SketchingDIS: Hand-drawn Sketching in HCI

DEFF Research Database (Denmark)

Lewis, Makayla; Sturdee, Miriam; Alexander, Jason

2017-01-01

DIS: Hand-drawn sketching in HCI' SketchingDIS.wordpress.com, a one-day workshop will bring together researchers from various disciplines that have incorporated hand-drawn sketching into their everyday research practice, to share knowledge and methodologies, generate ideas, practice collaborative sketching...

49 CFR 219.701 - Standards for drug and alcohol testing.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

46 CFR 10.219 - Fees.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Fees. 10.219 Section 10.219 Shipping COAST GUARD... Requirements for All Merchant Mariner Credentials § 10.219 Fees. (a) Use table 10.219(a) of this section to calculate the mandatory fees for MMCs and associated endorsements. Table 10.219(a) Fees If you apply for And...

The ribonuclease Dis3 is an essential regulator of the developmental transcriptome

Directory of Open Access Journals (Sweden)

Hou Dezhi

2012-08-01

Full Text Available Abstract Background Dis3 is ribonuclease that acts directly in the processing, turnover, and surveillance of a large number of distinct RNA species. Evolutionarily conserved from eubacteria to eukaryotes and a crucial component of the RNA processing exosome, Dis3 has been shown to be essential in yeast and fly S2 cells. However, it is not known whether Dis3 has essential functions in a metazoan. This study inquires whether Dis3 is required for Drosophila development and viability and how Dis3 regulates the transcriptome in the developing fly. Results Using transgenic flies, we show that Dis3 knock down (Dis3KD retards growth, induces melanotic tumor formation, and ultimately results in 2nd instar larval lethality. In order to determine whether Dis3KD fly phenotypes were a consequence of disrupting developmentally regulated RNA turnover, we performed RNA deep sequencing analysis on total RNA isolated from developmentally staged animals. Bioinformatic analysis of transcripts from Dis3KD flies reveals substantial transcriptomic changes, most notably down-regulation in early expressed RNAs. Finally, gene ontology analysis of this early stage shows that Dis3 regulates transcripts related to extracellular structure and remodelling, neurogenesis, and nucleotide metabolism. Conclusions We conclude that Dis3 is essential for early Drosophila melanogaster development and has specific and important stage-specific roles in regulating RNA metabolism. In showing for the first time that Dis3 is required for the development of a multicellular organism, our work provides mechanistic insight into how Dis3—either independent of or associated with the RNA processing exosome—participates in cell type-specific RNA turnover in metazoan development.

Drilling Information System (DIS and Core Scanner

Directory of Open Access Journals (Sweden)

Ronald Conze

2016-04-01

Full Text Available The Drilling Information System is a modular structure of databases, tailored user applications as well as web services and instruments including appropriate interfaces to DIS. This tool set has been developed for geoscientific drilling projects but is applicable to other distributed scientific operations. The main focuses are the data acquisition on drill sites (ExpeditionDIS, and the curation of sample material e.g., in core repositories (CurationDIS. Due to the heterogeneity of scientific drilling projects, a project-specific DIS is arranged and adjusted from a collection of existing templates and modules according to the user requirements during a one week training course. The collected data are provided to the Science Team of the drilling project by secured Web services, and stored in long-term archives hosted at GFZ. At the end the data sets and sample material are documented in an Operational Report (e.g., Lorenz et al., 2015 and published with assigned DOI (Digital Object Identifier and IGSN (International Geo Sample Number; for physical samples by GFZ Data Services.

36 CFR 219.18 - Role of advisory committees.

Science.gov (United States)

2010-07-01

... PLANNING National Forest System Land and Resource Management Planning Collaborative Planning for... variety of public purposes, particularly those groups organized to develop landscape goals (§ 219.12(b...

Radiological accidents: methodologies of radio nuclides dis incorporation

International Nuclear Information System (INIS)

Jimenez F, E. A.; Paredes G, L.; Cortes, A.

2014-08-01

Derived of the radioactive or nuclear material management, exists the risk that accidents can happen where people cases are presented with internal radioactive contamination, who will receive specialized medical care to accelerate the radioactive dis incorporation with the purpose of diminishing the absorbed dose and the associate biological effects. In this work treatments of radioactive dis incorporation were identified, in function of the radionuclide, radiation type, radioactive half life, biological half life, critical organ, ingestion duct and patient type. The factor time is decisive for the effectiveness of the selected treatment in the blockade stage (before the accident) or dis incorporation (after the accident); this factor is related with the radioactive and biological half lives. So to achieve dis incorporation efficiencies of more to 70%, the patient clinical treatment will begin before the first third of the biological half life of the radionuclide that generated the internal contamination. (Author)

48 CFR 219.7104 - Developmental assistance costs eligible for reimbursement or credit.

Science.gov (United States)

2010-10-01

... costs eligible for reimbursement or credit. 219.7104 Section 219.7104 Federal Acquisition Regulations... reimbursement or credit. (a) Developmental assistance provided under an approved mentor-protege agreement is... eligible for reimbursement are set forth in appendix I. (b) Before incurring any costs under the Program...

48 CFR 252.219-7003 - Small business subcontracting plan (DoD contracts).

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Small business... AND CONTRACT CLAUSES Text of Provisions And Clauses 252.219-7003 Small business subcontracting plan (DoD contracts). As prescribed in 219.708(b)(1)(A), use the following clause: Small Business...

47 CFR 25.219 - [Reserved

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false [Reserved] 25.219 Section 25.219 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.219 [Reserved] ...

49 CFR 219.17 - Construction.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Construction. 219.17 Section 219.17 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE General § 219.17 Construction. Nothing in this part— (a) Restricts...

Developing and promoting an intranet site for a drug information service.

Science.gov (United States)

Costerison, Emily C; Graham, Angie S

2008-04-01

The development and promotion of a drug information service (DIS) intranet site are described. Stanford Hospital and Clinics (SHC) is an acute and tertiary care facility with 613 licensed inpatient beds and 48 outpatient clinics. A DIS intranet site was developed to allow better accessibility to pharmacy forms and products (e.g., drug shortage list, reference guides) and to reduce repetitive requests to the DIS. The goal was to continue to provide information to SHC health care providers but allow the drug information specialist to focus on answering clinical questions. The intranet site was completed over a four-month period. The intranet site was divided into seven webpages: DIS overview, pharmacy and therapeutics, frequently asked questions, quick drug reference guide, ask the pharmacist, drug information resources, and referral center. The preparation for and implementation of the promotional phase took approximately two months. Promotional strategies included the creation and dissemination of brochures and stickers. The intranet site went live on January 1, 2007, and the advertising campaign began one month later. The utility of the site was measured for five months by tracking the number of visits to the site, the number of visits to each webpage, and the number of downloaded files. Request volume, caller affiliation, and question types received by the DIS call center were also recorded. Establishing a DIS intranet site required a considerable time investment and a willingness to work with existing infrastructures, such as the marketing and communications department and Web marketing staff.

22 CFR 219.140 - Employment.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment. 219.140 Section 219.140 Foreign... DEVELOPMENT § 219.140 Employment. No qualified handicapped person shall, on the basis of handicap, be subjected to discrimination in employment under any program or activity conducted by the agency. The...

36 CFR 219.2 - Principles.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Principles. 219.2 Section 219... Forest System Land and Resource Management Planning Purpose and Principles § 219.2 Principles. The planning regulations in this subpart are based on the following principles: (a) The first priority for...

Do you know DIS? a novel passive individual dosimeterd. Direct Ion Storage dosimeter DIS-1 officially approved in Switzerland

International Nuclear Information System (INIS)

Fiechtner, A.; Wernli, C.

2001-01-01

For individual monitoring film and TLD are the most often used types of dosimeters. On a smaller scale phosphate glasses and detectors based on optically stimulated luminescence (OSL) are also in use. As a new addition to the list of available personnel dosimeters the direct ion storage (DIS) system became legally approved for the first time in Switzerland. At the Paul Scherrer Institute (PSI) the RADOS dosimetry system DIS-1 is in official use since beginning of 2001. (orig.) [de

15 CFR 280.219 - Settlement.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Settlement. 280.219 Section 280.219... Enforcement § 280.219 Settlement. (a) Cases may be settled before service of a charging letter. In cases in which settlement is reached before service of a charging letter, a proposed charging letter will be...

DisEpi: Compact Visualization as a Tool for Applied Epidemiological Research.

Science.gov (United States)

Benis, Arriel; Hoshen, Moshe

2017-01-01

Outcomes research and evidence-based medical practice is being positively impacted by proliferation of healthcare databases. Modern epidemiologic studies require complex data comprehension. A new tool, DisEpi, facilitates visual exploration of epidemiological data supporting Public Health Knowledge Discovery. It provides domain-experts a compact visualization of information at the population level. In this study, DisEpi is applied to Attention-Deficit/Hyperactivity Disorder (ADHD) patients within Clalit Health Services, analyzing the socio-demographic and ADHD filled prescription data between 2006 and 2016 of 1,605,800 children aged 6 to 17 years. DisEpi's goals facilitate the identification of (1) Links between attributes and/or events, (2) Changes in these relationships over time, and (3) Clusters of population attributes for similar trends. DisEpi combines hierarchical clustering graphics and a heatmap where color shades reflect disease time-trends. In the ADHD context, DisEpi allowed the domain-expert to visually analyze a snapshot summary of data mining results. Accordingly, the domain-expert was able to efficiently identify that: (1) Relatively younger children and particularly youngest children in class are treated more often, (2) Medication incidence increased between 2006 and 2011 but then stabilized, and (3) Progression rates of medication incidence is different for each of the 3 main discovered clusters (aka: profiles) of treated children. DisEpi delivered results similar to those previously published which used classical statistical approaches. DisEpi requires minimal preparation and fewer iterations, generating results in a user-friendly format for the domain-expert. DisEpi will be wrapped as a package containing the end-to-end discovery process. Optionally, it may provide automated annotation using calendar events (such as policy changes or media interests), which can improve discovery efficiency, interpretation, and policy implementation.

Intersectionality Dis/ability Research: How Dis/ability Research in Education Engages Intersectionality to Uncover the Multidimensional Construction of Dis/abled Experiences

Science.gov (United States)

Hernández-Saca, David I.; Gutmann Kahn, Laurie; Cannon, Mercedes A.

2018-01-01

The purpose of this chapter is to systematically review the research within the field of education that explicitly examined how various social constructions of identity intersect with dis/ability to qualitatively affect young adults' experiences by asking the following question: What are the key findings in education research focusing on youth and…

Functional analysis of the OCA-B promoter.

Science.gov (United States)

Stevens, S; Wang, L; Roeder, R G

2000-06-15

OCA-B was identified as a B cell-specific coactivator that functions with either Oct-1 or Oct-2 to mediate efficient cell type-specific transcription via the octamer site (ATGCAAAT) both in vivo and in vitro. Mice lacking OCA-B exhibit normal Ag-independent B cell maturation. In contrast, Ag-dependent functions, including production of secondary Ig isotypes and germinal center formation, are greatly affected. To better understand OCA-B expression and, ultimately, the defects observed in the OCA-B knockout mice, we have cloned the OCA-B promoter and examined its function in both transformed and primary B cells. We show here that the OCA-B promoter is developmentally regulated, with activity increasing throughout B cell differentiation. Through physical and functional assays, we have found an activating transcription factor/cAMP response element binding protein binding site (or cAMP response element) that is crucial for OCA-B promoter activity. Furthermore, we demonstrate that IL-4 and anti-CD40 induce both the OCA-B promoter and octamer-dependent promoters, thus implicating OCA-B in B cell signaling events in the nucleus.

49 CFR 219.13 - Preemptive effect.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Preemptive effect. 219.13 Section 219.13 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE General § 219.13 Preemptive effect. (a) Under...

45 CFR 150.219 - Final determination.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Final determination. 150.219 Section 150.219... Are Failing To Substantially Enforce HIPAA Requirements § 150.219 Final determination. If, after... the State a written notice of its final determination. The notice includes the following: (a...

DisVis: Visualizing Discussion Threads in Online Health Communities.

Science.gov (United States)

Nakikj, Drashko; Mamykina, Lena

2016-01-01

An increasing number of individuals turn to online health communities (OHC) for information, advice and support about their health condition or disease. As a result of users' active participation, these forums store overwhelming volumes of information, which can make access to this information challenging and frustrating. To help overcome this problem we designed a discussion visualization tool DisVis. DisVis includes features for overviewing, browsing and finding particular information in a discussion. In a between subjects study, we tested the impact of DisVis on individuals' ability to provide an overview of a discussion, find topics of interest and summarize opinions. The study showed that after using the tool, the accuracy of participants' answers increased by 68% (p-value = 0.023) while at the same time exhibiting trends for reducing the time to answer by 38% with no statistical significance (p-value = 0.082). Qualitative interviews showed general enthusiasm regarding tools for improving browsing and searching for information within discussion forums, suggested different usage scenarios, highlighted opportunities for improving the design of DisVis, and outlined new directions for visualizing user-generated content within OHCs.

Conceptual design report, 219-S secondary containment upgrade, Project W-178

International Nuclear Information System (INIS)

Beyer, J.J.

1993-05-01

The 219-S Facility is located in the 200-West Area on the Hanford Site and was constructed in 1951. The facility receives and treats liquid, low-level mixed waste from the 222-S Laboratory prior to transfer of that waste to the SY Tank Farm. The 219-S Facility consists of Cell A containing Tanks 101 and 102 and Cell B containing Tank 103 and a spare space. Project W-178 will modify the 219-S Facility to bring it into compliance with the tank system standards in WAC 173-303-640. The secondary containment upgrade will consist of a stainless steel cell liner in both Cell A and the spare space in Cell B. Additionally, Cell B will be modified by taking Tank 103 out of service and installing a new tank: Tank 104. The construction work will be accomplished in phases to minimize service interruption to the 222-S Laboratory. The proposed design and construction method is the most cost effective of four alternatives evaluated during a value engineering session. Project W-178 is a fiscal year 1995 Line Item. Total estimated construction costs of the project are $2,600,000; other project costs are $710,000. The total project cost is $3,300,000

49 CFR 21.9 - Compliance information.

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Compliance information. 21.9 Section 21.9 Transportation Office of the Secretary of Transportation NONDISCRIMINATION IN FEDERALLY-ASSISTED PROGRAMS OF THE DEPARTMENT OF TRANSPORTATION-EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 21.9 Compliance information. (a) Cooperation and...

20 CFR 219.35 - Evidence that a marriage has ended.

Science.gov (United States)

2010-04-01

... divorce or annulment; or (2) Evidence of the death (See § 219.23) of a party to the marriage. (b) Other..., the claimant must explain the reason therefor and submit other convincing evidence that the marriage...

36 CFR 219.4 - Identification and consideration of issues.

Science.gov (United States)

2010-07-01

... capabilities and available resources, including current and likely Forest Service budgets; (iv) The scientific... restore ecological conditions that are similar to the biological and physical range of expected variability (§ 219.20(b)(1)); and (vii) Opportunities to contribute to knowledge about and preservation of...

Adler Function, DIS sum rules and Crewther Relations

International Nuclear Information System (INIS)

Baikov, P.A.; Chetyrkin, K.G.; Kuehn, J.H.

2010-01-01

The current status of the Adler function and two closely related Deep Inelastic Scattering (DIS) sum rules, namely, the Bjorken sum rule for polarized DIS and the Gross-Llewellyn Smith sum rule are briefly reviewed. A new result is presented: an analytical calculation of the coefficient function of the latter sum rule in a generic gauge theory in order O(α s 4 ). It is demonstrated that the corresponding Crewther relation allows to fix two of three colour structures in the O(α s 4 ) contribution to the singlet part of the Adler function.

48 CFR 653.219 - Small business programs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Small business programs. 653.219 Section 653.219 Federal Acquisition Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.219 Small business programs. ...

48 CFR 52.219-9 - Small business subcontracting plan.

Science.gov (United States)

2010-10-01

... Clauses 52.219-9 Small business subcontracting plan. As prescribed in 19.708(b), insert the following clause: Small Business Subcontracting Plan (OCT 2010) (a) This clause does not apply to small business... business, and women-owned small business concerns. If the offeror is submitting an individual contract plan...

(Dis)organizing through imbrications of human and material agencies

DEFF Research Database (Denmark)

Tavella, Elena

and material agencies. However there is a lack of insight into how human and material agencies are imbricated during the emergence of (dis)order, and how different imbrications lead to (dis)order. This paper addresses this gap by presenting a content analysis of a book reporting the Battle of Stalingrad during...... World War II. Drawing on the theory of affordances, the author identifies how different materials were used by the German and Soviet armies to organize specific activities, and whether and how those activities led to order and/or disorder. The analysis suggests that soldiers used different materials...... to organize different activities within one and the same organizational context, which led to (dis)order. Whether order or disorder emerged was dependent on how human and material agencies were imbricated within the conduct of particular activities, and how they related to internal or external influencing...

DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.

Science.gov (United States)

Gándara, Carolina; Alonso, Juan C

2015-03-01

Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA, which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to elicit repair of DNA damage generated by alkyl groups and H2O2, respectively, during vegetative growth. disA forms an operon with radA (also termed sms) that encodes a protein distantly related to RecA. Among different DNA damage agents tested, only methyl methane sulfonate (MMS) affected disA null strain viability, while radA showed sensitivity to all of them. A strain lacking both disA and radA was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di-AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to repair DNA damage caused by MMS and in less extent by H2O2, while high levels of c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate cyclase, CdaS) increased cell survival. Taken together, our results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth. Copyright © 2015 Elsevier B.V. All rights reserved.

38 CFR 21.219 - Supplies consisting of clothing, magazines and periodicals, and items which may be personally...

Science.gov (United States)

2010-07-01

... clothing, magazines and periodicals, and items which may be personally used by the veteran. 21.219 Section....219 Supplies consisting of clothing, magazines and periodicals, and items which may be personally used... will be supplied. (b) Furnishing magazines and periodicals. Appropriate past issues of magazines...

On the production of clandestine dis/abled bodies

DEFF Research Database (Denmark)

Galis, Vasilis; Tzokas, Spyros; Tympas, Aristotle

paper makes a notice of this literature but moves on to discuss the co-production of technological borders and migrants with dis/abilities. In this case, dis/ability may be a cause or consequence of migration, and may become a barrier to both accessing protection and to entering a country. Nonetheless...... of policing technologies, repressive techniques and military technics. Instead, however, of staying at the technology of a fast patrolling boat with electronic eyes, we move on to show how exactly this EU electronic boat has clashed with a humble migrant floating device. We are interested...

20 CFR 219.1 - Introduction.

Science.gov (United States)

2010-04-01

... Annuity), 234 (Lump-Sum Payments), and 222 (Family Relationships), certain requirements must be met before... used as evidence. Part 222 defines and explains family relationships for which evidence requirements... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Introduction. 219.1 Section 219.1 Employees...

22 CFR 219.160 - Communications.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Communications. 219.160 Section 219.160 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN... communication with applicants, participants, personnel of other Federal entities, and members of the public. (1...

48 CFR 1353.219 - Small business programs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Small business programs. 1353.219 Section 1353.219 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CLAUSES AND FORMS FORMS Prescription of Forms 1353.219 Small business programs. Use Form CD-570, Small Business Set...

20 CFR 219.2 - Definitions.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Definitions. 219.2 Section 219.2 Employees... some other person. Benefit means any employee annuity, spouse annuity, survivor annuity, or lump-sum... proves to the satisfaction of the Board that an individual meets a requirement for eligibility for...

3-dimensional interactive space (3DIS)

International Nuclear Information System (INIS)

Veitch, S.; Veitch, J.; West, S.J.

1991-01-01

This paper reports on the 3DIS security system which uses standard CCTV cameras to create 3-Dimensional detection zones around valuable assets within protected areas. An intrusion into a zone changes light values and triggers an alarm that is annunciated, while images from multiple cameras are recorded. 3DIS lowers nuisance alarm rates and provides superior automated surveillance capability. Performance is improved over 2-D systems because activity around, above or below the zone does to cause an alarm. Invisible 3-D zones protect assets as small as a pin or as large as a 747 jetliner. Detection zones are created by excising subspaces from the overlapping fields of view of two or more video cameras. Hundred of zones may co-exist, operating simultaneously. Intrusion into any 3-D zone will cause a coincidental change in light values, triggering an alarm specific to that space

48 CFR 552.219-76 - Mentor Requirements and Evaluation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Mentor Requirements and....219-76 Mentor Requirements and Evaluation. As prescribed in 519.7017(b), insert the following clause: Mentor Requirements and Evaluation (SEP 2009) (a) The purpose of the GSA Mentor-Protégé Program is for a...

48 CFR 752.219-71 - Mentor requirements and evaluation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Mentor requirements and....219-71 Mentor requirements and evaluation. As prescribed in AIDAR 719.273-11(b), insert the following clause: Mentor Requirements and Evaluation (July 13, 2007) (a) Mentor and Protégé firms shall submit an...

Exploring the diversity of conceptualizations of work (dis)ability: a scoping review of published definitions.

Science.gov (United States)

Lederer, Valérie; Loisel, Patrick; Rivard, Michèle; Champagne, François

2014-06-01

Researchers are confronted to numerous definitions of work ability/disability, influenced by their context of emergence, discipline, purpose, underlying paradigm and relationship to time. This study provides an in-depth analysis of the concept through a systematic scoping review and the development of an integrative concept map of work (dis)ability. The research questions are: How has work (dis)ability been conceptualized from the perspectives of research, practice, policy and industry in the published scientific literature? How has the conceptualization of work (dis)ability evolved over time? A search strategy was designed with a library scientist to retrieve scientific publications containing explicit definition(s) of work (dis)ability in leading-edge databases. The screening and the extraction of the definitions were achieved by duplicate assessment. The definitions were subject to a comparative analysis based on the grounded theory approach. In total, 423 abstracts were retrieved from the bibliographic databases. After removing duplicates, 280 unique records were screened for inclusion. A final set of 115 publications containing unique original conceptual definitions served as basis for analysis. The scientific literature does not reflect a shared, integrated vision of the exact nature and dimensions of work (dis)ability. However, except for a few definitions, there seems to be a consensus that work (dis)ability is a relational concept resulting from the interaction of multiple dimensions that influence each other through different ecological levels. The conceptualization of work (dis)ability also seems to have become more dynamic over time. The way work (dis)ability is defined has important implications for research, compensation and rehabilitation.

49 CFR 1542.219 - Supplementing law enforcement personnel.

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Supplementing law enforcement personnel. 1542.219 Section 1542.219 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRPORT SECURITY Operations § 1542.219 Supplementing law...

Di-jet production and angular correlations in DIS at NLO

International Nuclear Information System (INIS)

Jaliflian-Marian, J.

2016-01-01

Angular correlations are a sensitive probe of the dynamics of QCD at high energy. In particular azimuthal angular correlations between two hadrons produced in Deeply Inelastic Scattering (DIS) of a virtual photon on a hadron or nucleus offer the best environment in which to investigate high gluon density (gluon saturation) effects expected to arise at small x. Here we give a progress report on our derivation of Next to Leading Order (NLO) corrections to di-jet (di-hadron) production in DIS. (author)

36 CFR 219.17 - Interaction with private landowners.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Interaction with private landowners. 219.17 Section 219.17 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF... Sustainability § 219.17 Interaction with private landowners. The responsible official must seek to collaborate...

Evaluation of Nitrogen Uptake and Growth Performance of Advanced Mutant Lines MR219-4 and MR219-9 Grown Under Aerobic Conditions

International Nuclear Information System (INIS)

Shyful Azizi Abdul Rahman; Abdul Rahim Harun; Rusli Ibrahim; Khairuddin Abdul Rahim

2014-01-01

Developing a good crop production management package; drought resistance variety, effective water and nutrient management in rice production practices is crucial for global climate change adaptation. A research project under IAEA RAS5065 (Supporting Climate-Proofing Rice Production Systems (CRiPS) Based on Nuclear Applications) was conducted from 2012 to 2013, in collaboration with MARDI. Two advanced mutant lines, MR219-4 and MR219-9 were used in this research project to evaluate growth, yield potential and fertilizer uptake under different water input condition (flooded and aerobic). The advanced mutant line MR219-9 showed comparable growth, yield and nitrogen uptake under both flooded and aerobic conditions. The yield and yield components are not significantly different from the parent variety (MR219) but total N uptake was lower than MR219 regardless of water regime. The field trial showed that MR219-9 has a better total N content which is comparable to the aerobic rice variety (MRIA 1) and this indicates that this advance mutant line MR219-9 is a potential aerobic rice variety. (author)

37 CFR 1.219 - Early publication.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Early publication. 1.219... COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Publication of Applications § 1.219 Early publication. Applications that will be published under § 1.211 may be published...

20 CFR 219.23 - Evidence to prove death.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence to prove death. 219.23 Section 219... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.23 Evidence to prove death. (a) Preferred evidence of death. The best evidence of a person's death is— (1) A certified copy of or extract from the...

36 CFR 219.19 - Ecological, social, and economic sustainability.

Science.gov (United States)

2010-07-01

... economic sustainability. 219.19 Section 219.19 Parks, Forests, and Public Property FOREST SERVICE..., Social, and Economic Sustainability § 219.19 Ecological, social, and economic sustainability. Sustainability, composed of interdependent ecological, social, and economic elements, embodies the Multiple-Use...

Dis3- and exosome subunit-responsive 3′ mRNA instability elements

International Nuclear Information System (INIS)

Kiss, Daniel L.; Hou, Dezhi; Gross, Robert H.; Andrulis, Erik D.

2012-01-01

Highlights: ► Successful use of a novel RNA-specific bioinformatic tool, RNA SCOPE. ► Identified novel 3′ UTR cis-acting element that destabilizes a reporter mRNA. ► Show exosome subunits are required for cis-acting element-mediated mRNA instability. ► Define precise sequence requirements of novel cis-acting element. ► Show that microarray-defined exosome subunit-regulated mRNAs have novel element. -- Abstract: Eukaryotic RNA turnover is regulated in part by the exosome, a nuclear and cytoplasmic complex of ribonucleases (RNases) and RNA-binding proteins. The major RNase of the complex is thought to be Dis3, a multi-functional 3′–5′ exoribonuclease and endoribonuclease. Although it is known that Dis3 and core exosome subunits are recruited to transcriptionally active genes and to messenger RNA (mRNA) substrates, this recruitment is thought to occur indirectly. We sought to discover cis-acting elements that recruit Dis3 or other exosome subunits. Using a bioinformatic tool called RNA SCOPE to screen the 3′ untranslated regions of up-regulated transcripts from our published Dis3 depletion-derived transcriptomic data set, we identified several motifs as candidate instability elements. Secondary screening using a luciferase reporter system revealed that one cassette—harboring four elements—destabilized the reporter transcript. RNAi-based depletion of Dis3, Rrp6, Rrp4, Rrp40, or Rrp46 diminished the efficacy of cassette-mediated destabilization. Truncation analysis of the cassette showed that two exosome subunit-sensitive elements (ESSEs) destabilized the reporter. Point-directed mutagenesis of ESSE abrogated the destabilization effect. An examination of the transcriptomic data from exosome subunit depletion-based microarrays revealed that mRNAs with ESSEs are found in every up-regulated mRNA data set but are underrepresented or missing from the down-regulated data sets. Taken together, our findings imply a potentially novel mechanism of m

Application of the Drilling Impact Study (DIS) to Forsmark groundwaters

International Nuclear Information System (INIS)

Gascoyne, Mel; Gurban, Ioana

2008-01-01

Characterisation of a geological formation as a repository for nuclear fuel waste requires deep drilling into the bedrock to gain an understanding of the geological structure, rock types, groundwater flow and the chemical composition of groundwater and the adjacent rock. The methods of characterisation from a hydrogeochemical point of view, might be affected by the various drilling activities and techniques for determining groundwater composition have been employed so that the composition can be corrected for these activities. SKB has developed and supported the Drilling Impact Study (DIS) project in which a tracer is used as an indicator of contamination to attempt to correct the groundwater composition for dilution or contamination by surface waters. The project began about five years ago with the intention of developing a routine method for determining the extent of contamination of borehole groundwater by drilling water. The main objectives of this work were: 1. Determine the extent of drilling water contamination in permeable zones in a test borehole on the Forsmark site. 2. Correct measured chemical compositions of the groundwaters based on contamination results. 3. Provide a workable methodology for routine correction of groundwater composition. 4. Apply the modified DIS model to suitable borehole zones at the Forsmark site in a systematic fashion 5. Determine uncertainties in DIS modelling. A memorandum was prepared by describing the characteristics of borehole KFM06 and its drilling history. Estimates were made of the amount of drilling water in permeable zones in the borehole and the various approaches to applying results of DIS were described and recommendations made, with an example calculation

Disability Critical Race Theory: Exploring the Intersectional Lineage, Emergence, and Potential Futures of DisCrit in Education

Science.gov (United States)

Annamma, Subini Ancy; Ferri, Beth A.; Connor, David J.

2018-01-01

In this review, we explore how intersectionality has been engaged with through the lens of disability critical race theory (DisCrit) to produce new knowledge. In this chapter, we (1) trace the intellectual lineage for developing DisCrit, (2) review the body of interdisciplinary scholarship incorporating DisCrit to date, and (3) propose the future…

Issues in leading particle and charm production in DIS at HERA

International Nuclear Information System (INIS)

Chekanov, S. V.

1999-01-01

A Monte Carlo simulation based on Ο(α s ) QCD matrix elements matched to parton showers shows that final-state hadrons in DIS can be used to tag events with a single (anti)quark recoiled against the proton. The method is particularly suited to study the mean charge of leading particles, which is sensitive to fragmentation and sea quark contribution to the proton structure function. They also discuss methods to study the charm production in DIS using the Breit frame

Dis-Equality: Exploring the Juxtaposition of Disability and Equality

Directory of Open Access Journals (Sweden)

Bronagh Byrne

2018-03-01

Full Text Available The (inequality issues facing disabled people are extensive and long-enduring. The way(s in which equality is conceptualised has important consequences for understandings of disability. The ambiguity of what I call dis-equality theory is two-fold; the apparent failure of mainstream equality theorising in, firstly, embracing disability concepts at all, and secondly, in fully incorporating the logistics of disability, particularly in relation to the social construction of such. Practices of institutional and more complex forms of discrimination are part of those deeper structures of domination and oppression which maintain disabled people in positions of disadvantage. Everyday practices, in the ‘ordinary order of things’ (Bourdieu, 2000, continue to be misrecognised as natural and taken for granted. This article critically explores the complexity of dis-equality theorising utilising a Bourdieusian lens which explicitly incorporates complex and subtle forms of discrimination, and by examining the UN Convention on the Rights of Persons with Disabilities’ approach to equality. I argue that the way forward for dis-equality theorising in today’s rights based era must be one that considers the nuances of the ‘rules of the game’ (Young, 1990 if it is to be effective in challenging the inequalities to which disabled people have long been subject.

30 CFR 219.102 - Method of payment.

Science.gov (United States)

2010-07-01

... writing to the Minerals Management Service, Minerals Revenue Management, P.O. Box 5760, Denver, Colorado... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Method of payment. 219.102 Section 219.102 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT...

The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition.

Science.gov (United States)

Moll, Lorna; Ben-Gedalya, Tziona; Reuveni, Hadas; Cohen, Ehud

2016-04-01

The discovery that the alteration of aging by reducing the activity of the insulin/IGF-1 signaling (IIS) cascade protects nematodes and mice from neurodegeneration-linked, toxic protein aggregation (proteotoxicity) raises the prospect that IIS inhibitors bear therapeutic potential to counter neurodegenerative diseases. Recently, we reported that NT219, a highly efficient IGF-1 signaling inhibitor, protects model worms from the aggregation of amyloid β peptide and polyglutamine peptides that are linked to the manifestation of Alzheimer's and Huntington's diseases, respectively. Here, we employed cultured cell systems to investigate whether NT219 promotes protein homeostasis (proteostasis) in mammalian cells and to explore its underlying mechanisms. We found that NT219 enhances the aggregation of misfolded prion protein and promotes its deposition in quality control compartments known as "aggresomes." NT219 also elevates the levels of certain molecular chaperones but, surprisingly, reduces proteasome activity and impairs autophagy. Our findings show that IGF-1 signaling inhibitors in general and NT219 in particular can promote proteostasis in mammalian cells by hyperaggregating hazardous proteins, thereby bearing the potential to postpone the onset and slow the progression of neurodegenerative illnesses in the elderly.-Moll, L., Ben-Gedalya, T., Reuveni, H., Cohen, E. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition. © FASEB.

40 CFR 86.219-94 - CVS calibration.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false CVS calibration. 86.219-94 Section 86.219-94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Later Model Year Gasoline-Fueled New Light-Duty Vehicles, New Light-Duty Trucks and New Medium-Duty...

49 CFR 173.219 - Life-saving appliances.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Life-saving appliances. 173.219 Section 173.219... Life-saving appliances. (a) A life-saving appliance, self-inflating or non-self-inflating, containing small quantities of hazardous materials that are required as part of the life-saving appliance must...

7 CFR 58.219 - High pressure pumps and lines.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false High pressure pumps and lines. 58.219 Section 58.219....219 High pressure pumps and lines. High pressure lines may be cleaned-in-place and shall be of such construction that dead ends, valves and the high pressure pumps can be disassembled for hand cleaning. The high...

PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-control Study of U.S. Military Service Members

Science.gov (United States)

2013-06-24

other relevant exposures which may influ- ence DNA methylation , such as dietary factors ( folate , vitamin B12 intake) (Fenech, 2001; Piyathilake and...ARTICLE published: 24 June 2013 doi: 10.3389/fpsyt.2013.00056 PTSD and DNA methylation in select immune function gene promoter regions: a repeated measures...largely unknown. Dis- tinct expression signatures for PTSD have been found, in particular for immune activation transcripts. DNA methylation may be

A socio-cultural reframing of science and dis/ability in education: past problems, current concerns, and future possibilities

Science.gov (United States)

Connor, David J.; Valle, Jan W.

2015-12-01

In this article we assert the value of a socio-cultural reframing of science and dis/ability in education. We begin by problematizing current issues in education pertaining to the often-unquestioned concept of dis/ability and the impact that has upon research, theory, practice, and policy. As our topic is broad, we have chosen to focus upon four interconnected areas: (1) the historical mistrust of science and pseudo-science by people with dis/abilities; (2) the pervasive use of pseudo-science within the contemporary field of special education; (3) the use of dis/ability studies in education (DSE) to provide a contrast between a traditional positivist framing and a socio-cultural framing of dis/ability, and; (4) a brief exploration of what a DSE/socio-cultural grounding looks like for both schools and classroom teachers. In sum, our intention is to engage science educators to reject deficit-notions of dis/ability in favor of understanding it as part of human variation, and consider the personal and professional benefits of this shift.

[Estimation of cost-saving for reducing radioactive waste from nuclear medicine facilities by implementing decay in storage (DIS) in Japan].

Science.gov (United States)

Kida, Tetsuo; Hiraki, Hitoshi; Yamaguchi, Ichirou; Fujibuchi, Toshioh; Watanabe, Hiroshi

2012-01-01

DIS has not yet been implemented in Japan as of 2011. Therefore, even if risk was negligible, medical institutions have to entrust radioactive temporal waste disposal to Japan Radio Isotopes Association (JRIA) in the current situation. To decide whether DIS should be implemented in Japan or not, cost-saving effect of DIS was estimated by comparing the cost that nuclear medical facilities pay. By implementing DIS, the total annual cost for all nuclear medical facilities in Japan is estimated to be decreased to 30 million yen or less from 710 million yen. DIS would save 680 million yen (96%) per year.

Estimation of cost-saving for reducing radioactive waste from nuclear medicine facilities by implementing decay in storage (DIS) in Japan

International Nuclear Information System (INIS)

Kida, Tetsuo; Hiraki, Hitoshi; Yamaguchi, Ichirou; Fujibuchi, Toshioh; Watanabe, Hiroshi

2012-01-01

DIS has not yet been implemented in Japan as of 2011. Therefore, even if risk was negligible, medical institutions have to entrust radioactive temporal waste disposal to Japan Radio Isotopes Association (JRIA) in the current situation. To decide whether DIS should be implemented in Japan or not, cost-saving effect of DIS was estimated by comparing the cost that nuclear medical facilities pay. By implementing DIS, the total annual cost for all nuclear medical facilities in Japan is estimated to be decreased to 30 million yen or less from 710 million yen. DIS would save 680 million yen (96%) per year. (author)

Radiological accidents: methodologies of radio nuclides dis incorporation; Accidentes radiologicos: metodologias de desincorporacion de radionuclidos

Energy Technology Data Exchange (ETDEWEB)

Jimenez F, E. A. [Universidad Autonoma del Estado de Mexico, Facultad de Medicina, Paseo Tollocan s/n, 50180 Toluca, Estado de Mexico (Mexico); Paredes G, L. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Cortes, A., E-mail: lydia.paredes@inin.gob.mx [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Jose Ma. Barragan No. 779, Col. Narvarte, 03020 Mexico D. F. (Mexico)

2014-08-15

Derived of the radioactive or nuclear material management, exists the risk that accidents can happen where people cases are presented with internal radioactive contamination, who will receive specialized medical care to accelerate the radioactive dis incorporation with the purpose of diminishing the absorbed dose and the associate biological effects. In this work treatments of radioactive dis incorporation were identified, in function of the radionuclide, radiation type, radioactive half life, biological half life, critical organ, ingestion duct and patient type. The factor time is decisive for the effectiveness of the selected treatment in the blockade stage (before the accident) or dis incorporation (after the accident); this factor is related with the radioactive and biological half lives. So to achieve dis incorporation efficiencies of more to 70%, the patient clinical treatment will begin before the first third of the biological half life of the radionuclide that generated the internal contamination. (Author)

48 CFR 52.219-20 - Notice of Emerging Small Business Set-Aside.

Science.gov (United States)

2010-10-01

... Clauses 52.219-20 Notice of Emerging Small Business Set-Aside. As prescribed in 19.1008(b), insert the following provision: Notice of Emerging Small Business Set-Aside (JAN 1991) Offers or quotations under this acquisition are solicited from emerging small business concerns only. Offers that are not from an emerging...

48 CFR 52.219-7 - Notice of Partial Small Business Set-Aside.

Science.gov (United States)

2010-10-01

... Clauses 52.219-7 Notice of Partial Small Business Set-Aside. As prescribed in 19.508(d), insert the following clause: Notice of Partial Small Business Set-Aside (JUN 2003) (a) Definitions. Small business..., and qualified as a small business under the size standards in this solicitation. (b) General. (1) A...

36 CFR 219.12 - Collaboration and cooperatively developed landscape goals.

Science.gov (United States)

2010-07-01

... cooperatively developed landscape goals. 219.12 Section 219.12 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PLANNING National Forest System Land and Resource Management Planning Collaborative Planning for Sustainability § 219.12 Collaboration and cooperatively developed landscape goals. (a...

48 CFR 52.219-6 - Notice of Total Small Business Set-Aside.

Science.gov (United States)

2010-10-01

... Clauses 52.219-6 Notice of Total Small Business Set-Aside. As prescribed in 19.508(c), insert the following clause: Notice of Total Small Business Set-Aside (JUN 2003) (a) Definition. Small business concern... qualified as a small business under the size standards in this solicitation. (b) General. (1) Offers are...

The Microbial DNA Index System (MiDIS): A tool for microbial pathogen source identification

Energy Technology Data Exchange (ETDEWEB)

Velsko, S. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2010-08-09

The microbial DNA Index System (MiDIS) is a concept for a microbial forensic database and investigative decision support system that can be used to help investigators identify the sources of microbial agents that have been used in a criminal or terrorist incident. The heart of the proposed system is a rigorous method for calculating source probabilities by using certain fundamental sampling distributions associated with the propagation and mutation of microbes on disease transmission networks. This formalism has a close relationship to mitochondrial and Y-chromosomal human DNA forensics, and the proposed decision support system is somewhat analogous to the CODIS and SWGDAM mtDNA databases. The MiDIS concept does not involve the use of opportunistic collections of microbial isolates and phylogenetic tree building as a basis for inference. A staged approach can be used to build MiDIS as an enduring capability, beginning with a pilot demonstration program that must meet user expectations for performance and validation before evolving into a continuing effort. Because MiDIS requires input from a a broad array of expertise including outbreak surveillance, field microbial isolate collection, microbial genome sequencing, disease transmission networks, and laboratory mutation rate studies, it will be necessary to assemble a national multi-laboratory team to develop such a system. The MiDIS effort would lend direction and focus to the national microbial genetics research program for microbial forensics, and would provide an appropriate forensic framework for interfacing to future national and international disease surveillance efforts.

Polarized 3 parton production in inclusive DIS at small x

Energy Technology Data Exchange (ETDEWEB)

Ayala, Alejandro [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Apartado Postal 70-543, Ciudad de México 04510 (Mexico); Centre for Theoretical and Mathematical Physics, and Department of Physics, University of Cape Town, Rondebosch 7700 (South Africa); Hentschinski, Martin, E-mail: hentschinski@correo.nucleares.unam.mx [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Apartado Postal 70-543, Ciudad de México 04510 (Mexico); Facultad de Ciencias Físico Matemáticas, Benemérita Universidad Autónoma de Puebla, Puebla 1152 (Mexico); Jalilian-Marian, Jamal [Department of Natural Sciences, Baruch College, CUNY, 17 Lexington Avenue, New York, NY 10010 (United States); CUNY Graduate Center, 365 Fifth Avenue, New York, NY 10016 (United States); Tejeda-Yeomans, Maria Elena [Departamento de Física, Universidad de Sonora, Boulevard Luis Encinas J. y Rosales, Colonia Centro, Hermosillo, Sonora 83000 (Mexico)

2016-10-10

Azimuthal angular correlations between produced hadrons/jets in high energy collisions are a sensitive probe of the dynamics of QCD at small x. Here we derive the triple differential cross section for inclusive production of 3 polarized partons in DIS at small x. The target proton or nucleus is described using the Color Glass Condensate (CGC) formalism. The resulting expressions are used to study azimuthal angular correlations between produced partons in order to probe the gluon structure of the target hadron or nucleus. Our analytic expressions can also be used to calculate the real part of the Next to Leading Order (NLO) corrections to di-hadron production in DIS by integrating out one of the three final state partons.

Polarized 3 parton production in inclusive DIS at small x

International Nuclear Information System (INIS)

Ayala, Alejandro; Hentschinski, Martin; Jalilian-Marian, Jamal; Tejeda-Yeomans, Maria Elena

2016-01-01

Azimuthal angular correlations between produced hadrons/jets in high energy collisions are a sensitive probe of the dynamics of QCD at small x. Here we derive the triple differential cross section for inclusive production of 3 polarized partons in DIS at small x. The target proton or nucleus is described using the Color Glass Condensate (CGC) formalism. The resulting expressions are used to study azimuthal angular correlations between produced partons in order to probe the gluon structure of the target hadron or nucleus. Our analytic expressions can also be used to calculate the real part of the Next to Leading Order (NLO) corrections to di-hadron production in DIS by integrating out one of the three final state partons.

MicroRNA-219-2-3p functions as a tumor suppressor in gastric cancer and is regulated by DNA methylation.

Directory of Open Access Journals (Sweden)

Huizi Lei

Full Text Available BACKGROUND AIMS: Gastric cancer is the most frequent gastrointestinal tumor in adults and is the most lethal form of human cancer. Despite of the improvements in treatments, the underlying mechanism of gastric carcinogenesis is not well known. To define novel modulators that regulate susceptibility to tumorgenesis, we focused on miR-219-2-3p. METHODS: Quantitative RT-PCR was employed to investigate the level of miR-219-2-3p in gastric cancer (GC tissues (n = 113 and their matched adjacent normal tissues (n = 113. In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate biological effects of miR-219-2-3p. Since silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorgenesis, GC cells were treated with 5-aza-2'-deoxycytidine and trichostatin A, and expression changes of miR-219-2-3p were subsequently examined by quantitative RT-PCR. Finally, the methylation status of CpG island upstream of miR-219-2-3p was analyzed by methylation-specific PCR in GC tissues (n = 22. RESULTS: miR-219-2-3p was down-regulated in GC and cell lines. In addition, the experiments documented the lower expression of miR-219-2-3p in GC specimens with higher grade and later stage tumors. Meanwhile, miR-219-2-3p exerted antiproliferative, proapoptotic, and antimetastatic roles and reduced levels of p-ERK1/2 in GC cells. Furthermore, 5-aza-2'-deoxycytidine and trichostatin A increased the expression (~2 fold of miR-219-2-3p in GC cells. By methylation-specific PCR, DNA methylation in the upstream region of miR-219-2-3p was detected in both adjacent normal tissues and cancer tissues. As expected, the methylation level was considerably higher in the miR-219-2-3p down-regulated group than up-regulated group. CONCLUSIONS: miR-219-2-3p is potentially involved in gastric cancer progression and metastasis by regulating ERK1/2-related signal pathways, which may provide a novel therapeutic strategy

Talking (and Not Talking) about Race, Social Class and Dis/Ability: Working Margin to Margin

Science.gov (United States)

Ferri, Beth A.; Connor, David J.

2014-01-01

In this article we examine some of the omnipresent yet unacknowledged discourses of social and economic disadvantage and dis/ability within schools in the US. First, we document ways that social class, race, and dis/ability function within schools to further disadvantage and exclude already marginalized students. Next, we show how particular ways…

Polarized 3 parton production in inclusive DIS at small x

Directory of Open Access Journals (Sweden)

Alejandro Ayala

2016-10-01

Full Text Available Azimuthal angular correlations between produced hadrons/jets in high energy collisions are a sensitive probe of the dynamics of QCD at small x. Here we derive the triple differential cross section for inclusive production of 3 polarized partons in DIS at small x. The target proton or nucleus is described using the Color Glass Condensate (CGC formalism. The resulting expressions are used to study azimuthal angular correlations between produced partons in order to probe the gluon structure of the target hadron or nucleus. Our analytic expressions can also be used to calculate the real part of the Next to Leading Order (NLO corrections to di-hadron production in DIS by integrating out one of the three final state partons.

Advancement in Watershed Modelling Using Dynamic Lateral and Longitudinal Sediment (Dis)connectivity Prediction

Science.gov (United States)

Mahoney, D. T.; al Aamery, N. M. H.; Fox, J.

2017-12-01

The authors find that sediment (dis)connectivity has seldom taken precedence within watershed models, and the present study advances this modeling framework and applies the modeling within a bedrock-controlled system. Sediment (dis)connectivity, defined as the detachment and transport of sediment from source to sink between geomorphic zones, is a major control on sediment transport. Given the availability of high resolution geospatial data, coupling sediment connectivity concepts within sediment prediction models offers an approach to simulate sediment sources and pathways within a watershed's sediment cascade. Bedrock controlled catchments are potentially unique due to the presence of rock outcrops causing longitudinal impedance to sediment transport pathways in turn impacting the longitudinal distribution of the energy gradient responsible for conveying sediment. Therefore, the authors were motivated by the need to formulate a sediment transport model that couples sediment (dis)connectivity knowledge to predict sediment flux for bedrock controlled catchments. A watershed-scale sediment transport model was formulated that incorporates sediment (dis)connectivity knowledge collected via field reconnaissance and predicts sediment flux through coupling with the Partheniades equation and sediment continuity model. Sediment (dis)connectivity was formulated by coupling probabilistic upland lateral connectivity prediction with instream longitudinal connectivity assessments via discretization of fluid and sediment pathways. Flux predictions from the upland lateral connectivity model served as an input to the instream longitudinal connectivity model. Disconnectivity in the instream model was simulated via the discretization of stream reaches due to barriers such as bedrock outcroppings and man-made check dams. The model was tested for a bedrock controlled catchment in Kentucky, USA for which extensive historic water and sediment flux data was available. Predicted sediment

12 CFR 219.1 - Authority, purpose and scope.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Authority, purpose and scope. 219.1 Section 219.1 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM REIMBURSEMENT FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS...

Quark-antiquark production in DIS diffractive dissociation

International Nuclear Information System (INIS)

Bartels, J.; Lotter, H.; Wuesthoff, M.

1996-02-01

We calculate the cross section for the production of two jets with large transverse momenta k 2 in DIS diffractive dissociation for both transverse and longitudinally polarized photons. The scale which defines the hardness of the Pomeron is found to be k 2 (Q 2 +M 2 )/M 2 . We present analytic expressions and discuss numerical results relevant for the diffractive dissociation at HERA. (orig.)

Polarized DIS Structure Functions from Neural Networks

International Nuclear Information System (INIS)

Del Debbio, L.; Guffanti, A.; Piccione, A.

2007-01-01

We present a parametrization of polarized Deep-Inelastic-Scattering (DIS) structure functions based on Neural Networks. The parametrization provides a bias-free determination of the probability measure in the space of structure functions, which retains information on experimental errors and correlations. As an example we discuss the application of this method to the study of the structure function g 1 p (x,Q 2 )

Evaluation and characterization of advanced rice mutant line of rice (Oryza sativa), MR219-4 and MR219-9 under drought condition

International Nuclear Information System (INIS)

Abdul Rahim Harun; Zarith Shafika Kamarudin; Abdullah, M.Z.; Anna, L.P.K.; Sobri Hussain; Rusli Ibrahim; Khairuddin abdul Rahim

2012-01-01

Two advance rice mutant lines, MR219-4 and MR219-9 derived from mutagenesis of Oryza sativa cv. MR219 with gamma radiation at 300 Gy were evaluated in simulated drought condition in the greenhouse at Malaysian Nuclear Agency. The mutants were evaluated simultaneously with ARN1, a drought resistant variety and MR211 a susceptible cultivar as a check. Randomized complete block design with three replicates was used in the experiment. The evaluation and selection were done based on leaf rolling and leaf drying as well as other agronomic traits, such as, number of tillers per plant, plant height, flag leaf area, grain weight per plant, grain yield per plant, 100-grain weight, harvest index, panicle length and plant biomass. The mutants MR219-4 showed moderate tolerance and MR219-9 showed tolerance to drought respectively as compare to the check variety (ARN1, MR211) and control MR219. Leaf rolling, leaf drying, days to flowering and days to maturity are valuable secondary traits that may provide additional information for selection because of associating with the plant survival under water stress. Further research on expression of drought-tolerant lines under different drought conditions is essential in order to identify particular traits that are associated with drought tolerance and high yield potential. Similarly the importance of secondary traits, relative to other putative traits for drought tolerance, needs to be tested in various environments. (author)

Radiological risk of actinon (219Rn)

International Nuclear Information System (INIS)

Crawford, D.J.

1981-12-01

The research reported was designed to provide information on the following subjects: (1) development of the functional relations between exposure to the 219 Rn decay chain and pertinent health effects; (2) specification of the circumstances under which a significant concentration of the decay chain may occur; (3) recommendation of an exposure standard which will provide protection of the public from significant elevation of health effects; and (4) an assessment of the impact of 219 Rn on determinations of the concentration of the 222 Rn decay chain and/or its precursors

14 CFR 21.9 - Replacement and modification articles.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to be...

20 CFR 219.43 - Evidence of child's dependency.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of child's dependency. 219.43... EVIDENCE REQUIRED FOR PAYMENT Evidence of Relationship § 219.43 Evidence of child's dependency. (a) When the dependency requirement must be met. Usually the dependency requirement must be met at one of the...

48 CFR 3052.219-71 - DHS mentor-protégé program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false DHS mentor-protégÃ... CONTRACT CLAUSES Text of Provisions and Clauses 3052.219-71 DHS mentor-protégé program. As prescribed in (HSAR) 48 CFR 3019.708-70(b), insert the following clause: DHS Mentor-Protégé Program (JUN 2006) (a...

Planning in All its (Dis)guises: Spheres of Government, Functional ...

African Journals Online (AJOL)

Planning in All its (Dis)guises: Spheres of Government, Functional Areas and ... Draft legislation such as the Spatial Planning and Land Use Management Bill ... of co-operative government where uncertainty and conflict exist is examined, ...

48 CFR 352.219-71 - Mentor-protégé program reporting requirements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Mentor-protégé program... Clauses 352.219-71 Mentor-protégé program reporting requirements. As prescribed in 319.270-1(b), the Contracting Officer shall insert the following clause: Mentor-Protégé Program Reporting Requirements (January...

20 CFR 219.24 - Evidence of presumed death.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of presumed death. 219.24 Section... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.24 Evidence of presumed death. When a person cannot be proven dead but evidence of death is needed, the Board may presume he or she died at a certain...

the organizing principle at the interface of biological (dis)order

Indian Academy of Sciences (India)

Complexity: the organizing principle at the interface of biological (dis)order ... in a quantifiable fashion, as the amount of information, an informatic template ... We propose that the complexity of living systems can be understood through two ...

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

DEFF Research Database (Denmark)

Kocerha, Jannet; Faghihi, Mohammad Ali; Lopez-Toledano, Miguel A

2009-01-01

significantly modulated behavioral responses associated with disrupted NMDA receptor transmission. Furthermore, pretreatment with the antipsychotic drugs haloperidol and clozapine prevented dizocilpine-induced effects on miR-219. Taken together, these data support an integral role for miR-219 in the expression...

Performances of Student Activism: Sound, Silence, Gender, and Dis/ability

Science.gov (United States)

Pasque, Penny A.; Vargas, Juanita Gamez

2014-01-01

This chapter explores the various performances of activism by students through sound, silence, gender, and dis/ability and how these performances connect to social change efforts around issues such as human trafficking, homeless children, hunger, and children with varying abilities.

DIS - The Next Generation: A perspective for European Space Programmes

NARCIS (Netherlands)

Jense, G.J.; Kuijpers, N.H.L.

1996-01-01

During the past decade, requirements within the US defence community for simulation-based tools to support acquisition, planning, (team) training, and analysis, have resulted in a standard for distributed simulation known as DIS (Distributed Interactive Simulation). The potential advantages of

DIS - the next generation : a perspective for European space programmes

NARCIS (Netherlands)

Jense, Hans; Kuijpers, N.H.L.

1996-01-01

During the past decade, requirements within the US defence community for simulation-based tools to support acquisition, planning, (team) training, and analysis, have resulted in a standard for distributed simulation known as DIS (Distributed Interactive Simulation). The potential advantages of

Project management plan for Project W-178, 219-S secondary containment

International Nuclear Information System (INIS)

Buckles, D.I.

1995-01-01

This Project Management Plan (PMP) establishes the organizational responsibilities, control systems, and procedures for managing the execution of project activities for Project W-178, the 219-S Secondary Containment Upgrade. The scope of this project will provide the 219-S Facility with secondary containment for all tanks and piping systems. Tank 103 will be replaced with a new tank which will be designated as Tank 104. Corrosion protection shall be installed as required. The cells shall be cleaned and the surface repaired as required. The 219-S Waste Handling Facility (219-S Facility), located in the 200 West Area, was constructed in 1951 to support the 222-S Laboratory Facility. The 219-S Facility has three tanks, TK-101, TK-102, and TK-103, which receive and neutralize low level radioactive wastes from the 222-S Laboratory. For purposes of the laboratory, the different low level waste streams have been designated as high activity and intermediate activity. The 219-S Facility accumulates and treats the liquid waste prior to transferring it to SY Tank Farm in the 200-W Area. Transfers are normally made by pipeline from the 219-S Facility to the 241-SY Tank Farm. Presently transfers are being made by tanker truck to the 200-E Area Tank Farms due to the diversion box catch tank which has been removed from service

48 CFR 552.219-72 - Preparation, Submission, and Negotiation of Subcontracting Plans.

Science.gov (United States)

2010-10-01

..., and Negotiation of Subcontracting Plans. 552.219-72 Section 552.219-72 Federal Acquisition Regulations... Text of Provisions and Clauses 552.219-72 Preparation, Submission, and Negotiation of Subcontracting... Negotiation of Subcontracting Plans (JUN 2005) (a) An offeror, other than a small business concern, submitting...

49 CFR 219.207 - Fatality.

Science.gov (United States)

2010-10-01

... TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.207 Fatality. (a) In the..., United States Code (but not the agent of the Secretary for purposes of the Federal Tort Claims Act...

48 CFR 1852.219-73 - Small business subcontracting plan.

Science.gov (United States)

2010-10-01

... Provisions and Clauses 1852.219-73 Small business subcontracting plan. As prescribed in 1819.708-70(a), insert the following provision: Small Business Subcontracting Plan (MAY 1999) (a) This provision is not... contain FAR clause 52.219-9, “Small Business Subcontracting Plan.” The apparent low bidder must submit the...

36 CFR 219.15 - Interaction with American Indian tribes and Alaska Natives.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Interaction with American Indian tribes and Alaska Natives. 219.15 Section 219.15 Parks, Forests, and Public Property FOREST... Collaborative Planning for Sustainability § 219.15 Interaction with American Indian tribes and Alaska Natives...

Radiological risk of actinon (/sup 219/Rn)

Energy Technology Data Exchange (ETDEWEB)

Crawford, D.J.

1981-12-01

The research reported was designed to provide information on the following subjects: (1) development of the functional relations between exposure to the /sup 219/Rn decay chain and pertinent health effects; (2) specification of the circumstances under which a significant concentration of the decay chain may occur; (3) recommendation of an exposure standard which will provide protection of the public from significant elevation of health effects; and (4) an assessment of the impact of /sup 219/Rn on determinations of the concentration of the /sup 222/Rn decay chain and/or its precursors.

Comment: 219 [Taxonomy Icon

Lifescience Database Archive (English)

Full Text Available Japanese medaka Oryzias latipes Oryzias_latipes_L.png 219.png Taxonomy icon (c) Database Center for Life Sci...ence licensed under CC Attribution2.1 Japan アイコン:メダカ HNI-Ⅱ系統バージョン bando 2010/02/15 15:31:07 2010/02/16 09:53:27 ...

43 CFR 2.19 - When will bureaus waive fees?

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false When will bureaus waive fees? 2.19 Section... OF INFORMATION ACT Requests for Records under the FOIA § 2.19 When will bureaus waive fees? (a) Fees... section and appendix D to this part. The burden is on you to justify entitlement to a fee waiver. Requests...

36 CFR 219.1 - Purpose.

Science.gov (United States)

2010-07-01

... System Land and Resource Management Planning Purpose and Principles § 219.1 Purpose. (a) Land and... management of these lands. (3) Sustainability, composed of interdependent ecological, social, and economic elements, embodies the principles of multiple-use and sustained-yield without impairment to the...

Pion content of the nucleon in polarized semi-inclusive DIS

Energy Technology Data Exchange (ETDEWEB)

Melnitchouk, W. [Univ. of Regensburg (Germany); Thomas, A.W. [Univ. of Adelaide (Australia)

1994-04-01

An explicit pionic component of the nucleon may be identified by measuring polarized {Delta}{sup ++} fragments produced in deep-inelastic scattering (DIS) off polarized protons. The pion-exchange model predicts highly correlated polarizations of the {Delta}{sup ++} and target proton, in marked contrast with the competing diquark fragmentation process.

Velocidad de crecimiento de grietas por corrosión bajo tensión en soldaduras disímiles

Directory of Open Access Journals (Sweden)

Fernández, María del Pilar

2000-02-01

Full Text Available Dissimilar welds, used to join different sections in light water reactors, are potentially susceptible to stress corrosion cracking (SCC in aqueous mediums characteristic of nuclear plants. However, the study of these welds has been limited to evaluating the weld material susceptibility in these mediums. Little scarce data are available on crack growth rates due, fundamentally, to inadequate testing techniques. In order to address this lack of information the crack growth rate at the interface of ferritic SA533B-1 alloy and alloy 1-82, in a dissimilar weld (SA533B-1/I-82/316L, was studied. Experiments were conducted in water at 288 °C, 8 ppm of O₂ and 1 μS/cm conductivity.

Las soldaduras disímiles, que son utilizadas para unir diferentes partes en los reactores de agua ligera, son potencialmente susceptibles de experimentar corrosión bajo tensión (SCC en los medios acuosos característicos de las plantas nucleares. Sin embargo, el estudio de estas soldaduras ha estado limitado a evaluar en dichos medios la susceptibilidad a SCC de los materiales que componen las mismas por separado, existiendo pocos datos de velocidad de crecimiento de grietas debido fundamentalmente a la falta de estandarización de este tipo de ensayos. En este trabajo se ha pretendido determinar la velocidad de crecimiento de grietas en la interfase formada por el acero ferrítico SA533B-1y la aleación I-82 dentro de la soldadura disímil compuesta por el acero SA533B-1/I-82/316L en unas condiciones de química del agua correspondientes a 8 ppm de O₂, una conductividad de 1 μS/cm y a una temperatura de 288 °C.

Health Promotion, Governmentality and the Challenges of Theorizing Pleasure and Desire

DEFF Research Database (Denmark)

Karlsen, Mads Peter; Villadsen, Kaspar

2015-01-01

to foster a ‘well-balanced subject’ straddling pleasure and asceticism. The article seeks to develop the Foucauldian analytical framework by foregrounding a strategy of subjectivation that integrates desire, pleasure and enjoyment into health promotion. The point of departure is the overwhelming emphasis......, in order to analyse the transformation of interpellation in recent health promotion, we must recognize the mechanism of self-distance or dis-identification as an integral part of the procedure of subjectification....

48 CFR 2452.219-70 - Small business subcontracting plan compliance.

Science.gov (United States)

2010-10-01

... of Provisions and Clauses 2452.219-70 Small business subcontracting plan compliance. As prescribed in 2419.708(d), insert the following provision: Small Business Subcontracting Plan Compliance (FEB 2006... the clause at FAR 52.219-9, Small Business Subcontracting Plan. (c) The government will consider...

25 CFR 166.219 - How do I acquire a permit through negotiation?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How do I acquire a permit through negotiation? 166.219 Section 166.219 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GRAZING PERMITS Permit Requirements Obtaining A Permit § 166.219 How do I acquire a permit through negotiation? (a) Permits may be negotiated and granted by th...

Safety, efficacy, and intraoperative characteristics of DisCoVisc and Healon ophthalmic viscosurgical devices for cataract surgery

Directory of Open Access Journals (Sweden)

Modi SS

2011-09-01

Full Text Available Satish S Modi1, James A Davison2, Tom Walters3 1Seeta Eye Centers, Poughkeepsie, NY, USA; 2Wolfe Clinic, Marshalltown, IA, USA; 3Texas Eye Care, Austin, TX, USA Purpose: To evaluate the safety and efficacy of DisCoVisc ophthalmic viscosurgical device (OVD, Alcon Laboratories, Inc with respect to a comparator, Healon OVD (Advanced Medical Optics, Inc. Patients and methods: In this prospective study, patients with cataracts were randomized to an OVD, and then received phacoemulsification and injection of an intraocular lens. After each surgery, unmasked investigators completed subjective questionnaires about OVD characteristics during each stage of the procedure. Masked technicians evaluated objective safety parameters of intraocular pressure (IOP and endothelial cell density, with 90 days of follow-up. Results: The DisCoVisc OVD group (128 eyes and the Healon OVD group (121 eyes had statistically similar outcomes for IOP and for endothelial cell loss. Subjectively assessed viscosity was statistically different (P < 0.0001, with Healon OVD most often rated “cohesive” and DisCoVisc OVD most often rated “both dispersive and cohesive”. Workspace maintenance differed between groups (P < 0.0001, with workspace most frequently rated “full chamber maintained” when using DisCoVisc OVD and most frequently rated “workspace maintained” when using Healon OVD. “Flat” or “shallow” workspace ratings occurred only in the Healon OVD group. Conclusion: DisCoVisc OVD had both cohesive and dispersive properties, and was safe and effective for every stage of cataract surgery. Keywords: cataract, endothelial cell density, viscoelastic, phacoemulsification

48 CFR 219.800 - General.

Science.gov (United States)

2010-10-01

... (Acquisition, Technology, and Logistics) its authority under paragraph 8(a)(1)(A) of the Small Business Act (15... DEFENSE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Contracting With the Small Business Administration (The 8(a) Program) 219.800 General. (a) By Partnership Agreement (PA) between the Small Business...

A Socio-Cultural Reframing of Science and Dis/ability in Education: Past Problems, Current Concerns, and Future Possibilities

Science.gov (United States)

Connor, David J.; Valle, Jan W.

2015-01-01

In this article we assert the value of a socio-cultural reframing of science and dis/ability in education. We begin by problematizing current issues in education pertaining to the often-unquestioned concept of dis/ability and the impact that has upon research, theory, practice, and policy. As our topic is broad, we have chosen to focus upon four…

20 CFR 219.30 - When evidence of marriage is required.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When evidence of marriage is required. 219.30... EVIDENCE REQUIRED FOR PAYMENT Evidence of Relationship § 219.30 When evidence of marriage is required. (a) When an application is filed for benefits. Documentary evidence of marriage is required when an...

Network protocol changes can improve DisCom WAN performance : evaluating TCP modifications and SCTP in the ASC tri-lab environment.

Energy Technology Data Exchange (ETDEWEB)

Tolendino, Lawrence F.; Hu, Tan Chang

2005-06-01

The Advanced Simulation and Computing (ASC) Distance Computing (DisCom) Wide Area Network (WAN) is a high performance, long distance network environment that is based on the ubiquitous TCP/IP protocol set. However, the Transmission Control Protocol (TCP) and the algorithms that govern its operation were defined almost two decades ago for a network environment vastly different from the DisCom WAN. In this paper we explore and evaluate possible modifications to TCP that purport to improve TCP performance in environments like the DisCom WAN. We also examine a much newer protocol, SCTP (Stream Control Transmission Protocol) that claims to provide reliable network transport while also implementing multi-streaming, multi-homing capabilities that are appealing in the DisCom high performance network environment. We provide performance comparisons and recommendations for continued development that will lead to network communications protocol implementations capable of supporting the coming ASC Petaflop computing environments.

20 CFR 219.33 - Evidence of a deemed valid marriage.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of a deemed valid marriage. 219.33... EVIDENCE REQUIRED FOR PAYMENT Evidence of Relationship § 219.33 Evidence of a deemed valid marriage. (a) Preferred evidence. Preferred evidence of a deemed valid marriage is— (1) Evidence of a ceremonial marriage...

20 CFR 219.32 - Evidence of a common-law marriage.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of a common-law marriage. 219.32... EVIDENCE REQUIRED FOR PAYMENT Evidence of Relationship § 219.32 Evidence of a common-law marriage. (a) Preferred evidence. Evidence of a common-law marriage must give the reasons why the informant believes that...

Short-range and long-range correlations in DIS at HERA

International Nuclear Information System (INIS)

Chekanov, S. V.; Zawiejski, L.

1999-01-01

Correlations in deep-inelastic scattering (DIS) at HERA are investigated in order to test perturbative QCD and quark fragmentation universality. Two-particle correlations at small angular separations are measured in the Breit frame and compared to e + e - collisions. Also presented are the correlations between the current and target regions of the Breit frame

Association between ε2/3/4, Promoter Polymorphism (−491A/T, −427T/C, and −219T/G at the Apolipoprotein E Gene, and Mental Retardation in Children from an Iodine Deficiency Area, China

Directory of Open Access Journals (Sweden)

Jun Li

2014-01-01

Full Text Available Background. Several common single-nucleotide polymorphisms (SNPs at apolipoprotein E (ApoE have been linked with late onset sporadic Alzheimer’s disease and declining normative cognitive ability in elder people, but we are unclear about their relationship with cognition in children. Results. We studied -491A/T, -427T/C, and -219G/T promoter polymorphisms and ε2/ε3/ε4 at ApoE among children with mental retardation (MR, n=130, borderline MR (n=124, and controls (n=334 from an iodine deficiency area in China. The allelic and genotypic distribution of individual locus did not significantly differ among three groups with Mantel-Haenszel χ2 test (P>0.05. However, frequencies of haplotype of -491A/-427T/-219T/ε4 were distributed as MR > borderline MR > controls (P uncorrected = 0.004, indicating that the presence of this haplotype may increase the risk of disease. Conclusions. In this large population-based study in children, we did not find any significant association between single locus of the four common ApoE polymorphisms (-491A/T, -427T/C, -219T/G, and ε2/3/4 and MR or borderline MR. However, we found that the presence of ATTε4 haplotype was associated with an increased risk of MR and borderline MR. Our present work may help enlarge our knowledge of the cognitive role of ApoE across the lifespan and the mechanisms of human cognition.

Time evolution of hadronization and grey tracks in DIS off nuclei

International Nuclear Information System (INIS)

Ciofi degli Atti, C.; Kopeliovich, B.Z.

2005-01-01

The analysis of the grey tracks produced in deep inelastic scattering (DIS) off nuclei provides important information on the space-time development of hadronization in nuclear medium. This method is complementary to the measurement of nuclear attenuation of leading inclusive hadrons. While the latter is focused on the hadronization dynamics for the quite rare process of leading hadrons production, the former covers the main bulk of inelastic events, and its Q 2 dependence is a very sensitive tool to discriminate between different models of hadronization. Employing the model of perturbative hadronization developed earlier, we calculate the Q 2 and x Bj dependences of the number of collisions and relate it to the mean number of grey tracks, using an empirical relation obtained from the analysis of data from the Fermilab E665 experiment on DIS of muons off the Xe nucleus. We found the number of grey tracks to rise steeply with Q 2 in good agreement with the experimental data

36 CFR 219.36 - Definitions.

Science.gov (United States)

2010-07-01

... Forest System Land and Resource Management Planning Definitions § 219.36 Definitions. Definitions of the... vision for a specific area of land or type of land within the plan area. Statements of desired conditions... species of plants or animals which are not indigenous to an area but valued for their contribution to...

Exonuclease hDIS3L2 specifies an exosome-independent 3'-5' degradation pathway of human cytoplasmic mRNA

DEFF Research Database (Denmark)

Lubas, Michal Szymon; Damgaard, Christian Kroun; Tomecki, Rafal

2013-01-01

Turnover of mRNA in the cytoplasm of human cells is thought to be redundantly conducted by the monomeric 5'-3' exoribonuclease hXRN1 and the 3'-5' exoribonucleolytic RNA exosome complex. However, in addition to the exosome-associated 3'-5' exonucleases hDIS3 and hDIS3L, the human genome encodes...

Gluon saturation: Survival probability for leading neutrons in DIS

International Nuclear Information System (INIS)

Levin, Eugene; Tapia, Sebastian

2012-01-01

In this paper we discuss the example of one rapidity gap process: the inclusive cross sections of the leading neutrons in deep inelastic scattering with protons (DIS). The equations for this process are proposed and solved, giving the example of theoretical calculation of the survival probability for one rapidity gap processes. It turns out that the value of the survival probability is small and it decreases with energy.

[Promotion effects of vitamin B12 on the degradation of 2, 4, 4'-trichlorobiphenyl by Nostoc PD-2].

Science.gov (United States)

Liu, Jia-Yu; Xiao, Wen-Feng; Lu, Li-Ping; Zhang, Hang-Jun

2014-08-01

Polychlorinated biphenyls are typical persistent chlorinated organic compounds in the environment. Bioremediation of PCB-contaminated environment has become one of the hot issues. In this study, vitamin B12 (VB12) and chlorine-free culture medium were applied to study the effects of VB12 on the degradation of 2,4,4'-trichlorobiphenyl (PCB28) by Nostoc PD-2 and the gene expression during the PCB-degradation process. Results showed that addition of different concentrations of vitamin B12 could improve the PCB-biodegradation rates by Nostoc PD-2. Compared with the control group, the 7-day degradation rate in 10 microg x L(-1), 100 microg x L(-1), and 1 000 microg x L(-1) VB12-treated groups increased by 11.0%, 19.7%, and 21.9% , respectively. The degradation half-time decreased from 5.53 days (treated with 10 microg x L(-1) VB12) to 3.08 days (treated with 100 microg x L(-1) VB12). The expression of cytochrome b6f complex iron-sulfur protein gene and dioxygenase gene showed significant correlation with PCB28-degradation by Nostoc PD-2. While the expression of iron-sulfur protein gene showed more significant correlation with PCB28-degradation. Results in this study indicated that adding VB12 could promote PCB28-degradation by Nostoc PD-2. Moreover, VB12 addition improved the PCB-degradation activity of Nostoc PD-2 at the gene level. The above conclusions could provide a new choice for developing efficient bioremediation technology for PCB-contaminated environment and a new insight into the PCB-biodegradation mechanism by Nostoc PD-2.

49 CFR 219.5 - Definitions.

Science.gov (United States)

2010-10-01

... TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE General § 219.5 Definitions. As used in this part— Accident or... alcohol) that has known mind- or function-altering effects on a human subject, specifically including any... ownership or control of the railroad and not operated or staffed by a salaried officer or employee of the...

40 CFR 80.219 - Designation and downstream requirements for GPA gasoline.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Designation and downstream requirements for GPA gasoline. 80.219 Section 80.219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... sold or dispensed for use in motor vehicles at a retail outlet or wholesale purchaser-consumer facility...

20 CFR 219.42 - When evidence of child's dependency is required.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When evidence of child's dependency is required. 219.42 Section 219.42 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... child's dependency is required. Evidence of a child's dependency on the employee is required when— (a...

48 CFR 1552.219-71 - Procedures for Participation in the EPA Mentor-Protege Program.

Science.gov (United States)

2010-10-01

... Participation in the EPA Mentor-Protege Program. 1552.219-71 Section 1552.219-71 Federal Acquisition Regulations... Texts of Provisions and Clauses 1552.219-71 Procedures for Participation in the EPA Mentor-Protege... EPA Mentor-Protege Program (OCT 2000) (a) This provision sets forth the procedures for participation...

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

DEFF Research Database (Denmark)

Klein, Ditte Kjærsgaard; Hoffmann, Saskia; Ahlskog, Johanna K

2015-01-01

an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme...... that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein...

Scripted Curriculum: What Movies Teach about Dis/ability and Black Males

Science.gov (United States)

Agosto, Vonzell

2014-01-01

Background/Context: Tropes of dis/ability in the movies and master-narratives of Black males in education and society are typically treated in isolation. Furthermore, education research on Hollywood movies has typically focused on portrayals of schools, principals, and teachers even though education professionals are exposed to a broader range of…

12 CFR 219.6 - Payment procedures.

Science.gov (United States)

2010-01-01

... obtain payment of costs incurred prior to the time the financial institution receives this notice. [Reg... PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S) Reimbursement to Financial Institutions for Providing Financial Records § 219.6 Payment procedures. (a) Notice...

36 CFR 219.20 - Ecological sustainability.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Ecological sustainability... Sustainability § 219.20 Ecological sustainability. To achieve ecological sustainability, the responsible official... diversity and species diversity are components of ecological sustainability. The planning process must...

Isolation and functional characterization of Lycopene β-cyclase (CYC-B promoter from Solanum habrochaites

Directory of Open Access Journals (Sweden)

Chinnusamy Viswanathan

2010-04-01

Full Text Available Abstract Background Carotenoids are a group of C40 isoprenoid molecules that play diverse biological and ecological roles in plants. Tomato is an important vegetable in human diet and provides the vitamin A precursor β-carotene. Genes encoding enzymes involved in carotenoid biosynthetic pathway have been cloned. However, regulation of genes involved in carotenoid biosynthetic pathway and accumulation of specific carotenoid in chromoplasts are not well understood. One of the approaches to understand regulation of carotenoid metabolism is to characterize the promoters of genes encoding proteins involved in carotenoid metabolism. Lycopene β-cyclase is one of the crucial enzymes in carotenoid biosynthesis pathway in plants. Its activity is required for synthesis of both α-and β-carotenes that are further converted into other carotenoids such as lutein, zeaxanthin, etc. This study describes the isolation and characterization of chromoplast-specific Lycopene β-cyclase (CYC-B promoter from a green fruited S. habrochaites genotype EC520061. Results A 908 bp region upstream to the initiation codon of the Lycopene β-cyclase gene was cloned and identified as full-length promoter. To identify promoter region necessary for regulating developmental expression of the ShCYC-B gene, the full-length promoter and its three different 5' truncated fragments were cloned upstream to the initiation codon of GUS reporter cDNA in binary vectors. These four plant transformation vectors were separately transformed in to Agrobacterium. Agrobacterium-mediated transient and stable expression systems were used to study the GUS expression driven by the full-length promoter and its 5' deletion fragments in tomato. The full-length promoter showed a basal level activity in leaves, and its expression was upregulated > 5-fold in flowers and fruits in transgenic tomato plants. Deletion of -908 to -577 bp 5' to ATG decreases the ShCYC-B promoter strength, while deletion of -908

27 CFR 28.219 - Return of wine withdrawn for export with benefit of drawback.

Science.gov (United States)

2010-04-01

... Exportation of Wine With Benefit of Drawback § 28.219 Return of wine withdrawn for export with benefit of... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Return of wine withdrawn for export with benefit of drawback. 28.219 Section 28.219 Alcohol, Tobacco Products and Firearms...

The etiology of mathematical and reading (dis)ability covariation in a sample of Dutch twins.

Science.gov (United States)

Markowitz, Ezra M; Willemsen, Gonneke; Trumbetta, Susan L; van Beijsterveldt, Toos C E M; Boomsma, Dorret I

2005-12-01

The genetic etiology of mathematical and reading (dis)ability has been studied in a number of distinct samples, but the true nature of the relationship between the two remains unclear. Data from the Netherlands Twin Register was used to determine the etiology of the relationship between mathematical and reading (dis)ability in adolescent twins. Ratings of mathematical and reading problems were obtained from parents of over 1500 twin pairs. Results of bivariate structural equation modeling showed a genetic correlation around .60, which explained over 90% of the phenotypic correlation between mathematical and reading ability. The genetic model was the same for males and females.

48 CFR 219.702 - Statutory requirements.

Science.gov (United States)

2010-10-01

..., DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS The Small Business Subcontracting Program 219.702 Statutory requirements. (1) Section 834 of Public Law 101-189, as amended (15 U.S.C. 637... on a corporate, division, or plant-wide basis will reduce administrative burdens while enhancing...

Template Dimerization Promotes an Acceptor Invasion-Induced Transfer Mechanism during Human Immunodeficiency Virus Type 1 Minus-Strand Synthesis

Science.gov (United States)

Balakrishnan, Mini; Roques, Bernard P.; Fay, Philip J.; Bambara, Robert A.

2003-01-01

The biochemical mechanism of template switching by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the role of template dimerization were examined. Homologous donor-acceptor template pairs derived from the HIV-1 untranslated leader region and containing the wild-type and mutant dimerization initiation sequences (DIS) were used to examine the efficiency and distribution of transfers. Inhibiting donor-acceptor interaction was sufficient to reduce transfers in DIS-containing template pairs, indicating that template dimerization, and not the mere presence of the DIS, promotes efficient transfers. Additionally, we show evidence that the overall transfer process spans an extended region of the template and proceeds through a two-step mechanism. Transfer is initiated through an RNase H-facilitated acceptor invasion step, while synthesis continues on the donor template. The invasion then propagates towards the primer terminus by branch migration. Transfer is completed with the translocation of the primer terminus at a site distant from the invasion point. In our system, most invasions initiated before synthesis reached the DIS. However, transfer of the primer terminus predominantly occurred after synthesis through the DIS. The two steps were separated by 60 to 80 nucleotides. Sequence markers revealed the position of primer terminus switch, whereas DNA oligomers designed to block acceptor-cDNA interactions defined sites of invasion. Within the region of homology, certain positions on the template were inherently more favorable for invasion than others. In templates with DIS, the proximity of the acceptor facilitates invasion, thereby enhancing transfer efficiency. Nucleocapsid protein enhanced the overall efficiency of transfers but did not alter the mechanism. PMID:12663778

Colour-singlet exchange and tests of models of diffractive DIS

International Nuclear Information System (INIS)

Williams, J.C.

2000-03-01

Diffractive deep-inelastic scattering events observed at the HERA electron-proton collider are interpreted as an interaction involving a virtual photon scattering off a colour-singlet state within the proton. Models which attempt to describe the colour-singlet exchanged in diffractive interactions range from the purely phenomenological Donnachie-Landshoff form factor approach to the QCD-motivated gluon-exchange models and the scalar-pomeron model. It is important to find ways to test these models. In this thesis colour-singlet exchange models of diffractive DIS are compared with cross section and structure function data from the H1 detector. H1 select diffractive data by requiring there to be a large angle between the forward proton direction and any other significant detector activity. This pseudo-rapidity gap cut extracts colour-singlet exchange events from the standard DIS data sample. For a wide range of the parameter space covered by the HERA experiments, however, the pseudo-rapidity gap cuts restrict the final-state phase space available for diffractive scattering. One consequence is that pseudo-rapidity gap cuts can be used to select diffractive events in which the colour-singlet only couples to off-shell partons. To leading order in the strong coupling constant, the diffractive final state consists of a quark-antiquark pair. Higher-order events include diffractive production of quark-antiquark-gluon states. In the region where pseudo-rapidity gap cuts restrict the accessible phase space, the cuts reject low transverse momentum quark-antiquark diffractive events. Pseudo-rapidity gap data selection cuts also allow selection of an enhanced 3-jet data sample. The structure function and transverse momentum distribution data can be described by either a two-gluon model or by the Donnachie-Landshoff model, both models requiring a significant contribution from quark-antiquark-gluon diffractive final states to fit the full kinematic range of the diffractive data

Functional requirements document for NASA/MSFC Earth Science and Applications Division: Data and information system (ESAD-DIS). Interoperability, 1992

Science.gov (United States)

Stephens, J. Briscoe; Grider, Gary W.

1992-01-01

These Earth Science and Applications Division-Data and Information System (ESAD-DIS) interoperability requirements are designed to quantify the Earth Science and Application Division's hardware and software requirements in terms of communications between personal and visualization workstation, and mainframe computers. The electronic mail requirements and local area network (LAN) requirements are addressed. These interoperability requirements are top-level requirements framed around defining the existing ESAD-DIS interoperability and projecting known near-term requirements for both operational support and for management planning. Detailed requirements will be submitted on a case-by-case basis. This document is also intended as an overview of ESAD-DIs interoperability for new-comers and management not familiar with these activities. It is intended as background documentation to support requests for resources and support requirements.

Morphological differentiation of Streptomyces viridochromogenes E-219 on solid culture

International Nuclear Information System (INIS)

Liang Xinle; Zhu Jing; Jin Yingyan

2012-01-01

The Streptomyces viridochromogenes E-219 was derived from Streptomyces viridochromogenes CGMCC4.1119 treated with 60 Co γ-rays irradiation and protoplast fusion. With the help of fluorescent probes, fluorescence microscope and electron microscopy, the morphology and development of E-219 on solid surface culture were investigated in this study. The effect of agarslant culture time on the production of Avilamycin was also studied to provide theoretical basis for industrial fermentation of selecting the appropriate seed to culture on the agarslant culture medium. The results implied that the development of colonies of Streptomyces viridochromogenes accompanied the intermittent hyhae apoptosis, and the production of spores was from the active mycelium. The colonial morphology of strain E-219 was significantly different from the original strain CGMCC4h1119. There were variegated hyphae formation in the stage of spore germination and initial hyphae development (10 h) with the live and dead segments alternated in a highly regular fashion within the same hypha. After the early single colony formation, the third phase was followed by profuse growth of the live segments derived from the variegated hypha, then the second apoptosis of the mycelia (48 h) was occurred with another quick growth, and sporulation was occurred at 96 h. Strain CGMCC4.1119 had spiral sporotrichial and round conidiophores with spike, whereas strain E-219 had linear sporotrichial, smooth and dylindrical conidiophore. The results of shake flask experiments indicated that the spores of E-219 had that highest activity when cultured on agarslant culture medium and incubated for 106 h with the production of avilamycin up to 1200 mg/L. (authors)

48 CFR 752.219-8 - Utilization of small business concerns and small disadvantaged business concerns.

Science.gov (United States)

2010-10-01

... business concerns and small disadvantaged business concerns. 752.219-8 Section 752.219-8 Federal... AND CONTRACT CLAUSES Texts of Provisions and Clauses 752.219-8 Utilization of small business concerns and small disadvantaged business concerns. The Foreign Assistance Act calls for USAID to give small...

Measuring the (Dis) Satisfaction of the Employees in the Macedonian Companies

Science.gov (United States)

Mitreva, Elizabeta; Krivokapic, Zdravko; Taskov, Nako; Jovanovic, Jelena

2018-01-01

The (dis)satisfaction of the employees who create and realize activities is as much important as the satisfaction of the buyers. In this paper, we have presented the results from the research in the Macedonian companies concerning the capacity of the leadership to motivate the employees to do their job efficiently and to preserve their initiative…

Transformative social innovation and (dis)empowerment

DEFF Research Database (Denmark)

Avelino, Flor; Wittmayer, Julia; Pel, Bonno

2017-01-01

This article responds to increasing public and academic discourses on social innovation, which often rest on the assumption that social innovation can drive societal change and empower actors to deal with societal challenges and a retreating welfare state. In order to scrutinise this assumption......, this article proposes a set of concepts to study the dynamics of transformative social innovation and underlying processes of multi-actor (dis)empowerment. First, the concept of transformative social innovation is unpacked by proposing four foundational concepts to help distinguish between different pertinent...... ‘shades’ of change and innovation: 1) social innovation, (2) system innovation, (3) game-changers, and (4) narratives of change. These concepts, invoking insights from transitions studies and social innovations literature, are used to construct a conceptual account of how transformative social innovation...

School Choice or the Politics of Desperation? Black and Latinx Parents of Students with Dis/Abilities Selecting Charter Schools in Chicago

Science.gov (United States)

Waitoller, Federico R.; Super, Gia

2017-01-01

In this paper, we focus on the city of Chicago to examine how Black and Latinx parents of students with dis/abilities1 engage with school choice. Using analytical tools from grounded theory (Strauss & Corbin, 1990) and a theoretical lens informed by critical notions of space, race and dis/ability, we analyze interviews with parents of students…

Characterization of the promoter region of the human c-erbB-2 protooncogene

International Nuclear Information System (INIS)

Ishii, S.; Imamoto, F.; Yamanashi, Y.; Toyoshima, K.; Yamamoto, T.

1987-01-01

Three overlapping genomic clones that contain the 5'-terminal portion of the human c-erbB-2 gene (ERBB2) were isolated. The promoter region was identified by nuclease S1 mapping with c-erbB-2 mRNA. Seven transcriptional start sites were identified. DNA sequence analysis showed that the promoter region contains a TATA box and a CAAT box about 30 and 80 base pairs (bp), respectively, upstream of the most downstream RNA initiation site. Two putative binding sites for transcription factor Sp1 were identified about 50 and 110 bp upstream of the CAAT box, and six GGA repeats were found between the CAAT box and the TATA box. This region had strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into monkey CV-1 cells. These data indicate that the promoter of the human c-erbB-2 protooncogene is different from that of the protooncogene c-erbB-1 (epidermal growth factor receptor gene), which does not contain either a TATA box or a CAAT box. Comparison of the promoter sequences and activities of the two protooncogenes should be helpful in analysis of the regulatory mechanism of expression of their gene products, which are growth-factor receptors

48 CFR 1052.219-73 - Department of the Treasury Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... Mentor-Protégé Program. 1052.219-73 Section 1052.219-73 Federal Acquisition Regulations System... and Clauses 1052.219-73 Department of the Treasury Mentor-Protégé Program. As described in DTAR 1019.202-70, insert the following provision: Department of the Treasury Mentor-Protégé Program (JAN 2000...

Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

DEFF Research Database (Denmark)

Rohlin, A; Engwall, Y; Fritzell, K

2011-01-01

inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require......Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half...... of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance...

Reduced expression of APC-1B but not APC-1A by the deletion of promoter 1B is responsible for familial adenomatous polyposis.

Science.gov (United States)

Yamaguchi, Kiyoshi; Nagayama, Satoshi; Shimizu, Eigo; Komura, Mitsuhiro; Yamaguchi, Rui; Shibuya, Tetsuo; Arai, Masami; Hatakeyama, Seira; Ikenoue, Tsuneo; Ueno, Masashi; Miyano, Satoru; Imoto, Seiya; Furukawa, Yoichi

2016-05-24

Germline mutations in the tumor suppressor gene APC are associated with familial adenomatous polyposis (FAP). Here we applied whole-genome sequencing (WGS) to the DNA of a sporadic FAP patient in which we did not find any pathological APC mutations by direct sequencing. WGS identified a promoter deletion of approximately 10 kb encompassing promoter 1B and exon1B of APC. Additional allele-specific expression analysis by deep cDNA sequencing revealed that the deletion reduced the expression of the mutated APC allele to as low as 11.2% in the total APC transcripts, suggesting that the residual mutant transcripts were driven by other promoter(s). Furthermore, cap analysis of gene expression (CAGE) demonstrated that the deleted promoter 1B region is responsible for the great majority of APC transcription in many tissues except the brain. The deletion decreased the transcripts of APC-1B to 39-45% in the patient compared to the healthy controls, but it did not decrease those of APC-1A. Different deletions including promoter 1B have been reported in FAP patients. Taken together, our results strengthen the evidence that analysis of structural variations in promoter 1B should be considered for the FAP patients whose pathological mutations are not identified by conventional direct sequencing.

49 CFR 219.800 - Annual reports.

Science.gov (United States)

2010-10-01

..., DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Annual Report § 219.800 Annual reports. (a) Each... also use the electronic version of the MIS form provided by the DOT. The Administrator may designate... submission to FRA. For information on where to submit MIS forms and for the electronic version of the form...

Hydroxysteroid sulfotransferase SULT2B1b promotes hepatocellular carcinoma cells proliferation in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Xiaoming Yang

Full Text Available Hydroxysteroid sulfotransferase 2B1b (SULT2B1b is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.

20 CFR 219.50 - When evidence of “living with” is required.

Science.gov (United States)

2010-04-01

... with” is required. Evidence of “living with” (see part 222 of this chapter on Family Relationships) is... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When evidence of âliving withâ is required. 219.50 Section 219.50 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD...

A New Theoretical Approach to Postsecondary Student Disability: Disability-Diversity (Dis)Connect Model

Science.gov (United States)

Aquino, Katherine C.

2016-01-01

Disability is often viewed as an obstacle to postsecondary inclusion, but not a characteristic of student diversity. Additionally, current theoretical frameworks isolate disability from other student diversity characteristics. In response, a new conceptual framework, the Disability-Diversity (Dis)Connect Model (DDDM), was created to address…

Thermal (dis)comfort experienced from physiological movements across indoor, transitional and outdoor spaces in Singapore: A pilot study

Science.gov (United States)

Li Heng, Su; Chow, Winston

2017-04-01

Human thermal comfort research is important as climate discomfort can adversely affect both health and work productivity in cities; however, such biometeorological work in low-latitude urban areas is still relatively unstudied hitherto. In the tropical metropolis of Singapore, a suite of policies have been implemented aimed at improving environmental sustainability via increasing car-free commutes and pedestrian movement during work/school journeys, with the consequence that individuals will likely have increased personal exposure through a variety of spaces (and climates) during typical daily activities. As such, research into exploring the thermal (dis)comfort experienced during pedestrian movements across these indoor, outdoor and transitional (semi-outdoor) spaces would yield interesting applied biometerological insights. This pilot study thus investigates how pedestrian thermal comfort varies spatially across a university campus, and how the physical intensity of pedestrian travel affects thermal comfort across these spaces. Over a 10-week period, we profiled six students for both their objective and subjective pedestrian thermal comfort during traverses across different spaces. Data were obtained through use of (a.) of a heat stress sensor, (b.) a fitness tracker, and (b.) a questionnaire survey to record traverse measurements of the microclimate, their physiological data, and their perceived microclimate comfort respectively. Measured climate and physiological data were used to derive commonly-used thermal comfort indices like wet-bulb globe temperature (WBGT) and physiological equivalent temperature (PET). Further, interviews were conducted with all six subjects at the end of the fieldwork period to ascertain details on individual acclimatization behavior and adaptation strategies. The results indicate that (a.) more than 50% of the microclimatic conditions within each indoor, semi-outdoor, and outdoor space exceeded heat stress thresholds of both PET and

12 CFR 219.5 - Conditions for payment.

Science.gov (United States)

2010-01-01

... financial records prior to the time the financial institution is notified of such event. (c) Itemized bill... FOR PROVIDING FINANCIAL RECORDS; RECORDKEEPING REQUIREMENTS FOR CERTAIN FINANCIAL RECORDS (REGULATION S) Reimbursement to Financial Institutions for Providing Financial Records § 219.5 Conditions for...

Hydrogen induced dis-proportionation studies on Zr-Co-M (M=Ni, Fe, Ti) ternary alloys

International Nuclear Information System (INIS)

Jat, Ram Avtar; Pati, Subhasis; Parida, S.C.; Agarwal, Renu; Mukerjee, S.K.; Sastry, P.U.; Jayakrishnan, V.B.

2016-01-01

The intermetallic compound ZrCo is considered as a suitable material for storage, supply and recovery of hydrogen isotopes in International Thermonuclear Experimental Reactor (ITER). However, upon repeated hydriding-dehydriding cycles, the hydrogen storage capacity of ZrCo decreases, which is attributed to the disproportionate reaction ZrCo + H 2 ↔ ZrH 2 + ZrCo 2 . The reduction of hydrogen storage capacity of ZrCo is not desirable for its use in tritium facilities. In our previous studies, attempts were made to improve the durability of ZrCo against dis-proportionation by including a third element. The present study is aimed to investigate the hydrogen induced dis-proportionation of Zr-Co-M (M=Ni, Fe and Ti) ternary alloys under hydrogen delivery conditions

Extraction and purification of {sup 227}Ac and development of solid {sup 219}Rn source

Energy Technology Data Exchange (ETDEWEB)

Tang, Quan; Qiu, Shoukang; Xiao, Detao; Zhou, Yaohui; An, Xiaogang [University of South China, Hengyang (China). Radon Key Laboratory of Hunan Province/School of Nuclear Science and Technology

2014-04-01

The method of {sup 227}Ac extraction and purification from high-grade uranium ore and the test results of solid {sup 219}Rn source made from {sup 227}Ac are reported in this paper. With five years of follow-up monitoring, radiochemical purity of {sup 227}Ac and the emanation power of solid {sup 219}Rn source has been checked by emanation method and γ-spectrometry, the results showed that {sup 228}Th, {sup 231}Pa and {sup 226}Ra have been effectively removed and the emanation power of {sup 219}Rn source is about 80%. The long-term test results also showed that the {sup 219}Rn emanation rate remains stable in a wide air humidity range (40% ∝ 90%). Though the {sup 219}Rn source has not been accurately calibrated yet, it has been applied in the research for delay coincidence measurement of {sup 223}Ra. (orig.)

EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.

Science.gov (United States)

McKinney, Nicole; Yuan, Liangping; Zhang, Hongying; Liu, Jingbo; Cho, Yoon-Jae; Rushing, Elisabeth; Schniederjan, Matthew; MacDonald, Tobey J

2015-01-01

Eph receptors and ephrin ligands are master regulators of oncogenic signaling required for proliferation, migration, and metastasis. Yet, Eph/ephrin expression and activity in medulloblastoma (MB), the most common malignant brain tumor of childhood, remains poorly defined. We hypothesized that Eph/ephrins are differentially expressed by sonic hedgehog (SHH) and non-SHH MB and that specific members contribute to the aggressive phenotype. Affymetrix gene expression profiling of 29 childhood MB, separated into SHH (N = 11) and non-SHH (N = 18), was performed followed by protein validation of selected Eph/ephrins in another 60 MB and two MB cell lines (DAOY, D556). Functional assays were performed using MB cells overexpressing or deleted for selected ephrins. We found EPHB4 and EFNA4 almost exclusively expressed by SHH MB, whereas EPHA2, EPHA8, EFNA1 and EFNA3 are predominantly expressed by non-SHH MB. The remaining family members, except EFNB1, are ubiquitously expressed by over 70-90 % MB, irrespective of subgroup. EFNB1 is the only member differentially expressed by 28 % of SHH and non-SHH MB. Corresponding protein expression for EphB/ephrinB1 and B2 was validated in MB. Only ephrinB2 was also detected in fetal cerebellum, indicating that EphB/ephrinB1 expression is MB-specific. EphrinB1 immunopositivity localizes to tumor cells within MB with the highest proliferative index. EphrinB1 overexpression promotes EphB activation, alters F-actin distribution and morphology, decreases adhesion, and significantly promotes proliferation. Either silencing or overexpression of ephrinB1 impairs migration. These results indicate that EphrinB1 is uniquely dysregulated in MB and promotes oncogenic responses in MB cells, implicating ephrinB1 as a potential target.

9 CFR 93.219 - Declaration for poultry.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Declaration for poultry. 93.219... AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMALS, BIRDS, FISH, AND POULTRY, AND CERTAIN ANIMAL, BIRD, AND POULTRY PRODUCTS; REQUIREMENTS...

21 CFR 2.19 - Methods of analysis.

Science.gov (United States)

2010-04-01

... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ADMINISTRATIVE RULINGS AND DECISIONS General Provisions § 2.19 Methods of analysis. Where the method of analysis... issues of the “Journal of the Association of Official Analytical Chemists”), which are incorporated by...

Configurations and level structure of 219Rn

International Nuclear Information System (INIS)

Sheline, R.K.; Liang, C.F.; Paris, P.

1998-01-01

The level structure of 219 Rn has been studied using the alpha decay of 223 Ra and coincident gamma rays. While only modest changes are required in the level structure, and only above 342.8 keV, severe changes are required throughout the level scheme in the spin assigments. These changes allow the assignment of two sets of anomalous bands with K=5/2 ± and K=3/2 ± . The K=5/2 ± bands have configurations intermediate between the reflection asymmetric configuration and the g 9/2 shell model configuration, while the K=3/2 ± bands have configurations intermediate between the mixed reflection asymmetric configuration and the i 11/2 shell model configuration. Comparison of the systematics of 219 Rn with neighboring isotones, isobars, and isotopes shows clearly the collapse of the quadrupole-octupole-type configurations into the less degenerate shell model configurations. copyright 1998 The American Physical Society

The salutogenic model of health in health promotion research.

Science.gov (United States)

Mittelmark, Maurice B; Bull, Torill

2013-06-01

Despite health promotion's enthusiasm for the salutogenic model of health, researchers have paid little attention to Antonovsky's central ideas about the ease/dis-ease continuum, defined in terms of 'breakdown' (the severity of pain and functional limitations, and the degree medical care is called for, irrespective of specific diseases). Rather, salutogenesis research has a strong focus on how sense of coherence relates to a wide range of specific diseases and illness endpoints. We address two questions: Why has Antonovsky's health concept failed to stimulate research on breakdown, and how can the present emphasis on disease be complemented by an emphasis on positive well-being in the salutogenic model? We show that (i) the breakdown concept of health as specified by Antonovsky is circular in definition, (ii) it is not measured on the 'required' ease/dis-ease continuum, (iii) it is not measureable by any validated or reliability-tested assessment tool, and (iv) it has not so much been rejected by health promotion, as it has not been considered at all. We show that Antonovsky came to view breakdown as but one aspect of well-being. He was open to the idea of well-being as something more positive than the absence of pain, suffering and need for medical care. We suggest ways to move salutogenesis research in the direction of well-being in its positive sense.

48 CFR 53.219 - Small Business Programs.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Small Business Programs... (CONTINUED) CLAUSES AND FORMS FORMS Prescription of Forms 53.219 Small Business Programs. (a) The following form may be used in reporting small disadvantaged business contracting data: OF 312 (10/00), Small...

B-Cell Activation and Tolerance Mediated by B-Cell Receptor, Toll-Like Receptor, and Survival Signal Crosstalk in SLE Pathogenesis

Science.gov (United States)

2017-09-01

Dec, 2016 "Integrating innate , adaptive, & survival signals to control B cell selection, homeostasis and tolerance" Pasteur Institute of Shanghai...secondary lymphoid tissues. Aging Dis. 2: 361–373. 8. Goenka, R., J. L. Scholz, M. S. Naradikian, and M. P. Cancro. 2014. Memory B cells form in aged...Scholz, and M. P. Cancro. 2011. A B- cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 118: 1294–1304. 10. Rubtsov, A

FERREIRA, Maria Alice Araújo; SOUZA, Germana Henriques Pereira de; GOROVITZ, Sabine (Org. Ensaios de Teoria e Prática de Tradução. A tradução na sala de aula. (Org.. Brasília: Editora da UnB, 2014. 219 p.

Directory of Open Access Journals (Sweden)

Marie Hélène C. Torres

2014-12-01

Full Text Available Ensaios de Teoria e Prática de Tradução. A tradução na sala de aula. Maria Alice Araújo Ferreira, Germana Henriques Pereira de Souza e Sabine Gorovitz (Org., Brasília: Editora da UnB, 2014. 219 p.

219-S CORROSION STUDY

International Nuclear Information System (INIS)

DIVINE, J.R.; PARSONS, G.L.

2008-01-01

A minor leak was detected in a drain line for Hood 2B located in the 222-S Laboratory. The line transfers radioactive waste, spent analytical standards, and chemicals used in various analytical procedures. Details are in the report provided by David Comstock, 2B NDE June 2008, work package LAB-WO-07-2012. Including the noted leak, the 222-S Laboratory has experienced two drain line leaks in approximately the last two years of operation. As a consequence, CH2M HILL Hanford Group, Inc. (CH2M HILL) requested the support of ChemMet, Ltd., PC (ChemMet) at the Hanford Site 222-S Laboratory. The corrosion expertise from ChemMet was required prior to preparation of a compatibility assessment for the 222-S Laboratory waste transfer system to assure the expected life of the piping system is extended as much as practicable. The system includes piping within the 222-S Laboratory and the 219-S Waste Storage and Transfer Facility and Operations Process. The ChemMet support was required for an assessment by 222-S staff to analyze what improvements to operational activities may be implemented to extend the tank/piping system life. This assessment will include a summary of the various material types, age, and locations throughout the facility. The assessment will also include a discussion of materials that are safe for drain line disposal on a regular basis, materials that are safe for disposal on a case-by-case basis including specific additional requirements such as flushing, neutralization to a specific pH, and materials prohibited from disposal. The assessment shall include adequate information for 222-S Laboratory personnel to make informed decisions in the future disposal of specific material types by discussing types of compatibility of system materials and potential wastes. The assessment is expected to contain some listing of acceptable waste materials but is not anticipated to be a complete or comprehensive list. Finally the assessment will encompass a brief discussion of

The (Dis)Locative Effect of Noise: Globalisation, Disorientation and Noise in Marc Isaacs’ Lift

NARCIS (Netherlands)

Martin, N.

2016-01-01

This essay considers how thinking about noise can help us explore the relationship between disorientation and globalisation. It introduces the idea of the (dis)locative function of noise as a concept that enables the investigation of everyday disorientation. Such disorientation is encountered not as

DisGeNET-RDF: harnessing the innovative power of the Semantic Web to explore the genetic basis of diseases.

Science.gov (United States)

Queralt-Rosinach, Núria; Piñero, Janet; Bravo, Àlex; Sanz, Ferran; Furlong, Laura I

2016-07-15

DisGeNET-RDF makes available knowledge on the genetic basis of human diseases in the Semantic Web. Gene-disease associations (GDAs) and their provenance metadata are published as human-readable and machine-processable web resources. The information on GDAs included in DisGeNET-RDF is interlinked to other biomedical databases to support the development of bioinformatics approaches for translational research through evidence-based exploitation of a rich and fully interconnected linked open data. http://rdf.disgenet.org/ support@disgenet.org. © The Author 2016. Published by Oxford University Press.

[(Dis)satisfaction with mental healthcare work: a study in Psychosocial Care Centers].

Science.gov (United States)

Guimarães, José Maria Ximenes; Jorge, Maria Salete Bessa; Assis, Marluce Maria Araújo

2011-04-01

The scope of this article is to analyze satisfaction in the workplace of mental healthcare professionals who serve in Psychosocial Care Centers (Caps). The research is of a qualitative nature and the data-collecting medium was semistructured interviews with 19 workers of three Caps in Fortaleza, in the Northern Brazilian State of Ceará. The treatment of the empirical material was based upon the analysis of content with an emphasis on the thematic bias. The results revealed the determinants of (dis)satisfaction present in the daily routine of these workers. The relationships established with the users were singled out as the main source of satisfaction, whereas the work and wage conditions were the main motives for dissatisfaction. In addition to these aspects, consequences of (dis)satisfaction at work in the private, social and organizational field of the workers' life in the Caps were revealed, mainly in physical and mental health. Lastly, they emphasized the urgent need for implementation - on the part of public administration - of strategies that seek to reduce the precariousness of healthcare work, especially in mental health, with a view to mitigating damages potentially caused by such work.

MetSigDis: a manually curated resource for the metabolic signatures of diseases.

Science.gov (United States)

Cheng, Liang; Yang, Haixiu; Zhao, Hengqiang; Pei, Xiaoya; Shi, Hongbo; Sun, Jie; Zhang, Yunpeng; Wang, Zhenzhen; Zhou, Meng

2017-08-22

Complex diseases cannot be understood only on the basis of single gene, single mRNA transcript or single protein but the effect of their collaborations. The combination consequence in molecular level can be captured by the alterations of metabolites. With the rapidly developing of biomedical instruments and analytical platforms, a large number of metabolite signatures of complex diseases were identified and documented in the literature. Biologists' hardship in the face of this large amount of papers recorded metabolic signatures of experiments' results calls for an automated data repository. Therefore, we developed MetSigDis aiming to provide a comprehensive resource of metabolite alterations in various diseases. MetSigDis is freely available at http://www.bio-annotation.cn/MetSigDis/. By reviewing hundreds of publications, we collected 6849 curated relationships between 2420 metabolites and 129 diseases across eight species involving Homo sapiens and model organisms. All of these relationships were used in constructing a metabolite disease network (MDN). This network displayed scale-free characteristics according to the degree distribution (power-law distribution with R2 = 0.909), and the subnetwork of MDN for interesting diseases and their related metabolites can be visualized in the Web. The common alterations of metabolites reflect the metabolic similarity of diseases, which is measured using Jaccard index. We observed that metabolite-based similar diseases are inclined to share semantic associations of Disease Ontology. A human disease network was then built, where a node represents a disease, and an edge indicates similarity of pair-wise diseases. The network validated the observation that linked diseases based on metabolites should have more overlapped genes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

12 CFR 219.23 - Recordkeeping and reporting requirements.

Science.gov (United States)

2010-01-01

... Funds § 219.23 Recordkeeping and reporting requirements. (a) Domestic and international funds transfers... recordkeeping and reporting requirements for domestic and international funds transfers by insured depository... usefulness in criminal, tax, or regulatory investigations or proceedings. These regulations are codified at...

B cells promote obesity-associated periodontitis and oral pathogen-associated inflammation.

Science.gov (United States)

Zhu, Min; Belkina, Anna C; DeFuria, Jason; Carr, Jordan D; Van Dyke, Thomas E; Gyurko, Robert; Nikolajczyk, Barbara S

2014-08-01

Individuals with T2D and PD suffer significantly from the ability of one disease to intensify the other. Disease-associated inflammation is one mechanism thought to fuel this pathogenic feed-forward loop. Several lines of evidence indicate that proinflammatory B cells promote T2D and PD; thus, B cells are top candidates for a cell type that predisposes PD in T2D. To test directly the role of B cells in T2D-associated PD, we compared outcomes from oral Porphyromonas gingivalis challenge of lean WT or B cell-null mice with outcomes from mice that were obese and insulin-resistant before challenge. Obese WT mice responded to oral P. gingivalis challenge with significant periodontal bone loss, whereas obese B cell-null mice were protected completely from PD. By contrast, lean WT and B cell-null mice suffer similar periodontal bone loss in response to oral pathogen. B cells from obese/insulin-resistant hosts also support oral osteoclastogenesis and both oral and systemic production of inflammatory cytokines, including pro-osteoclastogenic TNF-α and MIP-2, an ortholog of human IL-8. B cells furthermore impact AT inflammation in obese, P. gingivalis-infected hosts. Taken together, these data show that fundamentally different mechanisms regulate PD in lean and obese hosts, with B cells able to promote PD only if the hosts are "primed" by obesity. These results justify more intense analysis of obesity-associated changes in B cells that predispose PD in human T2D. © 2014 Society for Leukocyte Biology.

Intersectional harassment and deviant embodiment among Autistic adults: (dis)ability, gender and sexuality.

Science.gov (United States)

Barnett, Jessica Penwell

2017-11-01

Harassment scholarship increasingly attends to the intersectional nature of harassment and its function within systems of domination. However, little of this work includes disability. In-depth interviews with 24 adults on the autism spectrum in the USA demonstrate the intersections of gender, sexuality and (dis)ability in the construction of deviant embodiments as targets for harassment. These intersections also shape how participants made sense of these experiences of violence. Participants' disability characteristics were often read as gender or sexual variance, with harassers relying on sexist and heterosexist constructs to frighten, demean or humiliate them for disability characteristics. Participant experiences demonstrate the cisgender basis of 'able-bodied' identity as well as the 'able-bodied' basis of cisgender and heterosexual identities and experiences. The interdependency of gender, sexuality and (dis)ability embodiment point to how it is critical for scholars and activists to account for the role of gender and heterosexist harassment in ableist oppression and disability harassment in (hetero)sexist oppression, as well as the limits of current US law enforcement structures in providing redress for harassment.

ProDis-ContSHC: learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval.

Science.gov (United States)

Wang, Jingyan; Gao, Xin; Wang, Quanquan; Li, Yongping

2012-05-08

The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database. In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N(i) and N(j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N(i) and N(j).Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update the Protein Hierarchial

Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication.

Science.gov (United States)

Ren, Xiaodi; Siegel, Rachael; Kim, Unkyu; Roeder, Robert G

2011-05-06

B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in Igh promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3' enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3' enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

APC promoter 1B deletion in seven American families with familial adenomatous polyposis.

Science.gov (United States)

Snow, A K; Tuohy, T M F; Sargent, N R; Smith, L J; Burt, R W; Neklason, D W

2015-10-01

Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation-dependent probe amplification (MLPA) probes specific for APC promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the APC locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele-specific expression of APC mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42-98%, depending on tissue type. This study confirms the importance of APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

25 CFR 2.19 - Action by Area Directors and Education Programs officials on appeal.

Science.gov (United States)

2010-04-01

... Programs officials on appeal. (a) Area Directors, Area Education Programs Administrators, Agency... 25 Indians 1 2010-04-01 2010-04-01 false Action by Area Directors and Education Programs officials on appeal. 2.19 Section 2.19 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR PROCEDURES...

Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells

International Nuclear Information System (INIS)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-ming

2016-01-01

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.

Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells

Energy Technology Data Exchange (ETDEWEB)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-ming, E-mail: zengshenming@gmail.com

2016-04-22

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.

Wangai et al., Afr. J. Infect. Dis. (2011) 5(1): 1 - 6 SENSITIVITY OF ...

African Journals Online (AJOL)

AJTCAM

Wangai et al., Afr. J. Infect. Dis. (2011) 5(1): 1 - 6. 1. SENSITIVITY OF MICROSCOPY COMPARED TO MOLECULAR DIAGNOSIS OF P. FALCIPARUM: IMPLICATIONS ON MALARIA TREATMENT IN EPIDEMIC AREAS IN. KENYA. Laura Nyawira Wangai 1,2, Muriira Geoffrey Karau 3, Paul Nthakanio Njiruh 4, Omar Sabah 5 ...

Better Targeting, Better Efficiency for Wide-scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B

Directory of Open Access Journals (Sweden)

Kasey L Jackson

2016-11-01

Full Text Available Widespread genetic modification of cells in the central nervous system (CNS with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin hybrid (CBA promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered AAV-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS-related protein TDP-43 with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

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.

Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B.

Science.gov (United States)

Jackson, Kasey L; Dayton, Robert D; Deverman, Benjamin E; Klein, Ronald L

2016-01-01

Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3′ Uridylated Intermediates Degraded by DIS3L2

Directory of Open Access Journals (Sweden)

Marshall P. Thomas

2015-05-01

Full Text Available Apoptosis is a tightly coordinated cell death program that damages mitochondria, DNA, proteins, and membrane lipids. Little is known about the fate of RNA as cells die. Here, we show that mRNAs, but not noncoding RNAs, are rapidly and globally degraded during apoptosis. mRNA decay is triggered early in apoptosis, preceding membrane lipid scrambling, genomic DNA fragmentation, and apoptotic changes to translation initiation factors. mRNA decay depends on mitochondrial outer membrane permeabilization and is amplified by caspase activation. 3′ truncated mRNA decay intermediates with nontemplated uridylate-rich tails are generated during apoptosis. These tails are added by the terminal uridylyl transferases (TUTases ZCCHC6 and ZCCHC11, and the uridylated transcript intermediates are degraded by the 3′ to 5′ exonuclease DIS3L2. Knockdown of DIS3L2 or the TUTases inhibits apoptotic mRNA decay, translation arrest, and cell death, whereas DIS3L2 overexpression enhances cell death. Our results suggest that global mRNA decay is an overlooked hallmark of apoptosis.

ProDis-ContSHC: Learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval

KAUST Repository

Wang, Jim Jing-Yan

2012-05-08

Background: The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database.Results: In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N (i) and N (j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N (i) and N (j). Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update

The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model.

Science.gov (United States)

Murai, Kiyohito; Sun, Guoqiang; Ye, Peng; Tian, E; Yang, Su; Cui, Qi; Sun, Guihua; Trinh, Daniel; Sun, Olivia; Hong, Teresa; Wen, Zhexing; Kalkum, Markus; Riggs, Arthur D; Song, Hongjun; Ming, Guo-li; Shi, Yanhong

2016-03-11

Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation.

PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

Science.gov (United States)

Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

2016-04-07

Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

Controversial Embodiment: Sport, Masculinity, Dis/Ability

Directory of Open Access Journals (Sweden)

Marilena Parlati

2015-11-01

Full Text Available This essay is an attempt at investigating visible forms of complex, indeed controversial embodiment, with the specific intention of concentrating on the ways they interrogate delicate issues such as disability, masculinity and prosthetic sport performance. I intend to sound the shifting boundaries between dis-ability and super-ability as manifested in iconic figures such as Stelarc and, in other fields, Oscar Pistorius, whose unsteady position as privileged/disabled bladerunner seems to require – and indeed to gather – particularly intense scrutiny. I shall introduce a few contemporary discourses on corporeality and embodiment, which focus on the ‘troubling’ nature of auxiliary organs Freud refers to in the much contended paragraph I adopt as epigraph and guiding procedural light; I shall move from Butler and Giddens to Jean-Luc Nancy’s work on transplants and/as prostheses to include theoretical debates on disintegrating embodiment and disability studies, in order to proceed towards an analysis of the short-circuiting of allegedly secure practices of (masculine embodiment in sport culture and theory.

The etiology of mathematical and reading (dis)ability covariation in a sample of Dutch twins

NARCIS (Netherlands)

Markowitz, E.M.; Willemsen, A.H.M.; Trumbetta, S.L.; van Beijsterveldt, C.E.M.; Boomsma, D.I.

2005-01-01

The genetic etiology of mathematical and reading (dis)ability has been studied in a number of distinct samples, but the true nature of the relationship between the two remains unclear. Data from the Netherlands Twin Register was used to determine the etiology of the relationship between mathematical

Polycystin-1 promotes PKCα-mediated NF-κB activation in kidney cells

International Nuclear Information System (INIS)

Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky; Mangolini, Alessandra; Pinton, Paolo; Witzgall, Ralph; Rizzuto, Rosario; Senno, Laura del

2006-01-01

Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-κB signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293 CTT ), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-κB nuclear levels and NF-κB-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-κB promoter activation was mediated by PKCα because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293 CTT cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-κB inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKCα-mediated NF-κB signalling and cell survival

48 CFR 52.219-2 - Equal Low Bids.

Science.gov (United States)

2010-10-01

.... If the bidder is awarded a contract as a result of receiving priority consideration under this... AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 52.219-2 Equal...) amount to more than 50 percent of the contract price. (c) Failure to identify the labor surplus areas as...

Some Remarks on Methods of QCD Analysis of Polarized DIS Data

CERN Document Server

Leader, Elliot; Stamenov, Dimiter B

2009-01-01

The results on polarized parton densities (PDFs) obtained using different methods of QCD analysis of the present polarized DIS data are discussed. Their dependence on the method used in the analysis, accounting or not for the kinematic and dynamic 1/Q^2 corrections to spin structure function g_1, is demonstrated. It is pointed out that the precise data in the preasymptotic region require a more careful matching of the QCD predictions to the data in this region in order to determine the polarized PDFs correctly.

Code Assessment of SPACE 2.19 using LSTF Steam Generator Tube Rupture Test

Energy Technology Data Exchange (ETDEWEB)

Kim, Minhee; Kim, Seyun [KHNP CRI, Daejeon (Korea, Republic of)

2016-10-15

The SPACE is a best estimated two-phase three-field thermal-hydraulic analysis code used to analyze the safety and performance of pressurized water reactors. As a result of the development, the 2.19 version of the code was released through the successive various verification and validation works. The present work is on the line of expanding the work by Kim et al. In this study, results produced by the SPACE 2.19 code were compared with the experimental data from JAERI's LSTF Test Run LSTF SB-SG-06 experiment simulating a Steam Generator Tube Rupture (SGTR) transient. In order to identify the predictability of SPACE 2.19, the LSTF steam generator tube rupture test was simulated. To evaluate the computed results, LSTF SB-SG-06 test data simulating the SGTR and the RELAP5/ MOD3.1 are used. The calculation results indicate that the SPACE 2.19 code predicted well the sequence of events and the major phenomena during the transient, such as the asymmetric loop behavior, reactor coolant system cooldown and heat transfer by natural circulation, the primary and secondary system depressurization by the pressurizer auxiliary spray and the steam dump using the intact loop steam generator relief valve.

48 CFR 852.219-72 - Evaluation factor for participation in the VA mentor-protégé program.

Science.gov (United States)

2010-10-01

... participation in the VA mentor-protégé program. 852.219-72 Section 852.219-72 Federal Acquisition Regulations... Texts of Provisions and Clauses 852.219-72 Evaluation factor for participation in the VA mentor-protégé... the VA Mentor-Protégé Program (DEC2009) This solicitation contains an evaluation factor or sub-factor...

Ascites promotes cell migration through the repression of miR-125b in ovarian cancer.

Science.gov (United States)

Yang, Lan; Zhang, Xiaoli; Ma, Yiming; Zhao, Xinhua; Li, Bin; Wang, Hongying

2017-08-01

Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. Here, we investigated the molecular mechanisms by which malignant ascites promote the metastasis of ovarian cancer. It was found that ovarian cancer ascites promoted ovarian cancer cell migration which was attenuated by either heat inactivation or antibody blockade of TGF-β. High level (at ng/ml level) of TGF-β was detected in the ascites. In addition, ascites repressed the expression of miRNA-125b in a TGF-β-dependent manner. Mimic of miR-125b blocked ascites-induced cell migration. Furthermore, Gab2 (a target gene of miR-125b) was elevated by ascites in a TGF-β-dependent manner. And forced expression of Gab2 reversed the inhibition of migration induced by miR-125b mimic. Most importantly, the expression of miR-125b and Gab2 mRNA was negatively correlated in ovarian cancer specimens. Taken together, our finding suggested that TGF-β in ascites promoted cancer cell migration through repression of miR-125b in ovarian cancer. This might provide a novel therapeutic target for ovarian cancer in the future.

33 CFR 135.219 - Notification of changes affecting certification.

Science.gov (United States)

2010-07-01

... SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OFFSHORE OIL POLLUTION COMPENSATION FUND Financial Responsibility for Offshore Facilities § 135.219 Notification of changes affecting... Fund Administrator in writing when any changes occur which prevent the owner, operator, or guarantor...

25 CFR 39.219 - What happens if a residential program does not maintain residency levels required by this subpart?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What happens if a residential program does not maintain residency levels required by this subpart? 39.219 Section 39.219 Indians BUREAU OF INDIAN AFFAIRS..., Student Counts, and Verifications Residential Programs § 39.219 What happens if a residential program does...

20 CFR 725.219 - Duration of entitlement; child.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Duration of entitlement; child. 725.219... of entitlement; child. (a) An individual is entitled to benefits as a child for each month beginning... month in which any one of the following events first occurs: (1) The child dies; (2) The child marries...

FERREIRA, Maria Alice Araújo; SOUZA, Germana Henriques Pereira de; GOROVITZ, Sabine (Org. Ensaios de Teoria e Prática de Tradução. A tradução na sala de aula. (Org.. Brasília: Editora da UnB, 2014. 219 p.

Directory of Open Access Journals (Sweden)

Marie Hélène C. Torres

2014-12-01

Full Text Available http://dx.doi.org/10.5007/2175-7968.2014v2n34p294 Ensaios de Teoria e Prática de Tradução. A tradução na sala de aula. Maria Alice Araújo Ferreira, Germana Henriques Pereira de Souza e Sabine Gorovitz (Org., Brasília: Editora da UnB, 2014. 219 p.

FERREIRA, Maria Alice Araújo; SOUZA, Germana Henriques Pereira de; GOROVITZ, Sabine (Org.) Ensaios de Teoria e Prática de Tradução. A tradução na sala de aula. (Org.). Brasília: Editora da UnB, 2014. 219 p.

OpenAIRE

Torres, Marie Hélène C.

2014-01-01

http://dx.doi.org/10.5007/2175-7968.2014v2n34p294 Ensaios de Teoria e Prática de Tradução. A tradução na sala de aula. Maria Alice Araújo Ferreira, Germana Henriques Pereira de Souza e Sabine Gorovitz (Org.), Brasília: Editora da UnB, 2014. 219 p.

Genome-wide function of H2B ubiquitylation in promoter and genic regions.

Science.gov (United States)

Batta, Kiran; Zhang, Zhenhai; Yen, Kuangyu; Goffman, David B; Pugh, B Franklin

2011-11-01

Nucleosomal organization in and around genes may contribute substantially to transcriptional regulation. The contribution of histone modifications to genome-wide nucleosomal organization has not been systematically evaluated. In the present study, we examine the role of H2BK123 ubiquitylation, a key regulator of several histone modifications, on nucleosomal organization at promoter, genic, and transcription termination regions in Saccharomyces cerevisiae. Using high-resolution MNase chromatin immunoprecipitation and sequencing (ChIP-seq), we map nucleosome positioning and occupancy in mutants of the H2BK123 ubiquitylation pathway. We found that H2B ubiquitylation-mediated nucleosome formation and/or stability inhibits the assembly of the transcription machinery at normally quiescent promoters, whereas ubiquitylation within highly active gene bodies promotes transcription elongation. This regulation does not proceed through ubiquitylation-regulated histone marks at H3K4, K36, and K79. Our findings suggest that mechanistically similar functions of H2B ubiquitylation (nucleosome assembly) elicit different functional outcomes on genes depending on its positional context in promoters (repressive) versus transcribed regions (activating).

Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

Directory of Open Access Journals (Sweden)

Mariana Schroeder

2018-03-01

Full Text Available Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. Objective: We attempted to address the issue of individual differences in the response to weight cycling in male mice. Methods: We first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH of an additional mouse cohort and performed a full metabolic assessment. Results: Exposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype. Conclusions: Our results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling. Keywords: Weight cycling, Metabolic syndrome, miRNAs, Ventromedial hypothalamus, High fat diet, Diabetes

Heterogeneous performances of conceptual dis/continuity: a dialectic reading of Brown and Kloser's article

Science.gov (United States)

Hwang, Sungwon; Kim, Mijung

2009-12-01

We review Brown and Kloser's article, "Conceptual continuity and the science of baseball: using informal science literacy to promote students science learning" from a Vygotskian cultural-historical and dialectic perspective. Brown and Kloser interpret interview data with student baseball players and claim that students' conceptual understanding articulated in vernacular genres involves continuities (similarities) with the canonical scientific explanations. In this commentary, we suggest that the authors' approach presupposes the dichotomy of the formal and the informal, which brings the authors' attention to continuity into the separation of cognition from language. We propose a Vygotskian approach that points out the problem of theorizing cognition (conceptual understanding) by depending on specific forms of representation (e.g., scientific terms). As alternative, we envision a Vygotskian cultural-historical approach to language, which considers different, irreducible modes of communication as an integrated whole and therefore allows theorizing cognition without dichotomizing it from the concrete ways by which human being communicates. We provide an exemplary analysis of a lecture talk in a university physics classroom and exemplify dialectic theories that explain the development of conceptual understanding. We discuss that this Vygotskian dialectic approach shows that people communicate scientific concepts through hybridization, which does not reproduce a genre self-identically; the continuity of conceptual understanding involves dis/continuity.

48 CFR 52.219-19 - Small Business Concern Representation for the Small Business Competitiveness Demonstration Program.

Science.gov (United States)

2010-10-01

... Representation for the Small Business Competitiveness Demonstration Program. 52.219-19 Section 52.219-19 Federal... Representation for the Small Business Competitiveness Demonstration Program. As prescribed in 19.1008(a), insert the following provision: Small Business Concern Representation for the Small Business Competitiveness...

bTSSfinder: a novel tool for the prediction of promoters in Cyanobacteria andEscherichia coli

KAUST Repository

Shahmuradov, Ilham Ayub

2016-09-29

Motivation: The computational search for promoters in prokaryotes remains an attractive problem in bioinformatics. Despite the attention it has received for many years, the problem has not been addressed satisfactorily. In any bacterial genome, the transcription start site is chosen mostly by the sigma (σ) factor proteins, which control the gene activation. The majority of published bacterial promoter prediction tools target σ70 promoters in Escherichia coli. Moreover, no σ-specific classification of promoters is available for prokaryotes other than for E. coli. Results: Here, we introduce bTSSfinder, a novel tool that predicts putative promoters for five classes of σ factors in Cyanobacteria (σA, σC, σH, σG and σF) and for five classes of sigma factors in E. coli (σ70, σ38, σ32, σ28 and σ24). Comparing to currently available tools, bTSSfinder achieves higher accuracy (MCC=0.86, F1-score=0.93) compared to the next best tool with MCC=0.59, F1-score=0.79) and covers multiple classes of promoters.

[The nursing team and Maslow: (dis)satisfaction in the work].

Science.gov (United States)

Vitória Regis, Lorena Fagundes Ladeia; Porto, Isaura Setenta

2006-01-01

This text tries to understand the Nursing team and their (dis)satisfactions in the work. We consider the association with the theory of basic human needs of Abraham Maslow as a way to systemize and to comprehend the recurrent situations and the day-by-day Nursing issues. The necessities are structuralized hierarchically in physiological, security, social, auto-esteem and auto-accomplishment indicating the degree of satisfaction (from the disease to the fullness) of an individual or group. The advantage of this approach consists of being able to use the solid, depth and rich Maslow theory in concrete and particular situations of the Nursing team.

Study of the Role of siRNA Mediated Promoter Methylation in DNMT3B Knockdown and Alteration of Promoter Methylation of CDH1, GSTP1 Genes in MDA-MB -453 Cell Line.

Science.gov (United States)

Naghitorabi, Mojgan; Mir Mohammad Sadeghi, Hamid; Mohammadi Asl, Javad; Rabbani, Mohammad; Jafarian-Dehkordi, Abbas

2017-01-01

Promoter methylation is one of the main epigenetic mechanisms that leads to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifically knock down the DNMTs at mRNA level. Also many studies have focused on transcriptional gene silencing in mammalian cells via siRNA mediated promoter methylation. The present study was designed to assess the role of siRNA mediated promoter methylation in DNMT3B knockdown and alteration of promoter methylation of Cadherin-1 (CDH1), Glutathione S-Transferase Pi 1(GSTP1), and DNMT3B genes in MDA-MB-453 cell line. MDA-MB-453 cells were transfected with siDNMT targeting DNMT3B promoter and harvested at 24 and 48 h post transfection to monitor gene silencing and promoter methylation respectively. DNMT3B expression was monitored by quantitative RT-PCR method. Promoter methylation was quantitatively evaluated using differential high resolution melting analysis. A non-significant 20% reduction in DNMT3B mRNA level was shown only after first transfection with siDNMT, which was not reproducible. Promoter methylation levels of DNMT3B, CDH1, and GSTP1 were detected at about 15%, 70% and 10% respectively, in the MDA-MB-453 cell line, with no significant change after transfection. Our results indicated that siDNMT sequence were not able to affect promoter methylation and silencing of DNMT3B in MDA-MB-453 cells. However, quantitation of methylation confirmed a hypermethylated phenotype at CDH1 and GSTP1 promoters as well as a differential methylation pattern at DNMT3B promoter in breast cancer.

Thumbs Up for Refugees? : Influences of Online News Content and (Dis)Likes on Self-Reported Perceptions.

NARCIS (Netherlands)

Greijdanus, Hedy

2016-01-01

An extensive body of research on social validation indicates that people feel strengthened in their views and opinions when others agree with them. Notions of the extent of others' (dis)agreement can stem from conversations or other forms of interpersonal communication, but also from what one reads

Im/mobilities and dis/connectivities in medical globalisation: How global is Global Health?

Science.gov (United States)

Dilger, Hansjörg; Mattes, Dominik

2018-03-01

The interdisciplinary, politically contested field of Global Health has often been described as a consequence of, and response to, an intensification of the mobilities of, and connectivities between, people, pathogens, ideas, and infrastructure across national borders and large distances. However, such global mobilities and connectivities are not as omnidirectional and unpatterned as the rhetoric of many Global Health actors suggests. Instead, we argue that they are suffused by a plethora of institutional, national, and global political agendas, and substantially shaped by transnational and postcolonial power relations. Furthermore, the configurations that are typically subsumed under the category of Global Health represent only a minor part of the range of im/mobilities and dis/connectivities that are essential for understanding transformations of epidemiological patterns, health care infrastructures, and the responses to health-related challenges in a globalising world. In order to broaden such a limiting analytical perspective, we propose to expand the analytical focus in studying Global Health phenomena by paying close attention to the myriad ways in which particular im/mobilities and dis/connectivities constitute medicine and well-being in global and transnational settings. Pursuing a conceptual shift from studies of 'Global Health' to studying 'medical globalization' may carve out new analytical ground for such an endeavour.

Insulated hsp70B' promoter: stringent heat-inducible activity in replication-deficient, but not replication-competent adenoviruses.

Science.gov (United States)

Rohmer, Stanimira; Mainka, Astrid; Knippertz, Ilka; Hesse, Andrea; Nettelbeck, Dirk M

2008-04-01

Key to the realization of gene therapy is the development of efficient and targeted gene transfer vectors. Therapeutic gene transfer by replication-deficient or more recently by conditionally replication-competent/oncolytic adenoviruses has shown much promise. For specific applications, however, it will be advantageous to provide vectors that allow for external control of gene expression. The efficient cellular heat shock system in combination with available technology for focused and controlled hyperthermia suggests heat-regulated transcription control as a promising tool for this purpose. We investigated the feasibility of a short fragment of the human hsp70B' promoter, with and without upstream insulator elements, for the regulation of transgene expression by replication-deficient or oncolytic adenoviruses. Two novel adenoviral vectors with an insulated hsp70B' promoter were developed and showed stringent heat-inducible gene expression with induction ratios up to 8000-fold. In contrast, regulation of gene expression from the hsp70B' promoter without insulation was suboptimal. In replication-competent/oncolytic adenoviruses regulation of the hsp70B' promoter was lost specifically during late replication in permissive cells and could not be restored by the insulators. We developed novel adenovirus gene transfer vectors that feature improved and stringent regulation of transgene expression from the hsp70B' promoter using promoter insulation. These vectors have potential for gene therapy applications that benefit from external modulation of therapeutic gene expression or for combination therapy with hyperthermia. Furthermore, our study reveals that vector replication can deregulate inserted cellular promoters, an observation which is of relevance for the development of replication-competent/oncolytic gene transfer vectors. (c) 2008 John Wiley & Sons, Ltd.

Structural Insights into the Association of Hif1 with Histones H2A-H2B Dimer and H3-H4 Tetramer.

Science.gov (United States)

Zhang, Mengying; Liu, Hejun; Gao, Yongxiang; Zhu, Zhongliang; Chen, Zijun; Zheng, Peiyi; Xue, Lu; Li, Jixi; Teng, Maikun; Niu, Liwen

2016-10-04

Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

MicroRNA-128b suppresses tumor growth and promotes apoptosis by targeting A2bR in gastric cancer

Energy Technology Data Exchange (ETDEWEB)

Wang, Ping; Guo, Xueyan; Zong, Wei [Department of Gastroenterology, The Third Affiliated Hospital, College of Medicine, Xi' an Jiaotong University, Xi' an 710068 (China); Song, Bin [Department of General Surgery, The Third Affiliated Hospital, College of Medicine, Xi' an Jiaotong University, Xi' an 710068 (China); Liu, Guisheng [Department of Gastroenterology, The Third Affiliated Hospital, College of Medicine, Xi' an Jiaotong University, Xi' an 710068 (China); He, Shuixiang, E-mail: fisrstsxianghe@163.com [Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Xi' an Jiaotong University, Xi' an 710061 (China)

2015-11-27

MicroRNAs (miRNAs) play crucial roles in the development and progression of human cancers, including gastric cancer (GC). The discovery of miRNAs may provide a new and powerful tool for studying the mechanism, diagnosis, and treatment of GC. In this study, we aimed to investigate the role and mechanism of miR-128b in the development and progression of GC. Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of miR-128b in GC tissues and cell lines. We found that miR-128b was significantly down-regulated in GC tissues and cell lines. In addition, over-expression of miR-128b inhibited GC cell proliferation, migration and invasion of GC cells in vitro. Gain-of-function in vitro experiments further showed that the miR-128b mimic significantly promoted GC cell apoptosis. Subsequent dual-luciferase reporter assay identified one of the proto-oncogene A2bR as direct target of miR-128b. Therefore, our results indicate that miR-128b is a proto-oncogene miRNA that can suppresses GC proliferation and migration through down-regulation of the oncogene gene A2bR. Taken together, our results indicate that miR-128b could serve as a potential diagnostic biomarker and therapeutic option for human GC in the near future. - Highlights: • The expression of MiR-128b is significantly down-regulated in GC tissues and cell lines. • Ectopic expression of miR-128b directly affects cell proliferation, migration and invasion in vitro. • Overexpression of miR-128b increases apoptosis in GC cells. • A2bR is a candidate target gene of miR-128b. • MiR-128b represses cell proliferation, migration and invasion and promotes apoptosis by targeting A2bR in GC.

Wnt-10b secreted from lymphocytes promotes differentiation of skin epithelial cells

International Nuclear Information System (INIS)

Ouji, Yukiteru; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

2006-01-01

Wnt-10b was originally isolated from lymphoid tissue and is known to be involved in a wide range of biological actions, while recently it was found to be expressed early in the development of hair follicles. However, few studies have been conducted concerning the role of Wnt-10b with the differentiation of skin epithelial cells. To evaluate its role in epithelial differentiation, we purified Wnt-10b from the supernatant of a concanavalin A-stimulated lymphocyte culture using an affinity column and investigated its effects on the differentiation of adult mouse-derived primary skin epithelial cells (MPSEC). MPSEC cultured with Wnt-10b showed morphological changes from cuboidal to spindle-shaped with inhibited proliferation, and also obtained characteristics of the hair shaft and inner root sheath of the hair follicle, represented by red-colored Ayoub Shklar staining, and reactions to AE-13 and AE-15 as seen with immunocytology. Further, RT-PCR analysis demonstrated the expression of mRNA for keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5, in Wnt-10b-treated MPSEC. In addition, involvement of the canonical Wnt signal pathway was demonstrated by a TCF reporter (pTOPFLASH) assay. These results suggest that Wnt-10b promotes the differentiation of MPSEC and may play an important role in hair follicle development by promoting differentiation of epithelial cells

26 CFR 1.219-2 - Definition of active participant.

Science.gov (United States)

2010-04-01

... individuals whose compensation exceeds a certain amount accrue benefits under the plan. An individual whose... participant. However, any benefit that may vary with future compensation of an individual provides additional... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Definition of active participant. 1.219-2...

48 CFR 952.219-70 - DOE Mentor-Protege program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false DOE Mentor-Protege program... FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.219-70 DOE Mentor.... DOE Mentor-Protege Program (MAY 2000) The Department of Energy has established a Mentor-Protege...

Chains of (dis)trust : Exploring the underpinnings of knowledge-sharing and quality care across mental health services

NARCIS (Netherlands)

Brown, P.R.; Calnan, M.W.

Quality and safety in healthcare settings are underpinned by organisational cultures, which facilitate or impede the refinement, sharing and application of knowledge. Avoiding the use of the term culture as a residual category, we focus specifically on describing chains of (dis)trust, analysing

Egwuatu et al., Afr., J. Infect. Dis. (2017) 11 (1): 18-25 http://dx.doi ...

African Journals Online (AJOL)

PROF ADEWUNMI

Dis. (2017) 11 (1): 18-25 http://dx.doi.org/10.21010/ajid.v11i1.3. 18. EFFECT OF ... resistant isolates of Escherichia coli in HIV-infected adult patients in Lagos. .... Institute for Medical Research (NIMR), Yaba both in Nigeria. ..... with HIV/AIDS in Africa 2000. http://www.unaids.org/publications/documents/care/general/ ...

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

Directory of Open Access Journals (Sweden)

Bonnet Amandine

2012-09-01

Full Text Available Abstract Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1 is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

Science.gov (United States)

Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

2012-09-25

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the

Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

International Nuclear Information System (INIS)

Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

2008-01-01

Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

Low LET radiation-induced telomerase catalytic subunit promoter activation is mediated by nuclear factor Kappa B

International Nuclear Information System (INIS)

Natarajan, M.; Hong, F.A.; Mohan, S.; Herman, T.S.

2003-01-01

Full text: The objective of this study is to understand whether low doses of low LET radiation induces survival advantage in normal cells. As an increase in telomerase activity is associated with longevity and cell proliferation, we examined the telomerase response following gamma-irradiation in normal aortic endothelial cells. Telomeric Repeat Amplification Protocol assay following low LET radiation showed an increase in telomerase enzyme activity as early as 8 h post irradiation and reaches its maximum at 24 h. Subsequent analysis revealed that the increased telomerse enzyme activity is due to increased synthesis resulting from an increased transcription. Examination of transcriptional activation of telomerase reverse transcriptase (TERT) promoter regulation showed an enhanced transcription of the telomerse gene following gamma-irradiation. In our previous reports we documented an increase in NF-kB DNA-binding property following low LET radiation (3). Therefore, to determine whether the activation of NF-kB-signaling is responsible for induced TERT promoter activation, cells transiently transfected with minimal promoter region of TERT containing wild type or mutant NF-kB binding site were examined following low LET radiation. TERT promoter activation was induced in wild type transfected cells whereas, in mutant kB binding site, the activation remained at the basal level similar to that of un-irradiated cells. More significantly, the gamma-ray mediated promoter activation of telomerase gene as well as induce telomerase enzyme activity was abrogated by ectopically expressing the IkBa mutant (IkBa (S32A/S36A)), which blocks NF-kB activation. The results thus suggest that exposure to low LET radiation could induce telomerase activity and the activation is at least, in part, mediated by the transcription factor NF-kB. Sustained activation of telomerase in these cells after low LET radiation may impart extended life span

48 CFR 1852.219-79 - Mentor requirements and evaluation.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Mentor requirements and... and Clauses 1852.219-79 Mentor requirements and evaluation. As prescribed in 1819.7215, insert the following clause: Mentor Requirements and Evaluation (MAY 2009) (a) The purpose of the NASA Mentor-Protégé...

Diffractive D{sup *}-mesons production in DIS at HERA

Energy Technology Data Exchange (ETDEWEB)

Vinokurova, Svetlana

2010-05-15

This thesis presents a measurement of the cross sections for the production of the charmed mesons in diffractive deep inelastic positron-proton scattering (DIS) interactions of the type ep{yields}eXY, where the system X is separated from a low-mass system Y, by a large rapidity gap where no particles are observed. These diffractive processes can be explained as a result of the exchange of a strongly interacting colour singlet object between the final state particles. In this measurement data taken with the H1 detector in the years 1999-2000, corresponding to an integrated luminosity of L{sub int}=46.7 pb{sup -1} are used. Inclusive DIS events are selected in the kinematic range with the momentum transfer Q{sup 2} element of [2;100] GeV and inelasticity y{sub bj} element of [0.05;07]. The charm quark is tagged by requiring a D{sup *} meson decaying into the channel D{sup *}{yields}D{sup 0}{pi}{sub slow}{yields}K{pi}{pi}{sub slow} inside the central tracking system with transverse momenta p{sub t}(D{sup *})>2 GeV. The forward components of the H1 detector are used to select genuine diffractive events on the basis of the forward sub-detectors activity and of the presence a large rapidity gap in the final state hadrons. The visible charm production cross sections are measured in the diffractive kinematic range M{sub Y} < 1.6 GeV, vertical stroke t vertical stroke < 1 GeV{sup 2} and x{sub P} < 0.04 to be {sigma}(ep{yields}e{sup '}(D{sup *}X)Y)=249{+-}31(stat.){+-}30(sys) pb, where the first uncertainty is statistical and the second systematic. The shape of the differential distributions for diffractive D{sup *} production are well described by the collinear factorisation model which is implemented in the Monte Carlo simulation RAPGAP. (orig.)

Prayer and the Registered Nurse (PRN): nurses' reports of ease and dis-ease with patient-initiated prayer request.

Science.gov (United States)

Minton, Mary E; Isaacson, Mary; Banik, Deborah

2016-09-01

To explore nurse comfort with patient-initiated prayer request scenarios. Spiritual care is fundamental to patient care evidenced by Joint Commission requirement of a spiritual assessment on a patient's hospital admission. Prayer is an assessment component. Patients may seek solace and support by requesting prayer from the bedside nurse, the nurse may lack confidence in responding. Absent in the literature are reports specific to nurses' comfort when patients initiate prayer requests. Cross-sectional mixed methods study. Data were collected in early 2014 from 134 nurses in the USA via an online survey using QuestionPro. The qualitative results reported here were collated by scenario and analysed using thematic analysis. The scenario responses revealed patterns of ease and dis-ease in response to patient requests for prayer. The pattern of ease of prayer with patients revealed three themes: open to voice of calm or silence; physical or spiritual; can I call the chaplain. For these nurses, prayer is a natural component of nursing care, as the majority of responses to all scenarios demonstrated an overwhelming ease in response and capacity to pray with patients on request. The pattern of dis-ease of prayer with patients distinguished two themes: cautious hesitancy and whose God. These nurses experienced dis-ease with the patient's request no matter the situation. Educators and administrators must nurture opportunities for students and nurses to learn about and engage in the reflective preparation needed to respond to patient prayer requests. © 2016 John Wiley & Sons Ltd.

MicroRNA-148b promotes proliferation of hair follicle cells by targeting NFAT5

Directory of Open Access Journals (Sweden)

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

2016-03-01

Full Text Available MicroRNAs (miRNAs, small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that miRNAs are important for hair follicle development and growth. In our study, we found by qRT-PCR that miR-148b was significantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148b could activate Wnt/β-catenin pathway and b-catenin, cycD, c-jun and PPARD were consistently upregulated accordingly. Furthermore, transcript factor nuclear factor of activated T cells type 5 (NFAT5 and Wnt10b were predicted to be the target of miR-148b and this was substantiated using a Dual-Luciferase reporter system. Subsequently NFAT5 was further identified as the target of miR-148b using western blotting. These results were considered to indicate that miR-148b could activate the Wnt/β-catenin signal pathway by targeting NFAT5 to promote the proliferation of human hair follicle cells.

Wnt-10b promotes differentiation of skin epithelial cells in vitro

International Nuclear Information System (INIS)

Ouji, Yukiteru; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

2006-01-01

To evaluate the role of Wnt-10b in epithelial differentiation, we investigated the effects of Wnt-10b on adult mouse-derived primary skin epithelial cells (MPSEC). Recombinant Wnt-10b protein (rWnt-10b) was prepared using a gene engineering technique and MPSEC were cultured in its presence, which resulted in morphological changes from cuboidal to spindle-shaped and inhibited their proliferation. Further, involvement of the canonical Wnt signal pathway was also observed. MPSEC treated with rWnt-10b showed characteristics of the hair shaft and inner root sheath of the hair follicle, in results of Ayoub Shklar staining and immunocytochemistry. Further, the cells expressed mRNA for differentiated epithelial cells, including keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5. These results suggest that Wnt-10b promotes the differentiation of MPSEC

41 CFR 302-3.219 - Is there a limit on how many times I may receive reimbursement for tour renewal travel?

Science.gov (United States)

2010-07-01

... many times I may receive reimbursement for tour renewal travel? 302-3.219 Section 302-3.219 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION....219 Is there a limit on how many times I may receive reimbursement for tour renewal travel? (a) If you...

Upregulation of TrkB promotes epithelial-mesenchymal transition and anoikis resistance in endometrial carcinoma.

Directory of Open Access Journals (Sweden)

Wei Bao

Full Text Available Mechanisms governing the metastasis of endometrial carcinoma (EC are poorly defined. Recent data support a role for the cell surface receptor tyrosine kinase TrkB in the progression of several human tumors. Here we present evidence for a direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF, are more highly expressed in EC than in normal endometrium. High TrkB levels correlated with lymph node metastasis (p<0.05 and lymphovascular space involvement (p<0.05 in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the migratory and invasive capacity of cancer cell lines in vitro and resulted in anoikis in suspended cells. Conversely, exogenous expression of TrkB increased cell migration and invasion and promoted anoikis resistance in suspension culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in altered the expression of molecular mediators of the epithelial-to-mesenchymal transition (EMT. RNA interference (RNAi-mediated depletion of the downstream regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial transition and anoikis in vivo. Our data support a novel function for TrkB in promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential therapeutic target in human EC.

48 CFR 52.219-1 - Small Business Program Representations.

Science.gov (United States)

2010-10-01

... section 8(a), 8(d), 9, or 15 of the Small Business Act or any other provision of Federal law that... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Small Business Program....219-1 Small Business Program Representations. As prescribed in 19.308(a)(1), insert the following...

5 CFR 591.219 - How does OPM compute shelter price indexes?

Science.gov (United States)

2010-01-01

... REGULATIONS ALLOWANCES AND DIFFERENTIALS Cost-of-Living Allowance and Post Differential-Nonforeign Areas Cost-Of-Living Allowances § 591.219 How does OPM compute shelter price indexes? (a) In addition to rental...

Code Assessment of SPACE 2.19 using LSTF 10% Main Steam-Line-Break Test

Energy Technology Data Exchange (ETDEWEB)

Kim, Minhee; Kim, Seyun [KHNP CRI, Daejeon (Korea, Republic of)

2016-10-15

The Safety and Performance Analysis Code for Nuclear Power Plants (SPACE) has been developed in recent years by the Korea Hydro and Nuclear Power Co. through collaborative works with other Korean nuclear industries and research institutes. As a result of the development, the 2.19 version of the code was released through the successive various verification and validation works. In this study, results produced by the SPACE 2.19 code were compared with the experimental data from JAERI's LSTF Test Run SBSL- 01 for a 10% main steam line break transient in a pressurized water reactor. The LSTF 10% main steam line break test were simulated using the SPACE 2.19 for code V and V work. The overall comparisons between the SPACE 2.19 code prediction and the LSTF Test Run SB-SL-01 experimental data are reasonably satisfactory. The comparisons were conducted in terms of the variations of mass flow rate, void fraction, pressure, collapsed liquid level, temperature, and system flow rate for the transient. In addition, the input model was modified for simulation accuracy of PZR pressure based on the calculated results. The correction of PORV setpoint affects to simulate the PORV open and close phenomena similarly with experiments. From the modification, the computed results show a reasonable agreement with experimental data in overall transient time.

36 CFR 219.11 - Monitoring and evaluation for adaptive management.

Science.gov (United States)

2010-07-01

... OF AGRICULTURE PLANNING National Forest System Land and Resource Management Planning The Framework for Planning § 219.11 Monitoring and evaluation for adaptive management. (a) Plan monitoring strategy... national, regional, and local supply and demand for products, services, and values. Special consideration...

MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

Energy Technology Data Exchange (ETDEWEB)

Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

2014-05-09

Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

Synergistic activation of the CMV promoter by NF-κB P50 and PKG

International Nuclear Information System (INIS)

He Bin; Weber, Georg F.

2004-01-01

Several DNA binding NF-κB subunits are substrates for cGMP-dependent kinase (PKG) and their transactivation from cognate sites is induced by phosphorylation. This includes p50, which does not have a transcriptional activation domain and therefore needs to bind to other proteins to mediate gene expression. Here, we describe the synergistic transactivation by p50 and PKG from the CMV promoter. This is caused not only by phosphorylation of p50, leading to increased DNA binding, but also by PKG-dependent activation of CRE sites in the promoter. One of the CRE sites is located directly adjacent to a NF-κB site and is essential for p50-mediated induction of transcription. According to the binding of CREB to p50 in pull-down assays and according to the inhibition of p50-dependent transactivation by dominant-negative CREB, this reflects the formation of a transcription factor complex containing CREB and p50. The nuclear translocation of NF-κB is insufficient to distinguish among the multitude of promoters that harbor cognate recognition sites. The phosphorylation of multiple transcription factors by an upstream kinase, such as PKG, can lead to the formation of transcription factor complexes and differential transactivation from a subset of NF-κB sites. These interactions may be relevant for the activation of viral gene expression

Synthesis, radiochemistry and biological evaluation of a new somatostatin analogue (SDZ 219-387) labelled with technetium-99m

International Nuclear Information System (INIS)

Maina, T.; Stolz, B.; Albert, R.; Bruns, C.; Koch, P.; Maecke, H.

1994-01-01

A new derivative of octreotide SDZ 219-387 [PnAO-(D)Phe 1 -octreotide] was synthesized, which binds specifically and with high affinity to somatostatin receptors in vitro (pK i =9.79±0.16). This new somatostatin analogue chelates technetium-99m under mild labelling conditions in good yields. The resulting [ 99m Tc]SDZ 219-387 was stable up to 6 h after labelling and could be isolated in a pure radiochemical and chemical form by high-perfomance liquid chromatographic purification. The intravenous administration of purified [ 99m Tc]SDZ 219-387 revealed that the radioligand was rapidly cleared from circulation, and tumour uptake of 0.38% ID/g was observed at 1.5 h post injection. [ 99m Tc]SDZ 219-387 specifically interacted with somatostatin binding sites on the tumour. However, the radioligand is highly lipophilic and excreted mainly through the hepatobiliary system. As a consequence, [ 99m Tc]SDZ 219-387 exhibits increased background activity and therefore is not appropriate for the in vivo visualization of somatostatin receptor-positive tumours and/or their metastases in the abdomen. (orig.)

Marker-assisted introgression of broad-spectrum blast resistance genes into the cultivated MR219 rice variety.

Science.gov (United States)

Miah, Gous; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam B; Rahim, Harun A; Latif, Mohammad A

2017-07-01

The rice cultivar MR219 is famous for its better yield and long and fine grain quality; however, it is susceptible to blast disease. The main objective of this study was to introgress blast resistance genes into MR219 through marker-assisted selection (MAS). The rice cultivar MR219 was used as the recurrent parent, and Pongsu Seribu 1 was used as the donor. Marker-assisted foreground selection was performed using RM6836 and RM8225 to identify plants possessing blast resistance genes. Seventy microsatellite markers were used to estimate recurrent parent genome (RPG) recovery. Our analysis led to the development of 13 improved blast resistant lines with Piz, Pi2 and Pi9 broad-spectrum blast resistance genes and an MR219 genetic background. The RPG recovery of the selected improved lines was up to 97.70% with an average value of 95.98%. Selected improved lines showed a resistance response against the most virulent blast pathogen pathotype, P7.2. The selected improved lines did not express any negative effect on agronomic traits in comparison with MR219. The research findings of this study will be a conducive approach for the application of different molecular techniques that may result in accelerating the development of new disease-resistant rice varieties, which in turn will match rising demand and food security worldwide. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

bTSSfinder: a novel tool for the prediction of promoters in Cyanobacteria andEscherichia coli

KAUST Repository

Shahmuradov, Ilham; Mohamad Razali, Rozaimi; Bougouffa, Salim; Radovanovic, Aleksandar; Bajic, Vladimir B.

2016-01-01

Results: Here, we introduce bTSSfinder, a novel tool that predicts putative promoters for five classes of σ factors in Cyanobacteria (σA, σC, σH, σG and σF) and for five classes of sigma factors in E. coli (σ70, σ38, σ32, σ28 and σ24). Comparing to currently available tools, bTSSfinder achieves higher accuracy (MCC=0.86, F1-score=0.93) compared to the next best tool with MCC=0.59, F1-score=0.79) and covers multiple classes of promoters.

Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

Directory of Open Access Journals (Sweden)

Juan Du

2018-04-01

Full Text Available Andrographolide (ANDRO has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains were subjected to 3 and 21% of O2 for various times (0–12 h to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

36 CFR 223.219 - Sustainable harvest of special forest products.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Sustainable harvest of....219 Sustainable harvest of special forest products. (a) Sustainable harvest levels. Prior to offering... product's sustainable harvest level. A special forest product's sustainable harvest level is the total...

Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass

DEFF Research Database (Denmark)

Kirchner, Henriette; Nylen, Carolina; Laber, Samantha

2014-01-01

methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1–2 days and 12± 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR). Results VLCD....... The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor...... decreased promoter methylation of PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB. Conclusion...

The corrosion Characteristics and Behaviors of the Ti-2.19Al-2.35Zr alloy

International Nuclear Information System (INIS)

Kim, Tae Hoon; Kang, Chang Sun; Baek, Jong Hyuk; Kim, Hyun Gil; Choi, Byoung Kwon; Jeong, Yong Hwan

2007-01-01

Ti-2.19Al-2.35Zr alloy is being considered as a steam generator tube material for the advanced pressurized water reactor (PWR) which is being developed by KAERI for the purpose of seawater desalination as well as a small scale electricity production. The main operational environment of SMART differs somewhat from that of a commercial PWR. That is, a heat-exchange tube is always exposed to a high temperature/pressure condition and an ammonia water chemistry is designed as a pH controlling agent without an addition of boric acid. The excellent mechanical and corrosion resistance properties are required for the steam generator tube material in SMART. Thus Ti-2.19Al-2.35Zr alloy was studied to investigate of the corrosion characteristics and behaviors of the Ti- 2.19Al-2.35Zr alloy in a simulated-SMART loop

The 160 bp insertion in the promoter of Rht-B1i plays a vital role in increasing wheat height

Directory of Open Access Journals (Sweden)

Xueyuan eLou

2016-03-01

Full Text Available The extensive use of two alleles (Rht-B1b and Rht-D1b at the Rht-1 locus in wheat allowed dramatic increases in yields, triggering the so-called Green Revolution. Here, we found that a new natural allelic variation (Rht-B1i containing a single missense SNP (A614G in the coding region significantly increased plant height against the genetic background of both Rht-D1a (11.68% and Rht-D1b (7.89%. To elucidate the molecular mechanism of Rht-B1i, we investigated the promoter region. Sequence analysis showed that the Rht-B1i promoter could be divided into two classes depending on the presence or absence of a specific 160 bp insertion: Rht-B1i-1 (with the 160 bp insertion and Rht-B1i-2 (without the 160 bp insertion. The promoter of Rht-B1i-1 contained 32 more possible cis-acting elements than Rht-B1a, including a unique auxin response element AUXREPSIAA4. Quantitative RT-PCR analysis indicated that the 160 bp insertion is likely to promote the transcription of the Rht-B1i-1 gene. The coleoptile lengths of wheat varieties treated with IAA, GA3, and IAA/GA3, combined with the histochemical staining of transgenic Arabidopsis containing the Rht-B1i-1 promoter, showed that the height-increasing effect of Rht-B1i-1 may be due to the synergistic action of IAA and GA3. These results augment our understanding of the regulatory mechanisms of Rht-1 in wheat and provide new genetic resources for wheat improvement.

Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Alessandra Mosca

2018-04-01

Full Text Available The risk for Alzheimer’s disease (AD is associated with the presence of the 4 allele of Apolipoprotein E (APOE gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD. Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE-4 and RNF219/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients.

The activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 to the distal CCAAT box of the RhoB promoter

International Nuclear Information System (INIS)

Ahn, Jiwon; Choi, Jeong-Hae; Won, Misun; Kang, Chang-Mo; Gyun, Mi-Rang; Park, Hee-Moon; Kim, Chun-Ho; Chung, Kyung-Sook

2011-01-01

Highlights: → Regulation of transcriptional activation of RhoB is still unclear. → We examine the effect of p38 MAPK inhibition, and c-Jun and RhoB depletion on UV-induced RhoB expression and apoptosis. → We identify the regions of RhoB promoter necessary to confer UV responsiveness using pRhoB-luciferase reporter assays. → c-Jun, ATF2 and p300 are dominantly associated with NF-Y on the distal CCAAT box. → The activation of p38 MAPK primarily contribute to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins on distal CCAAT box of RhoB promoter. -- Abstract: The Ras-related small GTP-binding protein RhoB is rapidly induced in response to genotoxic stresses caused by ionizing radiation. It is known that UV-induced RhoB expression results from the binding of activating transcription factor 2 (ATF2) via NF-Y to the inverted CCAAT box (-23) of the RhoB promoter. Here, we show that the association of c-Jun with the distal CCAAT box (-72) is primarily involved in UV-induced RhoB expression and p38 MAPK regulated RhoB induction through the distal CCAAT box. UV-induced RhoB expression and apoptosis were markedly attenuated by pretreatment with the p38 MAPK inhibitor. siRNA knockdown of RhoB, ATF2 and c-Jun resulted in decreased RhoB expression and eventually restored the growth of UV-irradiated Jurkat cells. In the reporter assay using luciferase under the RhoB promoter, inhibition of RhoB promoter activity by the p38 inhibitor and knockdown of c-Jun using siRNA occurred through the distal CCAAT box. Immunoprecipitation and DNA affinity protein binding assays revealed the association of c-Jun and p300 via NF-YA and the dissociation of histone deacetylase 1 (HDAC1) via c-Jun recruitment to the CCAAT boxes of the RhoB promoter. These results suggest that the activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins to the distal CCAAT box of the RhoB promoter in Jurkat cells.

Estimating isotopic ratios, spatial distribution and inventory of radionuclides at Nuclear Sites 201, 219 and 221

International Nuclear Information System (INIS)

Gilbert, R.O.; Simpson, J.C.; Engel, D.W.; Kinnison, R.R.

1984-03-01

For NS201 the estimated average 239 240 Pu to 241 Am ratios for vegetation and soil are 7.3 and 11.5, respectively, where the 241 Am data were obtained using wet chemistry. The geometric mean 90 Sr to 137 Cs ratios for vegetation and soil at NS201 are estimated to be 1.1 and 1.9. These results suggest that the true (population) median 239 240 Pu to 241 Am and 90 Sr to 137 Cs ratios are smaller for vegetation than for soil at NS201. For NS219 and NS221 the estimated average 239 240 Pu to 241 Am ratios for surface soil at NS219 and NS221 are 2.8 and 0.78, respectively. There is an obvious statistical difference in the average 239 240 Pu to 241 Am ratios at these sites. The geometric mean 239 240 Pu to 241 Am ratios for vegetation samples at NS219 and NS221 are estimated to be 3.2 and 0.82, respectively. The data suggest there may be a difference in the 239 240 Pu to 241 Am ratios for soil and vegetation at NS219, but not at NS221. The geometric mean 90 Sr to 137 Cs ratio for surface soil at NS219 and NS221 combined is 0.93. The geometric mean 90 Sr to 137 Cs ratio for vegetation for the two sites (pooled data) is estimated to be 1.8. 43 references, 42 figures, 7 tables

222-S radioactive liquid waste line replacement and 219-S secondary containment upgrade, Hanford Site, Richland, Washington

International Nuclear Information System (INIS)

1995-01-01

The U.S. Department of Energy (DOE) is proposing to: (1) replace the 222-S Laboratory (222-S) radioactive liquid waste drain lines to the 219-S Waste Handling Facility (219-S); (2) upgrade 219-S by replacing or upgrading the waste storage tanks and providing secondary containment and seismic restraints to the concrete cells which house the tanks; and (3) replace the transfer lines from 219-S to the 241-SY Tank Farm. This environmental assessment (EA) has been prepared in compliance with the National Environmental Policy Act (NEPA) of 1969, as amended, the Council on Environmental Quality Regulations for Implementing the Procedural Provisions of NEPA (40 Code of Federal Regulations [CFR] 1500-1508), and the DOE Implementing Procedures for NEPA (10 CFR 1021). 222-S is used to perform analytical services on radioactive samples in support of the Tank Waste Remediation System and Hanford Site environmental restoration programs. Activities conducted at 222-S include decontamination of analytical processing and support equipment and disposal of nonarchived radioactive samples. These activities generate low-level liquid mixed waste. The liquid mixed waste is drained through pipelines in the 222-S service tunnels and underground concrete encasements, to two of three tanks in 219-S, where it is accumulated. 219-S is a treatment, storage, and/or disposal (TSD) unit, and is therefore required to meet Washington Administrative Code (WAC) 173-303, Dangerous Waste Regulations, and the associated requirements for secondary containment and leak detection. The service tunnels are periodically inspected by workers and decontaminated as necessary to maintain as low as reasonably achievable (ALARA) radiation levels. Although no contamination is reaching the environment from the service tunnels, the risk of worker exposure is present and could increase. 222-S is expected to remain in use for at least the next 30 years to serve the Hanford Site environmental cleanup mission

Amoral, im/moral and dis/loyal: Children's moral status in child welfare.

Science.gov (United States)

Knezevic, Zlatana

2017-11-01

This article is a discursive examination of children's status as knowledgeable moral agents within the Swedish child welfare system and in the widely used assessment framework BBIC. Departing from Fricker's concept of epistemic injustice, three discursive positions of children's moral status are identified: amoral, im/moral and dis/loyal. The findings show the undoubtedly moral child as largely missing and children's agency as diminished, deviant or rendered ambiguous. Epistemic injustice applies particularly to disadvantaged children with difficult experiences who run the risk of being othered, or positioned as reproducing or accommodating to the very same social problems they may be victimised by.

Transition behavior of asymmetric polystyrene-b-poly(2-vinylpyridine) films: A stable hexagonally modulated layer structure

Energy Technology Data Exchange (ETDEWEB)

Park, Sungmin; Koo, Kyosung; Kim, Kyunginn; Ahn, Hyungju; Lee, Byeongdu; Park, Cheolmin; Ryu, Du Yeol

2015-03-09

The phase transitions in the films of an asymmetric polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) were investigated by grazing incidence small-angle X-ray scattering (GISAXS) and transmission electron microscopy (TEM). Compared with the sequential transitions in the bulk, hexagonally perforated layer (HPL) – gyroid (GYR) – disorder (DIS) upon heating, the transitions in film geometry were dramatically changed with decreasing thickness due to the growing preferential interactions from substrate, resulting in a thickness-dependent transition diagram including four different morphologies of hexagonally modulated layer (HML), coexisting (HML and GYR), GYR, and DIS. Particularly in the films ≤10Lo, where Lo is d-spacing at 150 °C, a stable HML structure was identified even above the order-to-disorder transition (ODT) temperature of the bulk, which was attributed to the suppressed compositional fluctuations by the enhanced substrate interactions.

Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L.

Science.gov (United States)

Nishino, H; Hayashi, T; Arisawa, M; Satomi, Y; Iwashima, A

1993-01-01

Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA-enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid.

18 CFR 367.2190 - Account 219, Accumulated other comprehensive income.

Science.gov (United States)

2010-04-01

... COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT UNIFORM SYSTEM OF ACCOUNTS FOR CENTRALIZED SERVICE COMPANIES SUBJECT TO THE PROVISIONS OF THE PUBLIC UTILITY HOLDING COMPANY ACT OF 2005, FEDERAL POWER ACT AND NATURAL GAS ACT Balance Sheet Chart of Accounts Proprietary Capital § 367.2190 Account 219...

Identification of SH2B2β as an Inhibitor for SH2B1- and SH2B2α-Promoted Janus Kinase-2 Activation and Insulin Signaling

OpenAIRE

Li, Minghua; Li, Zhiqin; Morris, David L.; Rui, Liangyou

2007-01-01

The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the ins...

Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun [Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai (China); Gu, Wei, E-mail: krisgu70@163.com [Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxp@sjtu.edu.cn [Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, Shanghai (China)

2014-03-28

Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

DisArticle: a web server for SVM-based discrimination of articles on traditional medicine.

Science.gov (United States)

Kim, Sang-Kyun; Nam, SeJin; Kim, SangHyun

2017-01-28

Much research has been done in Northeast Asia to show the efficacy of traditional medicine. While MEDLINE contains many biomedical articles including those on traditional medicine, it does not categorize those articles by specific research area. The aim of this study was to provide a method that searches for articles only on traditional medicine in Northeast Asia, including traditional Chinese medicine, from among the articles in MEDLINE. This research established an SVM-based classifier model to identify articles on traditional medicine. The TAK + HM classifier, trained with the features of title, abstract, keywords, herbal data, and MeSH, has a precision of 0.954 and a recall of 0.902. In particular, the feature of herbal data significantly increased the performance of the classifier. By using the TAK + HM classifier, a total of about 108,000 articles were discriminated as articles on traditional medicine from among all articles in MEDLINE. We also built a web server called DisArticle ( http://informatics.kiom.re.kr/disarticle ), in which users can search for the articles and obtain statistical data. Because much evidence-based research on traditional medicine has been published in recent years, it has become necessary to search for articles on traditional medicine exclusively in literature databases. DisArticle can help users to search for and analyze the research trends in traditional medicine.

48 CFR 52.219-8 - Utilization of small business concerns.

Science.gov (United States)

2010-10-01

... management and daily business operations of which are controlled by one or more veterans. Women-owned small... Clauses 52.219-8 Utilization of small business concerns. As prescribed in 19.708(a), insert the following clause: Utilization of Small Business Concerns (MAY 2004) (a) It is the policy of the United States that...

50 CFR 216.219 - Renewal and modifications of Letters of Authorization.

Science.gov (United States)

2010-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Taking of Marine Mammals Incidental to Explosive Severance.... Gulf of Mexico § 216.219 Renewal and modifications of Letters of Authorization. (a) A Letter of...

Thermodiffusion as a close-to-interface effect that matters in non-isothermal (dis)orderly protein aggregations

Energy Technology Data Exchange (ETDEWEB)

Gadomski, A., E-mail: agad@utp.edu.pl; Kruszewska, N., E-mail: nkruszewska@utp.edu.pl

2014-08-01

The goal of this discussion letter is to argue how and why an inherent nanoscale thermodiffusion (Soret-type) effect can be relevant in (dis)orderly protein aggregation. We propose a model in which the aggregation of proteins, in the presence of temperature gradient, is described in terms of Smoluchowski dynamics in the phase space of nuclei sizes. The Soret coefficient of the aggregation is proportional to the variations of the aggregation free energy over temperature. The free energy is related to the (interface) boundary condition of the system. When boundary condition is of equilibrium Gibbs–Thomson type, with a well-stated surface tension of the nucleus, to the system can be assigned a negative Soret effect. On the contrary, when a non-equilibrium perturbing (salting-out) term enters the boundary condition, a positive Soret effect may manifest. A zero-value Soret regime is expected to occur in between, yielding very soft (“fragile”) non-Kossel protein-type crystals. - Highlights: • Comprehension for non-isothermal formation of (dis)orderly protein aggregation. • Classification of temperature-sensitive morphologies in colloid-type aggregation. • Morphologies split into near-equilibrium and nonequilibrium structural outcomes. • Classification on mesoscopic nonequilibrium thermodynamics near local equilibrium.

VennDIS: a JavaFX-based Venn and Euler diagram software to generate publication quality figures.

Science.gov (United States)

Ignatchenko, Vladimir; Ignatchenko, Alexandr; Sinha, Ankit; Boutros, Paul C; Kislinger, Thomas

2015-04-01

Venn diagrams are graphical representations of the relationships among multiple sets of objects and are often used to illustrate similarities and differences among genomic and proteomic datasets. All currently existing tools for producing Venn diagrams evince one of two traits; they require expertise in specific statistical software packages (such as R), or lack the flexibility required to produce publication-quality figures. We describe a simple tool that addresses both shortcomings, Venn Diagram Interactive Software (VennDIS), a JavaFX-based solution for producing highly customizable, publication-quality Venn, and Euler diagrams of up to five sets. The strengths of VennDIS are its simple graphical user interface and its large array of customization options, including the ability to modify attributes such as font, style and position of the labels, background color, size of the circle/ellipse, and outline color. It is platform independent and provides real-time visualization of figure modifications. The created figures can be saved as XML files for future modification or exported as high-resolution images for direct use in publications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Capacitación a distancia (CapDis y el uso de plataformas virtuales. La experiencia del Centro Centroamericano de Población

Directory of Open Access Journals (Sweden)

Marín, Carmen

2006-01-01

Full Text Available Introducción.- Las NTIC abren nuevas posibilidades para la educación. Aprender en entornos mediados por NTIC supone flexibilidad en espacio y tiempo e interacción entre los participantes para el aprendizaje significativo. Las universidades al implementar ofertas formativas de carácter virtual deben reconsiderar sus modelos de enseñanza y de aprendizaje e iniciar procesos de análisis y revisión de las experiencias realizadas. El presente artículo pretende sistematizar el accionar del proyecto CapDis del Centro Centroamericano de Población (CCP al introducir el uso de las nuevas tecnologías de información y comunicación en la educación superior en la Universidad de Costa Rica (UCR.Métodos.- Se basa en un estudio de caso que aplica el método cualitativo mediante revisión documental y registro de eventos.Resultados.- En CapDis se identifican las siguientes etapas: I. Páginas web vinculadas; II. Páginas web integradas y III. Learning Management System. En las primeras dos etapas se dio soporte a los profesores y se asumió la mayor parte de las tareas de implementación y mantenimiento. Cuando se incorporó moodle.org, se facilitó la participación de más profesores quienes asumieron un rol más activo en CapDis. A marzo 2005, la comparación de metas y resultados evidencia que fueron superados los resultados esperados.Discusión.- El presente artículo se constituye en un insumo útil en la identificación de las dificultades, alcances y limitaciones de la incorporación de las NTIC en la docencia en educación superior en la Universidad de Costa Rica. Las etapas identificadas en CapDis han sido descritas en términos del alcance de los recursos NTIC puestos en práctica. Más allá de los aspectos tecnológicos y administrativos descritos, el proceso seguido por CapDis logró enriquecer la interacción de una modalidad asíncrona (diferida a una síncrona (inmediata, lo que abre la oportunidad de contribuir a una mejor comprensi

Factors Associated with Parent-Child (Dis)Agreement on Child Behavior and Parenting Problems in Chinese Immigrant Families

Science.gov (United States)

Fung, Joey J.; Lau, Anna S.

2010-01-01

We examined familial and cultural factors predicting parent-child (dis)agreement on child behavior and parenting problems. Immigrant Chinese parents (89.7% mothers; M age = 44.24 years) and their children (62 boys; 57.9%) between the ages of 9 and 17 years (M = 11.9 years, SD = 2.9) completed measures of parent punitive behavior and child…

20 CFR 219.31 - Evidence of a valid ceremonial marriage.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of a valid ceremonial marriage. 219... marriage. (a) Preferred evidence. Preferred evidence of a ceremonial marriage is— (1) A copy of the public record of the marriage, certified by the custodian of the record or by a Board employee; (2) A copy of a...

Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft growth

International Nuclear Information System (INIS)

Ouji, Yukiteru; Yoshikawa, Masahide; Moriya, Kei; Nishiofuku, Mariko; Matsuda, Ryosuke; Ishizaka, Shigeaki

2008-01-01

Although Wnts are expressed in hair follicles throughout life from embryo to adult, and considered to be critical for their development and maturation, their roles remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, Wnt-5a, Wnt-10b, and Wnt-11) on epithelial cell differentiation using adult mouse-derived primary skin epithelial cell (MPSEC) cultures and hair growth using hair follicle organ cultures. Only Wnt-10b showed evident promotion of epithelial cell differentiation and hair shaft growth, in contrast to Wnt-3a, 5a, and 11. Our results suggest that Wnt-10b is unique and plays an important role in differentiation of epithelial cells in the hair follicle

A novel cell growth-promoting factor identified in a B cell leukemia cell line, BALL-1

International Nuclear Information System (INIS)

Dao, T.; Holan, V.; Minowada, J.

1993-01-01

A novel leukemia cell growth-promoting activity has been identified in the culture supernatant from a human B cell leukemia cell line, BALL-1. The supernatant from unstimulated cultures of the BALL-1 cells significantly promoted the growth of 16 out of 24 leukemia/lymphoma cell lines of different lineages (T, B and non-lymphoid) in a minimal concentration of fetal bovine serum (FBS), and 5 out of 12 cases of fresh leukemia cells in FBS-free medium. The growth-promoting sieve filtration and dialysis. The MW of the factor was less than 10 kDa. The growth-promoting activity was heat and acid stable and resistant to trypsin treatment. The factor isolated from the BALL-1 supernatant was distinct from known polypeptide growth factors with MW below 10 kDa, such as epidermal growth factor, transforming growth factor α, insulin-like growth factor I (IGF-I), IGF-II and insulin, as determine by specific antibodies and by cell-growth-promoting tests. The factor is the BALL-1 supernatant did not promote the proliferation of normal human fresh peripheral blood lymphocytes or mouse fibroblast cell line, BALB/C 3T3. In addition to the BALL-1 supernatant, a similar growth-promoting activity was found in the culture supernatant from 13 of 17 leukemia/lymphoma cell lines tested. The activity in these culture supernatant promoted the growth of leukemia/lymphoma cell lines in autocrine and/or paracrine fashions. These observations suggest that the low MW cell growth-promoting activity found in the BALL-1 culture supernatant is mediated by a novel factor which may be responsible for the clonal expansion of particular leukemic clones. (author)

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

OpenAIRE

Shin, Jung Hoon; Park, Se-Ho

2013-01-01

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 ?-galactosylceramide (?-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-? by NKT cells, concomitant with a d...

CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

Science.gov (United States)

Zhai, Yue; Wu, Bo; Li, Jia; Yao, Xi-ying; Zhu, Ping; Chen, Zhi-nan

2016-01-01

TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients, where it induces proinflammatory cytokine secretion. However, in other cases, TNF will cause cell death. Considering the abnormal proliferation and activation of rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis could possibly relieve arthritis. However, the mechanism mediating TNF-induced synovioblast survival versus cell death in RA is not fully understood. Our objective was to study the role of CD147 in TNF downstream pathway preference in RA synovioblasts. We found that overexpressing TNF in synovial tissue did not increase the apoptotic level and, in vitro, TNF-induced mild synovioblast apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both increased the apoptotic rate and inhibited IκB kinase (IKK)/IκB/NF-κB pathway-dependent proinflammatory cytokine secretion. Further, we determined that it was the extracellular portion of CD147 and not the intracellular portion that was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody inhibited TNF-induced proinflammatory cytokine production but had no effect on apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced apoptosis by promoting IKK/IκB/NF-κB pathway, and the extracellular portion of CD147 is the functional region. CD147 inhibits TNF-stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits NF-κB-related cytokine secretion. CD147's extracellular portion is responsible for apoptosis resistance. CD147 antibody inhibits TNF-related cytokine secretion without additional apoptosis.

Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

Directory of Open Access Journals (Sweden)

Negin N Blattman

2014-04-01

Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

Directory of Open Access Journals (Sweden)

Marcell Cserhalmi

2017-09-01

Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

Higher order constraints on the Higgs production rate from fixed-target DIS data

International Nuclear Information System (INIS)

Alekhin, S.; Bluemlein, J.; Moch, S.

2011-01-01

The constraints of fixed-target DIS data in fits of parton distributions including QCD corrections to next-to-next-to leading order are studied. We point out a potential problem in the analysis of the NMC data which can lead to inconsistencies in the extracted value for α s (M Z ) and the gluon distribution at higher orders in QCD. The implications for predictions of rates for Standard Model Higgs boson production at hadron colliders are investigated. We conclude that the current range of excluded Higgs boson masses at the Tevatron appears to be much too large. (orig.)

Core promoter mutations 3 years after anti-hepatitis B e seroconversion in patients with chronic hepatitis B or hepatitis B and C infection and cancer remission.

Science.gov (United States)

Zampino, Rosa; Marrone, Aldo; Karayiannis, Peter; Cirillo, Grazia; del Giudice, Emanuele Miraglia; Rania, Giovanni; Utili, Riccardo; Ruggiero, Giuseppe

2002-09-01

In this study, we aimed to evaluate the persistence of hepatitis B virus (HBV) DNA and the role of HBV core promoter and precore region mutations in 28 young cancer survivor patients with HBV or HBV and hepatitis C virus (HCV) infections, and persistently normal ALT levels, after spontaneous or interferon (IFN)-induced anti-hepatitis B e (HBe) seroconversion. Sera from 15 patients with HBV and 13 with dual HBV-HCV infection were analyzed for the presence of HBV-DNA and HCV-RNA by polymerase chain reaction 3 yr after anti-HBe seroconversion. A total of 21 patients had seroconverted spontaneously and seven did so after IFN treatment. The core promoter and the precore regions were amplified sequenced directly. Among patients with HBV infection, HBV-DNA was detected in five of nine (55%) with spontaneous anti-HBe and in all six treated patients (p = 0.092). In the coinfected patients, four had cleared both HBV-DNA and HCV-RNA, five were HBV-DNA negative/HCV-RNA positive and four had the reverse viral pattern. Among the 15 patients with persistence of HBV-DNA, a 7-base pair nucleotide deletion in the core promoter (1757-1763) was present in seven of 10 patients with spontaneous and in one of five patients with IFN-induced seroconversion (p = 0.033). The G1896A precore stop codon mutation was never observed. HBV-DNA levels were significantly lower in patients with the core promoter deletion (p = 0.011). The 7-base pair deletion generated a truncated X protein at amino-acid position 132. A core promoter deletion after anti-HBe seroconversion was associated with low HBV-DNA levels, probably because of downregulation of pregenomic RNA production and truncation of the X protein. HBV-DNA persistence was a frequent event, even in the absence of active liver disease.

Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism

DEFF Research Database (Denmark)

Litjens, Nicolle H R; van der Plas, Mariena J A; Ravensbergen, Bep

2004-01-01

Psoriasis is a type-1 T cell-mediated, chronic inflammatory disease. Since interleukin (IL)-12p70 promotes the development of type-1 T cells, we investigated whether psoriasis is associated with an increased production of this cyctokine by blood cells. Results revealed that the production of IL-12p....... The frequencies of the various genotypes for the promoter region of the gene encoding IL-12p40 (IL12B) did not differ between psoriasis patients and controls. No association was observed between the various IL12B promoter genotypes and the LPS-stimulated production of IL-12p70 or IL-12p40 by blood cells. Together......, psoriasis is not associated with a promoter polymorphism in the IL12B gene nor with the production of IL-12p70 by LPS-stimulated blood cells....

Wnt5b-associated exosomes promote cancer cell migration and proliferation.

Science.gov (United States)

Harada, Takeshi; Yamamoto, Hideki; Kishida, Shosei; Kishida, Michiko; Awada, Chihiro; Takao, Toshifumi; Kikuchi, Akira

2017-01-01

Wnt5b is a member of the same family of proteins as Wnt5a, the overexpression of which is associated with cancer aggressiveness. Wnt5b is also suggested to be involved in cancer progression, however, details remain unclarified. We analyzed the biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b were essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a. In cultured-cell conditioned medium, Wnt5b was detected in supernatant or precipitation fractions that were separated by centrifugation at 100 000 g. In PANC-1 pancreatic cancer cells, 55% of secreted endogenous Wnt5b was associated with exosomes. Exosomes from wild-type PANC-1 cells, but not those from Wnt5b-knockout PANC-1 cells, activated Wnt5b signaling in CHO cells and stimulated migration and proliferation of A549 lung adenocarcinoma cells, suggesting that endogenous, Wnt5b-associated exosomes are active. The exosomes were taken up by CHO cells and immunoelectron microscopy revealed that Wnt5b is indeed associated with exosomes. In Caco-2 colon cancer cells, most Wnt5b was recovered in precipitation fractions when Wnt5b was ectopically expressed (Caco-2/Wnt5b cells). Knockdown of TSG101, an exosome marker, decreased the secretion of Wnt5b-associated exosomes from Caco-2/Wnt5b cells and inhibited Wnt5b-dependent cell proliferation. Exosomes secreted from Caco-2/Wnt5b cells stimulated migration and proliferation of A549 cells. These results suggest that Wnt5b-associated exosomes promote cancer cell migration and proliferation in a paracrine manner. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The diagnosis and molecular analysis of a novel 21.9kb deletion (Qinzhou type deletion) causing α+ thalassemia.

Science.gov (United States)

Long, Ju; Yan, Shanhuo; Lao, Kegan; Pang, Wanrong; Ye, Xuehe; Sun, Lei

2014-04-01

α-Thalassemia is a common single-gene genetic disease that can cause Hb Bart's hydrops fetalis and Hb H disease in tropical and subtropical regions. When examining conventional thalassemia genes, an only detected --(SEA) genotype sample needs further analysis. In doing so, we found a novel 21.9kb deletion (Qinzhou type deletion). The deletion position of the novel 21.9kb deletion is from 14373bp to 36299bp of the α-globin gene cluster (NG_000006.1); thus, there exists a 21927bp sequence deletion, into which a 29bp sequence is added. After sequence analysis, a group of Gap-PCR primers were synthesized to diagnose this novel thalassemia genotype. Through pedigree analysis, we deduced that the propositus obtained the novel alleles from her mother. The genotype of this propositus is --(SEA)/-α(21.9) and its phenotype conforms to the characteristics of Hb H disease, establishing that the combination between -α(21.9) genotype and α(0) genotype can lead to Hb H disease. By molecular analysis, we established that this case fits the characteristic of an α(+) thalassemia genotype. © 2013.

Flavor-Specific Inclusive B Decays to Charm

International Nuclear Information System (INIS)

Coan, T.E.; Fadeyev, V.; Korolkov, I.; Maravin, Y.; Narsky, I.; Shelkov, V.; Staeck, J.; Stroynowski, R.; Volobouev, I.; Ye, J.; Artuso, M.; Azfar, F.; Efimov, A.; Goldberg, M.; He, D.; Kopp, S.; Moneti, G.C.; Mountain, R.; Schuh, S.; Skwarnicki, T.; Stone, S.; Viehhauser, G.; Xing, X.; Bartelt, J.; Csorna, S.E.; Jain, V.; McLean, K.W.; Marka, S.; Godang, R.; Kinoshita, K.; Lai, I.C.; Pomianowski, P.; Schrenk, S.; Bonvicini, G.; Cinabro, D.; Greene, R.; Perera, L.P.; Zhou, G.J.; Barish, B.; Chadha, M.; Chan, S.; Eigen, G.; Miller, J.S.; OGrady, C.; Schmidtler, M.; Urheim, J.; Weinstein, A.J.; Wuerthwein, F.; Bliss, D.W.; Masek, G.; Paar, H.P.; Prell, S.; Sharma, V.; Asner, D.M.; Gronberg, J.; Hill, T.S.; Lange, D.J.; Morrison, R.J.; Nelson, H.N.; Nelson, T.K.; Richman, J.D.; Roberts, D.; Ryd, A.; Witherell, M.S.; Balest, R.; Behrens, B.H.; Ford, W.T.; Gritsan, A.; Park, H.; Roy, J.; Smith, J.G.; Alexander, J.P.; Bebek, C.; Berger, B.E.; Berkelman, K.; Bloom, K.; Boisvert, V.; Cassel, D.G.; Cho, H.A.; Crowcroft, D.S.; Dickson, M.; Dombrowski, S. von; Drell, P.S.; Ecklund, K.M.; Ehrlich, R.; Foland, A.D.; Gaidarev, P.; Gibbons, L.; Gittelman, B.; Gray, S.W.; Hartill, D.L.; Heltsley, B.K.; Hopman, P.I.; Kandaswamy, J.; Kim, P.C.; Kreinick, D.L.; Lee, T.; Liu, Y.; Mistry, N.B.; Ng, C.R.

1998-01-01

We have measured the branching fractions for B→ bar DX, B→DX, and B→ bar DX ell + ν. From these results and some previously measured branching fractions, we obtain B(b→c bar cs) =(21.9±3.7)%, B(b→sg) 0 →K - π + )=(3.69±0.20)%. Implications for the B semileptonic decay problem (measured branching fraction being below theoretical expectations) are discussed. With the increase in the value of B(b→c bar cs) due to B→DX, the discrepancy is no longer statistically compelling. copyright 1998 The American Physical Society

Generalized threshold resummation in inclusive DIS and semi-inclusive electron-positron annihilation

International Nuclear Information System (INIS)

Almasy, A.A.; Lo Presti, N.A.; Vogt, A.

2015-11-01

We present analytic all-order results for the highest three threshold logarithms of the space-like and time-like off-diagonal splitting functions and the corresponding coefficient functions for inclusive deep-inelastic scattering (DIS) and semi-inclusive e + e - annihilation. All these results, obtained through an order-by-order analysis of the structure of the corresponding unfactorized quantities in dimensional regularization, can be expressed in terms of the Bernoulli functions introduced by one of us and leading-logarithmic soft-gluon exponentials. The resulting numerical corrections are small for the splitting functions but large for the coefficient functions. In both cases more terms in the threshold expansion need to be determined in order to arrive at quantitatively reliable results.

48 CFR 1852.219-74 - Use of rural area small businesses.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Use of rural area small... and Clauses 1852.219-74 Use of rural area small businesses. As prescribed in 1819.7103, insert the following clause: Use of Rural Area Small Business (SEP 1990) (a) Definitions. Rural area means any county...

48 CFR 3052.219-72 - Evaluation of prime contractor participation in the DHS mentor-protégé program.

Science.gov (United States)

2010-10-01

... contractor participation in the DHS mentor-protégé program. 3052.219-72 Section 3052.219-72 Federal... Evaluation of prime contractor participation in the DHS mentor-protégé program. As prescribed in (HSAR) 48... the DHS Mentor-Protégé Program (JUN 2006) This solicitation contains a source selection factor or...

Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

Science.gov (United States)

Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

2016-09-01

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

Science.gov (United States)

Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

2017-03-01

Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

Amoral, im/moral and dis/loyal: Children’s moral status in child welfare

Science.gov (United States)

Knezevic, Zlatana

2017-01-01

This article is a discursive examination of children’s status as knowledgeable moral agents within the Swedish child welfare system and in the widely used assessment framework BBIC. Departing from Fricker’s concept of epistemic injustice, three discursive positions of children’s moral status are identified: amoral, im/moral and dis/loyal. The findings show the undoubtedly moral child as largely missing and children’s agency as diminished, deviant or rendered ambiguous. Epistemic injustice applies particularly to disadvantaged children with difficult experiences who run the risk of being othered, or positioned as reproducing or accommodating to the very same social problems they may be victimised by. PMID:29187776

Lactate dehydrogenase-B is silenced by promoter methylation in a high frequency of human breast cancers.

Directory of Open Access Journals (Sweden)

Nicola J Brown

Full Text Available Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer.Lactate Dehydrogenase (LDH isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA.Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/25 cases of breast cancer tissues, but not in 5/5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained, was seen in 23/26 (88% breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O(2, for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002, and T-47D cells (2.9 fold, p = 0.009, but not in MDA-MB-436 (-0.9 fold, p = 0.229, or MCF10AT (1.2 fold, p = 0.09 cells.Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia.

48 CFR 653.219-71 - DOS form DS-4053, Department of State Mentor-Protégé Program Application.

Science.gov (United States)

2010-10-01

..., Department of State Mentor-Protégé Program Application. 653.219-71 Section 653.219-71 Federal Acquisition...-4053, Department of State Mentor-Protégé Program Application. As prescribed in 619.102-70(i), DS-4053 is prescribed for use in applying for an agreement under the Department of State Mentor-Protégé...

Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms.

Science.gov (United States)

Yan, Hongxia; Zhang, Ping; Kong, Xue; Hou, Xianglian; Zhao, Li; Li, Tianhang; Yuan, Xiaozhou; Fu, Hongjun

2017-04-01

In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4 + CD49b + LAG-3 + T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25 + Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10 + Foxp3 - CD4 + T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.

48 CFR 852.219-9 - VA Small business subcontracting plan minimum requirements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false VA Small business... Provisions and Clauses 852.219-9 VA Small business subcontracting plan minimum requirements. As prescribed in subpart 819.709, insert the following clause: VA Small Business Subcontracting Plan Minimum Requirements...

KIF26B, a novel oncogene, promotes proliferation and metastasis by activating the VEGF pathway in gastric cancer.

Science.gov (United States)

Zhang, H; Ma, R-R; Wang, X-J; Su, Z-X; Chen, X; Shi, D-B; Guo, X-Y; Liu, H-T; Gao, P

2017-10-05

Tumor metastasis is the main reason of cancer-related death for gastric cancer (GC) patients and gene expression microarray data indicate that kinesin family member 26B (KIF26B) is one of the most upregulated genes in metastatic GC samples. Specifically, KIF26B expression was upregulated in a stepwise manner from non-tumorous gastric mucosa, primary GC tissues without metastasis, via primary GC tissues with metastasis, to secondary lymph node metastatic (LNM) foci. Increased expression of KIF26B was correlated with tumor size, positive LNM or distant metastases and poor prognosis. KIF26B, negatively regulated by miR-372, promoted GC cell proliferation and metastasis in vitro and in vivo. Mechanistic investigations confirmed that the main target of KIF26B was the vascular endothelial growth factor (VEGF) signaling pathway, particularly by inhibition or overexpression of VEGFA, PXN, FAK, PIK3CA, BCL2 and CREB1. Thus, KIF26B, a novel oncogene regulated by miR-372, promotes proliferation and metastasis through the VEGF pathway in GC.

Final-state interaction in semi-inclusive DIS off nuclei

CERN Document Server

Ciofi degli Atti, C

2003-01-01

The Final-State Interaction (FSI) in Deep-Inelastic Scattering (DIS) of leptons off a nucleus A, due to the propagation of the struck nucleon debris and its hadronization in the nuclear environment is considered. The effective cross-section of such a partonic system with the nucleons of the medium and its time dependence are estimated, for different values of the Bjorken scaling variable, on the basis of a model which takes into account both the production of hadrons due to the breaking of the color string, which is formed after a quark is knocked out off a bound nucleon, as well as the production of hadrons originating from gluon radiation. It is shown that the interaction, the evolution and the hadronization of the partonic system in the nuclear environment can be thoroughly investigated by a new type of semi-inclusive process, denoted A(e,e'(A-1))X, in which the scattered lepton is detected in coincidence with a heavy nuclear fragment, namely a nucleus (A-1) in low energy and momentum states. As a matter o...

Comparison on Promotion Effect of Various Types of Surfactants on HCFC-141b Hydrate Induction Time

Science.gov (United States)

Li, Juan; Sun, Zhigao; Liu, Chenggang; Zhu, Minggui

2018-03-01

Cold storage in air conditioning based on refrigerant hydrate is a new-type energy saving technology to reduce initial investment and running cost of air conditioning equipments and improve system stability. Refrigerant hydrate is generated under critical temperature and pressure condition, while surfactant is an effective medium to promote its phase equilibrium. In this paper, in order to research such promotion effect, different type of surfactants with unique mechanism, SDS, Tween80 and Span80, n-BA were selected to compare the respective impact on HCFC141b hydrate induction time based on temperature curve. Experimental results showed that no obvious change had been discovered when no surfactant was added into pure water system, which coincided with phase equilibrium diagram of HCFC141b. All the four kinds of surfactants had realized promotion effect to various degrees. For each hydration system, a large gap existed between the longest and the shortest induction time in 6 groups of parallel experiments, meaning relatively poor system stability. Under the combined effect of Tween80 (2wt%), Span80 (0.1wt%) and n-BA (0.1wt%), average and the shortest induction time was 20.9min and 17.5min respectively, corresponding to the best promotion effect.

I219V polymorphism in hMLH1 gene in patients affected with ulcerative colitis.

Science.gov (United States)

Vietri, Maria Teresa; Riegler, Gabriele; De Paola, Marialaura; Simeone, Serena; Boggia, Maria; Improta, Alessia; Parisi, Mariarita; Molinari, Anna Maria; Cioffi, Michele

2009-04-01

hMLH1 gene, lying on chromosome 3p21-23, is a key factor of the mismatch repair (MMR) complex, which amends DNA replication errors. MMR alterations are involved in the development of both hereditary and sporadic forms of colorectal carcinoma related to ulcerative colitis (UC). I219V Polymorphism is located on exon 8 of hMLH1 and provides an aminoacidic substitution of isoleucine to valine, on the protein codon 219. This may affect the speed and fidelity of protein synthesis because of a tRNA paucity or changes in the mRNA secondary structure. Most of the hereditary nonpolyposis colon cancer-associated missense mutations of hMLH1 cause structural changes of the amino- or carboxy-terminal regions, involving the domains that interact with ATP and hPMS2. In this study, we analyzed the hMLH1 I219V polymorphism frequency in colectomized patients with UC. Venous blood from 100 ulcerative patients and 97 apparently healthy subjects has been collected. Out of 100 patients affected with UC, 75 noncolectomized showed an alternating course of disease, while 25 did not respond to the common drugs, and underwent colectomy. Genotyping was performed by polymerase chain reaction and following enzymatic digestion by BccI. No significant differences were found between patients with UC and controls both for genotype and allele frequencies. However, our data show a significant association when colectomized and noncolectomized patients are compared. The frequencies of G homozygosity were 28% in colectomized and 10.7% in noncolectomized patients (p < 0.05, chi(2) = 4.4, Odds ratio = 3.3). The allele frequencies of allele A were 52% in colectomized and 68% in noncolectomized patients; while those of allele G were 48% and 32%, respectively. I219V polymorphism in hMLH1 could influence the clinical course of the disease and lead to resistance to therapy.

miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Li, Zhi [Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Jilin University (China); Li, Youjun, E-mail: liyoujunn@126.com [Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Jilin University (China); Wang, Nan; Yang, Lifeng; Zhao, Wei; Zeng, Xiandong [Central Hospital Affiliated to Shenyang Medical College (China)

2016-03-18

miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down-regulation of NKD2 mRNA and protein exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. - Highlights: • miR-130b is up-regulated and NKD2 is down-regulated in osteosarcoma cell lines. • Down-regulation of miR-130b inhibits proliferation of osteosarcoma cells. • Down-regulation of miR-130b promotes apoptosis of osteosarcoma cells. • miR-130b directly targets NKD2. • NKD2 regulates OS cell proliferation and apoptosis by inhibiting the Wnt signaling.

miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells

International Nuclear Information System (INIS)

Li, Zhi; Li, Youjun; Wang, Nan; Yang, Lifeng; Zhao, Wei; Zeng, Xiandong

2016-01-01

miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down-regulation of NKD2 mRNA and protein exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. - Highlights: • miR-130b is up-regulated and NKD2 is down-regulated in osteosarcoma cell lines. • Down-regulation of miR-130b inhibits proliferation of osteosarcoma cells. • Down-regulation of miR-130b promotes apoptosis of osteosarcoma cells. • miR-130b directly targets NKD2. • NKD2 regulates OS cell proliferation and apoptosis by inhibiting the Wnt signaling.

EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway.

Science.gov (United States)

Bonavia, R; Inda, M M; Vandenberg, S; Cheng, S-Y; Nagane, M; Hadwiger, P; Tan, P; Sah, D W Y; Cavenee, W K; Furnari, F B

2012-09-06

Sustaining a high growth rate requires tumors to exploit resources in their microenvironment. One example of this is the extensive angiogenesis that is a typical feature of high-grade gliomas. Here, we show that expression of the constitutively active mutant epidermal growth factor receptor, ΔEGFR (EGFRvIII, EGFR*, de2-7EGFR) is associated with significantly higher expression levels of the pro-angiogenic factor interleukin (IL)-8 in human glioma specimens and glioma stem cells. Furthermore, the ectopic expression of ΔEGFR in different glioma cell lines caused up to 60-fold increases in the secretion of IL-8. Xenografts of these cells exhibit increased neovascularization, which is not elicited by cells overexpressing wild-type (wt)EGFR or ΔEGFR with an additional kinase domain mutation. Analysis of the regulation of IL-8 by site-directed mutagenesis of its promoter showed that ΔEGFR regulates its expression through the transcription factors nuclear factor (NF)-κB, activator protein 1 (AP-1) and CCAAT/enhancer binding protein (C/EBP). Glioma cells overexpressing ΔEGFR showed constitutive activation and DNA binding of NF-κB, overexpression of c-Jun and activation of its upstream kinase c-Jun N-terminal kinase (JNK) and overexpression of C/EBPβ. Selective pharmacological or genetic targeting of the NF-κB or AP-1 pathways efficiently blocked promoter activity and secretion of IL-8. Moreover, RNA interference-mediated knock-down of either IL-8 or the NF-κB subunit p65, in ΔEGFR-expressing cells attenuated their ability to form tumors and to induce angiogenesis when injected subcutaneously into nude mice. On the contrary, the overexpression of IL-8 in glioma cells lacking ΔEGFR potently enhanced their tumorigenicity and produced highly vascularized tumors, suggesting the importance of this cytokine and its transcription regulators in promoting glioma angiogenesis and tumor growth.

Sediment tracing in the upper Hunter catchment using elemental and mineralogical compositions: Implications for catchment-scale suspended sediment (dis)connectivity and management

Science.gov (United States)

Fryirs, Kirstie; Gore, Damian

2013-07-01

River bed colmation layers clog the interstices of gravel-bed rivers, impeding the vertical exchange of water and nutrients that drives ecosystem function in the hyporheic zone. In catchments where fine-grained sediment supply has increased since human disturbance, understanding sediment provenance and the (dis)connectivity of supply allows practitioners to target sediment source problems and treat them within catchment management plans. Release of alluvial fine-grained sediment from channel bank erosion since European settlement has resulted in the formation of a colmation layer along the upper Hunter River at Muswellbrook, eastern Australia. X-ray fluorescence spectrometry (XRF) and X-ray diffractometry (XRD) are used to determine the elemental and mineralogical signatures of colmation layer and floodplain sediment sources across this 4480 km2 catchment. This sediment tracing technique is used to construct a picture of how suspended sediment supply and (dis)connectivity operates in this catchment. In this system, the primary source areas are subcatchments in which sediments are stored largely in partly confined floodplain pockets, but from which sediment supply is unimpeded and directly connected to the receiving reach. Subcatchments in which alluvial sediment storage is significant — and which contain large, laterally unconfined valleys — are essentially 'switched off' or disconnected from the receiving reach. This is because large sediment sinks act to trap fine-grained sediment before it reaches the receiving reach, forming a buffer along the sediment conveyor belt. Given the age structure of floodplains in the receiving reach, this pattern of source area contributions and (dis)connectivity must have occurred throughout the Holocene.

Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway.

Science.gov (United States)

Yu, Nan; Wang, Sinian; Song, Xiujun; Gao, Ling; Li, Wei; Yu, Huijie; Zhou, Chuanchuan; Wang, Zhenxia; Li, Fengsheng; Jiang, Qisheng

2018-04-01

For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

Science.gov (United States)

Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

2017-05-15

Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional

Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

International Nuclear Information System (INIS)

Ouji, Yukiteru; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

2006-01-01

We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/c nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis

Cysteine cathepsins B and X promote epithelial-mesenchymal transition of tumor cells.

Science.gov (United States)

Mitrović, Ana; Pečar Fonović, Urša; Kos, Janko

2017-09-01

Cathepsins B and X are lysosomal cysteine carboxypeptidases suggested as having a redundant role in cancer. They are involved in a number of processes leading to tumor progression but their role in the epithelial-mesenchymal transition (EMT) remains unknown. We have investigated the contribution of both cathepsins B and X in EMT using tumor cell lines differing in their expression of epithelial and mesenchymal markers and cell morphology. Higher levels of both cathepsins are shown to promote EMT and are associated with the mesenchymal-like cell phenotype. Moreover, simultaneous knockdown of the two peptidases triggers a reverse, mesenchymal to epithelial transition. Of the two cathepsins, cathepsin B appears to be the stronger promotor of EMT. Furthermore, we evaluated the involvement of cathepsin B and X in the transforming growth factor-β1 (TGF-β1) signaling pathway, one of the key signaling mechanisms triggering EMT in cancer. In MCF-7 cells the expression of cathepsin B was shown to depend on their activation with TGF-β1 while, for cathepsin X, a TGF-β1 independent mechanism of induction during EMT is indicated. EMT is thus shown to be another mechanism linking cathepsins B and X with tumor progression. With silencing of their expression or inhibition of enzymatic activity, the tumor cells could be reverted to less aggressive epithelial-like phenotype. Copyright © 2017 Elsevier GmbH. All rights reserved.

MAT2B promotes adipogenesis by modulating SAMe levels and activating AKT/ERK pathway during porcine intramuscular preadipocyte differentiation

Energy Technology Data Exchange (ETDEWEB)

Zhao, Cunzhen; Chen, Xiaochang; Wu, Wenjing; Wang, Wusu; Pang, Weijun; Yang, Gongshe, E-mail: gsyang999@hotmail.com

2016-05-15

Intramuscular fat (IMF) has been demonstrated as one of the crucial factors of livestock meat quality. The MAT2B protein with MAT2α catalyzes the formation of methyl donor S- adenosylmethionine (SAMe) to mediate cell metabolism including proliferation and apoptosis. However, the regulatory effect of MAT2B on IMF deposition is still unclear. In this study, the effect of MAT2B on adipogenesis and its potential mechanism during porcine intramuscular preadipocyte differentiation was studied. The results showed that overexpression of MAT2B promoted adipogenesis and significantly up-regulated the mRNA and protein levels of adipogenic marker genes including FASN, PPARγ and aP2, consistently, knockdown of MAT2B inhibited lipid accumulation and down-regulated the mRNA and protein levels of the above genes. Furthermore, flow cytometry and EdU-labeling assay indicated that MAT2B regulate adipogenesis was partly due to influence intracellular SAMe levels and further affect cell clonal expansion. Also, increased expression of MAT2B activated the phosphorylations of AKT and ERK1/2, whereas knockdown of MAT2B blocked AKT signaling and repressed the phosphorylation of ERK1/2. Moreover, the inhibitory effect of LY294002 (a specific PI3K inhibitor) on the activities of AKT and ERK1/2 was partially recovered by overexpression of MAT2B in porcine intramuscular adipocytes. Finally, Co-IP experiments showed that MAT2B can directly interact with AKT. Taken together, our findings suggested that MAT2B acted as a positive regulator through modifying SAMe levels as well as activating AKT/ERK signaling pathway to promote porcine intramuscular adipocyte differentiation. - Highlights: • MAT2B up-regulates the expression of adipogenic marker genes and promotes porcine intramuscular preadipocyte differentiation. • MAT2B influences intracellular SAMe levels and further affects cell clonal expansion. • MAT2B interacts with AKT and activates AKT/ERK signaling pathway.

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

Directory of Open Access Journals (Sweden)

Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

CHARACTERIZATION OF THE K2-19 MULTIPLE-TRANSITING PLANETARY SYSTEM VIA HIGH-DISPERSION SPECTROSCOPY, AO IMAGING, AND TRANSIT TIMING VARIATIONS

Energy Technology Data Exchange (ETDEWEB)

Narita, Norio; Hori, Yasunori; Kusakabe, Nobuhiko; Takeda, Yoichi; Tamura, Motohide [Astrobiology Center, 2-21-1 Osawa, Mitaka, Tokyo, 181-8588 (Japan); Hirano, Teruyuki [Department of Earth and Planetary Sciences, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan); Fukui, Akihiko; Yanagisawa, Kenshi [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Asakuchi, Okayama 719-0232 (Japan); Sanchis-Ojeda, Roberto [Department of Astronomy, University of California, Berkeley, CA 94720 (United States); Winn, Joshua N. [Department of Physics, and Kavli Institute for Astrophysics and Space Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ryu, Tsuguru; Onitsuka, Masahiro [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo, 181-8588 (Japan); Kudo, Tomoyuki [Subaru Telescope, 650 North A’ohoku Place, Hilo, HI 96720 (United States); Delrez, Laetitia; Gillon, Michael; Jehin, Emmanuel [Institut d’Astrophysique et de Géophysique, Université de Liège, Allée du 6 Août 17, Bat. B5C, B-4000 Liège (Belgium); McCormac, James [Department of Physics, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Holman, Matthew [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States); Izumiura, Hideyuki, E-mail: norio.narita@nao.ac.jp [SOKENDAI (The Graduate University for Advanced Studies), 2-21-1 Osawa, Mitaka, Tokyo, 181-8588 (Japan)

2015-12-10

K2-19 (EPIC201505350) is an interesting planetary system in which two transiting planets with radii ∼7 R{sub ⊕} (inner planet b) and ∼4 R{sub ⊕} (outer planet c) have orbits that are nearly in a 3:2 mean-motion resonance. Here, we present results of ground-based follow-up observations for the K2-19 planetary system. We have performed high-dispersion spectroscopy and high-contrast adaptive-optics imaging of the host star with the HDS and HiCIAO on the Subaru 8.2 m telescope. We find that the host star is a relatively old (≥8 Gyr) late G-type star (T{sub eff} ∼ 5350 K, M{sub s} ∼ 0.9 M{sub ⊙}, and R{sub s} ∼ 0.9 R{sub ⊙}). We do not find any contaminating faint objects near the host star that could be responsible for (or dilute) the transit signals. We have also conducted transit follow-up photometry for the inner planet with KeplerCam on the FLWO 1.2 m telescope, TRAPPISTCAM on the TRAPPIST 0.6 m telescope, and MuSCAT on the OAO 1.88 m telescope. We confirm the presence of transit timing variations (TTVs), as previously reported by Armstrong and coworkers. We model the observed TTVs of the inner planet using the synodic chopping formulae given by Deck and Agol. We find two statistically indistinguishable solutions for which the period ratios (P{sub c}/P{sub b}) are located slightly above and below the exact 3:2 commensurability. Despite the degeneracy, we derive the orbital period of the inner planet P{sub b} ∼ 7.921 days and the mass of the outer planet M{sub c} ∼ 20 M{sub ⊕}. Additional transit photometry (especially for the outer planet) as well as precise radial-velocity measurements would be helpful to break the degeneracy and to determine the mass of the inner planet.

The generation, validation and testing of a coupled 219-group neutron 36-group gamma ray AMPX-II library

International Nuclear Information System (INIS)

Panini, G.C.; Siciliano, F.; Lioi, A.

1987-01-01

The main characteristics of a P 3 coupled 219-group neutron 36-group gamma-ray library in the AMPX-II Master Interface Format obtained processing ENDF/B-IV data by means of various AMPX-II System modules are presented in this note both for the more reprocessing aspects and features of the generated component files-neutrons, photon and secondary gamma-ray production cross sections. As far as the neutron data are concerned there is the avaibility of 186 data sets regarding most significant fission products. Results of the additional validation of the neutron data pertaining to eighteen benchmark experiments are also given. Some calculational tests on both neutron and coupled data emphasize the important role of the secondary gamma-ray data in nuclear criticality safety calculations

UV light B-mediated inhibition of skin catalase activity promotes Gr-1+ CD11b+ myeloid cell expansion.

Science.gov (United States)

Sullivan, Nicholas J; Tober, Kathleen L; Burns, Erin M; Schick, Jonathan S; Riggenbach, Judith A; Mace, Thomas A; Bill, Matthew A; Young, Gregory S; Oberyszyn, Tatiana M; Lesinski, Gregory B

2012-03-01

Skin cancer incidence and mortality are higher in men compared with women, but the causes of this sex discrepancy remain largely unknown. UV light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1(+)CD11b(+) myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present in the skin, has been associated with skin carcinogenesis. We used the outbred, immune-competent Skh-1 hairless mouse model of UVB-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1(+)CD11b(+) myeloid cell percentage. Acute UVB exposure induced Gr-1(+)CD11b(+) myeloid cell skin infiltration, which was inhibited to a greater extent in male mice by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1(+)CD11b(+) myeloid cells was 55% higher in male tumor-bearing mice compared with their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced generation of Gr-1(+)CD11b(+) myeloid cells and subsequent skin carcinogenesis.

48 CFR 1852.219-77 - NASA Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NASA Mentor-ProtégÃ... and Clauses 1852.219-77 NASA Mentor-Protégé Program. As prescribed in 1819.7215, insert the following clause: NASA Mentor-Protégé Program (MAY 2009) (a) Prime contractors are encouraged to participate in the...

48 CFR 752.219-70 - USAID Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false USAID Mentor-ProtégÃ....219-70 USAID Mentor-Protégé Program. As prescribed in 719.273-11(a), insert the following provision: USAID Mentor-Protégé Program (July 13, 2007) (a) Large and small business are encouraged to participate...

48 CFR 552.219-75 - GSA Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false GSA Mentor-ProtégÃ....219-75 GSA Mentor-Protégé Program. As prescribed in 519.7017(a), insert the following clause: GSA Mentor-ProtéGé Program (SEP 2009) (a) Prime contractors, including small businesses, are encouraged to...

Identification of a second flagellin gene and functional characterization of a sigma70-like promoter upstream of a Leptospira borgpetersenii flaB gene.

Science.gov (United States)

Lin, Min; Dan, Hanhong; Li, Yijing

2004-02-01

Leptospira borgpetersenii, one of the causative agents of leptospirosis in both animals and humans, is a bacterial pathogen with characteristic motility that is mediated by the rotation of two periplasmic flagella (PF). The flaB gene coding for a core polypeptide subunit of PF was previously characterized by sequence analysis of its open reading frame (ORF) (M. Lin, J Biochem Mol Biol Biophys 2:181-187, 1999). The present study was undertaken to isolate and clone the uncharacterized sequence upstream of the flaB gene by using a PCR-based genome walking procedure. This has resulted in a 1470-bp genomic DNA sequence in which an 846-bp ORF coding for a 281-amino acid polypeptide (31.3 kDa) is identified 455 bp upstream from the flaB start codon. The encoded protein exhibits 72% amino acid identity to the deduced FlaB protein sequence of L. borgpetersenii and a high degree of sequence homology to the FlaB proteins of other spirochaetes. This has demonstrated for the first time that a second flaB gene homolog is present in a Leptospira species. The newly identified gene is designated flaB1, and the previously cloned flaB renamed flaB2. Within the intergenic sequence between flaB1 and flaB2, a potential stem-loop structure (12-bp inverted repeats) was identified 25 bp downstream of the flaB1 stop codon; this could serve as a transcription terminator for the flaB1 mRNA. Three E. coli-like promoter regions (I, II, and III) for binding Esigma(70), a regulatory sequence uncommonly found in flagellar genes, were predicted upstream of the flaB2 ORF. Only promoter region II contains a promoter that is functional in E. coli, as revealed at phenotypic and transcriptional levels by its capability of directing the expression of the chloramphenicol acetyltransferase (CAT) gene in the promoter probe vector pKK232-8. These observations may suggest that flaB1 and flaB2 are transcribed separately and do not form a transcriptional operon controlled by a single promoter.

B cells exposed to enterobacterial components suppress development of experimental colitis

DEFF Research Database (Denmark)

Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

2012-01-01

). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

Energy Technology Data Exchange (ETDEWEB)

Dai, Bin [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Hu, Zhiqiang, E-mail: zhiqhutg@126.com [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Huang, Hui; Zhu, Guangtong; Xiao, Zhiyong [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Wan, Weiqing; Zhang, Peng; Jia, Wang; Zhang, Liwei [Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050 (China)

2014-11-07

Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses.

Science.gov (United States)

Takahama, Michihiro; Fukuda, Mitsunori; Ohbayashi, Norihiko; Kozaki, Tatsuya; Misawa, Takuma; Okamoto, Toru; Matsuura, Yoshiharu; Akira, Shizuo; Saitoh, Tatsuya

2017-09-19

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

Directory of Open Access Journals (Sweden)

Michihiro Takahama

2017-09-01

Full Text Available Cyclic GMP-AMP synthase (cGAS is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5, in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING, the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis.

Nogo-B Promotes Angiogenesis in Proliferative Diabetic Retinopathy via VEGF/PI3K/Akt Pathway in an Autocrine Manner

Directory of Open Access Journals (Sweden)

Yuelu Zhang

2017-10-01

Full Text Available Background/Aims: Nogo-B, a conservative protein of endoplasmic reticulum, is a member of the reticulon family of proteins. Proliferative diabetic retinopathy (PDR is the major concerning problem of diabetic retinopathy. This study explored the role of Nogo-B in the regulation of angiogenesis in PDR patients and primary human retinal endothelial cells (HRMECs. Methods: Nogo-B was down-regulated through the use of Lentivirus-NogoB-RNAi, the effects of Nogo-B on angiogenesis under high glucose stimulation were evaluated via CCK-8 assay, wound closure assay, transwell assay, and tube formation assay. Expression of Nogo-B, VEGF, PI3K and Akt were determined by western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA. Co-culture systerm was used to explore cell communication. Results: Nogo-B was highly enriched in ocular tissues of PDR patients and in HRMECs exposed to high glucose. Down-regulation of Nogo-B attenuated high glucose induced cell migration and tube formation in HRMECs. Mechanistically, in comparison with the negative control group, Lentivirus-NogoB-RNAi group had exhibited reduced VEGF secretion, weakened PI3K and Akt activation. Besides, high glucose treatment promoted the secretion of Nogo-B and presented as a “long-term memory”. Conclusions: These data collectively indicated that Nogo-B promoted angiogenesis in HRMECs via VEGF/PI3K/Akt pathway in an autocrine manner.

Geometric scaling behavior of the scattering amplitude for DIS with nuclei

Science.gov (United States)

Kormilitzin, Andrey; Levin, Eugene; Tapia, Sebastian

2011-12-01

The main question, that we answer in this paper, is whether the initial condition can influence on the geometric scaling behavior of the amplitude for DIS at high energy. We re-write the non-linear Balitsky-Kovchegov equation in the form which is useful for treating the interaction with nuclei. Using the simplified BFKL kernel, we find the analytical solution to this equation with the initial condition given by the McLerran-Venugopalan formula. This solution does not show the geometric scaling behavior of the amplitude deeply in the saturation region. On the other hand, the BFKL Pomeron calculus with the initial condition at x=1/mR given by the solution to Balitsky-Kovchegov equation, leads to the geometric scaling behavior. The McLerran-Venugopalan formula is the natural initial condition for the Color Glass Condensate (CGC) approach. Therefore, our result gives a possibility to check experimentally which approach: CGC or BFKL Pomeron calculus, is more satisfactory.

Geometric scaling behavior of the scattering amplitude for DIS with nuclei

International Nuclear Information System (INIS)

Kormilitzin, Andrey; Levin, Eugene; Tapia, Sebastian

2011-01-01

The main question, that we answer in this paper, is whether the initial condition can influence on the geometric scaling behavior of the amplitude for DIS at high energy. We re-write the non-linear Balitsky–Kovchegov equation in the form which is useful for treating the interaction with nuclei. Using the simplified BFKL kernel, we find the analytical solution to this equation with the initial condition given by the McLerran–Venugopalan formula. This solution does not show the geometric scaling behavior of the amplitude deeply in the saturation region. On the other hand, the BFKL Pomeron calculus with the initial condition at x A =1/mR A given by the solution to Balitsky–Kovchegov equation, leads to the geometric scaling behavior. The McLerran–Venugopalan formula is the natural initial condition for the Color Glass Condensate (CGC) approach. Therefore, our result gives a possibility to check experimentally which approach: CGC or BFKL Pomeron calculus, is more satisfactory.

48 CFR 852.219-71 - VA mentor-protégé program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false VA mentor-protégÃ....219-71 VA mentor-protégé program. As prescribed in 819.7115(a), insert the following clause: VA Mentor-Protégé Program (DEC 2009) (a) Large businesses are encouraged to participate in the VA Mentor-Protégé...

The double bromodomain protein Brd2 promotes B cell expansion and mitogenesis.

Science.gov (United States)

Belkina, Anna C; Blanton, Wanda P; Nikolajczyk, Barbara S; Denis, Gerald V

2014-03-01

Bromodomain-containing transcriptional regulators represent new epigenetic targets in different hematologic malignancies. However, bromodomain-mediated mechanisms that couple histone acetylation to transcription in lymphopoiesis and govern mature lymphocyte mitogenesis are poorly understood. Brd2, a transcriptional coregulator that contains dual bromodomains and an extraterminal domain (the BET family), couples chromatin to cell-cycle progression. We reported previously the first functional characterization of a BET protein as an effector of mammalian mitogenic signal transduction: Eμ-Brd2 Tg mice develop "activated B cell" diffuse large B cell lymphoma. No other animal models exist for genetic or lentiviral expression of BET proteins, hampering testing of novel anti-BET anticancer drugs, such as JQ1. We transduced HSCs with Brd2 lentivirus and reconstituted recipient mice to test the hypothesis that Brd2 regulates hematopoiesis in BM and mitogenesis in the periphery. Forced expression of Brd2 provides an expansion advantage to the donor-derived B cell compartment in BM and increases mature B cell mitogenic responsiveness in vitro. Brd2 binds the cyclin A promoter in B cells, shown by ChIP, and increases cyclin A mRNA and protein levels, and S-phase progression in vitro in mitogen-stimulated primary B cells, but not T cells, reinforcing results from Eμ-Brd2 mice. The small molecule BET inhibitor JQ1 reduces B cell mitogenesis, consistent with the interpretation that BET inhibitors are antiproliferative. Brd2-specific knockdown experiments show that Brd2 is also required for hematopoiesis. We conclude that Brd2 plays a critical, independent role in regulation of mitogenic response genes, particularly cyclin A, in B cells.

Coxsackievirus B3 2A protease promotes encephalomyocarditis virus replication.

Science.gov (United States)

Song, Qin-Qin; Lu, Ming-Zhi; Song, Juan; Chi, Miao-Miao; Sheng, Lin-Jun; Yu, Jie; Luo, Xiao-Nuan; Zhang, Lu; Yao, Hai-Lan; Han, Jun

2015-10-02

To determine whether 2A protease of the enterovirus genus with type I internal ribosome entry site (IRES) effect on the viral replication of type II IRES, coxsackievirus B3(CVB3)-encoded protease 2A and encephalomyocarditis virus (EMCV) IRES (Type II)-dependent or cap-dependent report gene were transiently co-expressed in eukaryotic cells. We found that CVB3 2A protease not only inhibited translation of cap-dependent reporter genes through the cleavage of eIF4GI, but also conferred high EMCV IRES-dependent translation ability and promoted EMCV replication. Moreover, deletions of short motif (aa13-18 RVVNRH, aa65-70 KNKHYP, or aa88-93 PRRYQSH) resembling the nuclear localization signals (NLS) or COOH-terminal acidic amino acid motif (aa133-147 DIRDLLWLEDDAMEQ) of CVB3 2A protease decreased both its EMCV IRES-dependent translation efficiency and destroy its cleavage on eukaryotic initiation factor 4G (eIF4G) I. Our results may provide better understanding into more effective interventions and treatments for co-infection of viral diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

B physics from HQET in two-flavour lattice QCD

Energy Technology Data Exchange (ETDEWEB)

Bernardoni, F. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Blossier, B. [Paris-11 Univ., Orsay (France). Lab. de Physique Theorique; Bulava, J. [CERN, Geneva (Switzerland). Physics Department] [and others; Collaboration: ALPHA Collaboration

2012-11-15

We present our analysis of B physics quantities using non-perturbatively matched Heavy Quark Effective Theory (HQET) in N{sub f}=2 lattice QCD on the CLS ensembles. Using all-to-all propagators, HYP-smeared static quarks, and the Generalized Eigenvalue Problem (GEVP) approach with a conservative plateau selection procedure, we are able to systematically control all sources of error. With significantly increased statistics compared to last year, our preliminary results are anti m{sub b}(anti m{sub b})=4.22(10)(4){sub z} GeV for the MS b-quark mass, and f{sub B}=193(9){sub stat}(4){sub {chi}} MeV and f{sub B{sub s}}=219(12){sub stat} MeV for the B-meson decay constants.

On the energy dependence of DIS in the diffraction region of low x

Energy Technology Data Exchange (ETDEWEB)

Schildknecht, D. [Bielefeld, Univ., Fakultat fur Physik (Germany)

2005-07-01

The energy dependence of the virtual photoabsorption cross-section in deep inelastic scattering (DIS) at low x = Q{sup 2}/W{sup 2} < 0.1 may be described in terms of the saturation scale that in our approach depends on the energy, {lambda}{sup 2}{sub sat} = {lambda}{sup 2}{sub sat}(W{sup 2}). We briefly summarize our recent findings that allow us to predict the exponent C{sub 2} of {lambda}{sup 2}{sub sat}(W{sup 2}) {approx} (W{sup 2}){sup C{sub 2}} in agreement with the previous result obtained from fitting the experimental data. The exponent C{sub 2} depending on the relative magnitude of the longitudinal and transverse contribution to the structure function, direct measurements of the longitudinal part are urgently needed. (author)

Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

Directory of Open Access Journals (Sweden)

Dan He

2018-05-01

Full Text Available Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL oxidized by heme enzyme myeloperoxidase (MPO is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1 using human aorta endothelial cells (HAEC and SR-B1 (-/- mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/- mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

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.

Prevalence of hepatitis B virus subgenotypes and basal core promoter, precore variants in patients with acute hepatitis B in central Vietnam.

Science.gov (United States)

Hayashi, Kazuhiko; Katano, Yoshiaki; Chuong, Tran Xuan; Takeda, Yasushi; Ishigami, Masatoshi; Itoh, Akihiro; Hirooka, Yoshiki; Nakano, Isao; Huy, Tran Van; Minh, Nguyen Ngoc; Diem, Tran thi Minh; An, Dong thi Hoai; Phiet, Pham Hoang; Goto, Hidemi

2009-01-01

Hepatitis B virus (HBV) has been classified into 8 genotypes that have different geographic distributions. The clinical outcomes of acute hepatitis are dependent on genotype. The aim of this study was to investigate the distribution of HBV subgenotypes and basal core promoter (BCP)/precore (PC) regions in acute hepatitis patients in Central Vietnam to clarify the distributions and the clinical and virological differences. 27 patients with acute hepatitis B were studied. HBV subgenotypes and BCP/PC variants were determined by direct sequencing of the preS, BCP/PC regions, respectively. HBV subgenotypes B4/Ba (n = 22) and C1/Cs (n = 5) were detected. Of the 27 patients, 3 developed fulminant hepatic failure, and all were infected with B4/Ba. Three patients had a BCP mutation, and 10 patients had a PC mutation in subgenotype B4/Ba. Three patients with C1/Cs had a BCP mutation. Two of 3 patients who progressed to fulminant hepatic failure had T1762, A1764, and A1896 simultaneously. None of the patients with acute, self-limited hepatitis carried these triple mutations. The prevalent HBV subgenotypes in patients with acute hepatitis B in Central Vietnam were B4/Ba and C1/Cs. BCP/PC variants have an association with the development of fulminant hepatic failure in subgenotype B4/Ba. Copyright 2009 S. Karger AG, Basel.

The x rescaling parameter' formula of the extended x rescaling model and the nuclear effect l-A DIS process

International Nuclear Information System (INIS)

Gao Yonghua; He Mingzhong; Duan Chungui

2003-01-01

The authors present an x rescaling parameters' formula for partons in the extended x rescaling model, where we have established the connection between the rescaling parameter and the mean binding energy. Using x rescaling parameters obtained by the x rescaling parameters' formula, we calculate the average nucleon structure function ratio of DIS process in l-A (Al, Ca, Pb) collision to l-C collision respectively. The result is in good agreement with experimental data

Isolation and characterization of cyp19a1a and cyp19a1b promoters in the protogynous hermaphrodite orange-spotted grouper (Epinephelus coioides).

Science.gov (United States)

Zhang, Weimin; Lu, Huijie; Jiang, Haiyan; Li, Mu; Zhang, Shen; Liu, Qiongyou; Zhang, Lihong

2012-02-01

Aromatase (CYP19A1) catalyzes the conversion of androgens to estrogens. In teleosts, duplicated copies of cyp19a1 genes, namely cyp19a1a and cyp19a1b, were identified, however, the transcriptional regulation of these two genes remains poorly understood. In the present study, the 5'-flanking regions of the orange-spotted grouper cyp19a1a (gcyp19a1a) and cyp19a1b (gcyp19a1b) genes were isolated and characterized. The proximal promoter regions of both genes were relatively conserved when compared to those of the other teleosts. Notably, a conserved FOXO transcriptional factor binding site was firstly reported in the proximal promoter of gcyp19a1a, and deletion of the region (-112 to -60) containing this site significantly decreased the promoter activities. The deletion of the region (-246 to -112) containing the two conserved FTZ-F1 sites also dramatically decreased the transcriptional activities of gcyp19a1a promoter, and both two FTZ-F1 sites were shown to be stimulatory cis-acting elements. A FTZ-F1 homologue isolated from ricefield eel (eFTZ-F1) up-regulated gcyp19a1a promoter activities possibly via the FTZ-F1 sites, however, a previously identified orange-spotted grouper FTZ-F1 homologue (gFTZ-F1) did not activate the transcription of gcyp19a1a promoter unexpectedly. As to gcyp19a1b promoter, all the deletion constructs did not show good promoter activities in either TM4 or U251-MG cells. Estradiol (100nM) up-regulated gcyp19a1b promoter activities by about 13- and 36-fold in TM4 and U251-MG cells, respectively, via the conserved ERE motif, but did not stimulate gcyp19a1a promoter activities. These results are helpful to further elucidate the regulatory mechanisms of cyp19a1a and cyp19a1b expression in the orange-spotted grouper as well as other teleosts. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of food-related stress conditions and loss of agr and sigB on seb promoter activity in S. aureus.

Science.gov (United States)

Sihto, Henna-Maria; Stephan, Roger; Engl, Christoph; Chen, John; Johler, Sophia

2017-08-01

Staphylococcal enterotoxin B (SEB) causes staphylococcal food poisoning and is produced in up to ten times higher quantities than other major enterotoxins. While Staphylococcus aureus growth is often repressed by competing flora, the organism exhibits a decisive growth advantage under some stress conditions. So far, data on the influence of food-related stressors and regulatory mutations on seb expression is limited and largely based on laboratory strains, which were later reported to harbor mutations. Therefore, the aim of this study was to investigate the influence of stress and regulatory mutations on seb promoter activity. To this end, transcriptional fusions were created in two strains, USA300 and HG003, carrying different seb upstream sequences fused to a blaZ reporter. NaCl, nitrite, and glucose stress led to significantly decreased seb promoter activity, while lactic acid stress resulted in significantly increased seb promoter activity. Loss of agr decreased seb promoter activity and loss of sigB increased promoter activity, with the magnitude of change depending on the strain. These results demonstrate that mild stress conditions encountered during food production and preservation can induce significant changes in seb promoter activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physical activity 11-15 years old children with oncological disease: pilot study disHBSC

Directory of Open Access Journals (Sweden)

Tomáš Vyhlídal

2016-12-01

Full Text Available Background: As of 1993, the Czech and Slovak Republic, along with other countries of Europe and North America, participating in regular intervals to 4 year international project HBSC (Health Behavior in The School-aged Children, for our purposes disHBSC - "with disability". The main objective of this research study is to identify determinants of health and lifestyle pupils and compare the results on the international level. Up to this time, however, the research could not include pupils with disabilities and physical handicaps. On the initiative of WHO were within these categories in the survey also included pupils with cancer. In order to integrate these students, a new study disHBSC, which aims to increase knowledge of health and health behaviors, related to them this target group. Objectives: The aim of the research investigation is to determine the selected determinants affecting the participation of pupils with oncological diseases in the age 11-15 years in physical activities. Part of the aim is to find out their self-assessment and aspiration level, which with the realization of physical activities can immediately relate to. The purpose of the investigation is, however, in particular the pilot revealed any organizational and substantive uncertainties and upgrade research technique with regard to the needs and options of the target group. Methods: The research survey used a pilot version of the questionnaire protocol disHBSC. This pilot version is derived from the questionnaire protocol that was used in 2010 and based on the international version of the questionnaire HBSC. A pilot version of the questionnaire contained 41 questions, which are divided into several thematic areas - basic sociodemographic characteristics and behaviors specific areas (which have a significant relationship to physical and mental health of children and youth youth health, eating habits, physical activity and leisure use substance abuse, self-esteem and

A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.

Science.gov (United States)

Poudrier, J; Graber, P; Herren, S; Gretener, D; Elson, G; Berney, C; Gauchat, J F; Kosco-Vilbois, M H

1999-08-01

A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.

Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage

Science.gov (United States)

Leloup, Corinne; Hopkins, Kevin M.; Wang, Xiangyuan; Zhu, Aiping; Wolgemuth, Debra J.; Lieberman, Howard B.

2010-01-01

RAD9 participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue of RAD9 (named RAD9B) has been identified. To define the function of mouse Rad9b (Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generate Mrad9b mutant mice. Mrad9b−/− embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth. Mrad9b is expressed in embryonic brain and Mrad9b+/− embryos exhibit abnormal neural tube closure. Mrad9b−/− mouse embryonic fibroblasts are not viable. Mrad9b−/− ES cells are more sensitive to gamma rays and mitomycin C than Mrad9b+/+ controls, but show normal gamma-ray-induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability in Mrad9b−/− cells. Our findings thus indicate that Mrad9b is essential for embryonic development and mediates resistance to certain DNA damaging agents. PMID:20842695

Development and Validation of an Online Program for Promoting Self-Management among Korean Patients with Chronic Hepatitis B

Directory of Open Access Journals (Sweden)

Jinhyang Yang

2013-01-01

Full Text Available The hepatitis B virus is second only to tobacco as a known human carcinogen. However, chronic hepatitis B usually does not produce symptoms and people feel healthy even in the early stages of live cancer. Therefore, chronically infected people should perceive it as a serious health problem and move on to appropriate health behaviour. The purpose of this paper is to develop and validate an online program for promoting self-management among Korean patients with chronic hepatitis B. The online program was developed using a prototyping approach and system developing life cycle method, evaluated by users for their satisfaction with the website and experts for the quality of the site. To evaluate the application of the online program, knowledge and self-management compliance of the subjects were measured and compared before and after the application of the online program. There were statistically significant increases in knowledge and self-management compliance in the user group. An online program with high accessibility and applicability including information, motivation, and behavior skill factors can promote self-management of the patient with chronic hepatitis B. Findings from this study allow Korean patients with chronic hepatitis B to engage in proactive and effective health management in the community or clinical practice.

Occurrence of rhyolytic tuffs at deep sea drilling project site 219 on the Laccadive Ridge

Digital Repository Service at National Institute of Oceanography (India)

Siddiquie, H.N.; Sukheswala, R.N.

A study of thin sections from the lower and middle parts of Unit 5 (Paleocene) from Site 219 shows that these largely consist of acidic or rhyolitic tuffs. The overlying limestones in Unit 5 (Paleocene) and Unit 4 (Lower Eocene) also contain...

25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

Energy Technology Data Exchange (ETDEWEB)

Ichikawa, Tomohiro [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Sugiura, Hisatoshi, E-mail: sugiura@rm.med.tohoku.ac.jp [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan); Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Ichinose, Masakazu [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan)

2013-05-01

Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P<0.001) and collagen I (P<0.001) expression in HFL-1. 25-HC also significantly enhanced the release and activation of matrix metallaoproteinase (MMP)-2 (P<0.001) and MMP-9 (P<0.001) without any significant effect on the production of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. 25-HC stimulated transforming growth factor (TGF)-β{sub 1} production (P<0.01) and a neutralizing anti-TGF-β antibody restored these 25-HC-augmented pro-fibrotic responses. 25-HC significantly promoted the translocation of nuclear factor (NF)-κB p65 into the nuclei (P<0.01), but not phospholylated-c-jun, a complex of activator protein-1. Pharmacological inhibition of NF-κB restored the 25-HC-augmented pro-fibrotic responses and TGF-β{sub 1} release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway.

TNF-α-induced NF-κB activation promotes myofibroblast differentiation of LR-MSCs and exacerbates bleomycin-induced pulmonary fibrosis.

Science.gov (United States)

Hou, Jiwei; Ma, Tan; Cao, Honghui; Chen, Yabing; Wang, Cong; Chen, Xiang; Xiang, Zou; Han, Xiaodong

2018-03-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR-MSCs) and tumor necrosis factor-α (TNF-α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR-MSCs and TNF-α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro-inflammatory cytokine TNF-α and the transcription factor nuclear factor kappa B (NF-κB) p65 subunit were both upregulated in bleomycin-induced fibrotic lung tissue. In addition, we discovered that TNF-α promotes myofibroblast differentiation of LR-MSCs through activating NF-κB signaling. Interestingly, we also found that TNF-α promotes the expression of β-catenin. Moreover, we demonstrated that suppression of the NF-κB signaling could attenuate myofibroblast differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis which were accompanied with decreased expression of β-catenin. Our data implicates that inhibition of the NF-κB signaling pathway may provide a therapeutic strategy for pulmonary fibrosis, a disease that warrants more effective treatment approaches. © 2017 Wiley Periodicals, Inc.

Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.

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Li, Wen-Yuan; Zhang, Wei-Ting; Cheng, Yong-Xia; Liu, Yan-Cui; Zhai, Feng-Guo; Sun, Ping; Li, Hui-Ting; Deng, Ling-Xiao; Zhu, Xiao-Feng; Wang, Ying

2018-06-01

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

Exponentiation of the Drell-Yan an cross section near partonic threshold in the DIS and MS-bar schemes

International Nuclear Information System (INIS)

Eynck, Tim Oliver; Laenen, Eric; Magnea, Lorenzo

2003-01-01

It has been observed that in the DIS scheme the refactorization of the Drell-Yan cross section leading to exponentiation of threshold logarithms can also be used to organize a class of constant terms, most of which arise from the ratio of the timelike Sudakov form factor to its spacelike counterpart. We extend this exponentiation to include all constant terms, and demonstrate how a similar organization may be achieved in the MS-bar scheme. We study the relevance of these exponentiations in a two-loop analysis. (author)

Expression, purification, crystallization and preliminary X-ray crystallographic studies of hepatitis B virus core fusion protein corresponding to octahedral particles

International Nuclear Information System (INIS)

Kikuchi, Masaki; Iwabuchi, Shinichiro; Kikkou, Tatsuhiko; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi; Kawata, Masaaki; Sato, Chikara; Matsumoto, Osamu

2013-01-01

Novel hepatitis B virus-like particles of recombinant dimeric core–GFP fusion protein were expressed, purified and crystallized. The crystals diffracted to 2.15 Å resolution and belonged to space group F432, with unit-cell parameters a = b = c = 219.7 Å. Recombinant hepatitis B virus core proteins dimerize to form building blocks that are capable of self-assembly into a capsid. A core capsid protein dimer (CPD) linked to a green fluorescent protein variant, EGFP, at the C-terminus has been designed. The recombinant fusion CPD was expressed in Escherichia coli, assembled into virus-like particles (VLPs), purified and crystallized. The single crystal diffracted to 2.15 Å resolution and belonged to the cubic space group F432, with unit-cell parameters a = b = c = 219.7 Å. The fusion proteins assembled into icosahedral VLPs in aqueous solution, but were rearranged into octahedral symmetry through the crystal-packing process under the crystallization conditions

Analysis of Msx1 and Msx2 transactivation function in the context of the heat shock 70 (Hspa1b) gene promoter.

Science.gov (United States)

Zhuang, Fengfeng; Nguyen, Manuel P; Shuler, Charles; Liu, Yi-Hsin

2009-04-03

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent transactivation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and heat shock factors may play a contributing role.

PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling

Energy Technology Data Exchange (ETDEWEB)

Zheng, Peihao; Guo, Honggang [Department of Hematology, Navy General Hospital, Beijing 100048 (China); Li, Guangchao [School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Luo, Fei [Department of Stomatology, Jinling Hospital, Nanjing 210002 (China); Liu, Yi, E-mail: liuyi2033@163.com [Department of Hematology, Navy General Hospital, Beijing 100048 (China)

2015-03-06

Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies. - Highlights: • First reported upregulation of PSMB4 in MM plasma and cell lines. • PSMB4 promoted MM cell growth and colony forming ability. • Further found miR-21 was up-regulated by PSMB4 in MM plasma and cell lines. • PSMB4-induced miR-21 expression was modulated by NF-κB. • PSMB4-NF-κB-miR-21 axis may be potential therapeutic targets of MM.

NF-κB RelA renders tumor-associated macrophages resistant to and capable of directly suppressing CD8+ T cells for tumor promotion.

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Li, Liwen; Han, Lei; Sun, Fan; Zhou, Jingjiao; Ohaegbulam, Kim C; Tang, Xudong; Zang, Xingxing; Steinbrecher, Kris A; Qu, Zhaoxia; Xiao, Gutian

2018-01-01

Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8 + cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype.

Science.gov (United States)

Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

2016-07-27

Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development.

Hepatitis B seroprotection in children aged 10-15 years after completion of basic hepatitis B immunizations

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Novie Homenta Rampengan

2017-04-01

Full Text Available Background The prevalence of hepatitis B viral (HBV infection in Indonesia is high. The most effective way to control HBV infection is by hepatitis B (HB immunization. Many studies reported that hepatitis B surface antibody (anti-HBs seroprotection declines in children > 10 years of age. In addition many factors can influence anti-HBs titer. Objective To measure anti-HBs titer and evaluate possible factors associated with anti-HBs titer. Methods This cross sectional  study was conducted in children 10-15 years of age from ten schools at Tuminting District, Manado, North Sulawesi, from October to November 2014. All subjects had completed the hepatitis B immunization scheme. By stratified random sampling, 105 children were selected as subjects. Data was analyzed with SPSS version 22. Results. From 48 schools, we selected 10 schools from which to draw a total of 105 children, but only 23 (21.9% children had detectable anti-HBs . Of all subjects, 76 (72.4%  were female, 78 (74.3%  had good nutritional status, and 98 (93.3%  had birth weight ≥2,500 grams. Data from immunization record books showed that 26 (24.8% subjects received the HB-1 vaccination at ≤7 days of age and 45 (42.9% subjects had a ≥2 month interval between the HB-2 and HB-3 vaccinations. Multivariate analysis showed that administration of HB-1 at ≤7 days of age  and a ≥2 month interval between HB-2 and HB-3  had significant associations with anti-HB seroprotection in children. Conclusion A low proportion of subjects who had completed the hepatitis B immunization scheme had detectable anti-HBs titer (21.9%. Administration of HB-1 at ≤7 days of age and a ≥2-month interval between HB-2 and HB-3 vaccinations are important factors in anti-HB seroprotection in children aged 10-15 years.

48 CFR 652.219-72 - Department of State Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Department of State Mentor....219-72 Department of State Mentor-Protégé Program. As prescribed in 619.202-70(o)(1), insert the following provision: Department of State Mentor-Protégé Program (APR 2004) (a) Large and small businesses...

Transactivation of the Brassica napus napin promoter by ABI3 requires interaction of the conserved B2 and B3 domains of ABI3 with different cis-elements: B2 mediates activation through an ABRE, whereas B3 interacts with an RY/G-box.

Science.gov (United States)

Ezcurra, I; Wycliffe, P; Nehlin, L; Ellerström, M; Rask, L

2000-10-01

The transcriptional activator ABI3 is a key regulator of gene expression during embryo maturation in crucifers. In monocots, the related VP1 protein regulates the Em promoter synergistically with abscisic acid (ABA). We identified cis-elements in the Brassica napus napin napA promoter mediating regulation by ABI3 and ABA, by analyzing substitution mutation constructs of napA in transgenic tobacco plantlets ectopically expressing ABI3. In transient analysis using particle bombardment of tobacco leaf sections, a tetramer of the distB ABRE (abscisic acid-responsive element) mediated transactivation by ABI3 and ABI3-dependent response to ABA, whereas a tetramer of the composite RY/G complex, containing RY repeats and a G-box, mediated only ABA-independent transactivation by ABI3. Deletion of the conserved B2 and B3 domains of ABI3 abolished transactivation of napA by ABI3. The two domains of ABI3 interact with different cis-elements: B2 is necessary for ABA-independent and ABA-dependent activations through the distB ABRE, whereas B3 interacts with the RY/G complex. Thus B2 mediates the interaction of ABI3 with the protein complex at the ABRE. The regulation of napA by ABI3 differs from Em regulation by VP1, in that the B3 domain of ABI3 is essential for the ABA-dependent regulation of napA.

Anyalysis of Msx1 and Msx2 Transactivation Function in the Context of the Heat Shock 70 (Hspa1b) Gene Promoter

Science.gov (United States)

Zhuang, Fengfeng; Nguyen, Manuel P.; Shuler, Charles; Liu, Yi-Hsin

2009-01-01

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent trans-activation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and Heat shock factors may play a contributing role. PMID:19338779

DNMT3B -579 G>T Promoter Polymorphism and the Risk of Gastric Cancer in the West of Iran.

Science.gov (United States)

Ahmadi, Kulsom; Soleimani, Azam; Irani, Shiva; Kiani, Aliasghar; Ghanadi, Kourosh; Noormohamadi, Zahra; Sakinejad, Foroozan

2018-06-01

Many studies have suggested that modulation of DNMT3B function caused by single nucleotide polymorphisms of the DNMT3B promoter region may underlie the susceptibility to various cancers such as tumors of the digestive system. The aim of this study was to investigate the effect of -579 G>T polymorphism in the promoter of the DNMT3B gene on risk of gastric cancer in a population from West Iran. We conducted a case-control study in 100 gastric cancer patients and 112 cancer-free controls to assess the correlation between DNMT3B -579 G>T (rs1569686) polymorphism and the risk of gastric cancer. Detection of genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. There was no significant difference in the distribution of DNMT3B -579 G>T genotypes between the cases and controls. However, in the stratified analysis by clinicopathological characteristic types, we found that statistically, the risk susceptibility to gastric cancer was significantly associated with tumor grade II and GT/TT genotype of patients, compared to patients having GG genotype, (OR = 5.4737, 95% CI = 1.4746. 20.3184, P = 0.01). Our study suggested that the -579 T allele may increase the relative risk for the progression of clinicopathological characteristic of tumor grade of gastric cancer patients.

KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer

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Jun Ma

2015-08-01

Full Text Available Background/Aims: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers. Methods: Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research. Results: We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27, inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells. Conclusions: These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.

TNF-α promotes cell survival through stimulation of K+ channel and NFκB activity in corneal epithelial cells

International Nuclear Information System (INIS)

Wang Ling; Reinach, Peter; Lu, Luo

2005-01-01

Tumor necrosis factor (TNF-α) in various cell types induces either cell death or mitogenesis through different signaling pathways. In the present study, we determined in human corneal epithelial cells how TNF-α also promotes cell survival. Human corneal epithelial (HCE) cells were cultured in DMEM/F-12 medium containing 10% FBS. TNF-α stimulation induced activation of a voltage-gated K + channel detected by measuring single channel activity using patch clamp techniques. The effect of TNF-α on downstream events included NFκB nuclear translocation and increases in DNA binding activities, but did not elicit ERK, JNK, or p38 limb signaling activation. TNF-α induced increases in p21 expression resulting in partial cell cycle attenuation in the G 1 phase. Cell cycle progression was also mapped by flow cytometer analysis. Blockade of TNF-α-induced K + channel activity effectively prevented NFκB nuclear translocation and binding to DNA, diminishing the cell-survival protective effect of TNF-α. In conclusion, TNF-α promotes survival of HCE cells through sequential stimulation of K + channel and NFκB activities. This response to TNF-α is dependent on stimulating K + channel activity because following suppression of K + channel activity TNF-α failed to activate NFκB nuclear translocation and binding to nuclear DNA

Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density

DEFF Research Database (Denmark)

Barres, Romain; Osler, Megan E; Yan, Jie

2009-01-01

-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alpha (TNF-alpha) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non......-CpG methylation of PGC-1alpha and decreased mtDNA and PGC-1alpha mRNA. We provide evidence for PGC-1alpha hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1alpha promoter....

Witnessman: The software tool to design, analyse and assess a witness pack with respect to military and medical effects on an (UN)protected (DIS)mounted soldier

NARCIS (Netherlands)

Verhagen, Th.L.A.; Kemper, R.; Huisjes, H.; Knijnenburg, S.G.; Pronk, A.; Klink, M.H. van

2005-01-01

Witness packs are widely used to enable the characterization of fragments generated during ballistic experiments. To assess the effect of fragment impact on an exposed (dis)mounted soldier a follow-up Vulnerability/ Lethality (V/L) simulation is essential. The overall process is elaborative and time

Sustained Elevated Adenosine via ADORA2B Promotes Chronic Pain through Neuro-immune Interaction

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Xia Hu

2016-06-01

Full Text Available The molecular mechanisms of chronic pain are poorly understood and effective mechanism-based treatments are lacking. Here, we report that mice lacking adenosine deaminase (ADA, an enzyme necessary for the breakdown of adenosine, displayed unexpected chronic mechanical and thermal hypersensitivity due to sustained elevated circulating adenosine. Extending from Ada−/− mice, we further discovered that prolonged elevated adenosine contributed to chronic pain behaviors in two additional independent animal models: sickle cell disease mice, a model of severe pain with limited treatment, and complete Freund’s adjuvant paw-injected mice, a well-accepted inflammatory model of chronic pain. Mechanistically, we revealed that activation of adenosine A2B receptors on myeloid cells caused nociceptor hyperexcitability and promoted chronic pain via soluble IL-6 receptor trans-signaling, and our findings determined that prolonged accumulated circulating adenosine contributes to chronic pain by promoting immune-neuronal interaction and revealed multiple therapeutic targets.

The Nietzsche’s “Error”, God is not Dead: the (dis enchantment of the world

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Donizete Rodrigues

2017-10-01

Full Text Available From the Nietzsche’s emphasis that God is dead – basic principle of the secularization – and the concept of religion, from the substantivist and functionalist perspectives, this paper addresses the contribution of some authors, classical (Marx, Weber, Durkheim, Freud and modern (Eliade, Bourdieu, Habermas, Hervieu-Leger, Grace Davie, Heelas, in the important discussion of the (dis enchantment of the world. Another issue considered is the role of religion in the contemporary society, in the context of a “reenchanted” world, with significant changes in the “market of symbolic goods”, characterized by an individualization/privatization of faith, deterritorialization of the sacred space, religious pluralism (with new and diffused religious practices and by the phenomenon of Pentecostalism.

CD8 Follicular T Cells Promote B Cell Antibody Class Switch in Autoimmune Disease.

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Valentine, Kristen M; Davini, Dan; Lawrence, Travis J; Mullins, Genevieve N; Manansala, Miguel; Al-Kuhlani, Mufadhal; Pinney, James M; Davis, Jason K; Beaudin, Anna E; Sindi, Suzanne S; Gravano, David M; Hoyer, Katrina K

2018-05-09

CD8 T cells can play both a protective and pathogenic role in inflammation and autoimmune development. Recent studies have highlighted the ability of CD8 T cells to function as T follicular helper (Tfh) cells in the germinal center in the context of infection. However, whether this phenomenon occurs in autoimmunity and contributes to autoimmune pathogenesis is largely unexplored. In this study, we show that CD8 T cells acquire a CD4 Tfh profile in the absence of functional regulatory T cells in both the IL-2-deficient and scurfy mouse models. Depletion of CD8 T cells mitigates autoimmune pathogenesis in IL-2-deficient mice. CD8 T cells express the B cell follicle-localizing chemokine receptor CXCR5, a principal Tfh transcription factor Bcl6, and the Tfh effector cytokine IL-21. CD8 T cells localize to the B cell follicle, express B cell costimulatory proteins, and promote B cell differentiation and Ab isotype class switching. These data reveal a novel contribution of autoreactive CD8 T cells to autoimmune disease, in part, through CD4 follicular-like differentiation and functionality. Copyright © 2018 by The American Association of Immunologists, Inc.

Evaluation of 3 Inch SN-219 Failure and S and SX Tank Farm Saltwell Piping

International Nuclear Information System (INIS)

ELSEN, J.J.

2000-01-01

Evaluation of direct buried piping currently in use or designated for future Saltwell pumping in S and SX Farms. Documented evaluation of failed S-103 saltwell pumping transfer line 3 inch SN-219. This evaluation is intended to reflect current status of Saltwell piping, when taken in context with referenced documents

29 CFR 779.219 - Unified operation may be achieved without common control or common ownership.

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2010-07-01

... Act May Apply; Enterprise Coverage Unified Operation Or Common Control § 779.219 Unified operation may... through “unified operation.” It is clear from the definition that if the described activities are performed through unified operation they will be part of the enterprise whether they are performed by one...

PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT.

Science.gov (United States)

Liu, Xue; Chen, Qian; Hu, Xu-Gang; Zhang, Xian-Chao; Fu, Ti-Wei; Liu, Qing; Liang, Yan; Zhao, Xi-Long; Zhang, Xia; Ping, Yi-Fang; Bian, Xiu-Wu

2016-10-01

Metastasis is a complicated, multistep process and remains the major cause of cancer-related mortality. Exploring the molecular mechanisms underlying tumor metastasis is crucial for development of new strategies for cancer prevention and treatment. In this study, we found that protein tyrosine phosphatase 1B (PTP1B) promoted breast cancer metastasis by regulating phosphatase and tensin homolog (PTEN) but not epithelial-mesenchymal transition (EMT). By detecting PTP1B expression of the specimens from 128 breast cancer cases, we found that the level of PTP1B was higher in breast cancer tissues than the corresponding adjacent normal tissues. Notably, PTP1B was positively associated with lymph node metastasis (LNM) and estrogen receptor (ER) status. In vitro, disturbing PTP1B expression obviously attenuated cell migration and invasion. On the contrary, PTP1B overexpression significantly increased migration and invasion of breast cancer cells. Mechanistically, PTP1B knockdown upregulated PTEN, accompanied with an abatement of AKT phosphorylation and the expression of matrix metalloproteinase 2 (MMP2) and MMP7. Conversely, forced expression of PTP1B reduced PTEN and increased AKT phosphorylation as well as the expression of MMP2 and MMP7. Notably, neither EMT nor stemness of breast cancer cells was regulated by PTP1B. We also found that PTP1B acted as an independent prognostic factor and predicted poor prognosis in ER-positive breast cancer patients. Taken together, our findings provide advantageous evidence for the development of PTP1B as a potential therapeutic target for breast cancer, especially for ER-positive breast cancer patients.

BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

International Nuclear Information System (INIS)

Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao; Lu, Xin-Yang; Ning, Xiao-Fei; Yuan, Chuan-Tao; Wang, Ai-Liang

2015-01-01

Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth

[Shengqifuzheng Injection promotes the recovery of B cells in gut-associated lymphoid tissues of mice treated with cyclophosphamide].

Science.gov (United States)

Deng, Xiangliang; Huang, Rongrong; Wen, Ruyan; Luo, Xia; Zhou, Lian

2016-08-01

Objective To investigate the effect of Shengqifuzheng Injection (SQFZ) on the number recovery of B cells in gut-associated lymphoid tissues (GALTs) of mice receiving cyclophosphamide-based chemotherapy. Methods BALB/c mice were randomly divided into control group, cyclophosphamide (Cy) group and SQFZ group. Mice in Cy group and SQFZ group were injected intraperitoneally with Cy (100 mg/kg), while the control mice were injected with an equal volume of normal saline. Twenty-four hours later, mice in SQFZ group were administrated intragastricly with 1 mL SQFZ once daily for 10 consecutive days, and mice in the other groups were given the same volume of normal saline. Body mass of all the mice was measured every day. Mice were killed on day 10, and the indexes of spleen and thymus were measured. Cell cycles of bone marrow cells and the percentage of B cells in lymphocytes in mesenteric lymph node (MLN) and Peyer's patch (PP) were detected by flow cytometry. In vitro, after being treated with SQFZ, activity of lymphocytes was evaluzed by MTT assay; expression of CD86 on B cell surface was analyzed by flow cytometry; and B cell proliferation was tested by carboxyfluorescein succinimidyl ester (CFSE)-based lymphocyte proliferation assay. Results SQFZ alleviated the loss of body mass caused by Cy and promoted the recovery of thymus indexes, spleen indexes and B cell number in MLN and PP. But it did not alleviate the bone marrow suppression of mice in this condition. In vitro, SQFZ enhanced lymphocyte activity, and improved the activation and proliferation of B cells. Conclusion SQFZ could accelerate the recovery of B cells in GALTs of mice receiving chemotherapy and it might act by promoting B cell proliferation.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

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Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Ibrutinib synergizes with MDM-2 inhibitors in promoting cytotoxicity in B chronic lymphocytic leukemia.

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Voltan, Rebecca; Rimondi, Erika; Melloni, Elisabetta; Rigolin, Gian Matteo; Casciano, Fabio; Arcidiacono, Maria Vittoria; Celeghini, Claudio; Cuneo, Antonio; Zauli, Giorgio; Secchiero, Paola

2016-10-25

The aim of this study was to investigate the anti-leukemic activity of the Bruton tyrosine kinase inhibitor Ibrutinib in combination with the small molecule MDM-2 inhibitor Nutlin-3 in preclinical models. The potential efficacy of the Ibrutinib/Nutlin-3 combination was evaluated in vitro in a panel of B leukemic cell lines (EHEB, JVM-2, JVM-3, MEC-1, MEC-2) and in primary B-chronic lymphocytic leukemia (B-CLL) patient samples, by assessing cell viability, cell cycle profile, apoptosis and intracellular pathway modulations. Validation of the combination therapy was assessed in a B leukemic xenograft mouse model. Ibrutinib exhibited variable anti-leukemic activity in vitro and the combination with Nutlin-3 synergistically enhanced the induction of apoptosis independently from the p53 status. Indeed, the Ibrutinib/Nutlin-3 combination was effective in promoting cytotoxicity also in primary B-CLL samples carrying 17p13 deletion and/or TP53 mutations, already in therapy with Ibrutinib. Molecular analyses performed on both B-leukemic cell lines as well as on primary B-CLL samples, while confirming the switch-off of the MAPK and PI3K pro-survival pathways by Ibrutinib, indicated that the synergism of action with Nutlin-3 was independent by p53 pathway and was accompanied by the activation of the DNA damage cascade signaling through the phosphorylation of the histone protein H2A.X. This observation was confirmed also in the JVM-2 B leukemic xenograft mouse model. Taken together, our data emphasize that the Ibrutinib/Nutlin-3 combination merits to be further evaluated as a therapeutic option for B-CLL.

Study of the $H \\rightarrow b\\bar{b}$ in association with a single top quark

CERN Document Server

AUTHOR|(CDS)2266532

2017-01-01

The production of the Higgs boson in association with a single top quark. $tH$ is a very important process for testing the Standard Model theory. There are three production channels: associated production with $W$, t-channel and s-channel. In this study only $tHq$ production with $H\\rightarrow b\\bar{b}$ decay and top leptonic decay has been generated and analyzed. The $tH$ production is important for probing the sign of the Higgs-top Yukawa coupling, $y_{t}$. Namely, there is an interference between diagrams which depends on the relative sign of $y_{t}$. LO Madgraph is used as a tool for generating events, calculating the cross-sections and Feynmann diagrams. The cross-section is parameterized as a continuous function of $y_{t}$. The kinematics of the process appears to be dependent on the $y_{t}$ used. In addition, the dominant background from $t\\bar{t}$ production with heavy flavor jets has been generated and potential discriminating variables to separate $tH$ from this background have been analyzed and dis...

Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

International Nuclear Information System (INIS)

Yu, Ge; Wan, Rong; Hu, Yanling; Ni, Jianbo; Yin, Guojian; Xing, Miao; Shen, Jie; Tang, Maochun; Chen, Congying; Fan, Yuting; Xiao, Wenqin; Zhao, Yan; Wang, Xingpeng

2014-01-01

Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway

Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

Energy Technology Data Exchange (ETDEWEB)

Yu, Ge [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wan, Rong [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Hu, Yanling [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Ni, Jianbo [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Yin, Guojian; Xing, Miao [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Shen, Jie [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Tang, Maochun [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Chen, Congying [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Fan, Yuting; Xiao, Wenqin; Zhao, Yan [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wang, Xingpeng, E-mail: wangxingpeng@hotmail.com [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); and others

2014-01-31

Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

Chloroquine and its derivatives exacerbate B19V-associated anemia by promoting viral replication.

Directory of Open Access Journals (Sweden)

Claudia Bönsch

Full Text Available BACKGROUND: An unexpectedly high seroprevalence and pathogenic potential of human parvovirus B19 (B19V have been observed in certain malaria-endemic countries in parallel with local use of chloroquine (CQ as first-line treatment for malaria. The aims of this study were to assess the effect of CQ and other common antimalarial drugs on B19V infection in vitro and the possible epidemiological consequences for children from Papua New Guinea (PNG. METHODOLOGY/PRINCIPAL FINDINGS: Viral RNA, DNA and proteins were analyzed in different cell types following infection with B19V in the presence of a range of antimalarial drugs. Relationships between B19V infection status, prior 4-aminoquinoline use and anemia were assessed in 200 PNG children <10 years of age participating in a case-control study of severe infections. In CQ-treated cells, the synthesis of viral RNA, DNA and proteins was significantly higher and occurred earlier than in control cells. CQ facilitates B19V infection by minimizing intracellular degradation of incoming particles. Only amodiaquine amongst other antimalarial drugs had a similar effect. B19V IgM seropositivity was more frequent in 111 children with severe anemia (hemoglobin <50 g/L than in 89 healthy controls (15.3% vs 3.4%; P = 0.008. In children who were either B19V IgM or PCR positive, 4-aminoquinoline use was associated with a significantly lower admission hemoglobin concentration. CONCLUSIONS/SIGNIFICANCE: Our data strongly suggest that 4-aminoquinoline drugs and their metabolites exacerbate B19V-associated anemia by promoting B19V replication. Consideration should be given for choosing a non-4-aminoquinoline drug to partner artemisinin compounds in combination antimalarial therapy.

The Influence of (Dis)belief in Free Will on Immoral Behavior.

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Caspar, Emilie A; Vuillaume, Laurène; Magalhães De Saldanha da Gama, Pedro A; Cleeremans, Axel

2017-01-01

One of the hallmarks of human existence is that we all hold beliefs that determine how we act. Amongst such beliefs, the idea that we are endowed with free will appears to be linked to prosocial behaviors, probably by enhancing the feeling of responsibility of individuals over their own actions. However, such effects appear to be more complex that one might have initially thought. Here, we aimed at exploring how induced disbeliefs in free will impact the sense of agency over the consequences of one's own actions in a paradigm that engages morality. To do so, we asked participants to choose to inflict or to refrain from inflicting an electric choc to another participant in exchange of a small financial benefit. Our results show that participants who were primed with a text defending neural determinism - the idea that humans are a mere bunch of neurons guided by their biology - administered fewer shocks and were less vindictive toward the other participant. Importantly, this finding only held for female participants. These results show the complex interaction between gender, (dis)beliefs in free will and moral behavior.

MiR-27a Promotes Hemin-Induced Erythroid Differentiation of K562 Cells by Targeting CDC25B

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Dongsheng Wang

2018-03-01

Full Text Available Background/Aims: MicroRNAs (miRNAs play a crucial role in erythropoiesis. MiR-23a∼27a∼24-2 clusters have been proven to take part in erythropoiesis via some proteins. CDC25B (cell division control Cdc2 phosphostase B is also the target of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown. Methods: To evaluate the potential role of miR-27a during erythroid differentiation, we performed miR-27a gain- and loss-of-function experiments on hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation at different time points. At the same time, the γ-globin gene also was measured via real-time PCR. According to the results of the chips, we screened the target protein of miR-27a through a dual-luciferase reporter assay and identified it via Western blot analyses. To evaluate the function of CDC25B, benzidine staining and flow cytometry were employed to detect the cell differentiation and cell cycle. Results: We found that miR-27a promotes hemin-induced erythroid differentiation of human K562 cells by targeting cell division cycle 25 B (CDC25B. Overexpression of miR-27a promotes the differentiation of hemin-induced K562 cells, as demonstrated by γ-globin overexpression. The inhibition of miR-27a expression suppresses erythroid differentiation, thus leading to a reduction in the γ-globin gene. CDC25B was identified as a new target of miR-27a during erythroid differentiation. Overexpression of miR-27a led to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B affected erythroid differentiation, as assessed by γ-globin expression. Conclusion: This study is the first report of the interaction between miR-27a and CDC25B, and it improves the understanding of miRNA functions during erythroid differentiation.

Canonical and Non-Canonical NF-κB Signaling Promotes Breast Cancer Tumor-Initiating Cells

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Kendellen, Megan F.; Bradford, Jennifer W.; Lawrence, Cortney L.; Clark, Kelly S.; Baldwin, Albert S.

2014-01-01

Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors, and the development of metastases. TICs have been identified in various tumors, including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the NF-κB family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition (EMT) and by upregulating the expression of the inflammatory cytokines IL-1β and IL-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers. PMID:23474754

SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin.

Science.gov (United States)

Duan, Chaojun; Li, Minghua; Rui, Liangyou

2004-10-15

Leptin regulates energy homeostasis primarily by binding and activating its long form receptor (LRb). Deficiency of either leptin or LRb causes morbid obesity. Leptin stimulates LRb-associated JAK2, thus initiating multiple pathways including the Stat3 and phosphatidylinositol (PI) 3-kinase pathways that mediate leptin biological actions. Here we report that SH2-B, a JAK2-interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin. SH2-B directly bound, via its PH and SH2 domain, to both IRS1 and IRS2 both in vitro and in intact cells and mediated formation of a JAK2/SH2-B/IRS1 or IRS2 tertiary complex. Consequently, SH2-B dramatically enhanced leptin-stimulated tyrosine phosphorylation of IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt. SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin. Moreover, deletion of the SH2-B gene impaired leptin-stimulated tyrosine phosphorylation of endogenous IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B. Similarly, SH2-B promoted growth hormone-stimulated tyrosine phosphorylation of IRS1 in both HEK293 and MEF cells. Our data suggest that SH2-B is a novel mediator of the PI 3-kinase pathway in response to leptin or other hormones and cytokines that activate JAK2.

A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

Science.gov (United States)

Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong

2016-09-21

Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. Yellow fever is an acute viral hemorrhagic disease which threatens approximately one billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than seven decades, the low vaccination rate fails to prevent outbreaks in at

Isolating Barley ( Hordeum vulgare L.) B1 Hordein Gene Promoter ...

African Journals Online (AJOL)

Promoters play the most important role in determining the temporal and spatial expression pattern and transcript level of a gene. Some strong constitutive promoters, such as cauliflower mosaic virus 35s promoter, are widely used in plant genetic engineering research. However, the expression levels of the foreign genes in ...

Dis-harmony in European natural gas market(s). Discussion of standards and definitions

Energy Technology Data Exchange (ETDEWEB)

Karasz, Michael [The Energy House GmbH, Muenchen (Germany); Pustisek, Andrej [Hochschule fuer Technik, Stuttgart (Germany); Drasdo, Peter

2013-06-15

The European Union attempts to harmonise the European natural gas market(s). In general, this is supported on national levels. Nevertheless, such harmonisation is not yet fully accomplished: neither for the rules nor for the quality specifications nor for the physical quantities and their units. Even if the current economic impact of such dis-harmony is negligible, i.e. that market participants for the time being do not have to bear additional costs caused by the lack of harmonisation, participants in the commodity market are exposed to contractual risks. Potentially, this might lead to reduced competition and reduced liquidity of each single and the European internal market for natural gas. However, as the costs for a potential harmonisation of European gas markets are estimated to be significant, the dilemma is evident and the 'political' solution of the 'harmonisation problem' will necessarily deviate from the traders' one. (orig.)

ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a β-Cell-Induced Dedifferentiation.

Science.gov (United States)

Ripoche, Doriane; Charbord, Jérémie; Hennino, Ana; Teinturier, Romain; Bonnavion, Rémy; Jaafar, Rami; Goehrig, Delphine; Cordier-Bussat, Martine; Ritvos, Olli; Zhang, Chang X; Andersson, Olov; Bertolino, Philippe

2015-12-28

Loss of pancreatic β-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote β-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor β (TGF-β)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and β-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed β-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor β-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of β-cell maturity, islet plasticity, and progression of insulinoma through its participation in β-cell dedifferentiation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

EphB4 promotes or suppresses Ras/MEK/ERK pathway in a context-dependent manner: Implications for EphB4 as a cancer target.

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Xiao, Zhan; Carrasco, Rosa; Kinneer, Krista; Sabol, Darrin; Jallal, Bahija; Coats, Steve; Tice, David A

2012-06-01

EphB4 is a member of the Eph receptor tyrosine kinase family shown to act in neuronal guidance and mediate venal/arterial separation. In contrast to these more established roles, EphB4's function in cancer is much less clear. Here we illustrate both tumor promoting as well as suppressing roles of EphB4, by showing that its activation resulted in inhibition of the Ras/ERK pathway in endothelial cells but activation of the same pathway in MCF-7 breast cancer cells. This was true if EphB4 was stimulated with EphrinB2, its natural ligand, or an agonistic monoclonal antibody for EphB4. Correspondingly, EphB4 activation stimulated MCF7 growth while inhibiting HUVEC cell proliferation. The reason for these dramatic differences is due to functional coupling of EphB4 to different downstream effectors. Reduction of p120 RasGAP in HUVEC cells attenuated the inhibitory effect of EphB4 activation on the ERK pathway, whereas knockdown of PP2A in MCF7 cells attenuated EphB4 activation of the ERK pathway. This represents the first time a functional coupling between Eph receptor and PP2A has been demonstrated leading to activation of an oncogenic pathway. Our study illustrates the caveats and potential challenges of targeting EphB4 for cancer therapy due to the conflicting effects on cancer cell and endothelial cell compartments.

Identification of a single-nucleotide insertion in the promoter region affecting the sodC promoter activity in Brucella neotomae.

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Dina A Moustafa

Full Text Available Brucella neotomae is not known to be associated with clinical disease in any host species. Previous research suggested that B. neotomae might not express detectable levels of Cu/Zn superoxide dismutase (SOD, a periplasmic enzyme known to be involved in protecting Brucella from oxidative bactericidal effects of host phagocytes. This study was undertaken to investigate the genetic basis for the disparity in SOD expression in B. neotomae. Our Western blot and SOD enzyme assay analyses indicated that B. neotomae does express SOD, but at a substantially reduced level. Nucleotide sequence analysis of region upstream to the sodC gene identified a single-nucleotide insertion in the potential promoter region. The same single-nucleotide insertion was also detected in the sodC promoter of B. suis strain Thomsen, belonging to biovar 2 in which SOD expression was undetectable previously. Examination of the sodC promoter activities using translational fusion constructs with E. coli β-galactosidase demonstrated that the B. neotomae and B. suis biovar 2 promoters were very weak in driving gene expression. Site-directed mutation studies indicated that the insertion of A in the B. neotomae sodC promoter reduced the promoter activity. Increasing the level of SOD expression in B. neotomae through complementation with B. abortus sodC gene did not alter the bacterial survival in J774A.1 macrophage-like cells and in tissues of BALB/c and C57BL/6 mice. These results for the first time demonstrate the occurrence of a single-nucleotide polymorphism affecting promoter function and gene expression in Brucella.

Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

Energy Technology Data Exchange (ETDEWEB)

Dong, Wenjie, E-mail: dongwenjie200581@126.com [Department of Internal Medicine-Oncology, The First Affiliated Hospital, Zhengzhou University (China); Shen, Ruizhe; Cheng, Shidan [Department of Gastroenterology, Rui-jin Hospital, Shanghai Jiao Tong University, Shanghai (China)

2014-10-31

Highlights: • TIP30 expression is frequently suppressed in ESCC. • TIP30 was hypermethylated in ESCC. • Reduction of TIP30 was significantly correlated with LN metastasis. • miR-10b is a direct regulator of TIP30. - Abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3′untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3′UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.

A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

Science.gov (United States)

Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J; Kay, Chris; Collins, Jennifer A; Arenillas, David; Lilja, Tobias; Gaudenzi, Giulia; Manoharan, Shiana; Doty, Crystal N; Beck, Jessalyn; Lahiri, Nayana; Portales-Casamar, Elodie; Warby, Simon C; Connolly, Colúm; De Souza, Rebecca A G; Tabrizi, Sarah J; Hermanson, Ola; Langbehn, Douglas R; Hayden, Michael R; Wasserman, Wyeth W; Leavitt, Blair R

2015-06-01

Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.

The unusually strong hydrogen bond between the carbonyl of Q(A) and His M219 in the Rhodobacter sphaeroides reaction center is not essential for efficient electron transfer from Q(A)(-) to Q(B).

Science.gov (United States)

Breton, Jacques; Lavergne, Jérôme; Wakeham, Marion C; Nabedryk, Eliane; Jones, Michael R

2007-06-05

In native reaction centers (RCs) from photosynthetic purple bacteria the primary quinone (QA) and the secondary quinone (QB) are interconnected via a specific His-Fe-His bridge. In Rhodobacter sphaeroides RCs the C4=O carbonyl of QA forms a very strong hydrogen bond with the protonated Npi of His M219, and the Ntau of this residue is in turn coordinated to the non-heme iron atom. The second carbonyl of QA is engaged in a much weaker hydrogen bond with the backbone N-H of Ala M260. In previous work, a Trp side chain was introduced by site-directed mutagenesis at the M260 position in the RC of Rb. sphaeroides, resulting in a complex that is completely devoid of QA and therefore nonfunctional. A photochemically competent derivative of the AM260W mutant was isolated that contains a Cys side chain at the M260 position (denoted AM260(W-->C)). In the present work, the interactions between the carbonyl groups of QA and the protein in the AM260(W-->C) suppressor mutant have been characterized by light-induced FTIR difference spectroscopy of the photoreduction of QA. The QA-/QA difference spectrum demonstrates that the strong interaction between the C4=O carbonyl of QA and His M219 is lost in the mutant, and the coupled CO and CC modes of the QA- semiquinone are also strongly perturbed. In parallel, a band assigned to the perturbation of the C5-Ntau mode of His M219 upon QA- formation in the native RC is lacking in the spectrum of the mutant. Furthermore, a positive band between 2900 and 2400 cm-1 that is related to protons fluctuating within a network of highly polarizable hydrogen bonds in the native RC is reduced in amplitude in the mutant. On the other hand, the QB-/QB FTIR difference spectrum is essentially the same as for the native RC. The kinetics of electron transfer from QA- to QB were measured by the flash-induced absorption changes at 780 nm. Compared to native RCs the absorption transients are slowed by a factor of about 2 for both the slow phase (in the

Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

2004-01-01

's thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture......B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto...

Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

2004-01-01

B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...

7 CFR 1160.111 - Promotion.

Science.gov (United States)

2010-01-01

... demand for fluid milk products. (b) Advertising, which means any advertising or promotion program... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1160.111 Section 1160.111 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order...

New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

Science.gov (United States)

Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

2009-09-01

Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

Spectroscopy of nuclei 215Fr and 219 Ac: a contribution to the study of the nuclear structure of light actinides

International Nuclear Information System (INIS)

Khazrouni, S.

1985-06-01

Using α-particle and γ-ray spectroscopy, it has been possible to establish the high spin pattern in 215 Fr and propose a decay scheme up to I π = (47/2 + ) containing six isomeric states. These results are interpreted using the recent version of the deformed Woods-Saxon model and the Strutinsky normalisation technique. A similar study in 219 Ac has revealed the existence of two quasi-bands each formed of states of alternating parity and connected by strong E1 transitions. This data for 219 Ac fits better with the stable octupole deformation model, mainly because of the high-spin parity doublets observed for the first time, than with the α-cluster model [fr

Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins.

Science.gov (United States)

Chiou, Shiun-Kwei; Hoa, Neil; Hodges, Amy; Ge, Lishen; Jadus, Martin R

2014-09-01

Regular usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with reduced incidence of a variety of cancers. The molecular mechanisms underlying these chemopreventive effects remain poorly understood. This current investigation showed that in gastric cancer cells: (1) Indomethacin treatment enhanced the degradation of chromosomal passenger proteins, Survivin and Aurora B kinase; (2) Indomethacin treatment down-regulated Aurora B kinase activity in a cell cycle-independent fashion; (3) siRNA knockdown of Survivin level promoted Aurora B kinase protein degradation, and vice versa; (4) ectopic overexpression of Survivin blocked reduction of Aurora B kinase level and activity by indomethacin treatment, and vice versa; (5) siRNA knockdown of Aurora B kinase level and AZD1152 inhibition of its activity induced apoptosis, and overexpression of Aurora B kinase inhibited indomethacin-induced apoptosis; (6) indomethacin treatment reduced Aurora B kinase level, coinciding with reduction of Survivin level and induction of apoptosis, in KATO III and HT-29 cells, and in mouse gastric mucosa. A role for Aurora B kinase function in NSAID-induced apoptosis was not previously explored. Thus this report provides better understanding of the molecular mechanisms underlying the anti-cancer effect of NSAIDs by elucidating a significant role for Aurora B kinase in indomethacin-induced apoptosis.

Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter

DEFF Research Database (Denmark)

Herrmann, Susan; Seidelin, Michel; Bisgaard, Hanne Cathrine

2002-01-01

Indole-3-carbinol (I3C) is a naturally occurring substance that shows anti-carcinogenic properties in animal models. Besides its clear anti-carcinogenic effects, some studies indicate that I3C may sometimes act as a tumor promoter. Indolo[3,2-b]carbazole (ICZ), which is formed in the acidic...... environment of the stomach after intake of I3C, has a similar structure to, and shares biological effects with, the well-known tumor promoter 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD). Therefore, we hypothesized that ICZ could be responsible for the potential tumor-promoting activity of I3C. The aim...

Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

Energy Technology Data Exchange (ETDEWEB)

Wang, Juan; Xin, Beibei; Wang, Hui; He, Xiaodan [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China); Wei, Wei; Zhang, Ti [Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060 (China); Shen, Xiaohong, E-mail: zebal2014@163.com [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China)

2016-08-01

Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.

Aquilegia B gene homologs promote petaloidy of the sepals and maintenance of the C domain boundary

Directory of Open Access Journals (Sweden)

Bharti Sharma

2017-11-01

Full Text Available Abstract The model Aquilegia coerulea x “Origami” possesses several interesting floral features, including petaloid sepals that are morphologically distinct from the true petals and a broad domain containing many whorls of stamens. We undertook the current study in an effort to understand the former trait, but additionally uncovered data that inform on the latter. The Aquilegia B gene homolog AqPI is shown to contribute to the production of anthocyanin in the first whorl sepals, although it has no major role in their morphology. Surprisingly, knockdown of AqPI in Aquilegia coerulea x “Origami” also reveals a role for the B class genes in maintaining the expression of the C gene homolog AqAG1 in the outer whorls of stamens. These findings suggest that the transference of pollinator function to the first whorl sepals included a non-homeotic recruitment of the B class genes to promote aspects of petaloidy. They also confirm results in several other Ranunculales that have revealed an unexpected regulatory connection between the B and C class genes.

The Energy Industry Profile of ISO/DIS 19115-1: Facilitating Discovery and Evaluation of, and Access to Distributed Information Resources

Science.gov (United States)

Hills, S. J.; Richard, S. M.; Doniger, A.; Danko, D. M.; Derenthal, L.; Energistics Metadata Work Group

2011-12-01

A diverse group of organizations representative of the international community involved in disciplines relevant to the upstream petroleum industry, - energy companies, - suppliers and publishers of information to the energy industry, - vendors of software applications used by the industry, - partner government and academic organizations, has engaged in the Energy Industry Metadata Standards Initiative. This Initiative envisions the use of standard metadata within the community to enable significant improvements in the efficiency with which users discover, evaluate, and access distributed information resources. The metadata standard needed to realize this vision is the initiative's primary deliverable. In addition to developing the metadata standard, the initiative is promoting its adoption to accelerate realization of the vision, and publishing metadata exemplars conformant with the standard. Implementation of the standard by community members, in the form of published metadata which document the information resources each organization manages, will allow use of tools requiring consistent metadata for efficient discovery and evaluation of, and access to, information resources. While metadata are expected to be widely accessible, access to associated information resources may be more constrained. The initiative is being conducting by Energistics' Metadata Work Group, in collaboration with the USGIN Project. Energistics is a global standards group in the oil and natural gas industry. The Work Group determined early in the initiative, based on input solicited from 40+ organizations and on an assessment of existing metadata standards, to develop the target metadata standard as a profile of a revised version of ISO 19115, formally the "Energy Industry Profile of ISO/DIS 19115-1 v1.0" (EIP). The Work Group is participating on the ISO/TC 211 project team responsible for the revision of ISO 19115, now ready for "Draft International Standard" (DIS) status. With ISO 19115 an

SRSF1 Prevents DNA Damage and Promotes Tumorigenesis through Regulation of DBF4B Pre-mRNA Splicing

Directory of Open Access Journals (Sweden)

Linlin Chen

2017-12-01

Full Text Available Dysregulated alternative splicing events have been implicated in many types of cancer, but the underlying molecular mechanisms remain unclear. Here, we observe that the splicing factor SRSF1 regulates DBF4B exon6 splicing by specifically binding and promoting its inclusion. Knockdown of the exon6-containing isoform (DBF4B-FL significantly inhibits the tumorigenic potential of colon cancer cells in vitro and in mice, and SRSF1 inactivation phenocopies DBF4B-FL depletion. DBF4B-FL and SRSF1 are required for cancer cell proliferation and for the maintenance of genomic stability. Overexpression of DBF4B-FL can protect against DNA damage induced by SRSF1 knockdown and rescues growth defects in SRSF1-depleted cells. Increased DBF4B exon6 inclusion parallels SRSF1 upregulation in clinical colorectal cancer samples. Taken together, our findings identify SRSF1 as a key regulator of DBF4B pre-mRNA splicing dysregulation in colon cancer, with possible clinical implications as candidate prognostic factors in cancer patients.

Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection.

Science.gov (United States)

Li, Wenna; Ke, Yuehua; Wang, Yufei; Yang, Mingjuan; Gao, Junguang; Zhan, Shaoxia; Xinying, Du; Huang, Liuyu; Li, Wenfeng; Chen, Zeliang; Li, Juan

2016-08-26

Brucella spp. are known to avoid host immune recognition and weaken the immune response to infection. Brucella like accomplish this by employing two clever strategies, called the stealth strategy and hijacking strategy. The TIR domain-containing protein (TcpB/Btp1) of Brucella melitensis is thought to be involved in inhibiting host NF-κB activation by binding to adaptors downstream of Toll-like receptors. However, of the five TIR domain-containing adaptors conserved in mammals, whether MyD88 or MAL, even other three adaptors, are specifically targeted by TcpB has not been identified. Here, we confirmed the effect of TcpB on B.melitensis virulence in mice and found that TcpB selectively targets MAL. By using siRNA against MAL, we found that TcpB from B.melitensis is involved in intracellular survival and that MAL affects intracellular replication of B.melitensis. Our results confirm that TcpB specifically targets MAL/TIRAP to disrupt downstream signaling pathways and promote intra-host survival of Brucella spp. Copyright © 2016 Elsevier Inc. All rights reserved.

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...

75 FR 25844 - Class Deviation From FAR 52.219-7, Notice of Partial Small Business Set-Aside

Science.gov (United States)

2010-05-10

... Small Business Set-Aside AGENCY: Defense Logistics Agency, DoD. ACTION: Notice. SUMMARY: This is to...) regarding partial small business set-asides for Defense Logistics Agency (DLA), Defense Energy Support..., DESC is requesting a class deviation from FAR Clause 52.219-7, Notice of Partial Small Business Set...

Reflektuojančio būsimo specialiojo pedagogo profesinio apsisprendimo patirtys

OpenAIRE

Bubnys, Remigijus; Žydžiūnaitė, Vilma

2008-01-01

Fenomenologinės hermeneutikos rezultatai atskleidė būsimų specialiųjų pedagogų profesinį apsisprendimą lemiančius veiksnius. Studentų pasirinkimą studijuoti lemia į žmogų orientuoti ir savirealizacijos veiksniai: poreikis rūpintis kitais, meilė vaikams, noras padėti žmonėms, įgyti žinių bei poreikis perimti profesinį vaidmenį. Apsisprendimą nebūti specialiuoju pedagogu stiprina komplikuotas darbo pobūdis, asmeninių įgūdžių stoka bei specialiųjų ugdymosi poreikių turinčių vaikų individualūs el...

CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.

Directory of Open Access Journals (Sweden)

Aya Matsui

Full Text Available BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1, recruits immature myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+Gr1(+ myeloid-derived cells at tumor sites in mice and promoted CD31(+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+Gr1(highF4/80(- cells (≈ 90% with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b(+Gr1(+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.

Impact of Negative Reactance on Definiteness of B-Matrix and Feasibility of DC Power Flow

DEFF Research Database (Denmark)

Ding, Tao; Bo, Rui; Yang, Yongheng

2018-01-01

This paper reports an essential phenomenon on the existence of “negative reactance” in practical power system models. The negative reactance issue is important, as it could affect the definiteness of the B admittance matrix of power networks and the feasibility of DC power flow. With the graph th...... in “physical dis-connectivity” and make the linear system singular, so that the DC power flow will be infeasible. The results on several test systems show that the location and value of the negative reactance affect the DC power flow feasibility....

Designer bFGF-incorporated D-form self-assembly peptide nanofiber scaffolds to promote bone repair

Energy Technology Data Exchange (ETDEWEB)

He, Bin, E-mail: binheing@163.com [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Ou, Yunsheng; Chen, Shuo; Zhao, Weikang; Zhou, Ao [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhao, Jinqiu [Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Li, Hong [School of Physical Science and Technology, Sichuan University, Chengdu 610000 (China); Jiang, Dianming [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhu, Yong, E-mail: 568731668@qq.com [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China)

2017-05-01

D-Form and L-form peptide nanofiber scaffolds can spontaneously form stable β-sheet secondary structures and nanofiber hydrogel scaffolds, and hold some promise in hemostasis and wound healing. We report here on the synthetic self-assembling peptide D-RADA16 and L-RADA16 are both found to produce stable β-sheet secondary structure and nanofiber hydrogel scaffolds based on circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM) and rheology analysis etc. D-RADA16 hydrogel and L-RADA16 hydrogel can enhance obvious bone repair in femoral condyle defects of the Sprague-Dawley (SD) rat model compared to PBS treatment. Based on micro-computed tomography (CT), it was revealed that D-RADA16 hydrogel and L-RADA16 hydrogel were capable to obtain the extensive bone healing. Histological evaluation also found that these two hydrogels facilitate the presence of more mature bone tissue within the femoral condyle defects. Additionally, D-RADA16 hydrogel showed some potential in storing and releasing basic-fibroblast growth factor (bFGF) which was able to further promote bone regeneration based on micro-CT analysis. These results indicate that D-form peptide nanofiber hydrogel have some special capacity for bone repair. - Highlights: • Peptide D-RADA16 and L-RADA16 can form stable hydrogels. • D-RADA16 hydrogel can obtain the comparable and extensive promotion to bone healing compared to L-RADA16 hydrogel. • L-RADA16 hydrogel allows for slow release of bFGF.

A recombinant E1-deleted porcine adenovirus-3 as an expression vector

International Nuclear Information System (INIS)

Zakhartchouk, Alexander; Zhou Yan; Tikoo, Suresh Kumar

2003-01-01

Replication-defective E1-deleted porcine adenoviruses (PAVs) are attractive vectors for vaccination. As a prerequisite for generating PAV-3 vectors containing complete deletion of E1, we transfected VIDO R1 cells (fetal porcine retina cells transformed with E1 region of human adenovirus 5) with a construct containing PAV-3 E1B large coding sequences under the control of HCMV promoter. A cell line named VR1BL could be isolated that expressed E1B large of PAV-3 and also complemented PAV214 (E1A+E1B small deleted). The VR1BL cells could be efficiently transfected with DNA and allowed the rescue and propagation of recombinant PAV507 containing a triple stop codon inserted in the E1B large coding sequence. In addition, recombinant PAV227 containing complete deletion of E1 (E1A+E1B small + E1B large ) could be successfully rescued using VR1BL cell line. Recombinant PAV227 replicated as efficiently as wild-type in VR1BL cells but not in VIDO R1 cells, suggesting that E1B large was essential for replication of PAV-3. Next, we constructed recombinant PAV219 by inserting green fluorescent (GFP) protein gene flanked by a promoter and a poly(A) in the E1 region of the PAV227 genome. We demonstrated that PAV219 was able to transduce and direct expression of GFP in some human cell lines

Aberrant GSTP1 promoter methylation predicts short-term prognosis in acute-on-chronic hepatitis B liver failure.

Science.gov (United States)

Gao, S; Sun, F-K; Fan, Y-C; Shi, C-H; Zhang, Z-H; Wang, L-Y; Wang, K

2015-08-01

Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure. © 2015 John Wiley & Sons Ltd.

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis | Center for Cancer Research

Science.gov (United States)

We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high

Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

International Nuclear Information System (INIS)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia

2016-01-01

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia, E-mail: lixiaqi_dph@sina.com

2016-01-22

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

Matrix metalloproteinase 3 promotes cellular anti-dengue virus response via interaction with transcription factor NFκB in cell nucleus.

Science.gov (United States)

Zuo, Xiangyang; Pan, Wen; Feng, Tingting; Shi, Xiaohong; Dai, Jianfeng

2014-01-01

Dengue virus (DENV), the causative agent of human Dengue hemorrhagic fever, is a mosquito-borne virus of immense global health importance. Characterization of cellular factors promoting or inhibiting DENV infection is important for understanding the mechanism of DENV infection. In this report, MMP3 (stromelysin-1), a secretory endopeptidase that degrades extracellular matrices, has been shown promoting cellular antiviral response against DENV infection. Quantitative RT-PCR and Western Blot showed that the expression of MMP3 was upregulated in DENV-infected RAW264.7 cells. The intracellular viral loads were significantly higher in MMP3 silenced cells compared with controls. The expression level of selective anti-viral cytokines were decreased in MMP3 siRNA treated cells, and the transcription factor activity of NFκB was significantly impaired upon MMP3 silencing during DENV infection. Further, we found that MMP3 moved to cell nucleus upon DENV infection and colocalized with NFκB P65 in nucleus. Co-immunoprecipitation analysis suggested that MMP3 directly interacted with NFκB in nucleus during DENV infection and the C-terminal hemopexin-like domain of MMP3 was required for the interaction. This study suggested a novel role of MMP3 in nucleus during viral infection and provided new evidence for MMPs in immunomodulation.

Polychlorinated biphenyls (PCB) analysis report for solid sample from 219S tank 104

International Nuclear Information System (INIS)

Ross, G.A.

1998-01-01

A sample of solids was obtained from tank 104 of 219S via a peristaltic pump equipped with a stainless steel tube and Norprenel tubing (Phthalate free). The sample obtained in a glass jar with Teflon 2 lid, was analyzed for PCBs as Aroclor mixtures. A soxhlet extraction procedure was used to extract the Aroclors from the sample. Analysis was performed using dual column confirmation gas chromatography/electron capture detection (GC/ECD). The extraction method closely follows SW-846 method 3540C and the analysis follows SW-846 method

Polychlorinated biphenyls (PCB) analysis report for solid sample from 219S tank 101

International Nuclear Information System (INIS)

Diaz, L.A.

1998-01-01

One waste sample that was obtained with solids from tank 101 of 219S via a peristaltic pump equipped with a stainless steel tube and Norprene tubing (Phthalate free) was obtained in a glass jar with teflon lid was analyzed (with duplicate, matrix spike, and matrix spike duplicate) for PCBs as Aroclor mixtures by the Inorganic/Organic Chemistry Group. A soxhlet extraction procedure was used for extraction of the Aroclors from the sample. Analysis was performed using dual column confirmation gas chromatography/electron capture detection (GC/ECD). Results are presented

Methodology of radionuclides dis incorporation in people related to nuclear and radiological accidents

International Nuclear Information System (INIS)

Jimenez F, E. A.

2014-01-01

allow obtain a better result of the dis incorporation of the radioactive material. In this work, the attention is focused on the identification, classification and selection of the methodologies to accelerate the dis incorporation of radionuclides in people related to nuclear a radiological accidents, depending on the way of incorporation to the human body, the radionuclide, the radiotoxicity, the kind of radiation and its energy, the chemical compound, the half-life of the radioisotope, the target organ, the esteem of the absorbed dose, the characteristic of the accident, the clinical state of the patient and how long ago the accident happened. (Author)

Template Dimerization Promotes an Acceptor Invasion-Induced Transfer Mechanism during Human Immunodeficiency Virus Type 1 Minus-Strand Synthesis

OpenAIRE

Balakrishnan, Mini; Roques, Bernard P.; Fay, Philip J.; Bambara, Robert A.

2003-01-01

The biochemical mechanism of template switching by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the role of template dimerization were examined. Homologous donor-acceptor template pairs derived from the HIV-1 untranslated leader region and containing the wild-type and mutant dimerization initiation sequences (DIS) were used to examine the efficiency and distribution of transfers. Inhibiting donor-acceptor interaction was sufficient to reduce transfers in DIS-containin...

Anyalysis of Msx1 and Msx2 Transactivation Function in the Context of the Heat Shock 70 (Hspa1b) Gene Promoter

OpenAIRE

Zhuang, Fengfeng; Nguyen, Manuel P.; Shuler, Charles; Liu, Yi-Hsin

2009-01-01

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent trans-activation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in...

Genomic sequences of murine gamma B- and gamma C-crystallin-encoding genes: promoter analysis and complete evolutionary pattern of mouse, rat and human gamma-crystallins.

Science.gov (United States)

Graw, J; Liebstein, A; Pietrowski, D; Schmitt-John, T; Werner, T

1993-12-22

The murine genes, gamma B-cry and gamma C-cry, encoding the gamma B- and gamma C-crystallins, were isolated from a genomic DNA library. The complete nucleotide (nt) sequences of both genes were determined from 661 and 711 bp, respectively, upstream from the first exon to the corresponding polyadenylation sites, comprising more than 2650 and 2890 bp, respectively. The new sequences were compared to the partial cDNA sequences available for the murine gamma B-cry and gamma C-cry, as well as to the corresponding genomic sequences from rat and man, at both the nt and predicted amino acid (aa) sequence levels. In the gamma B-cry promoter region, a canonical CCAAT-box, a TATA-box, putative NF-I and C/EBP sites were detected. An R-repeat is inserted 366 bp upstream from the transcription start point. In contrast, the gamma C-cry promoter does not contain a CCAAT-box, but some other putative binding sites for transcription factors (AP-2, UBP-1, LBP-1) were located by computer analysis. The promoter regions of all six gamma-cry from mouse, rat and human, except human psi gamma F-cry, were analyzed for common sequence elements. A complex sequence element of about 70-80 bp was found in the proximal promoter, which contains a gamma-cry-specific and almost invariant sequence (crygpel) of 14 nt, and ends with the also invariant TATA-box. Within the complex sequence element, a minimum of three further features specific for the gamma A-, gamma B- and gamma D/E/F-cry genes can be defined, at least two of which were recently shown to be functional. In addition to these four sequence elements, a subtype-specific structure of inverted repeats with different-sized spacers can be deduced from the multiple sequence alignment. A phylogenetic analysis based on the promoter region, as well as the complete exon 3 of all gamma-cry from mouse, rat and man, suggests separation of only five gamma-cry subtypes (gamma A-, gamma B-, gamma C-, gamma D- and gamma E/F-cry) prior to species separation.

Leading order determination of the gluon polarisation from DIS events with high-$p_T$ hadron pairs

CERN Document Server

Adolph, C; Alexakhin, V Yu; Alexandrov, Yu; Alexeev, G D; Amoroso, A; Antonov, A A; Austregesilo, A; Badelek, B; Balestra, F; Barth, J; Baum, G; Bedfer, Y; Bernhard, J; Bertini, R; Bettinelli, M; Bicker, K; Bieling, J; Birsa, R; Bisplinghoff, J; Bordalo, P; Bradamante, F; Braun, C; Bravar, A; Bressan, A; Burtin, E; Chaberny, D; Chiosso, M; Chung, S U; Cicuttin, A; Crespo, M L; Dalla Torre, S; Das, S; Dasgupta, S S; Denisov, O.Yu; Dhara, L; Donskov, S V; Doshita, N; Duic, V; Dunnweber, W; Dziewiecki, M; Efremov, A; Elia, C; Eversheim, P D; Eyrich, W; Faessler, M; Ferrero, A; Filin, A; Finger, M; jr., M.Finger; Fischer, H; Franco, C; von Hohenesche, N.du Fresne; Friedrich, J M; Garfagnini, R; Gautheron, F; Gavrichtchouk, O P; Gazda, R; Gerassimov, S; Geyer, R; Giorgi, M; Gnesi, I; Gobbo, B; Goertz, S; Grabmuller, S; Grasso, A; Grube, B; Gushterski, R; Guskov, A; Guthorl, T; Haas, F; von Harrach, D; Hedicke, S; Heinsius, F H; Herrmann, F; Hess, C; Hinterberger, F; Horikawa, N; Hoppner, Ch; d'Hose, N; Huber, S; Ishimoto, S; Ivanov, O; Ivanshin, Yu; Iwata, T; Jahn, R; Jasinski, P; Joosten, R; Kabuss, E; Kang, D; Ketzer, B; Khaustov, G V; Khokhlov, Yu.A; Kisselev, Yu; Klein, F; Klimaszewski, K; Koblitz, S; Koivuniemi, J H; Kolosov, V N; Kondo, K; Konigsmann, K; Konorov, I; Konstantinov, V F; Korzenev, A; Kotzinian, A M; Kouznetsov, O; Kramer, M; Kroumchtein, Z V; Kunne, F.; Kurek, K; Lauser, L; Le Goff, J M; Lednev, A A; Lehmann, A; Levorato, S; Lichtenstadt, J; Maggiora, A; Magnon, A; Makke, N; Mallot, G K; Mann, A; Marchand, C; Martin, A; Marzec, J; Matsuda, T; Meyer, W; Michigami, T; Mikhailov, Yu.V; Moinester, M A; Morreale, A; Mutter, A; Nagaytsev, A; Nagel, T; Nassalski, J P; Nerling, F; Neubert, S; Neyret, D; Nikolaenko, V I; Nowak, W D; Nunes, A S; Olshevsky, A G; Ostrick, M; Padee, A; Panknin, R; Panzieri, D; Parsamyan, B; Paul, S.; Perevalova, E; Pesaro, G; Peshekhonov, D V; Piragino, G; Platchkov, S; Pochodzalla, J; Polak, J; Polyakov, V A; Pontecorvo, G; Pretz, J; Procureur, S L; Quaresma, M; Quintans, C; Rajotte, J F; Ramos, S; Rapatsky, V; Reicherz, G; Richter, A; Rocco, E; Rondio, E; Rossiyskaya, N S; Ryabchikov, D I; Samoylenko, V D; Sandacz, A; Sapozhnikov, M G; Sarkar, S.; Savin, I A; Sbrizzai, G; Schiavon, P; Schill, C.; Schluter, T; Schmidt, K; Schmitt, L; Schonning, K; Schopferer, S; Schott, M; Shevchenko, O.Yu; Silva, L; Sinha, L; Sissakian, A N; Slunecka, M; Smirnov, G I; Sosio, S; Sozzi, F; Srnka, A; Stolarski, M; Sulc, M; Sulej, R; Sznajder, P; Takekawa, S; Wolbeek, J.Ter; Tessaro, S; Tessarotto, F; Tkatchev, L G; Uhl, S; Uman, I; Vandenbroucke, M; Virius, M; Vlassov, N V; Wang, L; Windmolders, R; Wislicki, W; Wollny, H; Zaremba, K; Zavertyaev, M; Zemlyanichkina, E; Ziembicki, M; Zhuravlev, N; Zvyagin, A

2013-01-01

We present a determination of the gluon polarisation Delta g/g in the nucleon, based on the longitudinal double-spin asymmetry of DIS events with a pair of large transverse-momentum hadrons in the final state. The data were obtained by the COMPASS experiment at CERN using a 160 GeV/c polarised muon beam scattering off a polarised ^6LiD target. The gluon polarisation is evaluated by a Neural Network approach for three intervals of the gluon momentum fraction x_g covering the range 0.04 < x_g < 0.27. The values obtained at leading order in QCD do not show any significant dependence on x_g. Their average is Delta g/g = 0.125 +/- 0.060 (stat.) +/- 0.063 (syst.) at x_g=0.09 and a scale of mu^2 = 3~(GeV/c)^2.

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.

ECNJEFI. A JEFI based 219-group neutron cross-section library: User's manual

International Nuclear Information System (INIS)

Stad, R.C.L. van der; Gruppelaar, H.

1992-07-01

This manual describes the contents of the ECNJEF1 library. The ECNJEF1 library is a JEF1.1 based 219-group AMPX-Master library for reactor calculations with the AMPX/SCALE-system, e.g. the PASC-3 system as implemented at the Netherlands Energy Research Foundation in Petten, Netherlands. The group cross-section data were generated with NJOY and NPTXS/XLACS-2 from the AMPX system. The data on the ECNJEF1 library allows resolved-resonance treatment by NITAWL and/or unresolved resonance self-shielding by BONAMI. These codes are based upon the Nordheim and Bondarenko methods, respectively. (author). 10 refs., 7 tabs

5 CFR 531.243 - Promotion of a GM employee.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Promotion of a GM employee. 531.243... Promotion of a GM employee. (a) Upon promotion, an employee's status as a GM employee ends, as provided in § 531.241(b). (b) When an employee loses status as a GM employee because of a temporary promotion and is...

Annexin A4 fucosylation enhances its interaction with the NF-kB p50 and promotes tumor progression of ovarian clear cell carcinoma.

Science.gov (United States)

Wang, Huimin; Deng, Lu; Cai, Mingbo; Zhuang, Huiyu; Zhu, Liancheng; Hao, Yingying; Gao, Jian; Liu, Juanjuan; Li, Xiao; Lin, Bei

2017-12-08

To study the structural relationship between annexin A4 and the Lewis y antigen and compare their expression and significance in ovarian clear cell carcinoma, and to explore how annexin A4 fucose glycosylation effects the interaction between annexin A4 and NF-kB p50, and how it promotes tumour progression of ovarian clear cell carcinoma. Structural relationships between annexin A4 and Lewis y antigen were detected using immunoprecipitation. Annexin A4 and Lewis y antigen expression in various subtypes of ovarian cancer tissues was detected by immunohistochemistry, and the relation between their expression was examined. Any interactions between annexin A4 and NF-kB p50 in ovarian clear cell carcinoma were detected by co-immunoprecipitation. Then looked for changes in expression of Lewis y antigen, annexin A4, NF-kB p50 and a number of downstream related molecules before and after transfection annexin A4 or FUT1, and also analyzed changes in biological processes. Lewis y antigen is a part of annexin A4 structure. The expression rate of both annexin A4 and Lewis y antigen was significantly higher in ovarian clear cell carcinoma than in other subtypes of epithelial ovarian cancer, and are associated with the clinical stages, chemotherapy resistance and poor prognostic. The interaction between annexin A4 and NF-kB p50 promoted cell proliferation, adhesion, invasion, metastasis ability and autophagy, and inhibits apoptosis, Lewis y enhanced this interaction. Annexin A4 contains Lewis y structure, Lewis y antigen modification of annexin A4 enhances its interaction with NF-kB p50, which promotes ovarian clear cell carcinoma malignancy progression.

Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner.

Science.gov (United States)

Shen, Mo; Duan, Xiuzhi; Zhou, Ping; Zhou, Wu; Wu, Xiuling; Xu, Siqi; Chen, Yuhua; Tao, Zhihua

2015-02-01

Bladder cancer (BCa) is the most common tumor of the urinary system. Chronic inflammation in the papillary urothelial neoplasm of low malignant potential (PUNLMP)may contribute to carcinogenesis, including that of BCa, via poorly understood mechanisms. In this study, we show that the lymphotoxin β receptor (LTβR) is upregulated in BCa via activation of the canonical and non-canonical nuclear factor-κB (NF-κB) pathways. The mRNA expression of LTβR in 81 BCa, 10 chronic cystitis and 23 healthy bladder mucosa tissues was investigated by reverse transcription-fluorescent quantitative polymerase chain reaction (RT-FQ-PCR), and protein expression was studied in 73 BCa, 30 cystitis and 15 healthy paraffin-embedded tissue sections by immunohistochemistry. Both LTβR mRNA and protein were upregulated in BCa and cystitis compared to the healthy group (P<0.05). The mRNA level of the downstream NF-κB canonical pathway p65 gene and of the non-canonical pathway RelB gene were higher in the BCa and cystitis groups compared to the healthy one. The level of phosphorylated p65 (p-p65) protein of the canonical NF-κB pathway and that of p52, a protein of the non-canonical NF-κB pathway, were also higher in the BCa and cystitis group compared to the healthy group. The levels of these proteins significantly correlated to the pathological grade, clinical stage and lymph node metastasis of BCa patients (P<0.05). In addition, there was a positive correlation between LTβR and NF-κB pathway proteins. Thus, LTβR signaling may be involved in promoting BCa through the NF-κB pathway, and which may represent the molecular link between inflammation and BCa.

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-kappaB and NFAT.

Science.gov (United States)

Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

2008-11-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.

Promotion of hepatic preneoplastic lesions in male B6C3F1 mice by unleaded gasoline.

Science.gov (United States)

Standeven, A M; Wolf, D C; Goldsworthy, T L

1995-01-01

In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promoter and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen in male mice. However, UG vapor had similar transient mitogenic effects in nonlesioned liver of both male and female mice under the conditions of the cancer bioassay. We used an initiation-promotion protocol to determine whether UG vapor acts as a liver tumor promoter in male mice and to examine proliferative effects that may be critical to tumor development. Twelve-day-old male B6C3F1 mice were injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5 days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN-initiated mice, whereas no macroscopic masses were observed in non-initiated mice. Altered hepatic foci (AHF), which were predominantly basophilic in phenotype, were found almost exclusively in DEN-initiated mice. UG treatment significantly increased both the mean volume (threefold) and the volume fraction (twofold) of the AHF without increasing the number of AHF per unit area. UG also induced hepatic pentoxyresorufin-O-dealkylase (PROD) activity, a marker of CYP2B, by more than 12-fold over control with or without DEN cotreatment. To study hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2'-deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured hepatocyte BrdU labeling index (LI) in AHF and nonlesioned liver.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. PMID:7588481

E1B-55K mediated regulation of RNF4 STUbL promotes HAdV gene expression.

Science.gov (United States)

Müncheberg, Sarah; Hay, Ron T; Ip, Wing H; Meyer, Tina; Weiß, Christina; Brenke, Jara; Masser, Sawinee; Hadian, Kamyar; Dobner, Thomas; Schreiner, Sabrina

2018-04-25

HAdV E1B-55K is a multifunctional regulator of productive viral replication and oncogenic transformation in non-permissive mammalian cells. These functions depend on E1B-55K's posttranslational modification with the SUMO protein and its binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to form an E3 Ubiquitin ligase complex that targets antiviral host substrates for proteasomal degradation. Recently, we reported that the PML-NB-associated factor Daxx represses efficient HAdV productive infection and is proteasomally degraded via a SUMO-E1B-55K-dependent, E4orf6-independent pathway, the details of which remained to be established.RNF4, a cellular SUMO-targeted Ubiquitin ligase (STUbL), induces ubiquitinylation of specific SUMOylated proteins and plays an essential role during DNA repair. Here, we show that E1B-55K recruits RNF4 to the insoluble nuclear matrix fraction of the infected cell to support RNF4/Daxx association, promoting Daxx PTM, and thus inhibiting this antiviral factor. Removing RNF4 from infected cells using RNAi resulted in blocking the proper establishment of viral replication centers and significantly diminished viral gene expression. These results provide a model for how HAdV antagonize the antiviral host responses by exploiting the functional capacity of cellular STUbLs. Thus, RNF4 and its STUbL function represent a positive factor during lytic infection and a novel candidate for future therapeutic antiviral intervention strategies. IMPORTANCE Daxx is a PML-NB-associated transcription factor, which was recently shown to repress efficient HAdV productive infection. To counteract this antiviral measurement during infection, Daxx is degraded via a novel pathway including viral E1B-55K and host proteasomes. This virus-mediated degradation is independent of the classical HAdV E3 Ubiquitin ligase complex, which is essential during viral infection to target other host antiviral substrates. To maintain productive viral life

Developing theoretically based and culturally appropriate interventions to promote hepatitis B testing in 4 Asian American populations, 2006-2011.

Science.gov (United States)

Maxwell, Annette E; Bastani, Roshan; Glenn, Beth A; Taylor, Victoria M; Nguyen, Tung T; Stewart, Susan L; Burke, Nancy J; Chen, Moon S

2014-05-01

Hepatitis B infection is 5 to 12 times more common among Asian Americans than in the general US population and is the leading cause of liver disease and liver cancer among Asians. The purpose of this article is to describe the step-by-step approach that we followed in community-based participatory research projects in 4 Asian American groups, conducted from 2006 through 2011 in California and Washington state to develop theoretically based and culturally appropriate interventions to promote hepatitis B testing. We provide examples to illustrate how intervention messages addressing identical theoretical constructs of the Health Behavior Framework were modified to be culturally appropriate for each community. Intervention approaches included mass media in the Vietnamese community, small-group educational sessions at churches in the Korean community, and home visits by lay health workers in the Hmong and Cambodian communities. Use of the Health Behavior Framework allowed a systematic approach to intervention development across populations, resulting in 4 different culturally appropriate interventions that addressed the same set of theoretical constructs. The development of theory-based health promotion interventions for different populations will advance our understanding of which constructs are critical to modify specific health behaviors.

Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

DEFF Research Database (Denmark)

Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

2011-01-01

the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

Science.gov (United States)

Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

2015-09-29

Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

IL-21 May Promote Granzyme B-Dependent NK/Plasmacytoid Dendritic Cell Functional Interaction in Cutaneous Lupus Erythematosus.

Science.gov (United States)

Salvi, Valentina; Vermi, William; Cavani, Andrea; Lonardi, Silvia; Carbone, Teresa; Facchetti, Fabio; Bosisio, Daniela; Sozzani, Silvano

2017-07-01

Autoimmune skin lesions are characterized by a complex cytokine milieu and by the accumulation of plasmacytoid dendritic cells (pDCs). Granzyme B (GrB) transcript is abundant in activated pDCs, though its mechanisms of regulation and biological role are largely unknown. Here we report that IL-21 was the only T helper 1/T helper 17 cytokine able to induce the expression and secretion of GrB by pDCs and that this action was counteracted by the autocrine production of type I IFNs. In lupus erythematosus skin lesions, the percentage of GrB + pDCs directly correlated with the IL-21/MxA ratio, indicating that the interplay between these two cytokines finely tunes the levels of pDC-dependent GrB also in vivo. In lupus erythematosus, pDCs colocalized with professional cytotoxic cells at sites of epithelial damage, suggesting a role in keratinocyte killing. Accordingly, we demonstrate that supernatants of IL-21-activated pDCs promoted autologous keratinocyte killing by natural killer cells and this action was dependent on GrB. These results propose a GrB-dependent functional interaction between pDCs and natural killer cells and highlight a negative feedback regulation by type I IFNs in vitro and in vivo that may function to limit excessive tissue damage. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Identification of Three Types of α-Thalassemia Deletion, -α21.9, -α2.4, and - -THAI, and Their Frequencies, in One Family in the Population of Southern Guangxi Zhuang Autonomous Region, People's Republic of China.

Science.gov (United States)

Pang, Wanrong; Long, Ju; Weng, Xunjin; Fan, Qiongying; Sun, Lei; Pan, Zhijian; Fan, Zuqian

2018-01-01

Different types of deletional α-thalassemia (α-thal) have been reported by researchers in China. This study describes one family carrying -α 21.9 (NG_000006.1: g.14373_36299delinsGGGAAGGGTGGGTGGGAATAACAGCTTTT), -α 2.4 (NG_000006.1: g.36860_39251del) and - - THAI (Thailand) (NG_000006.1: g.10664_44164del) alleles in Guangxi Zhuang Autonomous Region, People's Republic of China (PRC), and reports the frequencies of these types in the population of this region. The proband was a 4-year-old girl, who screened positive for thalassemia, although the thalassemia genotype results were normal when screened using the routine kits. Samples of the proband's parents were also collected to perform further analyses. Two real-time gap-polymerase chain reaction (gap-PCR) systems were designed for separate detection of - - THAI and screening for -α 21.9 and -α 2.4 . The genotype of the proband was -α 21.9 /-α 2.4 , and the two variants were inherited from her parents. In the frequency study, five - - THAI , four -α 21.9 and 11 -α 2.4 positive individuals were detected in the 3410 random samples. Thus, allele frequencies of -α 21.9 , - - THAI and -α 2.4 in the population of southern Guangxi were determined as 0.059, 0.073 and 0.161%, respectively. This is the first report of an individual carrying the -α 21.9 /-α 2.4 genotype, and the first report of the detection of -α 21.9 , -α 2.4 and - - THAI in a single family. The total frequency for these alleles was 0.293% in southern Guangxi, suggesting that the thalassemia clinical center in this region should utilize a screening kit that allows detection of these types of deletions for a more comprehensive evaluation of thalassemia risk.

Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

International Nuclear Information System (INIS)

Sahu, Geetaram; Farley, Kalamo; El-Hage, Nazira; Aiamkitsumrit, Benjamas; Fassnacht, Ryan; Kashanchi, Fatah; Ochem, Alex; Simon, Gary L.; Karn, Jonathan; Hauser, Kurt F.; Tyagi, Mudit

2015-01-01

Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR

Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

Energy Technology Data Exchange (ETDEWEB)

Sahu, Geetaram; Farley, Kalamo [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); El-Hage, Nazira [Virginia Commonwealth University, Richmond, VA (United States); Aiamkitsumrit, Benjamas; Fassnacht, Ryan [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Kashanchi, Fatah [George Mason University, Manassas, VA (United States); Ochem, Alex [ICGEB, Wernher and Beit Building, Anzio Road, Observatory, 7925 Cape Town (South Africa); Simon, Gary L. [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Karn, Jonathan [Case Western Reserve University, Cleveland, OH (United States); Hauser, Kurt F. [Virginia Commonwealth University, Richmond, VA (United States); Tyagi, Mudit, E-mail: tmudit@email.gwu.edu [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037 (United States)

2015-09-15

Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR.

Impact of varying physical activity levels on airway sensitivity and bronchodilation in healthy humans.

Science.gov (United States)

Smith, Joshua R; Kurti, Stephanie P; Johnson, Ariel M; Kolmer, Sarah A; Harms, Craig

2015-12-01

The purpose of this study was to determine if the amount of physical activity influences airway sensitivity and bronchodilation in healthy subjects across a range of physical activity levels. Thirty healthy subjects (age, 21.9 ± 2.6 years; 13 men/17 women) with normal pulmonary function reported to the laboratory on 2 separate occasions where they were randomized to breathe either hypertonic saline (HS) (nebulized hypertonic saline (25%) for 20 min) or HS followed by 5 deep inspirations (DIs), which has been reported to bronchodilate the airways. Pulmonary function tests (PFTs) were performed prior to both conditions and following the HS breathing or 5 DIs. Moderate to vigorous physical activity (MVPA) level was measured via accelerometer worn for 7 days. Following the HS breathing, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) significantly decreased from baseline by -11.8% ± 8.4% and -9.3% ± 6.7%, respectively. A 2-segment linear model determined significant relationships between MVPA and percent change in FEV1 (r = 0.50) and FVC (r = 0.55). MVPA above ∼497 and ∼500 min/week for FEV1 and FVC, respectively, resulted in minor additional improvements (p > 0.05) in PFTs following the HS breathing. Following the DIs, FEV1 and FVC decreased (p 0.05) to MVPA. In conclusion, these data demonstrate that higher MVPA levels attenuated airway sensitivity but not bronchodilation in healthy subjects.

WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

Science.gov (United States)

Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

2007-11-01

We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

Effect of promoter strength and signal sequence on the periplasmic ...

African Journals Online (AJOL)

Two plasmids, pFLAG-ATS and pET 26b(+), were studied for the periplasmic expression of recombinant human interferon-2b (IFN-2b) in Escherichia coli. The pFLAG-ATS contains ompA signal sequence and tac promoter while pET 26b(+) contains pelB signal sequence and T7lac promoter. It was observed that periplasmic ...

Calreticulin Fragment 39-272 Promotes B16 Melanoma Malignancy through Myeloid-Derived Suppressor Cells In Vivo

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Xiao-Yan He

2017-10-01

Full Text Available Calreticulin (CRT, a multifunctional Ca2+-binding glycoprotein mainly located in the endoplasmic reticulum, is a tumor-associated antigen that has been shown to play protective roles in angiogenesis suppression and anti-tumor immunity. We previously reported that soluble CRT (sCRT was functionally similar to heat shock proteins or damage-associated molecular patterns in terms of ability to activate myeloid cells and elicit strong inflammatory cytokine production. In the present study, B16 melanoma cell lines expressing recombinant CRT fragment 39-272 (sCRT/39-272 in secreted form (B16-CRT, or recombinant enhanced green fluorescence protein (rEGFP (B16-EGFP, were constructed for investigation on the roles of sCRT in tumor development. When s.c. inoculated into C57BL/6 mice, the B16-CRT cells were significantly more aggressive (in terms of solid tumor growth rate than B16-EGFP controls in a TLR4- and myeloid-derived suppressor cells (MDSC-dependent manner. The B16-CRT-bearing mice showed increased Gr1+ MDSC infiltration in tumor tissues, accelerated proliferation of CD11b+Ly6G+Ly6Clow (G-MDSC precursors in bone marrow, and higher percentages of G-MDSCs in spleen and blood, which was mirrored by decreased percentage of dendritic cells (DC in periphery. In in vitro studies, recombinant sCRT/39-272 was able to promote migration and survival of tumor-derived MDSCs via interaction with TLR4, inhibit MDSC differentiation into DC, and also elicit expression of inflammatory proteins S100A8 and S100A9 which are essential for functional maturation and chemotactic migration of MDSCs. Our data provide solid evidence for CRT as a double-edged sword in tumor development.

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

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Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

2016-01-01

Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

Combination of the inclusive DIS e"±p cross sections from HERA, QCD and EW analyses and the need for low-Q"2 higher-twist corrections

International Nuclear Information System (INIS)

Myronenko, Volodymyr

2017-01-01

A combination of the inclusive lepton-proton cross sections from the ZEUS and H1 experiments is presented. The data are combined taking into account correlations of the systematic uncertainties of the measurements. The resulting combined inclusive neutral- and charged-current e"±p cross sections derived from ∝1 fb"-"1 of data, cover the kinematic region of 0.045≤Q"2≤50000 GeV"2 and 6.10"-"7≤x_B_j≤0.65. The combined data is an unique legacy of the HERA collider and the core of any parton-density-function extraction. The parton distribution functions are essential ingredients in the evaluation of QCD predictions for the high-energy processes, studied at modern proton colliders. The methodology of HERAPDF fits is used as an ansatz for the global QCD fit. The charm- and beauty-quark mass parameters in the analyses at next-next-to-leading order were found to be M"o"p"t_c=1.43 GeV and M"o"p"t_b=4.5 GeV, respectively. HERAPDF2.0 sets give reasonable DIS data description. The effect of higher-twist corrections on the DIS structure functions was studied. The twist-4 corrections were introduced to the F_2 and F_L structure functions. A minimal improvement in the data description was found for the F_2 correction. The introduction of a higher-twist correction to the F_L structure function improved the QCD fit quality by up to Δχ"2=47, predominantly affecting the low-x_B_j and low-Q"2 regions. The twist-4 correction causes an unphysical rise of the predicted F_L in the low x_B_j region. The results indicate a need for further investigations. The electroweak parameters and PDFs are determined simultaneously using the HERA inclusive cross sections together with information on the lepton beam polarisation. The vector- and axial-vector couplings of the u- and d-type quarks to the Z"0 boson are determined simultaneously. The u-type quark couplings were found to be a_u=0.532"+"0"."1"0"7_-_0_._0_6_3, v_u.144"+"0"."0"6"6_-_0_._0_5_8, which are the most precise measurements

miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.

Science.gov (United States)

Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yanrong; Zhang, Meng; Yuan, Keng; Min, Weiping

2016-05-09

Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs, and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer.

Fisetin Attenuates AKT Associated Growth Promoting Events in AflatoxinB1 Induced Hepatocellular Carcinoma.

Science.gov (United States)

Maurya, Brajesh Kumar; Trigun, Surendra Kumar

2017-12-29

Recently we have reported that Fisetin, a natural flavonol, is able to regress Aflatoxin-B1 (AFB1) induced hepatocellular carcinoma (HCC) by suppressing reactive oxygen species (ROS) led pro-inflammatory factors in rats. In the current study, we aimed to delineate whether Fisetin does so by modulating the cell growth promoting signaling cascade in HCC. The reciprocal interplay of 3-phosphoinositol kinase (PI3K) vs phosphatase and tensin homologue deleted on chromosome 10 (PTEN) displays Akt, a protein kinase B, to get phosphorylated at Thr308 by a 3-phosphoinositol dependent kinase 1 (PDK1). This commits cells of neoplastic niche to undergo rapid proliferation by p-Akt thr308 dependent phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9 position. In this study, the effect of in vivo treatment of 20 mg/kg b.w. Fisetin on relative profile of all these factors were studied in the liver from the HCC rats induced by two doses of 1mg/kg b.w. AFB1 i.p. As compared to the untreated HCC liver, liver from Fisetin treated HCC group rats showed a significant decline in the activity and level of p-Aktthr308 which was consistent with a similar decline in PDK1 level. Concordantly, the level of p-GSK3βSer 9 was also found to be declined significantly in those Fisetin-treated HCC livers. A concomitant decline in immunohistochemically detected number of the proliferating cell nuclear antigen (PCNA), a cell proliferation marker, in the HCC liver, further confirmed anti-cell proliferative role of Fisetin during HCC growth in vivo. This findings suggest that Fisetin is able to suppress Akt dependent cell growth signaling mechanisms in HCC mainly by down regulating PDK1 dependent Akt phosphorylation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rs4705342 polymorphism is involved in the tumorigenesis of HBV positive HCC by altering the binding affinity of HBV induced NF-kB with the promoter region of microRNA-143.

Science.gov (United States)

Yin, Xiuli; Sun, Shiying; Zhao, Junyan; Yang, Jing; Lei, Xiaofei; Xu, Changqing; Li, Kun

2017-12-13

The objective of this study was to explore the role of rs4705342 located in the miR-143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. A luciferase assay was performed to explore the factors which influenced miR-143 transcription activity and the target gene of miR-143. This would further be confirmed by ChIP assay. Western blot and real-time PCR were performed to identify the relationship between miR-143 and ORP8. Luciferase activity of miR-143 SNP was increased with the presence of C allele. The presence of T allele partially restored the transcription ability. NF-κB displayed a much higher degree of luciferase activity in relation to the cells transfected with vectors containing either T or C allele rather than control cells with a greater extent in C allele group than T allele group. At the same time, ChIP assay indicated that the affinity of NF-ΚB in the miR-143 promoter was higher in C/C cells. The over-expression of HBX promotes NF-kB expression thus increasing the extent of binding of NF-kB on the CC allele of the miR-143 promoter. The binding is also abolished by NF-kB siRNA. ORP8 was proven to be a target gene of miR-143 using bioinformatics algorithm analysis. It was further confirmed by the luciferase assay that miR-143 substantially inhibited luciferase activities of wild-type ORP8. However, it did not affect the mutant ORP8. HBx induced by HBV infection up-regulated miR-143 expression. NF- kB can partially abolish the promotion effect of HBx on the miR-143 level in cells genotyped as CC but not in cells genotyped as TT. Tissues derived from participants genotyped as CC exhibited a higher level of miR-143, but a lower level of ORP8. The presence of the minor allele of rs4705342 in the promoter of miR-143 attenuated the transcription ability. This promoted ORP8 expression and could be a factor contributing to the oncogenesis in HBV positive HCC. © 2017 Wiley Periodicals, Inc.

Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

Science.gov (United States)

Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

2014-01-31

Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis

International Nuclear Information System (INIS)

Patel, Divya; Chaudhary, Jaideep

2012-01-01

Highlights: ► E2A, considered as a tumor suppressor is highly expressed in prostate cancer. ► Silencing of E2A attenuates cell proliferation and promotes apoptosis. ► E2A regulates c-myc, Id1, Id3 and CDKN1A expression. ► Loss of E2A promotes doxorubicin dependent apoptosis in prostate cancer cells. ► Results suggest that E2A acts as a tumor promoter at least in prostate cancer. -- Abstract: E2A (TCF3) is a multifunctional basic helix loop helix (bHLH), transcription factor. E2A regulates transcription of target genes by homo- or heterodimerization with cell specific bHLH proteins. In general, E2A promotes cell differentiation, acts as a negative regulator of cell proliferation in normal cells and cancer cell lines and is required for normal B-cell development. Given the diverse biological pathways regulated/influenced by E2A little is known about its expression in cancer. In this study we investigated the expression of E2A in prostate cancer. Unexpectedly, E2A immuno-histochemistry demonstrated increased E2A expression in prostate cancer as compared to normal prostate. Silencing of E2A in prostate cancer cells DU145 and PC3 led to a significant reduction in proliferation due to G1 arrest that was in part mediated by increased CDKN1A(p21) and decreased Id1, Id3 and c-myc. E2A silencing in prostate cancer cell lines also resulted in increased apoptosis due to increased mitochondrial permeability and caspase 3/7 activation. Moreover, silencing of E2A increased sensitivity to doxorubicin induced apoptosis. Based on our results, we propose that E2A could be an upstream regulator of Id1 and c-Myc which are highly expressed in prostate cancer. These results for the first time demonstrate that E2A could in fact acts as a tumor promoter at least in prostate cancer.

Cancer cell-associated cytoplasmic B7–H4 is induced by hypoxia through hypoxia-inducible factor-1α and promotes cancer cell proliferation

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Jeon, You-Kyoung [Department of Microbiology and Immunology, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Park, Sae-Gwang; Choi, Il-Whan [Department of Microbiology and Immunology, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Lee, Soo-Woong [Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Lee, Sang Min [Department of Internal Medicine, Division of Hematology/Oncology, Busan Paik Hospital, Inje University, Busan 614-735 (Korea, Republic of); Choi, Inhak, E-mail: miccih@inje.ac.kr [Department of Microbiology and Immunology, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614-735 (Korea, Republic of)

2015-04-03

Aberrant B7–H4 expression in cancer tissues serves as a novel prognostic biomarker for poor survival in patients with cancer. However, the factor(s) that induce cancer cell-associated B7–H4 remain to be fully elucidated. We herein demonstrate that hypoxia upregulates B7–H4 transcription in primary CD138{sup +} multiple myeloma cells and cancer cell lines. In support of this finding, analysis of the Multiple Myeloma Genomics Portal (MMGP) data set revealed a positive correlation between the mRNA expression levels of B7–H4 and the endogenous hypoxia marker carbonic anhydrogenase 9. Hypoxia-induced B7–H4 expression was detected in the cytoplasm, but not in cancer cell membranes. Chromatin immunoprecipitation analysis demonstrated binding of hypoxia-inducible factor-1α (HIF-1α) to proximal hypoxia-response element (HRE) sites within the B7–H4 promoter. Knockdown of HIF-1α and pharmacological inhibition of HIF-1α diminished B7–H4 expression. Furthermore, knockdown of cytoplasmic B7–H4 in MCF-7 decreased the S-phase cell population under hypoxia. Finally, MMGP analysis revealed a positive correlation between the transcript levels of B7–H4 and proliferation-related genes including MKI67, CCNA1, and Myc in several patients with multiple myeloma. Our results provide insight into the mechanisms underlying B7–H4 upregulation and its role in cancer cell proliferation in a hypoxic tumor microenvironment. - Highlights: • Hypoxia upregulates B7–H4 transcription and protein expression. • Hypoxia-induced B7–H4 is detected in the cytoplasm, but not on membrane. • ChIP assay reveals a binding of HIF-1α to B7–H4 promoter at HRE site. • Knockdown and pharmacological inhibition of HIF-1α reduce B7–H4 expression. • B7–H4 knockdown decrease the number of cells in S-phase of cell cycle.

Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors

Science.gov (United States)

Kermani, Pouneh; Rafii, Dahlia; Jin, David K.; Whitlock, Paul; Schaffer, Wendy; Chiang, Anne; Vincent, Loic; Friedrich, Matthias; Shido, Koji; Hackett, Neil R.; Crystal, Ronald G.; Rafii, Shahin; Hempstead, Barbara L.

2005-01-01

The neurotrophin brain-derived neurotrophic factor (BDNF) is required for the maintenance of cardiac vessel wall stability during embryonic development through direct angiogenic actions on endothelial cells expressing the tropomysin receptor kinase B (TrkB). However, the role of BDNF and a related neurotrophin ligand, neurotrophin-4 (NT-4), in the regulation of revascularization of the adult tissues is unknown. To study the potential angiogenic capacity of BDNF in mediating the neovascularization of ischemic and non-ischemic adult mouse tissues, we utilized a hindlimb ischemia and a subcutaneous Matrigel model. Recruitment of endothelial cells and promotion of channel formation within the Matrigel plug by BDNF and NT-4 was comparable to that induced by VEGF-A. The introduction of BDNF into non-ischemic ears or ischemic limbs induced neoangiogenesis, with a 2-fold increase in the capillary density. Remarkably, treatment with BDNF progressively increased blood flow in the ischemic limb over 21 days, similar to treatment with VEGF-A. The mechanism by which BDNF enhances capillary formation is mediated in part through local activation of the TrkB receptor and also by recruitment of Sca-1+CD11b+ pro-angiogenic hematopoietic cells. BDNF induces a potent direct chemokinetic action on subsets of marrow-derived Sca-1+ hematopoietic cells co-expressing TrkB. These studies suggest that local regional delivery of BDNF may provide a novel mechanism for inducing neoangiogenesis through both direct actions on local TrkB-expressing endothelial cells in skeletal muscle and recruitment of specific subsets of TrkB+ bone marrow–derived hematopoietic cells to provide peri-endothelial support for the newly formed vessels. PMID:15765148

25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

International Nuclear Information System (INIS)

Ichikawa, Tomohiro; Sugiura, Hisatoshi; Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki; Ichinose, Masakazu

2013-01-01

Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P 1 production (P 1 release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway

Project specific quality assurance plan for Project W-178, 219-S secondary containment

International Nuclear Information System (INIS)

Buckles, D.I.

1994-01-01

The scope of this Quality Assurance Program Plan (QAPP) is to provide a system of Quality Assurance reviews and verifications on the design, procurement and construction of the 219-S Secondary Containment Upgrade. The reviews and verifications will be on activities associated with design, procurement, and construction of the Secondary Containment Upgrade which includes, but is not limited to demolition, removal, new tank installation, tank 103 isolation, tank cell refurbishment, electrical, instrumentation, piping/tubing including supports, pump and valves, and special coatings. The full project scope is defined in the project Functional Design Criteria (FDC), SD-W178-FDC-001, and all activities must be in compliance with this FDC and related design documentation

Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males.

Directory of Open Access Journals (Sweden)

Chunli Wang

Full Text Available The variation of G>T in the MUC5B promoter (rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF and familial interstitial pneumonia (FIP in Caucasians, but no information is available regarding this variant in the Chinese population. We recruited 405 patients with interstitial lung diseases (ILD, including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs were recruited as disease controls. Our results indicated that the prevalence of the minor allele (T of the polymorphism rs35705950 in healthy Chinese subjects was approximately 0.66%, which was lower than that described in the Caucasian population. The frequencies of the T allele were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were significantly higher than those of healthy controls (P = 0.001, OR = 4.332 for IPF, and P = 0.002, OR = 2.855 for ILD. A stratified analysis showed that this variant in MUC5B associated with the risk for ILD mainly in older male Chinese subjects. No difference was observed between patients with pneumonia, AD patients, and healthy controls.

B2-B2.5 code benchmarking

Energy Technology Data Exchange (ETDEWEB)

Dekeyser, W.; Baelmans, M; Voskoboynikov, S.; Rozhansky, V.; Reiter, D.; Wiesen, S.; Kotov, V.; Boerner, P.

2011-01-15

ITER-IO currently (and since about 15 years) employs the SOLPS4.xxx code for its divertor design, currently version SOLPS4.3. SOLPS.xxx is a special variant of the B2-EIRENE code, which was originally developed by an European consortium (FZ Juelich, AEA Culham, ERM Belgium/KU Leuven) in the late eighties and early nineties of the last century under NET contracts. Until today even the very similar edge plasma codes within the SOLPS family, if run on a seemingly identical choice of physical parameters, still sometimes disagree significantly with each other. It is obvious that in computational engineering applications, as they are carried out for the various ITER divertor aspects with SOLPS4.3 for more than a decade now, any transition from one to another code must be fully backward compatible, or, at least, the origin of differences in the results must be identified and fully understood quantitatively. In this report we document efforts undertaken in 2010 to ultimately eliminate the third issue. For the kinetic EIRENE part within SOLPS this backward compatibility (back until 1996) was basically achieved (V. Kotov, 2004-2006) and SOLPS4.3 is now essentially up to date with the current EIRENE master maintained at FZ Juelich. In order to achieve a similar level of reproducibility for the plasma fluid (B2, B2.5) part, we follow a similar strategy, which is quite distinct from the previous SOLPS benchmark attempts: the codes are ''disintegrated'' and pieces of it are run on smallest (i.e. simplest) problems. Only after full quantitative understanding is achieved, the code model is enlarged, integrated, piece by piece again, until, hopefully, a fully backward compatible B2 / B2.5 ITER edge plasma simulation will be achieved. The status of this code dis-integration effort and its findings until now (Nov. 2010) are documented in the present technical note. This work was initiated in a small workshop by the three partner teams of KU Leuven, St. Petersburg

BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

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Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

2013-05-10

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

Rab27A mediated by NF-κB promotes the stemness of colon cancer cells via up-regulation of cytokine secretion.

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Feng, Feixue; Jiang, Yinghao; Lu, Huanyu; Lu, Xiaozhao; Wang, Shan; Wang, Lifeng; Wei, Mengying; Lu, Wei; Du, Zhichao; Ye, Zichen; Yang, Guodong; Yuan, Fang; Ma, Yanxia; Lei, Xiaoying; Lu, Zifan

2016-09-27

Recent evidences have unveiled critical roles of cancer stem cells (CSCs) in tumorigenicity, but how interactions between CSC and tumor environments help maintain CSC initiation remains obscure. The small GTPases Rab27A regulates autocrine and paracrine cytokines by monitoring exocytosis of extracellular vesicles, and is reported to promote certain tumor progression. We observe that overexpression of Rab27A increased sphere formation efficiency (SFE) by increasing the proportion of CD44+ and PKH26high cells in HT29 cell lines, and accelerating the growth of colosphere with higher percentage of cells at S phase. Mechanism study revealed that the supernatant derived from HT29 sphere after Rab27A overexpression was able to expand sphere numbers with elevated secretion of VEGF and TGF-β. In tumor implanting nude mice model, tumor initiation rates and tumor sizes were enhanced by Rab27A with obvious angiogenesis. As a contrast, knocking down Rab27A impaired the above effects. More importantly, the correlation between higher p65 level and Rab27A in colon sphere was detected, p65 was sufficient to induce up-regulation of Rab27A and a functional NF-κB binding site in the Rab27A promoter was demonstrated. Altogether, our findings reveal a unique mechanism that tumor environment related NF-κB signaling promotes various colon cancer stem cells (cCSCs) properties via an amplified paracrine mechanism regulated by higher Rab27A level.

Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

DEFF Research Database (Denmark)

Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien

2006-01-01

Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c......-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis....

miR-26b promotes granulosa cell apoptosis by targeting ATM during follicular atresia in porcine ovary.

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Fei Lin

Full Text Available More than 99% of ovarian follicles undergo atresia in mammals, but the mechanism of follicular atresia remains to be elucidated. In this study, we explored microRNA (miRNA regulation of follicular atresia in porcine ovary. A miRNA expression profile was constructed for healthy, early atretic, and progressively atretic follicles, and the differentially expressed miRNAs were selected and analyzed. We found that miR-26b, which was upregulated during follicular atresia, increased the number of DNA breaks and promoted granulosa cell apoptosis by targeting the ataxia telangiectasia mutated gene directly in vitro.

5 CFR 9701.353 - Setting pay upon promotion.

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2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Setting pay upon promotion. 9701.353... upon promotion. (a) Except as otherwise provided in this section, upon an employee's promotion, DHS... basic pay after promotion may not be less than the minimum rate of the higher band. (b) DHS will issue...

SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

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Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

2015-08-07

SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.

Science.gov (United States)

Lee, Chih-Yung Sean; Lu, Tu; Seydoux, Geraldine

2017-11-07

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.