Quality Assurance for Operation of Nuclear Facilities

International Nuclear Information System (INIS)

Park, C. G.; Kwon, H. I.; Kim, K. H.; Oh, Y. W.; Lee, Y. G.; Ha, J. H.; Lim, N. J.

2008-12-01

This report describes QA activities performed within 'Quality Assurance for Nuclear facility project' and results thereof. Efforts were made to maintain and improve quality system of nuclear facilities. Varification activities whether quality system was implemented in compliance with requirements. QA department assisted KOLAS accredited testing and calibration laboratories, ISO 9001 quality system, establishment of QA programs for R and D, and carried out reviews and surveys for development of quality assurance technologies. Major items of this report are as follows : - Development and Improvement of QA Programs - QA Activities - Assessment of Effectiveness and Adequacy for QA Programs

B-Cell waste classification sampling and analysis plan

International Nuclear Information System (INIS)

HOBART, R.L.

1999-01-01

This report documents the methods used to collect and analyze samples to obtain data necessary to verify and/or determine the radionuclide content of the 324 Facility B-Cell decontamination and decommissioning waste stream

75 FR 78952 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

Science.gov (United States)

2010-12-17

... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants; Commonwealth of Virginia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator (HMIWI) Units, Negative... Quality, 629 East Main Street, Richmond, Virginia 23219. FOR FURTHER INFORMATION CONTACT: James B. Topsale...

Hot-cell verification facility

International Nuclear Information System (INIS)

Eschenbaum, R.A.

1981-01-01

The Hot Cell Verification Facility (HCVF) was established as the test facility for the Fuels and Materials Examination Facility (FMEF) examination equipment. HCVF provides a prototypic hot cell environment to check the equipment for functional and remote operation. It also provides actual hands-on training for future FMEF Operators. In its two years of operation, HCVF has already provided data to make significant changes in items prior to final fabrication. It will also shorten the startup time in FMEF since the examination equipment will have been debugged and operated in HCVF

Hot cell verification facility update

International Nuclear Information System (INIS)

Titzler, P.A.; Moffett, S.D.; Lerch, R.E.

1985-01-01

The Hot Cell Verification Facility (HCVF) provides a prototypic hot cell mockup to check equipment for functional and remote operation, and provides actual hands-on training for operators. The facility arrangement is flexible and assists in solving potential problems in a nonradioactive environment. HCVF has been in operation for six years, and the facility is a part of the Hanford Engineering Development Laboratory

B cell remote-handled waste shipment cask alternatives study; TOPICAL

International Nuclear Information System (INIS)

RIDDELLE, J.G.

1999-01-01

The decommissioning of the 324 Facility B Cell includes the onsite transport of grouted remote-handled radioactive waste from the 324 Facility to the 200 Areas for disposal. The grouted waste has been transported in the leased ATG Nuclear Services 3-82B Radioactive Waste Shipping Cask (3-82B cask). Because the 3-82B cask is a U.S. Nuclear Regulatory Commission (NRC)-certified Type B shipping cask, the lease cost is high, and the cask operations in the onsite environment may not be optimal. An alternatives study has been performed to develop cost and schedule information on alternative waste transportation systems to assist in determining which system should be used in the future. Five alternatives were identified for evaluation. These included continued lease of the 3-82B cask, fabrication of a new 3-82B cask, development and fabrication of an onsite cask, modification of the existing U.S. Department of Energy-owned cask (OH-142), and the lease of a different commercially available cask. Each alternative was compared to acceptance criteria for use in the B Cell as an initial screening. Only continued leasing of the 3-82B cask, fabrication of a new 3-82B cask, and the development and fabrication of an onsite cask were found to meet all of the B Cell acceptance criteria

Quality management in nuclear facilities decommissioning

International Nuclear Information System (INIS)

Garonis, Omar H.

2002-01-01

Internationally, the decommissioning organizations of nuclear facilities carry out the decommissioning according to the safety requirements established for the regulatory bodies. Some of them perform their activities in compliance with a quality assurance system. This work establishes standardization through a Specifications Requirement Document, for the management system of the nuclear facilities decommissioning organizations. It integrates with aspects of the quality, environmental, occupational safety and health management systems, and also makes these aspects compatible with all the requirements of the nuclear industry recommended for the International Atomic Energy Agency (IAEA). (author)

Quality of the delivery services in health facilities in Northern Ethiopia.

Science.gov (United States)

Fisseha, Girmatsion; Berhane, Yemane; Worku, Alemayehu; Terefe, Wondwossen

2017-03-09

Substantial improvements have been observed in the coverage of and access to maternal health service, especially in skilled birth attendants, in Ethiopia. However, the quality of care has been lagging behind. Therefore, this study investigated the status of the quality of delivery services in Northern Ethiopia. A facility based survey was conducted from December 2014 to February 2015 in Northern Ethiopia. The quality of delivery service was assessed in 32 health facilities using a facility audit checklist, by reviewing delivery, by conducting in-depth interview and observation, and by conducting exit interviews with eligible mothers. Facilities were considered as 'good quality' if they scored positively on 75% of the quality indicators set in the national guidelines for all the three components; input (materials, infrastructure, and human resource), process (adherence to standard care procedures during intrapartum and immediate postpartum periods) and output (the mothers' satisfaction and utilization of lifesaving procedures). Overall 2 of 32 (6.3%) of the study facilities fulfilled all the three quality components; input, process and output. Two of the three components were assessed as good in 11 of the 32 (34.4%) health facilities. The input quality was the better of the other quality components; which was good in 21 out of the 32 (65.6%) health facilities. The process and output quality was good in only 10 of the 32 (31.3%) facilities. Only 6.3% of the studied health facilities had good quality in all three dimensions of quality measures that was done in accordance to the national delivery service guidelines. The most compromised quality component was the process. Systematic and sustained efforts need to be strengthened to improve all dimensions of quality in order to achieve the desired quality of delivery services and increase the proportion of births occurring in health facilities.

200 Area Liquid Effluent Facilities -- Quality assurance program plan

International Nuclear Information System (INIS)

Fernandez, L.

1995-01-01

This Quality Assurance Program Plan (QAPP) describes the quality assurance and management controls used by the 200 Area Liquid Effluent Facilities (LEF) to perform its activities in accordance with DOE Order 5700.6C. The 200 Area LEF consists of the following facilities: Effluent Treatment Facility (ETF); Treated Effluent Disposal Facility (TEDF); Liquid Effluent Retention facility (LERF); and Truck Loading Facility -- (Project W291). The intent is to ensure that all activities such as collection of effluents, treatment, concentration of secondary wastes, verification, sampling and disposal of treated effluents and solids related with the LEF operations, conform to established requirements

Considerations in setting up and planning a graft processing facility.

Science.gov (United States)

Koh, Mickey B C

2017-12-01

The graft processing facility forms one of the core components of a clinical haematopoietic stem cell transplant program. The quality of a graft is instrumental in leading to consistent and reproducible outcomes of engraftment and other parameters. As such, meticulous planning and consideration is required and will include core elements including physical design and clinical correlates. The successful running of such a facility depends on an overarching quality program and adherence to local and international regulatory guidelines. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

ART Attrition across Health Facilities Implementing Option B+ in Haiti.

Science.gov (United States)

Myrtil, Martine Pamphile; Puttkammer, Nancy; Gloyd, Stephen; Robinson, Julia; Yuhas, Krista; Domercant, Jean Wysler; Honoré, Jean Guy; Francois, Kesner

2018-01-01

Describing factors related to high attrition is important in order to improve the implementation of the Option B+ strategy in Haiti. We conducted a retrospective cohort study to describe the variability of antiretroviral therapy (ART) retention across health facilities among pregnant and lactating women and assess for differences in ART retention between Option B+ clients and other ART patients. There were 1989 Option B+ clients who initiated ART in 45 health facilities. The percentage of attrition varied from 9% to 81% across the facilities. The largest health facilities had 38% higher risk of attrition (relative risk [RR]: 1.38, 95% confidence interval [CI]: 1.08-1.77, P = .009). Private institutions had 18% less risk of attrition (RR: 0.82, 95% CI: 0.70-0.96, P = .020). Health facilities located in the West department and the South region had lower risk of attrition. Being on treatment in a large or public health facility or a facility located in the North region was a significant risk factor associated with high attrition among Option B+ clients. The implementation of the Option B+ strategy must be reevaluated in order to effectively eliminate mother-to-child HIV transmission.

Ia-restricted B-B cell interaction. I. The MHC haplotype of bone marrow cells present during B cell ontogeny dictates the self-recognition specificity of B cells in the polyclonal B cell activation by a B cell differentiation factor, B151-TRF2

International Nuclear Information System (INIS)

Ono, S.; Takahama, Y.; Hamaoka, T.

1987-01-01

We have demonstrated that B cell recognition of Ia molecules is involved in polyclonal B cell differentiation by B151-TRF2. The present study was undertaken to examine the Ia recognition specificity of B151-TRF2-responsive B cells in fully major histocompatibility complex (MHC)-allogeneic P1----P2, semiallogeneic P1----(P1 x P2)F1, and double donor (P1 + P2)----(P1 x P2)F1 and (P1 + P2)----P1 radiation bone marrow chimeras. The B cells from both P1----P2 and P1----(P1 x P2)F1 chimeras could give rise to in vitro immunoglobulin M-producing cells upon stimulation with B151-TRF2 comparable in magnitude to that of normal P1 B cells, and their responses were inhibited by anti-I-AP1 but not by anti-I-AP2 monoclonal antibody even in the presence of mitomycin C-treated T cell-depleted P2 spleen cells as auxiliary cells. In contrast, the B151-TRF2 responses of P1 B cells isolated from both (P1 + P2)----(P1 x P2)F1 and (P1 + P2)----P1 double bone marrow chimeras became sensitive to the inhibition of not only anti-I-AP1 but also anti-I-AP2 monoclonal antibody only when the culture was conducted in the presence of P2 auxiliary cells, demonstrating that they adaptively differentiate to recognize as self-structures allogeneic as well as syngeneic Ia molecules. Moreover, the experiments utilizing B cells from H-2-congenic mice and B cell hybridoma clones as auxiliary cells revealed that B151-TRF2-responsive B cells recognize Ia molecules expressed on B cells. Taken together, these results demonstrate that B151-TRF2-responsive B cells recognize Ia molecules expressed by B cells as self-structures and that their self-recognition specificity is dictated by the MHC haplotype of bone marrow cells present during the B cell ontogeny but not by the MHC haplotype of a radiation-resistant host environment

Quality control of conventional radiographic facilities in Kinshasa

International Nuclear Information System (INIS)

Woto, M.L.; Lukanda, M.V.; Mulumba, L.C.P.; Palangu

2009-01-01

The continuous development of medical applications of ionizing radiation, due to the benefit derived by diagnostic or therapeutic patients, their diversity, ease of implementation, explains the importance of medical exposure. The latter is currently the leading cause of human exposure to artificial origin. The purpose of this study is to contribute to the optimization of radiographic facilities in the city of Kinshasa. This study has revealed that city of Kinshasa has an average of 122 medical training with conventional radiology facilities distributed in six districts of health. Of the 122 facilities, only 30 (or 24.59%) are controlled from the point of view of quality assurance. Some generators and X-ray tubes are respectively controlled adjustment and de centered, and other devices are cannibalized. So, nationally and particularly in Kinshasa, quality control equipment and diagnostic facilities is at a generally delayed compared with international recommendations of X W. Major efforts must be made at government level to raise awareness and establish a quality assurance program in diagnostic radiology. An awareness of the entire medical profession and the competent administrative authorities of medical devices could be beneficial to the quality of care delivered to patients, limiting radiation exposure and improving image quality and only the financial balance of the health sector. The delivery of quality care passes through the justification of acts, the development and dissemination of good practice references and the establishment of quality control radiological installations.

Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells

Directory of Open Access Journals (Sweden)

Swadhinya Arjunaraja

2017-08-01

Full Text Available B cell Expansion with NF-κB and T cell Anergy (BENTA disease is a novel B cell lymphoproliferative disorder caused by germline, gain-of-function mutations in the lymphocyte scaffolding protein CARD11, which drives constitutive NF-κB signaling. Despite dramatic polyclonal expansion of naive and immature B cells, BENTA patients also present with signs of primary immunodeficiency, including markedly reduced percentages of class-switched/memory B cells and poor humoral responses to certain vaccines. Using purified naive B cells from our BENTA patient cohort, here we show that BENTA B cells exhibit intrinsic defects in B cell differentiation. Despite a profound in vitro survival advantage relative to normal donor B cells, BENTA patient B cells were severely impaired in their ability to differentiate into short-lived IgDloCD38hi plasmablasts or CD138+ long-lived plasma cells in response to various stimuli. These defects corresponded with diminished IgG antibody production and correlated with poor induction of specific genes required for plasma cell commitment. These findings provide important mechanistic clues that help explain both B cell lymphocytosis and humoral immunodeficiency in BENTA disease.

First Dutch Consensus of Pain Quality Indicators for Pain Treatment Facilities.

Science.gov (United States)

de Meij, Nelleke; van Grotel, Marloes; Patijn, Jacob; van der Weijden, Trudy; van Kleef, Maarten

2016-01-01

There is a general consensus about the need to define and improve the quality of pain treatment facilities. Although guidelines and recommendations to improve the quality of pain practice management have been launched, provision of appropriate pain treatment is inconsistent and the quality of facilities varies widely. The aim of the study was to develop an expert-agreed list of quality indicators applicable to pain treatment facilities. The list was also intended to be used as the basis for a set of criteria for registered status of pain treatment facilities. The University Pain Center Maastricht at the Department of Anesthesiology and Pain Management of the Maastricht University Medical Center conducted a 3-round Delphi study in collaboration with the Board of the Pain Section of the Dutch Society of Anesthesiologists (NVA). Twenty-five quality indicators were selected as relevant to 2 types of pain treatment facilities, pain clinics and pain centers. The final expert-agreed list consisted of 22 quality indicators covering 7 quality domains: supervision, availability of care, staffing level and patient load, quality policy, multidisciplinarity, regionalization, and research and education. This set of quality indicators may facilitate organizational evaluation and improve insight into service quality from the perspectives of patients, pain specialists, and other healthcare professionals. Recommendations for improvements to the current set of quality indicators are made. In 2014 the process of registering pain treatment facilities in the Netherlands started; facilities can register as a pain clinic or pain center. © 2015 World Institute of Pain.

Quality Assurance Project Plan for Facility Effluent Monitoring Plan activities

International Nuclear Information System (INIS)

Nickels, J.M.

1991-06-01

This Quality Assurance Project Plan addresses the quality assurance requirements for the Facility Monitoring Plans of the overall site-wide environmental monitoring plan. This plan specifically applies to the sampling and analysis activities and continuous monitoring performed for all Facility Effluent Monitoring Plan activities conducted by Westinghouse Hanford Company. It is generic in approach and will be implemented in conjunction with the specific requirements of individual Facility Effluent Monitoring Plans. This document is intended to be a basic road map to the Facility Effluent Monitoring Plan documents (i.e., the guidance document for preparing Facility Effluent Monitoring Plans, Facility Effluent Monitoring Plan determinations, management plan, and Facility Effluent Monitoring Plans). The implementing procedures, plans, and instructions are appropriate for the control of effluent monitoring plans requiring compliance with US Department of Energy, US Environmental Protection Agency, state, and local requirements. This Quality Assurance Project Plan contains a matrix of organizational responsibilities, procedural resources from facility or site manuals used in the Facility Effluent Monitoring Plans, and a list of the analytes of interest and analytical methods for each facility preparing a Facility Effluent Monitoring Plan. 44 refs., 1 figs., 2 tabs

Near-facility environmental monitoring quality assurance project plan

International Nuclear Information System (INIS)

McKinney, S.M.

1997-01-01

This Quality Assurance Project Plan addresses the quality assurance requirements for the activities associated with the preoperational and near facility environmental monitoring performed by Waste Management Federal Services, Inc., Northwest Operations and supersedes WHC-EP-0538-2. This plan applies to all sampling and monitoring activities performed by waste management Federal Services, Inc., Northwest Operations in implementing facility environmental monitoring at the Hanford Site

Concentrated fed-batch cell culture increases manufacturing capacity without additional volumetric capacity.

Science.gov (United States)

Yang, William C; Minkler, Daniel F; Kshirsagar, Rashmi; Ryll, Thomas; Huang, Yao-Ming

2016-01-10

Biomanufacturing factories of the future are transitioning from large, single-product facilities toward smaller, multi-product, flexible facilities. Flexible capacity allows companies to adapt to ever-changing pipeline and market demands. Concentrated fed-batch (CFB) cell culture enables flexible manufacturing capacity with limited volumetric capacity; it intensifies cell culture titers such that the output of a smaller facility can rival that of a larger facility. We tested this hypothesis at bench scale by developing a feeding strategy for CFB and applying it to two cell lines. CFB improved cell line A output by 105% and cell line B output by 70% compared to traditional fed-batch (TFB) processes. CFB did not greatly change cell line A product quality, but it improved cell line B charge heterogeneity, suggesting that CFB has both process and product quality benefits. We projected CFB output gains in the context of a 2000-L small-scale facility, but the output was lower than that of a 15,000-L large-scale TFB facility. CFB's high cell mass also complicated operations, eroded volumetric productivity, and showed our current processes require significant improvements in specific productivity in order to realize their full potential and savings in manufacturing. Thus, improving specific productivity can resolve CFB's cost, scale-up, and operability challenges. Copyright © 2015 Elsevier B.V. All rights reserved.

Near-Facility Environmental Monitoring Quality Assurance Project Plan

International Nuclear Information System (INIS)

MCKINNEY, S.M.

2000-01-01

This Quality Assurance Project Plan addresses the quality assurance requirements for the activities associated with the preoperational and near-facility environmental monitoring directed by Waste Management Technical Services and supersedes HNF-EP-0538-4. This plan applies to all sampling and monitoring activities performed by Waste Management Technical Services in implementing near-facility environmental monitoring at the Hanford Site. This Quality Assurance Project Plan is required by U.S. Department of Energy Order 5400.1 (DOE 1990) as a part of the Environmental Monitoring Plan (DOE-RL 1997) and is used to define: Environmental measurement and sampling locations used to monitor environmental contaminants near active and inactive facilities and waste storage and disposal sites; Procedures and equipment needed to perform the measurement and sampling; Frequency and analyses required for each measurement and sampling location; Minimum detection level and accuracy; Quality assurance components; and Investigation levels. Near-facility environmental monitoring for the Hanford Site is conducted in accordance with the requirements of U.S. Department of Energy Orders 5400.1 (DOE 1990), 5400.5 (DOE 1993), 5484.1 (DOE 1990), and 435.1 (DOE 1999), and DOE/EH-O173T (DOE 1991). It is Waste Management Technical Services' objective to manage and conduct near-facility environmental monitoring activities at the Hanford Site in a cost-effective and environmentally responsible manner that is in compliance with the letter and spirit of these regulations and other environmental regulations, statutes, and standards

T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection.

Science.gov (United States)

Pallikkuth, Suresh; de Armas, Lesley; Rinaldi, Stefano; Pahwa, Savita

2017-01-01

T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART), excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh-B cell interactions.

Inpatient Psychiatric Facility Quality Measure Data – by State

Data.gov (United States)

U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

B cells and B cell products-helping to restore cellular immunity?

OpenAIRE

Cascalho, Marilia; Platt, Jeffrey L.

2006-01-01

T cells that provide vital protection against tumors, viruses and intracellular bacteria are thought to develop independently of B cells. However, recent discoveries suggest that development of T cells depends on B cells. One way B cells promote T cell development is by providing diverse peptides that may promote positive selection of thymocytes. Diverse peptides and B cells help in diversification of the T cell receptor repertoire and may decrease cross-reactivity in the mature T cell compar...

Characterisation study of radionuclides in Hot Cell Facility

International Nuclear Information System (INIS)

Ghare, P.T.; Rath, D.P.; Govalkar, Atul; Mukherjee, Govinda; AniIKumar, S.; Yadav, R.K.B.; Mallik, G.K.

2016-01-01

Examination of different types of experimental as well as power reactor irradiated fuels and validation of fuel modeling codes is carried out in general Hot cell facility. The Hot cell facility has six concrete shielded hot cells, capable of handling radioactivity varying from 3.7 TBQ to 3700 TBq gamma activity. The facility was augmented with two hot cells having designed capacity to handle radioactivity of 9250 TBQ of equivalent activity of 60 Co. The study of characterization of various radionuclides present inside the hot cell of PIE facility was taken up. This study will help in providing valuable inputs for various radiological safety parameters to keep personnel exposure to ALARA level as per the mandate of radiation safety program

Quality Assurance Project Plan for Facility Effluent Monitoring Plan activities

International Nuclear Information System (INIS)

Frazier, T.P.

1994-01-01

This Quality Assurance Project Plan addresses the quality assurance requirements for the activities associated with the Facility Effluent Monitoring Plans, which are part of the overall Hanford Site Environmental Protection Plan. This plan specifically applies to the sampling and analysis activities and continuous monitoring performed for all Facility Effluent Monitoring Plan activities conducted by Westinghouse Hanford Company. It is generic in approach and will be implemented in conjunction with the specific requirements of the individual Facility Effluent Monitoring Plans

Cyclosporine A suppresses immunoglobulin G biosynthesis via inhibition of cyclophilin B in murine hybridomas and B cells.

Science.gov (United States)

Lee, Jisun; Choi, Tae Gyu; Ha, Joohun; Kim, Sung Soo

2012-01-01

Immunoglubulin G (IgG) is a major isotype of antibody, which is predominantly involved in immune response. The complete tetramer is needed to fold and assemble in endoplasmic reticulum (ER) prior to secretion from cells. Protein quality control guided by ER chaperons is most essential for full biological activity. Cyclophilin B (CypB) was initially identified as a high-affinity binding protein for the immunosuppressive drug Cyclosporine A (CsA). CsA suppresses organ rejection by halting productions of pro-inflammatory molecules in T cell and abolishes the enzymatic property of CypB that accelerates the folding of proteins by catalysing the isomerization of peptidyl-proline bonds in ER. Here, we reported that CsA significantly inhibited IgG biosynthesis at posttranslational level in antibody secreting cells. Moreover, CsA stimulated the extracellular secretion of CypB and induced ROS generation, leading to expressions of ER stress markers. In addition, the absence of intracellular CypB impaired the formation of ER multiprotein complex, which is most important for resisting ER stress. Interestingly, CsA interrupted IgG folding via occupying the PPIase domain of CypB in ER. Eventually, unfolded IgG is degraded via Herp-dependent ERAD pathway. Furthermore, IgG biosynthesis was really abrogated by inhibition of CypB in primary B cells. We established for the first time the immunosuppressive effect of CsA on B cells. Conclusively, the combined results of the current study suggest that CypB is a pivotal molecule for IgG biosynthesis in ER quality control. Copyright © 2011 Elsevier B.V. All rights reserved.

Improving Quality of Care in Primary Health-Care Facilities in Rural Nigeria

Science.gov (United States)

Ugo, Okoli; Ezinne, Eze-Ajoku; Modupe, Oludipe; Nicole, Spieker; Kelechi, Ohiri

2016-01-01

Background: Nigeria has a high population density but a weak health-care system. To improve the quality of care, 3 organizations carried out a quality improvement pilot intervention at the primary health-care level in selected rural areas. Objective: To assess the change in quality of care in primary health-care facilities in rural Nigeria following the provision of technical governance support and to document the successes and challenges encountered. Method: A total of 6 states were selected across the 6 geopolitical zones of the country. However, assessments were carried out in 40 facilities in only 5 states. Selection was based on location, coverage, and minimum services offered. The facilities were divided randomly into 2 groups. The treatment group received quality-of-care assessment, continuous feedback, and improvement support, whereas the control group received quality assessment and no other support. Data were collected using the SafeCare Healthcare Standards and managed on the SafeCare Data Management System—AfriDB. Eight core areas were assessed at baseline and end line, and compliance to quality health-care standards was compared. Result: Outcomes from 40 facilities were accepted and analyzed. Overall scores increased in the treatment facilities compared to the control facilities, with strong evidence of improvement (t = 5.28, P = .0004) and 11% average improvement, but no clear pattern of improvement emerged in the control group. Conclusion: The study demonstrated governance support and active community involvement offered potential for quality improvement in primary health-care facilities. PMID:28462280

Decommissioning of the Risoe hot cell facility

International Nuclear Information System (INIS)

Carlsen, H.

1992-02-01

Concise descriptions of actions taken in relation to the decommissioning of the hot cell facility at Risoe National Laboratory are presented. The removal of fissile material, of large contaminated equipment from the concrete cell line and a separate shielded storage facility, and the removal of large contaminated facilities such as out cell parts of a tube transport system between a concrete cell and a lead shielded steel box and a remotely operated Reichert Telatom microscope housed in a lead shielded glove box is described in addition to the initial mapping of radiation levels related to the decontamination of concrete cells. The dose commitment of 17.7 mSv was ascribed to 12 persons in the 2nd half of 1991. The work resulting in these doses was mainly handling of waste together with the frogman entrances in order to repair the in-cell crane and power manipulator. The overall time schedule for the project still appears to be applicable. (AB)

Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells

Science.gov (United States)

Patzelt, Thomas; Keppler, Selina J.; Gorka, Oliver; Thoene, Silvia; Wartewig, Tim; Reth, Michael; Förster, Irmgard; Lang, Roland; Buchner, Maike; Ruland, Jürgen

2018-01-01

The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1-deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate. Transcriptional analysis identified defective expression of the prosurvival Bcl-2 family gene Bcl2l1 encoding Bcl-xl in Foxp1-deficient B cells, and we identified Foxp1 binding in the regulatory region of Bcl2l1. Transgenic overexpression of Bcl2 rescued the survival defect in Foxp1-deficient mature B cells in vivo and restored peripheral B cell numbers. Thus, our results identify Foxp1 as a physiological regulator of mature B cell survival mediated in part via the control of Bcl-xl expression and imply that this pathway might contribute to the pathogenic function of aberrant Foxp1 expression in lymphoma. PMID:29507226

Study of the Relevance of the Quality of Care, Operating Efficiency and Inefficient Quality Competition of Senior Care Facilities.

Science.gov (United States)

Lin, Jwu-Rong; Chen, Ching-Yu; Peng, Tso-Kwei

2017-09-11

The purpose of this research is to examine the relation between operating efficiency and the quality of care of senior care facilities. We designed a data envelopment analysis, combining epsilon-based measure and metafrontier efficiency analyses to estimate the operating efficiency for senior care facilities, followed by an iterative seemingly unrelated regression to evaluate the relation between the quality of care and operating efficiency. In the empirical studies, Taiwan census data was utilized and findings include the following: Despite the greater operating scale of the general type of senior care facilities, their average metafrontier technical efficiency is inferior to that of nursing homes. We adopted senior care facility accreditation results from Taiwan as a variable to represent the quality of care and examined the relation of accreditation results and operating efficiency. We found that the quality of care of general senior care facilities is negatively related to operating efficiency; however, for nursing homes, the relationship is not significant. Our findings show that facilities invest more in input resources to obtain better ratings in the accreditation report. Operating efficiency, however, does not improve. Quality competition in the industry in Taiwan is inefficient, especially for general senior care facilities.

Decommissioning of the Risoe Hot Cell facility

International Nuclear Information System (INIS)

Carlsen, H.

1993-02-01

A concise description of the current status (December 31st, 1992) regarding the decommissioning of the hot cell facility at Risoe National Laboratory is given in this periodic report. During the second half of the year 1992, all remaining fissile material and a large amount of contaminated material were removed, major repair work was carried out on the in-cell crane, the shielded storage facility was decontaminated and sealed, iodine filters in the cell ventilation system were removed, remote cleaning was carried out on three concrete cells to radiation levels acceptable for final cleaning by frogmen, and the remaining work schedule was planned. These processes are briefly described. Some breakdowns of older, but vital equipment (i.e. the in-cell crane and the power manipulator) that was taken into extensive use led to a certain amount of delay. The collective radiation doses during this half-year were no higher than under normal operation of the facility, and amounted to 12 man-mSv ascribed to 14 persons. It was concluded that, when removing old epoxy paint in the cells using paint strippers applied by hand, personnel can wear polythene oversuits, although a technique for remote handling has been developed. Tables illustrate measured radiation levels in cells number 1,4,5 and 6, and a diagram describes the shielded storage facility. (AB)

Decommissioning of the Risoe Hot Cell facility

International Nuclear Information System (INIS)

Carlsen, H.

1994-06-01

Nuclear fuels have been handled and examined after irradiation by physical and chemical techniques, and radiotherapy sources, mainly 60 Co, have been produced at Risoe National Laboratory since 1964. The aims of decommissioning (during 1990-94, at IAEA Stage 2 level for reactors) were to obtain safe conditions for the remaining parts of the facility and to produce clean space areas for new projects. The facility comprises 6 concrete cells, several lead-shielded steel cells, glove boxes, shielded storage for waste, a remotely operated optical microscope, a frogman area for personnel access to the concrete cells, a decontamination facility, workshops and safety installations. All steel cells, glove boxes and the microscope were emptied and removed. The concrete cells were emptied of fissile material, scientific equipment, general tools and scrap. Decontamination should facilitate waste packing and reduce amount of waste to be stored temporarily at the Risoe waste treatment facility together with highly active waste. The concrete cells were cleaned remotely by wiping, hot spot removal, by mechanical means and vacuum cleaning. The interiors of 2 cells were decontaminated by high pressure water jetting. All master-slave manipulators and part of the contaminated ventilation system at the cells were removed. The cells are left in a non-ventilated state, connected to the atmosphere by an absolute filter. The main contaminants measured before cell closure were 60 Co, 137 Cs and alpha-emitters. Dismantling, decontamination waste disposal and received doses are described. Simple techniques involving low doses were found to be very effective. (AB)

Planning, Management and Organizational Aspects of the Decommissioning of a Hot Cell Facility

Energy Technology Data Exchange (ETDEWEB)

Strufe, N. [Danish Decommissioning, Roskilde (Denmark)

2013-08-15

This CRP project document ''Planning, Management and Organizational Aspects in Decommissioning of a Hot Cell Facility'' aims to describe the establishment of a management organization that ensures that the DD Hot Cell Project is properly and safely conducted and that staff members, who are seconded to the project, have a strong feeling of ownership and being an integral part of the project. The objectives of the decommissioning project of the hot cell facility is to decontaminate the facility and to remove items that cannot be decontaminated on site, in order for the entire hot cell building to become useable for other purposes without any radiological restrictions. The project requires proper communication and coordination with all stakeholders on-site, comprehensive work plans and strict control of the individual working areas and operations. A project of this type obviously requires a strong and well managed and coordinated project organization. DD has established a management system - KMS. The purposes of the KMS are twofold. The system aims to secure the fulfilment of the conditions and requirements of quality set by the nuclear authorities. The system also aims to provide the basis for a rational and economically feasible operation with a high level of safety. One of the main lessons learned in this project is clear that is to ensure that the necessary resources are available and the required expertise is allocated timely for the performance of the project(s) a strong coordination and great flexibility within the DD organization is required. This document describes the approach and considerations from the project management point of view. The document initially gives an introduction to the hot cell decommissioning project followed by issues of the general considerations and planning of the project within the DD, including aspects on organisation, quality assurance and coordination. (author)

Inpatient Psychiatric Facility Follow-Up After Hospitalization for Mental Illness (FUH) Quality Measure Data – by Facility

Data.gov (United States)

U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells.

Directory of Open Access Journals (Sweden)

Deborah Frenkel

2016-07-01

Full Text Available After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/- retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK cell-mediated cytotoxicity: i B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/- and FcγRIIIa deficient (CD16-/- C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii administration of NK1.1 specific IgG2a (mAb PK136 but not irrelevant IgG2a (myeloma M9144 prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei

[Implementation of quality management in medical rehabilitation--current challenges for rehabilitation facilities].

Science.gov (United States)

Enge, M; Koch, A; Müller, T; Vorländer, T

2010-12-01

The legal responsibilities imposed upon rehabilitation facilities under section 20 (2a) SGB IX, necessitate fundamental decisions to be taken regarding the development of quality management systems over and above the existing framework. This article is intended to provide ideas and suggestions to assist rehabilitation facilities in implementing a quality management system, which is required in addition to participation in the quality assurance programmes stipulated by the rehabilitation carriers. In this context, the additional internal benefit a functioning quality management system can provide for ensuring a high level of quality and for maintaining the competitiveness of the rehabilitation facility should be taken into account. The core element of these observations, hence, is a list of requirements which enables assessment of the quality of consultants' performance in setting up a quality management system. © Georg Thieme Verlag KG Stuttgart · New York.

The role of nuclear factor κB in the cellular response to different radiation qualities

International Nuclear Information System (INIS)

Koch, Kristina

2013-01-01

Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

The role of nuclear factor κB in the cellular response to different radiation qualities

Energy Technology Data Exchange (ETDEWEB)

Koch, Kristina

2013-04-11

Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

Project quality assurance plant: Sodium storage facility, project F-031

International Nuclear Information System (INIS)

Shultz, J.W.; Shank, D.R.

1994-11-01

The Sodium Storage Facility Project Quality Assurance Plan delineates the quality assurance requirements for construction of a new facility, modifications to the sodium storage tanks, and tie-ins to the FFTF Plant. This plan provides direction for the types of verifications necessary to satisfy the functional requirements within the project scope and applicable regulatory requirements determined in the Project Functional Design Criteria (FDC), WHC-SD-FF-FDC-009

Characteristics of administrators and quality of care in Ontario care facilities

OpenAIRE

Keays, Sean Charles

2007-01-01

This exploratory study investigated administrator and facility predictors of quality of care (QOC) in care facilities (CF). Surveys were mailed to all 602 CF administrators in Ontario; half of whom responded. Quality was measured using the last certification inspection report obtained from the Ontario Ministry of Health and Long-Term Care public report on certified CF. Quality predictors were found using multiple regression analysis. Education and experience as an administrator in current pos...

The Impact of Special Focus Facility Nursing Homes on Market Quality

Science.gov (United States)

Castle, Nicholas G.; Sonon, Kristen; Antonova, Jenya

2010-01-01

Purpose: Special Focus Facilities (SFFs) are nursing facilities designated by the Centers for Medicare & Medicaid Services to be of chronic poor quality. Relatively few nursing facilities are included in this initiative. The purpose of this research was to examine whether nursing facilities included in the 2007 SFF initiative subsequently…

Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

International Nuclear Information System (INIS)

Heizmann, Beate; Sellars, MacLean; Macias-Garcia, Alejandra; Chan, Susan; Kastner, Philippe

2016-01-01

The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Heizmann, Beate [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Sellars, MacLean [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Macias-Garcia, Alejandra [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Institute for Medical Engineering and Science at MIT, Cambridge, MA 02139 (United States); Chan, Susan, E-mail: scpk@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Kastner, Philippe, E-mail: scpk@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Faculté de Médecine, Université de Strasbourg, Strasbourg (France)

2016-02-12

The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

Current status of JAERI Tokai hot cell facilities

International Nuclear Information System (INIS)

Itami, Hiroharu; Morozumi, Minoru; Yamahara, Takeshi

1992-01-01

JAERI has 4 hot cell facilities in order to examine high radioactive materials. Three of them, the Research Hot Laboratory, the Reactor Fuel Examination Facility and the Waste Safety Testing Facility are located in the JAERI Tokai site, and the rest is the JMTR Hot Laboratory in the Oarai site. The Research Hot Laboratory (RHL) was constructed for post-irradiation examination (PIE), especially nuclear related basic research experiment, such as metallurgical, chemical and mechanical examination on fuels and materials irradiated in research and test reactors. This facility has 10 large dimension concrete and 38 lead cells. At present the RHL is used for various kinds of examinations of high radioactive samples such as fuels of research and test reactors, power reactors and high temperature testing reactor (HTTR), and structural materials. The Reactor Fuel Examination Facility (RFEF) was designed and constructed for carrying out PIE of irradiated full-size fuel assemblies of light water reactors (LWRs). This facility has a storage pool, 8 concrete and 5 lead cells. They are currently used for safety evaluation on high burnup and advanced lWR fuels as part of the national program. The Waste Safety Testing Facility (WASTEF) was designed and constructed for safety research on long-term storage and disposal of high level radioactive wastes, generated by fuel reprocessing. The WASTEF has 5 concrete cells and 1 lead cell. Examinations on the behavior of various long-lived fission products in a glass form and in a canister and, releasing behavior of them out of a canister are carrying out under the condition at storage. (author)

Does High School Facility Quality Affect Student Achievement? A Two-Level Hierarchical Linear Model

Science.gov (United States)

Bowers, Alex J.; Urick, Angela

2011-01-01

The purpose of this study is to isolate the independent effects of high school facility quality on student achievement using a large, nationally representative U.S. database of student achievement and school facility quality. Prior research on linking school facility quality to student achievement has been mixed. Studies that relate overall…

Refurbishment of an Analytical Laboratory Hot Cell Facility

International Nuclear Information System (INIS)

Rosenberg, K.; Henslee, S.P.; Michelbacher, J.A.; Coleman, R.M.

1997-01-01

An Analytical Laboratory Hot Cell (ALHC) Facility at Argonne National Laboratory-West (ANL-W) was in service for nearly thirty years. In order to comply with DOE regulations governing such facilities and meet ANL-W programmatic requirements, a major refurbishment effort was undertaken. All penetrations within the facility were sealed; the ventilation system was redesigned, upgraded and replaced; the manipulators were replaced; the hot cell windows were removed, refurbished, and reinstalled; all hot cell utilities were replaced; a lead-shielded glovebox housing an Inductively Coupled Plasma - Atomic Emission Spectrometer (ICP-AES) System was interfaced with the hot cells, and a new CO2 fire suppression system and other ALHC support equipment were installed

OPP og indkøb af Facilities Management ydelser

DEFF Research Database (Denmark)

Kristiansen, Kristian

Dette er den 3. og sidste rapport i forskningsprojektet om OPP og indkøb af Facilities Management ydelser. Fokus er denne gang rettet mod bestræbelserne på at skabe større integration i byggeprocessen. Det vil blive undersøgt, hvorvidt sådanne bestræbelser – som der kan findes eksempler på både i...... UK og i Danmark – vil kunne fremme en inddragelse af Facilities Management viden i planlægning, projektering og udførelse. Denne problemstilling skal ses i forlængelse af det forudgående arbejde i forskningsprojektet....

Quality Assurance Program Plan (QAPP) Waste Encapsulation and Storage Facility (WESF)

International Nuclear Information System (INIS)

ROBINSON, P.A.

2000-01-01

This Quality Assurance Plan describes how the Waste Encapsulation and Storage Facility (WESF) implements the quality assurance (QA) requirements of the Quality Assurance Program Description (QAPD) (HNF-Mp-599) for Project Hanford activities and products. This QAPP also describes the organizational structure necessary to successfully implement the program. The QAPP provides a road map of applicable Project Hanford Management System Procedures, and facility specific procedures, that may be utilized by WESF to implement the requirements of the QAPD

Preliminary siting characterization Salt Disposition Facility - Site B

International Nuclear Information System (INIS)

Wyatt, D.

2000-01-01

A siting and reconnaissance geotechnical program has been completed in S-Area at the Savannah River Site in South Carolina. This program investigated the subsurface conditions for the area known as ''Salt Disposition Facility (SDF), Site B'' located northeast of H-Area and within the S-Area. Data acquired from the Site B investigation includes both field exploration and laboratory test data

Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection.

Science.gov (United States)

Chang, J Judy; Sirivichayakul, Sunee; Avihingsanon, Anchalee; Thompson, Alex J V; Revill, Peter; Iser, David; Slavin, John; Buranapraditkun, Supranee; Marks, Pip; Matthews, Gail; Cooper, David A; Kent, Stephen J; Cameron, Paul U; Sasadeusz, Joe; Desmond, Paul; Locarnini, Stephen; Dore, Gregory J; Ruxrungtham, Kiat; Lewin, Sharon R

2009-08-01

Hepatitis B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+ T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+ T-cell count (P = 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+ T-cell count.

Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy.

Science.gov (United States)

Johnsen, Hans Erik; Bergkvist, Kim Steve; Schmitz, Alexander; Kjeldsen, Malene Krag; Hansen, Steen Møller; Gaihede, Michael; Nørgaard, Martin Agge; Bæch, John; Grønholdt, Marie-Louise; Jensen, Frank Svendsen; Johansen, Preben; Bødker, Julie Støve; Bøgsted, Martin; Dybkær, Karen

2014-06-01

Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.

Air quality impacts due to construction of LWR waste management facilities

International Nuclear Information System (INIS)

1977-06-01

Air quality impacts of construction activities and induced housing growth as a result of construction activities were evaluated for four possible facilities in the LWR fuel cycle: a fuel reprocessing facility, fuel storage facility, fuel fabrication plant, and a nuclear power plant. Since the fuel reprocessing facility would require the largest labor force, the impacts of construction of that facility were evaluated in detail

111-B Metal Examination Facility Concrete Tanks Characterization Plan

International Nuclear Information System (INIS)

Encke, D.B.

1997-08-01

The 111-B Metal Examination Facility was a single-story, wood frame 'L'-shaped building built on a concrete floor slab. The facility served as a fuel failure inspection facility. Irradiated fuel pieces were stored and examined in two below grade concrete storage tanks filled with water. The tanks have been filled with grout to stabilize the contamination they contained, and overall dimensions are 5 ft 9 in. (1.5 m 22.8 cm ) wide, 9 ft 1 in. (2.7 m 2.54 cm ) deep, and 10 ft 8 in. (3.0 m 20.32 cm) long, and are estimated to weigh 39 tons. The tanks were used to store and examine failed fuel rods, using water as a radiation shield. The tanks were lined with stainless steel; however, drawings show the liner has been removed from at least one tank (south tank) and was partially filled with grout. The south tank was used to contain the Sample Storage Facility, a multi-level metal storage rack for failed nuclear fuel rods (shown in drawings H-1-2889 and -2890). Both tanks were completely grouted sometime before decontamination and demolition (D ampersand D) of the above ground facility in 1984. The 111-B Metal Examination Facility contained two concrete tanks located below floor level for storage and examination of failed fuel. The tanks were filled with concrete as part of decommissioning the facility prior to 1983 (see Appendix A for description of previous work). Funding for removal and disposal of the tanks ran out before they could be properly disposed

Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

Energy Technology Data Exchange (ETDEWEB)

Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Deng, Tianzheng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an, 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Zhang Yongjie [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Feng Feng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Jin Yan [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)], E-mail: yanjin@fmmu.edu.cn

2008-07-28

The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 {mu}m) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering.

Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

International Nuclear Information System (INIS)

Huang Sha; Wang Yijuan; Deng, Tianzheng; Jin Fang; Liu Shouxin; Zhang Yongjie; Feng Feng; Jin Yan

2008-01-01

The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 μm) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering

233-S Plutonium Concentration Facility data quality objectives

International Nuclear Information System (INIS)

Encke, D.B.

1996-08-01

This document is a summary of the decision-making associated with the Data Quality Objective process that pertains to the characterization activities in the 233-S Plutonium Concentration Facility at the Hanford Site in Richland, Washington. The 233-S Plutonium Concentration Facility is located adjacent to, and north of, the REDOX Plant. The facility was used to concentrate the plutonium nitrate product solution from the REDOX facility. The 233-S Pipe Gallery, Control Room, SWP Change Room, Toilet, Equipment Room and the Electrical Cubicle are currently scheduled for decontamination and cleanout to support future demolition (D and D). Identification of the radiological contamination and presence of hazardous materials is needed to allow for disposal of the D and D debris

Operating experience and radiation protection problems in the working of the radio-metallurgy hot cell facilities at BARC

International Nuclear Information System (INIS)

Janardhanan, S.; Watamwar, S.B.; Mehta, S.K.; Pillai, P.M.B.; John, Jacob; Kutty, K.N.

1977-01-01

The Bhabha Atomic Research Centre at Bombay has six hot cell facilities for radiometallurgical investigations of irradiated/failed fuel elements. The hot cell facilities have been provided with certain built-in safety features, a ventilation system, radiation monitoring instruments for various purposes, a centralised air monitoring system and a central panel for display of various alarms. Procedures adopted for radiation protection and contamination control include : (1) radiation leak test for cells and filter efficiency evaluation before cell activation, (2) practices to be followed by frog suit personnel while working in hot cell areas, (3) receipt and handling of irradiated fuel elements, (4) cell filter change operation, (5) checks on high level drains and (6) effluent discharge and waste shipments. Operating experience in the working of these facilities along with radiation accident incidents is described. Data regarding release of activity during normal cell operations, dose rates during various metallurgical operations and personnel exposures are presented. (M.G.B.)

[Quality Indicators of Primary Health Care Facilities in Austria].

Science.gov (United States)

Semlitsch, Thomas; Abuzahra, Muna; Stigler, Florian; Jeitler, Klaus; Posch, Nicole; Siebenhofer, Andrea

2017-07-11

Background The strengthening of primary health care is one major goal of the current national health reform in Austria. In this context, a new interdisciplinary concept was developed in 2014 that defines structures and requirements for future primary health care facilities. Objective The aim of this project was the development of quality indicators for the evaluation of the scheduled primary health care facilities in Austria, which are in accordance with the new Austrian concept. Methods We used the RAND/NPCRDC method for the development and selection of the quality indicators. We conducted systematic literature searches for existing measures in international databases for quality indicators as well as in bibliographic databases. All retrieved measures were evaluated and rated by an expert panel in a 2-step process regarding relevance and feasibility. Results Overall, the literature searches yielded 281 potentially relevant quality indicators, which were summarized to 65 different quality measures for primary health care. Out of these, the panel rated and accepted 30 measures as relevant and feasible for use in Austria. Five of these indicators were structure measures, 14 were process measures and the remaining 11 were outcome measures. Based on the Austrian primary health care concept, the final set of quality indicators was grouped in the 5 following domains: Access to primary health care (5), quality of care (15), continuity of care (5), coordination of care (4), and safety (1). Conclusion This set of quality measures largely covers the four defined functions of primary health care. It enables standardized evaluation of primary health care facilities in Austria regarding the implementation of the Austrian primary health care concept as well as improvement in healthcare of the population. © Georg Thieme Verlag KG Stuttgart · New York.

An Evaluation of Taiwanese B&B Service Quality Using the IPA Model

Directory of Open Access Journals (Sweden)

Gao-Liang Wang

2012-09-01

Full Text Available According to a December 2011 report released by Taiwan’s Tourism Bureau, there were 3,763 bed-and-breakfast guesthouses (B&B in Taiwan, 3,367 of which were legal with a combined 13,389 rooms, increasing by 96 percent from December 2006. It seems that the B&B sector is quite a popular target for investors. As the word-of-mouth advertising has been considered one of the most influential marketing methods, those who invest in B&Bs must manage to utilize their limited resources to improve customer satisfaction in a fast-growing and competitive market. The best marketing approach in reaching out to B&B customers, as suggested by this study’s author, would be word-of-mouth adverting. A PZB framed questionnaire is used in this study to explore the expectations and satisfaction of B&B customers both before and after the accommodation period, with the Importance-Performance Analysis (IPA model applied to analyze and measure the service quality. Findings from the questionnaire survey showed 3 out of the totally 23 service factors falling in the “concentrated concerned” quadrant (i.e., tidiness, architectural characteristics, and reasonable rates; 6 factors falling in the “continued maintenance” quadrant (i.e., adequate parking place, commitment to customers, handling of customers’ opinions, legality of B&B, grievance handling, and the local specialties-ordering service; 10 factors falling in the “low priority” quadrant (i.e., modern facilities, safety devices, availability of breakfast, security of online reservations; 4 factors falling in the “over-strived” quadrant (i.e., the availability of custom-made services, the ability to grasp customers’ needs, the availability of tour packages, and the availability of experiences regarding local industries.

Quality along the continuum: a health facility assessment of intrapartum and postnatal care in Ghana.

Directory of Open Access Journals (Sweden)

Robin C Nesbitt

Full Text Available To evaluate quality of routine and emergency intrapartum and postnatal care using a health facility assessment, and to estimate "effective coverage" of skilled attendance in Brong Ahafo, Ghana.We conducted an assessment of all 86 health facilities in seven districts in Brong Ahafo. Using performance of key signal functions and the availability of relevant drugs, equipment and trained health professionals, we created composite quality categories in four dimensions: routine delivery care, emergency obstetric care (EmOC, emergency newborn care (EmNC and non-medical quality. Linking the health facility assessment to surveillance data we estimated "effective coverage" of skilled attendance as the proportion of births in facilities of high quality.Delivery care was offered in 64/86 facilities; only 3-13% fulfilled our requirements for the highest quality category in any dimension. Quality was lowest in the emergency care dimensions, with 63% and 58% of facilities categorized as "low" or "substandard" for EmOC and EmNC, respectively. This implies performing less than four EmOC or three EmNC signal functions, and/or employing less than two skilled health professionals, and/or that no health professionals were present during our visit. Routine delivery care was "low" or "substandard" in 39% of facilities, meaning 25/64 facilities performed less than six routine signal functions and/or had less than two skilled health professionals and/or less than one midwife. While 68% of births were in health facilities, only 18% were in facilities with "high" or "highest" quality in all dimensions.Our comprehensive facility assessment showed that quality of routine and emergency intrapartum and postnatal care was generally low in the study region. While coverage with facility delivery was 68%, we estimated "effective coverage" of skilled attendance at 18%, thus revealing a large "quality gap." Effective coverage could be a meaningful indicator of progress towards

Facile synthesis of cyclopentenone B1- and L1-type Phytoprostanes

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Alexandre eGuy

2015-07-01

Full Text Available Phytoprostanes (PhytoPs represent non-enzymatic metabolites of α-linolenic acid (ALA, the essential omega-3 polyunsaturated fatty acid (PUFA derived from plants. PhytoPs are present in the plant kingdom and represent endogenous mediators capable of protecting cells from oxidative stress damages in plants. Recently, it was found that such metabolites are present in cooking oil in high quantities, and also that B1-PhytoPs protect immature neurons from oxidant injury and promote differentiation of oligodendrocyte progenitors through PPAR-γ activation. We report a novel and facile synthesis of natural 2,3-substituted cyclopentenone PhytoPs, 16-B1-PhytoP and 9-L1-PhytoP. Our strategy is based on reductive alkylation at the 2-position of 1,3-cyclopentanedione using a recent protocol developed by Ramachary et al., and on a cross-coupling metathesis to access conjugate dienone system. In conclusion, this strategy permitted access to B1- and L1-PhytoPs in a relative short sequence process, and afford the possibility to easily develop analogs of PhytoPs.

Air Quality Facilities

Data.gov (United States)

Iowa State University GIS Support and Research Facility — Facilities with operating permits for Title V of the Federal Clean Air Act, as well as facilities required to submit an air emissions inventory, and other facilities...

Determinants of quality of shared sanitation facilities in informal settlements: case study of Kisumu, Kenya

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Sheillah Simiyu

2017-01-01

Full Text Available Abstract Background Shared facilities are not recognised as improved sanitation due to challenges of maintenance as they easily can be avenues for the spread of diseases. Thus there is need to evaluate the quality of shared facilities, especially in informal settlements, where they are commonly used. A shared facility can be equated to a common good whose management depends on the users. If users do not work collectively towards keeping the facility clean, it is likely that the quality may depreciate due to lack of maintenance. This study examined the quality of shared sanitation facilities and used the common pool resource (CPR management principles to examine the determinants of shared sanitation quality in the informal settlements of Kisumu, Kenya. Methods Using a multiple case study design, the study employed both quantitative and qualitative methods. In both phases, users of shared sanitation facilities were interviewed, while shared sanitation facilities were inspected. Shared sanitation quality was a score which was the dependent variable in a regression analysis. Interviews during the qualitative stage were aimed at understanding management practices of shared sanitation users. Qualitative data was analysed thematically by following the CPR principles. Results Shared facilities, most of which were dirty, were shared by an average of eight households, and their quality decreased with an increase in the number of households sharing. The effect of numbers on quality is explained by behaviour reflected in the CPR principles, as it was easier to define boundaries of shared facilities when there were fewer users who cooperated towards improving their shared sanitation facility. Other factors, such as defined management systems, cooperation, collective decision making, and social norms, also played a role in influencing the behaviour of users towards keeping shared facilities clean and functional. Conclusion Apart from hardware factors, quality

Facility effluent monitoring plan for the 325 Facility

International Nuclear Information System (INIS)

1998-01-01

The Applied Chemistry Laboratory (325 Facility) houses radiochemistry research, radioanalytical service, radiochemical process development, and hazardous and mixed hazardous waste treatment activities. The laboratories and specialized facilities enable work ranging from that with nonradioactive materials to work with picogram to kilogram quantities of fissionable materials and up to megacurie quantities of other radionuclides. The special facilities include two shielded hot-cell areas that provide for process development or analytical chemistry work with highly radioactive materials, and a waste treatment facility for processing hazardous, mixed, low-level, and transuranic wastes generated by Pacific Northwest Laboratory. Radioactive material storage and usage occur throughout the facility and include a large number of isotopes. This material is in several forms, including solid, liquid, particulate, and gas. Some of these materials are also heated during testing which can produce vapors. The research activities have been assigned to the following activity designations: High-Level Hot Cell, Hazardous Waste Treatment Unit, Waste Form Development, Special Testing Projects, Chemical Process Development, Analytical Hot Cell, and Analytical Chemistry. The following summarizes the airborne and liquid effluents and the results of the Facility Effluent Monitoring Plan (FEMP) determination for the facility. The complete monitoring plan includes characterization of effluent streams, monitoring/sampling design criteria, a description of the monitoring systems and sample analysis, and quality assurance requirements

10 CFR 140.13b - Amount of liability insurance required for uranium enrichment facilities.

Science.gov (United States)

2010-01-01

... enrichment facilities. 140.13b Section 140.13b Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FINANCIAL... required for uranium enrichment facilities. Each holder of a license issued under Parts 40 or 70 of this chapter for a uranium enrichment facility that involves the use of source material or special nuclear...

Controlled synthesis of TiO2-B nanowires and nanoparticles for dye-sensitized solar cells

International Nuclear Information System (INIS)

Qi Lihong; Liu Yongjun; Li Chunyan

2010-01-01

Controllable synthesis of the TiO 2 -B nanowires (NWs) and nanoparticles (NPs) had been achieved via a facile hydrothermal route, respectively, only by tuning the solution volume. The dye-sensitized solar cells prototypes had been fabricated using TiO 2 -B NW and NP electrodes, respectively. The TiO 2 -B NP cells had higher photocurrent and photoelectrical conversion efficiency than the TiO 2 -B NW cells though the latter exhibited larger photovoltage compared to the former. The key factors such as the photogenerated electron injection drive force, surface defects and the interfacial charge transfer, which determined the photoelectrical properties, had been systematically researched with the surface photovoltage spectra (SPS) and the electrochemical impedance spectra (EIS). The SPS proved that there was larger photoelectron injection drive force in TiO 2 -B NP photoelectrode than that in NW photoelectrode. And the electrochemical impedance spectra (EIS) revealed that TiO 2 -B NP cells had faster interface charge transfer compared to TiO 2 -B NW cells. Both proved that NP cells had the higher photocurrents.

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells.

Science.gov (United States)

Huang, Yu-Hsuan; Tsai, Kevin; Tan, Sara Y; Kang, Sohyeong; Ford, Mandy L; Harder, Kenneth W; Priatel, John J

2017-01-01

Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8 + T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a - / - CD8 + T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a - / - CD8 + T cells responded equivalently to wild-type CD8 + T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8 + T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8 + T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8 + T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas.

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells

Science.gov (United States)

2017-01-01

ABSTRACT Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein–Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8+ T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a−/− CD8+ T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a−/− CD8+ T cells responded equivalently to wild-type CD8+ T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8+ T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8+ T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8+ T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas. PMID:28344876

Recommendations for quality assurance programs in nuclear medicine facilities. Radiation recommendations series

International Nuclear Information System (INIS)

Segal, P.; Hamilton, D.R.

1984-10-01

The publication provides the elements that should be considered by nuclear medicine facilities to improve their existing programs or develop new quality assurance programs. The important administrative aspects of quality assurance programs are stressed. Each facility is encouraged to adopt those elements of the recommended program that are appropriate to its individual needs and resources

Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

Directory of Open Access Journals (Sweden)

Angela Fuery

Full Text Available Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months were significantly associated with post-boost (13 months SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.

Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

Directory of Open Access Journals (Sweden)

Sandrine Peruchon

Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

Requirements Doc for Refurb of JASPER Facility in B131HB

Energy Technology Data Exchange (ETDEWEB)

Knittel, Kenn M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-01-25

The Joint Actinide Shock Physics Experimental Research (JASPER) Program target fabrication facility is currently located in building 131 (B131) of the Lawrence Livermore National Laboratory (LLNL). A portion of this current facility has been committed to another program as part of a larger effort to consolidate LLNL capabilities into newer facilities. This facility assembles precision targets for scientific studies at the Nevada National Security Site (NNSS). B131 is also going through a modernization project to upgrade the infrastructure and abate asbestos. These activities will interrupt the continuous target fabrication efforts for the JASPER Program. Several options are explored to meet the above conflicting requirements, with the final recommendation to prepare a new facility for JASPER target fabrication operations before modernization efforts begin in the current facility assigned to JASPER. This recommendation fits within all schedule constraints and minimizes the disruption to the JASPER Program. This option is not without risk, as it requires moving an aged, precision coordinate measuring machine, which is essential to the JASPER Program’s success. The selected option balances the risk to the machine with continuity of operations.

EBI2 overexpression in mice leads to B1 B-cell expansion and chronic lymphocytic leukemia-like B-cell malignancies.

Science.gov (United States)

Niss Arfelt, Kristine; Barington, Line; Benned-Jensen, Tau; Kubale, Valentina; Kovalchuk, Alexander L; Daugvilaite, Viktorija; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Egerod, Kristoffer L; Bassi, Maria R; Spiess, Katja; Schwartz, Thue W; Wang, Hongsheng; Morse, Herbert C; Holst, Peter J; Rosenkilde, Mette M

2017-02-16

Human and mouse chronic lymphocytic leukemia (CLL) develops from CD5 + B cells that in mice and macaques are known to define the distinct B1a B-cell lineage. B1a cells are characterized by lack of germinal center (GC) development, and the B1a cell population is increased in mice with reduced GC formation. As a major mediator of follicular B-cell migration, the G protein-coupled receptor Epstein-Barr virus-induced gene 2 ( EBI2 or GPR183 ) directs B-cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols. Thus, upregulation of EBI2 drives the B cells toward the extrafollicular area, whereas downregulation is essential for GC formation. We therefore speculated whether increased expression of EBI2 would lead to an expanded B1 cell subset and, ultimately, progression to CLL. Here, we demonstrate that B-cell-targeted expression of human EBI2 (hEBI2) in mice reduces GC-dependent immune responses, reduces total immunoglobulin M (IgM) and IgG levels, and leads to increased proliferation and upregulation of cellular oncogenes. Furthermore, hEBI2 overexpression leads to an abnormally expanded CD5 + B1a B-cell subset (present as early as 4 days after birth), late-onset lymphoid cancer development, and premature death. These findings are highly similar to those observed in CLL patients and identify EBI2 as a promoter of B-cell malignancies.

Can resting B cells present antigen to T cells

International Nuclear Information System (INIS)

Ashwell, J.D.; DeFranco, A.L.; Paul, W.E.; Schwartz, R.H.

1985-01-01

Antigen stimulation of T lymphocytes can occur only in the presence of an antigen-presenting cell (APC). An ever-increasing number of cell types have been found to act as APCs; these include macrophages, splenic and lymph node dendritic cells, and Langerhans cells of the skin. Although activated B lymphocytes and B cell lymphomas are known to serve as APCs, it has been generally believed that resting B cells cannot perform this function. However, in recent studies the authors have found that resting B cells can indeed present soluble antigen to T cell clones as well as to antigen-primed T cells. The previous difficulty in demonstrating this activity can be explained by the finding that, in contrast to macrophages and dendritic cells, the antigen-presenting ability of resting B cells is very radiosensitive. Macrophages are usually irradiated with 2000-3300 rads to prevent them from incorporating [ 3 H]thymidine in the T cell proliferation assay. Resting B cells, however, begin to lose presenting function at 1500 rads and have completely lost this activity at 3300 rads. It was also possible to distinguish two distinct T cell clonal phenotypes when resting B cells were used as APCs on the basis of two different assays (T cell proliferation, and B cell proliferation resulting from T cell activation). The majority of T cell clones tested were capable of both proliferating themselves and inducing the proliferation of B cells. Some T cells clones, however, could not proliferate in the presence of antigen and B cell APCs, although they were very good at inducing the proliferation of B cells

Improving Quality of Care in Primary Health-Care Facilities in Rural Nigeria: Successes and Challenges.

Science.gov (United States)

Ugo, Okoli; Ezinne, Eze-Ajoku; Modupe, Oludipe; Nicole, Spieker; Winifred, Ekezie; Kelechi, Ohiri

2016-01-01

Nigeria has a high population density but a weak health-care system. To improve the quality of care, 3 organizations carried out a quality improvement pilot intervention at the primary health-care level in selected rural areas. To assess the change in quality of care in primary health-care facilities in rural Nigeria following the provision of technical governance support and to document the successes and challenges encountered. A total of 6 states were selected across the 6 geopolitical zones of the country. However, assessments were carried out in 40 facilities in only 5 states. Selection was based on location, coverage, and minimum services offered. The facilities were divided randomly into 2 groups. The treatment group received quality-of-care assessment, continuous feedback, and improvement support, whereas the control group received quality assessment and no other support. Data were collected using the SafeCare Healthcare Standards and managed on the SafeCare Data Management System-AfriDB. Eight core areas were assessed at baseline and end line, and compliance to quality health-care standards was compared. Outcomes from 40 facilities were accepted and analyzed. Overall scores increased in the treatment facilities compared to the control facilities, with strong evidence of improvement ( t = 5.28, P = .0004) and 11% average improvement, but no clear pattern of improvement emerged in the control group. The study demonstrated governance support and active community involvement offered potential for quality improvement in primary health-care facilities.

Alpha-Gamma Hot-Cell Facility at Argonne National Laboratory East

International Nuclear Information System (INIS)

Neimark, L.A.; Jackson, W.D.; Donahue, D.A.

1979-01-01

The Alpha-Gamma Hot-Cell Facility has been in operation at Argonne National Laboratory East (ANL-E) for 15 years. The facility was designed for plutonium research in support of ANL's LMFBR program. The facility consists of a kilocurie, nitrogen-atmosphere alpha-gamma hot cell and supporting laboratories. Modifications to the facility and its equipment have been made over the years as the workload and nature of the work changed. These modifications included inerting the entire hot cell, adding four work stations, modifying in-loading procedures and examination equipment to handle longer test articles, and changing to a new sodium-vapor lighting system. Future upgrading includes the addition of a decontamination and repair facility, use of radio-controlled transfer carts, refurbishment of the zinc bromide windows, and the installation of an Auger microprobe

Quality of antenatal care service provision in health facilities across sub-Saharan Africa: Evidence from nationally representative health facility assessments.

Science.gov (United States)

Kanyangarara, Mufaro; Munos, Melinda K; Walker, Neff

2017-12-01

Utilization of antenatal care (ANC) services has increased over the past two decades. Continued gains in maternal and newborn health will require an understanding of both access and quality of ANC services. We linked health facility and household survey data to examine the quality of service provision for five ANC interventions across health facilities in sub-Saharan Africa. Using data from 20 nationally representative health facility assessments - the Service Provision Assessment (SPA) and the Service Availability and Readiness Assessment (SARA), we estimated facility level readiness to deliver five ANC interventions: tetanus toxoid vaccine for pregnant women, intermittent preventive treatment for malaria in pregnancy (IPTp), syphilis detection and treatment in pregnancy, iron supplementation and hypertensive disease case management. Facility level indicators were stratified by health facility type, managing authority and location, then linked to estimates of ANC utilization in that stratum from the corresponding Demographic and Health Surveys (DHS) to generate population level estimates of the 'likelihood of appropriate care'. Finally, the association between estimates of the 'likelihood of appropriate care' from the linking approach and estimates of coverage levels from the DHS were assessed. A total of 10 534 health facilities were surveyed in the 20 health facility assessments, of which 8742 reported offering ANC services and were included in the analysis. Health facility readiness to deliver IPTp, iron supplementation, and tetanus toxoid vaccination was higher (median: 84.1%, 84.9% and 82.8% respectively) than readiness to deliver hypertensive disease case management and syphilis detection and treatment (median: 23.0% and 19.9% respectively). Coverage of at least 4 ANC visits ranged from 24.8% to 75.8%. Estimates of the likelihood of appropriate care derived from linking health facility and household survey data showed marked gaps for all interventions

Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function.

Science.gov (United States)

Suenaga, Tadahiro; Arase, Hisashi; Yamasaki, Sho; Kohno, Masayuki; Yokosuka, Tadashi; Takeuchi, Arata; Hattori, Takamichi; Saito, Takashi

2007-11-01

Lymphocyte proliferation is regulated by signals through antigen receptors, co-stimulatory receptors, and other positive and negative modulators. Several membrane tetraspanning molecules are also involved in the regulation of lymphocyte growth and death. We cloned a new B cell-specific tetraspanning (BTS) membrane molecule, which is similar to CD20 in terms of expression, structure and function. BTS is specifically expressed in the B cell line and its expression is increased after the pre-B cell stage. BTS is expressed in intracellular granules and on the cell surface. Overexpression of BTS in immature B cell lines induces growth retardation through inhibition of cell cycle progression and cell size increase without inducing apoptosis. This inhibitory function is mediated predominantly by the N terminus of BTS. The development of mature B cells is inhibited in transgenic mice expressing BTS, suggesting that BTS is involved in the in vivo regulation of B cells. These results indicate that BTS plays a role in the regulation of cell division and B cell growth.

OCA-B regulation of B-cell development and function.

Science.gov (United States)

Teitell, Michael A

2003-10-01

The transcriptional co-activator OCA-B [for Oct co-activator from B cells, also known as OBF-1 (OCT-binding factor-1) and Bob1] is not required for B-cell genesis but does regulate subsequent B-cell development and function. OCA-B deficient mice show strain-specific, partial blocks at multiple stages of B-cell maturation and a complete disruption of germinal center formation in all strains, causing humoral immune deficiency and susceptibility to infection. OCA-B probably exerts its effects through the regulation of octamer-motif controlled gene expression. The OCA-B gene encodes two proteins of distinct molecular weight, designated p34 and p35. The p34 isoform localizes in the nucleus, whereas the p35 isoform is myristoylated and is bound to the cytoplasmic membrane. p35 can traffic to the nucleus and probably activates octamer-dependent transcription, although this OCA-B isoform might regulate B cells through membrane-related signal transduction.

Vitamin B12 and Semen Quality.

Science.gov (United States)

Banihani, Saleem Ali

2017-06-09

Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive) using the key words "vitamin B12" and "cobalamin" versus "sperm". Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects.

Conceptual layout design of CFETR Hot Cell Facility

Energy Technology Data Exchange (ETDEWEB)

Gong, Zheng, E-mail: gongz@mail.ustc.edu.cn [University of Science and Technology of China, Hefei 230026 (China); Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Qi, Minzhong, E-mail: qiminzhong@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Cheng, Yong, E-mail: chengyong@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Song, Yuntao, E-mail: songyt@ipp.ac.cn [University of Science and Technology of China, Hefei 230026 (China); Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China)

2015-11-15

Highlights: • This article proposed a conceptual layout design for CFETR. • The design principles are to support efficient maintenance to ensure the realization of high duty time. • The preliminary maintenance process and logistics are described in detail. • Life cycle management, maneuverability, risk and safety are in the consideration of design. - Abstract: CFETR (China Fusion Engineering Test Reactor) is new generation of Tokomak device beyond EAST in China. An overview of hot cell layout design for CFETR has been proposed by ASIPP&USTC. Hot Cell, as major auxiliary facility, not only plays a pivotal role in supporting maintenance to meet the requirements of high duty time 0.3–0.5 but also supports installation and decommissioning. Almost all of the Tokomak devices are lateral handling internal components like ITER and JET, but CFETR maintain the blanket module from 4 vertical ports, which is quite a big challenge for the hot cell layout design. The activated in-vessel components and several diagnosis instruments will be repaired and refurbished in the Hot Cell Facility, so the appropriate layout is very important to the Hot Cell Facility to ensure the high duty time, it is divided into different parts equipped with a variety of RH equipment and diagnosis devices based on the functional requirements. The layout of the Hot Cell Facility should make maintenance process more efficient and reliable, and easy to service and rescue when a sudden events taking place, that is the capital importance issue considered in design.

B Cells and B Cell Blasts Withstand Cryopreservation While Retaining Their Functionality for Producing Antibody.

Science.gov (United States)

Fecher, Philipp; Caspell, Richard; Naeem, Villian; Karulin, Alexey Y; Kuerten, Stefanie; Lehmann, Paul V

2018-05-31

In individuals who have once developed humoral immunity to an infectious/foreign antigen, the antibodies present in their body can mediate instant protection when the antigen re-enters. Such antigen-specific antibodies can be readily detected in the serum. Long term humoral immunity is, however, also critically dependent on the ability of memory B cells to engage in a secondary antibody response upon re-exposure to the antigen. Antibody molecules in the body are short lived, having a half-life of weeks, while memory B cells have a life span of decades. Therefore, the presence of serum antibodies is not always a reliable indicator of B cell memory and comprehensive monitoring of humoral immunity requires that both serum antibodies and memory B cells be assessed. The prevailing view is that resting memory B cells and B cell blasts in peripheral blood mononuclear cells (PBMC) cannot be cryopreserved without losing their antibody secreting function, and regulated high throughput immune monitoring of B cell immunity is therefore confined to-and largely limited by-the need to test freshly isolated PBMC. Using optimized protocols for freezing and thawing of PBMC, and four color ImmunoSpot ® analysis for the simultaneous detection of all immunoglobulin classes/subclasses we show here that both resting memory B cells and B cell blasts retain their ability to secrete antibody after thawing, and thus demonstrate the feasibility of B cell immune monitoring using cryopreserved PBMC.

B Cells and B Cell Blasts Withstand Cryopreservation While Retaining Their Functionality for Producing Antibody

Directory of Open Access Journals (Sweden)

Philipp Fecher

2018-05-01

Full Text Available In individuals who have once developed humoral immunity to an infectious/foreign antigen, the antibodies present in their body can mediate instant protection when the antigen re-enters. Such antigen-specific antibodies can be readily detected in the serum. Long term humoral immunity is, however, also critically dependent on the ability of memory B cells to engage in a secondary antibody response upon re-exposure to the antigen. Antibody molecules in the body are short lived, having a half-life of weeks, while memory B cells have a life span of decades. Therefore, the presence of serum antibodies is not always a reliable indicator of B cell memory and comprehensive monitoring of humoral immunity requires that both serum antibodies and memory B cells be assessed. The prevailing view is that resting memory B cells and B cell blasts in peripheral blood mononuclear cells (PBMC cannot be cryopreserved without losing their antibody secreting function, and regulated high throughput immune monitoring of B cell immunity is therefore confined to—and largely limited by—the need to test freshly isolated PBMC. Using optimized protocols for freezing and thawing of PBMC, and four color ImmunoSpot® analysis for the simultaneous detection of all immunoglobulin classes/subclasses we show here that both resting memory B cells and B cell blasts retain their ability to secrete antibody after thawing, and thus demonstrate the feasibility of B cell immune monitoring using cryopreserved PBMC.

New facilities of the ECN hot cell laboratory

International Nuclear Information System (INIS)

Duijves, K.A.; Konings, R.J.M.

1996-04-01

A description is given of two recent expansions of the ECN Hot Cell Laboratory in Petten; a production facility for molybdenum-99 and an actinide laboratory, a special facility to investigate unirradiated alpha- and beta-active samples. (orig.)

The Role of Distance and Quality on Facility Selection for Maternal and Child Health Services in Urban Kenya.

Science.gov (United States)

Escamilla, Veronica; Calhoun, Lisa; Winston, Jennifer; Speizer, Ilene S

2018-02-01

Universal access to health care requires service availability and accessibility for those most in need of maternal and child health services. Women often bypass facilities closest to home due to poor quality. Few studies have directly linked individuals to facilities where they sought maternal and child health services and examined the role of distance and quality on this facility choice. Using endline data from a longitudinal survey from a sample of women in five cities in Kenya, we examine the role of distance and quality on facility selection for women using delivery, facility-based contraceptives, and child health services. A survey of public and private facilities offering reproductive health services was also conducted. Distances were measured between household cluster location and both the nearest facility and facility where women sought care. A quality index score representing facility infrastructure, staff, and supply characteristics was assigned to each facility. We use descriptive statistics to compare distance and quality between the nearest available facility and visited facility among women who bypassed the nearest facility. Facility distance and quality comparisons were also stratified by poverty status. Logistic regression models were used to measure associations between the quality and distance to the nearest facility and bypassing for each outcome. The majority of women bypassed the nearest facility regardless of service sought. Women bypassing for delivery traveled the furthest and had the fewest facility options near their residential cluster. Poor women bypassing for delivery traveled 4.5 km further than non-poor women. Among women who bypassed, two thirds seeking delivery and approximately 46% seeking facility-based contraception or child health services bypassed to a public hospital. Both poor and non-poor women bypassed to higher quality facilities. Our findings suggest that women in five cities in Kenya prefer public hospitals and are

A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production.

Science.gov (United States)

Srour, Nivine; Chemin, Guillaume; Tinguely, Aurélien; Ashi, Mohamad Omar; Oruc, Zéliha; Péron, Sophie; Sirac, Christophe; Cogné, Michel; Delpy, Laurent

2016-01-11

Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igκ exons promote exon-skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Unexpectedly, such ΔV-κLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding ΔV-κLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of ΔV-κLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing ΔV-κLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. ΔV-κLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress-associated apoptosis, making PCs producing ΔV-κLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igκ alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with ΔV-κLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. © 2016 Srour et al.

EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies

DEFF Research Database (Denmark)

Niss Arfelt, Kristine; Barington, Line; Benned-Jensen, Tau

2017-01-01

-targeted expression of human EBI2 in mice reduces germinal center-dependent immune responses, reduces total IgM and IgG levels, and leads to increased proliferation and upregulation of cellular oncogenes. Furthermore, hEBI2 overexpression leads to an abnormally expanded CD5+ B1a B cell subset present as early as 4......Human and mouse chronic lymphocytic leukemia (CLL) develop from CD5+ B cells that in mice and macaques are known to define the distinct B1a B cell lineage. B1a cells are characterized by lack of germinal center development and the B1a cell population is increased in mice with reduced germinal...... cells towards the extrafollicular area, whereas downregulation is essential for germinal center formation. We therefore speculated whether increased expression of EBI2 would lead to an expanded B1 cell subset and, ultimately, progression to chronic lymphocytic leukemia. Here we demonstrate that B cell...

Endothelial Plasmalemma Vesicle Associated Protein regulates the homeostasis of splenic immature B cell and B1 B cells

Science.gov (United States)

Elgueta, Raul; Tse, Dan; Deharvengt, Sophie J.; Luciano, Marcus R.; Carriere, Catherine; Noelle, Randolph J.; Stan, Radu V.

2016-01-01

Plasmalemma vesicle associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble antigens into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM+IgDlo B cells in both the spleen and peritoneal cavity. Tissue specific deletion of Plvap demonstrates that the defect is B cell extrinsic, as B cell and pan hematopoietic Plvap deletion has no effect on IgM+IgDlo B cell numbers. Endothelial specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype whereas endothelial specific reconstitution of Plvap under the Chd5 promoter rescues the IgM+IgDlo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM+ B cells in the spleen and peritoneal cavity. PMID:27742829

Entry of Francisella tularensis into Murine B Cells: The Role of B Cell Receptors and Complement Receptors.

Directory of Open Access Journals (Sweden)

Lenka Plzakova

Full Text Available Francisella tularensis, the etiological agent of tularemia, is an intracellular pathogen that dominantly infects and proliferates inside phagocytic cells but can be seen also in non-phagocytic cells, including B cells. Although protective immunity is known to be almost exclusively associated with the type 1 pathway of cellular immunity, a significant role of B cells in immune responses already has been demonstrated. Whether their role is associated with antibody-dependent or antibody-independent B cell functions is not yet fully understood. The character of early events during B cell-pathogen interaction may determine the type of B cell response regulating the induction of adaptive immunity. We used fluorescence microscopy and flow cytometry to identify the basic requirements for the entry of F. tularensis into B cells within in vivo and in vitro infection models. Here, we present data showing that Francisella tularensis subsp. holarctica strain LVS significantly infects individual subsets of murine peritoneal B cells early after infection. Depending on a given B cell subset, uptake of Francisella into B cells is mediated by B cell receptors (BCRs with or without complement receptor CR1/2. However, F. tularensis strain FSC200 ΔiglC and ΔftdsbA deletion mutants are defective in the ability to enter B cells. Once internalized into B cells, F. tularensis LVS intracellular trafficking occurs along the endosomal pathway, albeit without significant multiplication. The results strongly suggest that BCRs alone within the B-1a subset can ensure the internalization process while the BCRs on B-1b and B-2 cells need co-signaling from the co receptor containing CR1/2 to initiate F. tularensis engulfment. In this case, fluidity of the surface cell membrane is a prerequisite for the bacteria's internalization. The results substantially underline the functional heterogeneity of B cell subsets in relation to F. tularensis.

Hot cell renovation in the spent fuel conditioning process facility at the Korea Atomic Energy Research Institute

Energy Technology Data Exchange (ETDEWEB)

Yu, Seung Nam; Lee, Jong Kwang; Park, Byung Suk; Cho, Il Je; Kim, Ki Ho [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

The advanced spent fuel conditioning process facility (ACPF) of the irradiated materials examination facility (IMEF) at the Korea Atomic Energy Research Institute (KAERI) has been renovated to implement a lab scale electrolytic reduction process for pyroprocessing. The interior and exterior structures of the ACPF hot cell have been modified under the current renovation project for the experimentation of the electrolytic reduction process using spent nuclear fuel. The most important aspect of this renovation was the installation of the argon compartment within the hot cell. For the design and system implementation of the argon compartment system, a full-scale mock-up test and a three-dimensional (3D) simulation test were conducted in advance. The remodeling and repairing of the process cell (M8a), the maintenance cell (M8b), the isolation room, and their utilities were also planned through this simulation to accommodate the designed argon compartment system. Based on the considered refurbishment workflow, previous equipment in the M8 cell, including vessels and pipes, were removed and disposed of successfully after a zoning smear survey and decontamination, and new equipment with advanced functions and specifications were installed in the hot cell. Finally, the operating area and isolation room were also refurbished to meet the requirements of the improved hot cell facility.

B-cell exposure to self-antigen induces IL-10 producing B cells as well as IL-6- and TNF-α-producing B-cell subsets in healthy humans

DEFF Research Database (Denmark)

Langkjær, Anina; Kristensen, Birte; Hansen, Bjarke E

2012-01-01

Human B cells are able to secrete IL-10 after stimulation with mitogens, but their ability to produce IL-10 and regulate T-cell responses after stimulation with self-antigens is unclear. We co-cultured thyroglobulin-pulsed B cells from healthy donors with autologous T cells and observed production...... of IL-10 and TGF-β, in addition to TNF-α and IL-6. Pulsing with foreign antigen, tetanus toxoid (TT), induced a Th1-response with minimal IL-10 production. After thyroglobulin-pulsing, 1.10±0.50% of B cells and 1.00±0.20% of CD4(+) T cells produced IL-10, compared to 0.29±0.19% of B cells (P=0.01) and 0.......13±0.15% of CD4(+) T cells (P=0.006) following TT-pulsing. Thyroglobulin-stimulated, IL-10-secreting B cells were enriched within CD5(+) and CD24(high) cells. While thyroglobulin-pulsed B cells induced only modest proliferation of CD4(+) T cells, B cells pulsed with TT induced vigorous proliferation. Thus, B...

Crew Factors in Flight Operations XII: A Survey of Sleep Quantity and Quality in On-Board Crew Rest Facilities

Science.gov (United States)

Rosekind, Mark R.; Gregory, Kevin B.; Co, Elizabeth L.; Miller, Donna L.; Dinges, David F.

2000-01-01

Many aircraft operated on long-haul commercial airline flights are equipped with on-board crew rest facilities, or bunks, to allow crewmembers to rest during the flight. The primary objectives of this study were to gather data on how the bunks were used, the quantity and quality of sleep obtained by flight crewmembers in the facilities, and the factors that affected their sleep. A retrospective survey comprising 54 questions of varied format addressed demographics, home sleep habits, and bunk sleep habits. Crewmembers from three airlines with long-haul fleets carrying augmented crews consisting of B747-100/200, B747-400, and MD-11 aircraft equipped with bunks returned a total of 1404 completed surveys (a 37% response rate). Crewmembers from the three carriers were comparable demographically, although one carrier had older, more experienced flight crewmembers. Each group, on average, rated themselves as "good" or "very good" sleepers at home, and all groups obtained about the same average amount of sleep each night. Most were able to sleep in the bunks, and about two thirds indicated that these rest opportunities benefited their subsequent flight deck alertness and performance. Comfort, environment, and physiology (e.g., being ready for sleep) were identified as factors that most promoted sleep. Factors cited as interfering with sleep included random noise, thoughts, heat, and the need to use the bathroom. These factors, in turn, suggest potential improvements to bunk facilities and their use. Ratings of the three aircraft types suggested differences among facilities. Bunks in the MD-11 were rated significantly better than either of the B747 types, and the B747-400 bunks received better ratings than did the older, B747-100/200 facilities.

Vitamin B12 and Semen Quality

Directory of Open Access Journals (Sweden)

Saleem Ali Banihani

2017-06-01

Full Text Available Various studies have revealed the effects of vitamin B12, also named cobalamin, on semen quality and sperm physiology; however, these studies collectively are still unsummarized. Here, we systematically discuss and summarize the currently understood role of vitamin B12 on semen quality and sperm physiology. We searched the Web of Science, PubMed, and Scopus databases for only English language articles or abstracts from September 1961 to March 2017 (inclusive using the key words “vitamin B12” and “cobalamin” versus “sperm”. Certain relevant references were included to support the empirical as well as the mechanistic discussions. In conclusion, the mainstream published work demonstrates the positive effects of vitamin B12 on semen quality: first, by increasing sperm count, and by enhancing sperm motility and reducing sperm DNA damage, though there are a few in vivo system studies that have deliberated some adverse effects. The beneficial effects of vitamin B12 on semen quality may be due to increased functionality of reproductive organs, decreased homocysteine toxicity, reduced amounts of generated nitric oxide, decreased levels of oxidative damage to sperm, reduced amount of energy produced by spermatozoa, decreased inflammation-induced semen impairment, and control of nuclear factor-κB activation. However, additional research, mainly clinical, is still needed to confirm these positive effects.

Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.

Directory of Open Access Journals (Sweden)

Goran Periz

2015-04-01

Full Text Available Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B and lysine-specific demethylase 1 (LSD1, respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy.

Relationship Quality as Predictor of B2B Customer Loyalty

Directory of Open Access Journals (Sweden)

Shaimaa S. B. Ahmed Doma

2013-02-01

Full Text Available Relationship marketing has become extremely important recently due to the fierce competition in today's marketplace. Companies are required to build long-term profitable relationship with customers and to achieve customer loyalty. Also, switching behaviors frequently occur among most of targeted customers. Fewer studies, however, discuss the effects of relationship quality efforts on customer loyalty. Therefore, this study is aimed to investigate the impact of relationship quality on customer loyalty in B2B context in the Egyptian shipping services sector. Building on prior research, we propose relationship quality as a higher construct comprising trust, commitment and satisfaction. An analytical model is developed as a guideline to test the relationships between relationship quality dimensions and customer loyalty.

200 area liquid effluent facility quality assurance program plan. Revision 1

International Nuclear Information System (INIS)

Sullivan, N.J.

1995-01-01

Direct revision of Supporting Document WHC-SD-LEF-QAPP-001, Rev. 0. 200 Area Liquid Effluent Facilities Quality Assurance Program Plan. Incorporates changes to references in tables. Revises test to incorporate WHC-SD-LEF-CSCM-001, Computer Software Configuration Management Plan for 200 East/West Liquid Effluent Facilities

CHALLENGES IN SETTING UP QUALITY CONTROL IN DIAGNOSTIC RADIOLOGY FACILITIES IN NIGERIA.

Science.gov (United States)

Inyang, S O; Egbe, N O; Ekpo, E

2015-01-01

The Nigerian Nuclear Regulatory Authority (NNRA) was established to regulate and control the use of radioactive and radiation emitting sources in Nigeria. Quality control (QC) on diagnostic radiology equipment form part of the fundamental requirements for the authorization of diagnostic radiology facilities in the Country. Some quality control tests (output, exposure linearity and reproducibility) were measured on the x-ray machines in the facilities that took part in the study. Questionnaire was developed to evaluate the frequencies at which QC tests were conducted in the facilities and the challenges in setting up QC. Results show great variation in the values of the QC parameters measured. Inadequate cooperation by facilities management, lack of QC equipment and insufficient staff form the major challenges in setting up QC in the facilities under study. The responses on the frequencies at which QC tests should be conducted did not correspond to the recommended standards; indicating that personnel were not familiar with QC implementation and may require further training on QC.

Results of phase 1 groundwater quality assessment for Single-Shell Tank Waste Management Areas B-BX-BY at the Hanford Site

Energy Technology Data Exchange (ETDEWEB)

Narbutovskih, S.M.

1998-02-01

Pacific Northwest National Laboratory conducted a Phase 1 (or first determination) groundwater quality assessment for the US Department of Energy, Richland Operations Office, in accordance with the Federal Facility Compliance Agreement. The purpose of the assessment was to determine if the Single-Shell Tank Waste Management Area (WMA) B-BX-BY has impacted groundwater quality. This report will document the evidence demonstrating that the WMA has impacted groundwater quality.

Results of phase 1 groundwater quality assessment for Single-Shell Tank Waste Management Areas B-BX-BY at the Hanford Site

International Nuclear Information System (INIS)

Narbutovskih, S.M.

1998-02-01

Pacific Northwest National Laboratory conducted a Phase 1 (or first determination) groundwater quality assessment for the US Department of Energy, Richland Operations Office, in accordance with the Federal Facility Compliance Agreement. The purpose of the assessment was to determine if the Single-Shell Tank Waste Management Area (WMA) B-BX-BY has impacted groundwater quality. This report will document the evidence demonstrating that the WMA has impacted groundwater quality

Differential radiosensitivity among B cell subpopulations

International Nuclear Information System (INIS)

Riggs, J.E.

1988-01-01

The selective radiosensitivity of sIgM >> sIgD marginal zone B cells is associated with the selective loss of B cell function. The simultaneous restoration of impaired function and recovery of these cells with time supports this premise. B cell recovery, delayed one week after irradiation, is in progress at two weeks, and virtually complete by three weeks. XID mice reveal similar recovery kinetics although there are fewer recovering cells and these bear reduced levels of Ia. This observation represents additional evidence that xid B cells are distinct from those of normal mice. The simultaneous loss, and concurrent recovery, of sIgM >> sIgD B cells and TI-2 responsiveness in irradiated mice suggests the existence of a unique B cell subpopulation possessing both phenotypes. Additional support for this hypothesis is provided by demonstrating that splenocytes, depleted of IgD + cells adoptively reconstitute this response in XID mice. The peritoneal B cell pool, which, compared to the spleen, consist of increased numbers of sIgM >> sIgD B cells, is shown to be a source of radiosensitive B cells that are TI-2 responsive. These observations represent additional evidence for an association between sIgM >> sIgD B cells and TI-2 responsiveness

Final deactivation project report on the High Radiation Level Analytical Facility, Building 3019B at Oak Ridge National Laboratory, Oak Ridge, Tennessee

International Nuclear Information System (INIS)

1997-09-01

The purpose of this report is to document the condition of the High Radiation Level Analytical Facility (Building 3019B) at Oak Ridge National Laboratory (ORNL) after completion of deactivation activities. This report identifies the activities conducted to place the facility in a safe and environmentally sound condition prior to transfer to the Environmental Restoration EM-40 Program. This document provides a history and description of the facility prior to the commencement of deactivation activities and documents the condition of the building after completion of all deactivation activities. Turnover items, such as the Post-Deactivation Surveillance and Maintenance (S ampersand M) Plan, remaining hazardous materials inventory, radiological controls, safeguards and security, quality assurance, facility operations, and supporting documentation provided in the Nuclear Material and Facility Stabilization (EM-60) Turnover package are discussed. Building 3019B will require access to perform required S ampersand M activities to maintain the building safety envelope. Building 3019B was stabilized during deactivation so that when transferred to the EM-40 Program, only a minimal S ampersand M effort would be required to maintain the building safety envelope. Other than the minimal S ampersand M activities the building will be unoccupied and the exterior doors locked to prevent unauthorized access. The building will be entered only to perform the required S ampersand M until decommissioning activities begin

Final deactivation project report on the High Radiation Level Analytical Facility, Building 3019B at Oak Ridge National Laboratory, Oak Ridge, Tennessee

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-09-01

The purpose of this report is to document the condition of the High Radiation Level Analytical Facility (Building 3019B) at Oak Ridge National Laboratory (ORNL) after completion of deactivation activities. This report identifies the activities conducted to place the facility in a safe and environmentally sound condition prior to transfer to the Environmental Restoration EM-40 Program. This document provides a history and description of the facility prior to the commencement of deactivation activities and documents the condition of the building after completion of all deactivation activities. Turnover items, such as the Post-Deactivation Surveillance and Maintenance (S&M) Plan, remaining hazardous materials inventory, radiological controls, safeguards and security, quality assurance, facility operations, and supporting documentation provided in the Nuclear Material and Facility Stabilization (EM-60) Turnover package are discussed. Building 3019B will require access to perform required S&M activities to maintain the building safety envelope. Building 3019B was stabilized during deactivation so that when transferred to the EM-40 Program, only a minimal S&M effort would be required to maintain the building safety envelope. Other than the minimal S&M activities the building will be unoccupied and the exterior doors locked to prevent unauthorized access. The building will be entered only to perform the required S&M until decommissioning activities begin.

B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

Directory of Open Access Journals (Sweden)

Larimore Kevin

2012-06-01

Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

Endothelial Plasmalemma Vesicle-Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells.

Science.gov (United States)

Elgueta, Raul; Tse, Dan; Deharvengt, Sophie J; Luciano, Marcus R; Carriere, Catherine; Noelle, Randolph J; Stan, Radu V

2016-11-15

Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM + IgD lo B cells in both the spleen and the peritoneal cavity. Tissue-specific deletion of Plvap demonstrates that the defect is B cell extrinsic, because B cell and pan-hematopoietic Plvap deletion has no effect on IgM + IgD lo B cell numbers. Endothelial-specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype, whereas endothelial-specific reconstitution of Plvap under the Chd5 promoter rescues the IgM + IgD lo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM + B cells in the spleen and peritoneal cavity. Copyright © 2016 by The American Association of Immunologists, Inc.

Evaluate of environment quality for γ irradiation facilities using fuzzy comprehensive judgment method

International Nuclear Information System (INIS)

Ha Yiming

2002-01-01

The environment quality of Jining Irradiation Centre new γ radiation facility was evaluated by fuzzy comprehensive judgment method. The result showed that the place of γ radiation facility was well and the measures of radiate shelter and environment protect were effective. The environment quality of its area was not obvious change and the result of environment evaluation was first-rate

Human regulatory B cells control the TFH cell response.

Science.gov (United States)

Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

2017-07-01

Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

EVALUATION OF SERVICES’ QUALITY IN UPPER SILESIA ACCOMMODATION FACILITIES

Directory of Open Access Journals (Sweden)

Iwona Cieślik

2013-12-01

Full Text Available This paper presents the results of study about impact of accommodation services’ quality, particularly quality of work and qualifications of staff, on the guests’ opinion, and thus promoting the accommodation facilities, and making a choice of a hotel in the Upper Silesia. The study involved 200 people, taking into account their gender, age, place of residence, education and occupational status. The research tool was a survey questionnaire. The results indicate close correlation between the quality of staff services (individual approach, aesthetics, discretion, understanding and the customer is satisfaction. Particular attention was paid to the quality of service by the guests with high professional status, and higher education.

First Dutch Consensus of Pain Quality Indicators for Pain Treatment Facilities

NARCIS (Netherlands)

Meij, N. de; Grotel, M. van; Patijn, J.; Weijden, T.T. van der; Kleef, M. van

2016-01-01

BACKGROUND: There is a general consensus about the need to define and improve the quality of pain treatment facilities. Although guidelines and recommendations to improve the quality of pain practice management have been launched, provision of appropriate pain treatment is inconsistent and the

Quality Assurance of ARM Program Climate Research Facility Data

Energy Technology Data Exchange (ETDEWEB)

Peppler, RA; Kehoe, KE; Sonntag, KL; Bahrmann, CP; Richardson, SJ; Christensen, SW; McCord, RA; Doty, DJ; Wagener, Richard [BNL; Eagan, RC; Lijegren, JC; Orr, BW; Sisterson, DL; Halter, TD; Keck, NN; Long, CN; Macduff, MC; Mather, JH; Perez, RC; Voyles, JW; Ivey, MD; Moore, ST; Nitschke, DL; Perkins, BD; Turner, DD

2008-03-01

This report documents key aspects of the Atmospheric Radiation Measurement (ARM) Climate Research Facility (ACRF) data quality assurance program as it existed in 2008. The performance of ACRF instruments, sites, and data systems is measured in terms of the availability, usability, and accessibility of the data to a user. First, the data must be available to users; that is, the data must be collected by instrument systems, processed, and delivered to a central repository in a timely manner. Second, the data must be usable; that is, the data must be inspected and deemed of sufficient quality for scientific research purposes, and data users must be able to readily tell where there are known problems in the data. Finally, the data must be accessible; that is, data users must be able to easily find, obtain, and work with the data from the central repository. The processes described in this report include instrument deployment and calibration; instrument and facility maintenance; data collection and processing infrastructure; data stream inspection and assessment; the roles of value-added data processing and field campaigns in specifying data quality and haracterizing the basic measurement; data archival, display, and distribution; data stream reprocessing; and engineering and operations management processes and procedures. Future directions in ACRF data quality assurance also are presented.

Quality Assurance of ARM Program Climate Research Facility Data

International Nuclear Information System (INIS)

Peppler, R.A.; Kehoe, K.E.; Sonntag, K.L.; Bahramann, C.P.; Richardson, S.J.; Christensen, S.W.; McCord, R.A.; Doty, D.J.; Wagener, R.; Eagan, R.C.; Lijegren, J.C.; Orr, B.W.; Sisterson, D.L.; Halter, T.D.; Keck, N.N.; Long, C.N.; Macduff, M.C.; Mather, J.H.; Perez, R.C.; Voyles, J.W.; Ivey, M.D.; Moore, S.T.; Nitschke, D.L.; Perkins, B.D.; Turner, D.D.

2008-01-01

This report documents key aspects of the Atmospheric Radiation Measurement (ARM) Climate Research Facility (ACRF) data quality assurance program as it existed in 2008. The performance of ACRF instruments, sites, and data systems is measured in terms of the availability, usability, and accessibility of the data to a user. First, the data must be available to users; that is, the data must be collected by instrument systems, processed, and delivered to a central repository in a timely manner. Second, the data must be usable; that is, the data must be inspected and deemed of sufficient quality for scientific research purposes, and data users must be able to readily tell where there are known problems in the data. Finally, the data must be accessible; that is, data users must be able to easily find, obtain, and work with the data from the central repository. The processes described in this report include instrument deployment and calibration; instrument and facility maintenance; data collection and processing infrastructure; data stream inspection and assessment; the roles of value-added data processing and field campaigns in specifying data quality and characterizing the basic measurement; data archival, display, and distribution; data stream reprocessing; and engineering and operations management processes and procedures. Future directions in ACRF data quality assurance also are presented

Regulatory T cells and B cells: implication on autoimmune diseases

OpenAIRE

Wang, Ping; Zheng, Song Guo

2013-01-01

The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.

Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

Directory of Open Access Journals (Sweden)

Daniela Frasca

2017-08-01

Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

Decontamination of an Analytical Laboratory Hot Cell Facility

International Nuclear Information System (INIS)

Michelbacher, J.A.; Henslee, S.P.; Rosenberg, K.E.; Coleman, R.M.

1995-11-01

An Analytical Laboratory Hot Cell Facility at Argonne National Laboratory-West (ANL-W) had been in service for nearly thirty years. In order to comply with current DOE regulations governing such facilities and meet programmatic requirements, a major refurbishment effort was mandated. Due to the high levels of radiation and contamination within the cells, a decontamination effort was necessary to provide an environment that permitted workers to enter the cells to perform refurbishment activities without receiving high doses of radiation and to minimize the potential for the spread of contamination. State-of-the-art decontamination methods, as well as time-proven methods were utilized to minimize personnel exposure as well as maximize results

B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling.

Directory of Open Access Journals (Sweden)

Yuri Kasama

Full Text Available Hepatitis C virus (HCV infection leads to the development of hepatic diseases, as well as extrahepatic disorders such as B-cell non-Hodgkin's lymphoma (B-NHL. To reveal the molecular signalling pathways responsible for HCV-associated B-NHL development, we utilised transgenic (Tg mice that express the full-length HCV genome specifically in B cells and develop non-Hodgkin type B-cell lymphomas (BCLs. The gene expression profiles in B cells from BCL-developing HCV-Tg mice, from BCL-non-developing HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analysed by genome-wide microarray. In BCLs from HCV-Tg mice, the expression of various genes was modified, and for some genes, expression was influenced by the gender of the animals. Markedly modified genes such as Fos, C3, LTβR, A20, NF-κB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-κB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.

IL-15 inhibits pre-B cell proliferation by selectively expanding Mac-1+B220+ NK cells

International Nuclear Information System (INIS)

Nakajima, Shinsuke; Hida, Shigeaki; Taki, Shinsuke

2008-01-01

Natural killer (NK) cells are the cells critical for inhibition of repopulation of allogenic bone marrow cells. However, it is not well known if NK cells affect autologous lymphopoiesis. Here, we observed that NK cells could inhibit pre-B cell proliferation in vitro driven by interleukin (IL)-7 in a manner dependent on IL-15. Interestingly, the great majority of expanding NK cells were Mac-1 + B220 + , a recently identified potent interferon (IFN)-γ producer. Indeed, IFN-γ was produced in those cultures, and pre-B cells lacking IFN-γ receptors, but not those lacking type I IFN receptors, were resistant to such an inhibition. Furthermore, even NK cells from mice lacking β2-microglobulin, which were known to be functionally dampened, inhibited pre-B cell proliferation as well. Thus, activated NK cells, which were expanded selectively by IL-15, could potentially regulate B lymphopoiesis through IFN-γ beyond the selection imposed upon self-recognition

The cell biology of T-dependent B cell activation

DEFF Research Database (Denmark)

Owens, T; Zeine, R

1989-01-01

The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...... includes multipoint intermolecular interactions that probably involve aggregation of both polymorphic and monomorphic T cell surface molecules. Such aggregations have been shown in vitro to markedly enhance and, in some cases, induce T cell activation. The production of T-derived lymphokines that have been...... implicated in B cell activation is dependent on the T cell receptor for antigen and its associated CD3 signalling complex. T-dependent help for B cell activation is therefore similarly MHC-restricted and involves T-B intercellular interaction. Recent reports that describe antigen-independent B cell...

Conceptual designs for waste quality checking facilities for low level and intermediate level radioactive wastes and hazardous waste

International Nuclear Information System (INIS)

Driver, S.; Griffiths, M.; Leonard, C.D.; Smith, D.L.G.

1992-01-01

This report summarises work carried out on the design of facilities for the quality checking of Intermediate and Low Level Radioactive Waste and Hazardous Waste. The procedures used for the quality checking of these categories of waste are summarised. Three building options are considered: a separate LLW facility, a combined facility for LLW and HW and a Waste Quality Checking Facility for the three categories of waste. Budget Cost Estimates for the three facilities are given based on 1991 prices. (author)

HCV Infection and B-Cell Lymphomagenesis

Directory of Open Access Journals (Sweden)

Masahiko Ito

2011-01-01

Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

The 'SILOE' reactor at Grenoble, France and associated hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the SILOE reactor and associated hot cell facilities, with the main emphasis on experimental irradiation facilities, specialized irradiation devices (loops and capsules) and possibilities for post-irradiation examinations of samples. The information is presented in the form of eight information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; neutron spectra; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities; equipment and techniques available for post-irradiation examinations; utilization and specialization of the hot cell facilities

The 'OSIRIS' reactor at Saclay, France and available hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the OSIRIS reactor and associated hot cell facilities, with the main emphasis on experimental irradiation facilities, specialized irradiation devices (loops and capsules) and possibilities for post-irradiation examinations of samples. The information is presented in the form of eight information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; neutron spectra; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities; equipment and techniques available for post-irradiation examinations; utilization and specialization of the hot cell facilities

Decommissioning of the Risoe Hot Cell facility

International Nuclear Information System (INIS)

Carlsen, H.

1991-02-01

The Hot Cell facility at Risoe has been in active use since 1964. During the years several types of nuclear fuels have been handled and examined: test reactor fuel pins from the Danish reactor DR3, the Norwegian Halden reactor, etc; power reactor fuel pins from several foreign reactors, including plutonium enriched pins; HTGR fuel from the Dragon reactor. All kinds of physical and chemical non-destructive and destructive post irradiation examinations have been performed. Besides, different radiotherapy sources have been produced, mainly cobalt sources. The general object of the decommissioning programme for the Hot Cell facility was to obtain a safe condition for the total building that does not require the special safety provisions. The hot cell building will be usable for other purposes after decommissioning. The facilicy comprised six concrete cells, lead cells, glove boxes, a shielded unit for temporary storage of waste, frogman area, decontamination areas, workshops, various installations of importance for safe operation of the plant, offices, etc. The tasks comprised e.g. removal of all irradiated fuel items, removal of other radioactive items, removal of contaminated equipment, and decontamination of all the cells and rooms. The goal was to decontaminate all the concrete cells to a degree where no loose contamination exists in the cells, and where the radiation level is so low, that total removal of the cell structures can be done at any time in the future without significant dose commitments. (AB)

Implementation of a quality management system at the PHOENIX facility (CryoMaK)

International Nuclear Information System (INIS)

Urbach, Elisabeth; Bagrets, Nadezda; Weiss, Klaus-Peter

2013-01-01

Within a variety of mechanical tests in the Cryogenic Material Test Facility Karlsruhe (CryoMaK) at Karlsruhe Institute of Technology (KIT) the PHOENIX facility was prepared for multiple standard tensile tests in liquid helium, liquid nitrogen and at room temperature. With the multiple specimens holder 10 specimens can be tested within one cool down one after another. A quality management system is needed for ensuring reproducible preconditions. For the guarantee of the competence of the laboratory and the measurement equipment, a quality management system was implemented and prepared for accreditation according to DIN EN ISO/IEC 17025 (ISO 17025). The implementation of a quality management system allows high precision test results included the estimation of measurement uncertainty. This paper gives an overview of the management and technical requirements for the accreditation of the PHOENIX testing facility

Implementation of a quality management system at the PHOENIX facility (CryoMaK)

Energy Technology Data Exchange (ETDEWEB)

Urbach, Elisabeth, E-mail: elisabeth.urbach@kit.edu; Bagrets, Nadezda; Weiss, Klaus-Peter

2013-10-15

Within a variety of mechanical tests in the Cryogenic Material Test Facility Karlsruhe (CryoMaK) at Karlsruhe Institute of Technology (KIT) the PHOENIX facility was prepared for multiple standard tensile tests in liquid helium, liquid nitrogen and at room temperature. With the multiple specimens holder 10 specimens can be tested within one cool down one after another. A quality management system is needed for ensuring reproducible preconditions. For the guarantee of the competence of the laboratory and the measurement equipment, a quality management system was implemented and prepared for accreditation according to DIN EN ISO/IEC 17025 (ISO 17025). The implementation of a quality management system allows high precision test results included the estimation of measurement uncertainty. This paper gives an overview of the management and technical requirements for the accreditation of the PHOENIX testing facility.

NKT Cell Responses to B Cell Lymphoma.

Science.gov (United States)

Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

2014-06-01

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

Development of a quality system for a contract irradiation facility

International Nuclear Information System (INIS)

Siyakus, G.

2002-01-01

. Even, some conditions required by the primary producer may be impossible to apply because of the design parameters of the facility or economical reasons. The worst situation is, transforming the commodity to be processed into garbage, because of the any misapprehension among the customer and the organization running the facility, or any level of misleading among the internal communication chain of the organization. Therefore, every step of the process from delivery of the product by the principal manufacturer up to the release of the commodity after irradiation should be firmly defined, organized, documented, validated and certified. The purpose of the irradiation may be at variance from decontamination of a food commodity to the sterilization of a medical supply. To make things easier, the case study which will be presented in the scope of this paper is limited with the radiation sterilization of medical supplies at the Food Irradiation and Sterilization Department (FISD) of Ankara Nuclear Research Center of Agriculture and Animal Science (ANRCAAS). To meet the requirements stated by the contract, an appropriate quality management system should be implemented. Basic activities for implementing a quality management system should be: A policy for quality management, An appropriate work flow, Contract model to make certain the demand of the primary producer, Straightforward documentation of the management responsibilities, Suitable premises, equipment and materials, Well defined and documented procedures, processes to be applied on the product, Traceable batch, product and dosimetry records, Definitely the radiation, chemical and biological safety issues related to the personnel working in the quality control laboratories and irradiation facility are more essential issues than the above mentioned topics and should be included into the quality system

242-A Evaporator/Liquid Effluent Retention Facility data quality objectives

International Nuclear Information System (INIS)

Von Bargen, B.H.

1994-01-01

The purpose of data quality objectives (DQO) is to determine the most cost effective methods of gathering the essential data necessary to make decisions to support successful operation of the facility. The essential data is defined by such information as sample amount, sample location, required analyses, and how sampling and analyses are performed. Successful operation is defined as meeting the campaign objectives while operating within established requirements. This DQO document addresses that portion of the system from 242-A Evaporator candidate feed tanks through discharge of process condensate to the Liquid Effluent Retention of Facility (LERF). Later revisions will incorporate and integrate the entire system, including the Effluent Treatment Facility (ETF)

242-A Evaporator/Liquid Effluent Retention Facility data quality objectives

Energy Technology Data Exchange (ETDEWEB)

Von Bargen, B.H.

1994-09-29

The purpose of data quality objectives (DQO) is to determine the most cost effective methods of gathering the essential data necessary to make decisions to support successful operation of the facility. The essential data is defined by such information as sample amount, sample location, required analyses, and how sampling and analyses are performed. Successful operation is defined as meeting the campaign objectives while operating within established requirements. This DQO document addresses that portion of the system from 242-A Evaporator candidate feed tanks through discharge of process condensate to the Liquid Effluent Retention of Facility (LERF). Later revisions will incorporate and integrate the entire system, including the Effluent Treatment Facility (ETF).

B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.

Science.gov (United States)

Xiao, Gang; Chan, Lai N; Klemm, Lars; Braas, Daniel; Chen, Zhengshan; Geng, Huimin; Zhang, Qiuyi Chen; Aghajanirefah, Ali; Cosgun, Kadriye Nehir; Sadras, Teresa; Lee, Jaewoong; Mirzapoiazova, Tamara; Salgia, Ravi; Ernst, Thomas; Hochhaus, Andreas; Jumaa, Hassan; Jiang, Xiaoyan; Weinstock, David M; Graeber, Thomas G; Müschen, Markus

2018-04-05

B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1. Reflecting B-cell-specific transcriptional PPP-repression, glucose carbon utilization in B cells is heavily skewed in favor of glycolysis resulting in lack of PPP-dependent antioxidant protection. These findings reveal a gatekeeper function of the PPP in a broad range of B cell malignancies that can be efficiently targeted by small molecule inhibition of PP2A and G6PD. Copyright © 2018 Elsevier Inc. All rights reserved.

Measuring Inpatient Rehabilitation Facility Quality of Care: Discharge Self-Care Functional Status Quality Measure.

Science.gov (United States)

Pardasaney, Poonam K; Deutsch, Anne; Iriondo-Perez, Jeniffer; Ingber, Melvin J; McMullen, Tara

2018-06-01

To describe the calculation and psychometric properties of the discharge self-care functional status quality measure implemented in the Centers for Medicare & Medicaid Services' (CMS) Inpatient Rehabilitation Facility (IRF) Quality Reporting Program on October 1, 2016. Medicare fee-for-service (FFS) patients from 38 IRFs that participated in the CMS Post-Acute Care Payment Reform Demonstration were included in this cohort study. Data came from the Continuity Assessment Record and Evaluation Item Set, IRF-Patient Assessment Instrument, and Medicare claims. For each patient, we calculated an expected discharge self-care score, risk-adjusted for demographic and baseline clinical characteristics. The performance score of each IRF equaled the percentage of patient stays where the observed discharge self-care score met or exceeded the expected score. We assessed the measure's discriminatory ability across IRFs and reliability. IRFs. Medicare FFS patients aged ≥21 years (N=4769). Not applicable. Facility-level discharge self-care quality measure performance score. A total of 4769 patient stays were included; 57% of stays were in women, and 12.1% were in patients aged quality measure showed strong reliability, with intraclass correlation coefficients of .91. The discharge self-care quality measure showed strong discriminatory ability and reliability, representing an important initial step in evaluation of IRF self-care outcomes. A wide range in performance scores suggested a gap in quality of care across IRFs. Future work should include testing the measure with nationwide data from all IRFs. Published by Elsevier Inc.

Review of alternative residual contamination guides for the 324 Building B-Cell Cleanout Project. Phase 1

International Nuclear Information System (INIS)

Vargo, G.J.; Durham, J.S.; Brackenbush, L.W.

1995-09-01

This report provides a proposed residual contamination guide (RCG) for the 324 Building B-Cell Cleanout Project, Phase 1, at the Hanford Site. The RCG is expressed as a fraction of the amount of highly dispersible radioactive material that would result in offsite doses equal to the Pacific Northwest Laboratory radiological risk guidelines following the worst credible accident scenario for release of the holdup material. The proposed RCG is 10 -1 to 10 -2 of the PNL radiological risk guidelines. As part of the development of the RCG, a number of factors were considered. These include the need to provide an appropriate level of flexibility for other activities within the 324 Building that could contribute to the facility's overall radiological risk, uncertainties inherent in safety analyses, and the possible contribution of other 300 Area facilities to overall radiological risk. Because of these factors and the nature of the cleanout project, the RCG is expressed as a range rather than a point value. This report also provides guidance on determining conformance to the RCG, including inspection and measurement techniques, quality assurance requirements, and consideration of uncertainty

Impacts of iron and steelmaking facilities on soil quality.

Science.gov (United States)

Strezov, Vladimir; Chaudhary, Chandrakant

2017-12-01

Iron and steel are highly important materials used in a wide range of products with important contribution to the economic development. The processes for making iron and steel are energy intensive and known to contribute to local pollution. Deposition of the metals may also have adverse impacts on soil quality, which requires detailed assessment. The aim of this study was to investigate the impacts of iron and steelmaking facilities on the local soil quality. Soil samples were collected in the vicinity of two steelmaking sites in Australia, one based on blast furnace steelmaking operation, while the second site was based on electric arc furnace steel recycling. The soil samples were compared to a background site where no industrial impact is expected. The soil collected near industrial facilities contained larger toxic metal contents, however this concentration for all priority metals was within the Australian National Environmental Protection Measure guidelines for the acceptable recreational soil quality. When compared to the international soil quality guidelines, some of the soils collected near the industrial sites, particularly near the blast furnace operated steelmaking, exceeded the arsenic, iron and manganese (according to United States Environmental Protection Agency guidelines) and chromium, copper and nickel concentrations (according to the Canadian guidelines). The work further provided a novel environmental assessment model taking into consideration the environmental and health impacts of each element. The environmental assessment revealed most significant contribution of manganese, followed by titanium, zinc, chromium and lead. Titanium was the second most important contributor to the soil quality, however this metal is currently not included in any of the international soil quality guidelines. Copyright © 2017 Elsevier Ltd. All rights reserved.

B-cell activating factor detected on both naïve and memory B cells in bullous pemphigoid.

Science.gov (United States)

Qian, Hua; Kusuhara, Masahiro; Li, Xiaoguang; Tsuruta, Daisuke; Tsuchisaka, Atsunari; Ishii, Norito; Koga, Hiroshi; Hayakawa, Taihei; Ohara, Koji; Karashima, Tadashi; Ohyama, Bungo; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

2014-08-01

B-cell activating factor (BAFF), an important immune regulatory cytokine, is involved in development of autoimmune diseases. Although BAFF is expressed in various cells, including dendritic cells (DCs) and monocytes, BAFF expression on B cells has not been well documented. In the present study, BAFF molecules on DCs and naïve and memory B cells in autoimmune bullous diseases, including pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid (BP), were analysed by flow cytometry. Compared with healthy controls (HC), BAFF expression on naïve and memory B cells increased significantly in BP. No difference in BAFF receptor expression in naïve and memory B cells was shown among all study groups. Furthermore, BAFF expression in both naïve and memory B cells of BP, but not HC, was detected by confocal microscopic analysis. These results implied that BAFF expressed by B cells may play a pathogenic role in autoimmune bullous diseases, particularly BP. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

External quality assessment of malaria microscopy diagnosis in selected health facilities in Western Oromia, Ethiopia.

Science.gov (United States)

Sori, Getachew; Zewdie, Olifan; Tadele, Geletta; Samuel, Abdi

2018-06-18

Accurate early diagnosis and prompt treatment are one of the key strategies to control and prevent malaria disease. External quality assessment is the most effective method for evaluation of the quality of malaria microscopy diagnosis. The aim of this study was to assess the quality of malaria microscopy diagnosis and its associated factors in selected public health facility laboratories in East Wollega Zone, Western Ethiopia. Facility-based cross-sectional study design was conducted in 30 randomly selected public health facility laboratories from November 2014 to January 2015 in East Wollega Zone, Western Ethiopia. Ten validated stained malaria panel slides with known Plasmodium species, developmental stage and parasite density were distributed. Data were captured; cleaned and analyzed using SPSS version 20 statistical software-multivariate logistic regressions and the agreement in reading between the peripheral diagnostic centers and the reference laboratory were done using kappa statistics. A total of 30 health facility laboratories were involved in the study and the overall quality of malaria microscopy diagnosis was poor (62.3%). The associated predictors of quality in this diagnosis were in-service training [(AOR = 16, 95% CI (1.3, 1.96)], smearing quality [(AOR = 24, 95% CI (1.8, 3.13)], staining quality [(AOR = 15, 95% CI (2.35, 8.61), parasite detection [(AOR = 9, 95% CI (1.1, 8.52)] and identification skills [(AOR = 8.6, 95% CI (1.21, 1.63)]. Eighteen (60%) of health facility laboratories had in-service trained laboratory professionals on malaria microscopy diagnosis. Overall quality of malaria microscopy diagnosis was poor and a significant gap in this service was observed that could impact on its diagnostic services.

B cell lymphomas express CX3CR1 a non-B cell lineage adhesion molecule

DEFF Research Database (Denmark)

Andreasson, U.; Ek, S.; Merz, H.

2008-01-01

normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma......To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering...... the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which...

Comparison of EBV DNA viral load in whole blood, plasma, B-cells and B-cell culture supernatant.

Science.gov (United States)

Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard

2014-05-01

Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios. © 2013 Wiley Periodicals, Inc.

21 CFR 129.35 - Sanitary facilities.

Science.gov (United States)

2010-04-01

... HUMAN CONSUMPTION PROCESSING AND BOTTLING OF BOTTLED DRINKING WATER Buildings and Facilities § 129.35... is not considered water of a safe, sanitary quality as required for use in bottled water by paragraph... comply with bottled water quality standards (§ 165.110(b) of this chapter) and section 402(a)(1) and (a...

Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.

Science.gov (United States)

Dosenovic, Pia; Kara, Ervin E; Pettersson, Anna-Klara; McGuire, Andrew T; Gray, Matthew; Hartweger, Harald; Thientosapol, Eddy S; Stamatatos, Leonidas; Nussenzweig, Michel C

2018-04-16

The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.

Phenotypic characterization of autoreactive B cells--checkpoints of B cell tolerance in patients with systemic lupus erythematosus.

Directory of Open Access Journals (Sweden)

Annett M Jacobi

Full Text Available DNA-reactive B cells play a central role in systemic lupus erythematosus (SLE; DNA antibodies precede clinical disease and in established disease correlate with renal inflammation and contribute to dendritic cell activation and high levels of type 1 interferon. A number of central and peripheral B cell tolerance mechanisms designed to control the survival, differentiation and activation of autoreactive B cells are thought to be disturbed in patients with SLE. The characterization of DNA-reactive B cells has, however, been limited by their low frequency in peripheral blood. Using a tetrameric configuration of a peptide mimetope of DNA bound by pathogenic anti-DNA antibodies, we can identify B cells producing potentially pathogenic DNA-reactive antibodies. We, therefore, characterized the maturation and differentiation states of peptide, (ds double stranded DNA cross-reactive B cells in the peripheral blood of lupus patients and correlated these with clinical disease activity. Flow cytometric analysis demonstrated a significantly higher frequency of tetramer-binding B cells in SLE patients compared to healthy controls. We demonstrated the existence of a novel tolerance checkpoint at the transition of antigen-naïve to antigen-experienced. We further demonstrate that patients with moderately active disease have more autoreactive B cells in both the antigen-naïve and antigen-experienced compartments consistent with greater impairment in B cell tolerance in both early and late checkpoints in these patients than in patients with quiescent disease. This methodology enables us to gain insight into the development and fate of DNA-reactive B cells in individual patients with SLE and paves the way ultimately to permit better and more customized therapies.

LKB1 inhibition of NF-κB in B cells prevents T follicular helper cell differentiation and germinal center formation.

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Walsh, Nicole C; Waters, Lynnea R; Fowler, Jessica A; Lin, Mark; Cunningham, Cameron R; Brooks, David G; Rehg, Jerold E; Morse, Herbert C; Teitell, Michael A

2015-06-01

T-cell-dependent antigenic stimulation drives the differentiation of B cells into antibody-secreting plasma cells and memory B cells, but how B cells regulate this process is unclear. We show that LKB1 expression in B cells maintains B-cell quiescence and prevents the premature formation of germinal centers (GCs). Lkb1-deficient B cells (BKO) undergo spontaneous B-cell activation and secretion of multiple inflammatory cytokines, which leads to splenomegaly caused by an unexpected expansion of T cells. Within this cytokine response, increased IL-6 production results from heightened activation of NF-κB, which is suppressed by active LKB1. Secreted IL-6 drives T-cell activation and IL-21 production, promoting T follicular helper (TFH ) cell differentiation and expansion to support a ~100-fold increase in steady-state GC B cells. Blockade of IL-6 secretion by BKO B cells inhibits IL-21 expression, a known inducer of TFH -cell differentiation and expansion. Together, these data reveal cell intrinsic and surprising cell extrinsic roles for LKB1 in B cells that control TFH -cell differentiation and GC formation, and place LKB1 as a central regulator of T-cell-dependent humoral immunity. © 2015 The Authors.

Effect of selenium compounds on murine B16 melanoma cells and pigmented cloned pB16 cells

International Nuclear Information System (INIS)

Siwek, B.; Bahbouth, E.; Serra, M.A.; Sabbioni, E.; Pauw-Gillet, M.C. de; Bassleer, R.

1994-01-01

The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 μM and 10 μM) on B16 and pigmented cloned pB 16 murine melanoma cells were investigated in vitro. At the tested concentrations, B16 cells showed a greater sensitivity to the toxic effects of sodium selenite and seleno-DL-cystine than pB 16 cells, whereas no decrease of B 16 and pB 16 cell number was observed after incubation with sodium selenate or seleno-DL-methionine. Glutathione (GSH) percentages were strongly decreased only by selenite and seleno-DL-cystine; it was marked more in B 16 than in pB 16 cells. The pretreatment of B 16 cells with a GSH depleting agent (10 μM buthionine-[S,R]-sulfoximine) did not significantly influence the cytotoxic effects of selenite and seleno-DL-cystine. On both cell populations. GSH preincubation (50 μM) enhanced the cytotoxicity of selenite whereas the survival of seleno-DL-cystine treated cells was increased. Glutathione peroxidase (GSH-Px) activity in B 16 cells was more sensitive than in pB 16 cells to the activating effect of selenite, and particularly of seleno-DL-cystine; however, cell-free controls indicated that activation was mainly due to glutathione reductase. The rate of 75 Se (as sodium selenite) uptake in both cell populations was maximal within the first hour of incubation, with a preferential accumulation in the cytosol; after 24 h of incubation, the amount of 75 Se in cytosol and pellet was approximately the same. Gel filtration chromatography of lysed cells after incubation for 6 h with 10 μM 75 Se-selenite showed that the radioactivity was eluted as two peaks corresponding to low (4-9 kDa) and high (280-320 kDa) molecular weights. Possible toxicological mechanisms are discussed at molecular level. (orig./MG)

Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

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Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

2016-04-05

The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.

Eμ/miR-125b transgenic mice develop lethal B-cell malignancies.

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Enomoto, Y; Kitaura, J; Hatakeyama, K; Watanuki, J; Akasaka, T; Kato, N; Shimanuki, M; Nishimura, K; Takahashi, M; Taniwaki, M; Haferlach, C; Siebert, R; Dyer, M J S; Asou, N; Aburatani, H; Nakakuma, H; Kitamura, T; Sonoki, T

2011-12-01

MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (Eμ/miR-125b-TG mice). Eμ/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the Eμ/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.

Applicability of the 5S management method for quality improvement in health-care facilities: a review.

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Kanamori, Shogo; Shibanuma, Akira; Jimba, Masamine

2016-01-01

The 5S management method (where 5S stands for sort, set in order, shine, standardize, and sustain) was originally implemented by manufacturing enterprises in Japan. It was then introduced to the manufacturing sector in the West and eventually applied to the health sector for organizing and standardizing the workplace. 5S has recently received attention as a potential solution for improving government health-care services in low- and middle-income countries. We conducted a narrative literature review to explore its applicability to health-care facilities globally, with a focus on three aspects: (a) the context of its application, (b) its impacts, and (c) its adoption as part of government initiatives. To identify relevant research articles, we researched public health databases in English, including CINAHL, PubMed, ScienceDirect, and Web of Science. We found 15 of the 114 articles obtained from the search results to be relevant for full-text analysis of the context and impacts of the 5S application. To identify additional information particularly on its adoption as part of government initiatives, we also examined other types of resources including reference books, reports, didactic materials, government documents, and websites. The 15 empirical studies highlighted its application in primary health-care facilities and a wide range of hospital areas in Brazil, India, Jordan, Senegal, Sri Lanka, Tanzania, the UK, and the USA. The review also found that 5S was considered to be the starting point for health-care quality improvement. Ten studies presented its impacts on quality improvements; the changes resulting from the 5S application were classified into the three dimensions of safety, efficiency, and patient-centeredness. Furthermore, 5S was adopted as part of government quality improvement strategies in India, Senegal, Sri Lanka, and Tanzania. 5S could be applied to health-care facilities regardless of locations. It could be not only a tool for health workers and

CD25+ B-1a Cells Express Aicda

Directory of Open Access Journals (Sweden)

Hiroaki Kaku

2017-06-01

Full Text Available B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID, a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC B cells. We previously reported that B-1a cells can be subdivided based on CD25 expression. We show here that B-1a cell Aicda expression is concentrated in the CD25+ B-1a cell subpopulation. These results suggest the possibility that previous studies of memory B cells identified on the basis of Aicda expression may have inadvertently included an unknown number of CD25+ B-1a cells. Although B-1a cells develop normally in the absence of Aicda, a competitive reconstitution assay reveals enhanced vigor for AID KO B-1a cell bone marrow (BM progenitors, as compared with wild-type BM B-1 cell progenitors. These results suggest that AID inhibits the development of B-1a cells from BM B-1 cell progenitors in a competitive environment.

Microdosimetric measurements in the thermal neutron irradiation facility of LENA reactor

International Nuclear Information System (INIS)

Colautti, P.; Moro, D.; Chiriotti, S.; Conte, V.; Evangelista, L.; Altieri, S.; Bortolussi, S.; Protti, N.; Postuma, I.

2014-01-01

A twin TEPC with electric-field guard tubes has been constructed to be used to characterize the BNCT field of the irradiation facility of LENA reactor. One of the two mini TEPC was doped with 50 ppm of 10 B in order to simulate the BNC events occurring in BNCT. By properly processing the two microdosimetric spectra, the gamma, neutron and BNC spectral components can be derived with good precision (∼6%). However, direct measurements of 10 B in some doped plastic samples, which were used for constructing the cathode walls, point out the scarce accuracy of the nominal 10 B concentration value. The influence of the Boral ® door, which closes the irradiation channel, has been measured. The gamma dose increases significantly (+51%) when the Boral ® door is closed. The crypt-cell-regeneration weighting function has been used to measure the quality, namely the RBE µ value, of the radiation field in different conditions. The measured RBE µ values are only partially consistent with the RBE values of other BNCT facilities. - Highlights: • A counter with two mini TEPCs, both equipped with electrical-field guard tubes, has been constructed. • The microdosimetric spectrum of the LENA-reactor irradiation vane has been studied. • The radiation-field quality (RBE) assessment confirms that the D n /D tot ratio is not an accurate parameter to characterize the BNCT radiation field

The DIDO-reactor at Harwell, U.K. and ancillary hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the DIDO reactor and associated hot cell facilities, with the main emphasis on experimental irradiation facilities, specialized irradiation devices (loops and capsules) and possibilities for post-irradiation examinations of samples. The information is presented in the form of eight information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; neutron spectra; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities; equipment and techniques available for post-irradiation examinations; utilization and specialization of the hot cell facilities

B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade

Directory of Open Access Journals (Sweden)

Rebecca K. Martin

2018-02-01

Full Text Available Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mice. An IL-25-induced upregulation of IgE in B1 cells was also demonstrated. In T cell-reconstituted RAG1−/− mice, N. brasiliensis clearance was enhanced with the addition of B2 cells in an IgE-dependent manner. This enhanced clearance was impeded by reconstitution with IgE sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a regulatory response exploited by the helminth.

Safety evaluation report of hot cell facilities for demonstration of advanced spent fuel conditioning process

International Nuclear Information System (INIS)

You, Gil Sung; Choung, W. M.; Ku, J. H.; Cho, I. J.; Kook, D. H.; Park, S. W.; Bek, S. Y.; Lee, E. P.

2004-10-01

The advanced spent fuel conditioning process(ACP) proposed to reduce the overall volume of the PWR spent fuel and improve safety and economy of the long-term storage of spent fuel. In the next phase(2004∼2006), the hot test will be carried out for verification of the ACP in a laboratory scale. For the hot test, the hot cell facilities of α- type and auxiliary facilities are required essentially for safe handling of high radioactive materials. As the hot cell facilities for demonstration of the ACP, a existing hot cell of β- type will be refurbished to minimize construction expenditures of hot cell facility. Up to now, the detail design of hot cell facilities and process were completed, and the safety analysis was performed to substantiate secure of conservative safety. The design data were submitted for licensing which was necessary for construction and operation of hot cell facilities. The safety investigation of KINS on hot cell facilities was completed, and the license for construction and operation of hot cell facilities was acquired already from MOST. In this report, the safety analysis report submitted to KINS was summarized. And also, the questionnaires issued from KINS and answers of KAERI in process of safety investigation were described in detail

Splenic B cells and antigen-specific B cells process anti-Ig in a similar manner

International Nuclear Information System (INIS)

Myers, C.D.; Vitetta, E.S.

1989-01-01

B lymphocytes can process and present antigen to T cells. However, the fate of native antigen after its binding to specific B cells, i.e., the intracellular events involved in the processing and recycling of the antigenic fragments to the cell surface for antigen presentation, are not well understood. In the present study, we demonstrate that murine B cells degrade anti-Ig molecules bound to their surface and release acid soluble fragments into the supernatant. We also demonstrate that the kinetics of this process are identical for anti-mu, anti-delta, and anti-light chain antibodies, indicating that both surface IgM and surface IgD are equally effective in binding antigen and directing its processing. We also describe the effects of azide, chloroquine, and irradiation on this process. To extend these studies to the processing of specifically bound antigen, we demonstrate that highly purified trinitrophenyl antigen-binding cells degrade anti-Ig molecules with the same kinetics as unpurified splenic B cells. Thus, this purified population provides a suitable model system for the analysis of antigen degradation by antigen-specific cells

The role of service readiness and health care facility factors in attrition from Option B+ in Haiti: a joint examination of electronic medical records and service provision assessment survey data.

Science.gov (United States)

Lipira, Lauren; Kemp, Christopher; Domercant, Jean Wysler; Honoré, Jean Guy; Francois, Kesner; Puttkammer, Nancy

2018-01-01

Option B+ is a strategy wherein pregnant or breastfeeding women with HIV are enrolled in lifelong antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) of HIV. In Haiti, attrition from Option B+ is problematic and variable across health care facilities. This study explores service readiness and other facility factors as predictors of Option B+ attrition in Haiti. This analysis used longitudinal data from 2012 to 2014 from the iSanté electronic medical record system and cross-sectional data from Haiti's 2013 Service Provision Assessment. Predictors included Service Availability and Readiness Assessment (SARA) measures for antenatal care (ANC), PMTCT, HIV care services and ART services; general facility characteristics and patient-level factors. Multivariable Cox proportional hazards models modelled the time to first attrition. Analysis of data from 3147 women at 63 health care facilities showed no significant relationships between SARA measures and attrition. Having integrated ANC/PMTCT care and HIV-related training were significant protective factors. Being a public-sector facility, having a greater number of quality improvement activities and training in ANC were significant risk factors. Several facility-level factors were associated with Option B+ attrition. Future research is needed to explore unmeasured facility factors, clarify causal relationships, and incorporate community-level factors into the analysis of Option B+ attrition. © The Author(s) 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brucella abortus-infected B cells induce osteoclastogenesis.

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Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

2016-09-01

Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Evidence for idiotypic- and antiidiotypic B-B cellular interaction with the use of cloned antiidiotypic B cell line.

Science.gov (United States)

Bitoh, S; Fujimoto, S; Yamamoto, H

1990-03-15

Immunization of BALB/c mice with MOPC104E myeloma protein induces antiidiotypic B lymphocytes that have Id-specific enhancing activity on antibody production. The B-B cell interaction was restricted to both Igh and class II MHC. However, anti-Thy-1 and C-treated splenic B cells were maintained for more than 1 y in a mixture of Con A-stimulated splenocyte culture supernatant and synthetic medium. In applying the long term culture method, we have established a cloned B cell line named B19-1d, B19-1d cells are specific to MOPC104E or J558 cross-reactive Id and they express surface mu, lambda but no Ly-1. B19-1d do not spontaneously secrete Ig but produce them upon stimulation with bacterial LPS. The effect of B19-1d cell line on idiotypic antibody production was tested. Addition of only 10 to 100 B19-1d cells into dextran-immune B cell culture greatly enhanced the Id+ antidextran antibody responses. On the contrary, the antidextran antibody production was suppressed by the higher doses of B19-1d cells. The effective cooperation between dextran-immune B cells and B19-1d cloned B cells was restricted to class II MHC. The role of idiotypic- and antiidiotypic B-B cell interaction in immune regulation and repertoire generation was suggested.

The 'MELUSINE' reactor at Grenoble, France, and associated hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the MELUSINE reactor and associated hot cell facilities, with the main emphasis on experimental irradiation facilities and specialized irradiation devices (loops and capsules). The information is presented in the form of six information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; neutron spectra; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities

Quality Assessment of Family Planning Sterilization Services at Health Care Facilities: Case Record Audit.

Science.gov (United States)

Mathur, Medha; Goyal, Ram Chandra; Mathur, Navgeet

2017-05-01

Quality of sterilization services is a matter of concern in India because population control is a necessity. Family Planning Sterilization (FPS) services provided at public health care facilities need to be as per Standard Operating Procedures. To assess the quality of FPS services by audit of case records at selected health care facilities. This cross-sectional study was conducted for two and a half year duration at selected public health care facilities of central India by simple random sampling where FPS services were provided. As per the standards of Government of India, case records were audited and compliance was calculated to assess the quality of services. Results of record audit were satisfactory but important criteria like previous contraceptive history and postoperative counselling were found to be deviated from standards. At Primary Health Centres (PHCs) only 89.5% and at Community Health Centres (CHCs) 58.7% of records were having details of previous contraceptive history. Other criteria like mental illness (only 70% at CHCs) assessment were also inadequate. Although informed consent was found to be having 100% compliance in all records. Quality of care in FPS services is the matter of concern in present scenario for better quality of services. This study may enlighten the policy makers regarding improvements needed for providing quality care.

Discriminative facility and its role in the perceived quality of interactional experiences.

Science.gov (United States)

Cheng, C; Chiu, C Y; Hong, Y Y; Cheung, J S

2001-10-01

Discriminative facility refers to an individual's sensitivity to subtle cues about the psychological meaning of a situation. This research aimed at examining (a) the conceptual distinctiveness of discriminative facility, (b) the situation-appropriate aspect of this construct, and (c) the relationship between discriminative facility and interpersonal experiences. Discriminative facility was assessed by a new measure of situation-appropriate behaviors across a variety of novel stressful situations. Results from study 1 showed that discriminative facility had weak positive relationships with cognitive complexity and nonsignificant relationships with self-monitoring and social desirability, indicating that discriminative facility is a unique construct. Results from Study 2 revealed that higher levels of discriminative facility were associated with higher levels of perceived social support and a greater number of pleasant interpersonal events experienced, thus providing support for the theoretical proposition that discriminative facility is an aspect of social intelligence.

B Cell Tolerance in Health and Disease

Directory of Open Access Journals (Sweden)

Murali Gururajan

2014-02-01

Full Text Available B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids and have been shown to play crucial roles in the development of autoimmunity in several animal models. In the periphery availability of BAFF, a B cell survival factor plays a critical role in the survival of self-reactive B cells. Antibodies against BAFF have been found to be effective therapeutic agents in lupus like autoimmune diseases. Recent developments are targeting anergy to control the growth of chronic lymphocytic leukemia cells.

Design and fabrication of the superconducting-magnet system for the Mirror Fusion Test Facility (MFTF-B)

International Nuclear Information System (INIS)

Tatro, R.E.; Wohlwend, J.W.; Kozman, T.A.

1982-01-01

The superconducting magnet system for the Mirror Fusion Test Facility (MFTF-B) consists of 24 magnets; i.e. two pairs of C-shaped Yin-Yang coils, four C-shaped transition coils, four solenoidal axicell coils, and a 12-solenoid central cell. General Dynamics Convair Division has designed all the coils and is responsible for fabricating 20 coils. The two Yin-Yang pairs (four coils) are being fabricated by the Lawrence Livermore National Laboratory. Since MFTF-B is not a magnet development program, but rather a major physics experiment critical to the mirror fusion program, the basic philosophy has been to use proven materials and analytical techniques wherever possible. The transition and axicell coils are currently being analyzed and designed, while fabrication is under way on the solenoid magnets

Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

Science.gov (United States)

Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

2016-01-01

Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV ) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.

The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

Science.gov (United States)

van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

2017-03-01

The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level

DEFF Research Database (Denmark)

Kristiansen, Trine A; Jaensson Gyllenbäck, Elin; Zriwil, Alya

2016-01-01

. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs...... by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate...

B Cell Receptor-Mediated Internalization of Salmonella: A Novel Pathway for Autonomous B Cell Activation and Antibody Production

NARCIS (Netherlands)

Souwer, Yuri; Griekspoor, Alexander; Jorritsma, Tineke; de Wit, Jelle; Janssen, Hans; Neefjes, Jacques; van Ham, S. Marieke

2009-01-01

The present paradigm is that primary B cells are nonphagocytosing cells. In this study, we demonstrate that human primary B cells are able to internalize bacteria when the bacteria are recognized by the BCR. BCR-mediated internalization of Salmonella typhimurium results in B cell differentiation and

Interaction of the B cell-specific transcriptional coactivator OCA-B and galectin-1 and a possible role in regulating BCR-mediated B cell proliferation.

Science.gov (United States)

Yu, Xin; Siegel, Rachael; Roeder, Robert G

2006-06-02

OCA-B is a B cell-specific transcriptional coactivator for OCT factors during the activation of immunoglobulin genes. In addition, OCA-B is crucial for B cell activation and germinal center formation. However, the molecular mechanisms for OCA-B function in these processes are not clear. Our previous studies documented two OCA-B isoforms and suggested a novel mechanism for the function of the myristoylated, membrane-bound form of OCA-B/p35 as a signaling molecule. Here, we report the identification of galectin-1, and related galectins, as a novel OCA-B-interacting protein. The interaction of OCA-B and galectin-1 can be detected both in vivo and in vitro. The galectin-1 binding domain in OCA-B has been localized to the N terminus of OCA-B. In B cells lacking OCA-B expression, increased galectin-1 expression, secretion, and cell surface association are observed. Consistent with these observations, and a reported inhibitory interaction of galectin-1 with CD45, the phosphatase activity of CD45 is reduced modestly, but significantly, in OCA-B-deficient B cells. Finally, galectin-1 is shown to negatively regulate B cell proliferation and tyrosine phosphorylation upon BCR stimulation. Together, these results raise the possibility that OCA-B may regulate BCR signaling through an association with galectin-1.

B Cells and Autoantibodies in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Anne-Katrin Pröbstel

2015-07-01

Full Text Available While over the past decades T cells have been considered key players in the pathogenesis of multiple sclerosis (MS, it has only recently become evident that B cells have a major contributing role. Our understanding of the role of B cells has evolved substantially following the clinical success of B cell-targeting therapies and increasing experimental evidence for significant B cell involvement. Rather than mere antibody-producing cells, it is becoming clear that they are team players with the capacity to prime and regulate T cells, and function both as pro- and anti-inflammatory mediators. However, despite tremendous efforts, the target antigen(s of B cells in MS have yet to be identified. The first part of this review summarizes the clinical evidence and results from animal studies pointing to the relevance of B cells in the pathogenesis of MS. The second part gives an overview of the currently known potential autoantigen targets. The third part recapitulates and critically appraises the currently available B cell-directed therapies.

Gaps in perceived quality of facility services between stakeholders in the built learning environment

NARCIS (Netherlands)

Kok, Herman; Mobach, Mark P.; Omta, Onno; Alexander, K.

2013-01-01

Purpose - This paper aims to identify perception gaps on the quality of facility services among different users of educational buildings, and provide possible explanations for these perception gaps, and discussing the consequences regarding Facility Management (FM) governance.

Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

Science.gov (United States)

Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

2015-01-01

A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

Immunomodulatory effect of Mesenchymal Stem Cells on B cells

Directory of Open Access Journals (Sweden)

Marcella eFranquesa

2012-07-01

Full Text Available The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches.Mesenchymal Stem Cells (MSC are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

Glandular dose and image quality control in mammography facilities with computerized radiography systems

International Nuclear Information System (INIS)

Dantas, Marcelino Vicente de Almeida

2010-01-01

Breast cancer is the most common cancer among women, and early detection is critical to its diagnosis and treatment. To date, the most effective method for early detection of breast cancer has been x-ray mammography for which the screen/film (SF) technique has been the gold standard. However, even though SF combinations have been improved and optimized over the years for breast imaging, there are some critical limitations, including a narrow exposure range, image artifacts, film processing problems, and inflexibility in image processing and film management. In recent years, digital mammography has been introduced in cancer screening programmes with the screen/film techniques gradually being phased out. Computed radiography (CR), also commonly known as photostimulable phosphor (PSP) imaging or storage phosphor, employs reusable imaging plates and associated hardware and software to acquire and to display digital projection radiographs. In this work, a protocol model was tested for performing image quality control and average glandular dose (AGD) evaluation in 19 institutions with computed radiography systems for mammography. The protocol was validated through tests at the Laboratorio de Radioprotecao Aplicada a Mamografia (LARAM) from the Centro de Desenvolvimento da Tecnologia Nuclear (CDTN). The image quality visual evaluation of CDMAM phantom showed that 53% of the facilities were able to produce images of excellent quality. Furthermore, the automated evaluation of image quality, using the analyze software cdcom.exe, showed that 57% of the images were considered to be of good quality. The detector linearity test showed that the CR response is very linear, where 95% of facilities evaluated were considered to be compliant. For the image noise was found that only 20% of facilities are in agreement with the parameters established for this test. The average glandular doses, which patients may be getting to perform an examination, were below the action levels

Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Xu-Monette, Zijun Y; Li, Ling; Byrd, John C

2016-01-01

CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its...

Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

Directory of Open Access Journals (Sweden)

Diego Sanchez-Martinez

2016-10-01

Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

Generation of B-cell chronic lymphocytic leukemia (B-CLL)-reactive T-cell lines and clones from HLA class I-matched donors using modified B-CLL cells as stimulators: implications for adoptive immunotherapy.

Science.gov (United States)

Hoogendoorn, M; Wolbers, J Olde; Smit, W M; Schaafsma, M R; Barge, R M Y; Willemze, R; Falkenburg, J H F

2004-07-01

Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL). The curative potential of this procedure is mediated by donor-derived alloreactive T cells, resulting in a graft-versus-leukemia effect. However, B-CLL may escape T-cell-mediated immune reactivity since these cells lack expression of costimulatory molecules. We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts. CD40 activation in the presence of IL-4 induced strongest upregulation of costimulatory and adhesion molecules on B-CLL cells and induced the production of high amounts of IL-12 by the leukemic cells. In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors. These CTL lines and clones recognized and killed primary B-CLL as well as patient-derived lymphoblasts, but not donor cells. These results show the feasibility of ex vivo generation of B-CLL-reactive CD8(+) CTLs. This opens new perspectives for adoptive immunotherapy, following allogeneic stem cell transplantation in patients with advanced B-CLL.

Aborted germinal center reactions and B cell memory by follicular T cells specific for a B cell receptor V region peptide.

Science.gov (United States)

Heiser, Ryan A; Snyder, Christopher M; St Clair, James; Wysocki, Lawrence J

2011-07-01

A fundamental problem in immunoregulation is how CD4(+) T cells react to immunogenic peptides derived from the V region of the BCR that are created by somatic mechanisms, presented in MHC II, and amplified to abundance by B cell clonal expansion during immunity. BCR neo Ags open a potentially dangerous avenue of T cell help in violation of the principle of linked Ag recognition. To analyze this issue, we developed a murine adoptive transfer model using paired donor B cells and CD4 T cells specific for a BCR-derived peptide. BCR peptide-specific T cells aborted ongoing germinal center reactions and impeded the secondary immune response. Instead, they induced the B cells to differentiate into short-lived extrafollicular plasmablasts that secreted modest quantities of Ig. These results uncover an immunoregulatory process that restricts the memory pathway to B cells that communicate with CD4 T cells via exogenous foreign Ag.

Honeycomblike large area LaB6 plasma source for Multi-Purpose Plasma facility

International Nuclear Information System (INIS)

Woo, Hyun-Jong; Chung, Kyu-Sun; You, Hyun-Jong; Lee, Myoung-Jae; Lho, Taihyeop; Choh, Kwon Kook; Yoon, Jung-Sik; Jung, Yong Ho; Lee, Bongju; Yoo, Suk Jae; Kwon, Myeon

2007-01-01

A Multi-Purpose Plasma (MP 2 ) facility has been renovated from Hanbit mirror device [Kwon et al., Nucl. Fusion 43, 686 (2003)] by adopting the same philosophy of diversified plasma simulator (DiPS) [Chung et al., Contrib. Plasma Phys. 46, 354 (2006)] by installing two plasma sources: LaB 6 (dc) and helicon (rf) plasma sources; and making three distinct simulators: divertor plasma simulator, space propulsion simulator, and astrophysics simulator. During the first renovation stage, a honeycomblike large area LaB 6 (HLA-LaB 6 ) cathode was developed for the divertor plasma simulator to improve the resistance against the thermal shock fragility for large and high density plasma generation. A HLA-LaB 6 cathode is composed of the one inner cathode with 4 in. diameter and the six outer cathodes with 2 in. diameter along with separate graphite heaters. The first plasma is generated with Ar gas and its properties are measured by the electric probes with various discharge currents and magnetic field configurations. Plasma density at the middle of central cell reaches up to 2.6x10 12 cm -3 , while the electron temperature remains around 3-3.5 eV at the low discharge current of less than 45 A, and the magnetic field intensity of 870 G. Unique features of electric property of heaters, plasma density profiles, is explained comparing with those of single LaB 6 cathode with 4 in. diameter in DiPS

CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia.

Directory of Open Access Journals (Sweden)

Marco L Davila

Full Text Available Although many adults with B cell acute lymphoblastic leukemia (B-ALL are induced into remission, most will relapse, underscoring the dire need for novel therapies for this disease. We developed murine CD19-specific chimeric antigen receptors (CARs and an immunocompetent mouse model of B-ALL that recapitulates the disease at genetic, cellular, and pathologic levels. Mouse T cells transduced with an all-murine CD3ζ/CD28-based CAR that is equivalent to the one being used in our clinical trials, eradicate B-ALL in mice and mediate long-term B cell aplasias. In this model, we find that increasing conditioning chemotherapy increases tumor eradication, B cell aplasia, and CAR-modified T cell persistence. Quantification of recipient B lineage cells allowed us to estimate an in vivo effector to endogenous target ratio for B cell aplasia maintenance. In mice exhibiting a dramatic B cell reduction we identified a small population of progenitor B cells in the bone marrow that may serve as a reservoir for long-term CAR-modified T cell stimulation. Lastly, we determine that infusion of CD8+ CAR-modified T cells alone is sufficient to maintain long-term B cell eradication. The mouse model we report here should prove valuable for investigating CAR-based and other therapies for adult B-ALL.

Health facility challenges to the provision of Option B+ in western Kenya: a qualitative study.

Science.gov (United States)

Helova, Anna; Akama, Eliud; Bukusi, Elizabeth A; Musoke, Pamela; Nalwa, Wafula Z; Odeny, Thomas A; Onono, Maricianah; Spangler, Sydney A; Turan, Janet M; Wanga, Iris; Abuogi, Lisa L

2017-03-01

Current WHO guidelines recommend lifelong antiretroviral therapy (ART) for all HIV-positive individuals, including pregnant and breastfeeding women (Option B+) in settings with generalized HIV epidemics. While Option B+ is scaled-up in Kenya, insufficient adherence and retention to care could undermine the expected positive impact of Option B+. To explore challenges to the provision of Option B+ at the health facility level, we conducted forty individual gender-matched in-depth interviews with HIV-positive pregnant/postpartum women and their male partners, and four focus groups with thirty health care providers at four health facilities in western Kenya between September-November 2014. Transcripts were coded with the Dedoose software using a coding framework based on the literature, topics from interview guides, and emerging themes from transcripts. Excerpts from broad codes were then fine-coded using an inductive approach. Three major themes emerged: 1) Option B+ specific challenges (same-day initiation into treatment, health care providers unconvinced of the benefits of Option B+, insufficient training); 2) facility resource constraints (staff and drug shortages, long queues, space limitations); and 3) lack of client-friendly services (scolding of patients, inconvenient operating hours, lack of integration of services, administrative requirements). This study highlights important challenges at the health facility level related to Option B+ rollout in western Kenya. Addressing these specific challenges may increase linkage, retention and adherence to life-long ART treatment for pregnant HIV-positive women in Kenya, contribute towards elimination of mother-to-child HIV transmission, and improve maternal and child outcomes.

Shield wall evaluation of hot cell facility for advanced spent fuel conditioning process

International Nuclear Information System (INIS)

Cho, I. J.; Kuk, D. H.; Ko, J. H.; Jung, W. M.; Yoo, G. S.; Lee, E. P.; Park, S. W.

2002-01-01

The future hot cell is located in the Irradiated Material Experiment Facility (IMEF) at the Korea Atomic Energy Research Institute (KAERI). It is β-γ type hot cell that was constructed on the base floor in IMEF building for irradiated material testing. And this hot cell will be used for carrying out the Advanced spent fuel Conditioning Process (ACP). The radiation shielding capability of hot cell should be sufficient to meet the radiation dose requirements in the related regulations. Because the radioactive sources of ACP are expected to be higher than radioactive sources of IMEF design criteria, the future hot cell in current status is unsatisfactory to hot test of ACP. So the shielding analysis of the future hot cell is performed to evaluate shielding ability of concrete shield wall. The shielding analysis included (a) identification of ACP source term; (b) photon source spectrum; (c) shielding analysis by QADS and MCNP-4C; and (d) enhancement of concrete shield wall. In this research, dose rates are obtained according to ACP source, geometry and hot cell shield wall thickness. And the evaluation and reinforcement thickness of the shield wall about future hot cell are concluded

Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice

Science.gov (United States)

Fournier, Emilie M.; Velez, Maria-Gabriela; Leahy, Katelyn; Swanson, Cristina L.; Rubtsov, Anatoly V.; Torres, Raul M.

2012-01-01

Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG+ cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-κ B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-κ B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-κ B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG+ cells is partly dependent on Fas inactivation. Furthermore, dual-κ B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity. PMID:22927551

Docking of B-cell epitope antigen to specific hepatitis B antibody

Indian Academy of Sciences (India)

The interaction of pres1 region of hepatitis B virus B-cell epitope antigen with specific hepatitis B neutralizing monoclonal antibody was examined by docking study. We modelled the 3D complex structure of B-cell epitope antigen residues CTTPAQGNSMFPSCCCTKPTDGNCY by homology modelling and docked it with the ...

Lipid rafts and B cell signaling.

Science.gov (United States)

Gupta, Neetu; DeFranco, Anthony L

2007-10-01

B cells comprise an essential component of the humoral immune system. They are equipped with the unique ability to synthesize and secrete pathogen-neutralizing antibodies, and share with professional antigen presenting cells the ability to internalize foreign antigens, and process them for presentation to helper T cells. Recent evidence indicates that specialized cholesterol- and glycosphingolipid-rich microdomains in the plasma membrane commonly referred to as lipid rafts, serve to compartmentalize key signaling molecules during the different stages of B cell activation including B cell antigen receptor (BCR)-initiated signal transduction, endocytosis of BCR-antigen complexes, loading of antigenic peptides onto MHC class II molecules, MHC-II associated antigen presentation to helper T cells, and receipt of helper signals via the CD40 receptor. Here we review the recent literature arguing for a role of lipid rafts in the spatial organization of B cell function.

Decommissioning of the Risoe Hot Cell facility

International Nuclear Information System (INIS)

Carlsen, H.

1994-02-01

Concise description of progress in hot cell facility decommissioning at Risoe National Laboratory is presented. Removal of the large contaminated equipment has been completed, all the concrete cells have been finally cleaned. The total contamination left on the concrete walls is of the order of 1850 GBq. Preliminary smear tests proved the stack to be probably clean. The delay in project completion seems to be around 7 months, the remaining work being of rather conventional character. (EG)

Decommissioning of the Risoe Hot Cell facility

International Nuclear Information System (INIS)

Carlsen, H.

1991-08-01

Concise descriptions of actions taken in relation to the decommissioning of the hot cell facility at Risoe National Laboratory are presented. The removal of fissile material, removal and decontamination of large cell internals, and of large equipment such as glove boxes and steel boxes, in addition to dose commitments, are explained. Tables illustrating the analysis of smear tests, constants for contamination level examination, contamination and radiation levels after cleaning and total contamination versus measured radiation are included. (AB)

Murid herpesvirus-4 exploits dendritic cells to infect B cells.

Directory of Open Access Journals (Sweden)

Miguel Gaspar

2011-11-01

Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

Quality assurance system for sitting high risk facilities

International Nuclear Information System (INIS)

Rodriguez, Aymee; Peralta, Jose L.; Fernandez, Manuel

1999-01-01

The paper shows how we have conceived and designed the quality assurance system for the site selection process of an area for sitting the facility of high risk in correspondence with the approved methodology. The results obtained in the implementation of the system have permitted the satisfactory performance of each one the expected stage, defining the most favorable sectors in order to continue the studies of the repository site for the disposal of low and intermedium. (author)

DWPF remotable television and cell lighting facilities

International Nuclear Information System (INIS)

Heckendorn, F.M. II.

1984-01-01

The Defense Waste Processing Facility (DWPF) for radioactive waste vitrification at the Savannah River Plant (SRP) is now under construction. Development of specialized low cost television (TV) viewing equipment for in-cell and within-melter applications is now complete. High resolution TV cameras not originally designed for high radiation environments have been demonstrated in crane remotable packages to be well suited to the DWPF. High intensity in-cell lighting has also been demonstrated in crane remotable assemblies. These dual 1000 W units (2000 W total) are used to support the multiplicity of TV and cell window viewing requirements. 8 figures

SHIP-1 Deficiency in AID+ B Cells Leads to the Impaired Function of B10 Cells with Spontaneous Autoimmunity.

Science.gov (United States)

Chen, Yingjia; Hu, Fanlei; Dong, Xuejiao; Zhao, Meng; Wang, Jing; Sun, Xiaolin; Kim, Tae Jin; Li, Zhanguo; Liu, Wanli

2017-11-01

Unlike conventional B cells, regulatory B cells exhibit immunosuppressive functions to downregulate inflammation via IL-10 production. However, the molecular mechanism regulating the production of IL-10 is not fully understood. In this study, we report the finding that activation-induced cytidine deaminase (AID) is highly upregulated in the IL-10-competent B cell (B10) cell from Innp5d fl/fl Aicda Cre/+ mice, whereas the 5' inositol phosphatase SHIP-1 is downregulated. Notably, SHIP-1 deficiency in AID + B cells leads to a reduction in cell count and impaired IL-10 production by B10 cells. Furthermore, the Innp5d fl/fl Aicda Cre/+ mouse model shows B cell-dependent autoimmune lupus-like phenotypes, such as elevated IgG serum Abs, formation of spontaneous germinal centers, production of anti-dsDNA and anti-nuclear Abs, and the obvious deposition of IgG immune complexes in the kidney with age. We observe that these lupus-like phenotypes can be reversed by the adoptive transfer of B10 cells from control Innp5d fl/fl mice, but not from the Innp5d fl/fl Aicda Cre/+ mice. This finding highlights the importance of defective B10 cells in Innp5d fl/fl Aicda Cre/+ mice. Whereas p-Akt is significantly upregulated, MAPK and AP-1 activation is impaired in B10 cells from Innp5d fl/fl Aicda Cre/+ mice, resulting in the reduced production of IL-10. These results show that SHIP-1 is required for the maintenance of B10 cells and production of IL-10, and collectively suggests that SHIP-1 could be a new potential therapeutic target for the treatment of autoimmune diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

The DR 3 reactor at Risoe, Denmark and its associated hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the DR 2 reactor and associated hot cell facilities, with the main emphasis on experimental irradiation facilities, specialized irradiation devices (loops and capsules) and possibilities for post-irradiation examinations of samples. The information is presented in the form of seven information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities; equipment and techniques available for post-irradiation examinations; utilization and specialization of the hot cell facilities

Extinct type of human parvovirus B19 persists in tonsillar B cells

OpenAIRE

Pyöriä, Lari; Toppinen, Mari; Mantyla, Elina; Hedman, Lea; Aaltonen, Leena-Maija; Vihinen-Ranta, Maija; Ilmarinen, Taru; Soderlund-Venermo, Maria; Hedman, Klaus; Perdomo, Maria

2017-01-01

Parvovirus B19 (B19V) DNA persists lifelong in human tissues, but the cell type harbouring it remains unclear. We here explore B19V DNA distribution in B, T and monocyte cell lineages of recently excised tonsillar tissues from 77 individuals with an age range of 2?69 years. We show that B19V DNA is most frequent and abundant among B cells, and within them we find a B19V genotype that vanished from circulation >40 years ago. Since re-infection or re-activation are unlikely with this virus type...

Surface receptor Toso controls B cell-mediated regulation of T cell immunity.

Science.gov (United States)

Yu, Jinbo; Duong, Vu Huy Hoang; Westphal, Katrin; Westphal, Andreas; Suwandi, Abdulhadi; Grassl, Guntram A; Brand, Korbinian; Chan, Andrew C; Föger, Niko; Lee, Kyeong-Hee

2018-05-01

The immune system is tightly controlled by regulatory processes that allow for the elimination of invading pathogens, while limiting immunopathological damage to the host. In the present study, we found that conditional deletion of the cell surface receptor Toso on B cells unexpectedly resulted in impaired proinflammatory T cell responses, which led to impaired immune protection in an acute viral infection model and was associated with reduced immunopathological tissue damage in a chronic inflammatory context. Toso exhibited its B cell-inherent immunoregulatory function by negatively controlling the pool of IL-10-competent B1 and B2 B cells, which were characterized by a high degree of self-reactivity and were shown to mediate immunosuppressive activity on inflammatory T cell responses in vivo. Our results indicate that Toso is involved in the differentiation/maintenance of regulatory B cells by fine-tuning B cell receptor activation thresholds. Furthermore, we showed that during influenza A-induced pulmonary inflammation, the application of Toso-specific antibodies selectively induced IL-10-competent B cells at the site of inflammation and resulted in decreased proinflammatory cytokine production by lung T cells. These findings suggest that Toso may serve as a novel therapeutic target to dampen pathogenic T cell responses via the modulation of IL-10-competent regulatory B cells.

IL-10-produced by human transitional B-cells down-regulates CD86 expression on B-cells leading to inhibition of CD4+T-cell responses.

Science.gov (United States)

Nova-Lamperti, Estefania; Fanelli, Giorgia; Becker, Pablo D; Chana, Prabhjoat; Elgueta, Raul; Dodd, Philippa C; Lord, Graham M; Lombardi, Giovanna; Hernandez-Fuentes, Maria P

2016-01-22

A novel subset of human regulatory B-cells has recently been described. They arise from within the transitional B-cell subpopulation and are characterised by the production of IL-10. They appear to be of significant importance in regulating T-cell immunity in vivo. Despite this important function, the molecular mechanisms by which they control T-cell activation are incompletely defined. Here we show that transitional B-cells produced more IL-10 and expressed higher levels of IL-10 receptor after CD40 engagement compared to other B-cell subsets. Furthermore, under this stimulatory condition, CD86 expressed by transitional B-cells was down regulated and T-cell proliferation was reduced. We provide evidence to demonstrate that the down-regulation of CD86 expression by transitional B-cells was due to the autocrine effect of IL-10, which in turn leads to decreased T-cell proliferation and TNF-α production. This analysis was further extended to peripheral B-cells in kidney transplant recipients. We observed that B-cells from patients tolerant to the graft maintained higher IL-10 production after CD40 ligation, which correlates with lower CD86 expression compared to patients with chronic rejection. Hence, the results obtained in this study shed light on a new alternative mechanism by which transitional B-cells inhibit T-cell proliferation and cytokine production.

IL-10-produced by human transitional B-cells down-regulates CD86 expression on B-cells leading to inhibition of CD4+T-cell responses

Science.gov (United States)

Nova-Lamperti, Estefania; Fanelli, Giorgia; Becker, Pablo D.; Chana, Prabhjoat; Elgueta, Raul; Dodd, Philippa C.; Lord, Graham M.; Lombardi, Giovanna; Hernandez-Fuentes, Maria P.

2016-01-01

A novel subset of human regulatory B-cells has recently been described. They arise from within the transitional B-cell subpopulation and are characterised by the production of IL-10. They appear to be of significant importance in regulating T-cell immunity in vivo. Despite this important function, the molecular mechanisms by which they control T-cell activation are incompletely defined. Here we show that transitional B-cells produced more IL-10 and expressed higher levels of IL-10 receptor after CD40 engagement compared to other B-cell subsets. Furthermore, under this stimulatory condition, CD86 expressed by transitional B-cells was down regulated and T-cell proliferation was reduced. We provide evidence to demonstrate that the down-regulation of CD86 expression by transitional B-cells was due to the autocrine effect of IL-10, which in turn leads to decreased T-cell proliferation and TNF-α production. This analysis was further extended to peripheral B-cells in kidney transplant recipients. We observed that B-cells from patients tolerant to the graft maintained higher IL-10 production after CD40 ligation, which correlates with lower CD86 expression compared to patients with chronic rejection. Hence, the results obtained in this study shed light on a new alternative mechanism by which transitional B-cells inhibit T-cell proliferation and cytokine production. PMID:26795594

Preliminary Feasibility Study on the Construction of Steel Hot Cell Facility for Precise Manipulated Examinations

International Nuclear Information System (INIS)

Ahn, Sangbok; Kwon, Hyungmun; Kim, Heemoon; Kim, Dosik; Min, Duckkee; Hong, Kwonpyo

2006-01-01

Hot laboratory is essential facility to research and develop in the nuclear industries to examine radioactive materials. The post irradiation examinations for irradiated fuels and materials should be mainly conducted in the hot cell facility to protect radiations to operators. Hot cells are divided into a concrete hot cell and a steel hot cell according to the wall materials. Usually a concrete hot cell is applied to test for high level radioactive materials like as a fuel assembly, rods, and large structure specimens, and a steel hot cell for comparatively lower level activity materials in fuel fragments, and small structural materials. A steel hot cell has many benefits in a specimen manipulation, construction and maintenance costs. In recent the test for the irradiated materials is more frequently required a small and precise manipulating examination for higher degree tests of research and developments. Unfortunately hot laboratory facilities in domestics have mainly constituted of concrete hot cells, and not ready for techniques in steel hot cells. In this paper the construction feasibility of steel hot cell facility is preliminary reviewed in the points of the status of domestic facilities, the test demand prospect and detailed plans

Establishment of a novel feline leukemia virus (FeLV)-negative B-cell cell line from a cat with B-cell lymphoma.

Science.gov (United States)

Mochizuki, Hiroyuki; Takahashi, Masashi; Nishigaki, Kazuo; Ide, Tetsuya; Goto-Koshino, Yuko; Watanabe, Shinya; Sato, Hirofumi; Sato, Masahiko; Kotera, Yukiko; Fujino, Yasuhito; Ohno, Koichi; Uchida, Kazuyuki; Tsujimoto, Hajime

2011-04-15

We established a novel feline B-cell line, MS4, from the neoplastic pleural effusion of a cat with cutaneous B-cell lymphoma. Immunophenotype staining of the MS4 cells was positive for CD20, CD79α, and IgA and negative for CD3, CD4, CD5, CD8α, CD18, CD21, CD22, IgM, IgG, Ig light chain, and MHC class II. PCR analysis for immunoglobulin heavy chain gene rearrangements revealed a monoclonal rearrangement, whereas no clonal rearrangement of the T-cell receptor γ gene was detected. Southern blotting with an exogenous feline leukemia virus (FeLV) U3 probe revealed no integration of exogenous FeLV provirus. The MS4 cell line is the first FeLV-negative feline B-cell lymphoma cell line, and may be used to investigate the pathogenesis of spontaneously occurring feline lymphoma and the development of new therapies. Copyright © 2011 Elsevier B.V. All rights reserved.

Ocean Thermal Energy Converstion (OTEC) test facilities study program. Final report. Volume II. Part B

Energy Technology Data Exchange (ETDEWEB)

None

1977-01-17

Results are presented of an 8-month study to develop alternative non-site-specific OTEC facilities/platform requirements for an integrated OTEC test program which may include land and floating test facilities. Volume II--Appendixes is bound in three parts (A, B, and C) which together comprise a compendium of the most significant detailed data developed during the study. Part B provides an annotated test list and describes component tests and system tests.

Improving Quality of Care in Primary Health-Care Facilities in Rural Nigeria

OpenAIRE

Ugo, Okoli; Ezinne, Eze-Ajoku; Modupe, Oludipe; Nicole, Spieker; Winifred, Ekezie; Kelechi, Ohiri

2016-01-01

Background: Nigeria has a high population density but a weak health-care system. To improve the quality of care, 3 organizations carried out a quality improvement pilot intervention at the primary health-care level in selected rural areas. Objective: To assess the change in quality of care in primary health-care facilities in rural Nigeria following the provision of technical governance support and to document the successes and challenges encountered. Method: A total of 6 states were selected...

Water quality facility investigation report : final summary of project and evaluation of monitoring plan implementation.

Science.gov (United States)

2005-07-05

The Oregon Department of Transportation (ODOT) has installed several stormwater : treatment facilities throughout the State to improve the quality of runoff discharged from : highways. These facilities include a variety of both above ground and below...

Understanding B-cell activation and autoantibody repertoire selection in systemic lupus erythematosus: A B-cell immunomics approach.

Science.gov (United States)

Tipton, Christopher M; Hom, Jennifer R; Fucile, Christopher F; Rosenberg, Alexander F; Sanz, Inaki

2018-07-01

Understanding antibody repertoires and in particular, the properties and fates of B cells expressing potentially pathogenic antibodies is critical to define the mechanisms underlying multiple immunological diseases including autoimmune and allergic conditions as well as transplant rejection. Moreover, an integrated knowledge of the antibody repertoires expressed by B cells and plasma cells (PC) of different functional properties and longevity is essential to develop new therapeutic strategies, better biomarkers for disease segmentation, and new assays to measure restoration of B-cell tolerance or, at least, of normal B-cell homeostasis. Reaching these goals, however, will require a more precise phenotypic, functional and molecular definition of B-cell and PC populations, and a comprehensive analysis of the antigenic reactivity of the antibodies they express. While traditionally hampered by technical and ethical limitations in human experimentation, new technological advances currently enable investigators to address these questions in a comprehensive fashion. In this review, we shall discuss these concepts as they apply to the study of Systemic Lupus Erythematosus. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Safety Analysis Report: X17B2 beamline Synchrotron Medical Research Facility

International Nuclear Information System (INIS)

Gmuer, N.F.; Thomlinson, W.

1990-02-01

This report contains a safety analysis for the X17B2 beamline synchrotron medical research facility. Health hazards, risk assessment and building systems are discussed. Reference is made to transvenous coronary angiography

The regulatory roles of B cell subsets in transplantation.

Science.gov (United States)

Chu, Zhulang; Zou, Weilong; Xu, Yanan; Sun, Qiquan; Zhao, Yong

2018-02-01

B cells mediate allograft rejection through antigen presentation, and production of cytokines and antibodies. More and more immunosuppressive agents specifically targeting B cells and plasma cells have been applied in clinical transplantation. However, recent studies have indicated the regulatory roles of B cells. Therefore, it is vital to clarify the different effects of B cell subsets in organ transplantation so that we can completely understand the diverse functions of B cells in transplantation. Areas covered: This review focuses on the regulatory roles of B cells in transplantation. B cell subsets with immune modulation and factors mediating immunosuppressive functions of regulatory B (Breg) cells were analyzed. Therapies targeting B cells and the application of B cells for transplant tolerance induction were discussed. Expert commentary: Besides involving rejection, B cells could also play regulatory roles in transplantation. Breg cells and the related markers may be used to predict the immune tolerant state in transplant recipients. New therapeutic strategies targeting B cells should be explored to promote tolerance induction with less impact on the host's protective immunity in organ transplanted patients.

21 CFR 1000.55 - Recommendation for quality assurance programs in diagnostic radiology facilities.

Science.gov (United States)

2010-04-01

... facilities where more than one department operates x-ray equipment, to the chief medical officer of the..., improved image quality, and/or financial savings will compensate for the resources required for the program... generally be delegated a basic quality assurance role by the practitioner in charge. Responsibility for...

Quality assurance aspects of the major procurements for the Large Coil Test Facility

International Nuclear Information System (INIS)

Taylor, D.J.; Thompson, P.B.; Ryan, T.L.; Queen, C.C.; Halstead, E.L.; Murphy, J.L.; Wood, R.J.

1983-01-01

The Large Coil Test Facility (LCTF) project is comprised of the test stand, supporting cryogenic systems, instrumentation, data acquisition, and utilities necessary for testing the large superconducting coils of the Large Coil Program (LCP). A significant portion of the facility hardware has been obtained through procurement actions with industrial suppliers. This paper addresses the project's experience in formulation and execution of quality assurance (QA) actions relative to several of the major items procured. Project quality assurance planning and specific features related to procurement activities for several of the more specialized test facility components are described. These component procurements include: (1) the coil test stand's major structural item (the bucking post) purchased from foreign industry; (2) fabrication and testing of high-current power supplies; (3) industrial fabrication of specialized instrumentation (voltage-tap signal conditioning modules); and (4) fabrication, installation, and testing of the liquid helium piping system

Altered B cell homeostasis and Toll-like receptor 9-driven response in patients affected by autoimmune polyglandular syndrome Type 1: Altered B cell phenotype and dysregulation of the B cell function in APECED patients.

Science.gov (United States)

Perri, Valentina; Gianchecchi, Elena; Scarpa, Riccardo; Valenzise, Mariella; Rosado, Maria Manuela; Giorda, Ezio; Crinò, Antonino; Cappa, Marco; Barollo, Susi; Garelli, Silvia; Betterle, Corrado; Fierabracci, Alessandra

2017-02-01

APECED is a T-cell mediated disease with increased frequencies of CD8+ effector and reduction of FoxP3+ T regulatory cells. Antibodies against affected organs and neutralizing to cytokines are found in the peripheral blood. The contribution of B cells to multiorgan autoimmunity in Aire-/- mice was reported opening perspectives on the utility of anti-B cell therapy. We aimed to analyse the B cell phenotype of APECED patients compared to age-matched controls. FACS analysis was conducted on PBMC in basal conditions and following CpG stimulation. Total B and switched memory (SM) B cells were reduced while IgM memory were increased in patients. In those having more than 15 years from the first clinical manifestation the defect included also mature and transitional B cells; total memory B cells were increased, while SM were unaffected. In patients with shorter disease duration, total B cells were unaltered while SM and IgM memory behaved as in the total group. A defective B cell proliferation was detected after 4day-stimulation. In conclusion APECED patients show, in addition to a significant alteration of the B cell phenotype, a dysregulation of the B cell function involving peripheral innate immune mechanisms particularly those with longer disease duration. Copyright © 2016 Elsevier GmbH. All rights reserved.

Physiology of B cells in mice with X-linked immunodeficiency (xid). III. Disappearance of xid B cells in double bone marrow chimeras

International Nuclear Information System (INIS)

Sprent, J.; Bruce, J.

1984-01-01

Evidence is presented that B cells from mice with X-linked immunodeficiency (xid) differentiate at a slower rate than normal B cells. This conclusion stems from studies in which (B6 X CBA/J)F1 mice were heavily irradiated (1,000 rads) and reconstituted with a mixture of T-depleted marrow cells taken from (a) nondefective B6 mice (H-2b) and (b) xid CBA/N or nondefective CBA/Ca mice (both H-2k). With transfer of CBA/Ca plus B6 marrow cells, the irradiated recipients become repopulated with B cells derived from both parental marrow sources; except for an early imbalance (probably reflecting Hh resistance), the degree of chimerism remained relatively stable over a period of more than 6 months. Very different results occurred with transfer of a mixture of xid CBA/N and normal B6 marrow. Within the first 2 months after marrow reconstitution, a low but significant proportion of the B cells in both spleen and lymph nodes were of CBA/N origin. Thereafter the proportion of these cells fell progressively, and by 6-9 months virtually all of the B cells were of B6 origin. This gradual decline in CBA/N-derived cells did not apply to other cell types, i.e., T cells or pluripotential stem cells. Analogous results were obtained with transfer of CBA/N vs. CBA/Ca marrow cells into sublethally irradiated (750 rads) (CBA/N X DBA/2)F1 male vs. female mice. For example, CBA/N-marrow derived B cells differentiated effectively and survived for long periods in F1 male mice (xid----xid) but not in F1 female mice (xid----normal). The finding that xid B cells eventually disappear in the presence of normal B cells strengthens the view that xid B cells are an abnormal population not represented in normal mice

Induction of the nuclear IκB protein IκB-ζ upon stimulation of B cell antigen receptor

International Nuclear Information System (INIS)

Hijioka, Kuniaki; Matsuo, Susumu; Eto-Kimura, Akiko; Takeshige, Koichiro; Muta, Tatsushi

2007-01-01

The nuclear IκB protein IκB-ζ is barely detectable in resting cells and is induced in macrophages and fibroblasts following stimulation of innate immunity via Toll-like receptors. The induced IκB-ζ associates with nuclear factor (NF)-κB in the nucleus and plays crucial roles in its transcriptional regulation. Here, we examined the induction of IκB-ζ in B lymphocytes, one of the major players in adaptive immunity. Upon crosslinking of the surface immunoglobulin complex, IκB-ζ mRNA was robustly induced in murine B-lymphoma cell line A20 cells. While the crosslinking activated NF-κB and induced its target gene, IκB-α, co-crosslinking of Fcγ receptor IIB to the surface immunoglobulin complex inhibited NF-κB activation and the induction of IκB-ζ and IκB-α, suggesting critical roles for NF-κB in the induction. These results indicate that IκB-ζ is also induced by stimulation of B cell antigen receptor, suggesting that IκB-ζ is involved in the regulation of adaptive immune responses

Development of a coordinated allo T cell and auto B cell response against autosomal PTK2B after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Kremer, Anita N; van der Griendt, Judith C; van der Meijden, Edith D; Honders, M Willy; Ayoglu, Burcu; Schwenk, Jochen M; Nilsson, Peter; Falkenburg, J H Frederik; Griffioen, Marieke

2014-02-01

It is well known that allo-reactive T cells play a crucial role in graft-versus-leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloSCT). Allo-reactive CD4(+) T cells can mediate direct cytolysis, but may also stimulate production of IgG antibodies as helper cells. Immune complexes may subsequently be processed and presented by professional antigen presenting cells and stimulate induction of specific CD8(+) T cells. As such, proteins targeted in coordinated T- and B-cell responses may represent a class of immunodominant antigens in clinical responses after alloSCT. We previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid leukemia after HLA-matched alloSCT. Since PTK2B has also been described as antibody target, we here investigated whether a coordinated T- and B-cell response against PTK2B was induced. Patient serum before and after alloSCT and donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed observed development of a humoral immune response against PTK2B. Antibodies against PTK2B were only found after DLI and, in contrast to the CD4(+) T cells, recognized a monomorphic region of the protein. To our knowledge, this is the first description of a coordinated allo-reactive CD4(+) T-cell and auto-reactive antibody response against an autosomal antigen.

Pain treatment facilities: do we need quantity or quality?

Science.gov (United States)

de Meij, Nelleke; Köke, Albère; van der Weijden, Trudy; van Kleef, Maarten; Patijn, Jacob

2014-10-01

Chronic pain patients referred to a pain treatment facility have no guarantee that they will receive a proper diagnostic procedure or treatment. To obtain information about organizational aspects of pain treatment facilities and the content of their daily pain practice, we performed a questionnaire survey. The aim of the study was to evaluate the amount of pain treatment facilities, the content of organized specialized pain care and adherence to the criteria of the internationally accepted guidelines for pain treatment services. The University Pain Centre Maastricht in the Department of Anaesthesiology and Pain Management at Maastricht University Medical Centre developed a questionnaire survey based on the Recommendations for Pain Treatment Services of the International Association for the Study of Pain (IASP). The questionnaire was sent to the medical boards of all hospitals in the Netherlands (n=94). The response rate was 86% (n=81). Of all hospitals, 88.9% (n=72) reported the provision of organized specialized pain care, which was provided by a pain management team in 86.1% (n=62) and by an individual specialist in 13.9% (n=10). Insight was obtained from pain treatment facilities in five different domains: the organizational structure of pain management, composition of the pain team, pain team practice, patient characteristics, and research and education facilities. Although 88.9% of all hospitals stated that organized specialized pain care was provided, only a few hospitals could adhere to the criteria for pain treatment services of the IASP. The outcome of the questionnaire survey may help to define quality improvement standards for pain treatment facilities. © 2014 John Wiley & Sons, Ltd.

B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis

Czech Academy of Sciences Publication Activity Database

Bruhl, H.; Cihak, J.; Talke, Y.; Rodriguez-Gomez, M.; Hermann, F.; Goebel, N.; Renner, K.; Plachý, Jiří; Stangassinger, M.; Archemann, S.; Nimmerjahn, F.; Mack, M.

2015-01-01

Roč. 45, č. 3 (2015), s. 705-715 ISSN 0014-2980 Institutional support: RVO:68378050 Keywords : Arthritis * B cells * B-cell depletion * B-cell inhibition * CD79b * Humoral immune response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.179, year: 2015

B cells as a target of immune modulation

Directory of Open Access Journals (Sweden)

Hawker Kathleen

2009-01-01

Full Text Available B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts. MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell-targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.

Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast epithelial cells.

Science.gov (United States)

Hilmarsdottir, Bylgja; Briem, Eirikur; Halldorsson, Skarphedinn; Kricker, Jennifer; Ingthorsson, Sævar; Gustafsdottir, Sigrun; Mælandsmo, Gunhild M; Magnusson, Magnus K; Gudjonsson, Thorarinn

2017-05-11

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell-cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype.

Evaluation of CD307a expression patterns during normal B-cell maturation and in B-cell malignancies by flow cytometry.

Science.gov (United States)

Auat, Mariangeles; Cardoso, Chandra Chiappin; Santos-Pirath, Iris Mattos; Rudolf-Oliveira, Renata Cristina Messores; Matiollo, Camila; Lange, Bárbara Gil; da Silva, Jessica Pires; Dametto, Gisele Cristina; Pirolli, Mayara Marin; Colombo, Maria Daniela Holthausen Perico; Santos-Silva, Maria Claudia

2018-02-24

Flow cytometric immunophenotyping is deemed a fundamental tool for the diagnosis of B-cell neoplasms. Currently, the investigation of novel immunophenotypic markers has gained importance, as they can assist in the precise subclassification of B-cell malignancies by flow cytometry. Therefore, the purpose of the present study was to evaluate the expression of CD307a during normal B-cell maturation and in B-cell malignancies as well as to investigate its potential role in the differential diagnosis of these entities. CD307a expression was assessed by flow cytometry in normal precursor and mature B cells and in 115 samples collected from patients diagnosed with precursor and mature B-cell neoplasms. CD307a expression was compared between neoplastic and normal B cells. B-acute lymphoblastic leukemia cases exhibited minimal expression of CD307a, displaying a similar expression pattern to that of normal B-cell precursors. Mantle cell lymphoma (MCL) cases showed the lowest levels of CD307a among mature B-cell neoplasms. CD307a expression was statistically lower in MCL cases than in chronic B lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL) cases. No statistical differences were observed between CD307a expression in neoplastic and normal plasma cells. These results indicate that the assessment of CD307a expression by flow cytometry could be helpful to distinguish CLL from MCL, and the latter from MZL. Although these results are not entirely conclusive, they provide a basis for further studies in a larger cohort of patients. © 2018 International Clinical Cytometry Society. © 2018 International Clinical Cytometry Society.

Inpatient Psychiatric Facility Follow-Up After Hospitalization for Mental Illness (FUH) Quality Measure Data – National

Data.gov (United States)

U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

B Cells Negatively Regulate the Establishment of CD49b(+)T-bet(+) Resting Memory T Helper Cells in the Bone Marrow.

Science.gov (United States)

Hojyo, Shintaro; Sarkander, Jana; Männe, Christian; Mursell, Mathias; Hanazawa, Asami; Zimmel, David; Zhu, Jinfang; Paul, William E; Fillatreau, Simon; Löhning, Max; Radbruch, Andreas; Tokoyoda, Koji

2016-01-01

During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs) to the bone marrow (BM) in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b(+)T-bet(+) antigen-experienced CD4 T cells in the spleen. CD49b(+)T-bet(+) antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b(+)T-bet(+) precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.

IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate

Science.gov (United States)

Noviski, Mark; Mueller, James L; Satterthwaite, Anne; Garrett-Sinha, Lee Ann; Brombacher, Frank

2018-01-01

Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn−/− B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells. PMID:29521626

Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010.

Science.gov (United States)

Seña, Arlene C; Moorman, Anne; Njord, Levi; Williams, Roxanne E; Colborn, James; Khudyakov, Yury; Drobenuic, Jan; Xia, Guo-Liang; Wood, Hattie; Moore, Zack

2013-07-01

Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. Outbreak investigation with case-control studies. Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission.

The ANL X6B beamline at NSLS: A versatile facility

International Nuclear Information System (INIS)

Huang, K.G.; Ramanathan, M.; Montano, P.A.; Illinois Univ., Chicago, IL

1994-07-01

We have described the x-ray optics and beamline performance of the ANL X6B beam line at the NSLS. Considerable flexibility has been built into the beam line to accommodate a wide range of x-ray diffraction, scattering, and spectroscopy experiments with various requirements. We presented selected examples of experimental results and showed that with the high intensity, high energy resolution, high-q resolution, and energy tunability, the X6B beam line has become a versatile facility

Prospects of using synchrotron radiation facilities with diamond-anvil cells

International Nuclear Information System (INIS)

Manghani, M.H.; Ming, L.C.; Jamieson, J.C.

1980-01-01

Diamond-anvil pressure cells have proven versatile and useful for conducting high pressure research in the submegabar range. The interfacing of diamond-anvil cell technology with synchrotron facilities seems a logical new step for carrying out in situ X-ray diffraction studies of materials under extreme conditions of combined high pressure and temperature. The conventional film method of X-ray diffraction has definite limitations which call for the energy dispersive analysis techniques. Various potential high pressure-temperature studies in geophysis and related fields involving the use of diamond-anvil cell, synchrotron facilities and energy dispersive techniques are exemplified. For geophysical studies the conditions prevailing in 86% of the Earth's volume are capable of being simulated completely in pressure, and partially in pressure and temperature, simultaneously. (orig.)

The quality management journey: the progress of health facilities in Australia.

Science.gov (United States)

Carr, B J

1994-12-01

Many facilities in Australia have taken the Total Quality Management (TQM) step. The objective of this study was to examine progress of adopted formal quality systems in health. Sixty per cent of organizations surveyed have adopted formal systems. Of these, Deming adherents are the most common, followed by eclectic choices. Only 35% considered the quality transition as reasonably easy. There was no relationship between accreditation and formal quality systems identified. The most common improvement techniques were: flow charts, histograms, and cause and effect diagrams. Quality practitioners are happy to use several tools exceptionally well rather than have many tools at their disposal. The greatest impediment to the adoption of quality was the lack of top management support. This study did not support the view that clinicians are not readily actively supporting quality initiatives. Total Quality Management is not a mature concept; however, Chief Executive Officers are assured that rewards will be realized over time.

Assessment of quality of prescribing in patients of hypertension at primary and secondary health care facilities using the Prescription Quality Index (PQI) tool.

Science.gov (United States)

Suthar, Jalpa Vashishth; Patel, Varsha J

2014-01-01

To determine the quality of prescribing in hypertension in primary and secondary health care settings using the Prescription Quality Index (PQI) tool and to assess the reliability of this tool. An observational cross-sectional study was carried out for 6 months in order to assess quality of prescribing of antihypertensive drugs using Prescription Quality Index (PQI) at four primary (PHC) and two secondary (SHC) health care facilities. Patients attending these facilities for at least 3 months were included. Complete medical history and prescriptions received were noted. Total and criteria wise PQI scores were derived for each prescription. Prescriptions were categorized as poor (score of ≤31), medium (score 32-33) and high quality (score 34-43) based on PQI total score. Psychometric analysis using factor analysis was carried out to assess reliability and validity. Total 73 hypertensive patients were included. Mean age was 61.2 ± 11 years with 35 (48%) patients above 65 years of age. Total PQI score was 26 ± 11. There was a significant difference in PQI score between PHC and SHC (P hypertensive patients was poor, somewhat better in primary as compared to secondary health care facility. PQI is reliable for measuring prescribing quality in hypertension in Indian set up.

PSA Solar furnace: A facility for testing PV cells under concentrated solar radiation

Energy Technology Data Exchange (ETDEWEB)

Fernandez-Reche, J.; Canadas, I.; Sanchez, M.; Ballestrin, J.; Yebra, L.; Monterreal, R.; Rodriguez, J.; Garcia, G. [Concentration Solar Technologies, Plataforma Solar de Almeria-CIEMAT P.O. Box 22, Tabernas, E-04200 (Almeria) (Spain); Alonso, M.; Chenlo, F. [Photovoltaic Components and Systems, Renewable Energies Department-CIEMAT Avda. Complutense, 22, Madrid, E-28040 (Spain)

2006-09-22

The Plataforma Solar de Almeria (PSA), the largest centre for research, development and testing of concentration solar thermal technologies in Europe, has started to apply its knowledge, facilities and resources to development of the Concentration PV technology in an EU-funded project HiConPV. A facility for testing PV cells under solar radiation concentrated up to 2000x has recently been completed. The advantages of this facility are that, since it is illuminated by solar radiation, it is possible to obtain the appropriate cell spectral response directly, and the flash tests can be combined with prolonged PV-cell irradiation on large surfaces (up to 150cm{sup 2}), so the thermal response of the PV cell can be evaluated simultaneously. (author)

Translocation of the B cell receptor to lipid rafts is inhibited in B cells from BLV-infected, persistent lymphocytosis cattle

International Nuclear Information System (INIS)

Hamilton, Valerie T.; Stone, Diana M.; Cantor, Glenn H.

2003-01-01

Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion of CD5 + , IgM+ B lymphocytes known as persistent lymphocytosis (PL) in approximately 30% of infected cattle. There is evidence that this expanded B cell population has altered signaling, and resistance to apoptosis has been proposed as one mechanism of B cell expansion. In human and murine B cells, antigen binding initiates movement of the B cell receptor (BCR) into membrane microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid rafts include members of the Src-family kinases and exclude certain phosphatases. Inclusion of the BCR into lipid rafts plays an important role in regulation of early signaling events and subsequent antigen internalization. Viral proteins may also influence signaling events in lipid rafts. Here we demonstrate that the largely CD5 + B cell population in PL cattle has different mobilization and internalization of the BCR when compared to the largely CD5-negative B cells in BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and is only weakly internalized. Expression of viral proteins as determined by detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter these events in cells from PL cattle. This exclusion of the BCR from lipid rafts may, in part, explain signaling differences seen between B cells of BLV-infected, PL, and BLV-negative cattle and the resistance to apoptosis speculated to contribute to persistent lymphocytosis

B cells negatively regulate the establishment of CD49b+T-bet+ resting memory T helper cells in the bone marrow

Directory of Open Access Journals (Sweden)

Shintaro eHojyo

2016-02-01

Full Text Available During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs to the bone marrow (BM in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b+T-bet+ antigen-experienced CD4 T cells in the spleen. CD49b+T-bet+ antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b+T-bet+ precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.

Responses of single germinal-center B cells in T-cell-dependent microculture.

Science.gov (United States)

George, A; Cebra, J J

1991-01-01

B cells purified from the germinal centers (GCs) of murine Peyer's patches can be stimulated in a clonal microculture containing helper T cells and dendritic cells to divide and secrete immunoglobulin. Intraclonal isotype switching occurs, and a variety of immunoglobulin isotypes, including IgA, is secreted. Memory cells, which generate clones secreting IgA exclusively, are only rarely identified in the GC B-cell subset. Such memory cells can, however, be readily identified among unfractionated Peyer's patch B cells, and in non-GC subsets of B cells. The results suggest that the GC does not contain IgA memory cells that can be restimulated in vitro to secrete only IgA. When division of GC B cells is prevented by irradiation or aphidicholin treatment, a large subset that secretes IgA as the sole immunoglobulin isotype is seen, and the output of presumably single B cells is large enough to be scored by RIA. Both helper T cells and dendritic cells are required for the phenomenon. The data indicate that commitment to IgA secretion occurs in Peyer's patch GCs and suggest that the prolific cell division known to be supported in GCs may forestall terminal differentiation of preplasmablasts to immunoglobulin secretion.

Non-invasive quality evaluation of confluent cells by image-based orientation heterogeneity analysis.

Science.gov (United States)

Sasaki, Kei; Sasaki, Hiroto; Takahashi, Atsuki; Kang, Siu; Yuasa, Tetsuya; Kato, Ryuji

2016-02-01

In recent years, cell and tissue therapy in regenerative medicine have advanced rapidly towards commercialization. However, conventional invasive cell quality assessment is incompatible with direct evaluation of the cells produced for such therapies, especially in the case of regenerative medicine products. Our group has demonstrated the potential of quantitative assessment of cell quality, using information obtained from cell images, for non-invasive real-time evaluation of regenerative medicine products. However, image of cells in the confluent state are often difficult to evaluate, because accurate recognition of cells is technically difficult and the morphological features of confluent cells are non-characteristic. To overcome these challenges, we developed a new image-processing algorithm, heterogeneity of orientation (H-Orient) processing, to describe the heterogeneous density of cells in the confluent state. In this algorithm, we introduced a Hessian calculation that converts pixel intensity data to orientation data and a statistical profiling calculation that evaluates the heterogeneity of orientations within an image, generating novel parameters that yield a quantitative profile of an image. Using such parameters, we tested the algorithm's performance in discriminating different qualities of cellular images with three types of clinically important cell quality check (QC) models: remaining lifespan check (QC1), manipulation error check (QC2), and differentiation potential check (QC3). Our results show that our orientation analysis algorithm could predict with high accuracy the outcomes of all types of cellular quality checks (>84% average accuracy with cross-validation). Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Hot Cell Facility (HCF) Safety Analysis Report

Energy Technology Data Exchange (ETDEWEB)

MITCHELL,GERRY W.; LONGLEY,SUSAN W.; PHILBIN,JEFFREY S.; MAHN,JEFFREY A.; BERRY,DONALD T.; SCHWERS,NORMAN F.; VANDERBEEK,THOMAS E.; NAEGELI,ROBERT E.

2000-11-01

This Safety Analysis Report (SAR) is prepared in compliance with the requirements of DOE Order 5480.23, Nuclear Safety Analysis Reports, and has been written to the format and content guide of DOE-STD-3009-94 Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Safety Analysis Reports. The Hot Cell Facility is a Hazard Category 2 nonreactor nuclear facility, and is operated by Sandia National Laboratories for the Department of Energy. This SAR provides a description of the HCF and its operations, an assessment of the hazards and potential accidents which may occur in the facility. The potential consequences and likelihood of these accidents are analyzed and described. Using the process and criteria described in DOE-STD-3009-94, safety-related structures, systems and components are identified, and the important safety functions of each SSC are described. Additionally, information which describes the safety management programs at SNL are described in ancillary chapters of the SAR.

Hot Cell Facility (HCF) Safety Analysis Report

International Nuclear Information System (INIS)

MITCHELL, GERRY W.; LONGLEY, SUSAN W.; PHILBIN, JEFFREY S.; MAHN, JEFFREY A.; BERRY, DONALD T.; SCHWERS, NORMAN F.; VANDERBEEK, THOMAS E.; NAEGELI, ROBERT E.

2000-01-01

This Safety Analysis Report (SAR) is prepared in compliance with the requirements of DOE Order 5480.23, Nuclear Safety Analysis Reports, and has been written to the format and content guide of DOE-STD-3009-94 Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Safety Analysis Reports. The Hot Cell Facility is a Hazard Category 2 nonreactor nuclear facility, and is operated by Sandia National Laboratories for the Department of Energy. This SAR provides a description of the HCF and its operations, an assessment of the hazards and potential accidents which may occur in the facility. The potential consequences and likelihood of these accidents are analyzed and described. Using the process and criteria described in DOE-STD-3009-94, safety-related structures, systems and components are identified, and the important safety functions of each SSC are described. Additionally, information which describes the safety management programs at SNL are described in ancillary chapters of the SAR

To B or not to B cells-mediate a healthy start to life.

Science.gov (United States)

Nguyen, T G; Ward, C M; Morris, J M

2013-02-01

Maternal immune responses during pregnancy are critical in programming the future health of a newborn. The maternal immune system is required to accommodate fetal immune tolerance as well as to provide a protective defence against infections for the immunocompromised mother and her baby during gestation and lactation. Natural immunity and antibody production by maternal B cells play a significant role in providing such immunoprotection. However, aberrations in the B cell compartment as a consequence of maternal autoimmunity can pose serious risks to both the mother and her baby. Despite their potential implication in shaping pregnancy outcomes, the role of B cells in human pregnancy has been poorly studied. This review focuses on the role of B cells and the implications of B cell depletion therapy in pregnancy. It highlights the evidence of an association between aberrant B cell compartment and obstetric conditions. It also alludes to the potential mechanisms that amplify these B cell aberrances and thereby contribute to exacerbation of some maternal autoimmune conditions and poor neonatal outcomes. Clinical and experimental evidence suggests strongly that maternal autoantibodies contribute directly to the pathologies of obstetric and neonatal conditions that have significant implications for the lifelong health of a newborn. The evidence for clinical benefit and safety of B cell depletion therapies in pregnancy is reviewed, and an argument is mounted for further clinical evaluation of B cell-targeted therapies in high-risk pregnancy, with an emphasis on improving neonatal outcomes and prevention of neonatal conditions such as congenital heart block and fetal/neonatal alloimmune thrombocytopenia. © 2012 British Society for Immunology.

Relative Contributions of B Cells and Dendritic Cells from Lupus-Prone Mice to CD4+ T Cell Polarization.

Science.gov (United States)

Choi, Seung-Chul; Xu, Zhiwei; Li, Wei; Yang, Hong; Roopenian, Derry C; Morse, Herbert C; Morel, Laurence

2018-05-01

Mouse models of lupus have shown that multiple immune cell types contribute to autoimmune disease. This study sought to investigate the involvement of B cells and dendritic cells in supporting the expansion of inflammatory and regulatory CD4 + T cells that are critical for lupus pathogenesis. We used lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) and congenic C57BL/6J (B6) control mice to investigate how the genetic predisposition of these two cell types controls the activity of normal B6 T cells. Using an allogeneic in vitro assay, we showed that TC B1-a and conventional B cells expanded Th17 cells significantly more than their B6 counterparts. This expansion was dependent on CD86 and IL-6 expression and mapped to the Sle1 lupus-susceptibility locus. In vivo, TC B cells promoted greater differentiation of CD4 + T cells into Th1 and follicular helper T cells than did B6 B cells, but they limited the expansion of Foxp3 regulatory CD4 + T cells to a greater extent than did B6 B cells. Finally, when normal B6 CD4 + T cells were introduced into Rag1 -/- mice, TC myeloid/stromal cells caused their heightened activation, decreased Foxp3 regulatory CD4 + T cell differentiation, and increased renal infiltration of Th1 and Th17 cells in comparison with B6 myeloid/stromal cells. The results show that B cells from lupus mice amplify inflammatory CD4 + T cells in a nonredundant manner with myeloid/stromal cells. Copyright © 2018 by The American Association of Immunologists, Inc.

Qualification testing facility for type A, B and C packages to be used for transport and storage of radioactive materials

International Nuclear Information System (INIS)

Vieru, G.; Nistor, V.; Vasile, A.; Cojocaru, V.

2009-01-01

In accordance with the Economic Commission for Europe-Committee on inland transport (ADR- European Agreement-concerning the international carriage of dangerous goods by road, 2007 Edition) the Safety and Security of the dangerous goods class No. 7 - Radioactive Materials during transport in all different modes - by road, by rail, by sea, by inland rivers or by air - have to be ensured at a very high level. The radioactive materials (RAM) packaging have to comply to all transport conditions, routine or in accident conditions, possibly to occur during transportation operations. It is well known that the safety in the transport of RAM is dependent on packaging appropriate for the contents being shipped rather than on operational and/or administrative actions required for the package. The quality of these packages - type A, B or C has to be proved by performing qualification tests in accordance with the Romanian nuclear regulation conditions provided by CNCAN Order no. 357/22.12.2005- N orms for a Safe Transport of Radioactive Material , the IAEA Vienna Recommendation (1, 2) stipulated in the Safety standard TS-R-1- Regulation for the Safe Transport of Radioactive Material, 2005 Edition, and other applicable international recommendations. The paper will describe the components of the designed testing facilities, and the qualification testing to be performed for all type A, B and C packages subjected to the testing Quality assurance and quality controls measures taken in order to meet technical specification provided by the design are also presented and commented. The paper concludes that the new Romanian Testing Facilities for RAM packages will comply with the national safe standards as well as with the IAEA applicable recommendation provided by the TS-R-1 safety standard. (authors)

AECL hot-cell facilities and post-irradiation examination services

International Nuclear Information System (INIS)

Schankula, M.H.; Plaice, E.L.; Woodworth, L.G.

1998-04-01

This paper presents an overview of the post-irradiation examination (PIE) services available at AECL's hot-cell facilities (HCF). The HCFs are used primarily to provide PIE support for operating CANDU power reactors in Canada and abroad, and for the examination of experimental fuel bundles and core components irradiated in research reactors at the Chalk River Laboratories (CRL) and off-shore. A variety of examinations and analyses are performed ranging from non-destructive visual and dimensional inspections to detailed optical and scanning electron microscopic examinations. Several hot cells are dedicated to mechanical property testing of structural materials and to determine the fitness-for-service of reactor core components. Facility upgrades and the development of innovative examination techniques continue to improve AECL's PIE capabilities. (author)

AECL hot-cell facilities and post-irradiation examination services

International Nuclear Information System (INIS)

Schankula, M.H.; Plaice, E.L.; Woodworth, L.G.

1995-01-01

This paper presents an overview of the post-irradiation examination (PIE) services available at AECL's hot-cell facilities (HCF). The HCFs are used primarily to provide PIE support for operating CANDU power reactors in Canada and abroad, and for the examination of experimental fuel bundles and core components irradiated in research reactors at the Chalk River Laboratories (CRL) and off-shore. A variety of examinations and analysis are performed ranging from non-destructive visual and dimensional inspections to detailed optical and scanning electron microscopic examinations. Several hot cells are dedicated to mechanical property testing of structural materials and to determine the fitness-for-service of reactor core components. Facility upgrades and the development of innovative examination techniques continue to improve AECL's PIE capabilities. (author)

2006 B100 Quality Survey Results: Milestone Report

Energy Technology Data Exchange (ETDEWEB)

Alleman, T. L.; McCormick, R. L.; Deutch, S.

2007-05-01

In 2006, the National Renewable Energy Laboratory conducted a nationwide quality survey of pure biodiesel (B100) intended to be used as a blendstock. The study collected random samples throughout the United States and analyzed them for quality against the current and proposed ASTM D6751 fuel quality specifications.

Introduction of hot cell facility in research center Rez - Poster

International Nuclear Information System (INIS)

Petrickova, A.; Srba, O.; Miklos, M.; Svoboda, P.

2015-01-01

This poster presents the hot cell facility which is being constructed as part of the SUSEN project at the Rez research center (Czech Republic). Within this project a new complex of 10 hot cells and one semi-hot cell will be built. There will be 8 gamma hot cells and 2 alpha hot cells. In each hot cell a hermetic, removable box made of stainless steel will home different type of devices. The hot cells and semi hot cell will be equipped with devices for processing samples (cutting, welding, drilling, machining) as well as equipment for testing (sample preparation area, stress testing machine, fatigue machine, electromechanical creep machine, high frequency resonance pulsator...) and equipment for studying material microstructure (nano-indenter with nano-scratch tester and scanning electron microscope). An autoclave with water loop, installed in a cell will allow mechanical testing in control environment of water, pressure and temperature. A scheme shows the equipment of each cell. This hot laboratory will be able to cover all the process to study radioactive materials: receiving the material, the preparation of the samples, mechanical testing and microstructure observation. Our hot cells will be close to the research nuclear reactor LVR-15 and new irradiation facility (high irradiation by cobalt source) is planned to be built within the SUSEN project

B Cell Help by CD1d-Rectricted NKT Cells

Directory of Open Access Journals (Sweden)

Livia Clerici

2015-10-01

Full Text Available B cell activation and antibody production against foreign antigens is a central step of host defense. This is achieved via highly regulated multi-phase processes that involve a variety of cells of both innate and adaptive arms of the immune system. MHC class II-restricted CD4+ T cells specific for peptide antigens, which acquire professional follicular B cell helper functions, have been long recognized as key players in this process. Recent data, however, challenge this paradigm by showing the existence of other helper cell types. CD1d restricted NKT cells specific for lipid antigens are one such new player and can coopt bona fide follicular helper phenotypes. Their role in helping antigen-specific B cell response to protein antigens, as well as to the so called “help-less” antigens that cannot be recognized by T follicular helper cells, is being increasingly elucidated, highlighting their potential pathophysiological impact on the immune response, as well as on the design of improved vaccine formulations.

Metabolic activity is necessary for activation of T suppressor cells by B cells

International Nuclear Information System (INIS)

Elkins, K.L.; Stashak, P.W.; Baker, P.J.

1990-01-01

Ag-primed B cells must express cell-surface IgM, but not IgD or Ia Ag, and must remain metabolically active, in order to activate suppressor T cells (Ts) specific for type III pneumococcal polysaccharide. Ag-primed B cells that were gamma-irradiated with 1000r, or less, retained the ability to activate Ts; however, Ag-primed B cells exposed to UV light were not able to do so. gamma-Irradiated and UV-treated Ag-primed B cells both expressed comparable levels of cell-surface IgM, and both localized to the spleen after in vivo transfer; neither could proliferate in vitro in response to mitogens. By contrast, gamma-irradiated primed B cells were still able to synthesize proteins, whereas UV-treated primed B cells could not. These findings suggest that in order for Ag-primed B cells to activate Ts, they must (a) express cell-associated IgM (sIgM) antibody bearing the idiotypic determinants of antibody specific for type III pneumococcal polysaccharide, and (b) be able to synthesize protein for either the continued expression of sIgM after cell transfer, or for the elaboration of another protein molecule that is also required for the activation of Ts; this molecule does not appear to be Ia Ag

Quality of newborn care: a health facility assessment in rural Ghana using survey, vignette and surveillance data

NARCIS (Netherlands)

Vesel, Linda; Manu, Alexander; Lohela, Terhi J.; Gabrysch, Sabine; Okyere, Eunice; ten Asbroek, Augustinus H. A.; Hill, Zelee; Agyemang, Charlotte Tawiah; Owusu-Agyei, Seth; Kirkwood, Betty R.

2013-01-01

To assess the structural capacity for, and quality of, immediate and essential newborn care (ENC) in health facilities in rural Ghana, and to link this with demand for facility deliveries and admissions. Health facility assessment survey and population-based surveillance data. Seven districts in

CD79B limits response of diffuse large B cell lymphoma to ibrutinib.

Science.gov (United States)

Kim, Joo Hyun; Kim, Won Seog; Ryu, Kyungju; Kim, Seok Jin; Park, Chaehwa

2016-01-01

Blockage of B cell receptor signaling with ibrutinib presents a promising clinical approach for treatment of B-cell malignancies. However, many patients show primary resistance to the drug or develop secondary resistance. In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib. CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance. Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK. Combination of the AKT inhibitor or the MAPK inhibitor with ibrutinib resulted in circumvention of both primary and acquired resistance in ABC-DLBCL. Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.

Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells.

Science.gov (United States)

Grabinski, Nicole; Ewald, Florian

2014-12-01

Ibrutinib (formerly PCI-32765) is a specific, irreversible, and potent inhibitor of Burton's tyrosine kinase (BTK) developed for the treatment of several forms of blood cancer. It is now an FDA-approved drug marketed under the name Imbruvica(TM) (Pharmacyclics, Inc.) and successfully used as an orally administered second-line drug in the treatment of mantle cell lymphoma. Since BTK is predominantly expressed in hematopoietic cells, the sensitivity of solid tumor cells to Ibrutinib has not been analyzed. In this study, we determined the effect of Ibrutinib on breast cancer cells. We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines. Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer. Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer cells. Combination indices below 0.25 at 50% inhibition of cell viability were determined by the Chou-Talalay method. Therefore, the combination of Ibrutinib and canonical PI3K pathway inhibitors could be a new and effective approach in the treatment of breast cancer with activated ErbB receptors. Ibrutinib could thus become a valuable component of targeted therapy in aggressive ErbB2+ breast cancer.

Mirror Fusion Test Facility-B (MFTF-B) axicell configuration: NbTi magnet system. Manufacturing/producibility final report. Volume 2

International Nuclear Information System (INIS)

Ritschel, A.J.; White, W.L.

1985-05-01

This Final MFTF-B Manufacturing/Producibility Report covers facilities, tooling plan, manufacturing sequence, schedule and performance, producibility, and lessons learned for the solenoid, axicell, and transition coils, as well as a deactivation plan, conclusions, references, and appendices

Helium generation reaction rates for 6Li and 10B in benchmark facilities

International Nuclear Information System (INIS)

Farrar, Harry IV; Oliver, B.M.; Lippincott, E.P.

1980-01-01

The helium generation rates for 10 B and 6 Li have been measured in two benchmark reactor facilities having neutron spectra similar to those found in a breeder reactor. The irradiations took place in the Coupled Fast Reactivity Measurements Facility (CFRMF) and in the 10% enriched 235 U critical assembly, BIG-10. The helium reaction rates were obtained by precise high-sensitivity gas mass spectrometric analyses of the helium content of numerous small samples. Comparison of these reaction rates with other reaction rates measured in the same facilities, and with rates calculated from published cross sections and from best estimates of the neutron spectral shapes, indicate significant discrepancies in the calculated values. Additional irradiations in other benchmark facilities have been undertaken to better determine the energy ranges where the discrepancies lie

Restoring balance to B cells in ADA deficiency.

Science.gov (United States)

Luning Prak, Eline T

2012-06-01

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

Directory of Open Access Journals (Sweden)

Jean-Jacques Fournie

2011-03-01

Full Text Available The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

International Nuclear Information System (INIS)

Gross, Emilie; Quillet-Mary, Anne; Ysebaert, Loic; Laurent, Guy; Fournie, Jean-Jacques

2011-01-01

The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity

Data Quality Objectives Report for the 115-B Gas Tunnel

International Nuclear Information System (INIS)

Bauer, R.G.

1998-05-01

This workbook assisted the Data Quality Objectives Team in implementing the Data Quality Objectives Process through the use of a template which lists the important elements of the DQO. The completion of this workbook is a required element of the BHI-EE-01, Procedure 1.2, 'Data Quality Objectives.' The objective of this project is to define the sampling and analysis requirements for isolation and decontamination and decommissioning release of the 115- B Gas Tunnel. The 115-B Gas Tunnel is an underground concrete pipe tunnel that houses piping used to recirculate helium gas between the 105-B Reactor Building and the 115-B/C Gas Recirculation System

Primary care practice and facility quality orientation: influence on breast and cervical cancer screening rates.

Science.gov (United States)

Goldzweig, Caroline Lubick; Parkerton, Patricia H; Washington, Donna L; Lanto, Andrew B; Yano, Elizabeth M

2004-04-01

Despite the importance of early cancer detection, variation in screening rates among physicians is high. Insights into factors influencing variation can guide efforts to decrease variation and increase screening rates. To explore the association of primary care practice features and a facility's quality orientation with breast and cervical cancer screening rates. Cross-sectional study of screening rates among 144 Department of Veterans Affairs (VA) medical centers and for a national sample of women. We linked practice structure and quality improvement characteristics of individual VA medical centers from 2 national surveys (1 to primary care directors and 1 to a stratified random sample of employees) to breast and cervical cancer screening rates determined from a review of random medical records. We conducted bivariate analyses and multivariate logistic regression of primary care practice and facility features on cancer screening rates, above and below the median. While the national screening rates were high for breast (87%) and cervical cancer (90%), higher screening rates were more likely when primary care providers were consistently notified of specialty visits and when staff perceived a greater organizational commitment to quality and anticipated rewards and recognition for better performance. Organization and quality orientation of the primary care practice and its facility can enhance breast and cervical cancer screening rates. Internal recognition of quality performance and an overall commitment to quality improvement may foster improved prevention performance, with impact varying by clinical service.

The FR 2 reactor at Karlsruhe, F.R. Germany and associated hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the FR 2 reactor and associated hot cell facilities, specialized irradiation devices (loops and capsules) and possibilities for post-irradiation examinations of samples. The information is presented in the form of eight information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; neutron spectra; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities; equipment and techniques available for post-irradiation examinations; utilization and specialization of the hot cell facilities

Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.

Science.gov (United States)

Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert; Sen, Ranjan; Young, Howard A; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

2016-04-15

B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+)MHC class-I(Hi)CD86(Hi)B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-γR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8(+)T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8(+)T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

Operating instructions for LBL radon measurement facilities

International Nuclear Information System (INIS)

Ingersoll, J.G.

1980-06-01

This manual is intended for users of the radon-measuring facilities of the Radon Project of the Building Ventilation and Indoor Air Quality Program at Lawrence Berkeley Laboratory. The manual comprises three parts. Part 1 sets out the steps involved in collecting, transferring, and counting radon. Part 2 describes the calibration of the transfer system and of the Lucas cells in the counting system. Part 3 outlines the maintenance procedures for the facility

Inpatient Psychiatric Facility Follow-Up After Hospitalization for Mental Illness (FUH) Quality Measure Data – by State

Data.gov (United States)

U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

A facility for long term evaluation and quality assurance of LHCb Vertex Detector modules

CERN Document Server

Marinho, F; Dimattia, R; Doherty, F; Dumps, R; Gersabeck, M; Melone, J; Parkes, C; Saavedra, A; Tobin, M

2007-01-01

This note describes the facility developed for long term evaluation and quality assurance of the LHCb Vertex Detector modules, known as the 'Glasgow Burn-in System'. This facility was developed to ensure that the modules conform to stringent quality levels. The system was able to uncover any weaknesses that could be introduced during the manufacturing and assembly of the components or during the transport of the modules to CERN. The system consisted of: a high resolution microscope for visual inspections; and a burn-in system to operate cooled modules in vacuum. The main components of the burn-in system were a vacuum system, a cooling system and a DAQ system.

Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women.

Science.gov (United States)

Prather, Aric A; Gurfein, Blake; Moran, Patricia; Daubenmier, Jennifer; Acree, Michael; Bacchetti, Peter; Sinclair, Elizabeth; Lin, Jue; Blackburn, Elizabeth; Hecht, Frederick M; Epel, Elissa S

2015-07-01

Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean=35.4, SD=3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b=-56.8 base pairs per one point increase in PSQI, SE=20.4, p=0.007) and CD4+ T cells (b=-37.2, SE=15.9, p=0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and

Quality assurance and quality control for the confinement physics research facility (CPRF) and ZTH experiment

International Nuclear Information System (INIS)

Kewish, R.W. Jr.

1989-01-01

In compliance with DOE order 5700.6B, which establishes policies to assure quality achievement in DOE programs, the authors instituted a quality assurance and quality control program whose primary goal is to assure that reliable components are available with which to assemble the CPRF/ZTH experiment. The Code of Federal Regulations 10 CFR 50, Appendix B, and the ANSI standard N45.2 were used as a primary source of guidance in establishing a plan for our QA program. Accepted codes, such as the National Electric Code (NEC), and standards adopted by organizations such as ANSI, IEEE, ASME, and NEMA were used in the design and production of components in keeping with the primary goal of the CPRF program. In setting up the CPRF/ZTH quality assurance program it was their intention to have these standards apply to all suppliers, both within and outside the Laboratory. 5 refs., 5 figs

The FOX and the mutants in mature human B cells and DLBCL: The role of FOXP1 in mature human B cell biology and lymphomagenesis & prevalence of oncogenic MyD88 and CD79B mutations in diffuse large B cell lymphoma

NARCIS (Netherlands)

van Keimpema, M.

2015-01-01

The transcription factor FOXP1 is prominently expressed in mature B cells and is a potential oncogene in B cell non-Hodgkin lymphomas; however, the functions of FOXP1 in mature B cells and B cell lymphomagenesis have not yet been fully explored. In the first part of this thesis, the roles of FOXP1

Rituximab does not reset defective early B cell tolerance checkpoints

Science.gov (United States)

Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

2015-01-01

Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

The progeny of a single virgin B cell predominates the human recall B cell response to the capsular polysaccharide of Haemophilus influenzae type b

DEFF Research Database (Denmark)

Barington, T; Hougs, L; Juul, L

1996-01-01

of the cells originated from a common virgin B cell. Kinetic considerations implied that an extremely selected population of hypermutated memory B cells must have existed in these individuals before the first systemic immunization with the Ag. A possible role for the mucosal immune system in the priming...

B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction.

Science.gov (United States)

Shin, Jung Hoon; Park, Se-Ho

2013-10-01

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although α-galactosylceramide (α-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-γ by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.

SerpinB1 Promotes Pancreatic β Cell Proliferation

Energy Technology Data Exchange (ETDEWEB)

El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

2016-01-01

Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

The FRJ 1 reactor (MERLIN) at Juelich, F.R. Germany and associated hot cell facilities. Information sheets

International Nuclear Information System (INIS)

Hardt, P. von der; Roettger, H.

1981-01-01

Technical information is given on the FRJ 1 reactor and associated hot cell facilities, with the main emphasis on experimental irradiation facilities, specialized irradiation devices (loops and capsules) and possibilities for post-irradiation examinations of samples. The information is presented in the form of eight information sheets under the headings: main characteristics of the reactor; utilization and specialization of the reactor; experimental facilities; neutron spectra; main characteristics of specialized irradiation devices; main characteristics of hot cell facilities; equipment and techniques available for post-irradiation examinations; utilization and specialization of the hot cell facilities

The 18 basic requirement of quality assurance for American design NPP

International Nuclear Information System (INIS)

Baliza, Ana Rosa

2013-01-01

On April 17th, 1969, the Atomic Energy Commission (AEC) published in the U.S. Federal Register (FR), Volume 34, Number 73, a proposed amendment to 10CFR50 to insert Appendix B - 'Quality assurance criteria for Nuclear Power Plant'. This Appendix was officially approved on June 27th, 1970 and published in the FR, volume 35, number 125. Appendix B is the Quality Assurance document for U.S. nuclear facilities. This document establishes eighteen basic requirements (BR) to design, construction, manufacture and operation of structures, systems and components (SSC) related to safety. The 18 BR describe 'what' shall be done, but not 'how' to do. In order to standardize the actions of nuclear facilities during 10 CFR 50 App B implementation, the industry has developed some documents, the main ones are: ASME NQA-1 (Quality Assurance Requirements for Nuclear Facility Applications) and the series ANSI N 45.2 (Quality Assurance Program Requirements for Nuclear Facilities). Both documents are approved by the NRC (Nuclear Regulatory Commission). The NRC is the licensing body of U.S. nuclear facilities. In Brazil, the licensing body is CNEN (Comissao Nacional de Energia Nuclear). This paper describes the 18 BR for American Designed Nuclear Power Plant (NPP), applicable to Angra-1 NPP. (author)

Outline of NUCEF facility

International Nuclear Information System (INIS)

Takeshita, Isao

1996-01-01

NUCEF is a multipurpose research facility in the field of safety and advanced technology of nuclear fuel cycle back-end. Various experiment facilities and its supporting installations, in which nuclear fuel materials, radio isotopes and TRU elements can be handled, are arranged in more than one hundred rooms of two experiment buildings. Its construction was completed in middle of 1994 and hot experiments have been started since then. NUCEF is located on the site (30,000 m 2 ) of southeastern part in the Tokai Research Establishment of JAERI facing to the Pacific Ocean. The base of Experiment Buildings A and B was directly founded on the rock existing at 10-15 m below ground level taking the aseismatic design into consideration. Each building is almost same sized and composed of one basement and three floors of which area is 17,500 m 2 in total. In the basement, there are exhaust facilities of ventilation system, treatment system of solution fuel and radioactive waste solution and storage tanks of them. Major experiment facilities are located on the first or the second floors in each building. An air-inlet facility of ventilation system for each building is equipped on the third floor. Most of experiment facilities for criticality safety research including two critical facilities: Static Experiment Critical Facility (STACY) and Transient Experiment Critical Facility (TRACY) are installed in Experiment Building A. Experiment equipments for research on advanced fuel reprocessing process and on TRU waste management, which are named BECKY (Back End Fuel Cycle Key Elements Research Facility), are installed in laboratories and a-g cells in Experiment Building B. (J.P.N.)

Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

Science.gov (United States)

Tay, Christopher; Liu, Yu-Han; Kanellakis, Peter; Kallies, Axel; Li, Yi; Cao, Anh; Hosseini, Hamid; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2018-05-01

B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr -/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications. © 2018 American Heart Association, Inc.

The nanoscale spatial organization of B-cell receptors on immunoglobulin M- and G-expressing human B-cells.

Science.gov (United States)

Lee, Jinmin; Sengupta, Prabuddha; Brzostowski, Joseph; Lippincott-Schwartz, Jennifer; Pierce, Susan K

2017-02-15

B-cell activation is initiated by the binding of antigen to the B-cell receptor (BCR). Here we used dSTORM superresolution imaging to characterize the nanoscale spatial organization of immunoglobulin M (IgM) and IgG BCRs on the surfaces of resting and antigen--activated human peripheral blood B-cells. We provide insights into both the fundamental process of antigen-driven BCR clustering and differences in the spatial organization of IgM and IgG BCRs that may contribute to the characteristic differences in the responses of naive and memory B-cells to antigen. We provide evidence that although both IgM and IgG BCRs reside in highly heterogeneous protein islands that vary in size and number of BCR single-molecule localizations, both resting and activated B-cells intrinsically maintain a high -frequency of single isolated BCR localizations, which likely represent BCR monomers. IgG BCRs are more clustered than IgM BCRs on resting cells and form larger protein islands after antigen activation. Small, dense BCR clusters likely formed via protein-protein interactions are present on the surface of resting cells, and antigen activation induces these to come together to form less dense, larger islands, a process likely governed, at least in part, by protein-lipid interactions. © 2017 Lee, Sengupta, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Software quality assurance plan for the National Ignition Facility integrated computer control system

Energy Technology Data Exchange (ETDEWEB)

Woodruff, J.

1996-11-01

Quality achievement is the responsibility of the line organizations of the National Ignition Facility (NIF) Project. This Software Quality Assurance Plan (SQAP) applies to the activities of the Integrated Computer Control System (ICCS) organization and its subcontractors. The Plan describes the activities implemented by the ICCS section to achieve quality in the NIF Project`s controls software and implements the NIF Quality Assurance Program Plan (QAPP, NIF-95-499, L-15958-2) and the Department of Energy`s (DOE`s) Order 5700.6C. This SQAP governs the quality affecting activities associated with developing and deploying all control system software during the life cycle of the NIF Project.

Software quality assurance plan for the National Ignition Facility integrated computer control system

International Nuclear Information System (INIS)

Woodruff, J.

1996-11-01

Quality achievement is the responsibility of the line organizations of the National Ignition Facility (NIF) Project. This Software Quality Assurance Plan (SQAP) applies to the activities of the Integrated Computer Control System (ICCS) organization and its subcontractors. The Plan describes the activities implemented by the ICCS section to achieve quality in the NIF Project's controls software and implements the NIF Quality Assurance Program Plan (QAPP, NIF-95-499, L-15958-2) and the Department of Energy's (DOE's) Order 5700.6C. This SQAP governs the quality affecting activities associated with developing and deploying all control system software during the life cycle of the NIF Project

Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells.

Science.gov (United States)

Frölich, Daniela; Giesecke, Claudia; Mei, Henrik E; Reiter, Karin; Daridon, Capucine; Lipsky, Peter E; Dörner, Thomas

2010-09-01

Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V(H) genes.

Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

Directory of Open Access Journals (Sweden)

Itziar Ubillos

2017-08-01

Full Text Available In persistent infections that are accompanied by chronic immune activation, such as human immunodeficiency virus, hepatitis C virus, and malaria, there is an increased frequency of a phenotypically distinct subset of memory B cells lacking the classic memory marker CD27 and showing a reduced capacity to produce antibodies. However, critical knowledge gaps remain on specific B cell changes and immune adaptation in chronic infections. We hypothesized that expansion of atypical memory B cells (aMBCs and reduction of activated peripheral marginal zone (MZ-like B cells in constantly exposed individuals might be accompanied by phenotypic changes that would confer a tolerogenic profile, helping to establish tolerance to infections. To better understand malaria-associated phenotypic abnormalities on B cells, we analyzed peripheral blood mononuclear cells from 55 pregnant women living in a malaria-endemic area of Papua Nueva Guinea and 9 Spanish malaria-naïve individuals using four 11-color flow cytometry panels. We assessed the expression of markers of B cell specificity (IgG and IgM, activation (CD40, CD80, CD86, b220, TACI, and CD150, inhibition (PD1, CD95, and CD71, and migration (CCR3, CXCR3, and CD62l. We found higher frequencies of active and resting aMBC and marked reduction of MZ-like B cells, although changes in absolute cell counts could not be assessed. Highly exposed women had higher PD1+-, CD95+-, CD40+-, CD71+-, and CD80+-activated aMBC frequencies than non-exposed subjects. Malaria exposure increased frequencies of b220 and proapoptotic markers PD1 and CD95, and decreased expression of the activation marker TACI on MZ-like B cells. The increased frequencies of inhibitory and apoptotic markers on activated aMBCs and MZ-like B cells in malaria-exposed adults suggest an immune-homeostatic mechanism for maintaining B cell development and function while simultaneously downregulating hyperreactive B cells. This mechanism would keep the B cell

Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells

Energy Technology Data Exchange (ETDEWEB)

Lam, R.K.K. [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Han, Wei [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong (Hong Kong)

2015-12-15

Highlights: • Rescue effect was observed in both irradiated and HeLa and NIH/3T3 cells. • Novel setup and procedures to separate the rescue signals and the bystander signals. • Confirmed activation of NF-κB pathway in rescue effect using activation inhibitor. • Confirmed activation of NF-κB pathway in rescue effect using anti-NF-κB p65 antibody. - Abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased

Identification of a B cell-dependent subpopulation of multiple sclerosis by measurements of brain-reactive B cells in the blood.

Science.gov (United States)

Kuerten, Stefanie; Pommerschein, Giovanna; Barth, Stefanie K; Hohmann, Christopher; Milles, Bianca; Sammer, Fabian W; Duffy, Cathrina E; Wunsch, Marie; Rovituso, Damiano M; Schroeter, Michael; Addicks, Klaus; Kaiser, Claudia C; Lehmann, Paul V

2014-01-01

B cells are increasingly coming into play in the pathogenesis of multiple sclerosis (MS). Here, we screened peripheral blood mononuclear cells (PBMC) from patients with clinically isolated syndrome (CIS), MS, other non-inflammatory neurological, inflammatory neurological or autoimmune diseases, and healthy donors for their B cell reactivity to CNS antigen using the enzyme-linked immunospot technique (ELISPOT) after 96 h of polyclonal stimulation. Our data show that nine of 15 patients with CIS (60.0%) and 53 of 67 patients with definite MS (79.1%) displayed CNS-reactive B cells, compared to none of the control donors. The presence of CNS-reactive B cells in the blood of the majority of patients with MS or at risk to develop MS along with their absence in control subjects suggests that they might be indicative of a B cell-dependent subpopulation of the disease. Copyright © 2014. Published by Elsevier Inc.

Fear and overprotection in Australian residential aged-care facilities: The inadvertent impact of regulation on quality continence care.

Science.gov (United States)

Ostaszkiewicz, Joan; O'Connell, Beverly; Dunning, Trisha

2016-06-01

Most residents in residential aged-care facilities are incontinent. This study explored how continence care was provided in residential aged-care facilities, and describes a subset of data about staffs' beliefs and experiences of the quality framework and the funding model on residents' continence care. Using grounded theory methodology, 18 residential aged-care staff members were interviewed and 88 hours of field observations conducted in two facilities. Data were analysed using a combination of inductive and deductive analytic procedures. Staffs' beliefs and experiences about the requirements of the quality framework and the funding model fostered a climate of fear and risk adversity that had multiple unintended effects on residents' continence care, incentivising dependence on continence management, and equating effective continence care with effective pad use. There is a need to rethink the quality of continence care and its measurement in Australian residential aged-care facilities. © 2015 AJA Inc.

B Cell Help by CD1d-Rectricted NKT Cells

OpenAIRE

Livia Clerici; Giulia Casorati; Paolo Dellabona

2015-01-01

B cell activation and antibody production against foreign antigens is a central step of host defense. This is achieved via highly regulated multi-phase processes that involve a variety of cells of both innate and adaptive arms of the immune system. MHC class II-restricted CD4+ T cells specific for peptide antigens, which acquire professional follicular B cell helper functions, have been long recognized as key players in this process. Recent data, however, challenge this paradigm by showing th...

Assessing the quality of care in a new nation: South Sudan's first national health facility assessment.

Science.gov (United States)

Berendes, Sima; Lako, Richard L; Whitson, Donald; Gould, Simon; Valadez, Joseph J

2014-10-01

We adapted a rapid quality of care monitoring method to a fragile state with two aims: to assess the delivery of child health services in South Sudan at the time of independence and to strengthen local capacity to perform regular rapid health facility assessments. Using a two-stage lot quality assurance sampling (LQAS) design, we conducted a national cross-sectional survey among 156 randomly selected health facilities in 10 states. In each of these facilities, we obtained information on a range of access, input, process and performance indicators during structured interviews and observations. Quality of care was poor with all states failing to achieve the 80% target for 14 of 19 indicators. For example, only 12% of facilities were classified as acceptable for their adequate utilisation by the population for sick-child consultations, 16% for staffing, 3% for having infection control supplies available and 0% for having all child care guidelines. Health worker performance was categorised as acceptable in only 6% of cases related to sick-child assessments, 38% related to medical treatment for the given diagnosis and 33% related to patient counselling on how to administer the prescribed drugs. Best performance was recorded for availability of in-service training and supervision, for seven and ten states, respectively. Despite ongoing instability, the Ministry of Health developed capacity to use LQAS for measuring quality of care nationally and state-by-state, which will support efficient and equitable resource allocation. Overall, our data revealed a desperate need for improving the quality of care in all states. © 2014 John Wiley & Sons Ltd.

Profile of hepatitis B and C virus infection in prisoners in Lubuk Pakam correctional facilities

Science.gov (United States)

Rey, I.; Saragih, R. H.; Effendi-YS, R.; Sembiring, J.; Siregar, G. A.; Zain, L. H.

2018-03-01

Prisoners in correctional facilities are predisposed to chronic viral infections because of their high-risk behaviors or unsafe lifestyle. The economic and public health burden of chronic hepatitis B and C and its sequelae need to be addressed, such as by finding the risk factors and therefore reducing the spread of HCV and HBV infection in prisons. This study aimed to see the profile of Hepatitis B and C Virus Infection in prisoners in Lubuk Pakam Correctional Facilities. This cross-sectional study was in Lubuk Pakam Correctional Facilities in 2016. From 1114 prisoners in Lubuk Pakam correctional facility, we randomly examined 120 prisoners for HBV and HCV serology markers. From 120 prisoners, six prisoners were HBV positive, 21 prisoners were HCV positive and one prisoner positive for both HCV and HBV infection. The most common risk factors for prisoners getting HBV infection are tattoos and free sex (36.4% and 36.4%, respectively). The most common risk factors for HCV infection in prisoners are tattoos and free sex (40% and 35%, respectively).

Perivascular Adipose Tissue Harbors Atheroprotective IgM-Producing B Cells

Directory of Open Access Journals (Sweden)

Prasad Srikakulapu

2017-09-01

Full Text Available Adipose tissue surrounding major arteries (Perivascular adipose tissue or PVAT has long been thought to exist to provide vessel support and insulation. Emerging evidence suggests that PVAT regulates artery physiology and pathology, such as, promoting atherosclerosis development through local production of inflammatory cytokines. Yet the immune subtypes in PVAT that regulate inflammation are poorly characterized. B cells have emerged as important immune cells in the regulation of visceral adipose tissue inflammation and atherosclerosis. B cell-mediated effects on atherosclerosis are subset-dependent with B-1 cells attenuating and B-2 cells aggravating atherosclerosis. While mechanisms whereby B-2 cells aggravate atherosclerosis are less clear, production of immunoglobulin type M (IgM antibodies is thought to be a major mechanism whereby B-1 cells limit atherosclerosis development. B-1 cell-derived IgM to oxidation specific epitopes (OSE on low density lipoproteins (LDL blocks oxidized LDL-induced inflammatory cytokine production and foam cell formation. However, whether PVAT contains B-1 cells and whether atheroprotective IgM is produced in PVAT is unknown. Results of the present study provide clear evidence that the majority of B cells in and around the aorta are derived from PVAT. Interestingly, a large proportion of these B cells belong to the B-1 subset with the B-1/B-2 ratio being 10-fold higher in PVAT relative to spleen and bone marrow. Moreover, PVAT contains significantly greater numbers of IgM secreting cells than the aorta. ApoE−/− mice with B cell-specific knockout of the gene encoding the helix-loop-helix factor Id3, known to have attenuated diet-induced atherosclerosis, have increased numbers of B-1b cells and increased IgM secreting cells in PVAT relative to littermate controls. Immunostaining of PVAT on human coronary arteries identified fat associated lymphoid clusters (FALCs harboring high numbers of B cells, and flow

Polymyxin B Nephrotoxicity: From Organ to Cell Damage.

Directory of Open Access Journals (Sweden)

Maria de Fátima Fernandes Vattimo

Full Text Available Polymyxins have a long history of dose-limiting toxicity, but the underlying mechanism of polymyxin B-induced nephrotoxicity is unclear. This study investigated the link between the nephrotoxic effects of polymyxin B on renal metabolic functions and mitochondrial morphology in rats and on the structural integrity of LLC-PK1 cells. Fifteen Wistar rats were divided into two groups: Saline group, rats received 3 mL/kg of 0.9% NaCl intraperitoneally (i.p. once a day for 5 days; Polymyxin B group, rats received 4 mg/kg/day of polymyxin B i.p. once a day for 5 days. Renal function, renal hemodynamics, oxidative stress, mitochondrial injury and histological characteristics were assessed. Cell membrane damage was evaluated via lactate dehydrogenase and nitric oxide levels, cell viability, and apoptosis in cells exposed to 12.5 μM, 75 μM and 375 μM polymyxin B. Polymyxin B was immunolocated using Lissamine rhodamine-polymyxin B in LLC-PK1 cells. Polymyxin B administration in rats reduced creatinine clearance and increased renal vascular resistance and oxidative damage. Mitochondrial damage was confirmed by electron microscopy and cytosolic localization of cytochrome c. Histological analysis revealed tubular dilatation and necrosis in the renal cortex. The reduction in cell viability and the increase in apoptosis, lactate dehydrogenase levels and nitric oxide levels confirmed the cytotoxicity of polymyxin B. The incubation of LLC-PK1 cells resulted in mitochondrial localization of polymyxin B. This study demonstrates that polymyxin B nephrotoxicity is characterized by mitochondrial dysfunction and free radical generation in both LLC-PK1 cells and rat kidneys. These data also provide support for clinical studies on the side effects of polymyxin B.

The ISOLDE facility

Science.gov (United States)

Catherall, R.; Andreazza, W.; Breitenfeldt, M.; Dorsival, A.; Focker, G. J.; Gharsa, T. P.; J, Giles T.; Grenard, J.-L.; Locci, F.; Martins, P.; Marzari, S.; Schipper, J.; Shornikov, A.; Stora, T.

2017-09-01

The ISOLDE facility has undergone numerous changes over the last 17 years driven by both the physics and technical community with a common goal to improve on beam variety, beam quality and safety. Improvements have been made in civil engineering and operational equipment while continuing developments aim to ensure operations following a potential increase in primary beam intensity and energy. This paper outlines the principal technical changes incurred at ISOLDE by building on a similar publication of the facility upgrades by Kugler (2000 Hyperfine Interact. 129 23-42). It also provides an insight into future perspectives through a brief summary issues addressed in the HIE-ISOLDE design study Catherall et al (2013 Nucl. Instrum. Methods Phys. Res. B 317 204-207).

Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation.

Science.gov (United States)

Ringelstein-Harlev, Shimrit; Avivi, Irit; Fanadka, Mona; Horowitz, Netanel A; Katz, Tami

2018-02-15

Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia. Co-culture assays were used to examine the ability of CLL cells to suppress autologous T-cell immune responses. IL-10 potency of CLL cells was assessed following stimulation with activators of the toll-like receptor 9 (TLR9) or CD40 and was correlated with the inhibitory activity of the cells. TLR9-activated CLL cells were found to increase the frequency of CD4 + CD25 hi FOXp3 + regulatory T-cells (Tregs) and to inhibit autologous CD4 + T-cell proliferation. This signaling cascade proved to control IL-10 generation in CLL cells, which in turn promoted the inhibition of T-cell proliferation by CLL cells. However, CD40 activation of CLL cells, while exhibiting a similar ability to augment Treg frequency, did not either affect IL-10 generation or T-cell proliferation. In conclusion, CLL cells demonstrate a unique clonal quality of adopting Breg properties which promote modulation of T-cell characteristics. TLR9 appears to be a potent activator of regulatory abilities in CLL cells, possibly contributing to preferential immune escape of TLR9-responsive cells.

B-cell-mediated strategies to fight chronic allograft rejection

Directory of Open Access Journals (Sweden)

Ali H Dalloul

2013-12-01

Full Text Available Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after one year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of tolerant vs effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic

Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (-)-epigallocatechin gallate-treated cells.

Science.gov (United States)

Watanabe, Tatsuro; Kuramochi, Hiromi; Takahashi, Atsushi; Imai, Kazue; Katsuta, Naoko; Nakayama, Tomonobu; Fujiki, Hirota; Suganuma, Masami

2012-05-01

To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (-)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young's modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.

Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

DEFF Research Database (Denmark)

Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

2016-01-01

. We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia

Science.gov (United States)

... Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

Unique B cell differentiation profile in tolerant kidney transplant patients.

Science.gov (United States)

Chesneau, M; Pallier, A; Braza, F; Lacombe, G; Le Gallou, S; Baron, D; Giral, M; Danger, R; Guerif, P; Aubert-Wastiaux, H; Néel, A; Michel, L; Laplaud, D-A; Degauque, N; Soulillou, J-P; Tarte, K; Brouard, S

2014-01-01

Operationally tolerant patients (TOL) display a higher number of blood B cells and transcriptional B cell signature. As they rarely develop an allo-immune response, they could display an abnormal B cell differentiation. We used an in vitro culture system to explore T-dependent differentiation of B cells into plasma cells. B cell phenotype, apoptosis, proliferation, cytokine, immunoglobulin production and markers of differentiation were followed in blood of these patients. Tolerant recipients show a higher frequency of CD20(+) CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of abnormal B cell differentiation. B cells from TOL proliferate normally but produce more IL-10. In addition, B cells from tolerant recipients exhibit a defective expression of factors of the end step of differentiation into plasma cells and show a higher propensity for cell death apoptosis compared to patients with stable graft function. This in vitro profile is consistent with down-regulation of B cell differentiation genes and anti-apoptotic B cell genes in these patients in vivo. These data suggest that a balance between B cells producing IL-10 and a deficiency in plasma cells may encourage an environment favorable to the tolerance maintenance. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Piloting laboratory quality system management in six health facilities in Nigeria.

Directory of Open Access Journals (Sweden)

Henry Mbah

Full Text Available Achieving accreditation in laboratories is a challenge in Nigeria like in most African countries. Nigeria adopted the World Health Organization Regional Office for Africa Stepwise Laboratory (Quality Improvement Process Towards Accreditation (WHO/AFRO- SLIPTA in 2010. We report on FHI360 effort and progress in piloting WHO-AFRO recognition and accreditation preparedness in six health facility laboratories in five different states of Nigeria.Laboratory assessments were conducted at baseline, follow up and exit using the WHO/AFRO- SLIPTA checklist. From the total percentage score obtained, the quality status of laboratories were classified using a zero to five star rating, based on the WHO/AFRO quality improvement stepwise approach. Major interventions include advocacy, capacity building, mentorship and quality improvement projects.At baseline audit, two of the laboratories attained 1- star while the remaining four were at 0- star. At follow up audit one lab was at 1- star, two at 3-star and three at 4-star. At exit audit, four labs were at 4- star, one at 3-star and one at 2-star rating. One laboratory dropped a 'star' at exit audit, while others consistently improved. The two weakest elements at baseline; internal audit (4% and occurrence/incidence management (15% improved significantly, with an exit score of 76% and 81% respectively. The elements facility and safety was the major strength across board throughout the audit exercise.This effort resulted in measurable and positive impact on the laboratories. We recommend further improvement towards a formal international accreditation status and scale up of WHO/AFRO- SLIPTA implementation in Nigeria.

Analysis of epothilone B-induced cell death in normal ovarian cells.

Science.gov (United States)

Rogalska, Aneta; Gajek, Arkadiusz; Marczak, Agnieszka

2013-12-01

We have investigated the mode of cell death induced by a new microtubule-stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis, as well as spectrofluorimetric and colorimetric detection, we demonstrate that, compared to EpoB, PTX induced high time-dependent morphological and biochemical changes typical of apoptosis. Induction of apoptosis followed an early increase in p53 levels. Apoptosis reached its maximum at 24-48 h. At the same time, there was a significant increase in caspase-9 and -3 activity and PARP fragmentation, which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was increased more by PTX than EpoB, and also induced more necrosis responsible for inflammation (1.4-fold) than EpoB. © 2013 International Federation for Cell Biology.

Use of lasers at the Los Alamos Hot-Cell Facility

International Nuclear Information System (INIS)

Lazarus, M.E.

1983-01-01

An optical profilometer that uses a Techmet LaserMike scanning, focused, laser-beam, optical micrometer is installed in a remote alpha-gamma containment cell at the Los Alamos Hot-Cell Facility. A hot-cell extension chamber provides the nominal 30-cm (12-in.) working distance required by the LaserMike and, at the same time, keeps the LaserMike components outside the high-radiation-containment environment. This system provides measurement accuracy better than +- 5 μm (0.0002 in.) on diameters between 2 and 13 mm (0.88 and 0.5 in.) at a rate of 33 measurements per second. The Hot-Cell Facility also uses a Korad 20-J-output ruby pulsed laser to drill a hole in reactor-fuel-element cladding to sample fission gas. The laser is then used to reweld the hole so that the fuel element will not be contaminated and may be stored without an alpha-containment barrier. The wall thickness of the fuel elements sampled varies from 0.25 to 0.50 mm (0.010 to 0.020 in.)

Los Alamos Hot-Cell-Facility modifications for examining FFTF fuel pins

International Nuclear Information System (INIS)

Campbell, B.M.; Ledbetter, J.M.

1982-01-01

Commissioned in 1960, the Wing 9 Hot Cell Facility at Los Alamos was recently modified to meet the needs of the 1980s. Because fuel pins from the Fast Flux Test Facility (FFTF) at the Hanford Engineering Development Laboratory (HEDL) are too long for examination in the original hot cells, we modified cells to accommodate longer fuel pins and to provide other capabilities as well. For instance, the T-3 shipping cask now can be opened in an inert atmosphere that can be maintained for all nondestructive and destructive examinations of the fuel pins. The full-length pins are visually examined and photographed, the wire wrap is removed, and fission gas is sampled. After the fuel pin is cropped, a cap is seal-welded on the section containing the fuel column. This section is then transferred to other cells for gamma-scanning, radiography, profilometry, sectioning for metallography, and chemical analysis

Ultraviolet B Radiation Stimulates the Interaction between Nuclear Factor of Activated T Cells 5 (NFAT5) and Nuclear Factor-Kappa B (NF-κB) in Human Lens Epithelial Cells.

Science.gov (United States)

Chung, Inyoung; Hah, Young-Sool; Ju, SunMi; Kim, Ji-Hye; Yoo, Woong-Sun; Cho, Hee-Young; Yoo, Ji-Myong; Seo, Seong-Wook; Choi, Wan-Sung; Kim, Seong-Jae

2017-07-01

Nuclear factor-kappa B (NF-κB) has been proposed as a therapeutic target for the treatment of cataracts. The authors investigated the relationship between nuclear factor of activated T cells 5 (NFAT5) and NF-κB in ultraviolet B (UVB)-irradiated human lens epithelial (HLE) cells. Human lens epithelial B-3 (HLE-B3) cells were exposed to UVB light at a dose of 10 mJ/cm 2 and then incubated for 24 h. Cell viability was assessed by using the Cell Counting Kit-8 (CCK-8) assay. Gene expression level of NFAT5 was determined using real-time quantitative polymerase chain reaction (qPCR). Protein expression levels of NFAT5, NF-κB p65, and α-smooth muscle actin (α-SMA) and the association of NFAT5 with the NF-κB p65 subunit were measured by Western blot analysis and a co-immunoprecipitation assay, respectively. The cellular distribution of NFAT5 and NF-κB p65 was examined by triple immunofluorescence staining. At 24 h after UVB exposure, cell viability significantly decreased in a dose-dependent manner, and UVB light (15 and 20 mJ/cm 2 ) significantly increased the ROS generation. UVB irradiation increased NFAT5 mRNA and protein levels and increased phosphorylation of NF-κB in HLE-B3 cells. α-SMA protein levels were increased in the irradiated cells. In addition, NFAT5 and NF-κB translocated from the cytoplasm to the nucleus, and binding between the p65 subunit and NFAT5 was increased. Exposure to UVB radiation induces nuclear translocation and stimulates binding between NFAT5 and NF-κB proteins in HLE-B3 cells. These interactions may form part of the biochemical mechanism of cataractogenesis in UVB-irradiated HLECs.

Multi-Function Waste Tank Facility Quality Assurance Program Plan, Project W-236A. Revision 2

Energy Technology Data Exchange (ETDEWEB)

Hall, L.R.

1995-05-30

This document describes the Quality Assurance (QA) program for the Multi-Function Waste Tank Facility (MWTF) Project. The purpose of this QA program is to control project activities in such a manner as to achieve the mission of the MWTF Project in a safe and reliable manner. The QA program for the MWTF Project is founded on DOE Order 5700.6C, Quality Assurance, and implemented through the use of ASME NQA-1, Quality Assurance Program Requirements for Nuclear Facilities (ASME 1989 with addenda la-1989, lb-1991 and lc-1992). This document describes the program and planned actions which the Westinghouse Hanford Company (WHC) will implement to demonstrate and ensure that the project meets the requirements of DOE Order 5700.6C through the interpretive guidance of ASME NQA-1.

Multi-Function Waste Tank Facility Quality Assurance Program Plan, Project W-236A. Revision 2

International Nuclear Information System (INIS)

Hall, L.R.

1995-01-01

This document describes the Quality Assurance (QA) program for the Multi-Function Waste Tank Facility (MWTF) Project. The purpose of this QA program is to control project activities in such a manner as to achieve the mission of the MWTF Project in a safe and reliable manner. The QA program for the MWTF Project is founded on DOE Order 5700.6C, Quality Assurance, and implemented through the use of ASME NQA-1, Quality Assurance Program Requirements for Nuclear Facilities (ASME 1989 with addenda la-1989, lb-1991 and lc-1992). This document describes the program and planned actions which the Westinghouse Hanford Company (WHC) will implement to demonstrate and ensure that the project meets the requirements of DOE Order 5700.6C through the interpretive guidance of ASME NQA-1

Does Nursing Facility Use of Habilitation Therapy Improve Performance on Quality Measures?

Science.gov (United States)

Fitzler, Sandra; Raia, Paul; Buckley, Fredrick O; Wang, Mei

2016-12-01

The purpose of the project, Centers for Medicare & Medicaid Services (CMS) Innovation study, was to evaluate the impact on 12 quality measures including 10 Minimum Data Set (MDS) publicly reported measures and 2 nursing home process measures using habilitation therapy techniques and a behavior team to manage dementia-related behaviors. A prospective design was used to assess the changes in the measures. A total of 30 Massachusetts nursing homes participated in the project over a 12-month period. Project participation required the creation of an interdisciplinary behavior team, habilitation therapy training, facility visit by the program coordinator, attendance at bimonthly support and sharing calls, and monthly collection of process measure data. Participating facilities showed improvement in 9 of the 12 reported measures. Findings indicate potential quality improvement in having nursing homes learn habilitation therapy techniques and know how to use the interdisciplinary team to manage problem behaviors. © The Author(s) 2016.

Cryosat Level1b SAR/Sarin: Improving the Quality of the Baseline C Products

Science.gov (United States)

Scagliola, M.; Fornari, M.; Tagliani, N.; Frommknecht, B.; Bouffard, J.; Parrinello, T.

2014-12-01

CryoSat was launched on the 8th April 2010 and it is the first European ice mission dedicated to monitoring precise changes in the thickness of polar ice sheets and floating sea ice over a 3-year period. Cryosat carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. This allows to reach a significantly improved along track resolution with respect to traditional pulse-width limited altimeters. CryoSat is the first altimetry mission operating in SAR mode and continuous improvement in the Level1 Instrument Processing Facility (IPF1) are being identified, tested and validated in order to improve the quality of the Level1b products. Towards the release of the BaselineC of the CryoSat Level1b SAR/SARin products, that is expected at the end of 2014, several improvements have been identified: a datation bias of about -0.5195 ms will be corrected a range bias of about 0.6730 m will be corrected The range window size will be doubled with respect to BaselineB, so that the in Level1b products the waveforms will be doubled too Improved processing for 1Hz echoes to have sharper waveforms Surface sample stack weighting to filter out the single look echoes acquired at highest look angle, that results in a sharpening of the 20Hz waveforms Additional auxiliary information related to the mispointing angles of the instrument as well as to the stacks of single look echoes will be added This poster details the main quality improvements that are foreseen to be included in the CryoSat Level1b SAR/SARin products in BaselineC.

B cell biology: implications for treatment of systemic lupus erythematosus.

Science.gov (United States)

Anolik, J H

2013-04-01

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread

Survey of the prevalence and methodology of quality assurance for B-mode ultrasound image quality among veterinary sonographers.