's report, including triangulation and spirit leveling

USGS Publications Warehouse

Walcott, Charles D.

1897-01-01

The most important change in the field work was rendered necessary by the legislation providing for the establishment of levels and permanent monuments and bench marks. The clauses of the act embodying this legislation, and a full statement of the reasons for it, were given in the Introduction to Part I of the Seventeenth Annual Report, pages 7 to 11, and the subject is again referred to further on in this report. The actual cost of the leveling and monuments for the year was somewhat greater than it will be another year, as the expense of training men and initiating the new methods- of survey will not have to be met hereafter. During the year 10,840 miles of levels were run and 1,820 bench marks were established.

Importance of establishing radiation protection culture in Radiology Department.

PubMed

Ploussi, Agapi; Efstathopoulos, Efstathios P

2016-02-28

The increased use of ionization radiation for diagnostic and therapeutic purposes, the rapid advances in computed tomography as well as the high radiation doses delivered by interventional procedures have raised serious safety and health concerns for both patients and medical staff and have necessitated the establishment of a radiation protection culture (RPC) in every Radiology Department. RPC is a newly introduced concept. The term culture describes the combination of attitudes, beliefs, practices and rules among the professionals, staff and patients regarding to radiation protection. Most of the time, the challenge is to improve rather than to build a RPC. The establishment of a RPC requires continuing education of the staff and professional, effective communication among stakeholders of all levels and implementation of quality assurance programs. The RPC creation is being driven from the highest level. Leadership, professionals and associate societies are recognized to play a vital role in the embedding and promotion of RPC in a Medical Unit. The establishment of a RPC enables the reduction of the radiation dose, enhances radiation risk awareness, minimizes unsafe practices, and improves the quality of a radiation protection program. The purpose of this review paper is to describe the role and highlight the importance of establishing a strong RPC in Radiology Departments with an emphasis on promoting RPC in the Interventional Radiology environment.

Urban permeable pavement system design based on “sponge city” concept

NASA Astrophysics Data System (ADS)

Yu, M. M.; Zhu, J. W.; Gao, W. F.; Xu, D. P.; Zhao, M.

2017-08-01

Based on the “sponge city” concept, to implement the goal of building a city within the city to solve the sponge waterlogging, rational utilization of water resources, reduce water pollution this paper, combined with the city planning level in China, establishes the design system of city road flooding from the macro, medium and micro level, explore the design method of city water permeable pavement system, and has a practical significance the lower flood risk water ecological problems. On the macro level, we established an urban pavement sponge system under the regional ecological pattern by “spot permeable open space - low impact developing rain water road system - catchment area and catchment wetland”. On a medium level, this paper proposed the permeable suitability of pavement and the planning control indicators when combined with urban functional districts to conduct permeable pavement roads plans and controls. On micro level, the paper studied sponge technology design of permeable pavement from road structure, surface material, and other aspects aimed at the pavement permeability requirements.

Smarter Balanced Preliminary Performance Levels: Estimated MAP Scores Corresponding to the Preliminary Performance Levels of the Smarter Balanced Assessment Consortium (Smarter Balanced)

ERIC Educational Resources Information Center

Northwest Evaluation Association, 2015

2015-01-01

Recently, the Smarter Balanced Assessment Consortium (Smarter Balanced) released a document that established initial performance levels and the associated threshold scale scores for the Smarter Balanced assessment. The report included estimated percentages of students expected to perform at each of the four performance levels, reported by grade…

Establishing a STEM Pipeline: Trends in Male and Female Enrollment and Performance in Higher Level Secondary STEM Courses

ERIC Educational Resources Information Center

Bergeron, Liz; Gordon, Melissa

2017-01-01

The purpose of this study was to understand enrollment and performance differences between male and females in higher level secondary STEM courses. This study analyzes performance and enrollment of 355,688 secondary students in higher level STEM courses. This research also enabled an exploration of country level differences. The enrollment…

Validating the Use of pPerformance Risk Indices for System-Level Risk and Maturity Assessments

NASA Astrophysics Data System (ADS)

Holloman, Sherrica S.

With pressure on the U.S. Defense Acquisition System (DAS) to reduce cost overruns and schedule delays, system engineers' performance is only as good as their tools. Recent literature details a need for 1) objective, analytical risk quantification methodologies over traditional subjective qualitative methods -- such as, expert judgment, and 2) mathematically rigorous system-level maturity assessments. The Mahafza, Componation, and Tippett (2005) Technology Performance Risk Index (TPRI) ties the assessment of technical performance to the quantification of risk of unmet performance; however, it is structured for component- level data as input. This study's aim is to establish a modified TPRI with systems-level data as model input, and then validate the modified index with actual system-level data from the Department of Defense's (DoD) Major Defense Acquisition Programs (MDAPs). This work's contribution is the establishment and validation of the System-level Performance Risk Index (SPRI). With the introduction of the SPRI, system-level metrics are better aligned, allowing for better assessment, tradeoff and balance of time, performance and cost constraints. This will allow system engineers and program managers to ultimately make better-informed system-level technical decisions throughout the development phase.

Spread, establishment & prevalence of dengue vector Aedes aegypti (L.) in Konkan region, Maharashtra, India.

PubMed

Fulmali, P V; Walimbe, A; Mahadev, P V M

2008-06-01

Aedes aegypti (L.) (Diptera: Culicidae) was surveyed in the residential biotopes of Sindhudurg, Ratnagiri and Raigadh districts, Maharashtra State during dry (January-May & November- December) and wet (June-October) months in 2002 to update information on its distribution, to analyse post invasion establishment, and to study its prevalence. The survey was designed to unfold Ae. aegypti distributions at landscape, habitat and micro-habitat levels. Risks of distribution and establishment due to differences amongst settlements, households and habitat attributes were analysed by univariate and multivariate methods. Demographic/transport changes were surveyed for its breeding refugia during dry months and prevalence during the wet seasons. Chi square tests for difference and relative risks of container types were applied to assess container habitats preferences for Ae. aegypti breeding, thus contributing to the risk of establishment and prevalence through seasons. Ae. aegypti was present in 16 out of total 28 settlements in dry season and 22 of 25 in wet season; the Breteau index (BI) varied from 1.25 to 57.33 and the container index (CI) was 0.6 to 25.81 in the dry season and BI from 1.25 to 110-00 and CI - 0.2 to 11.37 in the wet season, respectively. At macro-level, rural settlements and ports showed higher odds ratios (OR>1) for presence of Ae. aegypti. At meso-level, OR were 65.8, 24.8 and 4.9 for Ae. aegypti breeding in compact houses, clustered housing and in houses with tap water source respectively. At micro-level the plastic drums and small plastic containers were the important key habitats of its breeding. In the non-residential areas Ae. aegypti breeding was noted in one port during dry season; 10-road transport tyre dumps and scrap, 5 of 7 seaports and none of the two railway station areas during wet season. At macro-geographic level Ae. aegypti distribution increased in 3 settlements, new establishment was seen in 7, new records in ten settlements and two were negative in past and present surveys. Logistic regression analyses indicated that the distribution was found to be more associated with ports and rural areas. At meso-geographic level the house aggregations and household drinking water supplies were of risk even at lower urbanization and rural levels. At micro-level, the site and potability were confounders; outdoor non potable water storage containers posed significant breeding risk, the potable water storage was significant but it contributed little to Ae. aegypti breeding. Further, Ae. aegypti breeding showed high preference to the plastic drums and other plastic miscellany. The results signified an expansion in the risk area of diseases borne by it in the context of urbanization, transport development and changing habitats.

The rate of radon remediation in Ireland 2011-2015: Establishing a base line rate for Ireland's National Radon Control Strategy.

PubMed

Dowdall, A; Fenton, D; Rafferty, B

2016-10-01

Radon is the greatest source of radiation exposure to the public. In Ireland, it is estimated that approximately 7% of the national housing stock have radon concentrations above the Reference Level of 200 Bq m -3 . A radon test can be carried out to identify homes with radon levels above the Reference Level. However there is no health benefit associated with radon testing unless it leads to remediation. Surveys to establish the rate of remediation in Ireland, that is the proportion of householders who having found levels of radon above the Reference Level proceed to carry out remediation work have been carried out in 2011 and 2013. Reasons for not carrying out remediation work were also investigated. In 2015 the survey was repeated to establish the current rate of remediation and reasons for not remediating. This report presents the results of that survey. It also compiles the data from all three surveys to identify any trends over time. The rate of remediation is an important parameter in estimating the effectiveness of programmes aimed at reducing radon levels. Currently the rate of remediation is 22% and the main reasons householders gave for not remediating were not certain there is a serious risk and concern about the cost of the work. In Ireland, this figure of 22% will be now used as a baseline metric against which the effectiveness of its National Radon Control Strategy will be measured over time. Copyright © 2016 Elsevier Ltd. All rights reserved.

33 CFR 95.025 - Adoption of State blood alcohol concentration levels.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Adoption of State blood alcohol... DANGEROUS DRUG § 95.025 Adoption of State blood alcohol concentration levels. (a) This section applies to... established by statute a blood alcohol concentration level for purposes of determining whether a person is...

33 CFR 95.025 - Adoption of State blood alcohol concentration levels.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Adoption of State blood alcohol... DANGEROUS DRUG § 95.025 Adoption of State blood alcohol concentration levels. (a) This section applies to... established by statute a blood alcohol concentration level for purposes of determining whether a person is...

33 CFR 95.025 - Adoption of State blood alcohol concentration levels.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Adoption of State blood alcohol... DANGEROUS DRUG § 95.025 Adoption of State blood alcohol concentration levels. (a) This section applies to... established by statute a blood alcohol concentration level for purposes of determining whether a person is...

33 CFR 95.025 - Adoption of State blood alcohol concentration levels.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Adoption of State blood alcohol... DANGEROUS DRUG § 95.025 Adoption of State blood alcohol concentration levels. (a) This section applies to... established by statute a blood alcohol concentration level for purposes of determining whether a person is...

33 CFR 95.025 - Adoption of State blood alcohol concentration levels.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Adoption of State blood alcohol... DANGEROUS DRUG § 95.025 Adoption of State blood alcohol concentration levels. (a) This section applies to... established by statute a blood alcohol concentration level for purposes of determining whether a person is...

10 CFR 850.31 - Release criteria.

Code of Federal Regulations, 2010 CFR

2010-01-01

... lowest contamination level practicable, but not to exceed the levels established in paragraphs (b) and (c... contamination level of equipment or item surfaces does not exceed the higher of 0.2 µg/100 cm 2 or the... the equipment or item and its future use and the nature of the beryllium contamination. (c) Before...

Antibiotics in the human food chain: establishing no effect levels of tetracycline, neomycin, and erythromycin using a chemostat model of the human colonic microflora.

PubMed

Carman, Robert J; Simon, Mary Alice; Petzold, H Earl; Wimmer, Robert F; Batra, Monica R; Fernández, A Haydée; Miller, Margaret A; Bartholomew, Mary

2005-11-01

A chemostat model of the healthy human large bowel ecosystem was used to establish no effect levels for tetracycline, neomycin, and erythromycin. For each compound, the equivalent to four oral doses (0, 1.5, 15, and 150 mg/60 kg person/d) was studied. Concentrations of the test compounds in the chemostat medium were intended to simulate fecal levels that might be expected following consumption of food containing antibiotic residue and were based on published oral doses and fecal levels. We monitored the following parameters: short chain fatty acids, bile acids, sulfate reduction, azoreductase and nitroreductase activities, beta-glucosidase and beta-glucuronidase activities, a range of bacterial counts and, lastly, the susceptibility among sentinel bacteria to each test compound. Neomycin and erythromycin reduced bile acid metabolism. Neomycin elevated propionate levels and caused a marginal diminution in azoreductase activity. Based on our results, the no observed effect level (NOEL) of both tetracycline and erythromycin was 15 mg/60 kg person/d. The NOEL for neomycin was 1.5 mg/60 kg person/d.

[The co-payment of the dependence from the structural reform of 2012 in Spain].

PubMed

Del Pozo-Rubio, Raúl; Pardo-García, Isabel; Escribano-Sotos, Francisco

The objective of this piece of work is to establish the cost of dependency and the cost of financing it. Specifically, we will determine the cost of co-payment for individual users following the modification introduced by the 13th of July 2012 Resolution as well as its allocation by the autonomous regions. The degree and level of dependency was established using the Survey on Disability, Personal Autonomy and Dependency Situations, 2008. The cost of dependency according to degree and level and autonomous regions was established with information from the System for Personal Autonomy and Care of Dependent Persons. The co-payment was established according to applicants' purchasing power. The rating of these services, and the contribution of individual users were done in agreement with 2012 legislation and with common indicators and benchmarks for the whole national territory. The total estimated cost is 10,598.8 million euros (1.03% of GDP), and Andalusia, the Valencian Community and Catalonia are those regions with the greatest costs. The average national co-payment per individual user is 53.54%, with differences due to degrees and levels of disability and autonomous regions, although, generally speaking, all of the users fund more than half of the care they receive. This change in legislation has meant that co-payment is higher than the 33% established by this law and that co-payments prior to 2012 were about 20%. If we add to this the differences in autonomous regions, it would be useful to reflect on the uneven application of the law. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Optimizing Staffing levels and Schedules for Railroad Dispatching Centers

DOT National Transportation Integrated Search

2004-09-01

This report presents the results of a study to explore approaches to establishing staffing levels and schedules for railroad dispatchers. The : work was conducted as follow-up to a prior study that found fatigue among dispatchers, particularly those ...

Organizing Performance Requirements For Dynamical Systems

NASA Technical Reports Server (NTRS)

Malchow, Harvey L.; Croopnick, Steven R.

1990-01-01

Paper describes methodology for establishing performance requirements for complicated dynamical systems. Uses top-down approach. In series of steps, makes connections between high-level mission requirements and lower-level functional performance requirements. Provides systematic delineation of elements accommodating design compromises.

Just-in-time: maximizing its success potential.

PubMed

Johnston, S K

1990-08-01

The effective implementation and use of JIT manufacturing practices depends largely on the education, training, and commitment of all levels of management to a fundamental quality-first policy. Management must transfer and demonstrate that commitment to every level and extension of the manufacturing endeavor. As a company establishes and reaches toward that goal, the move to JIT manufacturing practices becomes rational and justifiable. Failing to establish and commit to a quality directive greatly diminishes the potential benefits of JIT. If all levels of manufacturing participate in the JIT planning, implementing, and maintenance procedure, the realization of positive change and improvement drives the process. Total participation makes the task of JIT implementation not only possible, but practical. Enhanced mutual respect for all concerned is a likely consequence, advancing the productive environment.

Establishment of a Novel Permissive Cell Line for the Propagation of Hepatitis C Virus by Expression of MicroRNA miR122

PubMed Central

Kambara, Hiroto; Fukuhara, Takasuke; Shiokawa, Mai; Ono, Chikako; Ohara, Yuri; Kamitani, Wataru

2012-01-01

The robust cell culture systems for hepatitis C virus (HCV) are limited to those using cell culture-adapted clones (HCV in cell culture [HCVcc]) and cells derived from the human hepatoma cell line Huh7. However, accumulating data suggest that host factors, including innate immunity and gene polymorphisms, contribute to the variation in host response to HCV infection. Therefore, the existing in vitro systems for HCV propagation are not sufficient to elucidate the life cycle of HCV. A liver-specific microRNA, miR122, has been shown to participate in the efficient replication of HCV. In this study, we examined the possibility of establishing a new permissive cell line for HCV propagation by the expression of miR122. A high level of miR122 was expressed by a lentiviral vector placed into human liver cell lines at a level comparable to the endogenous level in Huh7 cells. Among the cell lines that we examined, Hep3B cells stably expressing miR122 (Hep3B/miR122) exhibited a significant enhancement of HCVcc propagation. Surprisingly, the levels of production of infectious particles in Hep3B/miR122 cells upon infection with HCVcc were comparable to those in Huh7 cells. Furthermore, a line of “cured” cells, established by elimination of HCV RNA from the Hep3B/miR122 replicon cells, exhibited an enhanced expression of miR122 and a continuous increase of infectious titers of HCVcc in every passage. The establishment of the new permissive cell line for HCVcc will have significant implications not only for basic HCV research but also for the development of new therapeutics. PMID:22114337

All-trans retinoic acid inhibits craniopharyngioma cell growth: study on an explant cell model.

PubMed

Li, Qiang; You, Chao; Zhou, Liangxue; Sima, Xiutian; Liu, Zhiyong; Liu, Hao; Xu, Jianguo

2013-05-01

The ratio between FABP5 and CRABPII determines cellular response to physiological level of retinoic acid; tumor cells undergo proliferation with high level of FABP5 and apoptosis with high level of CRABPII. We intended to study FABP5 and CRABPII expression in craniopharyngiomas, to establish craniopharyngioma cell model using explants method, and to study the effect of pharmacological dose of retinoic acid on craniopharyngioma cells. Expression of FABP5 and CRABPII in craniopharyngioma tissue from 20 patients was studied using immunohistochemistry. Primary craniopharyngioma cell cultures were established using tissue explants method. Craniopharyngioma cells were treated using various concentrations of all-trans retinoic acid, and cell growth curve, apoptosis, expression of FABP5, CRABPII and NF-κB were assayed in different groups. FABP5/CRABPII ratio was significantly higher in adamatinomatous group than that in papillary group. Cell cultures were established in 19 cases (95 %). Pharmacological level retinoic acid inhibited cell growth and induced cellular apoptosis in dose dependent manner, and apoptosis rate cells treated with 30 μM retinoic acid for 24 h was 43 %. Also, retinoic acid increased CRABPII, and decreased FABP5 and NF-κB expression in craniopharyngioma cells. High FABP5/CRABPII ratio is observed in adamatinomatous craniopharyngioma. Retinoic acid at pharmacological level induced craniopharyngioma cell apoptosis via increasing FABP5/CRABPII ratio and inhibiting NF-κB signaling pathway. Our study demonstrated that all-trans retinoic acid might be a candidate for craniopharyngioma adjuvant chemotherapy in future.

Micronuclei and erythrocytic abnormalities frequencies of freshwater fishes: Establishing a baseline for health status

NASA Astrophysics Data System (ADS)

Sousa, Debora Batista Pinheiro; Torres, Audalio Rebelo; Oliveira, Suelen Rosana Sampaio; Castro, Jonatas da Silva; Neta, Raimunda Nonata Fortes Carvalho

2017-11-01

Majority papers shows that micronucleus test and erythrocyte abnormalities are excellent tools such as tools for monitor fish health and the level of impact in aquatic ecosystems. Nevertheless, still do not know the baseline for those changes in freshwater fishes communities in the Brazilian Northeastern river. In this study, we show the level of basis of two species of freshwater fishes (Colossoma macropomum -tambaqui and Oreochromis niloticus - tilápia) with the aim of establish levels of background these species. The animals were collected from Ambude river in the protected area and blood collected from all fish for analysis. Erythrocyte indices—mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)—were calculated. Blood samples from all fish were examined for micronuclear changes after Giemsa staining. Micronuclei were found in fish from from Ambude River. The baseline values determined for tambaqui was (micronuclei= 0.0071±0.0026; MCV=0.0073±0.0037; MCHV=0.0071±0.0024) and tilapia (micronuclei= 0.0061±0.0026; MCV=0.0037±0.0017; MCHV=0.056±0.0036). We belive that, we propose using the genotoxic approach for estimating fish health status as the technique allows examination in locus of live fish without the need for animal euthanasia. Besides, baseline level can be to establish levels of background and patterns to pathological and physiological research of these species in future biomonitoring programs.

Measurement of fine breathable particles (PM(2.5)) as a marker of environmental smoke in catering establishments in Zaragoza.

PubMed

Nerín, Isabel; Alayeto, Carmen; Córdoba, Rodrigo; López, María José; Nebot, Manel

2011-04-01

To estimate the levels of small breathable suspended particles (PM(2.5)) as atmospheric markers of environmental tobacco smoke in catering establishments in Zaragoza, Spain. An observational study was conducted between October 2006 and April 2008 in various catering establishments in Zaragoza. A SidePack Aerosol Monitor (AM510 model) was used to sample and record the levels of breathable suspended particles (PM(2.5)) indoors and outdoors, and the following variables were collected: smoking policy (smoking allowed, completely banned, or partially banned with non-smoking sections, physically separated or not); percentage of smokers and presence of cigarette ends, ashtrays or smokers in non-smoking sections. A total of 111 venues were sampled. The level of PM(2.5) was eight times higher in smoking venues than in non-smoking ones and also higher than outdoors. The correlation between the level of particles and percentage of smokers was 0.61 (P<.01). In the non-smoking sections without physical separation the level of particles was twice as much as outdoors and similar to physically separated smokers sections. Only a complete ban on smoking in all workplaces, including leisure venues, has been shown to have a positive effect on workers and customers health. The measurement of PM(2.5) can be a simple method to assess the presence of environmental tobacco smoke. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

Establishing confidence in CCV/ACT technology

NASA Technical Reports Server (NTRS)

Holloway, R. B.; Shomber, H. A.

1976-01-01

Despite significant advancements in controls configured vehicles/active controls technology (CCV/ACT) in the past decade, few applications of this promising technology have appeared in recent aircraft designs. The status of CCV/ACT is summarized, and some of the constraints which are retarding its wider application are described. Suggestions toward establishing an increased level of confidence in the technology are given.

Identifying the Training Needs of Heads of Department in a Newly Established University in Vietnam

ERIC Educational Resources Information Center

Nguyen, Thi Lan Huong

2012-01-01

Although middle-level academic managers really need training in order to perform their roles adequately in the very changing context of higher education, little formal training is provided, particularly in less developed countries. This paper identifies the training needs of Heads of Department in a newly established university in Vietnam as a…

Plan Nacional de Desarrollo y Seguridad 1971-1975 (National Plan for Development and Security, 1971-1975).

ERIC Educational Resources Information Center

Boletin del Centro Nacional de Documentacion e Informacion Educativa, 1971

1971-01-01

This article discusses the education provisions established in the Argentine Plan for Development and Security (1971-1975). The statements on educational development call for a diagnostic study of the current cultural and educational situation, the establishment of objectives and strategies, goals for each level of education, steps for the…

77 FR 40255 - Special Conditions: Boeing, Model 737-800; Large Non-Structural Glass in the Passenger Compartment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

...-0499; Special Conditions No. 25-466-SC] Special Conditions: Boeing, Model 737-800; Large Non-Structural... with the installation of large non-structural glass items in the cabin area of an executive interior... Administrator considers necessary to establish a level of safety equivalent to that established by the existing...

76 FR 31454 - Special Conditions: Gulfstream Model GVI Airplane; Automatic Speed Protection for Design Dive Speed

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... the dive from non-symmetric attitudes, unless the airplane is protected by the flight control laws... necessary to establish a level of safety equivalent to that established by the existing airworthiness... 611 of Public Law 92-574, the ``Noise Control Act of 1972.'' The FAA issues special conditions, as...

Using Standardized Pre-Posttests to Establish Program Equivalency at Multiple Sites

ERIC Educational Resources Information Center

Ritchie, William F.; Kreitner, David

2005-01-01

Keiser College is a private, for-profit Level II institution with thirteen branch campuses throughout Florida. Most of its academic programs are offered at multiple sites. A major concern has been to establish and maintain the consistency of its academic offerings at all campuses as the College expands. Building on a pre- posttesting mechanism…

Grassroots branding.

PubMed

Ferris, Michael T

2005-04-01

In home care and hospice, effective branding begins at the grassroots level. Historically, high-level, widespread branding initiatives have proven relatively unsuccessful in these industries, and have not delivered a positive return on investment. This is generally because in home care and hospice, branding is most successfully implemented at individual and local levels. Since an agency's "brand" is established at this personal level, relationships are the crucial keys to sales and marketing success.

Presbycusis, sociocusis, and nosocusis

NASA Technical Reports Server (NTRS)

1984-01-01

The establishment of a baseline of normal hearing is investigated through the examination of pure tone hearing level surveys and variables such as age, sociocusis, sex, race, and otological disorders. Mathematical formulae used to predict hearing levels in industrial and nonindustrial surveys is included.

20 CFR 404.1670 - General.

Code of Federal Regulations, 2010 CFR

2010-04-01

...' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950... three established threshold levels, one being performance accuracy, for two consecutive quarters, and... period. During this 3-month period we will not require the State agency to meet the threshold levels...

20 CFR 416.1070 - General.

Code of Federal Regulations, 2010 CFR

2010-04-01

...' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED... three established threshold levels, one being performance accuracy, for two consecutive quarters, and... period. During this 3-month period we will not require the State agency to meet the threshold levels...

Design, innovation, and rural creative places: Are the arts the cherry on top, or the secret sauce?

PubMed Central

Nichols, Bonnie

2018-01-01

Objective Creative class theory explains the positive relationship between the arts and commercial innovation as the mutual attraction of artists and other creative workers by an unobserved creative milieu. This study explores alternative theories for rural settings, by analyzing establishment-level survey data combined with data on the local arts scene. The study identifies the local contextual factors associated with a strong design orientation, and estimates the impact that a strong design orientation has on the local economy. Method Data on innovation and design come from a nationally representative sample of establishments in tradable industries. Latent class analysis allows identifying unobserved subpopulations comprised of establishments with different design and innovation orientations. Logistic regression allows estimating the association between an establishment’s design orientation and local contextual factors. A quantile instrumental variable regression allows assessing the robustness of the logistic regression results with respect to endogeneity. An estimate of design orientation at the local level derived from the survey is used to examine variation in economic performance during the period of recovery from the Great Recession (2010–2014). Results Three distinct innovation (substantive, nominal, and non-innovators) and design orientations (design-integrated, “design last finish,” and no systematic approach to design) are identified. Innovation- and design-intensive establishments were identified in both rural and urban areas. Rural design-integrated establishments tended to locate in counties with more highly educated workforces and containing at least one performing arts organization. A quantile instrumental variable regression confirmed that the logistic regression result is robust to endogeneity concerns. Finally, rural areas characterized by design-integrated establishments experienced faster growth in wages relative to rural areas characterized by establishments using no systematic approach to design. PMID:29489884

Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.

PubMed

González-García, I; García-Arieta, A; Merino-Sanjuan, M; Mangas-Sanjuan, V; Bermejo, M

2018-07-01

Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and C max between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a controlled release formulation. Then, in order to compare this new approach with the classical one, six additional batches were simulated. For each batch, 1000 simulations of a dissolution assay were run. C max ratios between the reference formulation and each batch were calculated showing that the individual approach was more sensitive and able to detect differences between the reference and the batch formulation compared to the classical approach. Additionally, the new methodology displays wider dissolution specification limits than the classical approach, ensuring that any tablet from the new batch would generate in vivo profiles which its AUC or C max ratio will be out of the 0.8-1.25 range, taking into account the in vitro and in vivo variability of the new batches developed. Copyright © 2018 Elsevier B.V. All rights reserved.

Lipid and lipoprotein testing in resource-limited laboratories.

PubMed

Myers, Gary L

2003-01-01

The role of total cholesterol (TC) and lipoproteins in the assessment of coronary heart disease (CHD) is firmly established from population and intervention studies. Total and low-density lipoprotein cholesterol (LDLC) levels are positively associated with CHD, and high-density lipoprotein cholesterol (HDLC) levels are negatively associated with CHD. Efforts to identify and treat people at increased risk based on cholesterol and lipoprotein levels have led to more lipid testing and the need for very reliable test results. Thus, quality laboratory services are an essential component of healthcare delivery and play a vital role in any strategy to reduce morbidity and mortality from CHD. In laboratories with limited resources, establishing laboratory capability to measure CHD risk markers may be a considerable challenge. Laboratories face problems in selecting proper techniques, difficulties in equipment availability and maintenance, and shortage of supplies, staffing, and supervision. The Centers for Disease Control and Prevention (CDC) has been providing technical assistance for more than 30 years to laboratories that measure lipids and lipoproteins and is willing to provide technical assistance as needed for other laboratories to develop this capability. CDC can provide technical assistance to establish lipid and lipoprotein testing capability to support a CHD public health program in areas with limited laboratory resources. This assistance includes: selecting a suitable testing instrument; providing training for laboratory technicians; establishing a simple quality control plan; and instructing staff on how to prepare frozen serum control materials suitable for assessing accuracy of lipid and lipoprotein testing.

What does semantic tiling of the cortex tell us about semantics?

PubMed

Barsalou, Lawrence W

2017-10-01

Recent use of voxel-wise modeling in cognitive neuroscience suggests that semantic maps tile the cortex. Although this impressive research establishes distributed cortical areas active during the conceptual processing that underlies semantics, it tells us little about the nature of this processing. While mapping concepts between Marr's computational and implementation levels to support neural encoding and decoding, this approach ignores Marr's algorithmic level, central for understanding the mechanisms that implement cognition, in general, and conceptual processing, in particular. Following decades of research in cognitive science and neuroscience, what do we know so far about the representation and processing mechanisms that implement conceptual abilities? Most basically, much is known about the mechanisms associated with: (1) feature and frame representations, (2) grounded, abstract, and linguistic representations, (3) knowledge-based inference, (4) concept composition, and (5) conceptual flexibility. Rather than explaining these fundamental representation and processing mechanisms, semantic tiles simply provide a trace of their activity over a relatively short time period within a specific learning context. Establishing the mechanisms that implement conceptual processing in the brain will require more than mapping it to cortical (and sub-cortical) activity, with process models from cognitive science likely to play central roles in specifying the intervening mechanisms. More generally, neuroscience will not achieve its basic goals until it establishes algorithmic-level mechanisms that contribute essential explanations to how the brain works, going beyond simply establishing the brain areas that respond to various task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Communications and tracking expert systems study

NASA Technical Reports Server (NTRS)

Leibfried, T. F.; Feagin, Terry; Overland, David

1987-01-01

The original objectives of the study consisted of five broad areas of investigation: criteria and issues for explanation of communication and tracking system anomaly detection, isolation, and recovery; data storage simplification issues for fault detection expert systems; data selection procedures for decision tree pruning and optimization to enhance the abstraction of pertinent information for clear explanation; criteria for establishing levels of explanation suited to needs; and analysis of expert system interaction and modularization. Progress was made in all areas, but to a lesser extent in the criteria for establishing levels of explanation suited to needs. Among the types of expert systems studied were those related to anomaly or fault detection, isolation, and recovery.

40 CFR 63.505 - Parameter monitoring levels and excursions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... less than 4 hours in an operating day and more than two of the hours during the period of operation do... filling period for the storage vessel, is above the maximum level or below the minimum level established... plan, during the filling period for the storage vessel. (ii) If the monitoring plan does not specify...

Results of a Program Effectiveness Survey Used to Guide Curriculum Revision in a Middle Level Teacher Education Program

ERIC Educational Resources Information Center

Knorr, Ron; Medord, Lienne

2013-01-01

Teacher education programs are under extreme scrutiny as the demands for effectiveness and efficiency increase in the current political and operational environment. Within the framework established by This We Believe (AMLE, 2010) and the Position Statement on the Professional Preparation of Middle Level Teachers (AMLE, 2011), middle level teacher…

Setters and Samoyeds: The Emergence of Subordinate Level Categories as a Basis for Inductive Inference in Preschool-Age Children.

ERIC Educational Resources Information Center

Waxman, Sandra R.; Lynch, Elizabeth B.; Casey, K. Lyman; Baer, Leslie

1997-01-01

Three experiments examine how preschoolers partition their basic level categories to form subordinate level categories and whether these have inductive potential. Results suggest that contrastive information promotes the emergence of subordinate categories as a basis of inductive inference and newly established subordinate categories can retain…

40 CFR Table 2 to Subpart Sssss of... - Operating Limits

Code of Federal Regulations, 2010 CFR

2010-07-01

... activity level of the catalyst at least every 12 months. 7. Each affected batch process unit For each batch... activity level of the catalyst at least every 12 months. 10. Each new kiln that is used to process clay... across the DLA at or above the minimum levels established during the most recent performance test; and b...

40 CFR Table 2 to Subpart Sssss of... - Operating Limits

Code of Federal Regulations, 2011 CFR

2011-07-01

... activity level of the catalyst at least every 12 months. 7. Each affected batch process unit For each batch... activity level of the catalyst at least every 12 months. 10. Each new kiln that is used to process clay... across the DLA at or above the minimum levels established during the most recent performance test; and b...

40 CFR Table 8 to Subpart Sssss of... - Continuous Compliance with Operating Limits

Code of Federal Regulations, 2011 CFR

2011-07-01

... activity level of the catalyst at least every 12 months and taking any necessary corrective action, such as... temperature measured during the most recent performance test; and vi. Checking the activity level of the... hopper. c. Maintain the limestone feeder setting at or above the level established during the most recent...

Emotional and Behavioural Problems in Children with Language Impairments and Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Charman, Tony; Ricketts, Jessie; Dockrell, Julie E.; Lindsay, Geoff; Palikara, Olympia

2015-01-01

Background: Although it is well-established that children with language impairment (LI) and children with autism spectrum disorders (ASD) both show elevated levels of emotional and behavioural problems, the level and types of difficulties across the two groups have not previously been directly compared. Aims: To compare levels of emotional and…

Average Treatment Effect of School-Wide Positive Behavioral Interventions and Supports on School-Level Academic Achievement in Florida

ERIC Educational Resources Information Center

Gage, Nicholas A.; Leite, Walter; Childs, Karen; Kincaid, Don

2017-01-01

The relationship between school-wide positive behavioral interventions and supports (SWPBIS) and school-level academic achievement has not been established. Most experimental research has found little to no evidence that SWPBIS has a distal effect on school-level achievement. Yet, an underlying assumption of SWPBIS is that improving social…

5 CFR 530.304 - Establishing or increasing special rates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... otherwise payable to a category of employees in one or more areas or locations, grades or levels... made in one or more of the remaining rates of the affected grade or level. For any given grade, a.... A special rate may not exceed the rate for level IV of the Executive Schedule. (b) The circumstances...

Nebraska Schools 83-84 Immunization Levels.

ERIC Educational Resources Information Center

Nebraska State Dept. of Health, Lincoln.

The data contained in this report represents all of the 297,696 students, K-12, in the state of Nebraska. High levels of immunity are documented among children grades K-6. Some immunization levels of children grades 7-12 are yet below the 95 percent established as a minimum for the prevention of vaccine preventable diseases. Specifically, there…

Relationship between Organizational Justice Perceptions and Organizational Commitment Levels of School of Physical Education and Sports Academicians

ERIC Educational Resources Information Center

Ari, Abdil; Çaglayan, Hakan Salim

2017-01-01

This study was conducted to determine organizational justice perceptions and organizational commitment levels of the school of physical education and sports academicians and to establish whether there is a relation between their organizational justice perceptions and organizational commitment levels or not. In the study, a method for the…

Crossing levels in systems ergonomics: a framework to support 'mesoergonomic' inquiry.

PubMed

Karsh, Ben-Tzion; Waterson, Patrick; Holden, Richard J

2014-01-01

In this paper we elaborate and articulate the need for what has been termed 'mesoergonomics'. In particular, we argue that the concept has the potential to bridge the gap between, and integrate, established work within the domains of micro- and macroergonomics. Mesoergonomics is defined as an open systems approach to human factors and ergonomics (HFE) theory and research whereby the relationship between variables in at least two different system levels or echelons is studied, and where the dependent variables are human factors and ergonomic constructs. We present a framework which can be used to structure a set of questions for future work and prompt further empirical and conceptual inquiry. The framework consists of four steps: (1) establishing the purpose of the mesoergonomic investigation; (2) selecting human factors and ergonomics variables; (3) selecting a specific type of mesoergonomic investigation; and (4) establishing relationships between system levels. In addition, we describe two case studies which illustrate the workings of the framework and the value of adopting a mesoergonomic perspective within HFE. The paper concludes with a set of issues which could form part of a future agenda for research within systems ergonomics. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Is the density of alcohol establishments related to nonviolent crime?

PubMed

Toomey, Traci L; Erickson, Darin J; Carlin, Bradley P; Quick, Harrison S; Harwood, Eileen M; Lenk, Kathleen M; Ecklund, Alexandra M

2012-01-01

We examined the associations between the density of alcohol establishments and five types of nonviolent crime across urban neighborhoods. Data from the city of Minneapolis, MN, in 2009 were aggregated and analyzed at the neighborhood level. We examined the association between alcohol establishment density and five categories of nonviolent crime: vandalism, nuisance crime, public alcohol consumption, driving while intoxicated, and underage alcohol possession/consumption. A Bayesian approach was used for model estimation accounting for spatial auto-correlation and controlling for relevant neighborhood demographics. Models were estimated for total alcohol establishment density and then separately for off-premise establishments (e.g., liquor and convenience stores) and on-premise establishments (e.g., bars and restaurants). We found positive associations between density and each crime category. The association was strongest for public consumption and weakest for vandalism. We estimated that a 3.3%-10.9% increase across crime categories would result from a 20% increase in neighborhood establishment density. Similar results were seen for on- and off-premise establishments, although the strength of the associations was lower for off-premise density. Our results indicate that communities should consider the potential increase in nonviolent crime associated with an increase in the number of alcohol establishments within neighborhoods.

Validation of the BetaStar® Advanced for Tetracyclines Test Kit for the Screening of Bulk Tank and Tanker Truck Milks for the Presence of Tetracycline Drug Residues.

PubMed

Ankrapp, David; Schaus, Benjamin; Clements, Lauren; Klein, Frank; Rice, Jennifer; Rejman, John

2018-05-09

A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Tetracyclines) for detection of tetracycline antibiotic residues in raw, commingled bovine milk. The assay was demonstrated to detect tetracycline, chlortetracycline, and oxytetracycline at levels below the FDA tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. Results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. All three drugs at the approximate 90/95% sensitivity levels were detected in milk collected from cows that had been treated with the specific drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 881 control milk samples. Testing the estimated 90/95 sensitivity level for tetracycline (213 ppb), chlortetracycline (272 ppb), and oxytetracycline (180 ppb) and at 1000 ppb for each antibiotic resulted in 100% positive tests for each tetracycline. Results of ruggedness experiments established the operating parameter tolerances for the test. Results of cross-reactivity testing established that the assay detects certain other tetracycline drugs but does not cross-react with any of 32 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts (SCC) in raw milk produced no assay interference.

Independent Validation and Verification of automated information systems in the Department of Energy

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

Hunteman, W.J.; Caldwell, R.

1994-07-01

The Department of Energy (DOE) has established an Independent Validation and Verification (IV&V) program for all classified automated information systems (AIS) operating in compartmented or multi-level modes. The IV&V program was established in DOE Order 5639.6A and described in the manual associated with the Order. This paper describes the DOE IV&V program, the IV&V process and activities, the expected benefits from an IV&V, and the criteria and methodologies used during an IV&V. The first IV&V under this program was conducted on the Integrated Computing Network (ICN) at Los Alamos National Laboratory and several lessons learned are presented. The DOE IV&Vmore » program is based on the following definitions. An IV&V is defined as the use of expertise from outside an AIS organization to conduct validation and verification studies on a classified AIS. Validation is defined as the process of applying the specialized security test and evaluation procedures, tools, and equipment needed to establish acceptance for joint usage of an AIS by one or more departments or agencies and their contractors. Verification is the process of comparing two levels of an AIS specification for proper correspondence (e.g., security policy model with top-level specifications, top-level specifications with source code, or source code with object code).« less

46 CFR 15.715 - Automated vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS... automated system in establishing initial manning levels; however, until the system is proven reliable, a manning level adequate to operate in a continuously attended mode will be specified on a vessel's COI. It...

An investigation of toll plaza capacity and level of service.

DOT National Transportation Integrated Search

1991-01-01

This study was undertaken to accomplish two objectives pertinent to traffic characteristics at toll plaza areas: (1) to develop a methodology for evaluating the capacity of a toll plaza, and (2) to establish level-of-service criteria for toll area tr...

46 CFR 15.715 - Automated vessels.

Code of Federal Regulations, 2012 CFR

2012-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS... automated system in establishing initial manning levels; however, until the system is proven reliable, a manning level adequate to operate in a continuously attended mode will be specified on a vessel's COI. It...

46 CFR 15.715 - Automated vessels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS... automated system in establishing initial manning levels; however, until the system is proven reliable, a manning level adequate to operate in a continuously attended mode will be specified on a vessel's COI. It...

46 CFR 15.715 - Automated vessels.

Code of Federal Regulations, 2014 CFR

2014-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS... automated system in establishing initial manning levels; however, until the system is proven reliable, a manning level adequate to operate in a continuously attended mode will be specified on a vessel's COI. It...

46 CFR 15.715 - Automated vessels.

Code of Federal Regulations, 2013 CFR

2013-10-01

... GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS... automated system in establishing initial manning levels; however, until the system is proven reliable, a manning level adequate to operate in a continuously attended mode will be specified on a vessel's COI. It...

Establishment of new complete blood count reference values for healthy Thai adults.

PubMed

Wongkrajang, P; Chinswangwatanakul, W; Mokkhamakkun, C; Chuangsuwanich, N; Wesarachkitti, B; Thaowto, B; Laiwejpithaya, S; Komkhum, O

2018-04-28

Laboratory reference ranges are essential for diagnostic orientation and treatment decision. As complete blood count parameters are influenced by various factors, including gender, geographic origin, and ethnic origin, it is important to establish specific hematologic reference values for specific populations. This study was conducted at the Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Blood samples were taken from healthy adults aged 18-60 years that attended a health check-up program at our hospital during February 2015 to July 2015. Hematologic and routine chemistry analysis were performed. Participants were determined to be healthy based on medical history and routine medical examinations. Serum vitamin B12, folate, ferritin, and hemoglobin typing were also analyzed to exclude the possible presence of anemia. A statistically significant difference was observed between males and females for Hb level, hematocrit level, red blood cell count, mean corpuscular hemoglobin concentration, percentage neutrophils, monocytes and eosinophils, and absolute neutrophil, lymphocyte, basophil, and platelet counts. Accordingly, gender-specific reference intervals were established for all complete blood count parameters in healthy Thai adult population. The reference value ranges established in this study reflect significant differences between genders. It is possible that these reference ranges may be generalizable to adults living in Thailand. The findings of this study emphasize the importance of establishing specific hematologic reference values for specific populations. © 2018 John Wiley & Sons Ltd.

Do Transit-Oriented Developments (TODs) and Established Urban Neighborhoods Have Similar Walking Levels in Hong Kong?

PubMed

Lu, Yi; Gou, Zhonghua; Xiao, Yang; Sarkar, Chinmoy; Zacharias, John

2018-03-20

A sharp drop in physical activity and skyrocketing obesity rate has accompanied rapid urbanization in China. The urban planning concept of transit-oriented development (TOD) has been widely advocated in China to promote physical activity, especially walking. Indeed, many design features thought to promote walking-e.g., mixed land use, densification, and well-connected street network-often characterize both TODs and established urban neighborhoods. Thus, it is often assumed that TODs have similar physical activity benefits as established urban neighborhoods. To verify this assumption, this study compared walking behaviors in established urban neighborhoods and transit-oriented new towns in Hong Kong. To address the limitation of self-selection bias, we conducted a study using Hong Kong citywide public housing scheme, which assigns residents to different housing estates by flat availability and family size rather than personal preference. The results show new town residents walked less for transportation purpose than urban residents. New town residents far from the transit station (800-1200 m) walked less for recreational purpose than TOD residents close to a rail transit station (<400 m) or urban residents. The observed disparity in walking behaviors challenges the common assumption that TOD and established urban neighborhoods have similar impact on walking behavior. The results suggest the necessity for more nuanced planning strategies, taking local-level factors into account to promote walking of TOD residents who live far from transit stations.

Navy Training Lands Sustainability: Initiation Decision Report

DTIC Science & Technology

2004-06-01

Health Promotion and Preventative Medicine CLF Combat Logistics Force CMAQ Community Multiscale Air Quality CNEL Community Noise Equivalent Level...Environmental Consequences of Underwater Sound EDQW (DoD) Environmental Data Quality Workgroup EEZ Exclusive Economic Zone EFHA Essential Fish Habitat...Conservation Management Act established a 200-mile fishery conservation zone, which is now known as the Exclusive Economic Zone (EEZ), and established

75 FR 34959 - Five-Year Review of Oil Pipeline Pricing Index

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

... software should be filed in native applications or print-to-PDF format and not in a scanned format. Mail... F.3d 1424 (D.C. Cir. 1996). \\3\\ Order Establishing Index for Oil Price Change Ceiling Levels, 114... (2003), affirmed, Flying J Inc., et al., v. FERC, 363 F.3d 495 (DC Cir. 2004). \\6\\ Order Establishing...

Progressive Dysarthria and Augmentative and Alternative Communication in Conversation: Establishing the Reliability of the Dysarthria-in-Interaction Profile

ERIC Educational Resources Information Center

Bloch, Steven; Tuomainen, Jyrki

2017-01-01

Background: The Dysarthria-in-Interaction Profile's potential contribution to the clinical assessment of dysarthria-in-conversation has been outlined in the literature, but its consistency of use across different users has yet to be reported. Aims: To establish the level of consistency across raters on four different interaction categories. That…

An Empirical Examination of the Mechanisms Mediating between High-Performance Work Systems and the Performance of Japanese Organizations

ERIC Educational Resources Information Center

Takeuchi, Riki; Lepak, David P.; Wang, Heli; Takeuchi, Kazuo

2007-01-01

The resource-based view of the firm and social exchange perspectives are invoked to hypothesize linkages among high-performance work systems, collective human capital, the degree of social exchange in an establishment, and establishment performance. The authors argue that high-performance work systems generate a high level of collective human…

Teachers Training through Distance Mode in Allama Iqbal Open University (AIOU) Pakistan: A Case Study

ERIC Educational Resources Information Center

Jumani, Nabi Bux; Rahman, Fazalur; Chishti, Saeedul Hasan; Malik, Samina

2011-01-01

Allama Iqbal Open University (AIOU) is the first Open University in Asia and established in 1974 on the model of UKOU. AIOU uses different media for the delivery of instruction. It has a well established Institute of Educational Technology which has radio and TV production facilities and advance level of work in computer technology. AOU offers…

78 FR 11129 - Office of Engineering and Technology Seeks Comment on Updated OET-69 Software

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

... cell level, and also speeds calculations since the study grid only needs to be established one time... who choose to file by paper must file an original and one copy of each filing. If more than one docket... interface (implemented in Java), used to establish the parameters of the study and which draws data from...

Teaching Independent Learning Skills in the First Year: A Positive Psychology Strategy for Promoting Law Student Well-Being

ERIC Educational Resources Information Center

Field, Rachael; Duffy, James; Huggins, Anna

2015-01-01

Empirical evidence in Australia and overseas has established that in many university disciplines, students begin to experience elevated levels of psychological distress in their first year of study. There is now a considerable body of empirical data that establishes that this is a significant problem for law students. Psychological distress may…

Impact of Teachers' Implicit Theories and Perceived Pressures on the Establishment of an Autonomy Supportive Climate

ERIC Educational Resources Information Center

Leroy, Nadia; Bressoux, Pascal; Sarrazin, Philippe; Trouilloud, David

2007-01-01

According to self-determination theory, when teachers establish an autonomy supportive climate in the classroom, students demonstrate high levels of self-determination and are intrinsically motivated. The aim of this study was to identify factors leading teachers (N=336) to report that they create such a climate. We conducted a path analysis in…

Development of methods for the restoration of the American elm in forested landscapes

Treesearch

James M. Slavicek

2013-01-01

A project was initiated in 2003 to establish test sites to develop methods to reintroduce the American elm (Ulmus americana L.) in forested landscapes. American elm tree strains with high levels of tolerance to Dutch elm disease (DED) were established in areas where the trees can naturally regenerate and spread. The process of regeneration will...

Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

PubMed

Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

2014-11-01

Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

The clinical utility of tricyclic antidepressant blood levels: a review of the literature.

PubMed

Van Brunt, N

1983-01-01

An effort has been made to summarize clinical selection criteria for therapeutic drug monitoring for the tricyclic antidepressants (TCAs). A clear understanding of this would increase the number of patients who benefit from TCA blood-level determinations. Depression has been defined in terms of the old and new nomenclature in an attempt to clarify the ambiguities that necessarily exist in such an all-encompassing classification of disease. The biogenic amine hypothesis of depression is briefly reviewed, followed by the effect of pharmacokinetic parameters on the establishment of steady-state blood levels. The protein binding of the TCAs and the resulting effect on free versus total drug levels is discussed. Pharmaceuticals and other factors known to affect TCA blood levels are mentioned. Following a discussion of anticholinergic side effects and cardiotoxicity, therapeutic ranges for various TCAs are reviewed as to our current level of understanding. The remainder of the paper explores patient selection criteria for future clinical studies attempting to establish a drug level-effect relationship. Recent case histories are supplied throughout the text to illustrate the various subjects addressed. They also instruct the clinician and the laboratory scientist as to the potential use of TCA blood-level monitoring in the treatment of depression.

Assessment of serum leptin, pregnancy-associated plasma protein A and CRP levels as indicators of plaque vulnerability in patients with acute coronary syndrome.

PubMed

Lodh, Moushumi; Goswami, Binita; Parida, Ashok; Patra, Surajeet; Saxena, Alpana

2012-07-01

A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques. The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability. Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability. Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

Analyses of laboratory data and establishment of reference values and intervals for healthy elderly people.

PubMed

Kubota, K; Kadomura, T; Ohta, K; Koyama, K; Okuda, H; Kobayashi, M; Ishii, C; Fujiwara, Y; Nishiora, T; Ohmae, Y; Ohmae, T; Kitajima, M

2012-04-01

Protein-energy malnutrition is a common disorder in the elderly. Although serum albumin is commonly used as a nutritional marker, data is lacking on serum albumin levels in the elderly. The purpose of this study was to determine whether serum albumin levels decrease with advancing age and to establish reference value and interval of laboratory data for elderly people (75 years and over). Blood samples from 13821 healthy people, 42064 outpatients, and 15959 inpatients were collected during 2008. Blood from 127 of our nutrition support team (NST) patients was also collected during August 2006 and May 2009, and analyzed. Serum albumin, hemoglobin, total cholesterol levels and lymphocyte count were determined. We analyzed the change in each parameter in accordance with age, compared the data for elderly people with younger people, and established new reference values. Clinical outcomes were examined depending on the improved reference values. Albumin was lower in older persons than in younger persons. The estimated reference value and interval were 42 (48-36) g/l in older persons and was much lower in NST patients. Hemoglobin was decreased while cholesterol and lymphocyte count were not changed in older persons: all were markedly decreased in NST patients. Terms of hospital stay were significantly longer and mortality rates were significantly higher in older persons, comparing from above to below using a new reference value of albumin (36 g/l). The serum albumin level decreases with advancing age, but it was maintained to some extent in healthy older people. Serum albumin levels related to the clinical outcome. Hemoglobin and cholesterol levels and lymphocyte count were all lower in NST patients. These measurements may be valuable markers of nutritional status and can help in guiding the need for nutritional support.

The decrease in the population of Gluconacetobacter diazotrophicus in sugarcane after nitrogen fertilization is related to plant physiology in split root experiments.

PubMed

Rodríguez-Andrade, Osvaldo; Fuentes-Ramírez, Luis E; Morales-García, Yolanda E; Molina-Romero, Dalia; Bustillos-Cristales, María R; Martínez-Contreras, Rebeca D; Muñoz-Rojas, Jesús

2015-01-01

It has been established that a decrease in the population of Gluconacetobacter diazotrophicus associated with sugarcane occurs after nitrogen fertilization. This fact could be due to a direct influence of NH(4)NO(3) on bacterial cells or to changes in plant physiology after fertilizer addition, affecting bacterial establishment. In this work, we observed that survival of G. diazotrophicus was directly influenced when 44.8mM of NH(4)NO(3) (640mgN/plant) was used for in vitro experiments. Furthermore, micropropagated sugarcane plantlets were inoculated with G. diazotrophicus and used for split root experiments, in which both ends of the system were fertilized with a basal level of NH(4)NO(3) (0.35mM; 10mgN/plant). Twenty days post inoculation (dpi) one half of the plants were fertilized with a high dose of NH(4)NO(3) (6.3mM; 180 mgN/plant) on one end of the system. This nitrogen level was lower than that directly affecting G. diazotrophicus cells; however, it caused a decrease in the bacterial population in comparison with control plants fertilized with basal nitrogen levels. The decrease in the population of G. diazotrophicus was higher in pots fertilized with a basal nitrogen level when compared with the corresponding end supplied with high levels of NH4NO3 (100dpi; 80 days post fertilization) of the same plant system. These observations suggest that the high nitrogen level added to the plants induce systemic physiological changes that affect the establishment of G. diazotrophicus. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

In-beam γ -ray spectroscopy of Mn 63

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

Baugher, T.; Gade, A.; Janssens, R. V. F.

2016-01-01

Background: Neutron-rich, even-mass chromium and iron isotopes approaching neutron number N = 40 have been important benchmarks in the development of shell-model effective interactions incorporating the effects of shell evolution in the exotic regime. Odd-mass manganese nuclei have received less attention, but provide important and complementary sensitivity to these interactions. Purpose: We report the observation of two new γ -ray transitions in 63 Mn , which establish the ( 9 / 2 - ) and ( 11 / 2 - ) levels on top of the previously known ( 7 / 2 - ) first-excited state. The lifetime for themore » ( 7 / 2 - ) and ( 9 / 2 - ) excited states were determined for the first time, while an upper limit could be established for the ( 11 / 2 - ) level. Method: Excited states in 63 Mn have been populated in inelastic scattering from a 9 Be target and in the fragmentation of 65 Fe . γ γ coincidence relationships were used to establish the decay level scheme. A Doppler line-shape analysis for the Doppler-broadened ( 7 / 2 - ) → 5 / 2 - , ( 9 / 2 - ) → ( 7 / 2 - ) , and ( 11 / 2 - ) → ( 9 / 2 - ) transitions was used to determine (limits for) the corresponding excited-state lifetimes. Results: The low-lying level scheme and the excited-state lifetimes were compared with large-scale shell-model calculations using different model spaces and effective interactions in order to isolate important aspects of shell evolution in this region of structural change. Conclusions: While the theoretical ( 7 / 2 - ) and ( 9 / 2 - ) excitation energies show little dependence on the model space, the calculated lifetime of the ( 7 / 2 - ) level and calculated energy of the ( 11 / 2 - ) level reveal the importance of including the neutron g 9 / 2 and d 5 / 2 orbitals in the model space. The LNPS effective shell-model interaction provides the best overall agreement with the new data.« less

Establishment of primary mixed cell cultures from spontaneous canine mammary tumors: Characterization of classic and new cancer-associated molecules

PubMed Central

Gentile, Luciana B.; Nagamine, Marcia K.; Biondi, Luiz R.; Sanches, Daniel S.; Toyota, Fábio; Giovani, Tatiane M.; de Jesus, Isis P.; da Fonseca, Ivone I. M.; Queiroz-Hazarbassanov, Nicolle; Diaz, Bruno L.; Salles Gomes, Cristina de O. Massoco

2017-01-01

There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, β and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRβ and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development. PMID:28945747

Vitamin D in patients with intellectual and developmental disability in secure in-patient services in the North of England, UK.

PubMed

McKinnon, Iain; Lewis, Thomas; Mehta, Naomi; Imrit, Shahed; Thorp, Julie; Ince, Chris

2018-02-01

Aims and method To assess the benefits of the introduction of routine vitamin D serum sampling for all patients admitted to a secure in-patient hospital in the North of England providing medium security, low security and rehabilitation services for offenders with intellectual and developmental disability. The vitamin D levels of 100 patients were analysed at baseline. Those with insufficient or deficient levels were offered treatment and retested after 1 year. Vitamin D levels were analysed in the context of level of security, seasonality of test and co-prescription of psychotropic medications. Eighty-three per cent of patients had suboptimal vitamin D levels at initial test (41% deficient and 42% insufficient). This was seen among established patients and new admissions. Regression analysis of baseline vitamin D levels revealed no differences for levels of security, seasonality, whether patients were taking antipsychotic or anticonvulsant medication, or length of stay. Patients with deficiency or insufficiency were all offered supplementation. Those who opted in had significantly higher vitamin D levels at follow-up, compared with those who declined treatment. Clinical implications Established and newly admitted patients in our secure mental health services had substantial levels of vitamin D insufficiency. In the light of the morbidities that are associated with deficient vitamin D levels, routine screening and the offer of supplementation is advisable. Declaration of interest None.

National Coordination Office for Space-Based PNT

NASA Astrophysics Data System (ADS)

Shaw, M. E.

2008-12-01

In December 2004, President Bush issued the US Policy on space-based positioning, navigation, and timing (PNT), providing guidance on the management of the Global Positioning System (GPS) and other space- based PNT systems. The policy established the National Executive Committee (EXCOM) to advise and coordinate federal agencies on matters related to space-based PNT. Chaired jointly by the deputy secretaries of defense and transportation, the EXCOM includes equivalent level officials from the Departments of State, the Interior, Agriculture, Commerce, and Homeland Security, the Joint Chiefs of Staff, and the National Aeronautics and Space Administration (NASA). A National Coordination Office (NCO) supports the EXCOM through an interagency staff. Since establishing the EXCOM and NCO in 2005, the organizations have quickly grown in influence and effectiveness, leading or managing many interagency initiatives including the development of a Five-Year National Space-Based PNT Plan, the Space-Based PNT Interference Detection and Mitigation (IDM) Plan, and other strategic documents. The NCO has also facilitated interagency coordination on numerous policy issues and on external communications intended to spread a consistent, positive US message about space-based PNT. Role of the NCO - The purpose of the EXCOM is to provide top-level guidance to US agencies regarding space-based PNT infrastructure. The president established it at the deputy secretary level to ensure its strategic recommendations effect real change in agency budgets. Recognizing such high-level officials could only meet every few months, the president directed the EXCOM to establish an NCO to carry out its day-to-day business, including overseeing the implementation of EXCOM action items across the member agencies. These range from the resolution of funding issues to the assessment of strategic policy options. They also include the completion of specific tasks and documents requested by the EXCOM co-chairs. The NCO has established several processes for achieving interagency consensus on policy issues, including specialized staff-level working groups and an assistant secretary-level Executive Steering Group. The NCO also established a process for interagency coordination of US government communications related to space-based PNT, including speeches, presentations, and other externally released documents. The goal is to ensure government-wide consistency and accuracy in public and international statements made about space-based PNT. This is particularly important in addressing false or misleading information about GPS in the public arena. Conclusion - In less than three years, the NCO evolved from an idea into a highly active organization with substantial influence within the space-based PNT community. NCO efforts have helped build the EXCOM into an effective mechanism for raising issues to the attention of senior leadership and ensuring their guidance gets implemented. While it is still a work in progress, the NCO has many significant accomplishments. The organization will continue to mature as ongoing US government space-based PNT activities continue to bear fruit.

Office of Nuclear Energy Knowledge Management Program Situational Analysis Report

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

Kimberlyn C. Mousseau

2011-12-01

Knowledge management (KM) has been a high priority for the Department of Energy (DOE) Office of Nuclear Energy (NE) for the past several years. NE Programs are moving toward well-established knowledge management practices and a formal knowledge management program has been established. Knowledge management is being practiced to some level within each of the NE programs. Although it continues to evolve as NE programs evolve, a formal strategic plan that guides the implementation of KM has been developed. Despite the acceptance of KM within DOE NE, more work is necessary before the NE KM program can be considered fully successful.more » Per Dr. David J. Skyrme[1], an organization typically moves through the following evolutionary phases: (1) Ad-hoc - KM is being practiced to some level in some parts of the organization; (2) Formal - KM is established as a formal project or program; (3) Expanding - the use of KM as a discipline grows in practice across different parts of the organization; (4) Cohesive - there is a degree of coordination of KM; (5) Integrated - there are formal standards and approaches that give every individual access to most organizational knowledge through common interfaces; and (6) Embedded - KM is part-and-parcel of everyday tasks; it blends seamlessly into the background. According to the evolutionary phases, the NE KM program is operating at the two lower levels, Ad-hoc and Formal. Although KM is being practiced to some level, it is not being practiced in a consistent manner across the NE programs. To be fully successful, more emphasis must be placed on establishing KM standards and processes for collecting, organizing, sharing and accessing NE knowledge. Existing knowledge needs to be prioritized and gathered on a routine basis, its existence formally recorded in a knowledge inventory. Governance to ensure the quality of the knowledge being used must also be considered. For easy retrieval, knowledge must be organized according to a taxonomy that mimics nuclear energy programs. Technologies need to be established to make accessing the knowledge easier for the user. Finally, knowledge needs to be used as part of a well defined work process.« less

Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level (INO2 and INO4) on lipid metabolism in yeast.

PubMed

Chumnanpuen, Pramote; Nookaew, Intawat; Nielsen, Jens

2013-10-16

In the yeast Saccharomyces cerevisiae, genes containing UASINO sequences are regulated by the Ino2/Ino4 and Opi1 transcription factors, and this regulation controls lipid biosynthesis. The expression level of INO2 and INO4 genes (INO-level) at different nutrient limited conditions might lead to various responses in yeast lipid metabolism. In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components. In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components. Our analysis showed the strength of using a combination of transcriptome and lipidome analysis to illustrate the effect of INO-levels on phospholipid metabolism and based on our analysis we established a global regulatory map.