24 CFR 585.406 - Faith-based activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... out its mission, including the definition, practice, and expression of its religious beliefs, provided... program beneficiary or prospective program beneficiary on the basis of religion or religious belief. (e... activities. (a) Organizations that are religious or faith-based are eligible, on the same basis as any other...

24 CFR 585.406 - Faith-based activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... out its mission, including the definition, practice, and expression of its religious beliefs, provided... program beneficiary or prospective program beneficiary on the basis of religion or religious belief. (e... activities. (a) Organizations that are religious or faith-based are eligible, on the same basis as any other...

Epstein-Barr virus growth/latency III program alters cellular microRNA expression

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

Cameron, Jennifer E.; Tulane Cancer Center, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL79, New Orleans, LA 70112; Fewell, Claire

The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lowermore » in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers.« less

GENPLOT: A formula-based Pascal program for data manipulation and plotting

NASA Astrophysics Data System (ADS)

Kramer, Matthew J.

Geochemical processes involving alteration, differentiation, fractionation, or migration of elements may be elucidated by a number of discrimination or variation diagrams (e.g., AFM, Harker, Pearce, and many others). The construction of these diagrams involves arithmetic combination of selective elements (involving major, minor, or trace elements). GENPLOT utilizes a formula-based algorithm (an expression parser) which enables the program to manipulate multiparameter databases and plot XY, ternary, tetrahedron, and REE type plots without needing to change either the source code or rearranging databases. Formulae may be any quadratic expression whose variables are the column headings of the data matrix. A full-screen editor with limited equations and arithmetic functions (spreadsheet) has been incorporated into the program to aid data entry and editing. Data are stored as ASCII files to facilitate interchange of data between other programs and computers. GENPLOT was developed in Turbo Pascal for the IBM and compatible computers but also is available in Apple Pascal for the Apple Ile and Ill. Because the source code is too extensive to list here (about 5200 lines of Pascal code), the expression parsing routine, which is central to GENPLOT's flexibility is incorporated into a smaller demonstration program named SOLVE. The following paper includes a discussion on how the expression parser works and a detailed description of GENPLOT's capabilities.

A language comparison for scientific computing on MIMD architectures

NASA Technical Reports Server (NTRS)

Jones, Mark T.; Patrick, Merrell L.; Voigt, Robert G.

1989-01-01

Choleski's method for solving banded symmetric, positive definite systems is implemented on a multiprocessor computer using three FORTRAN based parallel programming languages, the Force, PISCES and Concurrent FORTRAN. The capabilities of the language for expressing parallelism and their user friendliness are discussed, including readability of the code, debugging assistance offered, and expressiveness of the languages. The performance of the different implementations is compared. It is argued that PISCES, using the Force for medium-grained parallelism, is the appropriate choice for programming Choleski's method on the multiprocessor computer, Flex/32.

Peers for Promotion: Achieving Academic Advancement through Facilitated Peer Mentoring

ERIC Educational Resources Information Center

Ockene, Judith K.; Milner, Robert J.; Thorndyke, Luanne E.; Congdon, John; Cain, Joanna M.

2017-01-01

The promotion process is challenging, particularly for non-tenure track faculty in academic medicine. To address this challenge, we implemented a facilitated peer mentoring program that included a structured curriculum with regular meetings, guided by two senior faculty mentors. Participants expressed satisfaction with the program, showed…

The School and Home Enrichment Program for Severely Handicapped Children.

ERIC Educational Resources Information Center

Gleason, Joni J.

1987-01-01

The School and Home Enrichment Program for Severely Handicapped Children includes 332 activities. Focus is on the development of sensory responsiveness, eating skills, fine motor skills, gross motor skills, expressive language, receptive language, personal hygiene, dressing, and social interaction that can be used by parents or teachers as a…

Improving Preservice Teachers' Expression in Read-Alouds

ERIC Educational Resources Information Center

Kerry-Moran, Kelli Jo

2016-01-01

Read-alouds play an important role in young children's literacy development. Teacher education programs include read-alouds as part of balanced literacy instruction and many preservice teachers are required to read aloud to others in their teacher education programs. There are many excellent resources teacher educators may use to help preservice…

Expressive Electronic Journal Writing: Freedom of Communication for Survivors of Acquired Brain Injury

ERIC Educational Resources Information Center

Fraas, Michael; Balz, Magdalen A.

2008-01-01

In addition to the impaired ability to effectively communicate, adults with acquired brain injury (ABI) also experience high incidences of depression, social isolation, and decreased quality of life. Expressive writing programs have been shown to be effective in alleviating these concomitant impairments in other populations including incarcerated…

Distributed Function Mining for Gene Expression Programming Based on Fast Reduction.

PubMed

Deng, Song; Yue, Dong; Yang, Le-chan; Fu, Xiong; Feng, Ya-zhou

2016-01-01

For high-dimensional and massive data sets, traditional centralized gene expression programming (GEP) or improved algorithms lead to increased run-time and decreased prediction accuracy. To solve this problem, this paper proposes a new improved algorithm called distributed function mining for gene expression programming based on fast reduction (DFMGEP-FR). In DFMGEP-FR, fast attribution reduction in binary search algorithms (FAR-BSA) is proposed to quickly find the optimal attribution set, and the function consistency replacement algorithm is given to solve integration of the local function model. Thorough comparative experiments for DFMGEP-FR, centralized GEP and the parallel gene expression programming algorithm based on simulated annealing (parallel GEPSA) are included in this paper. For the waveform, mushroom, connect-4 and musk datasets, the comparative results show that the average time-consumption of DFMGEP-FR drops by 89.09%%, 88.85%, 85.79% and 93.06%, respectively, in contrast to centralized GEP and by 12.5%, 8.42%, 9.62% and 13.75%, respectively, compared with parallel GEPSA. Six well-studied UCI test data sets demonstrate the efficiency and capability of our proposed DFMGEP-FR algorithm for distributed function mining.

Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma.

PubMed

Skala, Stephanie L; Liu, Tzu-Ying; Udager, Aaron M; Weizer, Alon Z; Montgomery, Jeffrey S; Palapattu, Ganesh S; Siddiqui, Javed; Cao, Xuhong; Fields, Kristina; Abugharib, Ahmed E; Soliman, Moaaz; Hafez, Khaled S; Miller, David; Lee, Cheryl T; Alva, Ajjai; Chinnaiyan, Arul M; Morgan, Todd M; Spratt, Daniel E; Jiang, Hui; Mehra, Rohit

2017-10-01

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC) account for approximately 5% of UCs but a significant subset are invasive and associated with poor clinical outcomes. To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC. UTUC cases from 1997-2016 were retrospectively identified from the surgical pathology database at a single large academic institution. The cohort included 149 cases: 27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole tumor sections using anti-PD-L1 primary antibody clone 5H1. PD-L1 expression was evaluated using a previously established cut-off for positivity (≥ 5% membranous staining). Association between PD-L1 IHC expression and clinicopathologic parameters was examined with Fisher's exact test; the effect of PD-L1 expression on cancer-specific mortality was assessed using the Cox proportional hazard model. Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression. Positive PD-L1 expression was associated with high histologic grade, high pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not significantly associated with positive PD-L1 expression using a 5% cut-off. Study limitations include the retrospective nature and the fact that PD-L1 expression by IHC is an imperfect surrogate for response to therapy. Positive PD-L1 expression in approximately one-third of primary invasive UTUC and association with high-risk clinicopathologic features provide a rational basis for further investigation of PD-L1-based immunotherapeutics in these patients. Upper tract urothelial carcinoma is often associated with poor clinical outcome. While current treatment options for advanced upper tract urothelial carcinoma are limited, programmed death-ligand 1 positivity in approximately one-third of invasive tumors provides a rational basis for further investigation of programmed death-ligand 1-based immunotherapeutics in these patients. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A dermal HOX transcriptional program regulates site-specific epidermal fate

PubMed Central

Rinn, John L.; Wang, Jordon K.; Allen, Nancy; Brugmann, Samantha A.; Mikels, Amanda J.; Liu, Helen; Ridky, Todd W.; Stadler, H. Scott; Nusse, Roel; Helms, Jill A.; Chang, Howard Y.

2008-01-01

Reciprocal epithelial–mesenchymal interactions shape site-specific development of skin. Here we show that site-specific HOX expression in fibroblasts is cell-autonomous and epigenetically maintained. The distal-specific gene HOXA13 is continually required to maintain the distal-specific transcriptional program in adult fibroblasts, including expression of WNT5A, a morphogen required for distal development. The ability of distal fibroblasts to induce epidermal keratin 9, a distal-specific gene, is abrogated by depletion of HOXA13, but rescued by addition of WNT5A. Thus, maintenance of appropriate HOX transcriptional program in adult fibroblasts may serve as a source of positional memory to differentially pattern the epithelia during homeostasis and regeneration. PMID:18245445

A dermal HOX transcriptional program regulates site-specific epidermal fate.

PubMed

Rinn, John L; Wang, Jordon K; Allen, Nancy; Brugmann, Samantha A; Mikels, Amanda J; Liu, Helen; Ridky, Todd W; Stadler, H Scott; Nusse, Roel; Helms, Jill A; Chang, Howard Y

2008-02-01

Reciprocal epithelial-mesenchymal interactions shape site-specific development of skin. Here we show that site-specific HOX expression in fibroblasts is cell-autonomous and epigenetically maintained. The distal-specific gene HOXA13 is continually required to maintain the distal-specific transcriptional program in adult fibroblasts, including expression of WNT5A, a morphogen required for distal development. The ability of distal fibroblasts to induce epidermal keratin 9, a distal-specific gene, is abrogated by depletion of HOXA13, but rescued by addition of WNT5A. Thus, maintenance of appropriate HOX transcriptional program in adult fibroblasts may serve as a source of positional memory to differentially pattern the epithelia during homeostasis and regeneration.

HAL/SM language specification. [programming languages and computer programming for space shuttles

NASA Technical Reports Server (NTRS)

Williams, G. P. W., Jr.; Ross, C.

1975-01-01

A programming language is presented for the flight software of the NASA Space Shuttle program. It is intended to satisfy virtually all of the flight software requirements of the space shuttle. To achieve this, it incorporates a wide range of features, including applications-oriented data types and organizations, real time control mechanisms, and constructs for systems programming tasks. It is a higher order language designed to allow programmers, analysts, and engineers to communicate with the computer in a form approximating natural mathematical expression. Parts of the English language are combined with standard notation to provide a tool that readily encourages programming without demanding computer hardware expertise. Block diagrams and flow charts are included. The semantics of the language is discussed.

Model for Evaluating Specialized and Traditional Programs in Marketing and Distributive Education. Final Report. University of Kentucky Research Series in Marketing and Distributive Education.

ERIC Educational Resources Information Center

Litchfield, Carolyn G.

A project was conducted to develop a model for evaluating specialized and traditional programs in marketing and distributive education. The project included a review of literature containing information regarding the points of view expressed by advocates of the specialized, traditional, and middle-of-the-road approaches to program planning in…

Computer program documentation for the dynamic analysis of a noncontacting mechanical face seal

NASA Technical Reports Server (NTRS)

Auer, B. M.; Etsion, I.

1980-01-01

A computer program is presented which achieves a numerical solution for the equations of motion of a noncontacting mechanical face seal. The flexibly-mounted primary seal ring motion is expressed by a set of second order differential equations for three degrees of freedom. These equations are reduced to a set of first order equations and the GEAR software package is used to solve the set of first order equations. Program input includes seal design parameters and seal operating conditions. Output from the program includes velocities and displacements of the seal ring about the axis of an inertial reference system. One example problem is described.

Beam-plasma dielectric tensor with Mathematica

NASA Astrophysics Data System (ADS)

Bret, A.

2007-03-01

We present a Mathematica notebook allowing for the symbolic calculation of the 3×3 dielectric tensor of an electron-beam plasma system in the fluid approximation. Calculation is detailed for a cold relativistic electron beam entering a cold magnetized plasma, and for arbitrarily oriented wave vectors. We show how one can elaborate on this example to account for temperatures, arbitrarily oriented magnetic field or a different kind of plasma. Program summaryTitle of program: Tensor Catalog identifier: ADYT_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYT_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: Computers: Any computer running Mathematica 4.1. Tested on DELL Dimension 5100 and IBM ThinkPad T42. Installations: ETSI Industriales, Universidad Castilla la Mancha, Ciudad Real, Spain Operating system under which the program has been tested: Windows XP Pro Programming language used: Mathematica 4.1 Memory required to execute with typical data: 7.17 Mbytes No. of bytes in distributed program, including test data, etc.: 33 439 No. of lines in distributed program, including test data, etc.: 3169 Distribution format: tar.gz Nature of the physical problem: The dielectric tensor of a relativistic beam plasma system may be quite involved to calculate symbolically when considering a magnetized plasma, kinetic pressure, collisions between species, and so on. The present Mathematica notebook performs the symbolic computation in terms of some usual dimensionless variables. Method of solution: The linearized relativistic fluid equations are directly entered and solved by Mathematica to express the first-order expression of the current. This expression is then introduced into a combination of Faraday and Ampère-Maxwell's equations to give the dielectric tensor. Some additional manipulations are needed to express the result in terms of the dimensionless variables. Restrictions on the complexity of the problem: Temperature effects are limited to small, i.e. non-relativistic, temperatures. The kinetic counterpart of the present Mathematica will usually not compute the required integrals. Typical running time: About 1 minute on a Intel Centrino 1.5 GHz Laptop with 512 MB of RAM. Unusual features of the program: None.

Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation

PubMed Central

Sáenz-de-Santa-María, Inés; Bernardo-Castiñeira, Cristóbal; Secades, Pablo; Bernaldo-de-Quirós, Sandra; Rodrigo, Juan Pablo; Astudillo, Aurora; Chiara, María-Dolores

2017-01-01

Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs. Cell-based analysis revealed that HIF-1α-driven metabolic program includes over-expression of glycolytic enzymes and the microRNA miR-210 coupled to down-regulation of its target, the iron-sulfur cluster assembly protein, ISCU. pH-regulator program entailed over-expression of CAIX, but not MCT1 or MCT4. Accordingly, significant overlapping exists between over-expression of HIF-1α and CAIX, but not HIF-1α and MCT1 or MCT4, in tumor cells. Increased miR-210 and concomitant decreased ISCU RNA levels were found in ~40% of tumors and this was significantly associated with HIF-1α and CAIX, but not MCT1 or MCT4, over-expression. HIF-1α and/or CAIX over-expression was associated with high recurrence rate and low overall survival of surgically treated patients. By contrast, clinically significant correlations were not found in tumors with MCT1 or MCT4 over-expression. This is the first study that provides in vivo evidences of coordinated activation of HIF-1α, CAIX, miR-210 and ISCU in carcinoma and association with poor prognosis, a finding with important implications for the development of metabolic-targeting therapies against hypoxia. PMID:28099149

Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation.

PubMed

Sáenz-de-Santa-María, Inés; Bernardo-Castiñeira, Cristóbal; Secades, Pablo; Bernaldo-de-Quirós, Sandra; Rodrigo, Juan Pablo; Astudillo, Aurora; Chiara, María-Dolores

2017-02-21

Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs. Cell-based analysis revealed that HIF-1α-driven metabolic program includes over-expression of glycolytic enzymes and the microRNA miR-210 coupled to down-regulation of its target, the iron-sulfur cluster assembly protein, ISCU. pH-regulator program entailed over-expression of CAIX, but not MCT1 or MCT4. Accordingly, significant overlapping exists between over-expression of HIF-1α and CAIX, but not HIF-1α and MCT1 or MCT4, in tumor cells. Increased miR-210 and concomitant decreased ISCU RNA levels were found in ~40% of tumors and this was significantly associated with HIF-1α and CAIX, but not MCT1 or MCT4, over-expression. HIF-1α and/or CAIX over-expression was associated with high recurrence rate and low overall survival of surgically treated patients. By contrast, clinically significant correlations were not found in tumors with MCT1 or MCT4 over-expression. This is the first study that provides in vivo evidences of coordinated activation of HIF-1α, CAIX, miR-210 and ISCU in carcinoma and association with poor prognosis, a finding with important implications for the development of metabolic-targeting therapies against hypoxia.

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

PubMed

Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

2018-06-01

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Creating Success! A Program for Behaviorally and Academically At-Risk Children.

ERIC Educational Resources Information Center

Akin, Terri; And Others

This document presents a program designed especially for behaviorally and academically at-risk children in kindergarten through sixth grade. It includes a collection of experiential activities that provides ways to infuse the elements of success into the regular classroom curriculum. Eight developmental areas are targeted: (1) expressing feelings;…

The Effects of a Multi-Component Intervention on Preschool Children's Literacy Skills

ERIC Educational Resources Information Center

Dennis, Lindsay R.

2016-01-01

This study examined the effects of a multi-component intervention program (i.e., extended instruction and iPad app technology) on preschool children's vocabulary. Instruction utilizing the intervention program was provided across 6 storybooks, 4 verbs per book, for a total of 24 verbs. Dependent variables included expressive vocabulary,…

Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

PubMed Central

Sääf, Annika M.; Halbleib, Jennifer M.; Chen, Xin; Yuen, Siu Tsan; Leung, Suet Yi

2007-01-01

Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. PMID:17699589

Aspects, Wrappers and Events

NASA Technical Reports Server (NTRS)

Filman, Robert E.

2003-01-01

This viewgraph presentation provides information on Object Infrastructure Framework (OIF), an Aspect-Oriented Programming (AOP) system. The presentation begins with an introduction to the difficulties and requirements of distributed computing, including functional and non-functional requirements (ilities). The architecture of Distributed Object Technology includes stubs, proxies for implementation objects, and skeletons, proxies for client applications. The key OIF ideas (injecting behavior, annotated communications, thread contexts, and pragma) are discussed. OIF is an AOP mechanism; AOP is centered on: 1) Separate expression of crosscutting concerns; 2) Mechanisms to weave the separate expressions into a unified system. AOP is software engineering technology for separately expressing systematic properties while nevertheless producing running systems that embody these properties.

xPerm: fast index canonicalization for tensor computer algebra

NASA Astrophysics Data System (ADS)

Martín-García, José M.

2008-10-01

We present a very fast implementation of the Butler-Portugal algorithm for index canonicalization with respect to permutation symmetries. It is called xPerm, and has been written as a combination of a Mathematica package and a C subroutine. The latter performs the most demanding parts of the computations and can be linked from any other program or computer algebra system. We demonstrate with tests and timings the effectively polynomial performance of the Butler-Portugal algorithm with respect to the number of indices, though we also show a case in which it is exponential. Our implementation handles generic tensorial expressions with several dozen indices in hundredths of a second, or one hundred indices in a few seconds, clearly outperforming all other current canonicalizers. The code has been already under intensive testing for several years and has been essential in recent investigations in large-scale tensor computer algebra. Program summaryProgram title: xPerm Catalogue identifier: AEBH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEBH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 93 582 No. of bytes in distributed program, including test data, etc.: 1 537 832 Distribution format: tar.gz Programming language: C and Mathematica (version 5.0 or higher) Computer: Any computer running C and Mathematica (version 5.0 or higher) Operating system: Linux, Unix, Windows XP, MacOS RAM:: 20 Mbyte Word size: 64 or 32 bits Classification: 1.5, 5 Nature of problem: Canonicalization of indexed expressions with respect to permutation symmetries. Solution method: The Butler-Portugal algorithm. Restrictions: Multiterm symmetries are not considered. Running time: A few seconds with generic expressions of up to 100 indices. The xPermDoc.nb notebook supplied with the distribution takes approximately one and a half hours to execute in full.

An interval logic for higher-level temporal reasoning

NASA Technical Reports Server (NTRS)

Schwartz, R. L.; Melliar-Smith, P. M.; Vogt, F. H.; Plaisted, D. A.

1983-01-01

Prior work explored temporal logics, based on classical modal logics, as a framework for specifying and reasoning about concurrent programs, distributed systems, and communications protocols, and reported on efforts using temporal reasoning primitives to express very high level abstract requirements that a program or system is to satisfy. Based on experience with those primitives, this report describes an Interval Logic that is more suitable for expressing such higher level temporal properties. The report provides a formal semantics for the Interval Logic, and several examples of its use. A description of decision procedures for the logic is also included.

BloodSpot: a database of gene expression profiles and transcriptional programs for healthy and malignant haematopoiesis

PubMed Central

Bagger, Frederik Otzen; Sasivarevic, Damir; Sohi, Sina Hadi; Laursen, Linea Gøricke; Pundhir, Sachin; Sønderby, Casper Kaae; Winther, Ole; Rapin, Nicolas; Porse, Bo T.

2016-01-01

Research on human and murine haematopoiesis has resulted in a vast number of gene-expression data sets that can potentially answer questions regarding normal and aberrant blood formation. To researchers and clinicians with limited bioinformatics experience, these data have remained available, yet largely inaccessible. Current databases provide information about gene-expression but fail to answer key questions regarding co-regulation, genetic programs or effect on patient survival. To address these shortcomings, we present BloodSpot (www.bloodspot.eu), which includes and greatly extends our previously released database HemaExplorer, a database of gene expression profiles from FACS sorted healthy and malignant haematopoietic cells. A revised interactive interface simultaneously provides a plot of gene expression along with a Kaplan–Meier analysis and a hierarchical tree depicting the relationship between different cell types in the database. The database now includes 23 high-quality curated data sets relevant to normal and malignant blood formation and, in addition, we have assembled and built a unique integrated data set, BloodPool. Bloodpool contains more than 2000 samples assembled from six independent studies on acute myeloid leukemia. Furthermore, we have devised a robust sample integration procedure that allows for sensitive comparison of user-supplied patient samples in a well-defined haematopoietic cellular space. PMID:26507857

Effectiveness of a co-taught handwriting program for first grade students.

PubMed

Case-Smith, Jane; Holland, Terri; White, Susan

2014-02-01

Our study examined the effects of Write Start, a classroom-embedded handwriting/writing program on handwriting and writing fluency for first grade students, co-taught by occupational therapists and teachers. Two first grade classrooms received the Write Start and two received standard handwriting instruction. This co-taught program included specific feedback during handwriting practice, small group activities, student self-evaluation, and peer supports. The students were evaluated on handwriting legibility, fluency, and written expression at baseline, immediately after the program, and 6 months later. When performance was compared between the two groups, the students in the Write Start program improved significantly more in legibility (d = .57) and fluency (d = .75) than students who received standard instruction. Gains in handwriting speed (d = .18), average legibility (d = .26), and written expression (d = .25) did not differ significantly between the two groups. A co-taught, inclusive handwriting/writing program can promote first grade students' achievement of lower case legibility and writing fluency.

Regulatory logic of pan-neuronal gene expression in C. elegans

PubMed Central

Stefanakis, Nikolaos; Carrera, Ines; Hobert, Oliver

2015-01-01

While neuronal cell types display an astounding degree of phenotypic diversity, most if not all neuron types share a core panel of terminal features. However, little is known about how pan-neuronal expression patterns are genetically programmed. Through an extensive analysis of the cis-regulatory control regions of a battery of pan-neuronal C.elegans genes, including genes involved in synaptic vesicle biology and neuropeptide signaling, we define a common organizational principle in the regulation of pan-neuronal genes in the form of a surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory modules that direct expression to broad, overlapping domains throughout the nervous system. These parallel-acting cis-regulatory modules are responsive to a multitude of distinct trans-acting factors. Neuronal gene expression programs therefore fall into two fundamentally distinct classes. Neuron type-specific genes are generally controlled by discrete and non-redundantly acting regulatory inputs, while pan-neuronal gene expression is controlled by diverse, coincident and seemingly redundant regulatory inputs. PMID:26291158

"Express testing" in STI clinics: extant literature and preliminary implementation data.

PubMed

O'Byrne, Patrick; Phillips, J Craig; Campbell, Barbara; Reynolds, Aideen; Metz, Gila

2016-02-01

In an era of stagnant resources for sexually transmitted infection (STI) and HIV testing clinics, and at a time of ongoing-and in some cases increasing-STI and HIV transmission, it is important to trial and evaluate novel STI/HIV testing strategies. Based on the extant literature, one such approach is express testing, which includes full STI/HIV testing (as per clinical indication and client request), altered pretest counseling, and no physical examination for both men and women. In this paper, we overview the available research about express testing, including the literature on less-invasive testing, the effects of risk reduction counseling HIV testin/HIV testing, available research on various HIV testing modalities, and the reasons people undergo such testing. Thereafter, we overview our express testing program, which includes a detailed review of our clinical processes (which are unique within the published literature). Lastly, we provide some preliminary pre-implementation data to support the proposed efficacy of express testing. Copyright © 2015 Elsevier Inc. All rights reserved.

The Media and Children's Issues. Final Report on the Children's Express Symposium III (New York, New York, June 11-12, 1990).

ERIC Educational Resources Information Center

Children's Express Foundation, Inc., New York, NY.

This document is a report of the Children's Express Symposium III, a forum for journalists on children's issues. Included in the report are the comments of news media executives, journalists, broadcasters, experts on children's issues, directors of children's programs, and young people affected by the policies and practices discussed. Opening…

Cosmetics-triggered percutaneous remote control of transgene expression in mice.

PubMed

Wang, Hui; Ye, Haifeng; Xie, Mingqi; Daoud El-Baba, Marie; Fussenegger, Martin

2015-08-18

Synthetic biology has significantly advanced the rational design of trigger-inducible gene switches that program cellular behavior in a reliable and predictable manner. Capitalizing on genetic componentry, including the repressor PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae pathovar tomato DC3000 to sense and resist plant-defence metabolites of the paraben class, we have designed a set of inducible and repressible mammalian transcription-control devices that could dose-dependently fine-tune transgene expression in mammalian cells and mice in response to paraben derivatives. With an over 60-years track record as licensed preservatives in the cosmetics industry, paraben derivatives have become a commonplace ingredient of most skin-care products including shower gels, cleansing toners and hand creams. As parabens can rapidly reach the bloodstream of mice following topical application, we used this feature to percutaneously program transgene expression of subcutaneous designer cell implants using off-the-shelf commercial paraben-containing skin-care cosmetics. The combination of non-invasive, transdermal and orthogonal trigger-inducible remote control of transgene expression may provide novel opportunities for dynamic interventions in future gene and cell-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cosmetics-triggered percutaneous remote control of transgene expression in mice

PubMed Central

Wang, Hui; Ye, Haifeng; Xie, Mingqi; Daoud El-Baba, Marie; Fussenegger, Martin

2015-01-01

Synthetic biology has significantly advanced the rational design of trigger-inducible gene switches that program cellular behavior in a reliable and predictable manner. Capitalizing on genetic componentry, including the repressor PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae pathovar tomato DC3000 to sense and resist plant-defence metabolites of the paraben class, we have designed a set of inducible and repressible mammalian transcription-control devices that could dose-dependently fine-tune transgene expression in mammalian cells and mice in response to paraben derivatives. With an over 60-years track record as licensed preservatives in the cosmetics industry, paraben derivatives have become a commonplace ingredient of most skin-care products including shower gels, cleansing toners and hand creams. As parabens can rapidly reach the bloodstream of mice following topical application, we used this feature to percutaneously program transgene expression of subcutaneous designer cell implants using off-the-shelf commercial paraben-containing skin-care cosmetics. The combination of non-invasive, transdermal and orthogonal trigger-inducible remote control of transgene expression may provide novel opportunities for dynamic interventions in future gene and cell-based therapies. PMID:25943548

75 FR 80561 - Community Express Pilot Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-22

... SMALL BUSINESS ADMINISTRATION Community Express Pilot Program AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of short-term extension and termination of the Community Express Pilot Program. SUMMARY: This notice announces the termination of the Community Express Pilot Program following a...

Radio occultation experiments with INAF-IRA radiotelescopes.

NASA Astrophysics Data System (ADS)

Pluchino, S.; Schillirò, F.; Salerno, E.; Pupillo, G.

The Radio Occultation research program performed at the Medicina and Noto Radioastronomical Stations of the Istituto Nazionale di Astrofisica (INAF) - Istituto di Radioastronomia (IRA) includes observations of spacecraft by satellite and satellite by satellite events. The Lunar Radio Occultation (LRO) part of the program consists in collecting data of the lunar Total Electron Content (TEC), at different limb longitudes and at different time, in order to study long term variation of the Moon's ionosphere. The LRO program started at Medicina in September 2006 with the observation of the European probe SMART-1 during its impact on the lunar soil. It proceeded in 2007 with the observation of the lunar occultations of Saturn and Venus, and with the observation of Mars in 2008. On this occasion the probes Cassini, Venus Express, Mars Express, Mars Reconaissance Orbiter and Mars Odissey were respectively occulted by the moon. On Dec 1st 2008 a Venus lunar occultation occurred. On that occasion we performed the first Italian-VLBI (I-VLBI) tracking experiment by detecting the carrier signals coming from the Venus Express (VEX) spacecraft with both the IRA radiotelescopes together with the Matera antenna of the Italian Space Agency. The second part of the radio occultation program includes the observation of satellite by satellite occultation events, as well as mutual occultations of Jupiter satellites. These events are referred to as mutual phenomena (PHEMU). These observations are aimed to measure the radio flux variation during the occultation and to derive surface spatial characteristics such as Io's hot spots. In this work preliminary results of the Radio Occultation program will be presented.

75 FR 473 - Community Express Pilot Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... SMALL BUSINESS ADMINISTRATION Community Express Pilot Program AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of extension of the Community Express Pilot Program. SUMMARY: This notice extends the Community Express Pilot Program in its current form through December 31, 2010. Based upon the...

A gene expression biomarker accurately predicts estrogen ...

EPA Pesticide Factsheets

The EPA’s vision for the Endocrine Disruptor Screening Program (EDSP) in the 21st Century (EDSP21) includes utilization of high-throughput screening (HTS) assays coupled with computational modeling to prioritize chemicals with the goal of eventually replacing current Tier 1 screening tests. The ToxCast program currently includes 18 HTS in vitro assays that evaluate the ability of chemicals to modulate estrogen receptor α (ERα), an important endocrine target. We propose microarray-based gene expression profiling as a complementary approach to predict ERα modulation and have developed computational methods to identify ERα modulators in an existing database of whole-genome microarray data. The ERα biomarker consisted of 46 ERα-regulated genes with consistent expression patterns across 7 known ER agonists and 3 known ER antagonists. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm by comparison to annotated gene expression data sets from experiments in MCF-7 cells. Using 141 comparisons from chemical- and hormone-treated cells, the biomarker gave a balanced accuracy for prediction of ERα activation or suppression of 94% or 93%, respectively. The biomarker was able to correctly classify 18 out of 21 (86%) OECD ER reference chemicals including “very weak” agonists and replicated predictions based on 18 in vitro ER-associated HTS assays. For 114 chemicals present in both the HTS data and the MCF-7 c

An alternative splicing program promotes adipose tissue thermogenesis

PubMed Central

Vernia, Santiago; Edwards, Yvonne JK; Han, Myoung Sook; Cavanagh-Kyros, Julie; Barrett, Tamera; Kim, Jason K; Davis, Roger J

2016-01-01

Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a splicing program that suppresses adipose tissue thermogenesis. Together, these data provide quantitative analysis of gene expression at exon-level resolution in obesity and identify a novel mechanism that contributes to the regulation of adipose tissue function and the maintenance of normal glycemia. DOI: http://dx.doi.org/10.7554/eLife.17672.001 PMID:27635635

Glossary of Mongolian Technical Terms. Program in Oriental Languages. Publications Series B--Aids--Number 13.

ERIC Educational Resources Information Center

Buck, Frederick H.

This glossary of Mongolian technical terms includes approximately 4,500 entries, covering such areas as political administration, economics, science, railways, stockfarming, agriculture, medicine, foreign affairs, military matters and miscellaneous items. A number of colloquial expressions are included, since they occur quite frequently and appear…

A survey of functional programming language principles

NASA Technical Reports Server (NTRS)

Holloway, C. M.

1986-01-01

Research in the area of functional programming languages has intensified in the 8 years since John Backus' Turing Award Lecture on the topic was published. The purpose of this paper is to present a survey of the ideas of functional programming languages. The paper assumes the reader is comfortable with mathematics and has knowledge of the basic principles of traditional programming languages, but does not assume any prior knowledge of the ideas of functional languages. A simple functional language is defined and used to illustrate the basic ideas. Topics discussed include the reasons for developing functional languages, methods of expressing concurrency, the algebra of functional programming languages, program transformation techniques, and implementations of functional languages. Existing functional languages are also mentioned. The paper concludes with the author's opinions as to the future of functional languages. An annotated bibliography on the subject is also included.

CrasyDSE: A framework for solving Dyson–Schwinger equations☆

PubMed Central

Huber, Markus Q.; Mitter, Mario

2012-01-01

Dyson–Schwinger equations are important tools for non-perturbative analyses of quantum field theories. For example, they are very useful for investigations in quantum chromodynamics and related theories. However, sometimes progress is impeded by the complexity of the equations. Thus automating parts of the calculations will certainly be helpful in future investigations. In this article we present a framework for such an automation based on a C++ code that can deal with a large number of Green functions. Since also the creation of the expressions for the integrals of the Dyson–Schwinger equations needs to be automated, we defer this task to a Mathematica notebook. We illustrate the complete workflow with an example from Yang–Mills theory coupled to a fundamental scalar field that has been investigated recently. As a second example we calculate the propagators of pure Yang–Mills theory. Our code can serve as a basis for many further investigations where the equations are too complicated to tackle by hand. It also can easily be combined with DoFun, a program for the derivation of Dyson–Schwinger equations.1 Program summary Program title: CrasyDSE Catalogue identifier: AEMY _v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEMY_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 49030 No. of bytes in distributed program, including test data, etc.: 303958 Distribution format: tar.gz Programming language: Mathematica 8 and higher, C++. Computer: All on which Mathematica and C++ are available. Operating system: All on which Mathematica and C++ are available (Windows, Unix, Mac OS). Classification: 11.1, 11.4, 11.5, 11.6. Nature of problem: Solve (large) systems of Dyson–Schwinger equations numerically. Solution method: Create C++ functions in Mathematica to be used for the numeric code in C++. This code uses structures to handle large numbers of Green functions. Unusual features: Provides a tool to convert Mathematica expressions into C++ expressions including conversion of function names. Running time: Depending on the complexity of the investigated system solving the equations numerically can take seconds on a desktop PC to hours on a cluster. PMID:25540463

The effect of an anger management program for family members of patients with alcohol use disorders.

PubMed

Son, Ju-Young; Choi, Yun-Jung

2010-02-01

This study was aimed to test the structured anger management nursing program for the family members of patients with alcohol use disorders (AUDs). Families with the AUDs suffer from the dysfunctional family dynamic caused by the patients' deteriorative disease processes of alcohol dependence. Family members of AUDs feel bitter and angry about the uncontrolled behaviors and relapses of the patients in spite of great effort for a long time. This chronic anger threatens the optimal function of the family as well as obstructs the family to help the patients who are suffering from AUDs. Sixty three subjects were participated who were referred from community mental health centers, alcohol consultation centers, and an alcohol hospital in Korea. Pre-post scores of the Korean Anger Expression Inventory were used to test the program. An anger management program was developed and implemented to promote anger expression and anger management for the family members of the patients with AUDs. The total anger expression score of the experimental group was significantly more reduced as compared with that of the control group. Subjects in the experimental group reported after the program that they felt more comfortable and their life was changed in a better way. The anger management program was effective to promote anger expression and anger management for family members of AUDs. Nurses need to include family members in their nursing process as well as to care of patients with AUDs to maximize nursing outcome and patient satisfaction. 2010 Elsevier Inc. All rights reserved.

Symbolic computer vector analysis

NASA Technical Reports Server (NTRS)

Stoutemyer, D. R.

1977-01-01

A MACSYMA program is described which performs symbolic vector algebra and vector calculus. The program can combine and simplify symbolic expressions including dot products and cross products, together with the gradient, divergence, curl, and Laplacian operators. The distribution of these operators over sums or products is under user control, as are various other expansions, including expansion into components in any specific orthogonal coordinate system. There is also a capability for deriving the scalar or vector potential of a vector field. Examples include derivation of the partial differential equations describing fluid flow and magnetohydrodynamics, for 12 different classic orthogonal curvilinear coordinate systems.

COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians.

PubMed

Cowles, Martis W; Omuro, Kerilyn C; Stanley, Brianna N; Quintanilla, Carlo G; Zayas, Ricardo M

2014-10-01

Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.

Seminar on Subminimum Wage for Youth. Executive Summary (New York, New York, April 21, 1981).

ERIC Educational Resources Information Center

1981

A seminar was held to examine the merits and feasibility of a subminimum wage for youth. Throughout the seminar panelists expressed general agreement on the fact that most youth want to work as well as on the value or potential value of employment and training programs, including the Comprehensive Employment and Training Act (CETA) programs. In…

Diversification of Root Hair Development Genes in Vascular Plants.

PubMed

Huang, Ling; Shi, Xinhui; Wang, Wenjia; Ryu, Kook Hui; Schiefelbein, John

2017-07-01

The molecular genetic program for root hair development has been studied intensively in Arabidopsis ( Arabidopsis thaliana ). To understand the extent to which this program might operate in other plants, we conducted a large-scale comparative analysis of root hair development genes from diverse vascular plants, including eudicots, monocots, and a lycophyte. Combining phylogenetics and transcriptomics, we discovered conservation of a core set of root hair genes across all vascular plants, which may derive from an ancient program for unidirectional cell growth coopted for root hair development during vascular plant evolution. Interestingly, we also discovered preferential diversification in the structure and expression of root hair development genes, relative to other root hair- and root-expressed genes, among these species. These differences enabled the definition of sets of genes and gene functions that were acquired or lost in specific lineages during vascular plant evolution. In particular, we found substantial divergence in the structure and expression of genes used for root hair patterning, suggesting that the Arabidopsis transcriptional regulatory mechanism is not shared by other species. To our knowledge, this study provides the first comprehensive view of gene expression in a single plant cell type across multiple species. © 2017 American Society of Plant Biologists. All Rights Reserved.

Diversification of Root Hair Development Genes in Vascular Plants1[OPEN

PubMed Central

Shi, Xinhui; Wang, Wenjia; Ryu, Kook Hui

2017-01-01

The molecular genetic program for root hair development has been studied intensively in Arabidopsis (Arabidopsis thaliana). To understand the extent to which this program might operate in other plants, we conducted a large-scale comparative analysis of root hair development genes from diverse vascular plants, including eudicots, monocots, and a lycophyte. Combining phylogenetics and transcriptomics, we discovered conservation of a core set of root hair genes across all vascular plants, which may derive from an ancient program for unidirectional cell growth coopted for root hair development during vascular plant evolution. Interestingly, we also discovered preferential diversification in the structure and expression of root hair development genes, relative to other root hair- and root-expressed genes, among these species. These differences enabled the definition of sets of genes and gene functions that were acquired or lost in specific lineages during vascular plant evolution. In particular, we found substantial divergence in the structure and expression of genes used for root hair patterning, suggesting that the Arabidopsis transcriptional regulatory mechanism is not shared by other species. To our knowledge, this study provides the first comprehensive view of gene expression in a single plant cell type across multiple species. PMID:28487476

BloodSpot: a database of gene expression profiles and transcriptional programs for healthy and malignant haematopoiesis.

PubMed

Bagger, Frederik Otzen; Sasivarevic, Damir; Sohi, Sina Hadi; Laursen, Linea Gøricke; Pundhir, Sachin; Sønderby, Casper Kaae; Winther, Ole; Rapin, Nicolas; Porse, Bo T

2016-01-04

Research on human and murine haematopoiesis has resulted in a vast number of gene-expression data sets that can potentially answer questions regarding normal and aberrant blood formation. To researchers and clinicians with limited bioinformatics experience, these data have remained available, yet largely inaccessible. Current databases provide information about gene-expression but fail to answer key questions regarding co-regulation, genetic programs or effect on patient survival. To address these shortcomings, we present BloodSpot (www.bloodspot.eu), which includes and greatly extends our previously released database HemaExplorer, a database of gene expression profiles from FACS sorted healthy and malignant haematopoietic cells. A revised interactive interface simultaneously provides a plot of gene expression along with a Kaplan-Meier analysis and a hierarchical tree depicting the relationship between different cell types in the database. The database now includes 23 high-quality curated data sets relevant to normal and malignant blood formation and, in addition, we have assembled and built a unique integrated data set, BloodPool. Bloodpool contains more than 2000 samples assembled from six independent studies on acute myeloid leukemia. Furthermore, we have devised a robust sample integration procedure that allows for sensitive comparison of user-supplied patient samples in a well-defined haematopoietic cellular space. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

An engineering approach to automatic programming

NASA Technical Reports Server (NTRS)

Rubin, Stuart H.

1990-01-01

An exploratory study of the automatic generation and optimization of symbolic programs using DECOM - a prototypical requirement specification model implemented in pure LISP was undertaken. It was concluded, on the basis of this study, that symbolic processing languages such as LISP can support a style of programming based upon formal transformation and dependent upon the expression of constraints in an object-oriented environment. Such languages can represent all aspects of the software generation process (including heuristic algorithms for effecting parallel search) as dynamic processes since data and program are represented in a uniform format.

Programming by early nutrition: an experimental approach.

PubMed

Lucas, A

1998-02-01

That events during critical or sensitive periods of development may "program" long-term or life-time structure or function of the organism is well recognized. Evidence for programming by nutrition is established in animals, in whom brief pre- or postnatal nutritional manipulations may program adult size, metabolism, blood lipids, diabetes, blood pressure, obesity, atherosclerosis, learning, behavior and life span. Human epidemiological data link potential markers of early nutrition (size at birth or in infancy) to cardiovascular disease and its risk factors in adulthood. However, these retrospective data cannot prove nutritional cause or underpin health policies. After 16 y, however, of ethical, randomized intervention studies of early nutrition in humans with long-term follow-up to test experimentally the nutritional programming hypothesis, we find that humans, like other species, have sensitive windows for nutrition in terms of later outcomes; for instance, perinatal diet influences neurodevelopment and bone mineralization into mid-childhood. Possible biological mechanisms for storing throughout life the "memory" of early nutritional experience and its expression in adulthood include adaptive changes in gene expression, preferential clonal selection of adapted cells in programmed tissues and programmed differential proliferation of tissue cell types. Animal and human evidence supporting nutritional programming has major potential biological and medical significance.

An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.

PubMed

Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D

2017-10-30

In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.

Development of a gene expression database and related analysis programs for evaluation of anticancer compounds.

PubMed

Ushijima, Masaru; Mashima, Tetsuo; Tomida, Akihiro; Dan, Shingo; Saito, Sakae; Furuno, Aki; Tsukahara, Satomi; Seimiya, Hiroyuki; Yamori, Takao; Matsuura, Masaaki

2013-03-01

Genome-wide transcriptional expression analysis is a powerful strategy for characterizing the biological activity of anticancer compounds. It is often instructive to identify gene sets involved in the activity of a given drug compound for comparison with different compounds. Currently, however, there is no comprehensive gene expression database and related application system that is; (i) specialized in anticancer agents; (ii) easy to use; and (iii) open to the public. To develop a public gene expression database of antitumor agents, we first examined gene expression profiles in human cancer cells after exposure to 35 compounds including 25 clinically used anticancer agents. Gene signatures were extracted that were classified as upregulated or downregulated after exposure to the drug. Hierarchical clustering showed that drugs with similar mechanisms of action, such as genotoxic drugs, were clustered. Connectivity map analysis further revealed that our gene signature data reflected modes of action of the respective agents. Together with the database, we developed analysis programs that calculate scores for ranking changes in gene expression and for searching statistically significant pathways from the Kyoto Encyclopedia of Genes and Genomes database in order to analyze the datasets more easily. Our database and the analysis programs are available online at our website (http://scads.jfcr.or.jp/db/cs/). Using these systems, we successfully showed that proteasome inhibitors are selectively classified as endoplasmic reticulum stress inducers and induce atypical endoplasmic reticulum stress. Thus, our public access database and related analysis programs constitute a set of efficient tools to evaluate the mode of action of novel compounds and identify promising anticancer lead compounds. © 2012 Japanese Cancer Association.

The Krüppel-like factor 4 controls biosynthesis of thyrotropin-releasing hormone during hypothalamus development.

PubMed

Pérez-Monter, Carlos; Martínez-Armenta, Miriam; Miquelajauregui, Amaya; Furlan-Magaril, Mayra; Varela-Echavarría, Alfredo; Recillas-Targa, Félix; May, Víctor; Charli, Jean-Louis; Pérez-Martínez, Leonor

2011-02-20

Embryonic neurogenesis is controlled by the activation of specific genetic programs. In the hypothalamus, neuronal thyrotropin-releasing hormone (TRH) populations control important physiological process, including energy homeostasis and autonomic function; however, the genetic program leading to the TRH expression is poorly understood. Here, we show that the Klf4 gene, encoding the transcription factor Krüppel-like factor 4 (Klf4), was expressed in the rat hypothalamus during development and regulated Trh expression. In rat fetal hypothalamic cells Klf4 regulated Trh promoter activity through CACCC and GC motifs present on the Trh gene promoter. Accordingly, hypothalamic Trh expression was down-regulated at embryonic day 15 in the Klf4(-/-) mice resulting in diminished bioactive peptide levels. Although at the neonatal stage the Trh transcript levels of the Klf4(-/-) mice were normal, the reduction in peptide levels persisted. Thus, our data indicate that Klf4 plays a key role in the maturation of TRH expression in hypothalamic neurons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

CrasyDSE: A framework for solving Dyson-Schwinger equations.

PubMed

Huber, Markus Q; Mitter, Mario

2012-11-01

Dyson-Schwinger equations are important tools for non-perturbative analyses of quantum field theories. For example, they are very useful for investigations in quantum chromodynamics and related theories. However, sometimes progress is impeded by the complexity of the equations. Thus automating parts of the calculations will certainly be helpful in future investigations. In this article we present a framework for such an automation based on a C++ code that can deal with a large number of Green functions. Since also the creation of the expressions for the integrals of the Dyson-Schwinger equations needs to be automated, we defer this task to a Mathematica notebook. We illustrate the complete workflow with an example from Yang-Mills theory coupled to a fundamental scalar field that has been investigated recently. As a second example we calculate the propagators of pure Yang-Mills theory. Our code can serve as a basis for many further investigations where the equations are too complicated to tackle by hand. It also can easily be combined with DoFun , a program for the derivation of Dyson-Schwinger equations. Program title : CrasyDSE Catalogue identifier : AEMY _v1_0 Program summary URL : http://cpc.cs.qub.ac.uk/summaries/AEMY_v1_0.html Program obtainable from : CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions : Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc. : 49030 No. of bytes in distributed program, including test data, etc. : 303958 Distribution format : tar.gz Programming language : Mathematica 8 and higher, C++ . Computer : All on which Mathematica and C++ are available. Operating system : All on which Mathematica and C++ are available (Windows, Unix, Mac OS). Classification : 11.1, 11.4, 11.5, 11.6. Nature of problem : Solve (large) systems of Dyson-Schwinger equations numerically. Solution method : Create C++ functions in Mathematica to be used for the numeric code in C++ . This code uses structures to handle large numbers of Green functions. Unusual features : Provides a tool to convert Mathematica expressions into C++ expressions including conversion of function names. Running time : Depending on the complexity of the investigated system solving the equations numerically can take seconds on a desktop PC to hours on a cluster.

The opportunities and challenges of large-scale molecular approaches to songbird neurobiology

PubMed Central

Mello, C.V.; Clayton, D.F.

2014-01-01

High-through put methods for analyzing genome structure and function are having a large impact in song-bird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the development of a brain atlas of gene expression. Key emerging findings include the identification of complex transcriptional programs active during singing, the robust brain expression of non-coding RNAs, evidence of profound variations in gene expression across brain regions, and the identification of molecular specializations within song production and learning circuits. Current challenges include the statistical analysis of large datasets, effective genome curations, the efficient localization of gene expression changes to specific neuronal circuits and cells, and the dissection of behavioral and environmental factors that influence brain gene expression. The field requires efficient methods for comparisons with organisms like chicken, which offer important anatomical, functional and behavioral contrasts. As sequencing costs plummet, opportunities emerge for comparative approaches that may help reveal evolutionary transitions contributing to vocal learning, social behavior and other properties that make songbirds such compelling research subjects. PMID:25280907

Georgia’s Brightest Future Includes Russia

DTIC Science & Technology

2012-03-01

partial fulfillment of the requirements of the Senior Service College Fellowship. The views expressed in this student academic research paper are...ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 01-03-2012 2. REPORT TYPE Civilian Research Paper 3. DATES COVERED (From - To) 01 AUG 2011 – 1 MAR...Service College Fellowship Program. The views expressed in this student academic research paper are those of the author and do not reflect the

A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes.

PubMed

Perron, Gabrielle; Jandaghi, Pouria; Solanki, Shraddha; Safisamghabadi, Maryam; Storoz, Cristina; Karimzadeh, Mehran; Papadakis, Andreas I; Arseneault, Madeleine; Scelo, Ghislaine; Banks, Rosamonde E; Tost, Jorg; Lathrop, Mark; Tanguay, Simon; Brazma, Alvis; Huang, Sidong; Brimo, Fadi; Najafabadi, Hamed S; Riazalhosseini, Yasser

2018-05-08

Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2. Modulation of these proteins in cancer cell lines alters the expression of pathways that are central to the disease and highlights RBPs as driving master regulators of RCC transcriptome. This study presents a framework for the screening of RBP activities based on computational modeling of mRNA stability programs in cancer and highlights the role of post-transcriptional gene dysregulation in RCC. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prediction of cancer class with majority voting genetic programming classifier using gene expression data.

PubMed

Paul, Topon Kumar; Iba, Hitoshi

2009-01-01

In order to get a better understanding of different types of cancers and to find the possible biomarkers for diseases, recently, many researchers are analyzing the gene expression data using various machine learning techniques. However, due to a very small number of training samples compared to the huge number of genes and class imbalance, most of these methods suffer from overfitting. In this paper, we present a majority voting genetic programming classifier (MVGPC) for the classification of microarray data. Instead of a single rule or a single set of rules, we evolve multiple rules with genetic programming (GP) and then apply those rules to test samples to determine their labels with majority voting technique. By performing experiments on four different public cancer data sets, including multiclass data sets, we have found that the test accuracies of MVGPC are better than those of other methods, including AdaBoost with GP. Moreover, some of the more frequently occurring genes in the classification rules are known to be associated with the types of cancers being studied in this paper.

LGR5/GPR49 is implicated in motor neuron specification in nervous system.

PubMed

Song, Shao-jun; Mao, Xing-gang; Wang, Chao; Han, An-guo; Yan, Ming; Xue, Xiao-yan

2015-01-01

The biological roles of stem cell marker LGR5, the receptor for the Wnt-agonistic R-spondins, for nervous system are poorly known. Bioinformatics analysis in normal human brain tissues revealed that LGR5 is closely related with neuron development and functions. Interestingly, LGR5 and its ligands R-spondins (RSPO2 and RSPO3) are specifically highly expressed in projection motor neurons in the spinal cord, brain stem and cerebral. Inhibition of Notch activity in neural stem cells (NSCs) increased the percentage of neuronal cells and promoted LGR5 expression, while activation of Notch signal decreased neuronal cells and inhibited the LGR5 expression. Furthermore, knockdown of LGR5 inhibited the expression of neuronal markers MAP2, NeuN, GAP43, SYP and CHRM3, and also reduced the expression of genes that program the identity of motor neurons, including Isl1, Lhx3, PHOX2A, TBX20 and NEUROG2. Our data demonstrated that LGR5 is highly expressed in motor neurons in nervous system and is involved in their development by regulating transcription factors that program motor neuron identity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

AFos Dissociates Cardiac Myocyte Hypertrophy and Expression of the Pathological Gene Program

PubMed Central

Jeong, Mark Y.; Kinugawa, Koichiro; Vinson, Charles; Long, Carlin S.

2005-01-01

Background Although induction of activator protein-1 (AP-1) transcription factor activity has been observed in cardiac hypertrophy, a direct role for AP-1 in myocardial growth and gene expression remains obscure. Methods and Results Hypertrophy was induced in cultured neonatal rat cardiomyocytes with phenylephrine or overexpression of a constitutively active MAP3K, MKK6. In both treatment groups, induction of the pathological gene profile was observed, ie, expression of β-myosin heavy chain (βMHC), atrial/brain natriuretic peptides (ANP/BNP), and skeletal α-actin (sACT) was increased, whereas expression for α-myosin heavy chain (αMHC) and the sarcoplasmic reticulum Ca2+-ATPase (SERCA) genes was repressed. The role of AP-1 in the hypertrophic phenotype was evaluated with the use of an adenoviral construct expressing a dominant negative mutant of the c-Fos proto-oncogene (AdAFos). Although AFos did not change the myocyte growth response, it abrogated the gene profile to both agonists, including the upregulation of both αMHC and SERCA expression. Conclusions Although c-Fos/AP-1 is necessary for induction of the pathological/fetal gene program, it does not appear to be critical for cardiomyocyte hypertrophy. PMID:15795322

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure

PubMed Central

Jorgensen, Elisa M.; Alderman, Myles H.; Taylor, Hugh S.

2016-01-01

Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)–binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERα. Gene–environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.—Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure. PMID:27312807

Using contingent valuation to value a noxious weeds control program: the effects of including an unsure response category

Treesearch

Patricia A. Champ; Anna Alberini; Ignacio Correas

2005-01-01

The National Oceanic and Atmospheric Administration Contingent Valuation panel recommended that a response category be included along with the vote in favor and vote against options associated with a referendum contingent valuation question that allows individuals to express lack of a well defined opinion. However, the recommendation did not include guidance on how to...

The Structure and Function of Non-Collagenous Bone Proteins

NASA Technical Reports Server (NTRS)

Hook, Magnus

1997-01-01

The long-term goal for this program is to determine the structural and functional relationships of bone proteins and proteins that interact with bone. This information will used to design useful pharmacological compounds that will have a beneficial effect in osteoporotic patients and in the osteoporotic-like effects experienced on long duration space missions. The first phase of this program, funded under a cooperative research agreement with NASA through the Texas Medical Center, aimed to develop powerful recombinant expression systems and purification methods for production of large amounts of target proteins. Proteins expressed in sufficient'amount and purity would be characterized by a variety of structural methods, and made available for crystallization studies. In order to increase the likelihood of crystallization and subsequent high resolution solution of structures, we undertook to develop expression of normal and mutant forms of proteins by bacterial and mammalian cells. In addition to the main goals of this program, we would also be able to provide reagents for other related studies, including development of anti-fibrotic and anti-metastatic therapeutics.

Nutritional programming of disease: unravelling the mechanism

PubMed Central

Langley-Evans, Simon C

2009-01-01

Nutritional programming is the process through which variation in the quality or quantity of nutrients consumed during pregnancy exerts permanent effects upon the developing fetus. Programming of fetal development is considered to be an important risk factor for non-communicable diseases of adulthood, including coronary heart disease and other disorders related to insulin resistance. The study of programming in relation to disease processes has been advanced by development of animal models, which have utilized restriction or over-feeding of specific nutrients in either rodents or sheep. These consistently demonstrate the biological plausibility of the nutritional programming hypothesis and, importantly, provide tools with which to examine the mechanisms through which programming may occur. Studies of animals subject to undernutrition in utero generally exhibit changes in the structure of key organs such as the kidney, heart and brain. These appear consistent with remodelling of development, associated with disruption of cellular proliferation and differentiation. Whilst the causal pathways which extend from this tissue remodelling to disease can be easily understood, the processes which lead to this disordered organ development are poorly defined. Even minor variation in maternal nutritional status is capable of producing important shifts in the fetal environment. It is suggested that these environmental changes are associated with altered expression of key genes, which are responsible for driving the tissue remodelling response and future disease risk. Nutrition-related factors may drive these processes by disturbing placental function, including control of materno-fetal endocrine exchanges, or the epigenetic regulation of gene expression. PMID:19175805

Essential Role of DAP12 Signaling in Macrophage Programming into a Fusion-Competent State

PubMed Central

Helming, Laura; Tomasello, Elena; Kyriakides, Themis R.; Martinez, Fernando O.; Takai, Toshiyuki; Gordon, Siamon; Vivier, Eric

2009-01-01

Multinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (TREM-2), and the downstream protein tyrosine kinase Syk is required for the cytokine-induced formation of giant cells and that overexpression of DAP12 potentiates macrophage fusion. We also present evidence that DAP12 is a general macrophage fusion regulator and is involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DC-STAMP and Cadherin 1. Thus, DAP12 is involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state. PMID:18957693

MARQ: an online tool to mine GEO for experiments with similar or opposite gene expression signatures.

PubMed

Vazquez, Miguel; Nogales-Cadenas, Ruben; Arroyo, Javier; Botías, Pedro; García, Raul; Carazo, Jose M; Tirado, Francisco; Pascual-Montano, Alberto; Carmona-Saez, Pedro

2010-07-01

The enormous amount of data available in public gene expression repositories such as Gene Expression Omnibus (GEO) offers an inestimable resource to explore gene expression programs across several organisms and conditions. This information can be used to discover experiments that induce similar or opposite gene expression patterns to a given query, which in turn may lead to the discovery of new relationships among diseases, drugs or pathways, as well as the generation of new hypotheses. In this work, we present MARQ, a web-based application that allows researchers to compare a query set of genes, e.g. a set of over- and under-expressed genes, against a signature database built from GEO datasets for different organisms and platforms. MARQ offers an easy-to-use and integrated environment to mine GEO, in order to identify conditions that induce similar or opposite gene expression patterns to a given experimental condition. MARQ also includes additional functionalities for the exploration of the results, including a meta-analysis pipeline to find genes that are differentially expressed across different experiments. The application is freely available at http://marq.dacya.ucm.es.

Navy-Marine Corps Amphibious and Maritime Prepositioning Ship Programs: Background and Oversight Issues for Congress

DTIC Science & Technology

2006-07-26

FY2008. Although the Navy’s proposed force of 31 amphibious ships includes 10 LPD-17 class ships, the Navy is planning to end LPD-17 procurement in...expresses concerns about the planned reduction in amphibious ships, the sea basing concept, and the MPF(F) program, and requires a report on sea basing...Ship Force Structure Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Sea Basing Concept of Operations

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

PubMed

Achard, V; Tassistro, V; Boullu-Ciocca, S; Grino, M

2011-12-01

Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

CrasyDSE: A framework for solving Dyson-Schwinger equations

NASA Astrophysics Data System (ADS)

Huber, Markus Q.; Mitter, Mario

2012-11-01

Dyson-Schwinger equations are important tools for non-perturbative analyses of quantum field theories. For example, they are very useful for investigations in quantum chromodynamics and related theories. However, sometimes progress is impeded by the complexity of the equations. Thus automating parts of the calculations will certainly be helpful in future investigations. In this article we present a framework for such an automation based on a C++ code that can deal with a large number of Green functions. Since also the creation of the expressions for the integrals of the Dyson-Schwinger equations needs to be automated, we defer this task to a Mathematica notebook. We illustrate the complete workflow with an example from Yang-Mills theory coupled to a fundamental scalar field that has been investigated recently. As a second example we calculate the propagators of pure Yang-Mills theory. Our code can serve as a basis for many further investigations where the equations are too complicated to tackle by hand. It also can easily be combined with DoFun, a program for the derivation of Dyson-Schwinger equations.

Multiprocessor smalltalk: Implementation, performance, and analysis

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

Pallas, J.I.

1990-01-01

Multiprocessor Smalltalk demonstrates the value of object-oriented programming on a multiprocessor. Its implementation and analysis shed light on three areas: concurrent programming in an object oriented language without special extensions, implementation techniques for adapting to multiprocessors, and performance factors in the resulting system. Adding parallelism to Smalltalk code is easy, because programs already use control abstractions like iterators. Smalltalk's basic control and concurrency primitives (lambda expressions, processes and semaphores) can be used to build parallel control abstractions, including parallel iterators, parallel objects, atomic objects, and futures. Language extensions for concurrency are not required. This implementation demonstrates that it is possiblemore » to build an efficient parallel object-oriented programming system and illustrates techniques for doing so. Three modification tools-serialization, replication, and reorganization-adapted the Berkeley Smalltalk interpreter to the Firefly multiprocessor. Multiprocessor Smalltalk's performance shows that the combination of multiprocessing and object-oriented programming can be effective: speedups (relative to the original serial version) exceed 2.0 for five processors on all the benchmarks; the median efficiency is 48%. Analysis shows both where performance is lost and how to improve and generalize the experimental results. Changes in the interpreter to support concurrency add at most 12% overhead; better access to per-process variables could eliminate much of that. Changes in the user code to express concurrency add as much as 70% overhead; this overhead could be reduced to 54% if blocks (lambda expressions) were reentrant. Performance is also lost when the program cannot keep all five processors busy.« less

The Invar tensor package: Differential invariants of Riemann

NASA Astrophysics Data System (ADS)

Martín-García, J. M.; Yllanes, D.; Portugal, R.

2008-10-01

The long standing problem of the relations among the scalar invariants of the Riemann tensor is computationally solved for all 6ṡ10 objects with up to 12 derivatives of the metric. This covers cases ranging from products of up to 6 undifferentiated Riemann tensors to cases with up to 10 covariant derivatives of a single Riemann. We extend our computer algebra system Invar to produce within seconds a canonical form for any of those objects in terms of a basis. The process is as follows: (1) an invariant is converted in real time into a canonical form with respect to the permutation symmetries of the Riemann tensor; (2) Invar reads a database of more than 6ṡ10 relations and applies those coming from the cyclic symmetry of the Riemann tensor; (3) then applies the relations coming from the Bianchi identity, (4) the relations coming from commutations of covariant derivatives, (5) the dimensionally-dependent identities for dimension 4, and finally (6) simplifies invariants that can be expressed as product of dual invariants. Invar runs on top of the tensor computer algebra systems xTensor (for Mathematica) and Canon (for Maple). Program summaryProgram title:Invar Tensor Package v2.0 Catalogue identifier:ADZK_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADZK_v2_0.html Program obtainable from:CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions:Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.:3 243 249 No. of bytes in distributed program, including test data, etc.:939 Distribution format:tar.gz Programming language:Mathematica and Maple Computer:Any computer running Mathematica versions 5.0 to 6.0 or Maple versions 9 and 11 Operating system:Linux, Unix, Windows XP, MacOS RAM:100 Mb Word size:64 or 32 bits Supplementary material:The new database of relations is much larger than that for the previous version and therefore has not been included in the distribution. To obtain the Mathematica and Maple database files click on this link. Classification:1.5, 5 Does the new version supersede the previous version?:Yes. The previous version (1.0) only handled algebraic invariants. The current version (2.0) has been extended to cover differential invariants as well. Nature of problem:Manipulation and simplification of scalar polynomial expressions formed from the Riemann tensor and its covariant derivatives. Solution method:Algorithms of computational group theory to simplify expressions with tensors that obey permutation symmetries. Tables of syzygies of the scalar invariants of the Riemann tensor. Reasons for new version:With this new version, the user can manipulate differential invariants of the Riemann tensor. Differential invariants are required in many physical problems in classical and quantum gravity. Summary of revisions:The database of syzygies has been expanded by a factor of 30. New commands were added in order to deal with the enlarged database and to manipulate the covariant derivative. Restrictions:The present version only handles scalars, and not expressions with free indices. Additional comments:The distribution file for this program is over 53 Mbytes and therefore is not delivered directly when download or Email is requested. Instead a html file giving details of how the program can be obtained is sent. Running time:One second to fully reduce any monomial of the Riemann tensor up to degree 7 or order 10 in terms of independent invariants. The Mathematica notebook included in the distribution takes approximately 5 minutes to run.

A review of recommendations for sequencing receptive and expressive language instruction.

PubMed

Petursdottir, Anna Ingeborg; Carr, James E

2011-01-01

We review recommendations for sequencing instruction in receptive and expressive language objectives in early and intensive behavioral intervention (EIBI) programs. Several books recommend completing receptive protocols before introducing corresponding expressive protocols. However, this recommendation has little empirical support, and some evidence exists that the reverse sequence may be more efficient. Alternative recommendations include teaching receptive and expressive skills simultaneously (M. L. Sundberg & Partington, 1998) and building learning histories that lead to acquisition of receptive and expressive skills without direct instruction (Greer & Ross, 2008). Empirical support for these recommendations also is limited. Future research should assess the relative efficiency of receptive-before-expressive, expressive-before-receptive, and simultaneous training with children who have diagnoses of autism spectrum disorders. In addition, further evaluation is needed of the potential benefits of multiple-exemplar training and other variables that may influence the efficiency of receptive and expressive instruction.

A REVIEW OF RECOMMENDATIONS FOR SEQUENCING RECEPTIVE AND EXPRESSIVE LANGUAGE INSTRUCTION

PubMed Central

Petursdottir, Anna Ingeborg; Carr, James E

2011-01-01

We review recommendations for sequencing instruction in receptive and expressive language objectives in early and intensive behavioral intervention (EIBI) programs. Several books recommend completing receptive protocols before introducing corresponding expressive protocols. However, this recommendation has little empirical support, and some evidence exists that the reverse sequence may be more efficient. Alternative recommendations include teaching receptive and expressive skills simultaneously (M. L. Sundberg & Partington, 1998) and building learning histories that lead to acquisition of receptive and expressive skills without direct instruction (Greer & Ross, 2008). Empirical support for these recommendations also is limited. Future research should assess the relative efficiency of receptive-before-expressive, expressive-before-receptive, and simultaneous training with children who have diagnoses of autism spectrum disorders. In addition, further evaluation is needed of the potential benefits of multiple-exemplar training and other variables that may influence the efficiency of receptive and expressive instruction. PMID:22219535

ASSIST - THE ABSTRACT SEMI-MARKOV SPECIFICATION INTERFACE TO THE SURE TOOL PROGRAM (SUN VERSION)

NASA Technical Reports Server (NTRS)

Johnson, S. C.

1994-01-01

ASSIST, the Abstract Semi-Markov Specification Interface to the SURE Tool program, is an interface that will enable reliability engineers to accurately design large semi-Markov models. The user describes the failure behavior of a fault-tolerant computer system in an abstract, high-level language. The ASSIST program then automatically generates a corresponding semi-Markov model. The abstract language allows efficient description of large, complex systems; a one-page ASSIST-language description may result in a semi-Markov model with thousands of states and transitions. The ASSIST program also includes model-reduction techniques to facilitate efficient modeling of large systems. Instead of listing the individual states of the Markov model, reliability engineers can specify the rules governing the behavior of a system, and these are used to automatically generate the model. ASSIST reads an input file describing the failure behavior of a system in an abstract language and generates a Markov model in the format needed for input to SURE, the semi-Markov Unreliability Range Evaluator program, and PAWS/STEM, the Pade Approximation with Scaling program and Scaled Taylor Exponential Matrix. A Markov model consists of a number of system states and transitions between them. Each state in the model represents a possible state of the system in terms of which components have failed, which ones have been removed, etc. Within ASSIST, each state is defined by a state vector, where each element of the vector takes on an integer value within a defined range. An element can represent any meaningful characteristic, such as the number of working components of one type in the system, or the number of faulty components of another type in use. Statements representing transitions between states in the model have three parts: a condition expression, a destination expression, and a rate expression. The first expression is a Boolean expression describing the state space variable values of states for which the transition is valid. The second expression defines the destination state for the transition in terms of state space variable values. The third expression defines the distribution of elapsed time for the transition. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. Although different solution techniques are utilized on different programs, it is possible to have a common input language. The Systems Validation Methods group at NASA Langley Research Center has created a set of programs that form the basis for a reliability analysis workstation. The set of programs are: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920); and the FTC fault tree tool (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree. PAWS/STEM and SURE are programs which interpret the same SURE language, but utilize different solution methods. ASSIST is a preprocessor that generates SURE language from a more abstract definition. SURE, ASSIST, and PAWS/STEM are also offered as a bundle. Please see the abstract for COS-10039/COS-10041, SARA - SURE/ASSIST Reliability Analysis Workstation, for pricing details. ASSIST was originally developed for DEC VAX series computers running VMS and was later ported for use on Sun computers running SunOS. The VMS version (LAR14193) is written in C-language and can be compiled with the VAX C compiler. The standard distribution medium for the VMS version of ASSIST is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The Sun version (LAR14923) is written in ANSI C-language. An ANSI compliant C compiler is required in order to compile this package. The standard distribution medium for the Sun version of ASSIST is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. Electronic copies of the documentation in PostScript, TeX, and DVI formats are provided on the distribution medium. (The VMS distribution lacks the .DVI format files, however.) ASSIST was developed in 1986 and last updated in 1992. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. SunOS, Sun3, and Sun4 are trademarks of Sun Microsystems, Inc. UNIX is a registered trademark of AT&T Bell Laboratories.

ASSIST - THE ABSTRACT SEMI-MARKOV SPECIFICATION INTERFACE TO THE SURE TOOL PROGRAM (VAX VMS VERSION)

NASA Technical Reports Server (NTRS)

Johnson, S. C.

1994-01-01

ASSIST, the Abstract Semi-Markov Specification Interface to the SURE Tool program, is an interface that will enable reliability engineers to accurately design large semi-Markov models. The user describes the failure behavior of a fault-tolerant computer system in an abstract, high-level language. The ASSIST program then automatically generates a corresponding semi-Markov model. The abstract language allows efficient description of large, complex systems; a one-page ASSIST-language description may result in a semi-Markov model with thousands of states and transitions. The ASSIST program also includes model-reduction techniques to facilitate efficient modeling of large systems. Instead of listing the individual states of the Markov model, reliability engineers can specify the rules governing the behavior of a system, and these are used to automatically generate the model. ASSIST reads an input file describing the failure behavior of a system in an abstract language and generates a Markov model in the format needed for input to SURE, the semi-Markov Unreliability Range Evaluator program, and PAWS/STEM, the Pade Approximation with Scaling program and Scaled Taylor Exponential Matrix. A Markov model consists of a number of system states and transitions between them. Each state in the model represents a possible state of the system in terms of which components have failed, which ones have been removed, etc. Within ASSIST, each state is defined by a state vector, where each element of the vector takes on an integer value within a defined range. An element can represent any meaningful characteristic, such as the number of working components of one type in the system, or the number of faulty components of another type in use. Statements representing transitions between states in the model have three parts: a condition expression, a destination expression, and a rate expression. The first expression is a Boolean expression describing the state space variable values of states for which the transition is valid. The second expression defines the destination state for the transition in terms of state space variable values. The third expression defines the distribution of elapsed time for the transition. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. Although different solution techniques are utilized on different programs, it is possible to have a common input language. The Systems Validation Methods group at NASA Langley Research Center has created a set of programs that form the basis for a reliability analysis workstation. The set of programs are: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920); and the FTC fault tree tool (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree. PAWS/STEM and SURE are programs which interpret the same SURE language, but utilize different solution methods. ASSIST is a preprocessor that generates SURE language from a more abstract definition. SURE, ASSIST, and PAWS/STEM are also offered as a bundle. Please see the abstract for COS-10039/COS-10041, SARA - SURE/ASSIST Reliability Analysis Workstation, for pricing details. ASSIST was originally developed for DEC VAX series computers running VMS and was later ported for use on Sun computers running SunOS. The VMS version (LAR14193) is written in C-language and can be compiled with the VAX C compiler. The standard distribution medium for the VMS version of ASSIST is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The Sun version (LAR14923) is written in ANSI C-language. An ANSI compliant C compiler is required in order to compile this package. The standard distribution medium for the Sun version of ASSIST is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. Electronic copies of the documentation in PostScript, TeX, and DVI formats are provided on the distribution medium. (The VMS distribution lacks the .DVI format files, however.) ASSIST was developed in 1986 and last updated in 1992. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. SunOS, Sun3, and Sun4 are trademarks of Sun Microsystems, Inc. UNIX is a registered trademark of AT&T Bell Laboratories.

Chronic Postnatal Stress Induces Depressive-like Behavior in Male Mice and Programs second-Hit Stress-Induced Gene Expression Patterns of OxtR and AvpR1a in Adulthood.

PubMed

Lesse, Alexandra; Rether, Kathy; Gröger, Nicole; Braun, Katharina; Bock, Jörg

2017-08-01

Chronic stress (CS) during early life represents a major risk factor for the development of mental disorders, including depression. According to the Two/Multiple-Hit hypothesis, the etiology of neuropsychiatric disorders usually involves multiple stressors experienced subsequently during different phases of life. However, the molecular and cellular mechanisms modulating neuronal and behavioral changes induced by multiple stress experiences are just poorly understood. Since the oxytocinergic and vasopressinergic systems are neuroendocrine modulators involved in environmentally driven adaptations of stress sensitivity we hypothesized that postnatal CS programs oxytocinergic and vasopressinergic receptor expression changes in response to a second stress exposure in young adulthood. First we investigated if postnatal CS (maternal separation + social isolation) induces depressive-like behavior and alters oxytocin receptor (OxtR) and arginine vasopressin receptor type 1a (AvpR1a) gene expression in the hippocampus (HC) of male mice and (2) if a second single stressor (forced swimming, FS) in young adulthood affects gene expression of OxtR and AvpR1a at adulthood dependent on CS pre-experience. We found that postnatal CS induced depressive-like behavior and enhanced AvpR1a expression in HC at young adulthood. Moreover, in line with our hypothesis, only combined stress exposure (CS + FS), but not CS or FS alone, resulted in increased gene expression of OxtR in HC at adulthood. In contrast, AvpR1a expression was decreased in both adult FS and CS + FS animals. Overall, our results provide evidence that CS programs neuroendocrine systems and thereby influences stress responses in later life periods.

Developmental programming by androgen affects the circadian timing system in female mice.

PubMed

Mereness, Amanda L; Murphy, Zachary C; Sellix, Michael T

2015-04-01

Circadian clocks play essential roles in the timing of events in the mammalian hypothalamo-pituitary-ovarian (HPO) axis. The molecular oscillator driving these rhythms has been localized to tissues of the HPO axis. It has been suggested that synchrony among these oscillators is a feature of normal reproductive function. The impact of fertility disorders on clock function and the role of the clock in the etiology of endocrine pathology remain unknown. Polycystic ovarian syndrome (PCOS) is a particularly devastating fertility disorder, affecting 5%-10% of women at childbearing age with features including a polycystic ovary, anovulation, and elevated serum androgen. Approximately 40% of these women have metabolic syndrome, marked by hyperinsulinemia, dyslipidemia, and insulin resistance. It has been suggested that developmental exposure to excess androgen contributes to the etiology of fertility disorders, including PCOS. To better define the role of the timing system in these disorders, we determined the effects of androgen-dependent developmental programming on clock gene expression in tissues of the metabolic and HPO axes. Female PERIOD2::luciferase (PER2::LUC) mice were exposed to androgen (dihydrotestosterone [DHT]) in utero (Days 16-18 of gestation) or for 9-10 wk (DHT pellet) beginning at weaning (pubertal androgen excess [PAE]). As expected, both groups of androgen-treated mice had disrupted estrous cycles. Analysis of PER2::LUC expression in tissue explants revealed that excess androgen produced circadian misalignment via tissue-dependent effects on phase distribution. In vitro treatment with DHT differentially affected the period of PER2::LUC expression in tissue explants and granulosa cells, indicating that androgen has direct and tissue-specific effects on clock gene expression that may account for the effects of developmental programming on the timing system. © 2015 by the Society for the Study of Reproduction, Inc.

RECA EXPRESSION IN RESPONSE TO SOLAR UVR IN THE MARINE BACTERIUM VIBRIO NATRIEGENS.

EPA Science Inventory

Medicinal plants may carry residuals of environmentally persistent pesticides or assimilate heavy metals in varying degrees. Several factors may influence contaminant accumulation, including species, level and duration of contaminant exposure, and topography. As part of a program...

Engineered human skin substitutes undergo large-scale genomic reprogramming and normal skin-like maturation after transplantation to athymic mice.

PubMed

Klingenberg, Jennifer M; McFarland, Kevin L; Friedman, Aaron J; Boyce, Steven T; Aronow, Bruce J; Supp, Dorothy M

2010-02-01

Bioengineered skin substitutes can facilitate wound closure in severely burned patients, but deficiencies limit their outcomes compared with native skin autografts. To identify gene programs associated with their in vivo capabilities and limitations, we extended previous gene expression profile analyses to now compare engineered skin after in vivo grafting with both in vitro maturation and normal human skin. Cultured skin substitutes were grafted on full-thickness wounds in athymic mice, and biopsy samples for microarray analyses were collected at multiple in vitro and in vivo time points. Over 10,000 transcripts exhibited large-scale expression pattern differences during in vitro and in vivo maturation. Using hierarchical clustering, 11 different expression profile clusters were partitioned on the basis of differential sample type and temporal stage-specific activation or repression. Analyses show that the wound environment exerts a massive influence on gene expression in skin substitutes. For example, in vivo-healed skin substitutes gained the expression of many native skin-expressed genes, including those associated with epidermal barrier and multiple categories of cell-cell and cell-basement membrane adhesion. In contrast, immunological, trichogenic, and endothelial gene programs were largely lacking. These analyses suggest important areas for guiding further improvement of engineered skin for both increased homology with native skin and enhanced wound healing.

Writing objectives and evaluating learning in the affective domain.

PubMed

Maier-Lorentz, M M

1999-01-01

Staff educators recognize the importance of affective competency for effective nursing practice. Inservice programs must include affective learning with objectives stated in measurable terms. Staff educators often express frustration in developing affective objectives and evaluating the learning outcome because attitudes and feelings are usually inferred from observations. This article presents affective learning objectives for a gerontological nursing inservice program and a rating scale that measures attitudes to evaluate the learning outcome.

Improving Demonstration Using Better Interaction Techniques

DTIC Science & Technology

1997-01-14

Programming by demonstration (PBD) can be used to create tools and methods that eliminate the need to learn difficult computer languages. Gamut is a...do this, Gamut uses advanced interaction techniques that make it easier for a software author to express all needed aspects of one’s program. These...techniques include a simplified way to demonstrate new examples, called nudges, and a way to highlight objects to show they are important. Also, Gamut

Developmental programming: effect of prenatal steroid excess on intraovarian components of insulin signaling pathway and related proteins in sheep.

PubMed

Ortega, Hugo H; Rey, Florencia; Velazquez, Melisa M L; Padmanabhan, Vasantha

2010-06-01

Prenatal testosterone (T) excess increases ovarian follicular recruitment, follicular persistence, insulin resistance, and compensatory hyperinsulinemia. Considering the importance of insulin in ovarian physiology, in this study, using prenatal T- and dihydrotestosterone (DHT, a nonaromatizable androgen)-treated female sheep, we tested the hypothesis that prenatal androgen excess alters the intraovarian insulin signaling cascade and metabolic mediators that have an impact on insulin signaling. Changes in ovarian insulin receptor (INSRB), insulin receptor substrate 1 (IRS1), mammalian target of rapamycin (MTOR), phosphatidylinositol 3-kinase (PIK3), peroxisome proliferator-activated receptor-gamma (PPARG), and adiponectin proteins were determined at fetal (Days 90 and 140), postpubertal (10 mo), and adult (21 mo) ages by immunohistochemistry. Results indicated that these proteins were expressed in granulosa, theca, and stromal compartments, with INSRB, IRS1, PPARG, and adiponectin increasing in parallel with advanced follicular differentiation. Importantly, prenatal T excess induced age-specific changes in PPARG and adiponectin expression, with increased PPARG expression evident during fetal life and decreased antral follicular adiponectin expression during adult life. Comparison of developmental changes in prenatal T and DHT-treated females found that the effects on PPARG were programmed by androgenic actions of T, whereas the effects on adiponectin were likely by its estrogenic action. These results suggest a role for PPARG in the programming of ovarian disruptions by prenatal T excess, including a decrease in antral follicular adiponectin expression and a contributory role for adiponectin in follicular persistence and ovulatory failure.

The temporal and spatial expression of Claudins in epidermal development and the accelerated program of epidermal differentiation in K14-CaSR transgenic mice.

PubMed

Troy, Tammy-Claire; Li, Yuhua; O'Malley, Lauren; Turksen, Kursad

2007-02-01

The importance of the epidermal permeability barrier (EPB) in protecting the mammalian species against harmful UV irradiation, microorganism invasion and water loss is well recognized, as is the role of calcium (Ca(2+)) in keratinocyte differentiation, cell-cell contact and the EPB. In a previous study, we reported that the overexpression of the Ca(2+)-sensing receptor (CaSR) in the undifferentiated basal cells of the epidermis induced a modified epidermal differentiation program including an accelerated EPB formation in transgenic mice, suggesting a role for CaSR signaling in the differentiation of embryonic epidermal cells during development. We now describe the expression profile of claudins (Cldns) and keratin markers in the accelerated EPB formation of K14-CaSR transgenic mice during development as compared to the wild type from E12.5 to newborn stages. Our data show that the transgenic epidermis undergoes an advanced epidermal differentiation program as compared to the wild type as evidenced morphologically as well as by the expression of K14, K1, loricrin, Cldn6, Cldn18 and Cldn11. In addition, we report for the first time the sequential expression of Cldns in epidermal development and describe that the localization of some Cldns change within the epidermis as it matures. Furthermore, we demonstrate that Cldn6 is expressed very early in epidermal morphogenesis, followed by Cldn18, Cldn11 and Cldn1.

Flexible language constructs for large parallel programs

NASA Technical Reports Server (NTRS)

Rosing, Matthew; Schnabel, Robert

1993-01-01

The goal of the research described is to develop flexible language constructs for writing large data parallel numerical programs for distributed memory (MIMD) multiprocessors. Previously, several models have been developed to support synchronization and communication. Models for global synchronization include SIMD (Single Instruction Multiple Data), SPMD (Single Program Multiple Data), and sequential programs annotated with data distribution statements. The two primary models for communication include implicit communication based on shared memory and explicit communication based on messages. None of these models by themselves seem sufficient to permit the natural and efficient expression of the variety of algorithms that occur in large scientific computations. An overview of a new language that combines many of these programming models in a clean manner is given. This is done in a modular fashion such that different models can be combined to support large programs. Within a module, the selection of a model depends on the algorithm and its efficiency requirements. An overview of the language and discussion of some of the critical implementation details is given.

Viral-induced Modulation of Multiple Checkpoint Proteins in Cancers.

PubMed

Nuovo, Gerard J; Folcik, Virginia A; Magro, Cynthia

2017-07-01

Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers. The expression of each checkpoint protein was significantly higher among 166 cases of viral-related (mostly human papillomavirus) cancers where expression of PD L1 was noted in 84%, PD L2 in 67%, IDO1 in 61%, and CTLA4 in 37% (each P value <0.001); 97% of the viral-related cancers showed expression of at least 1 checkpoint protein. In addition, over 90% of the CD8 cells in the viral-associated cancers were quiescent based on low coexpression of Ki-67 as well as pSTAT1. It is concluded that viral infection in cancers is associated with the increased expression of key checkpoint proteins. This indicates that cancers with productive viral infection may be better targets for checkpoint inhibitor therapy.

Brn3a and Islet1 act epistatically to regulate the gene expression program of sensory differentiation

PubMed Central

Dykes, Iain M.; Tempest, Lynne; Lee, Su-In; Turner, Eric E.

2011-01-01

The combinatorial expression of transcription factors frequently marks cellular identity in the nervous system, yet how these factors interact to determine specific neuronal phenotypes is not well understood. Sensory neurons of the trigeminal (TG) and dorsal root ganglia (DRG) co-express the homeodomain transcription factors Brn3a and Islet1, and past work has revealed partially overlapping programs of gene expression downstream of these factors. Here we examine sensory development in Brn3a/Islet1 double knockout mice (DKO mice). Sensory neurogenesis and the formation of the TG and DRG occur in DKO embryos, but the DRG are dorsally displaced, and the peripheral projections of the ganglia are markedly disturbed. Sensory neurons in DKO embryos show a profound loss of all early markers of sensory subtypes, including the Ntrk neurotrophin receptors, and the runt-family transcription factors Runx1 and Runx3. Examination of global gene expression in the E12.5 DRG of single and double mutant embryos shows that Brn3a and Islet1 are together required for nearly all aspects of sensory-specific gene expression, including several newly identified sensory markers. On a majority of targets Brn3a and Islet1 exhibit negative epistasis, in which the effects of the individual knockout alleles are less than additive in the DKO. Smaller subsets of targets exhibit positive epistasis, or are regulated exclusively by one factor. Brn3a/Islet1 double mutants also fail to developmentally repress neurogenic bHLH genes, and in vivo chromatin immunoprecipitation shows that Islet1 binds to a known Brn3a -regulated enhancer in the neurod4 gene, suggesting a mechanism of interaction between these genes. PMID:21734270

Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring

PubMed Central

Lee, Wei-Chia; Tain, You-Lin; Wu, Kay L. H.; Leu, Steve; Chan, Julie Y. H.

2016-01-01

Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE. PMID:27703194

Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring.

PubMed

Lee, Wei-Chia; Tain, You-Lin; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

2016-10-05

Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M 2 -, M 3 -muscarinic and P2X 1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE.

Programmed Death-1 Inhibition of Phosphatidylinositol 3-Kinase/AKT/Mechanistic Target of Rapamycin Signaling Impairs Sarcoidosis CD4+ T Cell Proliferation.

PubMed

Celada, Lindsay J; Rotsinger, Joseph E; Young, Anjuli; Shaginurova, Guzel; Shelton, Debresha; Hawkins, Charlene; Drake, Wonder P

2017-01-01

Patients with progressive sarcoidosis exhibit increased expression of programmed death-1 (PD-1) receptor on their CD4 + T cells. Up-regulation of this marker of T cell exhaustion is associated with a reduction in the proliferative response to T cell receptor (TCR) stimulation, a defect that is reversed by PD-1 pathway blockade. Genome-wide association studies and microarray analyses have correlated signaling downstream from the TCR with sarcoidosis disease severity, but the mechanism is not yet known. Reduced phosphatidylinositol 3-kinase (PI3K)/AKT expression inhibits proliferation by inhibiting cell cycle progression. To test the hypothesis that PD-1 expression attenuates TCR-dependent activation of PI3K/AKT activity in progressive systemic sarcoidosis, we analyzed PI3K/AKT/mechanistic target of rapamycin (mTOR) expression at baseline and after PD-1 pathway blockade in CD4 + T cells isolated from patients with sarcoidosis and healthy control subjects. We confirmed an increased percentage of PD-1 + CD4 + T cells and reduced proliferative capacity in patients with sarcoidosis compared with healthy control subjects (P < 0.001). There was a negative correlation with PD-1 expression and proliferative capacity (r = -0.70, P < 0.001). Expression of key mediators of cell cycle progression, including PI3K and AKT, were significantly decreased. Gene and protein expression levels reverted to healthy control levels after PD-1 pathway blockade. Reduction in sarcoidosis CD4 + T cell proliferative capacity is secondary to altered expression of key mediators of cell cycle progression, including the PI3K/AKT/mTOR pathway, via PD-1 up-regulation. This supports the concept that PD-1 up-regulation drives the immunologic deficits associated with sarcoidosis severity by inducing signaling aberrancies in key mediators of cell cycle progression.

Programmed Death-1 Inhibition of Phosphatidylinositol 3-Kinase/AKT/Mechanistic Target of Rapamycin Signaling Impairs Sarcoidosis CD4+ T Cell Proliferation

PubMed Central

Celada, Lindsay J.; Rotsinger, Joseph E.; Young, Anjuli; Shaginurova, Guzel; Shelton, Debresha; Hawkins, Charlene

2017-01-01

Patients with progressive sarcoidosis exhibit increased expression of programmed death-1 (PD-1) receptor on their CD4+ T cells. Up-regulation of this marker of T cell exhaustion is associated with a reduction in the proliferative response to T cell receptor (TCR) stimulation, a defect that is reversed by PD-1 pathway blockade. Genome-wide association studies and microarray analyses have correlated signaling downstream from the TCR with sarcoidosis disease severity, but the mechanism is not yet known. Reduced phosphatidylinositol 3-kinase (PI3K)/AKT expression inhibits proliferation by inhibiting cell cycle progression. To test the hypothesis that PD-1 expression attenuates TCR-dependent activation of PI3K/AKT activity in progressive systemic sarcoidosis, we analyzed PI3K/AKT/mechanistic target of rapamycin (mTOR) expression at baseline and after PD-1 pathway blockade in CD4+ T cells isolated from patients with sarcoidosis and healthy control subjects. We confirmed an increased percentage of PD-1+ CD4+ T cells and reduced proliferative capacity in patients with sarcoidosis compared with healthy control subjects (P < 0.001). There was a negative correlation with PD-1 expression and proliferative capacity (r = −0.70, P < 0.001). Expression of key mediators of cell cycle progression, including PI3K and AKT, were significantly decreased. Gene and protein expression levels reverted to healthy control levels after PD-1 pathway blockade. Reduction in sarcoidosis CD4+ T cell proliferative capacity is secondary to altered expression of key mediators of cell cycle progression, including the PI3K/AKT/mTOR pathway, via PD-1 up-regulation. This supports the concept that PD-1 up-regulation drives the immunologic deficits associated with sarcoidosis severity by inducing signaling aberrancies in key mediators of cell cycle progression. PMID:27564547

Globo H expression is associated with driver mutations and PD-L1 expressions in stage I non-small cell lung cancer.

PubMed

Yang, Ching-Yao; Lin, Mong-Wei; Chang, Yih-Leong; Wu, Chen-Tu

2017-12-12

Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in ⩾ 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment.

Androgen-induced programs for prostate epithelial growth and invasion arise in embryogenesis and are reactivated in cancer

PubMed Central

Schaeffer, EM; Marchionni, L; Huang, Z; Simons, B; Blackman, A; Yu, W; Parmigiani, G; Berman, DM

2008-01-01

Cancer cells differentiate along specific lineages that largely determine their clinical and biologic behavior. Distinct cancer phenotypes from different cells and organs likely result from unique gene expression repertoires established in the embryo and maintained after malignant transformation. We used comprehensive gene expression analysis to examine this concept in the prostate, an organ with a tractable developmental program and a high propensity for cancer. We focused on gene expression in the murine prostate rudiment at three time points during the first 48 h of exposure to androgen, which initiates proliferation and invasion of prostate epithelial buds into surrounding urogenital sinus mesenchyme. Here, we show that androgen exposure regulates genes previously implicated in prostate carcinogenesis comprising pathways for the phosphatase and tensin homolog (PTEN), fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), and Wnt signaling along with cellular programs regulating such ‘hallmarks’ of cancer as angiogenesis, apoptosis, migration and proliferation. We found statistically significant evidence for novel androgeninduced gene regulation events that establish and/or maintain prostate cell fate. These include modulation of gene expression through microRNAs, expression of specific transcription factors, and regulation of their predicted targets. By querying public gene expression databases from other tissues, we found that rather than generally characterizing androgen exposure or epithelial budding, the early prostate development program more closely resembles the program for human prostate cancer. Most importantly, early androgen-regulated genes and functional themes associated with prostate development were highly enriched in contrasts between increasingly lethal forms of prostate cancer, confirming a ‘reactivation’ of embryonic pathways for proliferation and invasion in prostate cancer progression. Among the genes with the most significant links to the development and cancer, we highlight coordinate induction of the transcription factor Sox9 and suppression of the proapoptotic phospholipid-binding protein Annexin A1 that link early prostate development to early prostate carcinogenesis. These results credential early prostate development as a reliable and valid model system for the investigation of genes and pathways that drive prostate cancer. PMID:18794802

10 CFR 707.16 - Records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... retrieval of all information pertaining to the individual urine specimens for a minimum period of five years... disclosure of such information shall be followed. Moreover, owing to DOE's express environmental, public..., DOE must be kept fully apprised of all aspects of the contractor's program, including such information...

10 CFR 707.16 - Records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... retrieval of all information pertaining to the individual urine specimens for a minimum period of five years... disclosure of such information shall be followed. Moreover, owing to DOE's express environmental, public..., DOE must be kept fully apprised of all aspects of the contractor's program, including such information...

Identifying Young People's Guidance Needs through Telephone Counseling.

ERIC Educational Resources Information Center

Cruz, Bettylu Rasmussen; San Martin, Alfredo Hidalgo; Gutierrez, Bertha Lidia Nuno; Farias, Martha Villasenor; Mora, Iliana Sahagun

2001-01-01

Examined needs expressed by young people in Guadalajara in Jalisco, Mexico, during phone calls to the Mexican Social Security Institute. Differences were significant by gender and age. Findings point to the need for more programs that reinforce good health practices, including avoiding risky behaviors. (BF)

The expression of selected molecular markers of immune tolerance in psoriatic patients.

PubMed

Bartosińska, Joanna; Purkot, Joanna; Kowal, Małgorzata; Michalak-Stoma, Anna; Krasowska, Dorota; Chodorowska, Grażyna; Giannopoulos, Krzysztof

2018-04-24

Psoriasis is a chronic autoinflammatory disease whose underlying molecular mechanisms remain unclear. The disease is mediated by the cells and molecules of both the innate and adaptive immune systems. Some T cell surface molecules, including neuropilin-1 (NRP1), programmed death 1 (PD-1) and the human leukocyte antigen G (HLA-G), are known to play a role in the maintenance of immune tolerance. The aim of this study was to investigate HLA-G, NRP1 and programmed cell death gene (PDCD1) mRNA expression in psoriatic patients. The study included 72 psoriatic patients and 35 healthy individuals. Twentyone patients (29.17%) suffered from concomitant psoriatic arthritis. The mRNA expression of HLA-G, NRP1, and PDCD1 were determined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The severity of skin lesions was assessed by means of the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), the Patient Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI). The median value of the PASI was 11.5, and of BSA was 15.8%. The expressions of NRP1 and PDCD1, but not HLA-G, were significantly lower in psoriatic patients in comparison with the control group. The expression of HLA-G, NRP1 and PDCD1 were not significantly different in the psoriatic arthritis and psoriasis vulgaris patients. The results of this study suggest that the molecular markers of immune tolerance, i.e., HLA-G, NRP1, and PD-1, may be involved in the immune response in psoriatic patients.

Individualism, acceptance and differentiation as attitude traits in the public's response to vaccination.

PubMed

Velan, Baruch; Boyko, Valentina; Lerner-Geva, Liat; Ziv, Arnona; Yagar, Yaakov; Kaplan, Giora

2012-09-01

The attitude of the general public to vaccination was evaluated through a survey conducted on a representative sample of the Israeli population (n = 2,018), in which interviewees were requested to express their standpoints regarding five different vaccination programs. These included: pandemic influenza vaccination, seasonal influenza vaccination, travel vaccines, Human Papilloma Virus vaccine and childhood vaccinations. Analysis of the responses reveal three major attitude traits: a) acceptance, characterized by the opinion that targets should be vaccinated; b) individualism, characterized by the opinion that vaccination should be left to personal choice; and c) differentiation, characterized by the tendency to express different attitudes when addressing different vaccination programs. Interestingly, direct opposition to vaccination was found to be a minor attitude trait in this survey. Groups within the population could be defined according to their tendency to assume these different attitudes as Acceptors, Judicious-acceptors, Differentiators, Soft-individualists, and Hard-individualists. These groups expressed different standpoints on all five vaccination programs as well as on other health recommendations, such as screening for early detection of cancer. Attitude traits could be also correlated, to a certain extent, with actual compliance with vaccination programs. Interestingly, attitudes to vaccination were not correlated with social profiles related to income or education, although younger individuals exhibited higher degrees of individualism and differentiation. Taken together, all this is in accordance with the current social settings, underlining the individual's tendency for critical evaluation and self-stirring. This should be taken into consideration by health authorities involved in vaccination programs.

A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

DOE PAGES

Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.; ...

2015-11-03

Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentallydynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ~50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclearlocalized. Splicemore » site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. Finally, we conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease.« less

A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

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

Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.

Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentallydynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ~50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclearlocalized. Splicemore » site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. Finally, we conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease.« less

Patient perspectives on an opioid overdose education and naloxone distribution program in the U.S. Department of Veterans Affairs.

PubMed

Oliva, Elizabeth M; Nevedal, Andrea; Lewis, Eleanor T; McCaa, Matthew D; Cochran, Michael F; Konicki, P Eric; Davis, Corey S; Wilder, Christine

2016-01-01

In an effort to prevent opioid overdose mortality among Veterans, Department of Veterans Affairs (VA) facilities began implementing opioid overdose education and naloxone distribution (OEND) in 2013 and a national program began in 2014. VA is the first national health care system to implement OEND. The goal of this study is to examine patient perceptions of OEND training and naloxone kits. Four focus groups were conducted between December 2014 and February 2015 with 21 patients trained in OEND. Participants were recruited from a VA residential facility in California with a substance use disorder treatment program (mandatory OEND training) and a homeless program (optional OEND training). Data were analyzed using matrices and open and closed coding approaches to identify participants' perspectives on OEND training including benefits, concerns, differing opinions, and suggestions for improvement. Veterans thought OEND training was interesting, novel, and empowering, and that naloxone kits will save lives. Some veterans expressed concern about using syringes in the kits. A few patients who never used opioids were not interested in receiving kits. Veterans had differing opinions about legal and liability issues, whether naloxone kits might contribute to relapse, and whether and how to involve family in training. Some veterans expressed uncertainty about the effects of naloxone. Suggested improvements included active learning approaches, enhanced training materials, and increased advertisement. OEND training was generally well received among study participants, including those with no indication for a naloxone kit. Patients described a need for OEND and believed it could save lives. Patient feedback on OEND training benefits, concerns, opinions, and suggestions provides important insights to inform future OEND training programs both within VA and in other health care settings. Training is critical to maximizing the potential for OEND to save lives, and this study includes specific suggestions for improving the effectiveness and acceptability of training.

Matrix elements of N-particle explicitly correlated Gaussian basis functions with complex exponential parameters

NASA Astrophysics Data System (ADS)

Bubin, Sergiy; Adamowicz, Ludwik

2006-06-01

In this work we present analytical expressions for Hamiltonian matrix elements with spherically symmetric, explicitly correlated Gaussian basis functions with complex exponential parameters for an arbitrary number of particles. The expressions are derived using the formalism of matrix differential calculus. In addition, we present expressions for the energy gradient that includes derivatives of the Hamiltonian integrals with respect to the exponential parameters. The gradient is used in the variational optimization of the parameters. All the expressions are presented in the matrix form suitable for both numerical implementation and theoretical analysis. The energy and gradient formulas have been programed and used to calculate ground and excited states of the He atom using an approach that does not involve the Born-Oppenheimer approximation.

Matrix elements of N-particle explicitly correlated Gaussian basis functions with complex exponential parameters.

PubMed

Bubin, Sergiy; Adamowicz, Ludwik

2006-06-14

In this work we present analytical expressions for Hamiltonian matrix elements with spherically symmetric, explicitly correlated Gaussian basis functions with complex exponential parameters for an arbitrary number of particles. The expressions are derived using the formalism of matrix differential calculus. In addition, we present expressions for the energy gradient that includes derivatives of the Hamiltonian integrals with respect to the exponential parameters. The gradient is used in the variational optimization of the parameters. All the expressions are presented in the matrix form suitable for both numerical implementation and theoretical analysis. The energy and gradient formulas have been programmed and used to calculate ground and excited states of the He atom using an approach that does not involve the Born-Oppenheimer approximation.

Defective GATA-3 expression in Th2 LCR-deficient mice.

PubMed

Hwang, Soo Seok; Kim, Kiwan; Lee, Gap Ryol

2011-07-15

Th2 cell differentiation is critically influenced by transcription factor GATA-3 and by various cis-acting elements including enhancers, silencers and a locus control region (LCR) in the Th2 cytokine locus. Th2 LCR-deficient Th2 cells completely lost the expression of GATA-3 and the phosphorylation of STAT6. Histone 3 lysine 4 (H3-K4) was hypomethylated in the gata3 locus in these cells. GATA-3 and STAT6 bound several regulatory regions in the gata3 locus and transactivated the expression of the gata3 gene. These results suggest that Th2 differentiation program stimulates feed-forward regulation of gata3 gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Communication-and-resolution programs: the challenges and lessons learned from six early adopters.

PubMed

Mello, Michelle M; Boothman, Richard C; McDonald, Timothy; Driver, Jeffrey; Lembitz, Alan; Bouwmeester, Darren; Dunlap, Benjamin; Gallagher, Thomas

2014-01-01

In communication-and-resolution programs (CRPs), health systems and liability insurers encourage the disclosure of unanticipated care outcomes to affected patients and proactively seek resolutions, including offering an apology, an explanation, and, where appropriate, reimbursement or compensation. Anecdotal reports from the University of Michigan Health System and other early adopters of CRPs suggest that these programs can substantially reduce liability costs and improve patient safety. But little is known about how these early programs achieved success. We studied six CRPs to identify the major challenges in and lessons learned from implementing these initiatives. The CRP participants we interviewed identified several factors that contributed to their programs' success, including the presence of a strong institutional champion, investing in building and marketing the program to skeptical clinicians, and making it clear that the results of such transformative change will take time. Many of the early CRP adopters we interviewed expressed support for broader experimentation with these programs even in settings that differ from their own, such as systems that do not own and control their liability insurer, and in states without strong tort reforms.

24 CFR 574.300 - Eligible activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... mission, including the definition, practice, and expression of its religious beliefs, provided that it... program beneficiary on the basis of religion or religious belief. (5) HOPWA funds may not be used for the... by HUD. (c) Faith-based activities. (1) Organizations that are religious or faith-based are eligible...

24 CFR 574.300 - Eligible activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... mission, including the definition, practice, and expression of its religious beliefs, provided that it... program beneficiary on the basis of religion or religious belief. (5) HOPWA funds may not be used for the... by HUD. (c) Faith-based activities. (1) Organizations that are religious or faith-based are eligible...

24 CFR 574.300 - Eligible activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... mission, including the definition, practice, and expression of its religious beliefs, provided that it... program beneficiary on the basis of religion or religious belief. (5) HOPWA funds may not be used for the...) Faith-based activities. (1) Organizations that are religious or faith-based are eligible, on the same...

24 CFR 574.300 - Eligible activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... mission, including the definition, practice, and expression of its religious beliefs, provided that it... program beneficiary on the basis of religion or religious belief. (5) HOPWA funds may not be used for the... by HUD. (c) Faith-based activities. (1) Organizations that are religious or faith-based are eligible...

24 CFR 574.300 - Eligible activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... mission, including the definition, practice, and expression of its religious beliefs, provided that it... program beneficiary on the basis of religion or religious belief. (5) HOPWA funds may not be used for the...) Faith-based activities. (1) Organizations that are religious or faith-based are eligible, on the same...

Linking Teacher Theories to Teacher Practices.

ERIC Educational Resources Information Center

Carrier, Carol; Melvin, Karla

This study examined the relationship of teaching style orientation, expressed perceptions of the teaching-learning process, actual classroom behavior, and learning styles of six full-time faculty in a dental auxiliary program at a large teaching institution. Data collection instruments used to assess this relationship included the Teaching Style…

Computer Intelligence: Unlimited and Untapped.

ERIC Educational Resources Information Center

Staples, Betsy

1983-01-01

Herbert Simon (Nobel prize-winning economist/professor) expresses his views on human and artificial intelligence, problem solving, inventing concepts, and the future. Includes comments on expert systems, state of the art in artificial intelligence, robotics, and "Bacon," a computer program that finds scientific laws hidden in raw data.…

Fungal dimorphism in the entomopathogenic fungus Metarhizium rileyi: detection of an in vivo quorum-sensing system

USDA-ARS?s Scientific Manuscript database

This investigation documents the expression of the in vivo dimorphic program exhibited by insect mycopathogen M. rileyi replicating. This insect mycopathogen represents the key mortality factor regulating various caterpillar populations in various legumes, including subtropical and tropical soybeans...

Stable expression of lipocalin-type prostaglandin D synthase in cultured preadipocytes impairs adipogenesis program independently of endogenous prostanoids

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

Hossain, Mohammad Salim; Chowdhury, Abu Asad; Rahman, Mohammad Sharifur

Lipocalin-type prostaglandin D synthase (L-PGDS) expressed preferentially in adipocytes is responsible for the synthesis of PGD{sub 2} and its non-enzymatic dehydration products, PGJ{sub 2} series, serving as pro-adipogenic factors. However, the role of L-PGDS in the regulation of adipogenesis is complex because of the occurrence of several derivatives from PGD{sub 2} and their distinct receptor subtypes as well as other functions such as a transporter of lipophilic molecules. To manipulate the expression levels of L-PGDS in cultured adipocytes, cultured preadipogenic 3T3-L1 cells were transfected stably with a mammalian expression vector having cDNA encoding murine L-PGDS oriented in the sense direction.more » The isolated cloned stable transfectants with L-PGDS expressed higher levels of the transcript and protein levels of L-PGDS, and synthesized PGD{sub 2} from exogenous arachidonic acid at significantly higher levels. By contrast, the synthesis of PGE{sub 2} remained unchanged, indicating no influence on the reactions of cyclooxygenase (COX) and PGE synthase. Furthermore, the ability of those transfectants to synthesize {Delta}{sup 12}-PGJ{sub 2} increased more greatly during the maturation phase. The sustained expression of L-PGDS in cultured stable transfectants hampered the storage of fats during the maturation phase of adipocytes, which was accompanied by the reduced gene expression of adipocyte-specific markers reflecting the down-regulation of the adipogenesis program. The suppressed adipogenesis was not rescued by either exogenous aspirin or peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists including troglitazone and {Delta}{sup 12}-PGJ{sub 2}. Taken together, the results indicate the negative regulation of the adipogenesis program by the enhanced expression of L-PGDS through a cellular mechanism involving the interference of the PPAR{gamma} signaling pathway without the contribution of endogenous pro-adipogenic prostanoids. -- Highlights: Black-Right-Pointing-Pointer Cultured preadipocytes were transfected with sense lipocalin-type PGD synthase. Black-Right-Pointing-Pointer The cloned transfectants had a higher ability to synthesize PGD{sub 2} and PGJ{sub 2} series. Black-Right-Pointing-Pointer The sustained expression of sense L-PGDS hampered the storage of fats. Black-Right-Pointing-Pointer Adipogenesis program was suppressed independently of endogenous prostanoids.« less

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

PubMed

Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Tena, Juan J; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F; Roy, Anna R; Galjart, Niels; Delgado-Olguin, Paul; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis; Manzanares, Miguel

2017-08-01

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

PubMed Central

Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F.; Roy, Anna R.; Galjart, Niels; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis

2017-01-01

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development. PMID:28846746

Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

NASA Technical Reports Server (NTRS)

Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.

2016-01-01

Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

Vitamin D increases programmed death receptor-1 expression in Crohn’s disease

PubMed Central

Bendix, Mia; Greisen, Stinne; Dige, Anders; Hvas, Christian L.; Bak, Nina; Jørgensen, Søren P.; Dahlerup, Jens F.; Deleuran, Bent; Agnholt, Jørgen

2017-01-01

Background: Vitamin D modulates inflammation in Crohns disease (CD). Programmed death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin D might modulate PD-1 signalling in CD. Aim: To investigate PD-1 expression on T cell subsets in CD patients treated with vitamin D or placebo. Methods: We included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma levels were measured by ELISA. Results: PD-1 expression upon T cell stimulation was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19% (range 10 39%) to 29% (11 79%)(p = 0.03) compared with placebo-treated patients. Vitamin D treatment, but not placebo, decreased the expression of the T cell activation marker CD69 from 42% (31 62%) to 33% (19 - 54%)(p = 0.01). Soluble PD-1 levels were not influenced by vitamin D treatment. Conclusions: Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in response to activation and reduces the CD69 expression in CD patients. PMID:28412753

DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

PubMed Central

Mellström, Britt; Sahún, Ignasi; Ruiz-Nuño, Ana; Murtra, Patricia; Gomez-Villafuertes, Rosa; Savignac, Magali; Oliveros, Juan C.; Gonzalez, Paz; Kastanauskaite, Asta; Knafo, Shira; Zhuo, Min; Higuera-Matas, Alejandro; Errington, Michael L.; Maldonado, Rafael; DeFelipe, Javier; Jefferys, John G. R.; Bliss, Tim V. P.; Dierssen, Mara

2014-01-01

Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K+ channel interacting protein 3), is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory. PMID:24366545

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

PubMed

Xu-Monette, Zijun Y; Zhou, Jianfeng; Young, Ken H

2018-01-04

Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1 + tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1 + T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas. © 2018 by The American Society of Hematology.

Whither Education for Health Care Delivery. A Florida Approach.

ERIC Educational Resources Information Center

Morgan, Margaret K., Ed.; Filson, Dolores, Ed.

The conference summarized in this monograph grew out of two expressed concerns of health care personnel educators: their desire for more information about future trends in health care delivery, and their desire for better articulation of the various levels of programs preparing health related personnel. Papers presented include these: Future…

Rejoinder to Commentaries by Ackerman, Ho, and Wainer on "Bad Questions"

ERIC Educational Resources Information Center

Thissen, David

2016-01-01

David Thissen is a professor in the Department of Psychology & Neuroscience, Quantitative Program at the University of North Carolina. His research interests include psychological testing, measurement, and item response theory. Here Thissen expresses his gratitude to Howard Wainer for his illuminating discussion of the oral presentation upon…

A Group Counseling and Educational Program for Students with Usher's Syndrome.

ERIC Educational Resources Information Center

Vernon, McCay; Hicks, Wanda

1983-01-01

Group counseling for secondary students with Usher's syndrome, a genetic condition resulting in hearing impairment at birth and gradual loss of vision, was intended to provide information and opportunities for expression. Results included practical changes in school environment, increased information about deaf-blindness for the students, and help…

Non-Leveled English Program.

ERIC Educational Resources Information Center

Hagler, Howard

This curriculum guide is divided into two parts, genre and language skills. Genre involves the specific explorations of the spoken and written word: drama, public speaking, non-fiction, the short story, the novel, and creative expression. Language skills directs itself to the mastery of the mechanics of English. For each course outline included in…

Arts and the Curriculum for the 80s.

ERIC Educational Resources Information Center

Major, Judith Strand

1983-01-01

Learning factors that are improved by K-12 arts programs include perception, awareness, concentration, uniqueness of thought style, expression, inventiveness and problem solving, confidence and self worth, and motivation. The arts have been taught as an addition to the basic curriculum, not as part of the basic curriculum. This will continue…

CNN Newsroom Classroom Guides. October 1995.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These classroom guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of October, provide program rundowns, suggestions for class activities and discussion, student handouts, and a list of related news terms. Topics covered by the guides include: bedroom community business, freedom of expression and…

Representing and reasoning about program in situation calculus

NASA Astrophysics Data System (ADS)

Yang, Bo; Zhang, Ming-yi; Wu, Mao-nian; Xie, Gang

2011-12-01

Situation calculus is an expressive tool for modeling dynamical system in artificial intelligence, changes in a dynamical world is represented naturally by the notions of action, situation and fluent in situation calculus. Program can be viewed as a discrete dynamical system, so it is possible to model program with situation calculus. To model program written in a smaller core programming language CL, notion of fluent is expanded for representing value of expression. Together with some functions returning concerned objects from expressions, a basic action theory of CL programming is constructed. Under such a theory, some properties of program, such as correctness and termination can be reasoned about.

Waking Up the Mind: Qualitative Study Findings About the Process Through Which Programs Combining Income Generation and Health Education Can Empower Indigenous Guatemalan Women.

PubMed

Gurman, Tilly A; Ballard, Anne; Kerr, Samantha; Walsh, Janée; Petrocy, Amy

2016-01-01

We explored the process through which two income-generation programs that include health education empower indigenous Guatemalan women artisans. Both artisans (n = 44) and program staff (n = 11) participated in semistructured interviews. Respondents expressed that women gained support about personal issues and experienced an awakening of the mind (despertar la mente). Through active participation, women's fear of strangers and speaking in public decreased. Women also gained mobility, awareness of their rights as women, and self-confidence from earning and managing their own income. Given our findings, we suggest that programs combining income generation and health education have the potential to empower women.

Implementing program-wide awareness about recovery in a large mental health and addictions program.

PubMed

McVanel-Viney, Sarah; Younger, Jodi; Doyle, Winnie; Kirkpatrick, Helen

2006-01-01

St. Joseph's Healthcare Hamilton conceptualized a multi-step plan for implementing a recovery oriented service delivery approach within their Mental Health and Addictions Program. This brief report discusses the first phase of this plan which included building awareness of recovery utilizing Anthony's (2000) system standards to develop a needs assessment for managers and senior team members. The survey had three purposes: to increase managers' awareness about recovery; to allow managers to express concerns that they had with this paradigm; and to afford managers an opportunity to explore the ways in which their service was and was not operating in a recovery oriented way. Initiatives designed to build awareness throughout the program are discussed.

Research in advanced formal theorem-proving techniques

NASA Technical Reports Server (NTRS)

Rulifson, J. F.

1971-01-01

The present status is summarized of a continuing research program aimed at the design and implementation of a language for expressing problem-solving procedures in several areas of artificial intelligence, including program synthesis, robot planning, and theorem proving. Notations, concepts, and procedures common to the representation and solution of many of these problems were abstracted and incorporated as features into the language. The areas of research covered are described, and abstracts of six papers that contain extensive description and technical detail of the work are presented.

Clock Technology Development in the Laser Cooling and Atomic Physics (LCAP) Program

NASA Technical Reports Server (NTRS)

Seidel, Dave; Thompson, R. J.; Klipstein, W. M.; Kohel, J.; Maleki, L.

2000-01-01

This paper presents the Laser Cooling and Atomic Physics (LCAP) program. It focuses on clock technology development. The topics include: 1) Overview of LCAP Flight Projects; 2) Space Clock 101; 3) Physics with Clocks in microgravity; 4) Space Clock Challenges; 5) LCAP Timeline; 6) International Space Station (ISS) Science Platforms; 7) ISS Express Rack; 8) Space Qualification of Components; 9) Laser Configuration; 10) Clock Rate Comparisons: GPS Carrier Phase Frequency Transfer; and 11) ISS Model Views. This paper is presented in viewgraph form.

NASA agenda for tomorrow

NASA Technical Reports Server (NTRS)

1988-01-01

Key elements of national policy, NASA goals and objectives, and other materials that comprise the framework for NASA planning are included. The contents are expressed as they existed through much of 1988; thus they describe the strategic context employed by NASA in planning both the FY 1989 program just underway and the proposed FY 1990 program. NASA planning will continue to evolve in response to national policy requirements, a changing environment, and new opportunities. Agenda for Tomorrow provides a status report as of the time of its publication.

Integrative Analysis Reveals Regulatory Programs in Endometriosis

PubMed Central

Yang, Huan; Kang, Kai; Cheng, Chao; Mamillapalli, Ramanaiah; Taylor, Hugh S.

2015-01-01

Endometriosis is a common gynecological disease found in approximately 10% of reproductive-age women. Gene expression analysis has been performed to explore alterations in gene expression associated with endometriosis; however, the underlying transcription factors (TFs) governing such expression changes have not been investigated in a systematic way. In this study, we propose a method to integrate gene expression with TF binding data and protein–protein interactions to construct an integrated regulatory network (IRN) for endometriosis. The IRN has shown that the most regulated gene in endometriosis is RUNX1, which is targeted by 14 of 26 TFs also involved in endometriosis. Using 2 published cohorts, GSE7305 (Hover, n = 20) and GSE7307 (Roth, n = 36) from the Gene Expression Omnibus database, we identified a network of TFs, which bind to target genes that are differentially expressed in endometriosis. Enrichment analysis based on the hypergeometric distribution allowed us to predict the TFs involved in endometriosis (n = 40). This included known TFs such as androgen receptor (AR) and critical factors in the pathology of endometriosis, estrogen receptor α, and estrogen receptor β. We also identified several new ones from which we selected FOXA2 and TFAP2C, and their regulation was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). Further, our analysis revealed that the function of AR and p53 in endometriosis is regulated by posttranscriptional changes and not by differential gene expression. Our integrative analysis provides new insights into the regulatory programs involved in endometriosis. PMID:26134036

Adjustable under-expression of yeast mating pathway proteins in Saccharomyces cerevisiae using a programmed ribosomal frameshift.

PubMed

Choi, Min-Yeon; Park, Sang-Hyun

2016-06-01

Experimental research in molecular biology frequently relies on the promotion or suppression of gene expression, an important tool in the study of its functions. Although yeast is among the most studied model systems with the ease of maintenance and manipulation, current experimental methods are mostly limited to gene deletion, suppression or overexpression of genes. Therefore, the ability to reduce protein expressions and then observing the effects would promote a better understanding of the exact functions and their interactions. Reducing protein expression is mainly limited by the difficulties associated with controlling the reduction level, and in some cases, the initial endogenous abundance is too low. For the under-expression to be useful as an experimental tool, repeatability and stability of reduced expression is important. We found that cis-elements in programmed -1 ribosomal frameshifting (-1RFS) of beet western yellow virus (BWYV) could be utilized to reduced protein expression in Saccharomyces cerevisiae. The two main advantages of using -1RFS are adjustable reduction rates and ease of use. To demonstrate the utility of this under-expression system, examples of reduced protein abundance were shown using yeast mating pathway components. The abundance of MAP kinase Fus3 was reduced to approximately 28-75 % of the wild-type value. Other MAP kinase mating pathway components, including Ste5, Ste11, and Ste7, were also under-expressed to verify that the -1RFS system works with different proteins. Furthermore, reduced Fus3 abundance altered the overall signal transduction outcome of the mating pathway, demonstrating the potential for further studies of signal transduction adjustment via under-expression.

Expedite the Processing of Unpressurized Payloads to the International Space Station Using the ExPRESS Pallet

NASA Technical Reports Server (NTRS)

Bacskay, Allen S.; Gilbert, Paul A. (Technical Monitor)

2002-01-01

The Expedite the PRocessing of Experiments to Space Station (ExPRESS) Pallet will be used as an experiment platform for external/unpressurized payloads to be flown aboard the International Space Station (ISS). The purpose of the ExPRESS Pallet is to provide an easy access to the ISS for Scientific Investigators that require an external platform for their experiment hardware. As the name of the ExPRESS Pallet implies, the objective of the ExPRESS program is to provide a simplified integration process in a short time period (24 months) for payloads to be flown on the ISS. The ExPRESS Pallet provides unique opportunities for research across many science disciplines, including earth observation, communications, solar and deep space viewing, and long-term exposure. The ExPRESS Pallet provides access to Ram, Wake, Nadir, Zenith and Earth Limb for viewing and exposure to the space environment. The ExPRESS Pallet will provide standard physical payload interfaces, and a standard integration template. The ExPS consists of the Pallet structure, payload Adapters, a subsystem assembly that includes data controller, power distribution and conversion, and Extra Vehicular Robotics compatibility. The ExPRESS Pallet provides the capability to changeout payloads on-orbit via the ExPRESS Pallet Adapter (ExPA). The following paragraphs will describe the Services and Accommodations available to the Payload developers by the ExPRESS Pallet and a brief description of the Integration process. More detailed information on the ExPRESS Pallet can be found in the ExPRESS Pallet Payload Accommodations Handbook, SSP 52000-PAH-EPP.

Exploring the Outcomes of a Novel Computer-Assisted Treatment Program Targeting Expressive-Grammar Deficits in Preschoolers with SLI

ERIC Educational Resources Information Center

Washington, Karla N.; Warr-Leeper, Genese; Thomas-Stonell, Nancy

2011-01-01

Purpose: The impact of a newly designed computer-assisted treatment ("C-AT") program, "My Sentence Builder", for the remediation of expressive-grammar deficits in children with specific language impairment (SLI) was explored. This program was specifically designed with features to directly address expressive-grammar difficulties, thought to be…

Flexible Language Constructs for Large Parallel Programs

DOE PAGES

Rosing, Matt; Schnabel, Robert

1994-01-01

The goal of the research described in this article is to develop flexible language constructs for writing large data parallel numerical programs for distributed memory (multiple instruction multiple data [MIMD]) multiprocessors. Previously, several models have been developed to support synchronization and communication. Models for global synchronization include single instruction multiple data (SIMD), single program multiple data (SPMD), and sequential programs annotated with data distribution statements. The two primary models for communication include implicit communication based on shared memory and explicit communication based on messages. None of these models by themselves seem sufficient to permit the natural and efficient expression ofmore » the variety of algorithms that occur in large scientific computations. In this article, we give an overview of a new language that combines many of these programming models in a clean manner. This is done in a modular fashion such that different models can be combined to support large programs. Within a module, the selection of a model depends on the algorithm and its efficiency requirements. In this article, we give an overview of the language and discuss some of the critical implementation details.« less

Job satisfaction among academic coordinators of clinical education in physical therapy.

PubMed

Harris, M J; Fogel, M; Blacconiere, M

1987-06-01

The Academic Coordinator of Clinical Education is the physical therapy faculty member who is responsible for the clinical component of the curriculum. The responsibilities involved in the ACCE's job are such that ACCEs seem to be at risk for job dissatisfaction and burnout. The purpose of this descriptive study was to investigate the levels and patterns of job satisfaction among ACCEs in physical therapy. A questionnaire, including a 32-item job satisfaction inventory, was sent to the ACCE at each accredited entry-level education program for physical therapists and physical therapist assistants (N = 169). One hundred twelve (66.3%) responses were received and analyzed. Demographic characteristics of the respondents are reported. The results of the study showed that ACCEs, in general, expressed low levels of occupational dissatisfaction and burnout. Satisfaction with the aspects of the job involving self-esteem, achievement, and creativity seems to outweight dissatisfaction with the time available, the work load, and organizational efficiency. Those ACCEs with doctoral degrees expressed the highest levels of dissatisfaction and burnout. Those ACCEs working in entry-level master's degree programs expressed the lowest level of dissatisfaction; those in tenure-track positions expressed the lowest level of burnout. Factors contributing to job satisfaction and dissatisfaction are discussed.

[PD-L1 expression: An emerging biomarker in non-small cell lung cancer].

PubMed

Adam, Julien; Planchard, David; Marabelle, Aurélien; Soria, Jean-Charles; Scoazec, Jean-Yves; Lantuéjoul, Sylvie

2016-01-01

Therapies targeting immune checkpoints, in particular programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1), are major new strategies for the treatment of several malignancies including mestatatic non-small cell lung cancer (NSCLC). The identification of predictive biomarkers of response is required, considering efficacy, cost and potential adverse events. Expression of PD-L1 by immunohistochemistry has been associated with higher response rate and overall survival in several clinical trials evaluating anti-PD-1 and anti-PD-L1 monoclonal antibodies. Thus, PD-L1 immunohistochemical companion assays could be required for treatment with some of these therapies in NSCLC. However, heterogeneity in methodologies of PD-L1 assays in terms of primary antibodies and scoring algorithms, and tumor heterogenity for PD-L1 expression are important issues to be considered. More studies are required to compare the different assays, ensure their harmonization and standardization and identify the optimal conditions for testing. PD-L1 expression is likely an imperfect predictive biomarker for patient selection and association with other markers of the tumor immune microenvironment will be probably necessary in the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

DARPA Orbital Express program: effecting a revolution in space-based systems

NASA Astrophysics Data System (ADS)

Whelan, David A.; Adler, E. A.; Wilson, Samuel B., III; Roesler, Gordon M., Jr.

2000-11-01

A primary goal of the Defense Advanced Research Projects Agency is to develop innovative, high-risk technologies with the potential of a revolutionary impact on missions of the Department of Defense. DARPA is developing a space experiment to prove the feasibility of autonomous on- orbit servicing of spacecraft. The Orbital Express program will demonstrate autonomous on-orbit refueling, as well as autonomous delivery of a small payload representing an avionics upgrade package. The maneuverability provided to spacecraft from a ready refueling infrastructure will enable radical new capabilities for the military, civil and commercial spacecraft. Module replacement has the potential to extend bus lifetimes, and to upgrade the performance of key subsystems (e.g. processors) at the pace of technology development. The Orbital Express technology development effort will include the necessary autonomy for a viable servicing infrastructure; a universal interface for docking, refueling and module transfers; and a spacecraft bus design compatible with this servicing concept. The servicer spacecraft of the future may be able to act as a host platform for microsatellites, extending their capabilities while reducing risk. An infrastructure based on Orbital Express also benefits from, and stimulates the development of, lower-cost launch strategies.

Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

PubMed

Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

2018-03-01

Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton.

PubMed

Song, Y; Hui, J N; Fu, K K; Richman, J M

2004-12-15

Endogenous retinoids are important for patterning many aspects of the embryo including the branchial arches and frontonasal region of the embryonic face. The nasal placodes express retinaldehyde dehydrogenase-3 (RALDH3) and thus retinoids from the placode are a potential patterning influence on the developing face. We have carried out experiments that have used Citral, a RALDH antagonist, to address the function of retinoid signaling from the nasal pit in a whole embryo model. When Citral-soaked beads were implanted into the nasal pit of stage 20 chicken embryos, the result was a specific loss of derivatives from the lateral nasal prominences. Providing exogenous retinoic acid residue development of the beak demonstrating that most Citral-induced defects were produced by the specific blocking of RA synthesis. The mechanism of Citral effects was a specific increase in programmed cell death on the lateral (lateral nasal prominence) but not the medial side (frontonasal mass) of the nasal pit. Gene expression studies were focused on the Bone Morphogenetic Protein (BMP) pathway, which has a well-established role in programmed cell death. Unexpectedly, blocking RA synthesis decreased rather than increased Msx1, Msx2, and Bmp4 expression. We also examined cell survival genes, the most relevant of which was Fgf8, which is expressed around the nasal pit and in the frontonasal mass. We found that Fgf8 was not initially expressed along the lateral side of the nasal pit at the start of our experiments, whereas it was expressed on the medial side. Citral prevented upregulation of Fgf8 along the lateral edge and this may have contributed to the specific increase in programmed cell death in the lateral nasal prominence. Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue most of the morphological defects and was able to prevent a decrease in retinoic acid receptorbeta (Rarbeta) expression caused by Citral. Together, our results demonstrate that endogenous retinoids act upstream of FGF8 and the balance of these two factors is critical for regulating programmed cell death and morphogenesis in the face. In addition, our data suggest a novel role for endogenous retinoids from the nasal pit in controlling the precise downregulation of FGF in the center of the frontonasal mass observed during normal vertebrate development.

Gene expression of placental hormones regulating energy balance in small for gestational age neonates.

PubMed

Struwe, Ellen; Berzl, Gabriele M; Schild, Ralf L; Dötsch, Jörg

2009-01-01

Fetal growth restriction is associated with an increased risk for metabolic and cardiovascular disease in later life. To further elucidate mechanisms that might be involved in the process of prenatal programming, we measured the adipokines leptin, resistin, and adiponectin and the GH-releasing hormone ghrelin in the placenta of small for gestational age (SGA) neonates. The control group included 24 placentas of appropriate for gestational age (AGA) newborns, in the study group were 16 placentas of SGA neonates. Gene expression of leptin, resistin, adiponectin, and ghrelin was examined. For hormones showing alterations in gene regulation placental protein expression was measured by Western blot. Placental mRNA expression of leptin was significantly increased in SGA placentas (p=0.0035, related to beta-actin). Protein concentration was increased, as well. There were no differences in placental resistin, adiponectin, or ghrelin gene expressions between SGA neonates and controls. Leptin was the only hormone to demonstrate a significant inverse correlation with birth weight (r=-0.44, p=0.01). Adiponectin correlated significantly with leptin (r=0.53, p=0.0023) and ghrelin (r=0.50, p=0.0045). Placental leptin gene expression and protein concentration showed the expected increase in the SGA group. Leptin was inversely correlated with birth weight. Positive correlation of adiponectin with leptin and ghrelin expression suggests an interaction between these hormones in the placenta. However, the unchanged expression of resistin, adiponectin, and ghrelin in SGA placentas and the absence of correlation with birth weight cast doubt whether these hormones produced in the placenta play a key role in fetal programming.

Individualism, acceptance and differentiation as attitude traits in the public’s response to vaccination

PubMed Central

Velan, Baruch; Boyko, Valentina; Lerner-Geva, Liat; Ziv, Arnona; Yagar, Yaakov; Kaplan, Giora

2012-01-01

The attitude of the general public to vaccination was evaluated through a survey conducted on a representative sample of the Israeli population (n = 2,018), in which interviewees were requested to express their standpoints regarding five different vaccination programs. These included: pandemic influenza vaccination, seasonal influenza vaccination, travel vaccines, Human Papilloma Virus vaccine and childhood vaccinations. Analysis of the responses reveal three major attitude traits: a) acceptance, characterized by the opinion that targets should be vaccinated; b) individualism, characterized by the opinion that vaccination should be left to personal choice; and c) differentiation, characterized by the tendency to express different attitudes when addressing different vaccination programs. Interestingly, direct opposition to vaccination was found to be a minor attitude trait in this survey. Groups within the population could be defined according to their tendency to assume these different attitudes as Acceptors, Judicious-acceptors, Differentiators, Soft-individualists, and Hard-individualists. These groups expressed different standpoints on all five vaccination programs as well as on other health recommendations, such as screening for early detection of cancer. Attitude traits could be also correlated, to a certain extent, with actual compliance with vaccination programs. Interestingly, attitudes to vaccination were not correlated with social profiles related to income or education, although younger individuals exhibited higher degrees of individualism and differentiation. Taken together, all this is in accordance with the current social settings, underlining the individual's tendency for critical evaluation and self-stirring. This should be taken into consideration by health authorities involved in vaccination programs. PMID:22894959

Duration of breast milk expression among working mothers enrolled in an employer-sponsored lactation program.

PubMed

Ortiz, Joan; McGilligan, Kathryn; Kelly, Patricia

2004-01-01

Maternal employment has been one of the greatest barriers to breastfeeding. Women are increasingly solving this problem by expressing milk at work and taking it home to their infants. The objective was to determine duration of breast milk expression among working mothers enrolled in an employer-sponsored lactation program. Retrospective reviews were conducted on the lactation records of 462 women employed by 5 corporations in order to describe and characterize their experiences. The lactation program included the employees' choice of (a) a class on the benefits of breastfeeding; (b) services of a certified lactation consultant (CLC); and (c) private room in the workplace with equipment for pumping. Breastfeeding was initiated by 97.5% of the participants, with 57.8% continuing for at least 6 months. Of the 435 (94.2%) who returned to work after giving birth, 343 (78.9%) attempted pumping milk at work, and 336 (98%) were successful. They expressed milk in the workplace for a mean of 6.3 months (SD = 3.9, range 2 weeks to 21 months). The mean age of infants when the mothers stopped pumping at work was 9.1 months (SD = 4.1, range 1.9 to 25 months). Most of the women who pumped their milk at work were working full time (84.2%). The mean postnatal maternity leave was 2.8 months. The proportion of women who chose to pump at work was higher among women who were salaried than among those who were paid hourly wages (p < 0.01). Company-sponsored lactation programs can enable employed mothers to provide breast milk for their infants as long as they wish, thus helping the nation attain the Healthy People 2010 goals of 50% of mothers breastfeeding until their infants are 6-months-old.

Retrogenic ICOS Expression Increases Differentiation of KLRG-1hi CD127lo CD8+ T Cells During Listeria Infection and Diminishes Recall Responses1

PubMed Central

Liu, Danya; Burd, Eileen M.; Coopersmith, Craig M.; Ford, Mandy L.

2016-01-01

Following T cell encounter with antigen, multiple signals are integrated to collectively induce distinct differentiation programs within antigen-specific CD8+ T cell populations. Several factors contribute to these cell fate decisions including the amount and duration of antigen, exposure to inflammatory cytokines, and degree of ligation of cosignaling molecules. The inducible costimulator (ICOS) is not expressed on resting T cells but is rapidly upregulated upon encounter with antigen. However, the impact of ICOS signaling on programmed differentiation is not well understood. In this study we therefore sought to determine the role of ICOS signaling on CD8+ T cell programmed differentiation. Through the creation of novel ICOS retrogenic antigen-specific TCR transgenic CD8+ T cells, we interrogated the phenotype, functionality, and recall potential of CD8+ T cells that receive early and sustained ICOS signaling during antigen exposure. Our results reveal that these ICOS signals critically impacted cell fate decisions of antigen-specific CD8+ T cells, resulting in increased frequencies of KLRG-1hiCD127lo cells, altered BLIMP-1, T-bet, and eomesodermin expression, and increased cytolytic capacity as compared to empty vector controls. Interestingly, however, ICOS retrogenic CD8+ T cells also preferentially homed to non-lymphoid organs, and exhibited reduced multi-cytokine functionality and reduced ability to mount secondary recall responses upon challenge in vivo. In sum, our results suggest that an altered differentiation program is induced following early and sustained ICOS expression, resulting in the generation of more cytolyticly potent, terminally differentiated effectors that possess limited capacity for recall response. PMID:26729800

Retrogenic ICOS Expression Increases Differentiation of KLRG-1hiCD127loCD8+ T Cells during Listeria Infection and Diminishes Recall Responses.

PubMed

Liu, Danya; Burd, Eileen M; Coopersmith, Craig M; Ford, Mandy L

2016-02-01

Following T cell encounter with Ag, multiple signals are integrated to collectively induce distinct differentiation programs within Ag-specific CD8(+) T cell populations. Several factors contribute to these cell fate decisions, including the amount and duration of Ag, exposure to inflammatory cytokines, and degree of ligation of cosignaling molecules. The ICOS is not expressed on resting T cells but is rapidly upregulated upon encounter with Ag. However, the impact of ICOS signaling on programmed differentiation is not well understood. In this study, we therefore sought to determine the role of ICOS signaling on CD8(+) T cell programmed differentiation. Through the creation of novel ICOS retrogenic Ag-specific TCR-transgenic CD8(+) T cells, we interrogated the phenotype, functionality, and recall potential of CD8(+) T cells that receive early and sustained ICOS signaling during Ag exposure. Our results reveal that these ICOS signals critically impacted cell fate decisions of Ag-specific CD8(+) T cells, resulting in increased frequencies of KLRG-1(hi)CD127(lo) cells, altered BLIMP-1, T-bet, and eomesodermin expression, and increased cytolytic capacity as compared with empty vector controls. Interestingly, however, ICOS retrogenic CD8(+) T cells also preferentially homed to nonlymphoid organs and exhibited reduced multicytokine functionality and reduced ability to mount secondary recall responses upon challenge in vivo. In sum, our results suggest that an altered differentiation program is induced following early and sustained ICOS expression, resulting in the generation of more cytolyticly potent, terminally differentiated effectors that possess limited capacity for recall response. Copyright © 2016 by The American Association of Immunologists, Inc.

Prognostic value of programmed cell death ligand 1 expression in patients with head and neck cancer: A systematic review and meta-analysis.

PubMed

Li, Ji; Wang, Ping; Xu, Youliang

2017-01-01

Programmed cell death ligand 1 (PD-L1) expression was reported to be correlated with poor prognosis in various cancers. However, the relationship between PD-L1 expression and the survival of patients with head and neck cancer (HNC) remains inconclusive. In the present study, we aimed to clarify the prognostic value of PD-L1 in HNC patients using meta-analysis techniques. A comprehensive database searching was conducted in the PubMed, EMBASE, Web of Science and Cochrane Library from inception to August 2016. Studies meeting the inclusion criteria were included. The methodological quality of included studies was assessed by the Newcastle-Ottawa quality assessment scale. Hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were pooled by STATA 11.0 for the outcome of overall survival (OS) and disease-free survival (DFS). A total of 17 studies with 2,869 HNC patients were included in the meta-analysis. The results of meta-analysis showed that there was no significant correlation between PD-L1 expression and OS (HR, 1.23; 95% CI, 0.99-1.53; P = 0.065) or DFS (HR, 1.42; 95% CI, 1.00-2.03; P = 0.052) of HNC patients. However, the subgroup analysis suggested that positive expression of PD-L1 was associated with poor OS (HR, 1.38; 95% CI, 1.12, 1.70; P = 0.003) and DFS (HR, 1.99; 95% CI, 1.59, 2.48; P = 0.001) in HNC patients from Asian countries/regions. The subgroup analysis also showed that the correlations between PD-L1 and prognosis are variant among different subtypes of HNC. When performing sensitive analyses, we found that the results of meta-analyses were not robust. The meta-analysis indicated that positive expression of PD-L1 could serve as a good predictor for poor prognosis of Asian patients with HNC. However, the findings still need to be confirmed by large-scale, prospective studies.

Development and implementation of an online program to improve how patients communicate emotional concerns to their oncology providers.

PubMed

Porter, Laura S; Pollak, Kathryn I; Farrell, David; Cooper, Meredith; Arnold, Robert M; Jeffreys, Amy S; Tulsky, James A

2015-10-01

Patients often struggle to express their emotional concerns to their oncology providers and may therefore experience unmet needs. This paper describes the development and implementation of an online program that teaches patients how to communicate their emotions to their oncology providers. The intervention was developed by a multidisciplinary team consisting of palliative care physicians, psychologists, and an intervention software developer and included input from patients. It incorporated elements of Social Cognitive Theory and validated cognitive behavioral strategies for communication skills training. Strategies to increase intervention adherence were implemented midway through the study. The intervention consists of four interactive, online modules to teach patients strategies for expressing emotional concerns to their providers and asking for support. In addition to skill-building, the intervention was designed to raise patients' expectations that expressing emotional concerns to providers would be helpful, to enhance their self-efficacy for doing so, and to help them overcome barriers to having these conversations. After implementing strategies to improve adherence, usage rates increased from 47 to 64 %. This intervention addresses an unmet educational need for patients with advanced cancer. Strategies to increase adherence led to improvements in usage rates in this population of older patients. We are currently evaluating the intervention in a randomized clinical trial to determine its efficacy in increasing patient expression of emotional concerns and requests for support. If successful, this intervention could serve as a model for future online patient education programs.

Development and implementation of an online program to improve how patients communicate emotional concerns to their oncology providers

PubMed Central

Porter, Laura S.; Pollak, Kathryn I.; Farrell, David; Cooper, Meredith; Arnold, Robert M.; Jeffreys, Amy S.; Tulsky, James A.

2015-01-01

Purpose Patients often struggle to express their emotional concerns to their oncology providers, and may therefore experience unmet needs. This paper describes the development and implementation of an online program that teaches patients how to communicate their emotions to their oncology providers. Methods The intervention was developed by a multidisciplinary team consisting of palliative care physicians, psychologists, and an intervention software developer, and included input from patients. It incorporated elements of Social Cognitive Theory and validated cognitive behavioral strategies for communication skills training. Strategies to increase intervention adherence were implemented midway through the study. Results The intervention consists of four interactive, online modules to teach patients strategies for expressing emotional concerns to their providers and asking for support. In addition to skill-building, the intervention was designed to raise patients’ expectations that expressing emotional concerns to providers would be helpful, to enhance their self-efficacy for doing so, and to help them overcome barriers to having these conversations. After implementing strategies to improve adherence, usage rates increased from 47% to 64%. Conclusions This intervention addresses an unmet educational need for patients with advanced cancer. Strategies to increase adherence led to improvements in usage rates in this population of older patients. We are currently evaluating the intervention in a randomized clinical trial to determine its efficacy in increasing patient expression of emotional concerns and requests for support. If successful, this intervention could serve as a model for future online patient education programs. PMID:25701437

Internal Medicine Program Directors' Perceptions of the "All In" Match Rule: A Cross-Sectional Survey.

PubMed

Alweis, Richard; Khan, Muhammad Sohail; Kuehl, Sapna; Wasser, Thomas; Donato, Anthony

2017-04-01

Since 2013, the National Resident Matching Program (NRMP) has asked all programs to declare themselves to be "all in" or "all out" for the NRMP. Before this rule was enacted, program directors who were surveyed expressed concerns about what they anticipated with the change, including resources for increased applications and potential delays with residency start times. This study investigated the positive and negative effects of the rule change on recruiting seen from the perspective of internal medicine (IM) program directors. In this mixed model cross-sectional survey, Accreditation Council for Graduate Medical Education-accredited IM program directors were surveyed regarding their impressions of the impact of the policy change. Data were aggregated using constant comparative analysis. A total of 127 of 396 (32%) IM program directors responded, and 122 of 127 (96%) identified their program as "all in." A total of 110 respondents expressed impressions of the rule change, with 48% (53 of 111) reporting positive responses, 28% (31 of 111) neutral responses, and 24% (27 of 111) negative responses. Programs with higher percentages of visa-holding residents had lower positive responses (37% [22 of 60] versus 61% [31 of 51]). Resident quality was felt to be unchanged or improved by most program directors (93%, 103 of 111), yet 24% (27 of 112) reported increases in delayed start times for visa-holding residents. Qualitative analysis identified increased fairness, at the expense of an increase in program resources as a result of the change. A slight majority of residency programs reported a neutral or negative impression of the rule change. Since the rule change, program directors noted increased application volume and delayed residency starts for visa-holding residents.

Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes

PubMed Central

Sääf, Annika M.; Tengvall-Linder, Maria; Chang, Howard Y.; Adler, Adam S.; Wahlgren, Carl-Fredrik; Scheynius, Annika; Nordenskjöld, Magnus; Bradley, Maria

2008-01-01

Background Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Methodology/Findings We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusions/Significance Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema. PMID:19107207

Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

PubMed Central

Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

2016-01-01

Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

Integration of a splicing regulatory network within the meiotic gene expression program of Saccharomyces cerevisiae

PubMed Central

Munding, Elizabeth M.; Igel, A. Haller; Shiue, Lily; Dorighi, Kristel M.; Treviño, Lisa R.; Ares, Manuel

2010-01-01

Splicing regulatory networks are essential components of eukaryotic gene expression programs, yet little is known about how they are integrated with transcriptional regulatory networks into coherent gene expression programs. Here we define the MER1 splicing regulatory network and examine its role in the gene expression program during meiosis in budding yeast. Mer1p splicing factor promotes splicing of just four pre-mRNAs. All four Mer1p-responsive genes also require Nam8p for splicing activation by Mer1p; however, other genes require Nam8p but not Mer1p, exposing an overlapping meiotic splicing network controlled by Nam8p. MER1 mRNA and three of the four Mer1p substrate pre-mRNAs are induced by the transcriptional regulator Ume6p. This unusual arrangement delays expression of Mer1p-responsive genes relative to other genes under Ume6p control. Products of Mer1p-responsive genes are required for initiating and completing recombination and for activation of Ndt80p, the activator of the transcriptional network required for subsequent steps in the program. Thus, the MER1 splicing regulatory network mediates the dependent relationship between the UME6 and NDT80 transcriptional regulatory networks in the meiotic gene expression program. This study reveals how splicing regulatory networks can be interlaced with transcriptional regulatory networks in eukaryotic gene expression programs. PMID:21123654

Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors.

PubMed

Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

2007-01-01

We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus.

Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors

PubMed Central

Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

2007-01-01

We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus. PMID:18466597

45 CFR 1050.3 - What conditions apply to the Charitable Choice provisions of the CSBG Act?

Code of Federal Regulations, 2010 CFR

2010-10-01

... its mission, including the definition, practice and expression of its religious beliefs, provided that... religious belief. (f) Religious organizations that receive funds under an applicable program are subject to... under the Community Services Block Grant Act. (a)(1) Religious organizations are eligible, on the same...

45 CFR 1050.3 - What conditions apply to the Charitable Choice provisions of the CSBG Act?

Code of Federal Regulations, 2013 CFR

2013-10-01

... its mission, including the definition, practice and expression of its religious beliefs, provided that... religious belief. (f) Religious organizations that receive funds under an applicable program are subject to... under the Community Services Block Grant Act. (a)(1) Religious organizations are eligible, on the same...

45 CFR 1050.3 - What conditions apply to the Charitable Choice provisions of the CSBG Act?

Code of Federal Regulations, 2012 CFR

2012-10-01

... its mission, including the definition, practice and expression of its religious beliefs, provided that... religious belief. (f) Religious organizations that receive funds under an applicable program are subject to... under the Community Services Block Grant Act. (a)(1) Religious organizations are eligible, on the same...

45 CFR 1050.3 - What conditions apply to the Charitable Choice provisions of the CSBG Act?

Code of Federal Regulations, 2011 CFR

2011-10-01

... its mission, including the definition, practice and expression of its religious beliefs, provided that... religious belief. (f) Religious organizations that receive funds under an applicable program are subject to... under the Community Services Block Grant Act. (a)(1) Religious organizations are eligible, on the same...

45 CFR 1050.3 - What conditions apply to the Charitable Choice provisions of the CSBG Act?

Code of Federal Regulations, 2014 CFR

2014-10-01

... its mission, including the definition, practice and expression of its religious beliefs, provided that... religious belief. (f) Religious organizations that receive funds under an applicable program are subject to... under the Community Services Block Grant Act. (a)(1) Religious organizations are eligible, on the same...

School Choice May Not Be a Shangri-La

ERIC Educational Resources Information Center

Jeynes, William H.

2017-01-01

For the past half century, the American public school system has been on the receiving end of a considerable amount of criticism. People of faith have often been at the forefront of expressing that criticism. Attached to their criticism religious people have often called for school choice programs that include faith-based schools as the…

Failing to Fulfill Tasks of Social Justice Weakens Country.

ERIC Educational Resources Information Center

USA Today, 1981

1981-01-01

Presents excerpts from an interview with Walter Mondale in which the former vice president expressed fears that the United States will be weakened by current policies of removing government from the tasks of social justice. Topics discussed include social security cuts, reduction of student loans, and elimination of the legal aid program. (DB)

California's New School Finance Law.

ERIC Educational Resources Information Center

Lindman, Erick L.

Following a touch-and-go struggle in the California legislature, a school finance reform law, known as the Property Tax Relief Act of 1972, was passed. The contents of this act were affected in part by the California Supreme Court decision--Serrano vs Priest. The new law includes boosts in foundation programs, expressed in dollar amounts per pupil…

Edo: Art in Japan 1615-1868. Teaching Program.

ERIC Educational Resources Information Center

Guth, Christine; Henderson, Anne; Hinish, Heidi; Moore, Barbara

The Edo period in Japan (1615-1868) saw the flowering of many forms of cultural expression, colorful and boisterous, muted and restrained, that today is thought of as typically Japanese. These include kabuki and no drama, the tea ceremony, martial arts, woodblock prints, and porcelain. This culturally diverse and vibrant period gets its name from…

A New Approach to Improving Science, Technology, Engineering, and Math Education. Backgrounder No. 2259

ERIC Educational Resources Information Center

Lips, Dan; McNeill, Jena Baker

2009-01-01

The authors express reservations about additional federal funding for the National Science Foundation, including new funding for science, technology, engineering, and math (STEM) education programs, provided by the American Recovery and Reinvestment Act of 2009. For more than 50 years, American political, business, military, and academic leaders…

A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution

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

Yap, Thai Leong; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551; Chen, Yen Liang

Crystals of the RNA-dependent RNA polymerase catalytic domain from the dengue virus NS5 protein have been obtained using a strategy that included expression screening of naturally occurring serotype variants of the protein, the addition of divalent metal ions and crystal dehydration. These crystals diffract to 1.85 Å resolution and are thus suitable for a structure-based drug-design program. Dengue virus, a member of the Flaviviridae genus, causes dengue fever, an important emerging disease with several million infections occurring annually for which no effective therapy exists. The viral RNA-dependent RNA polymerase NS5 plays an important role in virus replication and represents anmore » interesting target for the development of specific antiviral compounds. Crystals that diffract to 1.85 Å resolution that are suitable for three-dimensional structure determination and thus for a structure-based drug-design program have been obtained using a strategy that included expression screening of naturally occurring serotype variants of the protein, the addition of divalent metal ions and crystal dehydration.« less

Shuttle Data Center File-Processing Tool in Java

NASA Technical Reports Server (NTRS)

Barry, Matthew R.; Miller, Walter H.

2006-01-01

A Java-language computer program has been written to facilitate mining of data in files in the Shuttle Data Center (SDC) archives. This program can be executed on a variety of workstations or via Web-browser programs. This program is partly similar to prior C-language programs used for the same purpose, while differing from those programs in that it exploits the platform-neutrality of Java in implementing several features that are important for analysis of large sets of time-series data. The program supports regular expression queries of SDC archive files, reads the files, interleaves the time-stamped samples according to a chosen output, then transforms the results into that format. A user can choose among a variety of output file formats that are useful for diverse purposes, including plotting, Markov modeling, multivariate density estimation, and wavelet multiresolution analysis, as well as for playback of data in support of simulation and testing.

Effects of 2G on Gene Expression of Stress-Related Hormones in Rat Placenta

NASA Technical Reports Server (NTRS)

Benson, S.; Talyansky, Y.; Moyer, E. L.; Lowe, M.; Baer, L. A.; Ronca, A. E.

2017-01-01

Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and quantified the expression levels of the genes of interest relative to the GAPDH housekeeping gene, using RT-qPCR and gene-specific cDNA probes. Elucidation of glucocorticoid transfer and synthesis in the placenta can provide new insights into the unique dynamics of mammalian development in microgravity and guide future multi-generational studies in space.

Laser capture microdissection-microarray analysis of focal segmental glomerulosclerosis glomeruli.

PubMed

Bennett, Michael R; Czech, Kimberly A; Arend, Lois J; Witte, David P; Devarajan, Prasad; Potter, S Steven

2007-01-01

Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. In this report we used laser capture microdissection to purify diseased glomeruli, and microarrays to provide universal gene expression profiles. The results provide a deeper understanding of the molecular mechanisms of the disease process and suggest novel therapeutic strategies. Consistent with earlier studies, molecular markers of the differentiated podocyte, including WT1, nephrin, and VEGF, were dramatically downregulated in the diseased glomerulus. We also observed multiple changes consistent with increased TGF-beta signaling, including elevated expression of TGF-beta(2), TGF-beta(3), SMAD2, TGF-beta(1) receptor, and thrombospondin. In addition, there was relatively low level expression of Csf1r, a marker of macrophages, but elevated expression of the chemokines CXCL1, CXCL2, CCL3, and CXCL14. We also observed strongly upregulated expression of Sox9, a transcription factor that can drive a genetic program of chondrogenesis and fibrosis. Further, the gene with the greatest fold increase in expression in the diseased glomerulus was osteopontin, which has been previously strongly implicated in kidney fibrosis in the unilateral ureteral obstruction mouse model. These results confirm old findings, and indicate the involvement of new genetic pathways in the cause and progression of FSGS. Copyright 2007 S. Karger AG, Basel.

The potential of local farming on the Navajo Nation to improve fruit and vegetable intake: barriers and opportunities.

PubMed

Setala, Ashley; Bleich, Sara N; Speakman, Kristen; Oski, Jane; Martin, Tammy; Moore, Regina; Tohannie, Marcella; Gittelsohn, Joel

2011-01-01

American Indian populations have low produce intake compared to other ethnic groups and higher rates of diet-related chronic diseases. Programs linking farmers to their community (Farm-to-Table) are an innovative way to alter the food environment. We interviewed Navajo farmers (n = 20), storeowners (n = 7), and non-governmental organization representatives (n = 4) to better understand local farming practices and the potential of a Farm-to-Table program to increase produce intake. Barriers to participation in a Farm-to-Table program included lack of water, insufficient help, and exotic species. Participants expressed concern about high obesity rates and voiced support for a Farm-to-Table program if barriers could be adequately addressed.

Array data extractor (ADE): a LabVIEW program to extract and merge gene array data.

PubMed

Kurtenbach, Stefan; Kurtenbach, Sarah; Zoidl, Georg

2013-12-01

Large data sets from gene expression array studies are publicly available offering information highly valuable for research across many disciplines ranging from fundamental to clinical research. Highly advanced bioinformatics tools have been made available to researchers, but a demand for user-friendly software allowing researchers to quickly extract expression information for multiple genes from multiple studies persists. Here, we present a user-friendly LabVIEW program to automatically extract gene expression data for a list of genes from multiple normalized microarray datasets. Functionality was tested for 288 class A G protein-coupled receptors (GPCRs) and expression data from 12 studies comparing normal and diseased human hearts. Results confirmed known regulation of a beta 1 adrenergic receptor and further indicate novel research targets. Although existing software allows for complex data analyses, the LabVIEW based program presented here, "Array Data Extractor (ADE)", provides users with a tool to retrieve meaningful information from multiple normalized gene expression datasets in a fast and easy way. Further, the graphical programming language used in LabVIEW allows applying changes to the program without the need of advanced programming knowledge.

Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients.

PubMed

Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda; Fábián, Katalin; Pipek, Orsolya; Vágvölgyi, Attila; Agócs, László; Fillinger, János; Kajdácsi, Zita; Tímár, József; Döme, Balázs; Szállási, Zoltán; Moldvay, Judit

2018-04-19

While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy. PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin-gemcitabine combination (p = 0.020), while in the carboplatin-paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy. This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

Protection of the Photosynthetic Apparatus from Extreme Dehydration and Oxidative Stress in Seedlings of Transgenic Tobacco

PubMed Central

Personat, José-María; Tejedor-Cano, Javier; Lindahl, Marika; Diaz-Espejo, Antonio; Jordano, Juan

2012-01-01

A genetic program that in sunflower seeds is activated by Heat Shock transcription Factor A9 (HaHSFA9) has been analyzed in transgenic tobacco seedlings. The ectopic overexpression of the HSFA9 program protected photosynthetic membranes, which resisted extreme dehydration and oxidative stress conditions. In contrast, heat acclimation of seedlings induced thermotolerance but not resistance to the harsh stress conditions employed. The HSFA9 program was found to include the expression of plastidial small Heat Shock Proteins that accumulate only at lower abundance in heat-stressed vegetative organs. Photosystem II (PSII) maximum quantum yield was higher for transgenic seedlings than for non-transgenic seedlings, after either stress treatment. Furthermore, protection of both PSII and Photosystem I (PSI) membrane protein complexes was observed in the transgenic seedlings, leading to their survival after the stress treatments. It was also shown that the plastidial D1 protein, a labile component of the PSII reaction center, and the PSI core protein PsaB were shielded from oxidative damage and degradation. We infer that natural expression of the HSFA9 program during embryogenesis may protect seed pro-plastids from developmental desiccation. PMID:23227265

Intrinsic and extrinsic approaches for detecting genes in a bacterial genome.

PubMed Central

Borodovsky, M; Rudd, K E; Koonin, E V

1994-01-01

The unannotated regions of the Escherichia coli genome DNA sequence from the EcoSeq6 database, totaling 1,278 'intergenic' sequences of the combined length of 359,279 basepairs, were analyzed using computer-assisted methods with the aim of identifying putative unknown genes. The proposed strategy for finding new genes includes two key elements: i) prediction of expressed open reading frames (ORFs) using the GeneMark method based on Markov chain models for coding and non-coding regions of Escherichia coli DNA, and ii) search for protein sequence similarities using programs based on the BLAST algorithm and programs for motif identification. A total of 354 putative expressed ORFs were predicted by GeneMark. Using the BLASTX and TBLASTN programs, it was shown that 208 ORFs located in the unannotated regions of the E. coli chromosome are significantly similar to other protein sequences. Identification of 182 ORFs as probable genes was supported by GeneMark and BLAST, comprising 51.4% of the GeneMark 'hits' and 87.5% of the BLAST 'hits'. 73 putative new genes, comprising 20.6% of the GeneMark predictions, belong to ancient conserved protein families that include both eubacterial and eukaryotic members. This value is close to the overall proportion of highly conserved sequences among eubacterial proteins, indicating that the majority of the putative expressed ORFs that are predicted by GeneMark, but have no significant BLAST hits, nevertheless are likely to be real genes. The majority of the putative genes identified by BLAST search have been described since the release of the EcoSeq6 database, but about 70 genes have not been detected so far. Among these new identifications are genes encoding proteins with a variety of predicted functions including dehydrogenases, kinases, several other metabolic enzymes, ATPases, rRNA methyltransferases, membrane proteins, and different types of regulatory proteins. Images PMID:7984428

Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

PubMed

McKay, Jill A; Adriaens, Michiel; Evelo, Chris T; Ford, Dianne; Mathers, John C

2016-09-01

Early-life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed transcriptional changes in fetal liver in response to maternal folate depletion and hypothesized that these changes are concomitant with altered gene promoter methylation. Female C57BL/6J mice were fed diets containing 2 or 0.4 mg folic acid/kg for 4 wk before mating and throughout pregnancy. At 17.5-day gestation, genome-wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers. While 989 genes were differentially expressed, 333 promoters had altered methylation (247 hypermethylated, 86 hypomethylated) in response to maternal folate depletion. Only 16 genes had both expression and methylation changes. However, most methylation changes occurred in genomic regions neighboring expression changes. In response to maternal folate depletion, altered expression at the mRNA level was not associated with altered promoter methylation of the same gene in fetal liver. © 2016 The Authors. Molecular Nutrition & Food Research Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sugar Treatments Can Induce AcLEAFY COTYLEDON1 Expression and Trigger the Accumulation of Storage Products during Prothallus Development of Adiantum capillus-veneris

PubMed Central

Fang, Yu-Han; Li, Xia; Bai, Shu-Nong; Rao, Guang-Yuan

2017-01-01

A seed is an intricate structure. Of the two development processes involved in seed formation, seed maturation, or seed program includes accumulation of storage products, acquisition of desiccation tolerance, and induction of dormancy. Little is known about how these processes were originated and integrated into the life cycle of seed plants. While previous investigation on seed origin was almost exclusively through fossil comparison in paleobotany, a wealth of information about the key role of LEAFY COTYLEDON1 (LEC1) in seed formation of spermatophyte inspired a new approach to investigating the seed origin mystery. Here, we examined the expression pattern of AcLEC1 during the entire life cycle of Adiantum capillus-veneris, a non-seed plant, confirmed no AcLEC1 gene expression detectable in prothalli, demonstrated inductive expressed by both sucrose and glucose in prothalli. As expected, we found that sugar treatments delayed prothallus development, promoted differentiation of reproductive organs, and triggered accumulation of storage products. These findings demonstrated links between the sugar treatments and the induction of AcLEC1 expression, as well as the sugar treatments and the events such as accumulation of storage products, which is similar to those considered as seed maturation process in seed plants. These links support a modified hypothesis that inductive expression of LEC1 homologs during embryogenesis might be a key innovation for the origin of the seed program. PMID:28484470

Assessment of the efficacy of a psychological treatment for women victims of violence by their intimate male partner.

PubMed

Crespo, María; Arinero, María

2010-11-01

This study evaluates the long-term efficacy of a brief psychotherapeutic cognitive-behavioral program in group format for female victims of violence by their intimate partner. 53 battered women were randomized into one of two intervention programs: one including among others exposure technique (n = 28) and another one in which exposure procedures were substituted by communication skills training (n = 25). Additionally, both programs included: psycho-education, breath control, training to improve self-esteem, cognitive restructuring, problem-solving, planning pleasant activities, and relapse prevention. The treatment was carried out in 8 weekly sessions. Measures of posttraumatic symptoms, anxiety, depression, self-esteem and anger expression were analyzed at pre- and post-treatment, and at 1-, 3-, 6- and 12-months follow-ups. Results show a pronounced decrease of posttraumatic, depressive and anxiety symptoms, which maintained in the different measure moments, with scarce difference between the two programs. The results and their clinical implications are discussed.

An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

PubMed Central

Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

2014-01-01

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

Enrolling in Medicaid through the National School Lunch Program: outcome of a pilot project in California schools.

PubMed

Cousineau, Michael R; Wada, Eriko O; Hogan, Laura

2007-01-01

California has several health insurance programs for children. However, the system for enrolling into these programs is complex and difficult to manage for many families. Express Lane Eligibility is designed to streamline the Medicaid (called Medi-Cal in California) enrollment process by linking it to the National School Lunch Program. If a child is eligible for free lunch and the parents consent, the program provides two months of presumptive eligibility for Medi-Cal and a simplified application process for continuation in Medi-Cal. For those who are ineligible, it provides a referral to other programs. An evaluation of Express Lane shows that while many children were presumptively enrolled, nearly half of the applicants were already enrolled in Medi-Cal. Many Express Enrolled children failed to complete the full Medi-Cal enrollment process. Few were referred to the State Children's Health Insurance Program or county programs. Express Lane is less useful as a broad screening strategy, but can be one of many tools that communities use to enroll children in health insurance.

“Maternal Health and Family Planning Distance Education” experience among physicians: a three-phase study to determine the educational needs, develop education program, and evaluate efficacy of the education administered

PubMed Central

Ciftci, Bestami; Uzel, Nesibe; Ozel, M Onur; Zergeroglu, Sema; Deger, Cetin; Turasan, S Sare; Karakoc, Ayse Gul; Ozbalci, Semra

2016-01-01

Aim This study aims to assess the educational needs of family practitioners and evaluate the efficacy of the ongoing “Maternal Health and Family Planning Distance Education” program conducted by the General Directorate of Health Research (SAGEM) of the Turkish Ministry of Health. Methods This study consisted of three phases. In the first phase, an online survey on maternal health and family planning educational needs was sent to 20,611 physicians via e-mail. Of the 20,611 physicians, 4,729 completed the survey. In the second phase, of the 1,061 physicians registered to the education program, 632 physicians with active participation were included. In the third phase, the preeducation expectations of 287 physicians and posteducation satisfaction of 54 physicians were analyzed with a questionnaire. Results The majority of the physicians were employed in a family health center (97.4%) and practicing for 16–20 years (23.2%) without any prior in-service training (60.9%). High-to-very high educational need was expressed by 56.4% of physicians for pregnancy, delivery, and puerperality. Topics that the physicians, including both those with ≥16 years in practice and without prior in-service training, expressed need for more detailed content were pregnancy, delivery, and puerperality (37.5%); emergency obstetric approach in the primary care setting (33.1%); and gynecological infectious diseases and treatment approach (32.4%). Following the education program, the participants’ expectations were fulfilled in terms of refreshing their knowledge, particularly in the field of Maternal Health and Family Planning (87.1% and 75.9%) and the percentage of participants who expressed that they had sufficient high level knowledge increased from 55% to 68.5%. Conclusion The education on Maternal Health and Family Planning refreshed the knowledge of participants and highly met the preeducation expectations. Determining the educational needs and expectations of the target population prior to the education program seems to have an important role on determining its overall success. PMID:27354837

"Maternal Health and Family Planning Distance Education" experience among physicians: a three-phase study to determine the educational needs, develop education program, and evaluate efficacy of the education administered.

PubMed

Ciftci, Bestami; Uzel, Nesibe; Ozel, M Onur; Zergeroglu, Sema; Deger, Cetin; Turasan, S Sare; Karakoc, Ayse Gul; Ozbalci, Semra

2016-01-01

This study aims to assess the educational needs of family practitioners and evaluate the efficacy of the ongoing "Maternal Health and Family Planning Distance Education" program conducted by the General Directorate of Health Research (SAGEM) of the Turkish Ministry of Health. This study consisted of three phases. In the first phase, an online survey on maternal health and family planning educational needs was sent to 20,611 physicians via e-mail. Of the 20,611 physicians, 4,729 completed the survey. In the second phase, of the 1,061 physicians registered to the education program, 632 physicians with active participation were included. In the third phase, the preeducation expectations of 287 physicians and posteducation satisfaction of 54 physicians were analyzed with a questionnaire. The majority of the physicians were employed in a family health center (97.4%) and practicing for 16-20 years (23.2%) without any prior in-service training (60.9%). High-to-very high educational need was expressed by 56.4% of physicians for pregnancy, delivery, and puerperality. Topics that the physicians, including both those with ≥16 years in practice and without prior in-service training, expressed need for more detailed content were pregnancy, delivery, and puerperality (37.5%); emergency obstetric approach in the primary care setting (33.1%); and gynecological infectious diseases and treatment approach (32.4%). Following the education program, the participants' expectations were fulfilled in terms of refreshing their knowledge, particularly in the field of Maternal Health and Family Planning (87.1% and 75.9%) and the percentage of participants who expressed that they had sufficient high level knowledge increased from 55% to 68.5%. The education on Maternal Health and Family Planning refreshed the knowledge of participants and highly met the preeducation expectations. Determining the educational needs and expectations of the target population prior to the education program seems to have an important role on determining its overall success.

The State of Disability Awareness in American Medical Schools.

PubMed

Seidel, Erica; Crowe, Scott

2017-09-01

This study was designed to: (1) determine how many American medical schools include disability awareness in their curriculum, (2) explore the format of disability awareness programs in existence, and (3) understand why some schools do not include disability awareness in their curriculum. An online survey was sent to deans of medical education (or equivalent positions) at accredited allopathic and osteopathic American medical schools (N = 167) in 2015. Seventy-five schools (45%) completed surveys. Fifty-two percent (39/75) reported having a disability awareness program. The most common format was people with disabilities or caregivers speaking in a large group setting. Programs were most likely to focus on adults with physical disabilities. Among schools without a program, the top barriers were no one advocating for inclusion in the curriculum and time constraints. Nearly half of schools without a program expressed interest in adopting an awareness curriculum if one was made available. Such results indicate that efforts should be made to increase the number of schools that provide disability awareness education through increased advocacy and providing additional resources to schools without a curriculum.

Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats.

PubMed

Laughlin, M Harold; Padilla, Jaume; Jenkins, Nathan T; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Akter, Sadia; Davis, J Wade

2015-09-15

We employed next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second-order arterioles (D2a) and in the diaphragm feed artery (DFA) from Otsuka Long Evans Tokushima Fatty (OLETF) rats. Arterioles were isolated from the diaphragm of OLETF rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). Our hypothesis was that exercise training would have similar effects on gene expression in the diaphragm and soleus muscle arterioles because diaphragm blood flow increases during exercise to a similar extent as in soleus. Results reveal that several canonical pathways that were significantly altered by exercise in limb skeletal muscles were not among the pathways significantly changed in the diaphragm arterioles including actin cytoskeleton signaling, role of NFAT in regulation of immune response, protein kinase A signaling, and protein ubiquitination pathway. EX training altered the expression of a smaller number of genes than did SPRINT in the DFA but induced a larger number of genes with altered expression in the D2a than did SPRINT. In fact, FDR differential expression analysis (FDR, 10%) indicated that only two genes exhibited altered expression in D2a of SPRINT rats. Very few of the genes that exhibited altered expression in the DFA or D2a were also altered in limb muscle arterioles. Finally, results indicate that the 2a arterioles of soleus muscle (S2a) from endurance-trained animals and the DFA of SPRINT animals exhibited the largest number of genes with altered expression.

Milne, a routine for the numerical solution of Milne's problem

NASA Astrophysics Data System (ADS)

Rawat, Ajay; Mohankumar, N.

2010-11-01

The routine Milne provides accurate numerical values for the classical Milne's problem of neutron transport for the planar one speed and isotropic scattering case. The solution is based on the Case eigen-function formalism. The relevant X functions are evaluated accurately by the Double Exponential quadrature. The calculated quantities are the extrapolation distance and the scalar and the angular fluxes. Also, the H function needed in astrophysical calculations is evaluated as a byproduct. Program summaryProgram title: Milne Catalogue identifier: AEGS_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEGS_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 701 No. of bytes in distributed program, including test data, etc.: 6845 Distribution format: tar.gz Programming language: Fortran 77 Computer: PC under Linux or Windows Operating system: Ubuntu 8.04 (Kernel version 2.6.24-16-generic), Windows-XP Classification: 4.11, 21.1, 21.2 Nature of problem: The X functions are integral expressions. The convergence of these regular and Cauchy Principal Value integrals are impaired by the singularities of the integrand in the complex plane. The DE quadrature scheme tackles these singularities in a robust manner compared to the standard Gauss quadrature. Running time: The test included in the distribution takes a few seconds to run.

Definition and preliminary design of the Laser Atmospheric Wind Sounder (LAWS) phase 1. Volume 3: Program cost estimates

NASA Technical Reports Server (NTRS)

1990-01-01

Cost estimates for phase C/D of the laser atmospheric wind sounder (LAWS) program are presented. This information provides a framework for cost, budget, and program planning estimates for LAWS. Volume 3 is divided into three sections. Section 1 details the approach taken to produce the cost figures, including the assumptions regarding the schedule for phase C/D and the methodology and rationale for costing the various work breakdown structure (WBS) elements. Section 2 shows a breakdown of the cost by WBS element, with the cost divided in non-recurring and recurring expenditures. Note that throughout this volume the cost is given in 1990 dollars, with bottom line totals also expressed in 1988 dollars (1 dollar(88) = 0.93 1 dollar(90)). Section 3 shows a breakdown of the cost by year. The WBS and WBS dictionary are included as an attachment to this report.

Sonic-box method employing local Mach number for oscillating wings with thickness

NASA Technical Reports Server (NTRS)

Ruo, S. Y.

1978-01-01

A computer program was developed to account approximately for the effects of finite wing thickness in the transonic potential flow over an oscillating wing of finite span. The program is based on the original sonic-box program for planar wing which was previously extended to include the effects of the swept trailing edge and the thickness of the wing. Account for the nonuniform flow caused by finite thickness is made by application of the local linearization concept. The thickness effect, expressed in terms of the local Mach number, is included in the basic solution to replace the coordinate transformation method used in the earlier work. Calculations were made for a delta wing and a rectangular wing performing plunge and pitch oscillations, and the results were compared with those obtained from other methods. An input quide and a complete listing of the computer code are presented.

The Impact of PD-L1 Expression in Patients with Metastatic GEP-NETs

PubMed Central

Kim, Seung Tae; Ha, Sang Yun; Lee, Sujin; Ahn, Soomin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Kim, Kyoung-Mee; Park, Young Suk

2016-01-01

Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET. The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed. Primary sites were 24 foregut-derived GEP-NETs, including stomach (n=1), duodenum (n=2), biliary tract (n=7), and pancreas (n=14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p=0.008) but not with gender, primary site, and number of metastatic sites (p>0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p=0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p=0.037). The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs. PMID:26958083

Los Angeles congestion reduction demonstration express lanes program : national evaluation report.

DOT National Transportation Integrated Search

2015-08-01

This document presents the final report on the national evaluation of the Los Angeles Congestion Reduction Demonstration (LA CRD) ExpressLanes Program under the United States Department of Transportation (U.S. DOT) CRD Program. The LA CRD projects fo...

I Wanna Take Me a Picture: Teaching Photography and Writing to Children.

ERIC Educational Resources Information Center

Ewald, Wendy

Drawing on the author's classroom experiences and the curriculum in a program she established called "Literacy through Photography," the book presents a guide to teaching children to express themselves with photographic images. The book includes over 60 black and white photographs as well as anecdotes about the author's work. Five sections follow…

A Community Art Therapy Group for Adults with Chronic Pain

ERIC Educational Resources Information Center

O'Neill, Aimee; Moss, Hilary

2015-01-01

This paper describes a community art therapy group for people living with chronic pain. Nine adults were offered 12 weekly group art therapy sessions that included art therapy activities such as guided imagery focusing on body scans followed by art responses and artistic expressions of the pain experience. This pilot group art therapy program is…

Expressive electronic journal writing: freedom of communication for survivors of acquired brain injury.

PubMed

Fraas, Michael; Balz, Magdalen A

2008-03-01

In addition to the impaired ability to effectively communicate, adults with acquired brain injury (ABI) also experience high incidences of depression, social isolation, and decreased quality of life. Expressive writing programs have been shown to be effective in alleviating these concomitant impairments in other populations including incarcerated inmates (Lane, Writing as a road to self-discovery, F & W, Cincinnati 1993). In addition, computer applications such as email have been suggested as an effective means of improving communication and social isolation in adults with brain injury (Sohlberg et al. [2003]. Brain Injury, 17(7), 609-629). This investigation examines the effects of on-line expressive journal writing on the communication, emotional status, social integration and quality of life of individuals with brain injury.

Problematic communications during 2016 fellowship recruitment in internal medicine.

PubMed

Cornett, Patricia A; Williams, Chris; Alweis, Richard L; McConville, John; Frank, Michael; Dalal, Bhavin; Kopelman, Richard I; Luther, Vera P; O'connor, Alec B; Muchmore, Elaine A

2017-01-01

Some internal medicine residency program directors have expressed concerns that their third-year residents may have been subjected to inappropriate communication during the 2016 fellowship recruitment season. The authors sought to study applicants' interpersonal communication experiences with fellowship programs. Many respondents indicated that they had been asked questions that would constitute violations of the National Residency Matching Program (NRMP) Communications Code of Conduct agreement, including how they plan to rank specific programs. Moreover, female respondents were more likely to have been asked questions during interview experiences about other programs to which they applied, and about their family plans. Post-interview communication policies were not made clear to most applicants. These results suggest ongoing challenges for the internal medicine community to improve communication with applicants and uniform compliance with the NRMP communications code of conduct during the fellowship recruitment process.

A powerful graphical pulse sequence programming tool for magnetic resonance imaging.

PubMed

Jie, Shen; Ying, Liu; Jianqi, Li; Gengying, Li

2005-12-01

A powerful graphical pulse sequence programming tool has been designed for creating magnetic resonance imaging (MRI) applications. It allows rapid development of pulse sequences in graphical mode (allowing for the visualization of sequences), and consists of three modules which include a graphical sequence editor, a parameter management module and a sequence compiler. Its key features are ease to use, flexibility and hardware independence. When graphic elements are combined with a certain text expressions, the graphical pulse sequence programming is as flexible as text-based programming tool. In addition, a hardware-independent design is implemented by using the strategy of two step compilations. To demonstrate the flexibility and the capability of this graphical sequence programming tool, a multi-slice fast spin echo experiment is performed on our home-made 0.3 T permanent magnet MRI system.

Effects of Maternal Obesity on Fetal Programming: Molecular Approaches

PubMed Central

Neri, Caterina; Edlow, Andrea G.

2016-01-01

Maternal obesity has become a worldwide epidemic. Obesity and a high-fat diet have been shown to have deleterious effects on fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Although large epidemiological studies have shown an association between maternal obesity and adverse outcomes for offspring, the underlying mechanisms remain unclear. Molecular approaches have played a key role in elucidating the mechanistic underpinnings of fetal malprogramming in the setting of maternal obesity. These approaches include, among others, characterization of epigenetic modifications, microRNA expression, the gut microbiome, the transcriptome, and evaluation of specific mRNA expression via quantitative reverse transcription polmerase chain reaction (RT-qPCR) in fetuses and offspring of obese females. This work will review the data from animal models and human fluids/cells regarding the effects of maternal obesity on fetal and offspring neurodevelopment and cardiometabolic outcomes, with a particular focus on molecular approaches. PMID:26337113

A program for performing exact quantum dynamics calculations using cylindrical polar coordinates: A nanotube application

NASA Astrophysics Data System (ADS)

Skouteris, Dimitris; Gervasi, Osvaldo; Laganà, Antonio

2009-03-01

A program that uses the time-dependent wavepacket method to study the motion of structureless particles in a force field of quasi-cylindrical symmetry is presented here. The program utilises cylindrical polar coordinates to express the wavepacket, which is subsequently propagated using a Chebyshev expansion of the Schrödinger propagator. Time-dependent exit flux as well as energy-dependent S matrix elements can be obtained for all states of the particle (describing its angular momentum component along the nanotube axis and the excitation of the radial degree of freedom in the cylinder). The program has been used to study the motion of an H atom across a carbon nanotube. Program summaryProgram title: CYLWAVE Catalogue identifier: AECL_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECL_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 3673 No. of bytes in distributed program, including test data, etc.: 35 237 Distribution format: tar.gz Programming language: Fortran 77 Computer: RISC workstations Operating system: UNIX RAM: 120 MBytes Classification: 16.7, 16.10 External routines: SUNSOFT performance library (not essential) TFFT2D.F (Temperton Fast Fourier Transform), BESSJ.F (from Numerical Recipes, for the calculation of Bessel functions) (included in the distribution file). Nature of problem: Time evolution of the state of a structureless particle in a quasicylindrical potential. Solution method: Time dependent wavepacket propagation. Running time: 50000 secs. The test run supplied with the distribution takes about 10 minutes to complete.

PD-1 expression by tumor-associated macrophages inhibits phagocytosis and tumor immunity

PubMed Central

Gordon, Sydney R.; Maute, Roy L.; Dulken, Ben W.; Hutter, Gregor; George, Benson M.; McCracken, Melissa N.; Gupta, Rohit; Tsai, Jonathan M.; Sinha, Rahul; Corey, Daniel; Ring, Aaron M.; Connolly, Andrew J.; Weissman, Irving L.

2017-01-01

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells to induce immune tolerance.1,2 Tumor cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating escape from the immune system.3,4 Monoclonal antibodies blocking PD-1/PD-L1 have shown remarkable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small cell lung cancer, and Hodgkin’s lymphoma.5–9 Although it is well-established that PD-1/PD-L1 blockade activates T cells, little is known about the role that this pathway may have on tumor-associated macrophages (TAMs). Here we show that both mouse and human TAMs express PD-1. TAM PD-1 expression increases over time in mouse models, and with increasing disease stage in primary human cancers. TAM PD-1 expression negatively correlates with phagocytic potency against tumor cells, and blockade of PD-1/PD-L1 in vivo increases macrophage phagocytosis, reduces tumor growth, and lengthens survival in mouse models of cancer in a macrophage-dependent fashion. Our results suggest that PD-1/PD-L1 therapies may also function through a direct effect on macrophages, with significant implications for treatment with these agents. PMID:28514441

NaJAZh Regulates a Subset of Defense Responses against Herbivores and Spontaneous Leaf Necrosis in Nicotiana attenuata Plants[C][W][OA

PubMed Central

Oh, Youngjoo; Baldwin, Ian T.; Gális, Ivan

2012-01-01

The JASMONATE ZIM DOMAIN (JAZ) proteins function as negative regulators of jasmonic acid signaling in plants. We cloned 12 JAZ genes from native tobacco (Nicotiana attenuata), including nine novel JAZs in tobacco, and examined their expression in plants that had leaves elicited by wounding or simulated herbivory. Most JAZ genes showed strong expression in the elicited leaves, but NaJAZg was mainly expressed in roots. Another novel herbivory-elicited gene, NaJAZh, was analyzed in detail. RNA interference suppression of this gene in inverted-repeat (ir)JAZh plants deregulated a specific branch of jasmonic acid-dependent direct and indirect defenses: irJAZh plants showed greater trypsin protease inhibitor activity, 17-hydroxygeranyllinalool diterpene glycosides accumulation, and emission of volatile organic compounds from leaves. Silencing of NaJAZh also revealed a novel cross talk in JAZ-regulated secondary metabolism, as irJAZh plants had significantly reduced nicotine levels. In addition, irJAZh spontaneously developed leaf necrosis during the transition to flowering. Because the lesions closely correlated with the elevated expression of programmed cell death genes and the accumulations of salicylic acid and hydrogen peroxide in the leaves, we propose a novel role of the NaJAZh protein as a repressor of necrosis and/or programmed cell death during plant development. PMID:22496510

Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

PubMed Central

Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

2015-01-01

Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

Cultural Competency Training in Emergency Medicine.

PubMed

Mechanic, Oren J; Dubosh, Nicole M; Rosen, Carlo L; Landry, Alden M

2017-09-01

The Emergency Department is widely regarded as the epicenter of medical care for diverse and largely disparate types of patients. Physicians must be aware of the cultural diversity of their patient population to appropriately address their medical needs. A better understanding of residency preparedness in cultural competency can lead to better training opportunities and patient care. The objective of this study was to assess residency and faculty exposure to formal cultural competency programs and assess future needs for diversity education. A short survey was sent to all 168 Accreditation Council for Graduate Medical Education program directors through the Council of Emergency Medicine Residency Directors listserv. The survey included drop-down options in addition to open-ended input. Descriptive and bivariate analyses were used to analyze data. The response rate was 43.5% (73/168). Of the 68.5% (50/73) of residency programs that include cultural competency education, 90% (45/50) utilized structured didactics. Of these programs, 86.0% (43/50) included race and ethnicity education, whereas only 40.0% (20/50) included education on patients with limited English proficiency. Resident comfort with cultural competency was unmeasured by most programs (83.6%: 61/73). Of all respondents, 93.2% (68/73) were interested in a universal open-source cultural competency curriculum. The majority of the programs in our sample have formal resident didactics on cultural competency. Some faculty members also receive cultural competency training. There are gaps, however, in types of cultural competency training, and many programs have expressed interest in a universal open-source tool to improve cultural competency for Emergency Medicine residents. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship of In-Cylinder Gaseous and Particulate Concentration to Radiative Heat Transfer in Direct Injection-Type Diesel Combustion.

DTIC Science & Technology

1986-04-15

spectral reflectivities, a,.,, are included in the expression for the radiosity of surface 1, Bk1, as (I I l cos eI I(0)) 4 B cos e e 2 + B 2 cos 92 i...OAAG29-83-K-0042 (Scientific Program Officer, Dr. David M. Mann). NOMENCLATURE A band absorptance a constant determining species distribution 8 radiosity ...Fig. 1), the radiosity of the surface 1, 81, i.e., to compute the thermal and optical is expressed as properties of the species and to implement

Investigating the transcriptional control of cardiovascular development

PubMed Central

Kathiriya, Irfan S.; Nora, Elphege P.; Bruneau, Benoit G.

2015-01-01

Transcriptional regulation of thousands of genes instructs complex morphogenetic and molecular events for heart development. Cardiac transcription factors (TFs) choreograph gene expression at each stage of differentiation by interacting with co-factors, including chromatin-modifying enzymes, and by binding to a constellation of regulatory DNA elements. Here, we present salient examples relevant to cardiovascular development and heart disease and review techniques that can sharpen our understanding of cardiovascular biology. We discuss the interplay between cardiac TFs, cis-regulatory elements and chromatin as dynamic regulatory networks, to orchestrate sequential deployment of the cardiac gene expression program. PMID:25677518

Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

DTIC Science & Technology

2013-09-01

Bongarzone ER. Expression of sonic hedgehog targeted genes in peripheral blood mononuclear cells of patients with multiple sclerosis. Society for...Print Program#/Poster#: 322.13 Presentation Title: Expression of sonic  hedgehog  targeted genes in peripheral blood mononuclear cells of patients with...analyses. Gene array hybridization showed up­ regulation of various components of the Sonic  hedgehog  (Shh) pathway including, Olig1 and Olig2. Taken

Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism

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

Liu Jie; Xie Yaxiong; Cooper, Ryan

Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes relatedmore » to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17{beta}-hydroxysteroid dehydrogenase-7 (HSD17{beta}7; involved in estradiol production) and decreased expression of HSD17{beta}5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood.« less

Religion and adolescent sexuality.

PubMed

Stayton, W R

1985-06-01

The health professional can be helpful to the adolescent, the adolescent's family, and the community through participating in and initiating local sex education programs. Religious settings provide a great potential for sexuality education within a value framework. A helpful curriculum will include the meaning of sexuality; developing a positive concept of sexuality, and a healthy sexual identity; present the issues of adolescent sexuality, including the various health issues; and an understanding of quality relationships within the family and among peers. If health professions and the community religious institutions can joint together, they can reach the goals of most programs in human sexuality, namely, "learning to appreciate our sexuality as a positive potential for self-expression, fulfillment and intimacy; respect for the personhood and well-being of others; and responsible decision-making."

Project ExPreSS: Social studies and science remediation program for the Georgia High School Graduation Test

NASA Astrophysics Data System (ADS)

Shearouse, Randy

Over half of the states now require students to pass a high stakes exit exam before being allowed to graduate from high school. No Child Left Behind requires that standardized testing be included to determine whether or not a school makes Adequate Yearly Progress (AYP). The purpose of this study is to examine the results of the Georgia High School Graduation Test (GHSGT) of students who participated in the remedial program Project ExPreSS with those students who did not participate. Using a quantitative research design, the question that will be answered is whether Project ExPreSS makes a difference in passing the GHSGT in science and social studies among three groups: all Georgia students, African American students in one Georgia school system, and all students in one Georgia school system. A chi-square test was conducted and a determination was made that there is a statistically significant relationship between project participation and pass-fail status in all but one area. The majority of students in this study were 17--18 years of age and were taking the science or social studies section of the GHSGT for the second time. The findings of this study will be important not only for Georgia and the school system examined, but also for other states and systems that give High Stakes Exit Exams (HSEEs). The results indicate that highly focused remedial programs like Project ExPreSS make a difference for students who may not be successful on their first attempt at passing a HSEE.

Let's face it: patient and parent perspectives on incorporating a Facebook group into a multidisciplinary weight management program.

PubMed

Woolford, Susan J; Esperanza Menchaca, Alicia D M; Sami, Areej; Blake, Natalie

2013-08-01

Social media may have the potential to enhance weight management efforts. However, the acceptability of incorporating this entity into pediatrics is unknown. The objective of this project was to explore patients' and parents' perspectives about developing a Facebook group as a component of a pediatric weight management program. Semistructured interviews were performed between September, 2011, and February, 2012, with patients and parents in a multidisciplinary weight management program. Interviews explored participants' perceptions of potential benefits, concerns, and preferences related to a program-specific Facebook group. Transcripts were reviewed and themes identified. The study concluded when thematic saturation was achieved. Participants (n=32) were largely enthusiastic about the idea of a program-specific Facebook group for adolescents. Most preferred a secret group, where only participants would know of the group's existence or group members' identity. No parents expressed concern about security or privacy related to a program-specific Facebook group; one parent expressed concern about undesirable advertisements. Participants endorsed a variety of ideas for inclusion on the page, including weight loss tips, live chats with providers, quizzes, and an incentive system where participants could gain points for making healthy choices. Many parents requested a separate parent-focused page, an idea that was supported by the adolescents. This study suggests that participants perceive potential benefits from incorporating social media interventions into pediatric weight management efforts. Privacy and security issues do not appear to be major parental concerns. Future work should explore the impact of program-specific social media interventions on outcomes for patients in weight management programs.

Array data extractor (ADE): a LabVIEW program to extract and merge gene array data

PubMed Central

2013-01-01

Background Large data sets from gene expression array studies are publicly available offering information highly valuable for research across many disciplines ranging from fundamental to clinical research. Highly advanced bioinformatics tools have been made available to researchers, but a demand for user-friendly software allowing researchers to quickly extract expression information for multiple genes from multiple studies persists. Findings Here, we present a user-friendly LabVIEW program to automatically extract gene expression data for a list of genes from multiple normalized microarray datasets. Functionality was tested for 288 class A G protein-coupled receptors (GPCRs) and expression data from 12 studies comparing normal and diseased human hearts. Results confirmed known regulation of a beta 1 adrenergic receptor and further indicate novel research targets. Conclusions Although existing software allows for complex data analyses, the LabVIEW based program presented here, “Array Data Extractor (ADE)”, provides users with a tool to retrieve meaningful information from multiple normalized gene expression datasets in a fast and easy way. Further, the graphical programming language used in LabVIEW allows applying changes to the program without the need of advanced programming knowledge. PMID:24289243

Molecular Cooperativity Governs Diverse and Monoallelic Olfactory Receptor Expression

NASA Astrophysics Data System (ADS)

Xing, Jianhua; Tian, Xiaojun; Zhang, Hang; Sannerud, Jens

Multiple-objective optimization is common in biological systems. In the mammalian olfactory system, each sensory neuron stochastically expresses only one out of up to thousands of olfactory receptor (OR) gene alleles; at organism level the types of expressed ORs need to be maximized. The molecular mechanism of this Nobel-Prize winning puzzle remains unresolved after decades of extensive studies. Existing models focus only on monoallele activation, and cannot explain recent observations in mutants, especially the reduced global diversity of expressed ORs in G9a/GLP knockouts. In this work we integrated existing information on OR expression, and proposed an evolutionarily optimized three-layer regulation mechanism, which includes zonal segregation, epigenetic and enhancer competition coupled to a negative feedback loop. This model not only recapitulates monoallelic OR expression, but also elucidates how the olfactory system maximizes and maintains the diversity of OR expression. The model is validated by several experimental results, and particularly underscores cooperativity and synergy as a general design principle of multi-objective optimization in biology. The work is supported by the NIGMS/DMS Mathematical Biology program.

A systematic writing program as a tool in the grief process: part 1.

PubMed

Furnes, Bodil; Dysvik, Elin

2010-12-06

The basic aim of this paper is to suggest a flexible and individualized writing program as a tool for use during the grief process of bereaved adults. An open, qualitative approach following distinct steps was taken to gain a broad perspective on the grief and writing processes, as a platform for the writing program. Following several systematic methodological steps, we arrived at suggestions for the initiation of a writing program and its structure and substance, with appropriate guidelines. We believe that open and expressive writing, including free writing and focused writing, may have beneficial effects on a person experiencing grief. These writing forms may be undertaken and systematized through a writing program, with participation in a grief writing group and with diary writing, to achieve optimal results. A structured writing program might be helpful in promoting thought activities and as a tool to increase the coherence and understanding of individuals in the grief process. Our suggested program may also be a valuable guide to future program development and research.

UTP and Temporal Logic Model Checking

NASA Astrophysics Data System (ADS)

Anderson, Hugh; Ciobanu, Gabriel; Freitas, Leo

In this paper we give an additional perspective to the formal verification of programs through temporal logic model checking, which uses Hoare and He Unifying Theories of Programming (UTP). Our perspective emphasizes the use of UTP designs, an alphabetised relational calculus expressed as a pre/post condition pair of relations, to verify state or temporal assertions about programs. The temporal model checking relation is derived from a satisfaction relation between the model and its properties. The contribution of this paper is that it shows a UTP perspective to temporal logic model checking. The approach includes the notion of efficiency found in traditional model checkers, which reduced a state explosion problem through the use of efficient data structures

Family-Based Interventions for the Prevention of Substance Abuse and Other Impulse Control Disorders in Girls

PubMed Central

Kumpfer, K. L.

2014-01-01

Standardized family-based interventions are the most effective way of preventing or treating adolescent substance abuse and delinquency. This paper first reviews the incidence of adolescent substance abuse worldwide emphasizing gender and causes by etiological risk and protective factors. New epigenetic research is included suggesting that nurturing parenting significantly prevents the phenotypic expression of inherited genetic diseases including substance abuse. Evidence-based family interventions are reviewed including family change theories behind their success, principles and types of family-based interventions, research results, cultural adaptation steps for ethnic and international translation, and dissemination issues. The author's Strengthening Family Program is used as an example of how these principles of effective prevention and cultural adaptation can result in highly effective prevention programs not only for substance abuse, but for other impulse control disorders as well. The conclusions include recommendations for more use of computer technologies to cut the high cost of family interventions relative to youth-only prevention programs and increase the public health impact of evidence-based prevention programs. The paper recommends that to reduce health care costs these family-based approaches should be applied to the prevention and treatment of other impulse control disorders such as obesity and type 2 diabetes, sexually transmitted diseases, and delinquency. PMID:25938121

Identification and characterization of Rhox13, a novel X-linked mouse homeobox gene

PubMed Central

Geyer, Christopher B.; Eddy, Edward M.

2008-01-01

Homeobox genes encode transcription factors whose expression organizes programs of development. A number of homeobox genes expressed in reproductive tissues have been identified recently, including a colinear cluster on the X chromosome in mice. This has led to an increased interest in understanding the role(s) of homeobox genes in regulating development of reproductive tissues including the testis, ovary, and placenta. Here we report the identification and characterization of a novel homeobox gene of the paired-like class on the X chromosome distal to the reproductive homeobox (Rhox) cluster in mice. Transcripts are found in the testis and ovary as early as 13.5 days post-coitum (dpc). Transcription ceases in the ovary by 3 days post-partum (dpp), but continues in the testis through adulthood. The Rhox13 gene encodes a 25.3 kDa protein expressed in the adult testis in germ cells at the basal aspect of the seminiferous epithelium. PMID:18675325

Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells.

PubMed

Li, Deguan; Chen, Renxiang; Wang, Yi-Wen; Fornace, Albert J; Li, Heng-Hong

2018-05-01

In this study we addressed the question whether radiation-induced adverse effects on T cell activation are associated with alterations of T cell checkpoint receptors. Expression levels of checkpoint receptors on T cell subpopulations were analyzed at multiple post-radiation time points ranging from one to four weeks in mice receiving a single fraction of 1 or 4 Gy of γ-ray. T cell activation associated metabolic changes were assessed. Our results showed that prior irradiation resulted in significant elevated expression of programmed cell death protein 1 (PD-1) in both CD4+ and CD8+ populations, at all three post-radiation time points. T cells with elevated PD-1 mostly were either central memory or naïve cells. In addition, the feedback induction of PD-1 expression in activated T cells declined after radiation. Taken together, the elevated PD-1 level observed at weeks after radiation exposure is connected to T cell dysfunction. Recent preclinical and clinical studies have showed that a combination of radiotherapy and T cell checkpoint blockade immunotherapy including targeting the programmed death-ligand 1 (PD-L1)/PD-1 axis may potentiate the antitumor response. Understanding the dynamic changes in PD-1 levels in T cells after radiation should help in the development of a more effective therapeutic strategy.

Computational exploration of cis-regulatory modules in rhythmic expression data using the "Exploration of Distinctive CREs and CRMs" (EDCC) and "CRM Network Generator" (CNG) programs.

PubMed

Bekiaris, Pavlos Stephanos; Tekath, Tobias; Staiger, Dorothee; Danisman, Selahattin

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, "Exploration of Distinctive CREs and CRMs" (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, "CRM Network Generator" (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression.

Computational exploration of cis-regulatory modules in rhythmic expression data using the “Exploration of Distinctive CREs and CRMs” (EDCC) and “CRM Network Generator” (CNG) programs

PubMed Central

Staiger, Dorothee

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, “Exploration of Distinctive CREs and CRMs” (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, “CRM Network Generator” (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression. PMID:29298348

Participant satisfaction with a school telehealth education program using interactive compressed video delivery methods in rural Arkansas.

PubMed

Bynum, Ann B; Cranford, Charles O; Irwin, Cathy A; Denny, George S

2002-08-01

Socioeconomic and demographic factors can affect the impact of telehealth education programs that use interactive compressed video technology. This study assessed program satisfaction among participants in the University of Arkansas for Medical Sciences' School Telehealth Education Program delivered by interactive compressed video. Variables in the one-group posttest study were age, gender, ethnicity, education, community size, and program topics for years 1997-1999. The convenience sample included 3,319 participants in junior high and high schools. The School Telehealth Education Program provided information about health risks, disease prevention, health promotion, personal growth, and health sciences. Adolescents reported medium to high levels of satisfaction regarding program interest and quality. Significantly higher satisfaction was expressed for programs on muscular dystrophy, anatomy of the heart, and tobacco addiction (p < 0.001 to p = 0.003). Females, African Americans, and junior high school students reported significantly greater satisfaction (p < 0.001 to p = 0.005). High school students reported significantly greater satisfaction than junior high school students regarding the interactive video equipment (p = 0.011). White females (p = 0.025) and African American males (p = 0.004) in smaller, rural communities reported higher satisfaction than White males. The School Telehealth Education Program, delivered by interactive compressed video, promoted program satisfaction among rural and minority populations and among junior high and high school students. Effective program methods included an emphasis on participants' learning needs, increasing access in rural areas among ethnic groups, speaker communication, and clarity of the program presentation.

Sorting Through the Spheres of Influence: Using Modified Pile Sorting to Describe Who Influences Dairy Farmers' Decision-Making About Safety.

PubMed

Bendixsen, Casper; Barnes, Kathrine; Kieke, Burney; Schenk, Danielle; Simich, Jessica; Keifer, Matthew

2017-01-01

The primary goal of this study was to describe the mutually perceived influence of bankers and insurers on their agricultural clients' decision-making regarding health and safety. Semistructured interviews were conducted with 10 dairy farmers, 11 agricultural bankers, and 10 agricultural insurers from central Wisconsin. Three of the interview questions involved pile sorting. Pile sorting included 5-point Likert-like scales to help participants sort through 32 index cards. Each card represented an individual or group that was thought to possibly affect farmers' decision-making, both generally and about health and safety. Results (photographs of piles of cards quantified into spread sheets, fieldnotes, and interview transcripts) were analyzed with SAS and NVivo. All three groups expressed moderate-to-strong positive opinions about involving agricultural bankers (x2(2) = 2.8155, p = 0.2695), although bankers qualitatively expressed apprehension due to regulations on the industry. Insurance agents received more positive support, particularly from bankers but also from dairy farmers themselves, and expressed more confidence in being involved in designing and implementing a farm safety program. Agricultural bankers and insurers can influence individual farmer's decision-making about health and safety. Both are believed to be good purveyors of safety programs and knowledge, especially when leveraging financial incentives. Insurance agents are thought to be more critical in the design of safety programs. Insurers and bankers being financially tied to safety programs may prove both positive and negative, as farmers may be skeptical about the intention of the incentives, making messaging critical.

Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent

PubMed Central

van Erp, Anke E.M.; Versleijen-Jonkers, Yvonne M.H.; Hillebrandt-Roeffen, Melissa H.S.; van Houdt, Laurens; Gorris, Mark A.J.; van Dam, Laura S.; Mentzel, Thomas; Weidema, Marije E.; Savci-Heijink, C. Dilara; Desar, Ingrid M.E.; Merks, Hans H.M.; van Noesel, Max M.; Shipley, Janet; van der Graaf, Winette T.A.; Flucke, Uta E.; Meyer-Wentrup, Friederike A.G.

2017-01-01

In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described. PMID:29050367

Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent.

PubMed

van Erp, Anke E M; Versleijen-Jonkers, Yvonne M H; Hillebrandt-Roeffen, Melissa H S; van Houdt, Laurens; Gorris, Mark A J; van Dam, Laura S; Mentzel, Thomas; Weidema, Marije E; Savci-Heijink, C Dilara; Desar, Ingrid M E; Merks, Hans H M; van Noesel, Max M; Shipley, Janet; van der Graaf, Winette T A; Flucke, Uta E; Meyer-Wentrup, Friederike A G

2017-09-19

In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma ( n = 46), Ewing sarcoma ( n = 32), alveolar rhabdomyosarcoma ( n = 20), embryonal rhabdomyosarcoma ( n = 77), synovial sarcoma ( n = 22) and desmoplastic small round cell tumors (DSRCT) ( n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described.

"L'Atelier d'expression orale" (The Oral Expression Workshop).

ERIC Educational Resources Information Center

Tabensky, Alexis; Mesana, Corinne

1990-01-01

An extracurricular program in an Australian university French language program that brings together adults of varying ages and nationalities for oral language development activities is described. The program uses improvisation, psychodrama and role playing, and suggestopedia all together to develop a theme or in alternation, for creativity and…

Gender Expression, Violence, and Bullying Victimization: Findings From Probability Samples of High School Students in 4 US School Districts.

PubMed

Gordon, Allegra R; Conron, Kerith J; Calzo, Jerel P; White, Matthew T; Reisner, Sari L; Austin, S Bryn

2018-04-01

Young people may experience school-based violence and bullying victimization related to their gender expression, independent of sexual orientation identity. However, the associations between gender expression and bullying and violence have not been examined in racially and ethnically diverse population-based samples of high school students. This study includes 5469 students (13-18 years) from the 2013 Youth Risk Behavior Surveys conducted in 4 urban school districts. Respondents were 51% Hispanic/Latino, 21% black/African American, 14% white. Generalized additive models were used to examine the functional form of relationships between self-reported gender expression (range: 1 = Most gender conforming, 7 = Most gender nonconforming) and 5 indicators of violence and bullying victimization. We estimated predicted probabilities across gender expression by sex, adjusting for sexual orientation identity and potential confounders. Statistically significant quadratic associations indicated that girls and boys at the most gender conforming and nonconforming ends of the scale had elevated probabilities of fighting and fighting-related injury, compared to those in the middle of the scale (p < .05). There was a significant linear relationship between gender expression and bullying victimization; every unit increase in gender nonconformity was associated with 15% greater odds of experiencing bullying (p < .0001). School-based victimization is associated with conformity and nonconformity to gender norms. School violence prevention programs should include gender diversity education. © 2018, American School Health Association.

Evaluation and Validation of Reference Genes for qRT-PCR Normalization in Frankliniella occidentalis (Thysanoptera:Thripidae)

PubMed Central

Zheng, Yu-Tao; Li, Hong-Bo; Lu, Ming-Xing; Du, Yu-Zhou

2014-01-01

Quantitative real time PCR (qRT-PCR) has emerged as a reliable and reproducible technique for studying gene expression analysis. For accurate results, the normalization of data with reference genes is particularly essential. Once the transcriptome sequencing of Frankliniella occidentalis was completed, numerous unigenes were identified and annotated. Unfortunately, there are no studies on the stability of reference genes used in F. occidentalis. In this work, seven candidate reference genes, including actin, 18S rRNA, H3, tubulin, GAPDH, EF-1 and RPL32, were evaluated for their suitability as normalization genes under different experimental conditions using the statistical software programs BestKeeper, geNorm, Normfinder and the comparative ΔCt method. Because the rankings of the reference genes provided by each of the four programs were different, we chose a user-friendly web-based comprehensive tool RefFinder to get the final ranking. The result demonstrated that EF-1 and RPL32 displayed the most stable expression in different developmental stages; RPL32 and GAPDH showed the most stable expression at high temperatures, while 18S and EF-1 exhibited the most stable expression at low temperatures. In this study, we validated the suitable reference genes in F. occidentalis for gene expression profiling under different experimental conditions. The choice of internal standard is very important in the normalization of the target gene expression levels, thus validating and selecting the best genes will help improve the quality of gene expression data of F. occidentalis. What is more, these validated reference genes could serve as the basis for the selection of candidate reference genes in other insects. PMID:25356721

Evaluation and validation of reference genes for qRT-PCR normalization in Frankliniella occidentalis (Thysanoptera: Thripidae).

PubMed

Zheng, Yu-Tao; Li, Hong-Bo; Lu, Ming-Xing; Du, Yu-Zhou

2014-01-01

Quantitative real time PCR (qRT-PCR) has emerged as a reliable and reproducible technique for studying gene expression analysis. For accurate results, the normalization of data with reference genes is particularly essential. Once the transcriptome sequencing of Frankliniella occidentalis was completed, numerous unigenes were identified and annotated. Unfortunately, there are no studies on the stability of reference genes used in F. occidentalis. In this work, seven candidate reference genes, including actin, 18S rRNA, H3, tubulin, GAPDH, EF-1 and RPL32, were evaluated for their suitability as normalization genes under different experimental conditions using the statistical software programs BestKeeper, geNorm, Normfinder and the comparative ΔCt method. Because the rankings of the reference genes provided by each of the four programs were different, we chose a user-friendly web-based comprehensive tool RefFinder to get the final ranking. The result demonstrated that EF-1 and RPL32 displayed the most stable expression in different developmental stages; RPL32 and GAPDH showed the most stable expression at high temperatures, while 18S and EF-1 exhibited the most stable expression at low temperatures. In this study, we validated the suitable reference genes in F. occidentalis for gene expression profiling under different experimental conditions. The choice of internal standard is very important in the normalization of the target gene expression levels, thus validating and selecting the best genes will help improve the quality of gene expression data of F. occidentalis. What is more, these validated reference genes could serve as the basis for the selection of candidate reference genes in other insects.

Toddlers' Expressive Vocabulary Outcomes after One Year of Parent-Child Home Program Services

ERIC Educational Resources Information Center

Manz, Patricia H.; Bracaliello, Catherine B.; Pressimone, Vanessa J.; Eisenberg, Rachel A.; Gernhart, Amanda C.; Fu, Qiong; Zuniga, Cesar

2016-01-01

This quasi-experimental study examined expressive vocabulary outcomes for Parent-Child Home Program (PCHP) toddlers, after one year of home-visiting services. First, this study applied Rasch modelling to establish the construct validity and reliability of a widely used expressive vocabulary measure, as modified for a sample of ethnic and…

Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators.

PubMed

Desai, Mina; Han, Guang; Ross, Michael G

2016-04-01

Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Programmed Hyperphagia in Offspring of Obese Dams: Altered Expression of Hypothalamic Nutrient Sensors, Neurogenic Factors and Epigenetic Modulators

PubMed Central

Desai, Mina; Han, Guang; Ross, Michael G.

2016-01-01

Maternal overnutrition results in programmed offspring obesity, mediated in part, by hyperphagia. This is remarkably similar to the effects of maternal undernutrition on offspring hyperphagia and obesity. In view of the marked differences in the energy environment of the over and under-nutrition exposures, we studied the expression of select epigenetic modifiers associated with energy imbalance including neurogenic factors and appetite/satiety neuropeptides which are indicative of neurogenic differentiation. HF offspring were exposed to maternal overnutrition (high fat diet; HF) during pregnancy and lactation. We determined the protein expression of energy sensors (mTOR, pAMPK), epigenetic factors (DNA methylase, DNMT1; histone deacetylase, SIRT1/HDAC1), neurogenic factors (Hes1, Mash1, Ngn3) and appetite/satiety neuropeptides (AgRP/POMC) in newborn hypothalamus and adult arcuate nucleus (ARC). Despite maternal obesity, male offspring born to obese dams had similar body weight at birth as Controls. However, when nursed by the same dams, male offspring of obese dams exhibited marked adiposity. At 1 day of age, HF newborn males had significantly decreased energy sensors, DNMT1 including Hes1 and Mash1, which may impact neuroprogenitor cell proliferation and differentiation. This is consistent with increased AgRP in HF newborns. At 6 months of age, HF adult males had significantly increased energy sensors and decreased histone deactylases. In addition, the persistent decreased Hes1, Mash1 as well as Ngn3 are consistent with increased AgRP and decreased POMC. Thus, altered energy sensors and epigenetic responses which modulate gene expression and adult neuronal differentiation may contribute to hyperphagia and obesity in HF male offspring. PMID:26785315

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer.

PubMed

Bailey, Swneke D; Desai, Kinjal; Kron, Ken J; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A; Treloar, Aislinn E; Dowar, Mark; Thu, Kelsie L; Cescon, David W; Silvester, Jennifer; Yang, S Y Cindy; Wu, Xue; Pezo, Rossanna C; Haibe-Kains, Benjamin; Mak, Tak W; Bedard, Philippe L; Pugh, Trevor J; Sallari, Richard C; Lupien, Mathieu

2016-10-01

Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer.

Expression of immune checkpoints in T cells of esophageal cancer patients.

PubMed

Xie, Jinhua; Wang, Ji; Cheng, Shouliang; Zheng, Liangfeng; Ji, Feiyue; Yang, Lin; Zhang, Yan; Ji, Haoming

2016-09-27

Inhibition of immune checkpoint proteins (checkpoints) has become a promising anti-esophageal cancer strategy. We here tested expressions of immune checkpoints in human esophageal cancers. Our results showed the expressions of many immune checkpoints, including CD28, CD27, CD137L, programmed death 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), T cell Ig and ITIM domain (TIGIT), CD160, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD200, CD137 and CD158, were dysregulated in peripheral T cells of esophageal cancer patients. Further, the expressions of PD-1, TIM-3 and TIGIT were upregulated in tumor infiltrating lymphocytes (TILs), which might be associated with TILs exhaustion. Meanwhile, the expressions of PD-1 and TIM-3 on CD4+ T cells were closely associated with clinic pathological features of esophageal cancer patients. These results indicate that co-inhibitory receptors PD-1, TIM-3 and TIGIT may be potential therapeutic oncotargets for esophageal cancer.

Co-Option and De Novo Gene Evolution Underlie Molluscan Shell Diversity

PubMed Central

Aguilera, Felipe; McDougall, Carmel

2017-01-01

Abstract Molluscs fabricate shells of incredible diversity and complexity by localized secretions from the dorsal epithelium of the mantle. Although distantly related molluscs express remarkably different secreted gene products, it remains unclear if the evolution of shell structure and pattern is underpinned by the differential co-option of conserved genes or the integration of lineage-specific genes into the mantle regulatory program. To address this, we compare the mantle transcriptomes of 11 bivalves and gastropods of varying relatedness. We find that each species, including four Pinctada (pearl oyster) species that diverged within the last 20 Ma, expresses a unique mantle secretome. Lineage- or species-specific genes comprise a large proportion of each species’ mantle secretome. A majority of these secreted proteins have unique domain architectures that include repetitive, low complexity domains (RLCDs), which evolve rapidly, and have a proclivity to expand, contract and rearrange in the genome. There are also a large number of secretome genes expressed in the mantle that arose before the origin of gastropods and bivalves. Each species expresses a unique set of these more ancient genes consistent with their independent co-option into these mantle gene regulatory networks. From this analysis, we infer lineage-specific secretomes underlie shell diversity, and include both rapidly evolving RLCD-containing proteins, and the continual recruitment and loss of both ancient and recently evolved genes into the periphery of the regulatory network controlling gene expression in the mantle epithelium. PMID:28053006

Development of Amphibious Doctrine

DTIC Science & Technology

2010-06-11

Graduate Degree Programs Robert F. Baumann, Ph.D. The opinions and conclusions expressed herein are those of the student author and do not...battalion composed of six companies of Marines, its commander, Lieutenant Colonel Robert W. Huntington, finally received the mission of securing an...42,000 men. The participants included the Commanding Officer, Marine Corps Schools, Colonel Robert Dunlap, as well as the students and instructors

A Discussion on an Expression Written about Dimensional Analysis in a Physics Textbook

ERIC Educational Resources Information Center

Yildiz, Ali

2015-01-01

The purpose of this study is to discuss a wrong statement written about dimensional analysis in a physics text book prepared for the students who are studying in science, engineering and teaching undergraduate programs at universities and who have to take compulsory physics courses, to analyse the use of the text book including the wrong…

Oxygen and tissue culture affect placental gene expression.

PubMed

Brew, O; Sullivan, M H F

2017-07-01

Placental explant culture is an important model for studying placental development and functions. We investigated the differences in placental gene expression in response to tissue culture, atmospheric and physiologic oxygen concentrations. Placental explants were collected from normal term (38-39 weeks of gestation) placentae with no previous uterine contractile activity. Placental transcriptomic expressions were evaluated with GeneChip ® Human Genome U133 Plus 2.0 arrays (Affymetrix). We uncovered sub-sets of genes that regulate response to stress, induction of apoptosis programmed cell death, mis-regulation of cell growth, proliferation, cell morphogenesis, tissue viability, and protection from apoptosis in cultured placental explants. We also identified a sub-set of genes with highly unstable pattern of expression after exposure to tissue culture. Tissue culture irrespective of oxygen concentration induced dichotomous increase in significant gene expression and increased enrichment of significant pathways and transcription factor targets (TFTs) including HIF1A. The effect was exacerbated by culture at atmospheric oxygen concentration, where further up-regulation of TFTs including PPARA, CEBPD, HOXA9 and down-regulated TFTs such as JUND/FOS suggest intrinsic heightened key biological and metabolic mechanisms such as glucose use, lipid biosynthesis, protein metabolism; apoptosis, inflammatory responses; and diminished trophoblast proliferation, differentiation, invasion, regeneration, and viability. These findings demonstrate that gene expression patterns differ between pre-culture and cultured explants, and the gene expression of explants cultured at atmospheric oxygen concentration favours stressed, pro-inflammatory and increased apoptotic transcriptomic response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Promyelocytic leukemia zinc finger turns on the effector T cell program without requirement for agonist TCR signaling.

PubMed

Savage, Adam K; Constantinides, Michael G; Bendelac, Albert

2011-05-15

Thymocytes expressing the NKT cell semi-invariant αβ TCR are thought to undergo agonist interactions with CD1d ligands prior to expressing promyelocytic leukemia zinc finger (PLZF), a broad complex, tramtrack, bric-a-brac, poxvirus, and zinc finger transcription factor that directs acquisition of the effector program of these innate-like T cells. Whether PLZF can mediate this effector conversion independently of agonist signaling has not been investigated. We demonstrated that transgenic (Tg) expression of PLZF under the CD4 promoter induced the innate effector program in two different MHC class II-restricted TCR-Tg Rag1(-/-) models examined. In CD4 thymocytes expressing a fixed Tg TCR β-chain, the associated TCRα sequences in wild-type and PLZF-Tg mice overlapped extensively, further demonstrating that PLZF could induce the effector program in most CD4 T cells that would normally be selected as naive cells. In contrast, PLZF altered the negative selection of thymocytes expressing TCR β-chains reactive against several retroviral superantigens. Thus, PLZF is remarkable in that it is a transcription factor capable of inducing an effector program in the absence of T cell agonist interactions or cell division. Its expression may also enhance the survival of agonist-signaled thymocytes.

Emergency management training program: Guide to good practice

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

Not Available

1991-07-01

The Emergency Management Training Program Guide to Good Practice is a project of the Training Resources and Data Exchange (TRADE) Emergency Management Issues Special Interest Group (EMI SIG). EMI SIG members expressed interest in a resource to assist in development of a comprehensive emergency management training program. This publication provides guidelines, methods, and materials for EMI SIG members to use, assisting in complete and effective emergency management programs. The purposes of the Emergency Management Training Program Guide to Good Practice are: Provide guidance in the development and management of Emergency Management (EM) training programs; Assist EM trainers to incorporate componentsmore » of the DOE Emergency Management System philosophy of planning, preparedness, readiness assurance, and response into EM training programs; Help EM training managers meet EM training requirements and conditions established by current regulations and policies; Supplement other TRADE EMI SIG documents and complement individual facility training documents. This program is designed for emergency management personnel who are responsible for providing or overseeing EM training but who do not necessarily possess expertise in developing training. It provides good practices from the manager's point of view on how to produce, administer, and document facility EM training programs in the spirit of the DOE EM system philosophy. Basic guidance is also included for personnel who design, develop, deliver, and/or evaluate EM training programs or parts. This guidance includes key points of EM training programs and identifies other documents that contain useful and/or more detailed training information.« less

Emergency management training program: Guide to good practice

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

Not Available

1991-07-01

The Emergency Management Training Program Guide to Good Practice is a project of the Training Resources and Data Exchange (TRADE) Emergency Management Issues Special Interest Group (EMI SIG). EMI SIG members expressed interest in a resource to assist in development of a comprehensive emergency management training program. This publication provides guidelines, methods, and materials for EMI SIG members to use, assisting in complete and effective emergency management programs. The purposes of the Emergency Management Training Program Guide to Good Practice are: Provide guidance in the development and management of Emergency Management (EM) training programs; Assist EM trainers to incorporate componentsmore » of the DOE Emergency Management System philosophy of planning, preparedness, readiness assurance, and response into EM training programs; Help EM training managers meet EM training requirements and conditions established by current regulations and policies; Supplement other TRADE EMI SIG documents and complement individual facility training documents. This program is designed for emergency management personnel who are responsible for providing or overseeing EM training but who do not necessarily possess expertise in developing training. It provides good practices from the manager`s point of view on how to produce, administer, and document facility EM training programs in the spirit of the DOE EM system philosophy. Basic guidance is also included for personnel who design, develop, deliver, and/or evaluate EM training programs or parts. This guidance includes key points of EM training programs and identifies other documents that contain useful and/or more detailed training information.« less

Modulation of organic acids and sugar content in tomato fruits by an abscisic acid-regulated transcription factor.

PubMed

Bastías, Adriana; López-Climent, María; Valcárcel, Mercedes; Rosello, Salvador; Gómez-Cadenas, Aurelio; Casaretto, José A

2011-03-01

Growing evidence suggests that the phytohormone abscisic acid (ABA) plays a role in fruit development. ABA signaling components of developmental programs and responses to stress conditions include the group of basic leucine zipper transcriptional activators known as ABA-response element binding factors (AREBs/ABFs). AREB transcription factors mediate ABA-regulated gene expression involved in desiccation tolerance and are expressed mainly in seeds and in vegetative tissues under stress; however, they are also expressed in some fruits such as tomato. In order to get an insight into the role of ABA signaling in fruit development, the expression of two AREB-like factors were investigated during different developmental stages. In addition, tomato transgenic lines that overexpress and downregulate one AREB-like transcription factor, SlAREB1, were used to determine its effect on the levels of some metabolites determining fruit quality. Higher levels of citric acid, malic acid, glutamic acid, glucose and fructose were observed in SlAREB1-overexpressing lines compared with those in antisense suppression lines in red mature fruit pericarp. The higher hexose concentration correlated with increased expression of genes encoding a vacuolar invertase (EC 3.2.1.26) and a sucrose synthase (EC 2.4.1.13). No significant changes were found in ethylene content which agrees with the normal ripening phenotype observed in transgenic fruits. These results suggest that an AREB-mediated ABA signal affects the metabolism of these compounds during the fruit developmental program. Copyright © Physiologia Plantarum 2010.

Qualitative evaluation of a mobile phone and web-based collaborative care intervention for patients with type 2 diabetes.

PubMed

Lyles, Courtney Rees; Harris, Lynne T; Le, Tung; Flowers, Jan; Tufano, James; Britt, Diane; Hoath, James; Hirsch, Irl B; Goldberg, Harold I; Ralston, James D

2011-05-01

Drawing on previous web-based diabetes management programs based on the Chronic Care Model, we expanded an intervention to include care management through mobile phones and a game console web browser. The pilot intervention enrolled eight diabetes patients from the University of Washington in Seattle into a collaborative care program: connecting them to a care provider specializing in diabetes, providing access to their full electronic medical record, allowing wireless glucose uploads and e-mail with providers, and connecting them to the program's web services through a game system. To evaluate the study, we conducted qualitative thematic analysis of semistructured interviews. Participants expressed frustrations with using the cell phones and the game system in their everyday lives, but liked the wireless system for collaborating with a provider on uploaded glucoses and receiving automatic feedback on their blood sugar trends. A majority of participants also expressed that their participation in the trial increased their health awareness. Mobile communication technologies showed promise within a web-based collaborative care program for type 2 diabetes. Future intervention design should focus on integrating easy-to-use applications within mobile technologies already familiar to patients and ensure the system allows for sufficient collaboration with a care provider.

TSPP - A Collection of FORTRAN Programs for Processing and Manipulating Time Series

USGS Publications Warehouse

Boore, David M.

2008-01-01

This report lists a number of FORTRAN programs that I have developed over the years for processing and manipulating strong-motion accelerograms. The collection is titled TSPP, which stands for Time Series Processing Programs. I have excluded 'strong-motion accelerograms' from the title, however, as the boundary between 'strong' and 'weak' motion has become blurred with the advent of broadband sensors and high-dynamic range dataloggers, and many of the programs can be used with any evenly spaced time series, not just acceleration time series. This version of the report is relatively brief, consisting primarily of an annotated list of the programs, with two examples of processing, and a few comments on usage. I do not include a parameter-by-parameter guide to the programs. Future versions might include more examples of processing, illustrating the various parameter choices in the programs. Although these programs have been used by the U.S. Geological Survey, no warranty, expressed or implied, is made by the USGS as to the accuracy or functioning of the programs and related program material, nor shall the fact of distribution constitute any such warranty, and no responsibility is assumed by the USGS in connection therewith. The programs are distributed on an 'as is' basis, with no warranty of support from me. These programs were written for my use and are being publically distributed in the hope that others might find them as useful as I have. I would, however, appreciate being informed about bugs, and I always welcome suggestions for improvements to the codes. Please note that I have made little effort to optimize the coding of the programs or to include a user-friendly interface (many of the programs in this collection have been included in the software usdp (Utility Software for Data Processing), being developed by Akkar et al. (personal communication, 2008); usdp includes a graphical user interface). Speed of execution has been sacrificed in favor of a code that is intended to be easy to understand, although on modern computers speed of execution is rarely a problem. I will be pleased if users incorporate portions of my programs into their own applications; I only ask that reference be made to this report as the source of the programs.

Toward Enhancing OpenMP's Work-Sharing Directives

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

Chapman, B M; Huang, L; Jin, H

2006-05-17

OpenMP provides a portable programming interface for shared memory parallel computers (SMPs). Although this interface has proven successful for small SMPs, it requires greater flexibility in light of the steadily growing size of individual SMPs and the recent advent of multithreaded chips. In this paper, we describe two application development experiences that exposed these expressivity problems in the current OpenMP specification. We then propose mechanisms to overcome these limitations, including thread subteams and thread topologies. Thus, we identify language features that improve OpenMP application performance on emerging and large-scale platforms while preserving ease of programming.

For a Child, Life is a Creative Adventure: Supporting Development and Learning through Art, Music, Movement, and Dialogue. A Guide for Parents and Professionals. = Para los ninos, la vida es una aventura creativa: Como estimular el desarrollo y el aprendizaje por medio de las artes visuales, la musica, el movimiento y el dialogo. Guia para padres de familia y profesionales.

ERIC Educational Resources Information Center

Cohen, Elena

Recognizing that creativity facilitates children's learning and development, the Head Start Program Performance Standards require Head Start programs to include opportunities for creative self-expression. This guide with accompanying videotape, both in English- and Spanish- language versions, encourages and assists adults to support children's…

A beta1-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction.

PubMed

Sucharov, Carmen C; Mariner, Peter D; Nunley, Karin R; Long, Carlin; Leinwand, Leslie; Bristow, Michael R

2006-09-01

Beta-adrenergic signaling plays an important role in the natural history of dilated cardiomyopathies. Chronic activation of beta-adrenergic receptors (beta1-AR and beta2-AR) during periods of cardiac stress ultimately harms the failing heart by mechanisms that include alterations in gene expression. Here, we show that stimulation of beta-ARs with isoproterenol in neonate rat ventricular myocytes causes a "fetal" response in the relative activities of the human cardiac fetal and/or adult gene promoters that includes repression of the human and rat alpha-myosin heavy chain (alpha-MyHC) promoters with simultaneous activation of the human atrial natriuretic peptide (ANP) and rat beta-MyHC promoters. We also show that the promoter changes correlate with changes in endogenous gene expression as measured by mRNA expression. Furthermore, we show that these changes are specifically mediated by the beta1-AR, but not the beta2-AR, and are independent of alpha1-AR stimulation. We also demonstrate that the fetal gene response is independent of cAMP and protein kinase A, whereas inhibition of Ca2+/calmodulin-dependent protein kinase (CaMK) pathway blocks isoproterenol-mediated fetal gene program induction. Finally, we show that induction of the fetal program is dependent on activation of the L-type Ca2+ channel. We conclude that in neonatal rat cardiac myocytes, agonist-occupied beta1-AR mobilizes Ca2+ stores to activate fetal gene induction through cAMP independent pathways that involve CaMK.

TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells

PubMed Central

Nguyen, Trieu; Iyer, Dharini; Liu, Boxiang; Wang, Ting; Sazonova, Olga; Matic, Ljubica Perisic; Maegdefessel, Lars; Quertermous, Thomas

2017-01-01

Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g., tobacco smoke). Perturbation of TCF21 expression in human coronary artery smooth muscle cells (HCASMC) revealed that TCF21 promotes expression of AHR, its heterodimerization partner ARNT, and cooperates with these factors to upregulate a number of inflammatory downstream disease related genes including IL1A, MMP1, and CYP1A1. TCF21 was shown to bind in AHR, ARNT and downstream target gene loci, and co-localization was noted for AHR-ARNT and TCF21 binding sites genome-wide in regions of HCASMC open chromatin. These regions of co-localization were found to be enriched for GWAS signals associated with cardio-metabolic as well as chronic inflammatory disease phenotypes. Finally, we show that similar to TCF21, AHR gene expression is increased in atherosclerotic lesions in mice in vivo using laser capture microdissection, and AHR protein is localized in human carotid atherosclerotic lesions where it is associated with protein kinases with a critical role in innate immune response. These data suggest that TCF21 can cooperate with AHR to activate an inflammatory gene expression program that is exacerbated by environmental stimuli, and may contribute to the overall risk for CAD. PMID:28481916

Collaborating in the Community: Fostering Identity and Creative Expression in an Afterschool Program

ERIC Educational Resources Information Center

Cavendish, Leslie M.; Vess, Sarah F.; Li-Barber, Kirsten

2016-01-01

Nationwide budget cuts have forced many public school systems to significantly reduce opportunities for engaging in creative arts in the classroom despite the fact that such programs are associated with positive child outcomes. To address this deficit, we developed and executed the "Afterschool Creative Expression Program" (ASCEP) and…

State Programs for Migrant Children. Kansas Annual Evaluation Report, 1971.

ERIC Educational Resources Information Center

Ahlstrom, Clyde J., Comp.

Ten individual reports from the 1971 summer migrant educational programs in Kansas are summarized and evaluated. The goals of these programs were to (1) help children develop oral language and expression; (2) provide arts and crafts for personal expression; (3) provide swimming and other types of recreation for physical development and…

Genome-wide expression profiling in pediatric septic shock

PubMed Central

Wong, Hector R.

2013-01-01

For nearly a decade, our research group has had the privilege of developing and mining a multi-center, microarray-based, genome-wide expression database of critically ill children (≤ 10 years of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which will be reviewed. Fundamental observations include wide spread repression of gene programs corresponding to the adaptive immune system, and biologically significant differential patterns of gene expression across developmental age groups. The data have also identified gene expression-based subclasses of pediatric septic shock having clinically relevant phenotypic differences. The data have also been leveraged for the discovery of novel therapeutic targets, and for the discovery and development of novel stratification and diagnostic biomarkers. Almost a decade of genome-wide expression profiling in pediatric septic shock is now demonstrating tangible results. The studies have progressed from an initial discovery-oriented and exploratory phase, to a new phase where the data are being translated and applied to address several areas of clinical need. PMID:23329198

Poetic Expressions: Students of Color Express Resiliency through Metaphors and Similes

ERIC Educational Resources Information Center

Hall, Horace R.

2007-01-01

The after-school City School Outreach youth program captured the attention of high school male students by offering them a physically and psychologically safe environment to talk about issues they faced. The students of color who attended the program used various forms of creative written expression (i.e., poetry, spoken word, and hip hop) to…

EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1α and STAT3.

PubMed

Koh, Jaemoon; Jang, Ji-Young; Keam, Bhumsuk; Kim, Sehui; Kim, Moon-Young; Go, Heounjeong; Kim, Tae Min; Kim, Dong-Wan; Kim, Chul-Woo; Jeon, Yoon Kyung; Chung, Doo Hyun

2016-03-01

Programmed cell death (PD)-1/PD-1 ligand-1 (PD-L1)-targeted therapy has emerged as a promising therapeutic strategy for lung cancer. However, whether EML4-ALK regulates PD-L1 expression in lung cancer remains unknown. A total of 532 pulmonary adenocarcinomas (pADCs), including 58 ALK -translocated tumors, were immunohistochemically evaluated for PD-L1 and PD-1. H23 ( EGFR Wild-type EML4-ALK - PD-L1 Low ) and H2228 ( EGFR Wild-type EML4-ALK + PD-L1 High ) cells were transfected with EML4-ALK or ALK short interfering RNAs and used to investigate the alterations in PD-L1 expression. PD-L1 expression was detected in 81% of ALK -translocated pADCs; this value was significantly higher than those of pADCs with EGFR mutation, KRAS mutation or lacking ALK, EGFR or KRAS mutation ( p <0.005 for all). Moreover, ALK -translocated pADC with PD-L1 expression showed significantly higher numbers of tumor-infiltrating PD-1 + cells. ALK knockdown or inhibition (crizotinib treatment) in H2228 cells downregulated PD-L1 expression. Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment. This ALK-dependent upregulation of PD-L1 expression was mediated by STAT3 and hypoxia-inducible factor (HIF)-1α under normoxia and hypoxia. Furthermore, EML4-ALK enhanced HIF-1α expression through increasing transcription and decreasing ubiquitination of HIF-1α. In ALK -translocated pADC tissues, significant positive correlations between PD-L1 and nuclear HIF-1α ( p < 0.05) or pSTAT3 expression levels ( p <0.005) were observed. Among patients with ALK -translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free ( p = 0.001) and overall survival ( p = 0.002) after crizotinib treatment. Collectively, our findings demonstrate that ALK- derived pADCs increase PD-L1 expression via HIF-1α and/or STAT3, thus providing a rationale for PD-1/PD-L1 pathway-targeted therapy in ALK -translocated lung cancer.

WinTRAX: A raytracing software package for the design of multipole focusing systems

NASA Astrophysics Data System (ADS)

Grime, G. W.

2013-07-01

The software package TRAX was a simulation tool for modelling the path of charged particles through linear cylindrical multipole fields described by analytical expressions and was a development of the earlier OXRAY program (Grime and Watt, 1983; Grime et al., 1982) [1,2]. In a 2005 comparison of raytracing software packages (Incerti et al., 2005) [3], TRAX/OXRAY was compared with Geant4 and Zgoubi and was found to give close agreement with the more modern codes. TRAX was a text-based program which was only available for operation in a now rare VMS workstation environment, so a new program, WinTRAX, has been developed for the Windows operating system. This implements the same basic computing strategy as TRAX, and key sections of the code are direct translations from FORTRAN to C++, but the Windows environment is exploited to make an intuitive graphical user interface which simplifies and enhances many operations including system definition and storage, optimisation, beam simulation (including with misaligned elements) and aberration coefficient determination. This paper describes the program and presents comparisons with other software and real installations.

MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their Role in Obesity and Related Pathologies.

PubMed

Matoušková, Petra; Hanousková, Barbora; Skálová, Lenka

2018-04-14

Glutathione peroxidases (GPxs) belong to the eight-member family of phylogenetically related enzymes with different cellular localization, but distinct antioxidant function. Several GPxs are important selenoproteins. Dysregulated GPx expression is connected with severe pathologies, including obesity and diabetes. We performed a comprehensive bioinformatic analysis using the programs miRDB, miRanda, TargetScan, and Diana in the search for hypothetical microRNAs targeting 3'untranslated regions (3´UTR) of GPxs. We cross-referenced the literature for possible intersections between our results and available reports on identified microRNAs, with a special focus on the microRNAs related to oxidative stress, obesity, and related pathologies. We identified many microRNAs with an association with oxidative stress and obesity as putative regulators of GPxs. In particular, miR-185-5p was predicted by a larger number of programs to target six GPxs and thus could play the role as their master regulator. This microRNA was altered by selenium deficiency and can play a role as a feedback control of selenoproteins' expression. Through the bioinformatics analysis we revealed the potential connection of microRNAs, GPxs, obesity, and other redox imbalance related diseases.

Information Management Strategies for Program Tracking and Formative Evaluation

NASA Astrophysics Data System (ADS)

Siegfried, D.; Detrick, L.; Valaitis, S.; Johnson, A.; Thomas, S. H.; Fauver, A.

2013-05-01

The Institute for Broadening Participation (IBP) has developed information management systems to facilitate programmatic formative evaluation, tracking and outreach activities. Nearly a decade of design solutions and technical implementations in support of IBP's professional development and mentoring programs for students (including the "Pathways to Ocean Science," "Minorities Striving and Pursuing Higher Degrees of Success" in Earth System Science, and "Pathways to Engineering") has provided IBP with a toolbox of proven strategies for addressing program engagement and participant tracking, outreach, and a variety of other information management needs. In this session, IBP will use case-specific examples to share general design strategies for program participant and activities data collection in REUs and other program types. The cases will illustrate an approach that begins with a review of program logic, objectives, expected outcomes, constraints and requirements, which then informs a comprehensive system design. When implemented, such information systems improve administrative efficiency through streamlined data collection processes and easy-to-use data capture forms, and a corresponding set of reporting tools provides access to data that is crucial for ongoing program improvement. IBP presents this information in response to collaborations with administrators of Research Experience for Undergraduates (REU) programs as well as longer duration programs, who have expressed the need for more comprehensive and easy to use information systems. Recently IBP has also worked with the directors of NSF and NASA funded programs seeking assistance in addressing their formative evaluation needs including system design, information collection, and reporting efforts.

Let's Face It: Patient and Parent Perspectives on Incorporating a Facebook Group into a Multidisciplinary Weight Management Program

PubMed Central

Esperanza Menchaca, Alicia D. M.; Sami, Areej; Blake, Natalie

2013-01-01

Abstract Background Social media may have the potential to enhance weight management efforts. However, the acceptability of incorporating this entity into pediatrics is unknown. The objective of this project was to explore patients' and parents' perspectives about developing a Facebook group as a component of a pediatric weight management program. Methods Semistructured interviews were performed between September, 2011, and February, 2012, with patients and parents in a multidisciplinary weight management program. Interviews explored participants' perceptions of potential benefits, concerns, and preferences related to a program-specific Facebook group. Transcripts were reviewed and themes identified. The study concluded when thematic saturation was achieved. Results Participants (n=32) were largely enthusiastic about the idea of a program-specific Facebook group for adolescents. Most preferred a secret group, where only participants would know of the group's existence or group members' identity. No parents expressed concern about security or privacy related to a program-specific Facebook group; one parent expressed concern about undesirable advertisements. Participants endorsed a variety of ideas for inclusion on the page, including weight loss tips, live chats with providers, quizzes, and an incentive system where participants could gain points for making healthy choices. Many parents requested a separate parent-focused page, an idea that was supported by the adolescents. Conclusions This study suggests that participants perceive potential benefits from incorporating social media interventions into pediatric weight management efforts. Privacy and security issues do not appear to be major parental concerns. Future work should explore the impact of program-specific social media interventions on outcomes for patients in weight management programs. PMID:23869854

Academic Leadership Development: A Case Study.

PubMed

Berman, Audrey

2015-01-01

A dean at a private school of nursing implemented a leadership development program for early- to mid-career nursing faculty consisting of one 4-hour evening session per academic quarter for 7 quarters. Eight faculty members who had expressed interest in assuming a leadership role or been recommended by their supervisors as having strong leadership potential were invited to join. Program topics included leadership pathways, legal issues, budgeting and governance, diversity, the political arena, human resources, and student issues. Interviews with participants revealed 6 themes: the support a peer cohort provided, a desire for real-life application, a lack of previous exposure to related content or experiences, new perceptions of themselves as academic nurse leaders, the value of the program as preparation for academic nursing leadership roles, and broad program applicability. Copyright © 2015 Elsevier Inc. All rights reserved.

Express Authorization Questions and Answers about What is Generally the Content of a Program Revision Application?

EPA Pesticide Factsheets

Frequently asked questions about express authorization with answers organized into five categories: attorney general's statement, statutory checklist, rule checklists, program description, and state initiated regulatory changes.

The use of open source bioinformatics tools to dissect transcriptomic data.

PubMed

Nitsche, Benjamin M; Ram, Arthur F J; Meyer, Vera

2012-01-01

Microarrays are a valuable technology to study fungal physiology on a transcriptomic level. Various microarray platforms are available comprising both single and two channel arrays. Despite different technologies, preprocessing of microarray data generally includes quality control, background correction, normalization, and summarization of probe level data. Subsequently, depending on the experimental design, diverse statistical analysis can be performed, including the identification of differentially expressed genes and the construction of gene coexpression networks.We describe how Bioconductor, a collection of open source and open development packages for the statistical programming language R, can be used for dissecting microarray data. We provide fundamental details that facilitate the process of getting started with R and Bioconductor. Using two publicly available microarray datasets from Aspergillus niger, we give detailed protocols on how to identify differentially expressed genes and how to construct gene coexpression networks.

VIZARD: analysis of Affymetrix Arabidopsis GeneChip data

NASA Technical Reports Server (NTRS)

Moseyko, Nick; Feldman, Lewis J.

2002-01-01

SUMMARY: The Affymetrix GeneChip Arabidopsis genome array has proved to be a very powerful tool for the analysis of gene expression in Arabidopsis thaliana, the most commonly studied plant model organism. VIZARD is a Java program created at the University of California, Berkeley, to facilitate analysis of Arabidopsis GeneChip data. It includes several integrated tools for filtering, sorting, clustering and visualization of gene expression data as well as tools for the discovery of regulatory motifs in upstream sequences. VIZARD also includes annotation and upstream sequence databases for the majority of genes represented on the Affymetrix Arabidopsis GeneChip array. AVAILABILITY: VIZARD is available free of charge for educational, research, and not-for-profit purposes, and can be downloaded at http://www.anm.f2s.com/research/vizard/ CONTACT: moseyko@uclink4.berkeley.edu.

Programming of mouse obesity by maternal exposure to concentrated ambient fine particles.

PubMed

Chen, Minjie; Wang, Xiaoke; Hu, Ziying; Zhou, Huifen; Xu, Yanyi; Qiu, Lianglin; Qin, Xiaobo; Zhang, Yuhao; Ying, Zhekang

2017-06-23

Many diseases including obesity may originate through alterations in the early-life environment that interrupts fetal development. Increasing evidence has shown that exposure to ambient fine particles (PM 2.5 ) is associated with abnormal fetal development. However, its long-term metabolic effects on offspring have not been systematically investigated. To determine if maternal exposure to PM 2.5 programs offspring obesity, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) during pre-conception, pregnancy, and lactation, and the developmental and metabolic responses of offspring were assessed. The growth trajectory of offspring revealed that maternal exposure to CAP significantly decreased offspring birth weight but increased body weight of adult male but not female offspring, and the latter was expressed as increased adiposity. These adult male offspring had increased food intake, but were sensitive to exogenous leptin. Their hypothalamic expression of Socs3 and Pomc, two target genes of leptin, was not changed, and the hypothalamic expression of NPY, an orexigenic peptide that is inhibited by leptin, was significantly increased. These decreases in central anorexigenic signaling were accompanied by reduced plasma leptin and its expression in adipose tissues, the primary source of circulating leptin. In contrast, maternal exposure did not significantly change any of these indexes in adult female offspring. Pyrosequencing demonstrated that the leptin promoter methylation of adipocytes was significantly increased in CAP-exposed male but not female offspring. Our data indicate that maternal exposure to ambient PM 2.5 programs obesity in male offspring probably through alterations in the methylation of the promoter region of the leptin gene.

A Transcriptional Program for Arbuscule Degeneration during AM Symbiosis Is Regulated by MYB1.

PubMed

Floss, Daniela S; Gomez, S Karen; Park, Hee-Jin; MacLean, Allyson M; Müller, Lena M; Bhattarai, Kishor K; Lévesque-Tremblay, Veronique; Maldonado-Mendoza, Ignacio E; Harrison, Maria J

2017-04-24

During the endosymbiosis formed between plants and arbuscular mycorrhizal (AM) fungi, the root cortical cells are colonized by branched hyphae called arbuscules, which function in nutrient exchange with the plant [1]. Despite their positive function, arbuscules are ephemeral structures, and their development is followed by a degeneration phase, in which the arbuscule and surrounding periarbuscular membrane and matrix gradually disappear from the root cell [2, 3]. Currently, the root cell's role in this process and the underlying regulatory mechanisms are unknown. Here, by using a Medicago truncatula pt4 mutant in which arbuscules degenerate prematurely [4], we identified arbuscule degeneration-associated genes, of which 38% are predicted to encode secreted hydrolases, suggesting a role in disassembly of the arbuscule and interface. Through RNAi and analysis of an insertion mutant, we identified a symbiosis-specific MYB-like transcription factor (MYB1) that suppresses arbuscule degeneration in mtpt4. In myb1, expression of several degeneration-associated genes is reduced. Conversely, in roots constitutively overexpressing MYB1, expression of degeneration-associated genes is increased and subsequent development of symbiosis is impaired. MYB1-regulated gene expression is enhanced by DELLA proteins and is dependent on NSP1 [5], but not NSP2 [6]. Furthermore, MYB1 interacts with DELLA and NSP1. Our data identify a transcriptional program for arbuscule degeneration and reveal that its regulators include MYB1 in association with two transcriptional regulators, NSP1 and DELLA, both of which function in preceding phases of the symbiosis. We propose that the combinatorial use of transcription factors enables the sequential expression of transcriptional programs for arbuscule development and degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

ExpressionDB: An open source platform for distributing genome-scale datasets.

PubMed

Hughes, Laura D; Lewis, Scott A; Hughes, Michael E

2017-01-01

RNA-sequencing (RNA-seq) and microarrays are methods for measuring gene expression across the entire transcriptome. Recent advances have made these techniques practical and affordable for essentially any laboratory with experience in molecular biology. A variety of computational methods have been developed to decrease the amount of bioinformatics expertise necessary to analyze these data. Nevertheless, many barriers persist which discourage new labs from using functional genomics approaches. Since high-quality gene expression studies have enduring value as resources to the entire research community, it is of particular importance that small labs have the capacity to share their analyzed datasets with the research community. Here we introduce ExpressionDB, an open source platform for visualizing RNA-seq and microarray data accommodating virtually any number of different samples. ExpressionDB is based on Shiny, a customizable web application which allows data sharing locally and online with customizable code written in R. ExpressionDB allows intuitive searches based on gene symbols, descriptions, or gene ontology terms, and it includes tools for dynamically filtering results based on expression level, fold change, and false-discovery rates. Built-in visualization tools include heatmaps, volcano plots, and principal component analysis, ensuring streamlined and consistent visualization to all users. All of the scripts for building an ExpressionDB with user-supplied data are freely available on GitHub, and the Creative Commons license allows fully open customization by end-users. We estimate that a demo database can be created in under one hour with minimal programming experience, and that a new database with user-supplied expression data can be completed and online in less than one day.

Patriot Express Program Could Be More Cost-Effective for Overseas Permanent Change of Station and Temporary Duty Travel

DTIC Science & Technology

2015-07-06

Department of Defense F r a u d , W a s t e & A b u s e Results in Brief Patriot Express Program Could Be More Cost-Effective for Overseas...availability for passengers traveling overseas. July 6, 2015 As a result , DoD did not maximize its return on investment in the Patriot Express Program and...comments from the Commander, Naval Supply Systems Command, partially addressed Recommendation 3.b. As a result of management comments, we redirected

Epidermal cornification is preceded by the expression of a keratinocyte-specific set of pyroptosis-related genes.

PubMed

Lachner, Julia; Mlitz, Veronika; Tschachler, Erwin; Eckhart, Leopold

2017-12-12

The homeostasis of the epidermis depends on keratinocyte differentiation and cornification, a mode of programmed cell death that does not elicit inflammation. Here, we report that cornification is associated with the expression of specific genes that control multiple steps of pyroptosis, another form of cell death that involves the processing and release of interleukin-1 family (IL1F) cytokines. Expression levels of pro-inflammatory IL1A and IL1B and of the pyroptotic pore-forming gasdermin (GSDM) D were downregulated during terminal differentiation of human keratinocytes in vitro. By contrast, negative regulators of IL-1 processing, including NLR family pyrin domain containing 10 (NLRP10) and pyrin domain-containing 1 (PYDC1), the anti-inflammatory IL1F members IL-37 (IL1F7) and IL-38 (IL1F10), and GSDMA, were strongly induced in differentiated keratinocytes. In human tissues, these keratinocyte differentiation-associated genes are expressed in the skin at higher levels than in any other organ, and mammalian species, that have lost the epidermal cornification program during evolution, i.e. whales and dolphins, lack homologs of these genes. Together, our results suggest that human epidermal cornification is accompanied by a tight control of pyroptosis and warrant further studies of potential defects in the balance between cornification and pyroptosis in skin pathologies.

"Like a family but better because you can actually trust each other": the Expect Respect dating violence prevention program for at-risk youth.

PubMed

Ball, Barbara; Kerig, Patricia K; Rosenbluth, Barri

2009-01-01

Expect Respect, a teen dating violence prevention program, was among four programs selected by the Centers for Disease Control and Prevention to participate in an empowerment evaluation project. As one aspect of this project, a qualitative study was designed to investigate the effects of Expect Respect support groups for at-risk youth. The goal was to understand the "how and why" of the program's impact on participants. Group interviews were conducted with five boys' and five girls' support groups after completion of the program. Settings included public middle and high schools and alternative schools in juvenile detention. Participants were asked to describe significant learning experiences in support groups as well as changes in their relationships resulting from program participation. Youths across all groups reported learning new skills including improved communication, anger control, and alternatives to violence. They reported increased knowledge about healthy relationships and warning signs of dating violence and expanded awareness of their own and others' abusive behaviors. Changed relationship norms were uniquely expressed by a boys' group in juvenile detention. Findings indicate that the experience of emotional safety in groups and positive relationships among group members were instrumental in the learning process.

Oligo Design: a computer program for development of probes for oligonucleotide microarrays.

PubMed

Herold, Keith E; Rasooly, Avraham

2003-12-01

Oligonucleotide microarrays have demonstrated potential for the analysis of gene expression, genotyping, and mutational analysis. Our work focuses primarily on the detection and identification of bacteria based on known short sequences of DNA. Oligo Design, the software described here, automates several design aspects that enable the improved selection of oligonucleotides for use with microarrays for these applications. Two major features of the program are: (i) a tiling algorithm for the design of short overlapping temperature-matched oligonucleotides of variable length, which are useful for the analysis of single nucleotide polymorphisms and (ii) a set of tools for the analysis of multiple alignments of gene families and related short DNA sequences, which allow for the identification of conserved DNA sequences for PCR primer selection and variable DNA sequences for the selection of unique probes for identification. Note that the program does not address the full genome perspective but, instead, is focused on the genetic analysis of short segments of DNA. The program is Internet-enabled and includes a built-in browser and the automated ability to download sequences from GenBank by specifying the GI number. The program also includes several utilities, including audio recital of a DNA sequence (useful for verifying sequences against a written document), a random sequence generator that provides insight into the relationship between melting temperature and GC content, and a PCR calculator.

Faith Is Confidence: The Implication of Psychosocial Components in Faith-Based Educational Programs on Expressive Communication Skills of Adult Learners

ERIC Educational Resources Information Center

Lynch, Erin M.

2016-01-01

Faith-based programs for adult learners have environmental factors that differentiate them from non-faith based programs, but explicit empirical studies evaluating the impact of the psychosocial factors have been lacking in the literature. This study comparatively examines the achievement level of expressive communication skills as measured…

Evaluation of a Classroom Program of Creative Expression Workshops for Refugee and Immigrant Children

ERIC Educational Resources Information Center

Rousseau, Cecile; Drapeau, Aline; Lacroix, Louise; Bagilishya, Deogratias; Heusch, Nicole

2005-01-01

Objective: This evaluative study assessed the effect of a creative expression program designed to prevent emotional and behavioral problems and to enhance self-esteem in immigrant and refugee children attending multiethnic schools. Method: The 12-week program involved 138 children, aged 7 to 13, registered in both integration classes designed for…

NTS American Indian Religious Freedom Act Compliance Program complying with AIRFA: A literature review and evaluation

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

Pippin, L.C.

The First Amendment to the United States Constitution guarantees the inherent right of all Americans to freedom of religion. However, since the religious practices of Native Americans are significantly different from those of the majority of Americans, their religious freedom has often restricted. Section 2 of the American Indian Religious Freedom Act (AIRFA) of 1978 (Public Law 95-341) directs federal agencies to consult with Native Americans to determine appropriate procedures to protect the inherent rights of Native Americans to believe, express, and exercise their traditional religions including, but not limited to access to sites, use and possession of sacred objects,more » and freedom to worship through ceremonials and traditional rites. The NTS AIRFA Compliance Program was initiated in October 1989 to assist DOE in expanding its compliance with AIRFA to incorporate all weapons testing activities on the NTS. It is directed at the development and implementation of a consultation plan designed to solicit, on behalf of DOE, Native American comments regarding the effects of the DOE's nuclear testing activities on historic properties of Native American origin and the expression and exercise of traditional Native American religions. The program has been developed around a phased approach that includes; (1) literature review and evaluation, (2) preparation of a baseline document, (3) preparation of a study design, (4) consultation with Native Americans, (5) preparation of a draft report, (6) Native American and State consultation and review, and (7) preparation of a final report.« less

NTS American Indian Religious Freedom Act Compliance Program complying with AIRFA: A literature review and evaluation

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

Pippin, L.C.

The First Amendment to the United States Constitution guarantees the inherent right of all Americans to freedom of religion. However, since the religious practices of Native Americans are significantly different from those of the majority of Americans, their religious freedom has often restricted. Section 2 of the American Indian Religious Freedom Act (AIRFA) of 1978 (Public Law 95-341) directs federal agencies to consult with Native Americans to determine appropriate procedures to protect the inherent rights of Native Americans to believe, express, and exercise their traditional religions including, but not limited to access to sites, use and possession of sacred objects,more » and freedom to worship through ceremonials and traditional rites. The NTS AIRFA Compliance Program was initiated in October 1989 to assist DOE in expanding its compliance with AIRFA to incorporate all weapons testing activities on the NTS. It is directed at the development and implementation of a consultation plan designed to solicit, on behalf of DOE, Native American comments regarding the effects of the DOE`s nuclear testing activities on historic properties of Native American origin and the expression and exercise of traditional Native American religions. The program has been developed around a phased approach that includes; (1) literature review and evaluation, (2) preparation of a baseline document, (3) preparation of a study design, (4) consultation with Native Americans, (5) preparation of a draft report, (6) Native American and State consultation and review, and (7) preparation of a final report.« less

Low-rank regularization for learning gene expression programs.

PubMed

Ye, Guibo; Tang, Mengfan; Cai, Jian-Feng; Nie, Qing; Xie, Xiaohui

2013-01-01

Learning gene expression programs directly from a set of observations is challenging due to the complexity of gene regulation, high noise of experimental measurements, and insufficient number of experimental measurements. Imposing additional constraints with strong and biologically motivated regularizations is critical in developing reliable and effective algorithms for inferring gene expression programs. Here we propose a new form of regulation that constrains the number of independent connectivity patterns between regulators and targets, motivated by the modular design of gene regulatory programs and the belief that the total number of independent regulatory modules should be small. We formulate a multi-target linear regression framework to incorporate this type of regulation, in which the number of independent connectivity patterns is expressed as the rank of the connectivity matrix between regulators and targets. We then generalize the linear framework to nonlinear cases, and prove that the generalized low-rank regularization model is still convex. Efficient algorithms are derived to solve both the linear and nonlinear low-rank regularized problems. Finally, we test the algorithms on three gene expression datasets, and show that the low-rank regularization improves the accuracy of gene expression prediction in these three datasets.

Landowner Satisfaction with the Wetland Reserve Program in Texas: A Mixed-Methods Analysis

NASA Astrophysics Data System (ADS)

Stroman, Dianne; Kreuter, Urs P.

2016-01-01

Using mail survey data and telephone interviews, we report on landowner satisfaction with permanent easements held by the Natural Resources Conservation Service (NRCS) throughout Texas. This study found that landowners were dissatisfied with the NRCS Wetland Reserve Program (WRP), conflicting with results of previous studies. The objective of this study was to explore specific reasons for frustration expressed by landowners with the program. We found three predominant themes underpinning program dissatisfaction: (1) upfront restoration failures, (2) overly restrictive easement constraints, and (3) bureaucratic hurdles limiting landowners' ability to conduct adaptive management on their easement property. The implications of this study suggest that attitudes of landowners participating in the WRP may limit the long-term effectiveness of this program. Suggestions for improving the program include implementing timely, ecologically sound restoration procedures and streamlining and simplifying the approval process for management activity requests. In addition, the NRCS should consider revising WRP restriction guidelines in order to provide more balance between protection goals and landowner autonomy.

Optometric Child Vision Care and Guidance. A Series of Papers Released by the Optometric Extension Program to its Membership 1966-1967.

ERIC Educational Resources Information Center

Optometric Extension Program, Duncan, OK.

The diagnosis and treatment of early learning problems and their relation to visual development is the subject of a series of 12 articles. The optometric viewpoint expressed is that vision is learned. A child's method of organizing his world, and manifestations of his disorganized behavior, including poor early academic achievement, probably…

Decentralized Real-Time Scheduling

DTIC Science & Technology

1990-08-01

must provide several alternative resource management policies, including FIFO and deadline queueing for shared resources that are not available. 5...When demand exceeds the supply of shared resources (even within a single switch), some calls cannot be completed. In that case, a call’s priority...associated chiefly with the need to manage resources in a timely and decentralized fashion. The Alpha programming model permits the convenient expression of

Inhibiting NANOG Enhances Efficacy of BH3 Mimetics | Center for Cancer Research

Cancer.gov

BCL-2 family proteins regulate cell fate. Some members promote cell survival while others induce programmed cell death. A third group, the BH3-only members, modulates the activities of the rest of the family. Some cancers, including those of the colon and rectum, express elevated levels of pro-survival BCL-2 members, which may protect cancer cells from chemotherapy. BH3

Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease

PubMed Central

Viola, Luciane F.; Nunes, Paula V.; Yassuda, Monica S.; Aprahamian, Ivan; Santos, Franklin S.; Santos, Glenda D.; Brum, Paula S.; Borges, Sheila M.; Oliveira, Alexandra M.; Chaves, Gisele F. S.; Ciasca, Eliane C.; Ferreira, Rita C. R.; de Paula, Vanessa J. R.; Takeda, Oswaldo H.; Mirandez, Roberta M.; Watari, Ricky; Falcão, Deusivania V. S.; Cachioni, Meire; Forlenza, Orestes V.

2011-01-01

OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatric symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment. PMID:21915490

The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

PubMed

Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

2015-07-10

Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions.

Research activities at the Loma Linda University and Proton Treatment Facility--an overview

NASA Technical Reports Server (NTRS)

Nelson, G. A.; Green, L. M.; Gridley, D. S.; Archambeau, J. O.; Slater, J. M.

2001-01-01

The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion-irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation.

TWIST1-induced microRNA-424 reversibly drives mesenchymal programming while inhibiting tumor initiation

PubMed Central

Drasin, David J.; Guarnieri, Anna L.; Neelakantan, Deepika; Kim, Jihye; Cabrera, Joshua H.; Wang, Chu-An; Zaberezhnyy, Vadym; Gasparini, Pierluigi; Cascione, Luciano; Huebner, Kay; Tan, Aik-Choon; Ford, Heide L.

2015-01-01

Epithelial-to-mesenchymal transition (EMT) is a dynamic process that relies on cellular plasticity. Recently, the process of an oncogenic EMT, followed by a reverse mesenchymal-to-epithelial transition (MET), has been implicated as critical in the metastatic colonization of carcinomas. Unlike governance of epithelial programming, regulation of mesenchymal programming is not well understood in EMT. Here, we describe and characterize the first microRNA that enhances exclusively mesenchymal programming. We demonstrate that microRNA-424 is upregulated early during a TWIST1 or SNAI1-induced EMT, and that it causes cells to express mesenchymal genes without affecting epithelial genes, resulting in a mixed/intermediate EMT. Furthermore, microRNA-424 increases motility, decreases adhesion and induces a growth arrest, changes associated with a complete EMT, that can be reversed when microRNA-424 expression is lowered, concomitant with an MET-like process. Breast cancer patient microRNA-424 levels positively associate with TWIST1/2 and EMT-like gene signatures, and miR-424 is increased in primary tumors versus matched normal breast. However, microRNA-424 is downregulated in patient metastases versus matched primary tumors. Correspondingly, microRNA-424 decreases tumor initiation and is post-transcriptionally downregulated in macrometastases in mice, suggesting the need for biphasic expression of miR-424 to transit the EMT-MET axis. Next-generation RNA sequencing revealed microRNA-424 regulates numerous EMT and cancer stemness-associated genes, including TGFBR3, whose downregulation promotes mesenchymal phenotypes, but not tumor-initiating phenotypes. Instead, we demonstrate that increased MAPK/ERK signaling is critical for miR-424-mediated decreases in tumor-initiating phenotypes. These findings suggest microRNA-424 plays distinct roles in tumor progression, potentially facilitating earlier, but repressing later, stages of metastasis by regulating an EMT-MET axis. PMID:25716682

PAVE: program for assembling and viewing ESTs.

PubMed

Soderlund, Carol; Johnson, Eric; Bomhoff, Matthew; Descour, Anne

2009-08-26

New sequencing technologies are rapidly emerging. Many laboratories are simultaneously working with the traditional Sanger ESTs and experimenting with ESTs generated by the 454 Life Science sequencers. Though Sanger ESTs have been used to generate contigs for many years, no program takes full advantage of the 5' and 3' mate-pair information, hence, many tentative transcripts are assembled into two separate contigs. The new 454 technology has the benefit of high-throughput expression profiling, but introduces time and space problems for assembling large contigs. The PAVE (Program for Assembling and Viewing ESTs) assembler takes advantage of the 5' and 3' mate-pair information by requiring that the mate-pairs be assembled into the same contig and joined by n's if the two sub-contigs do not overlap. It handles the depth of 454 data sets by "burying" similar ESTs during assembly, which retains the expression level information while circumventing time and space problems. PAVE uses MegaBLAST for the clustering step and CAP3 for assembly, however it assembles incrementally to enforce the mate-pair constraint, bury ESTs, and reduce incorrect joins and splits. The PAVE data management system uses a MySQL database to store multiple libraries of ESTs along with their metadata; the management system allows multiple assemblies with variations on libraries and parameters. Analysis routines provide standard annotation for the contigs including a measure of differentially expressed genes across the libraries. A Java viewer program is provided for display and analysis of the results. Our results clearly show the benefit of using the PAVE assembler to explicitly use mate-pair information and bury ESTs for large contigs. The PAVE assembler provides a software package for assembling Sanger and/or 454 ESTs. The assembly software, data management software, Java viewer and user's guide are freely available.

2009 Canadian Radiation Oncology Resident Survey

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

Debenham, Brock, E-mail: debenham@ualberta.net; Banerjee, Robyn; Fairchild, Alysa

2012-03-15

Purpose: Statistics from the Canadian post-MD education registry show that numbers of Canadian radiation oncology (RO) trainees have risen from 62 in 1999 to approximately 150 per year between 2003 and 2009, contributing to the current perceived downturn in employment opportunities for radiation oncologists in Canada. When last surveyed in 2003, Canadian RO residents identified job availability as their main concern. Our objective was to survey current Canadian RO residents on their training and career plans. Methods and Materials: Trainees from the 13 Canadian residency programs using the national matching service were sought. Potential respondents were identified through individual programmore » directors or chief resident and were e-mailed a secure link to an online survey. Descriptive statistics were used to report responses. Results: The eligible response rate was 53% (83/156). Similar to the 2003 survey, respondents generally expressed high satisfaction with their programs and specialty. The most frequently expressed perceived weakness in their training differed from 2003, with 46.5% of current respondents feeling unprepared to enter the job market. 72% plan on pursuing a postresidency fellowship. Most respondents intend to practice in Canada. Fewer than 20% of respondents believe that there is a strong demand for radiation oncologists in Canada. Conclusions: Respondents to the current survey expressed significant satisfaction with their career choice and training program. However, differences exist compared with the 2003 survey, including the current perceived lack of demand for radiation oncologists in Canada.« less

State-by-state variations in cardiac rehabilitation participation are associated with educational attainment, income, and program availability.

PubMed

Gaalema, Diann E; Higgins, Stephen T; Shepard, Donald S; Suaya, Jose A; Savage, Patrick D; Ades, Philip A

2014-01-01

Wide geographic variations in cardiac rehabilitation (CR) participation in the United States have been demonstrated but are not well understood. Socioeconomic factors such as educational attainment are robust predictors of many health-related behaviors, including smoking, obesity, physical activity, substance abuse, and cardiovascular disease. We investigated potential associations between state-level differences in educational attainment, other socioeconomic factors, CR program availability, and variations in CR participation. A retrospective database analysis was conducted using data from the US Census Bureau, the Centers for Disease Control and Prevention, and the 1997 Medicare database. The outcome of interest was CR participation rates by state, and predictors included state-level high school (HS) graduation rates (in 2001 and 1970), median household income, smoking rates, density of CR program (programs per square mile and per state population), sex and race ratios, and median age. The relationship between HS graduation rates and CR participation by state was significant for both 2001 and 1970 (r = 0.64 and 0.44, respectively, P < .01). Adding the density of CR programs (per population) and income contributed significantly with a cumulative r value of 0.74 and 0.71 for the models using 2001 and 1970, respectively (Ps < .01). The amount of variance accounted for by each of the 3 variables differed between the 2000 and 1970 graduation rates, but both models were unaltered by including additional variables. State-level HS graduation rates, CR programs expressed as programs per population, and median income were strongly associated with geographic variations in CR participation rates.

SYMBMAT: Symbolic computation of quantum transition matrix elements

NASA Astrophysics Data System (ADS)

Ciappina, M. F.; Kirchner, T.

2012-08-01

We have developed a set of Mathematica notebooks to compute symbolically quantum transition matrices relevant for atomic ionization processes. The utilization of a symbolic language allows us to obtain analytical expressions for the transition matrix elements required in charged-particle and laser induced ionization of atoms. Additionally, by using a few simple commands, it is possible to export these symbolic expressions to standard programming languages, such as Fortran or C, for the subsequent computation of differential cross sections or other observables. One of the main drawbacks in the calculation of transition matrices is the tedious algebraic work required when initial states other than the simple hydrogenic 1s state need to be considered. Using these notebooks the work is dramatically reduced and it is possible to generate exact expressions for a large set of bound states. We present explicit examples of atomic collisions (in First Born Approximation and Distorted Wave Theory) and laser-matter interactions (within the Dipole and Strong Field Approximations and different gauges) using both hydrogenic wavefunctions and Slater-Type Orbitals with arbitrary nlm quantum numbers as initial states. Catalogue identifier: AEMI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEMI_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC license, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 71 628 No. of bytes in distributed program, including test data, etc.: 444 195 Distribution format: tar.gz Programming language: Mathematica Computer: Single machines using Linux or Windows (with cores with any clock speed, cache memory and bits in a word) Operating system: Any OS that supports Mathematica. The notebooks have been tested under Windows and Linux and with versions 6.x, 7.x and 8.x Classification: 2.6 Nature of problem: The notebooks generate analytical expressions for quantum transition matrix elements required in diverse atomic processes: ionization by ion, electron, or photon impact and ionization within the framework of strong field physics. In charged-particle collisions approaches based on perturbation theory enjoy widespread utilization. Accordingly, we have chosen the First Born Approximation and Distorted Wave theories as examples. In light-matter interactions, the main ingredient for many types of calculations is the dipole transition matrix in its different formulations, i.e. length, velocity, and acceleration gauges. In all these cases the transitions of interest occur between a bound state and a continuum state which can be described in different ways. With the notebooks developed in the present work it is possible to calculate transition matrix elements analytically for any set of quantum numbers nlm of initial hydrogenic states or Slater-Type Orbitals and for plane waves or Coulomb waves as final continuum states. Solution method: The notebooks employ symbolic computation to generate analytical expressions for transition matrix elements used in both collision and light-matter interaction physics. fba_hyd.nb - This notebook computes analytical expressions for the transition matrix of collision-induced ionization in the First Born Approximation (FBA). The transitions considered are from a bound hydrogenic state with arbitrary quantum numbers nlm to a continuum state represented by a plane wave (PW) or a Coulomb wave (CW). distorted_hyd.nb - This notebook computes analytical expressions for the transition matrix of collision-induced ionization in Distorted Wave (DW) theories. The transitions considered are from a (distorted) bound hydrogenic state with arbitrary quantum numbers nlm to a distorted-wave continuum state. The computations are based on scalar and vectorial integrals (see the text for details). dipoleLength_hyd.nb - This notebook computes analytical expressions for the dipole transition matrix in length gauge. The transitions considered are from a bound hydrogenic state with arbitrary quantum numbers nlm to a continuum state represented by a PW (the Strong Field Approximation (SFA)) or a CW (the Coulomb-Volkov Approximation (CVA)). dipoleVelocity_hyd.nb - This notebook computes analytical expressions for the dipole transition matrix in velocity gauge. The transitions considered are from a bound hydrogenic state with arbitrary quantum numbers nlm to a continuum state represented by a PW (the SFA) or a CW (the CVA). dipoleAcceleration_hyd.nb - This notebook computes analytical expressions for the dipole transition matrix in acceleration gauge. The transitions considered are from a bound hydrogenic state with arbitrary quantum numbers nlm to a continuum state represented by a PW (the SFA). For the case of the CVA we only include the transition from the 1s state to a continuum state represented by a CW. fba_STO.nb - This notebook computes analytical expressions for the transition matrix of collision-induced ionization in the FBA. The transitions considered are from a Slater-Type Orbital (STO) with arbitrary quantum numbers nlm to a continuum state represented by a PW or a CW. distorted_STO.nb - This notebook computes analytical expressions for the transition matrix of collision-induced ionization in DW theories. The transitions considered are from a (distorted) STO with arbitrary quantum numbers nlm to a distorted-wave continuum state. The computations are based on scalar and vectorial integrals (see the text for details). dipoleLength_STO.nb - This notebook computes analytical expressions for the dipole transition matrix in length gauge. The transitions considered are from an STO with arbitrary quantum numbers nlm to a continuum state represented by a PW (the SFA) or a CW (the CVA). dipoleVelocity_STO.nb - This notebook computes analytical expressions for the dipole transition matrix in velocity gauge. The transitions considered are from an STO with arbitrary quantum numbers nlm to a continuum state represented by a PW (the SFA) or a CW (the CVA). dipoleAcceleration_STO.nb - This notebook computes analytical expressions for the dipole transition matrix in acceleration gauge. The transitions considered are from an STO with arbitrary quantum numbers nlm to a continuum state represented by a PW (the SFA). The symbolic expressions obtained within each notebook can be exported to standard programming languages such as Fortran or C using the Format.m package (see the text and Ref. Sofroniou (1993) [16] for details). Running time: Computational times vary according to the transition matrix selected and quantum numbers nlm of the initial state used. The typical running time is several minutes, but it will take longer for large values of nlm.

Dexamethasone and sex regulate placental glucocorticoid receptor isoforms in mice.

PubMed

Cuffe, James S M; Saif, Zarqa; Perkins, Anthony V; Moritz, Karen M; Clifton, Vicki L

2017-08-01

Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocorticoid receptor (GR) isoforms to regulate gene transcription and cellular signaling. We hypothesized that sexually dimorphic placental responses to glucocorticoids are due to differences in GR isoforms present in the placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5 until E14.5 (1 µg/kg/h) before the collection of placentae. Cytoplasmic and nuclear protein fractions were extracted from placentae of male and female fetuses for Western blot analysis of GR isoforms. Eight known isoforms of the GR were detected in the mouse placenta including the translational isoforms GRα-A, B, C and D1-3 and the splice variants GRA and GRP. The expression of GRA, GRP and each of the GRα isoforms were altered by dexamethasone in relation to fetal sex and cellular location. Placentae of female fetuses had higher GRα-A and GRP expression in the cytoplasm than males, and GRα-C was more highly expressed in the nucleus of females than that in males. Dexamethasone significantly increased the cytoplasmic expression of GRα-A, but reduced the expression of GRα-C in placentae of males. Dexamethasone increased the expression of the GRα-C-regulated genes Sgk1 and Bcl2l11 , particularly in females. The cleaved caspase-3 staining in placental sections indicated GRα-C may mediate sex differences in dexamethasone-induced apoptosis. These findings may underlie the sex-specific placental adaptations that regulate different growth profiles in males and females and different risks for programmed disease outcomes in offspring. © 2017 Society for Endocrinology.

Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression.

PubMed

Schwarz, Jaclyn M; Hutchinson, Mark R; Bilbo, Staci D

2011-12-07

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene × early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior.

Early-Life Experience Decreases Drug-Induced Reinstatement of Morphine CPP in Adulthood via Microglial-Specific Epigenetic Programming of Anti-Inflammatory IL-10 Expression

PubMed Central

Schwarz, Jaclyn M.; Hutchinson, Mark R.; Bilbo, Staci D.

2012-01-01

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat Nucleus Accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with Ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene X early-life environment interaction on morphine-induced glial activation, and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior. PMID:22159099

Genetic analyses of Per.C6 cell clones producing a therapeutic monoclonal antibody regarding productivity and long-term stability.

PubMed

Tsuruta, Lilian Rumi; Lopes Dos Santos, Mariana; Yeda, Fernanda Perez; Okamoto, Oswaldo Keith; Moro, Ana Maria

2016-12-01

Genetic characterization of protein-producing clones represents additional value to cell line development. In the present study, ten Per.C6 clones producing a Rebmab100 monoclonal antibody were selected using two cloning methods: six clones originated from limiting dilution cloning and four by the automated colony picker ClonePix FL. A stability program was performed for 50 generations, including 4 batches distributed along the timeframe to determine specific productivity (Qp) maintenance. Four stable clones (two from limiting dilution and two from ClonePix FL) were further evaluated. The relative mRNA expression levels of both heavy chain (HC) and light chain (LC) genes were verified at generations 0, 30-35, and 50-55 of the stability program. At generations 0 and 30-35, LC gene expression level was higher than HC gene, whereas at generation 50-55, the opposite prevailed. A high correlation was observed between Qp and HC or LC mRNA expression level for all clones at each generation analyzed along the continuous culture. The mRNA stability study was performed at steady-state culture. The LC gene displayed a higher half-life and lower decay constant than HC gene, accounting for the higher observed expression level of LC mRNA in comparison to HC mRNA. Clone R6 was highlighted due its high Qp, mRNA expression levels, and mRNA stability. Besides the benefits of applying genetic characterization for the selection of stable and high-producing clones, the present study shows for the first time the correlation between Qp and HC or LC expression levels and also mRNA stability in clones derived from human cell line Per.C6(®).

Interspecific and host-related gene expression patterns in nematode-trapping fungi.

PubMed

Andersson, Karl-Magnus; Kumar, Dharmendra; Bentzer, Johan; Friman, Eva; Ahrén, Dag; Tunlid, Anders

2014-11-11

Nematode-trapping fungi are soil-living fungi that capture and kill nematodes using special hyphal structures called traps. They display a large diversity of trapping mechanisms and differ in their host preferences. To provide insights into the genetic basis for this variation, we compared the transcriptome expressed by three species of nematode-trapping fungi (Arthrobotrys oligospora, Monacrosporium cionopagum and Arthrobotrys dactyloides, which use adhesive nets, adhesive branches or constricting rings, respectively, to trap nematodes) during infection of two different plant-pathogenic nematode hosts (the root knot nematode Meloidogyne hapla and the sugar beet cyst nematode Heterodera schachtii). The divergence in gene expression between the fungi was significantly larger than that related to the nematode species being infected. Transcripts predicted to encode secreted proteins and proteins with unknown function (orphans) were overrepresented among the highly expressed transcripts in all fungi. Genes that were highly expressed in all fungi encoded endopeptidases, such as subtilisins and aspartic proteases; cell-surface proteins containing the carbohydrate-binding domain WSC; stress response proteins; membrane transporters; transcription factors; and transcripts containing the Ricin-B lectin domain. Differentially expressed transcripts among the fungal species encoded various lectins, such as the fungal fruit-body lectin and the D-mannose binding lectin; transcription factors; cell-signaling components; proteins containing a WSC domain; and proteins containing a DUF3129 domain. A small set of transcripts were differentially expressed in infections of different host nematodes, including peptidases, WSC domain proteins, tyrosinases, and small secreted proteins with unknown function. This is the first study on the variation of infection-related gene expression patterns in nematode-trapping fungi infecting different host species. A better understanding of these patterns will facilitate the improvements of these fungi in biological control programs, by providing molecular markers for screening programs and candidates for genetic manipulations of virulence and host preferences.

PD-L1 expression in extrahepatic cholangiocarcinoma.

PubMed

Walter, Dirk; Herrmann, Eva; Schnitzbauer, Andreas A; Zeuzem, Stefan; Hansmann, Martin Leo; Peveling-Oberhag, Jan; Hartmann, Sylvia

2017-09-01

To investigate the expression of the programmed cell death 1 (PD-1) receptor-programmed cell death ligand 1 (PD-L1) pathway and the clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). Tissue samples from patients with eCCA [n = 69; perihilar cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression, and correlations with clinicopathological characteristics, including survival data, were determined. PD-L1 was found on both tumour cells of eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant correlations of PD-L1 expression on cancer cells with venous invasion (P = 0.031) and poor differentiation of the tumour (P = 0.048) were observed. In 19 of 69 (27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas infiltration with CD3-positive and CD163-positive cells was found in 63 of 69 (91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five CD3-positive cells per high-power field was significantly correlated with poorer differentiation (P = 0.015) and venous invasion (P < 0.001) of CCA. PD-L1 expression was not correlated with patient survival, but PD-L1 expression on tumour cells combined with low infiltration of CD3-positive TILs was associated with an unfavourable outcome (P = 0.027). Only a small number of eCCA patients are PD-L1-positive, which might be important for future application of PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more invasive growth and worse overall survival. © 2017 John Wiley & Sons Ltd.

Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non-Small Cell Lung Cancer.

PubMed

Sepesi, Boris; Cuentas, Edwin Parra; Canales, Jaime Rodriguez; Behrens, Carmen; Correa, Arlene M; Vaporciyan, Ara; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar; Swisher, Stephen; Wistuba, Ignacio

2017-01-01

Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis. Statistics included recursive partitioning, univariable, multivariable, and Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87) experienced significantly better overall survival (OS) (P = 0.001) than patients with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N = 24) also experienced significantly better (P = 0.005) OS than patients with >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1 expression in both tumor and macrophages with 5-year OS of 94% (N = 17). Contrarily, patients with high PD-L1 expression in both tumor and macrophages experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in the TIMs was independently associated with survival in multivariable analysis (P = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and in the TIMs seems to be associated with significantly better OS in surgically resected stage I lung cancer. Additional studies are needed to validate PD-L1 as a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Nutrition Interventions for Prevention and Management of Childhood Obesity: What Do Parents Want from an eHealth Program?

PubMed

Burrows, Tracy; Hutchesson, Melinda; Chai, Li Kheng; Rollo, Megan; Skinner, Geoff; Collins, Clare

2015-12-15

With the growth of Internet technologies, offering interventions for child and family weight management in an online format may address barriers to accessing services. This study aimed to investigate (i) whether an eHealth family healthy lifestyle program would be of interest to parents; and (ii) preferences and/or expectations for program components and features. Parents of children aged four to18 years were recruited through social media and completed an online survey (54 items) including closed and open-ended questions. Responses were collated using descriptive statistics and thematic analysis. Seventy-five participants were included (92% mothers, mean age 39.1 ± 8.6 years, mean BMI 27.6 ± 6.3 kg/m²). The index child had a mean age of 11 ± 6.2 years with 24% overweight/obese. The majority of parents (90.3%) reported interest in an online program, with preference expressed for a non-structured program to allow flexibility users to log-on and off as desired. Parents wanted a program that was easy to use, practical, engaging, endorsed by a reputable source, and able to provide individual tailoring and for their children to be directly involved. The current study supports the need for online delivery of a healthy lifestyle program that targets greater parental concerns of diet rather than child weight.

Molecular Validation of Chondrogenic Differentiation and Hypoxia Responsiveness of Platelet-Lysate Expanded Adipose Tissue-Derived Human Mesenchymal Stromal Cells.

PubMed

Galeano-Garces, Catalina; Camilleri, Emily T; Riester, Scott M; Dudakovic, Amel; Larson, Dirk R; Qu, Wenchun; Smith, Jay; Dietz, Allan B; Im, Hee-Jeong; Krych, Aaron J; Larson, A Noelle; Karperien, Marcel; van Wijnen, Andre J

2017-07-01

To determine the optimal environmental conditions for chondrogenic differentiation of human adipose tissue-derived mesenchymal stromal/stem cells (AMSCs). In this investigation we specifically investigate the role of oxygen tension and 3-dimensional (3D) culture systems. Both AMSCs and primary human chondrocytes were cultured for 21 days in chondrogenic media under normoxic (21% oxygen) or hypoxic (2% oxygen) conditions using 2 distinct 3D culture methods (high-density pellets and poly-ε-caprolactone [PCL] scaffolds). Histologic analysis of chondro-pellets and the expression of chondrocyte-related genes as measured by reverse transcriptase quantitative polymerase chain reaction were used to evaluate the efficiency of differentiation. AMSCs are capable of expressing established cartilage markers including COL2A1, ACAN, and DCN when grown in chondrogenic differentiation media as determined by gene expression and histologic analysis of cartilage markers. Expression of several cartilage-related genes was enhanced by low oxygen tension, including ACAN and HAPLN1. The pellet culture environment also promoted the expression of hypoxia-inducible cartilage markers compared with cells grown on 3D scaffolds. Cell type-specific effects of low oxygen and 3D environments indicate that mesenchymal cell fate and differentiation potential is remarkably sensitive to oxygen. Genetic programming of AMSCs to a chondrocytic phenotype is effective under hypoxic conditions as evidenced by increased expression of cartilage-related biomarkers and biosynthesis of a glycosaminoglycan-positive matrix. Lower local oxygen levels within cartilage pellets may be a significant driver of chondrogenic differentiation.

Consumer acceptance of irradiated food: theory and reality

NASA Astrophysics Data System (ADS)

Bruhn, Christine M.

1998-06-01

For years most consumers have expressed less concern about food irradiation than other food processing technologies. Attitude studies have demonstrated that when given science-based information, from 60% to 90% of consumers prefer the advantages irradiation processing provides. When information is accompanied by samples, acceptance may increase to 99%. Information on irradiation should include product benefits, safety and wholesomeness, address environmental safety issues, and include endorsements by recognized health authorities. Educational and marketing programs should now be directed toward retailers and processors. Given the opportunity, consumers will buy high quality, safety-enhanced irradiated food.

Artificial Intelligence Tools for Scaling Up of High Shear Wet Granulation Process.

PubMed

Landin, Mariana

2017-01-01

The results presented in this article demonstrate the potential of artificial intelligence tools for predicting the endpoint of the granulation process in high-speed mixer granulators of different scales from 25L to 600L. The combination of neurofuzzy logic and gene expression programing technologies allowed the modeling of the impeller power as a function of operation conditions and wet granule properties, establishing the critical variables that affect the response and obtaining a unique experimental polynomial equation (transparent model) of high predictability (R 2 > 86.78%) for all size equipment. Gene expression programing allowed the modeling of the granulation process for granulators of similar and dissimilar geometries and can be improved by implementing additional characteristics of the process, as composition variables or operation parameters (e.g., batch size, chopper speed). The principles and the methodology proposed here can be applied to understand and control manufacturing process, using any other granulation equipment, including continuous granulation processes. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Stress-responsive microRNAs are involved in re-programming of metabolic functions in hibernators.

PubMed

Arfat, Yasir; Chang, Hui; Gao, Yunfang

2018-04-01

Mammalian hibernation includes re-programing of metabolic capacities, partially, encouraged by microRNAs (miRNAs). Albeit much is known about the functions of miRNAs, we need learning on low temperature miRNAs target determination. As hibernators can withstand low body temperatures (TB) for a long time without anguish tissue damage, understanding the means and mechanisms that empower them to do as such are of restorative intrigue. Nonetheless, these mechanisms by which miRNAs and the hibernators react to stressful conditions are not much clear. It is evident from recent data that the gene expression and the translation of mRNA to protein are controlled by miRNAs. The miRNAs also influence regulation of major cellular processes. As the significance of miRNAs in stress conditions adaptation are getting clearer, this audit article abridges the key alterations in miRNA expression and the mechanism that facilitates stress survival. © 2017 Wiley Periodicals, Inc.

Lack of A-factor production induces the expression of nutrient scavenging and stress-related proteins in Streptomyces griseus.

PubMed

Birkó, Zsuzsanna; Swiatek, Magdalena; Szájli, Emília; Medzihradszky, Katalin F; Vijgenboom, Erik; Penyige, András; Keseru, Judit; van Wezel, Gilles P; Biró, Sándor

2009-10-01

The small gamma-butyrolactone A-factor is an important autoregulatory signaling molecule for the soil-inhabiting streptomycetes. Starvation is a major trigger for development, and nutrients are provided by degradation of the vegetative mycelium via a process of programmed cell death, reusing proteins, nucleic acids, and cell wall material. The A-factor regulon includes many extracellular hydrolases. Here we show via proteomics analysis that many nutrient-scavenging and stress-related proteins were overexpressed in an A-factor non-producing mutant of Streptomyces griseus B-2682. Transcript analysis showed that this is primarily due to differential transcription of the target genes during early development. The targets include proteins relating to nutrient stress and environmental stress and an orthologue of the Bacillus sporulation control protein Spo0M. The enhanced expression of these proteins underlines the stress that is generated by the absence of A-factor. Wild-type developmental gene expression was restored to the A-factor non-producing mutant by the signaling protein Factor C in line with our earlier observation that Factor C triggers A-factor production.

The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

PubMed

Ortega-Molina, Ana; Boss, Isaac W; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A; Gascoyne, Randy D; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M; Wendel, Hans-Guido

2015-10-01

The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.

The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development

PubMed Central

Ortega-Molina, Ana; Boss, Isaac W.; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W.; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A.; Gascoyne, Randy D.; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M.; Wendel, Hans-Guido

2015-01-01

The lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). However, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center (GC) involution, impedes B cell differentiation and class switch recombination (CSR). Integrative genomic analyses indicate that KMT2D affects H3K4 methylation and expression of a specific set of genes including those in the CD40, JAK-STAT, Toll-like receptor, and B cell receptor pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3, and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell activating pathways. PMID:26366710

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway

PubMed Central

Ahmed, Mohammed I.; Alam, Majid; Emelianov, Vladimir U.; Poterlowicz, Krzysztof; Patel, Ankit; Sharov, Andrey A.; Mardaryev, Andrei N.

2014-01-01

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging. PMID:25422376

Aspect-Oriented Programming

NASA Technical Reports Server (NTRS)

Elrad, Tzilla (Editor); Filman, Robert E. (Editor); Bader, Atef (Editor)

2001-01-01

Computer science has experienced an evolution in programming languages and systems from the crude assembly and machine codes of the earliest computers through concepts such as formula translation, procedural programming, structured programming, functional programming, logic programming, and programming with abstract data types. Each of these steps in programming technology has advanced our ability to achieve clear separation of concerns at the source code level. Currently, the dominant programming paradigm is object-oriented programming - the idea that one builds a software system by decomposing a problem into objects and then writing the code of those objects. Such objects abstract together behavior and data into a single conceptual and physical entity. Object-orientation is reflected in the entire spectrum of current software development methodologies and tools - we have OO methodologies, analysis and design tools, and OO programming languages. Writing complex applications such as graphical user interfaces, operating systems, and distributed applications while maintaining comprehensible source code has been made possible with OOP. Success at developing simpler systems leads to aspirations for greater complexity. Object orientation is a clever idea, but has certain limitations. We are now seeing that many requirements do not decompose neatly into behavior centered on a single locus. Object technology has difficulty localizing concerns invoking global constraints and pandemic behaviors, appropriately segregating concerns, and applying domain-specific knowledge. Post-object programming (POP) mechanisms that look to increase the expressiveness of the OO paradigm are a fertile arena for current research. Examples of POP technologies include domain-specific languages, generative programming, generic programming, constraint languages, reflection and metaprogramming, feature-oriented development, views/viewpoints, and asynchronous message brokering. (Czarneclu and Eisenecker s book includes a good survey of many of these technologies).

The Mediator complex and transcription regulation

PubMed Central

Poss, Zachary C.; Ebmeier, Christopher C.

2013-01-01

The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

No boundaries: genomes, organisms, and ecological interactions responsible for divergence and reproductive isolation.

PubMed

Etges, William J

2014-01-01

Revealing the genetic basis of traits that cause reproductive isolation, particularly premating or sexual isolation, usually involves the same challenges as most attempts at genotype-phenotype mapping and so requires knowledge of how these traits are expressed in different individuals, populations, and environments, particularly under natural conditions. Genetic dissection of speciation phenotypes thus requires understanding of the internal and external contexts in which underlying genetic elements are expressed. Gene expression is a product of complex interacting factors internal and external to the organism including developmental programs, the genetic background including nuclear-cytotype interactions, epistatic relationships, interactions among individuals or social effects, stochasticity, and prevailing variation in ecological conditions. Understanding of genomic divergence associated with reproductive isolation will be facilitated by functional expression analysis of annotated genomes in organisms with well-studied evolutionary histories, phylogenetic affinities, and known patterns of ecological variation throughout their life cycles. I review progress and prospects for understanding the pervasive role of host plant use on genetic and phenotypic expression of reproductive isolating mechanisms in cactophilic Drosophila mojavensis and suggest how this system can be used as a model for revealing the genetic basis for species formation in organisms where speciation phenotypes are under the joint influences of genetic and environmental factors. © The American Genetic Association. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Metabolic Adaptation to Nutrients Involves Coregulation of Gene Expression by the RNA Helicase Dbp2 and the Cyc8 Corepressor in Saccharomyces cerevisiae.

PubMed

Wang, Siwen; Xing, Zheng; Pascuzzi, Pete E; Tran, Elizabeth J

2017-07-05

Cells fine-tune their metabolic programs according to nutrient availability in order to maintain homeostasis. This is achieved largely through integrating signaling pathways and the gene expression program, allowing cells to adapt to nutritional change. Dbp2, a member of the DEAD-box RNA helicase family in Saccharomyces cerevisiae , has been proposed to integrate gene expression with cellular metabolism. Prior work from our laboratory has reported the necessity of DBP2 in proper gene expression, particularly for genes involved in glucose-dependent regulation. Here, by comparing differentially expressed genes in dbp2 ∆ to those of 700 other deletion strains from other studies, we find that CYC8 and TUP1 , which form a complex and inhibit transcription of numerous genes, corepress a common set of genes with DBP2 Gene ontology (GO) annotations reveal that these corepressed genes are related to cellular metabolism, including respiration, gluconeogenesis, and alternative carbon-source utilization genes. Consistent with a direct role in metabolic gene regulation, loss of either DBP2 or CYC8 results in increased cellular respiration rates. Furthermore, we find that corepressed genes have a propensity to be associated with overlapping long noncoding RNAs and that upregulation of these genes in the absence of DBP2 correlates with decreased binding of Cyc8 to these gene promoters. Taken together, this suggests that Dbp2 integrates nutrient availability with energy homeostasis by maintaining repression of glucose-repressed, Cyc8-targeted genes across the genome. Copyright © 2017 Wang et al.

The Humans in Space Art Program - Engaging the Mind, and the Heart, in Science

NASA Astrophysics Data System (ADS)

McPhee, J. C.

2017-12-01

How can we do a better job communicating about space, science and technology, getting more people engaged, understanding the impact that future space exploration will have on their lives, and thinking about how they can contribute? Humans naturally express their visions and interests through various forms of artistic expression because art is inherently capable of expressing not only the "what and how" but also the "why" of ideas. Offering opportunities that integrate space, science and technology with art allows more people to learn about space, relay their visions of the future, and discuss why exploration and research are important. The Humans in Space Art Program, managed by the nonprofit SciArt Exchange, offers a science-integrated-with-art opportunity. Through international online competitions, we invite participants to share their visions of the future using visual, literary, musical and video art. We then use their artwork in multi-media displays and live performances online, locally worldwide, and in space to engage listeners and viewers. The Program has three projects, targeting different types of participants: the Youth Competition (ages 10-18), the Challenge (college and early career) and Celebrity Artist-Fed Engagement (CAFÉ: professional artists). To date, the Program has received 3400 artworks from over 52 countries and displayed the artwork in 110 multi-media events worldwide, on the International Space Station and bounced off the Moon. 100,000's have thus viewed artwork considering topics such as: why we explore; where and how we will go and when; and what we will do when we arrive. The Humans in Space Art Program is a flexible public engagement model applicable to multiple settings, including classrooms, art and entertainment events, and scientific conferences. It provides a system to accessibly inspire all ages about space, science and technology, making them hungry to learn more and to take a personal role.

The Keys to Success in Doctoral Studies: A Preimmersion Course.

PubMed

Salani, Deborah; Albuja, Laura Dean; Azaiza, Khitam

2016-01-01

This article will review an innovative on-line preimmersion course for a hybrid doctor of nursing practice (DNP) program and a traditional face-to-face doctor of philosophy nursing program. The doctoral candidates include both postbaccalaureate and postmaster's students. The authors of the preimmersion course developed and initiated the course in order to address various issues that have surfaced in discussions between students and faculty. Examples of common themes identified include writing skills, statistics, life-work-school balance, and navigating instructional technology. Doctoral studies may pose challenges to students studying nursing, in regard to academic rigor and experiencing on-line education for the first time, especially for students who have been out of school for an extended amount of time or are not accustomed to a nontraditional classroom; thus, having a preimmersion course established may facilitate a smooth transition to rigorous academic studies in a hybrid program. The course, which was developed and delivered through Blackboard, a learning management system, includes the following 9 preimmersion modules: academic strategies (learning styles, creating an effective PowerPoint presentation), library support (introduction to the university library, literature review tutorial, and citation styles), mindfulness, wellness, statistics essentials, writing express, DNP capstone, netiquette, and DNP/doctor of philosophy mentorship. Each module consists of various tools that may promote student success in specific courses and the programs in general. The purpose of designing the preimmersion course is to decrease attrition rates and increase success of the students. While the majority of students have succeeded in their coursework and been graduated from the program, the authors of this article found that many students struggled with the work, life, and school balance. Future work will include the evaluation of results from graduate students enrolled in the program. Copyright © 2016 Elsevier Inc. All rights reserved.

User's guide to PHREEQC (Version 2) : a computer program for speciation, batch-reaction, one-dimensional transport, and inverse geochemical calculations

USGS Publications Warehouse

Parkhurst, David L.; Appelo, C.A.J.

1999-01-01

PHREEQC version 2 is a computer program written in the C programming language that is designed to perform a wide variety of low-temperature aqueous geochemical calculations. PHREEQC is based on an ion-association aqueous model and has capabilities for (1) speciation and saturation-index calculations; (2) batch-reaction and one-dimensional (1D) transport calculations involving reversible reactions, which include aqueous, mineral, gas, solid-solution, surface-complexation, and ion-exchange equilibria, and irreversible reactions, which include specified mole transfers of reactants, kinetically controlled reactions, mixing of solutions, and temperature changes; and (3) inverse modeling, which finds sets of mineral and gas mole transfers that account for differences in composition between waters, within specified compositional uncertainty limits.New features in PHREEQC version 2 relative to version 1 include capabilities to simulate dispersion (or diffusion) and stagnant zones in 1D-transport calculations, to model kinetic reactions with user-defined rate expressions, to model the formation or dissolution of ideal, multicomponent or nonideal, binary solid solutions, to model fixed-volume gas phases in addition to fixed-pressure gas phases, to allow the number of surface or exchange sites to vary with the dissolution or precipitation of minerals or kinetic reactants, to include isotope mole balances in inverse modeling calculations, to automatically use multiple sets of convergence parameters, to print user-defined quantities to the primary output file and (or) to a file suitable for importation into a spreadsheet, and to define solution compositions in a format more compatible with spreadsheet programs. This report presents the equations that are the basis for chemical equilibrium, kinetic, transport, and inverse-modeling calculations in PHREEQC; describes the input for the program; and presents examples that demonstrate most of the program's capabilities.

OCT4 expression mediates partial cardiomyocyte reprogramming of mesenchymal stromal cells.

PubMed

Yannarelli, Gustavo; Pacienza, Natalia; Montanari, Sonia; Santa-Cruz, Diego; Viswanathan, Sowmya; Keating, Armand

2017-01-01

Mesenchymal stem/stromal cells (MSCs) are in numerous cell therapy clinical trials, including for injured myocardium. Acquisition of cardiomyocyte characteristics by MSCs may improve cardiac regeneration but the mechanisms regulating this process are unclear. Here, we investigated whether the pluripotency transcription factor OCT4 is involved in the activation of cardiac lineage genetic programs in MSCs. We employed our established co-culture model of MSCs with rat embryonic cardiomyocytes showing co-expression of cardiac markers on MSCs independent of cell fusion. Bone marrow-derived MSCs were isolated from transgenic mice expressing GFP under the control of the cardiac-specific α-myosin heavy chain promoter. After 5 days of co-culture, MSCs expressed cardiac specific genes, including Nkx2.5, atrial natriuretic factor and α-cardiac actin. The frequency of GFP+ cells was 7.6±1.9%, however, these cells retained the stromal cell phenotype, indicating, as expected, only partial differentiation. Global OCT4 expression increased 2.6±0.7-fold in co-cultured MSCs and of interest, 87±5% vs 79±4% of MSCs expressed OCT4 by flow cytometry in controls and after co-culture, respectively. Consistent with the latter observation, the GFP+ cells did not express nuclear OCT4 and showed a significant increase in OCT4 promoter methylation compared with undifferentiated MSCs (92% vs 45%), inferring that OCT4 is regulated by an epigenetic mechanism. We further showed that siRNA silencing of OCT4 in MSCs resulted in a reduced frequency of GFP+ cells in co-culture to less than 1%. Our data infer that OCT4 expression may have a direct effect on partial cardiomyocyte reprogramming of MSCs and suggest a new mechanism(s) associated with MSC multipotency and a requirement for crosstalk with the cardiac microenvironment.

OCT4 expression mediates partial cardiomyocyte reprogramming of mesenchymal stromal cells

PubMed Central

Montanari, Sonia; Santa-Cruz, Diego; Viswanathan, Sowmya; Keating, Armand

2017-01-01

Mesenchymal stem/stromal cells (MSCs) are in numerous cell therapy clinical trials, including for injured myocardium. Acquisition of cardiomyocyte characteristics by MSCs may improve cardiac regeneration but the mechanisms regulating this process are unclear. Here, we investigated whether the pluripotency transcription factor OCT4 is involved in the activation of cardiac lineage genetic programs in MSCs. We employed our established co-culture model of MSCs with rat embryonic cardiomyocytes showing co-expression of cardiac markers on MSCs independent of cell fusion. Bone marrow-derived MSCs were isolated from transgenic mice expressing GFP under the control of the cardiac-specific α-myosin heavy chain promoter. After 5 days of co-culture, MSCs expressed cardiac specific genes, including Nkx2.5, atrial natriuretic factor and α-cardiac actin. The frequency of GFP+ cells was 7.6±1.9%, however, these cells retained the stromal cell phenotype, indicating, as expected, only partial differentiation. Global OCT4 expression increased 2.6±0.7-fold in co-cultured MSCs and of interest, 87±5% vs 79±4% of MSCs expressed OCT4 by flow cytometry in controls and after co-culture, respectively. Consistent with the latter observation, the GFP+ cells did not express nuclear OCT4 and showed a significant increase in OCT4 promoter methylation compared with undifferentiated MSCs (92% vs 45%), inferring that OCT4 is regulated by an epigenetic mechanism. We further showed that siRNA silencing of OCT4 in MSCs resulted in a reduced frequency of GFP+ cells in co-culture to less than 1%. Our data infer that OCT4 expression may have a direct effect on partial cardiomyocyte reprogramming of MSCs and suggest a new mechanism(s) associated with MSC multipotency and a requirement for crosstalk with the cardiac microenvironment. PMID:29216265

Evidence for transgenerational metabolic programming in Drosophila

PubMed Central

Buescher, Jessica L.; Musselman, Laura P.; Wilson, Christina A.; Lang, Tieming; Keleher, Madeline; Baranski, Thomas J.; Duncan, Jennifer G.

2013-01-01

SUMMARY Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie) feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon. PMID:23649823

Attitudes of Jordanian Adolescent Students Toward Overweight and Obesity.

PubMed

Abu Baker, Nesrin N; Al-Ali, Nahla; Al-Ajlouni, Ranyah

2018-01-01

Obesity is a serious public health problem especially among adolescents. Understanding adolescents' attitudes toward obesity and healthy lifestyle is a crucial step to develop effective health programs to treat and prevent obesity. To examine the attitudes toward overweight and obesity among Jordanian adolescent students and to identify the components of obesity prevention program that the students perceive as important. A sample of 1000 students in 8 th to 10 th grades was randomly selected from 16 schools in Irbid, Jordan. A self-reported questionnaire including attitude related questions was used in a descriptive, cross-sectional study. Generally, the students expressed positive attitudes toward obesity; which means that their attitudes were consistent with societal norms in terms of health and social functioning (mean= 3.5, SD=0.39). Furthermore, the students expressed positive attitudes toward lifestyle; which means that their attitudes were consistent with healthy behaviors (mean=3.7, SD=0.58). However, boys had significantly more positive attitudes than girls (p =0.04). The prevalence of overweight and obesity was 23.8%, while obese and non-obese students had similar attitudes toward lifestyle and obesity. Finally, around 20% to 30% of students desired a prevention program out of school time shared with their families and friends and involves eating healthy food and getting more exercise. More efforts are needed to build effective obesity prevention programs that focus on eating healthy diet and getting more exercise considering gender differences.

Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks

PubMed Central

Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang; Thomson, James A.; Stewart, Ron; Gasch, Audrey P.

2013-01-01

Regulatory networks that control gene expression are important in diverse biological contexts including stress response and development. Each gene's regulatory program is determined by module-level regulation (e.g. co-regulation via the same signaling system), as well as gene-specific determinants that can fine-tune expression. We present a novel approach, Modular regulatory network learning with per gene information (MERLIN), that infers regulatory programs for individual genes while probabilistically constraining these programs to reveal module-level organization of regulatory networks. Using edge-, regulator- and module-based comparisons of simulated networks of known ground truth, we find MERLIN reconstructs regulatory programs of individual genes as well or better than existing approaches of network reconstruction, while additionally identifying modular organization of the regulatory networks. We use MERLIN to dissect global transcriptional behavior in two biological contexts: yeast stress response and human embryonic stem cell differentiation. Regulatory modules inferred by MERLIN capture co-regulatory relationships between signaling proteins and downstream transcription factors thereby revealing the upstream signaling systems controlling transcriptional responses. The inferred networks are enriched for regulators with genetic or physical interactions, supporting the inference, and identify modules of functionally related genes bound by the same transcriptional regulators. Our method combines the strengths of per-gene and per-module methods to reveal new insights into transcriptional regulation in stress and development. PMID:24146602

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

PubMed

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

2013-06-14

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

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

PubMed Central

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

2013-01-01

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

Transfer of communication skills to the workplace: impact of a 38-hour communication skills training program designed for radiotherapy teams.

PubMed

Merckaert, Isabelle; Delevallez, France; Gibon, Anne-Sophie; Liénard, Aurore; Libert, Yves; Delvaux, Nicole; Marchal, Serge; Etienne, Anne-Marie; Bragard, Isabelle; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; Coucke, Philippe; Razavi, Darius

2015-03-10

This study assessed the efficacy of a 38-hour communication skills training program designed to train a multidisciplinary radiotherapy team. Four radiotherapy teams were randomly assigned to a training program or a waiting list. Assessments were scheduled at baseline and after training for the training group and at baseline and 4 months later for the waiting list group. Assessments included an audio recording of a radiotherapy planning session to assess team members' communication skills and expression of concerns of patients with breast cancer (analyzed with content analysis software) and an adapted European Organisation for Research and Treatment of Cancer satisfaction with care questionnaire completed by patients at the end of radiotherapy. Two hundred thirty-seven radiotherapy planning sessions were recorded. Compared with members of the untrained teams, members of the trained teams acquired, over time, more assessment skills (P = .003) and more supportive skills (P = .050) and provided more setting information (P = .010). Over time, patients interacting with members of the trained teams asked more open questions (P = .022), expressed more emotional words (P = .025), and exhibited a higher satisfaction level regarding nurses' interventions (P = .028). The 38-hour training program facilitated transfer of team member learned communication skills to the clinical practice and improved patients' satisfaction with care. © 2015 by American Society of Clinical Oncology.

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

PubMed Central

Bailey, Swneke D.; Desai, Kinjal; Kron, Ken J.; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A.; Treloar, Aislinn E.; Dowar, Mark; Thu, Kelsie L.; Cescon, David W.; Silvester, Jennifer; Yang, S. Y. Cindy; Wu, Xue; Pezo, Rossanna C.; Haibe-Kains, Benjamin; Mak, Tak W.; Bedard, Philippe L.; Pugh, Trevor J.; Sallari, Richard C.; Lupien, Mathieu

2016-01-01

Sustained expression of the oestrogen receptor alpha (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon oestrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers2–5, implying that other mechanisms underlie the persistent expression of ESR1. We report the significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by a functional inherited single nucleotide variant (SNV) rs9383590 that accounts for several breast cancer risk-loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. PMID:27571262

Unraveling the Tangled Skein: The Evolution of Transcriptional Regulatory Networks in Development.

PubMed

Rebeiz, Mark; Patel, Nipam H; Hinman, Veronica F

2015-01-01

The molecular and genetic basis for the evolution of anatomical diversity is a major question that has inspired evolutionary and developmental biologists for decades. Because morphology takes form during development, a true comprehension of how anatomical structures evolve requires an understanding of the evolutionary events that alter developmental genetic programs. Vast gene regulatory networks (GRNs) that connect transcription factors to their target regulatory sequences control gene expression in time and space and therefore determine the tissue-specific genetic programs that shape morphological structures. In recent years, many new examples have greatly advanced our understanding of the genetic alterations that modify GRNs to generate newly evolved morphologies. Here, we review several aspects of GRN evolution, including their deep preservation, their mechanisms of alteration, and how they originate to generate novel developmental programs.

Programmed Cell Death Ligand 1 Expression in Primary Central Nervous System Lymphomas: A Clinicopathological Study.

PubMed

Hayano, Azusa; Komohara, Yoshihiro; Takashima, Yasuo; Takeya, Hiroto; Homma, Jumpei; Fukai, Junya; Iwadate, Yasuo; Kajiwara, Koji; Ishizawa, Shin; Hondoh, Hiroaki; Yamanaka, Ryuya

2017-10-01

Programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) have been shown to predict response to PD-L1/PD-1-targeted therapy. We analyzed PD-L1 expression in primary central nervous system lymphomas (PCNSLs). PD-L1 protein and mRNA expression were evaluated in 64 PCNSL tissue samples. IFN-γ, IL-10, CD4, and CD8 mRNA expression was also evaluated. PD-L1 protein was detected in tumor cells in 2 (4.1%) cases and in tumor microenvironments in 25 (52%) cases. PD-L1 mRNA positively correlated with IFN-γ (p=0.0024) and CD4 (p=0.0005) mRNA expression. IFN-γ mRNA positively correlated with CD8 mRNA expression (p=0.0001). Furthermore, tumor cell PD-L1 expression correlated positively with overall survival (p=0.0177), whereas microenvironmental PD-L1 expression exhibited an insignificant negative trend with overall survival (p=0.188). PD-L1 was expressed on both tumor and/or tumor-infiltrating immune cells in PCNSL. The biological roles of this marker warrant further investigation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Impact of TimeSlips, a Creative Expression Intervention Program, on Nursing Home Residents with Dementia and their Caregivers

ERIC Educational Resources Information Center

Fritsch, Thomas; Kwak, Jung; Grant, Stacey; Lang, Josh; Montgomery, Rhonda R.; Basting, Anne D.

2009-01-01

Purpose: Creative expression (CE) programs are emerging interventions to improve the quality of care and life of persons with dementia (PWDs) in long-term care settings. However, limited empirical evidence exists to support the effectiveness of these programs. Here, we report the findings from an assessment of the impact of TimeSlips (TS), a group…

Transcriptional regulation of development in heterocyst-forming cyanobacteria.

PubMed

Flores, Enrique; Picossi, Silvia; Valladares, Ana; Herrero, Antonia

2018-04-30

Filamentous, heterocyst-forming cyanobacteria are among the simplest multicellular systems in Nature. In the absence of combined nitrogen, the filaments consist of vegetative cells that fix CO 2 through oxygenic photosynthesis and micro-oxic heterocysts specialized for the fixation of N 2 in a proportion of about 10 to 1. The development of a heterocyst-containing filament involves differentiation of vegetative cells into heterocysts in a process that requires a distinct gene expression program. Two transcription factors are strictly required, NtcA and HetR. The CRP-family protein NtcA directly activates the expression of multiple genes during heterocyst differentiation - in some cases assisted by coactivators including HetR - and in mature heterocysts, whereas HetR is needed to build high NtcA levels in differentiating heterocysts and directly activates some particular genes. A few other regulators of gene expression participate at specific differentiation steps, and a specific transcription factor, CnfR, activates nif gene expression under the micro-oxic conditions of the heterocyst. Copyright © 2018 Elsevier B.V. All rights reserved.

SIMD Optimization of Linear Expressions for Programmable Graphics Hardware

PubMed Central

Bajaj, Chandrajit; Ihm, Insung; Min, Jungki; Oh, Jinsang

2009-01-01

The increased programmability of graphics hardware allows efficient graphical processing unit (GPU) implementations of a wide range of general computations on commodity PCs. An important factor in such implementations is how to fully exploit the SIMD computing capacities offered by modern graphics processors. Linear expressions in the form of ȳ = Ax̄ + b̄, where A is a matrix, and x̄, ȳ and b̄ are vectors, constitute one of the most basic operations in many scientific computations. In this paper, we propose a SIMD code optimization technique that enables efficient shader codes to be generated for evaluating linear expressions. It is shown that performance can be improved considerably by efficiently packing arithmetic operations into four-wide SIMD instructions through reordering of the operations in linear expressions. We demonstrate that the presented technique can be used effectively for programming both vertex and pixel shaders for a variety of mathematical applications, including integrating differential equations and solving a sparse linear system of equations using iterative methods. PMID:19946569

Conditional Lineage Ablation to Model Human Diseases

NASA Astrophysics Data System (ADS)

Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

1998-09-01

Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

Controlling Citrate Synthase Expression by CRISPR/Cas9 Genome Editing for n-Butanol Production in Escherichia coli.

PubMed

Heo, Min-Ji; Jung, Hwi-Min; Um, Jaeyong; Lee, Sang-Woo; Oh, Min-Kyu

2017-02-17

Genome editing using CRISPR/Cas9 was successfully demonstrated in Esherichia coli to effectively produce n-butanol in a defined medium under microaerobic condition. The butanol synthetic pathway genes including those encoding oxygen-tolerant alcohol dehydrogenase were overexpressed in metabolically engineered E. coli, resulting in 0.82 g/L butanol production. To increase butanol production, carbon flux from acetyl-CoA to citric acid cycle should be redirected to acetoacetyl-CoA. For this purpose, the 5'-untranslated region sequence of gltA encoding citrate synthase was designed using an expression prediction program, UTR designer, and modified using the CRISPR/Cas9 genome editing method to reduce its expression level. E. coli strains with decreased citrate synthase expression produced more butanol and the citrate synthase activity was correlated with butanol production. These results demonstrate that redistributing carbon flux using genome editing is an efficient engineering tool for metabolite overproduction.

The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the Brachyury gene regulatory network

PubMed Central

José-Edwards, Diana S.; Kerner, Pierre; Kugler, Jamie E.; Deng, Wei; Jiang, Di; Di Gregorio, Anna

2013-01-01

The notochord is the distinctive characteristic of chordates; however, the knowledge of the complement of transcription factors governing the development of this structure is still incomplete. Here we present the expression patterns of seven transcription factor genes detected in the notochord of the ascidian Ciona intestinalis at various stages of embryonic development. Four of these transcription factors, Fos-a, NFAT5, AFF and Klf15, have not been directly associated with the notochord in previous studies, while the others, including Spalt-like-a, Lmx-like and STAT5/6-b, display evolutionarily conserved expression in this structure as well as in other domains. We examined the hierarchical relationships between these genes and the transcription factor Brachyury, which is necessary for notochord development in all chordates. We found that Ciona Brachyury regulates the expression of most, although not all, of these genes. These results shed light on the genetic regulatory program underlying notochord formation in Ciona and possibly other chordates. PMID:21594950

TALE factors use two distinct functional modes to control an essential zebrafish gene expression program.

PubMed

Ladam, Franck; Stanney, William; Donaldson, Ian J; Yildiz, Ozge; Bobola, Nicoletta; Sagerström, Charles G

2018-06-18

TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages - a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs. © 2018, Ladam et al.

The eye of the begetter: predicting infant attachment disorganization from women's prenatal interpretations of infant facial expressions.

PubMed

Bernstein, Rosemary E; Tenedios, Catherine M; Laurent, Heidemarie K; Measelle, Jeffery R; Ablow, Jennifer C

2014-01-01

Infant-caregiver attachment disorganization has been linked to many long-term negative psychosocial outcomes. While various prevention programs appear to be effective in preventing disorganized attachment, methods currently used to identify those at risk are unfortunately either overly general or impractical. The current investigation tested whether women's prenatal biases in identifying infant expressions of emotion--tendencies previously shown to relate to some of the maternal variables associated with infant attachment, including maternal traumatization, trauma symptoms, and maternal sensitivity--could predict infant attachment classification at 18 months postpartum. Logistic regression analyses revealed that together with women's adult history of high betrayal traumatization, response concordance with a normative reference sample in labeling infant expressions as negatively valenced, and the number of infant facial expressions that participants classified as "sad" and "angry" predicted subsequent infant attachment security versus disorganization. Implications for screening and prevention are discussed. © 2014 Michigan Association for Infant Mental Health.

Barriers and facilitators to tobacco cessation in a nationwide sample of addiction treatment programs

PubMed Central

Pagano, Anna; Tajima, Barbara; Guydish, Joseph

2016-01-01

Introduction Smoking rates among addiction treatment clients are 3–4 times higher than those of the general population. Recent studies indicate that ceasing tobacco use during treatment may improve recovery outcomes. Across the United States, publicly funded addiction treatment programs vary widely in terms of their tobacco policies and tobacco cessation services offered to clients. Methods The study reported here is the qualitative component of a larger study. Twenty-four programs were recruited from a random sample of publicly funded programs participating in the NIDA Clinical Trials Network. Semistructured interviews were administered by phone to program directors. ATLAS.ti software was used to facilitate thematic analysis of interview transcripts. Findings While all directors expressed interest in helping clients to quit smoking, they cited numerous barriers to implementing tobacco policies and services. These included smoking culture, client resistance, lack of resources, staff smoking, and environmental barriers. Directors also cited several factors that they believed would support tobacco cessation. These included financial support, enhanced leadership, and state mandates against smoking in addiction treatment programs. Conclusion Addiction treatment programs are beginning to place more emphasis on tobacco cessation during treatment. However, furthering this goal requires substantial infrastructural and cultural change. These qualitative study findings may help to inform Single State Agencies (SSAs) to support publicly funded addiction treatment programs in their tobacco cessation efforts. In order to maximize effectiveness, state-level policies regarding tobacco cessation during treatment should be informed by ongoing dialogue between service providers and SSAs. PMID:27296658

Thai Vocabulary. American Council of Learned Societies Program in Oriental Languages, Publications Series A - Texts - Number 2.

ERIC Educational Resources Information Center

Haas, Mary R.

This dictionary is intended to serve an interim need as a short dictionary of the Thai language. It contains vocabulary entries derived from the "Thai Reader" and a selection of words and examples from other sources, including (1) the words and expressions found in "Spoken Thai" (Haas and Subhanka, Henry Holt and Co.) and (2) McFarland's list of…

Impact of the Medicare Chronic Disease Management program on the conduct of Australian dietitians' private practices.

PubMed

Jansen, Sarah; Ball, Lauren; Lowe, Catherine

2015-04-01

This study explored private practice dietitians' perceptions of the impact of the Australian Chronic Disease Management (CDM) program on the conduct of their private practice, and the care provided to patients. Twenty-five accredited practising dietitians working in primary care participated in an individual semistructured telephone interview. Interview questions focussed on dietitians' perceptions of the proportion of patients receiving care through the CDM program, fee structures, adhering to reporting requirements and auditing. Transcript data were thematically analysed using a process of open coding. Half of the dietitians (12/25) reported that most of their patients (>75%) received care through the CDM program. Many dietitians (19/25) reported providing identical care to patients using the CDM program and private patients, but most (17/25) described spending substantially longer on administrative tasks for CDM patients. Dietitians experienced pressure from doctors and patients to keep their fees low or to bulk-bill patients using the CDM program. One-third of interviewed dietitians (8/25) expressed concern about the potential to be audited by Medicare. Recommendations to improve the CDM program included increasing the consultation length and subsequent rebate available for dietetic consultations, and increasing the number of consultations to align with dietetic best-practice guidelines. The CDM program creates challenges for dietitians working in primary care, including how to sustain the quality of patient-centred care and yet maintain equitable business practices. To ensure the CDM program appropriately assists patients to receive optimal care, further review of the CDM program within the scope of dietetics is required.

Distinct regulation of Snail in two muscle lineages of the ascidian embryo achieves temporal coordination of muscle development.

PubMed

Tokuoka, Miki; Kobayashi, Kenji; Satou, Yutaka

2018-06-06

The transcriptional repressor Snail is required for proper differentiation of the tail muscle of ascidian tadpole larvae. Two muscle lineages (B5.1 and B6.4) contribute to the anterior tail muscle cells, and are consecutively separated from a transcriptionally quiescent germ cell lineage at the 16- and 32-cell stages. Concomitantly, cells of these lineages begin to express Tbx6.b ( Tbx6-r.b ) at the 16- and 32-cell stages, respectively. Meanwhile, Snail expression begins in these two lineages simultaneously at the 32-cell stage. Here, we show that Snail expression is regulated differently between these two lineages. In the B5.1 lineage, Snail was activated through Tbx6.b , which is activated by maternal factors, including Zic-r.a. In the B6.4 lineage, the MAPK pathway was cell-autonomously activated by a constitutively active form of Raf, enabling Zic-r.a to activate Snail independently of Tbx6.b As a result, Snail begins to be expressed at the 32-cell stage simultaneously in these two lineages. Such shortcuts might be required for coordinating developmental programs in embryos in which cells become separated progressively from stem cells, including germline cells. © 2018. Published by The Company of Biologists Ltd.

Transcriptome assembly and candidate genes involved in nutritional programming in the swordtail fish Xiphophorus multilineatus.

PubMed

Lu, Yuan; Klimovich, Charlotte M; Robeson, Kalen Z; Boswell, William; Ríos-Cardenas, Oscar; Walter, Ronald B; Morris, Molly R

2017-01-01

Nutritional programming takes place in early development. Variation in the quality and/or quantity of nutrients in early development can influence long-term health and viability. However, little is known about the mechanisms of nutritional programming. The live-bearing fish Xiphophorus multilineatus has the potential to be a new model for understanding these mechanisms, given prior evidence of nutritional programming influencing behavior and juvenile growth rate. We tested the hypotheses that nutritional programming would influence behaviors involved in energy homeostasis as well gene expression in X. multilineatus. We first examined the influence of both juvenile environment (varied in nutrition and density) and adult environment (varied in nutrition) on behaviors involved in energy acquisition and energy expenditure in adult male X. multilineatus . We also compared the behavioral responses across the genetically influenced size classes of males. Males stop growing at sexual maturity, and the size classes of can be identified based on phenotypes (adult size and pigment patterns). To study the molecular signatures of nutritional programming, we assembled a de novo transcriptome for X. multilineatus using RNA from brain, liver, skin, testis and gonad tissues, and used RNA-Seq to profile gene expression in the brains of males reared in low quality (reduced food, increased density) and high quality (increased food, decreased density) juvenile environments. We found that both the juvenile and adult environments influenced the energy intake behavior, while only the adult environment influenced energy expenditure. In addition, there were significant interactions between the genetically influenced size classes and the environments that influenced energy intake and energy expenditure, with males from one of the four size classes (Y-II) responding in the opposite direction as compared to the other males examined. When we compared the brains of males of the Y-II size class reared in a low quality juvenile environment to males from the same size class reared in high quality juvenile environment, 131 genes were differentially expressed, including metabolism and appetite master regulator agrp gene. Our study provides evidence for nutritional programming in X. multilineatus , with variation across size classes of males in how juvenile environment and adult diet influences behaviors involved in energy homeostasis. In addition, we provide the first transcriptome of X. multilineatus , and identify a group of candidate genes involved in nutritional programming.

Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study

PubMed Central

Chang, Anne Lynn S; Bitter, Patrick H; Qu, Kun; Lin, Meihong; Rapicavoli, Nicole A; Chang, Howard Y

2013-01-01

Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3′-end sequencing for expression quantification (“3-seq”) to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed “skin aging”), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became “rejuvenated” after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3′-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process. PMID:22931923

Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

PubMed Central

Xiong, Fuxia; Zhang, Lubo

2012-01-01

Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

Systems toxicology identifies mechanistic impacts of 2-amino-4,6-dinitrotoluene (2A-DNT) exposure in Northern Bobwhite.

PubMed

Gust, Kurt A; Nanduri, Bindu; Rawat, Arun; Wilbanks, Mitchell S; Ang, Choo Yaw; Johnson, David R; Pendarvis, Ken; Chen, Xianfeng; Quinn, Michael J; Johnson, Mark S; Burgess, Shane C; Perkins, Edward J

2015-08-07

A systems toxicology investigation comparing and integrating transcriptomic and proteomic results was conducted to develop holistic effects characterizations for the wildlife bird model, Northern bobwhite (Colinus virginianus) dosed with the explosives degradation product 2-amino-4,6-dinitrotoluene (2A-DNT). A subchronic 60 d toxicology bioassay was leveraged where both sexes were dosed via daily gavage with 0, 3, 14, or 30 mg/kg-d 2A-DNT. Effects on global transcript expression were investigated in liver and kidney tissue using custom microarrays for C. virginianus in both sexes at all doses, while effects on proteome expression were investigated in liver for both sexes and kidney in males, at 30 mg/kg-d. As expected, transcript expression was not directly indicative of protein expression in response to 2A-DNT. However, a high degree of correspondence was observed among gene and protein expression when investigating higher-order functional responses including statistically enriched gene networks and canonical pathways, especially when connected to toxicological outcomes of 2A-DNT exposure. Analysis of networks statistically enriched for both transcripts and proteins demonstrated common responses including inhibition of programmed cell death and arrest of cell cycle in liver tissues at 2A-DNT doses that caused liver necrosis and death in females. Additionally, both transcript and protein expression in liver tissue was indicative of induced phase I and II xenobiotic metabolism potentially as a mechanism to detoxify and excrete 2A-DNT. Nuclear signaling assays, transcript expression and protein expression each implicated peroxisome proliferator-activated receptor (PPAR) nuclear signaling as a primary molecular target in the 2A-DNT exposure with significant downstream enrichment of PPAR-regulated pathways including lipid metabolic pathways and gluconeogenesis suggesting impaired bioenergetic potential. Although the differential expression of transcripts and proteins was largely unique, the consensus of functional pathways and gene networks enriched among transcriptomic and proteomic datasets provided the identification of many critical metabolic functions underlying 2A-DNT toxicity as well as impaired PPAR signaling, a key molecular initiating event known to be affected in di- and trinitrotoluene exposures.

Tailoring mind-body therapies to individual needs: patients' program preference and psychological traits as moderators of the effects of mindfulness-based cancer recovery and supportive-expressive therapy in distressed breast cancer survivors.

PubMed

Carlson, Linda E; Tamagawa, Rie; Stephen, Joanne; Doll, Richard; Faris, Peter; Dirkse, Dale; Speca, Michael

2014-11-01

Mindfulness-based cancer recovery (MBCR) and supportive-expressive therapy (SET) are well-validated psycho-oncological interventions, and we have previously reported health benefits of both programs. However, little is known about patients' characteristics or program preferences that may influence outcomes. Therefore, this study examined moderators of the effects of MBCR and SET on psychological well-being among breast cancer survivors. A multi-site randomized controlled trial was conducted between 2007 and 2012 in two Canadian cities (Calgary and Vancouver). A total of 271 distressed stage I-III breast cancer survivors were randomized into MBCR, SET or a 1-day stress management seminar (SMS). Baseline measures of moderator variables included program preference, personality traits, emotional suppression, and repressive coping. Outcome measures of mood, stress symptoms, quality of life, spiritual well-being, post-traumatic growth, social support, and salivary cortisol were measured pre- and post intervention. Hierarchical regression analyses were used to assess moderator effects on outcomes. The most preferred program was MBCR (55%). Those who were randomized to their preference improved more over time on quality of life and spiritual well-being post-intervention regardless of the actual intervention type received. Women with greater psychological morbidity at baseline showed greater improvement in stress symptoms and quality of life if they received their preferred versus nonpreferred program. Patients' program preference and baseline psychological functioning, rather than personality, were predictive of program benefits. These results suggest incorporating program preference can maximize the efficacy of integrative oncology interventions, and emphasize the methodological importance of assessing and accommodating for preferences when conducting mind-body clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Toward implementation of a regional quality assurance program in cytopathology: the Hong Kong experience.

PubMed

Ng, Wai-Kuen; Chiu, Conrad S C; Cheng, Yue; Chan, Eva T Y; Chiu, Fanny L L; Collins, Robert J

2006-01-01

To develop a local quality assurance program in cytopathology based on circulation of patient specimens on glass slides, with limited resources. A working group was set up for design and running of the program. Participation is on a laboratory basis. The scope and frequency of testing are defined. Well-documented cases (including gynecologic, nongynecologic and fine needle aspiration cytology) with commonly encountered diagnoses are collected. Consensus concerning the diagnosis, interpretive menu and scoring system is sought before the actual slide circulations using express mail. After returning their answers to the program organizer, the participating laboratories receive immediate feedback on their scores, with reference answers, explanatory notes, "whole-mount" images of glass slides and cumulative responses of peer laboratories for on-site checking. At the end of each year, an electronic file containing representative photomicrographs of all cases examined is provided to individual laboratories for their permanent records and training purposes. The program was launched in mid-2003. There were 24 and 27 participating laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date, >150 well-documented cytology cases are available in the slide pool and ready for circulation. As the revenue is mainly to cover the expenses of express mail, the program can be carried out at a relatively low cost. In order to have any cytology quality assurance program accepted by local laboratories, it has to be fair and practical. Strict confidentiality needs to be observed throughout the process. This program emphasizes both performance assessment and educational value. Adequate representation from experienced local cytology workers, detailed documentation support from authorities and assistance from dedicated staff are essential to the success of any external proficiency testing scheme. Regular review and evaluation are also necessary for continuous improvement. The Hong Kong experience can serve as an example of running a glass slide-based cytology quality assurance program in a small region with limited resources.

Structural conceptualization of learning experiences in nursing master's degree programs utilized in occupational health nursing activities.

PubMed

Aoyama, Wakako; Tatsumi, Asami

2017-01-31

In this study, concepts were constructed that express learning experiences in nursing master's degree programs utilized in occupational health nursing activities with the aim of clarifying those characteristics. This was based on the idea that elucidation of the characteristics of learning experiences in nursing master's degree programs used in occupational health nursing activities would be meaningful in providing high-quality occupational health services that respond to the needs of society. Semi-structured interviews were conducted with 10 people who fulfilled the three conditions of having completed a master's degree programs, working as an occupational health nurse after completion of the program, and not continuing on to a doctoral program. The nursing conceptualization method of Naomi Funashima was used. From the obtained data, 512 code items expressing learning experiences in master's degree programs utilized in occupational health nursing activities were identified. These items included five core categories (concepts), 34 categories, and 69 subcategories. The five concepts constructed were "Pursuit of expertise and self-evaluation," "Mutual understanding of various people that leads to human resources utilization," "Theoretical and academic learning that influences changes in activities," "Research learning that lead to activities based on scientific evidence," and "Learning that leads to high-quality activities making use of expertise." It was found that various learning experiences in the master's program to pursue the specialty of occupational health nurses in order to recognize their roles as well as the experiences to take the initiative in learning had been integrated in their activities after completion of the course and had contributed to their high-quality occupational health nursing activities. It was suggested that the learning experiences in the master's program, which had been revealed in this study, were the experiences necessary for providing high-quality occupational health nursing activities to satisfy the social needs.

RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4.

PubMed

Poria, D K; Guha, A; Nandi, I; Ray, P S

2016-03-31

Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3'-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a 'miRNA sponge' to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.

Quantum probabilistic logic programming

NASA Astrophysics Data System (ADS)

Balu, Radhakrishnan

2015-05-01

We describe a quantum mechanics based logic programming language that supports Horn clauses, random variables, and covariance matrices to express and solve problems in probabilistic logic. The Horn clauses of the language wrap random variables, including infinite valued, to express probability distributions and statistical correlations, a powerful feature to capture relationship between distributions that are not independent. The expressive power of the language is based on a mechanism to implement statistical ensembles and to solve the underlying SAT instances using quantum mechanical machinery. We exploit the fact that classical random variables have quantum decompositions to build the Horn clauses. We establish the semantics of the language in a rigorous fashion by considering an existing probabilistic logic language called PRISM with classical probability measures defined on the Herbrand base and extending it to the quantum context. In the classical case H-interpretations form the sample space and probability measures defined on them lead to consistent definition of probabilities for well formed formulae. In the quantum counterpart, we define probability amplitudes on Hinterpretations facilitating the model generations and verifications via quantum mechanical superpositions and entanglements. We cast the well formed formulae of the language as quantum mechanical observables thus providing an elegant interpretation for their probabilities. We discuss several examples to combine statistical ensembles and predicates of first order logic to reason with situations involving uncertainty.

Epigenetic Basis of Neuronal and Synaptic Plasticity.

PubMed

Karpova, Nina N; Sales, Amanda J; Joca, Samia R

2017-01-01

Neuronal network and plasticity change as a function of experience. Altered neural connectivity leads to distinct transcriptional programs of neuronal plasticity-related genes. The environmental challenges throughout life may promote long-lasting reprogramming of gene expression and the development of brain disorders. The modifications in neuronal epigenome mediate gene-environmental interactions and are required for activity-dependent regulation of neuronal differentiation, maturation and plasticity. Here, we highlight the latest advances in understanding the role of the main players of epigenetic machinery (DNA methylation and demethylation, histone modifications, chromatin-remodeling enzymes, transposons, and non-coding RNAs) in activity-dependent and long- term neural and synaptic plasticity. The review focuses on both the transcriptional and post-transcriptional regulation of gene expression levels, including the processes of promoter activation, alternative splicing, regulation of stability of gene transcripts by natural antisense RNAs, and alternative polyadenylation. Further, we discuss the epigenetic aspects of impaired neuronal plasticity and the pathogenesis of neurodevelopmental (Rett syndrome, Fragile X Syndrome, genomic imprinting disorders, schizophrenia, and others), stressrelated (mood disorders) and neurodegenerative Alzheimer's, Parkinson's and Huntington's disorders. The review also highlights the pharmacological compounds that modulate epigenetic programming of gene expression, the potential treatment strategies of discussed brain disorders, and the questions that should be addressed during the development of effective and safe approaches for the treatment of brain disorders.

The Landscape of Graduate Admissions: Surveying Physics Programs about Doctoral Admissions Practices

NASA Astrophysics Data System (ADS)

Potvin, Geoff

2014-03-01

Sustaining or improving the best graduate programs as well as increasing the diversity of the physics community requires us to better understand the critical gatekeeping role played by graduate admissions. Admissions processes determine not only who is allowed to begin graduate study but can also influence who chooses to even consider applying. Recently, in concert with some of the activities of the APS Bridge Program, a survey was conducted of directors of graduate admissions and associated faculty in doctoral-granting departments about their admissions practices. Receiving responses from over 75% of departments that award PhDs in physics, respondents were probed about their admissions decisions with special attention on the criteria used in admissions and their relative importance, and how student representation considerations are dealt with in the admissions process (if at all). Results indicate a number of important issues for future students, faculty, and administrators to consider including the importance placed on GRE scores. Results also indicate a sizable number of departments express a latent demand for greater numbers of students from traditionally-underrepresented backgrounds (including women) but simultaneously report a dearth of such students who even apply to their doctoral programs. Implications of these and other findings will be discussed.

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5

PubMed Central

Belian, Elisa; Noseda, Michela; Abreu Paiva, Marta S.; Leja, Thomas; Sampson, Robert; Schneider, Michael D.

2015-01-01

Adult cardiac stem cells (CSCs) express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd)—a co-activator not only for serum response factor, but also for Gata4 and Tbx5—is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT), and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains). MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized. In summary: (1) GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2) Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3) Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate. PMID:26047103

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5.

PubMed

Belian, Elisa; Noseda, Michela; Abreu Paiva, Marta S; Leja, Thomas; Sampson, Robert; Schneider, Michael D

2015-01-01

Adult cardiac stem cells (CSCs) express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd)-a co-activator not only for serum response factor, but also for Gata4 and Tbx5-is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT), and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains). MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized. (1) GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2) Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3) Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate.

EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1α and STAT3

PubMed Central

Koh, Jaemoon; Jang, Ji-Young; Keam, Bhumsuk; Kim, Sehui; Kim, Moon-Young; Go, Heounjeong; Kim, Tae Min; Kim, Dong-Wan; Kim, Chul-Woo; Jeon, Yoon Kyung; Chung, Doo Hyun

2016-01-01

ABSTRACT Programmed cell death (PD)-1/PD-1 ligand-1 (PD-L1)-targeted therapy has emerged as a promising therapeutic strategy for lung cancer. However, whether EML4-ALK regulates PD-L1 expression in lung cancer remains unknown. A total of 532 pulmonary adenocarcinomas (pADCs), including 58 ALK-translocated tumors, were immunohistochemically evaluated for PD-L1 and PD-1. H23 (EGFRWild-typeEML4-ALK−PD-L1Low) and H2228 (EGFRWild-typeEML4-ALK+PD-L1High) cells were transfected with EML4-ALK or ALK short interfering RNAs and used to investigate the alterations in PD-L1 expression. PD-L1 expression was detected in 81% of ALK-translocated pADCs; this value was significantly higher than those of pADCs with EGFR mutation, KRAS mutation or lacking ALK, EGFR or KRAS mutation (p <0.005 for all). Moreover, ALK-translocated pADC with PD-L1 expression showed significantly higher numbers of tumor-infiltrating PD-1+ cells. ALK knockdown or inhibition (crizotinib treatment) in H2228 cells downregulated PD-L1 expression. Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment. This ALK-dependent upregulation of PD-L1 expression was mediated by STAT3 and hypoxia-inducible factor (HIF)-1α under normoxia and hypoxia. Furthermore, EML4-ALK enhanced HIF-1α expression through increasing transcription and decreasing ubiquitination of HIF-1α. In ALK-translocated pADC tissues, significant positive correlations between PD-L1 and nuclear HIF-1α (p < 0.05) or pSTAT3 expression levels (p<0.005) were observed. Among patients with ALK-translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free (p = 0.001) and overall survival (p = 0.002) after crizotinib treatment. Collectively, our findings demonstrate that ALK-derived pADCs increase PD-L1 expression via HIF-1α and/or STAT3, thus providing a rationale for PD-1/PD-L1 pathway-targeted therapy in ALK-translocated lung cancer. PMID:27141364

Sexually Selected Traits: A Fundamental Framework for Studies on Behavioral Epigenetics

PubMed Central

Jašarević, Eldin; Geary, David C.; Rosenfeld, Cheryl S.

2012-01-01

Emerging evidence suggests that epigenetic-based mechanisms contribute to various aspects of sex differences in brain and behavior. The major obstacle in establishing and fully understanding this linkage is identifying the traits that are most susceptible to epigenetic modification. We have proposed that sexual selection provides a conceptual framework for identifying such traits. These are traits involved in intrasexual competition for mates and intersexual choice of mating partners and generally entail a combination of male–male competition and female choice. These behaviors are programmed during early embryonic and postnatal development, particularly during the transition from the juvenile to adult periods, by exposure of the brain to steroid hormones, including estradiol and testosterone. We evaluate the evidence that endocrine-disrupting compounds, including bisphenol A, can interfere with the vital epigenetic and gene expression pathways and with the elaboration of sexually selected traits with epigenetic mechanisms presumably governing the expression of these traits. Finally, we review the evidence to suggest that these steroid hormones can induce a variety of epigenetic changes in the brain, including the extent of DNA methylation, histone protein alterations, and even alterations of noncoding RNA, and that many of the changes differ between males and females. Although much previous attention has focused on primary sex differences in reproductive behaviors, such as male mounting and female lordosis, we outline why secondary sex differences related to competition and mate choice might also trace their origins back to steroid-induced epigenetic programming in disparate regions of the brain. PMID:23744965

Combat Wound Initiative program.

PubMed

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

PubMed Central

LaRocca, Timothy J.; Stivison, Elizabeth A.; Hod, Eldad A.; Spitalnik, Steven L.; Cowan, Peter J.; Randis, Tara M.

2014-01-01

ABSTRACT A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. PMID:25161188

Qualitative assessment of take-home naloxone program participant and law enforcement interactions in British Columbia.

PubMed

Deonarine, Andrew; Amlani, Ashraf; Ambrose, Graham; Buxton, Jane A

2016-05-21

The British Columbia take-home naloxone (BCTHN) program has been in operation since 2012 and has resulted in the successful reversal of over 581 opioid overdoses. The study aims to explore BCTHN program participant perspectives about the program, barriers to participants contacting emergency services (calling "911") during an overdose, and perspectives of law enforcement officials on naloxone administration by police officers. Two focus groups and four individual interviews were conducted with BCTHN program participants; interviews with two law enforcement officials were also conducted. Qualitative analysis of all transcripts was performed. Positive themes about the BCTHN program from participants included easy to understand training, correcting misperceptions in the community, and positive interactions with emergency services. Potential barriers to contacting emergency services during an overdose include concerns about being arrested for outstanding warrants or for other illegal activities (such as drug possession) and confiscation of kits. Law enforcement officials noted that warrants were complex situational issues, kits would normally not be confiscated, and admitted arrests for drug possession or other activities may not serve the public good in an overdose situation. Law enforcement officials were concerned about legal liability and jurisdictional/authorization issues if naloxone administration privileges were expanded to police. Program participants and law enforcement officials expressed differing perspectives about warrants, kit confiscation, and arrests. Facilitating communication between BCTHN program participants and other stakeholders may address some of the confusion and remove potential barriers to further improving program outcomes. Naloxone administration by law enforcement would require policies to address jurisdiction/authorization and liability issues.

Expression of a repressor form of the Arabidopsis thaliana transcription factor TCP16 induces the formation of ectopic meristems.

PubMed

Uberti-Manassero, Nora G; Coscueta, Ezequiel R; Gonzalez, Daniel H

2016-11-01

Plants that express a fusion of the Arabidopsis thaliana class I TCP transcription factor TCP16 to the EAR repressor domain develop several phenotypic alterations, including rounder leaves, short petioles and pedicels, and delayed elongation of sepals, petals and anthers. In addition, these plants develop lobed cotyledons and ectopic meristems. Ectopic meristems are formed on the adaxial side of cotyledon petioles and arise from a cleft that is formed at this site. Analysis of the expression of reporter genes indicated that meristem genes are reactivated at the site of emergence of ectopic meristems, located near the bifurcation of cotyledon veins. The plants also show increased transcript levels of the boundary-specific CUP-SHAPED COTYLEDON (CUC) genes. The results suggest that TCP16 is able to modulate the induction of meristematic programs and the differentiation state of plant cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia.

PubMed

Wan, Liling; Wen, Hong; Li, Yuanyuan; Lyu, Jie; Xi, Yuanxin; Hoshii, Takayuki; Joseph, Julia K; Wang, Xiaolu; Loh, Yong-Hwee E; Erb, Michael A; Souza, Amanda L; Bradner, James E; Shen, Li; Li, Wei; Li, Haitao; Allis, C David; Armstrong, Scott A; Shi, Xiaobing

2017-03-09

Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Recognition of modified histones by 'reader' proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors. We recently identified the YEATS domain as an acetyl-lysine-binding module, but its functional importance in human cancer remains unknown. Here we show that the YEATS domain-containing protein ENL, but not its paralogue AF9, is required for disease maintenance in acute myeloid leukaemia. CRISPR-Cas9-mediated depletion of ENL led to anti-leukaemic effects, including increased terminal myeloid differentiation and suppression of leukaemia growth in vitro and in vivo. Biochemical and crystal structural studies and chromatin-immunoprecipitation followed by sequencing analyses revealed that ENL binds to acetylated histone H3, and co-localizes with H3K27ac and H3K9ac on the promoters of actively transcribed genes that are essential for leukaemia. Disrupting the interaction between the YEATS domain and histone acetylation via structure-based mutagenesis reduced the recruitment of RNA polymerase II to ENL-target genes, leading to the suppression of oncogenic gene expression programs. Notably, disrupting the functionality of ENL further sensitized leukaemia cells to BET inhibitors. Together, our data identify ENL as a histone acetylation reader that regulates oncogenic transcriptional programs in acute myeloid leukaemia, and suggest that displacement of ENL from chromatin may be a promising epigenetic therapy, alone or in combination with BET inhibitors, for aggressive leukaemia.

Prevention of diabetes in overweight/obese children through a family based intervention program including supervised exercise (PREDIKID project): study protocol for a randomized controlled trial.

PubMed

Arenaza, Lide; Medrano, María; Amasene, María; Rodríguez-Vigil, Beatriz; Díez, Ignacio; Graña, Manuel; Tobalina, Ignacio; Maiz, Edurne; Arteche, Edurne; Larrarte, Eider; Huybrechts, Inge; Davis, Catherine L; Ruiz, Jonatan R; Ortega, Francisco B; Margareto, Javier; Labayen, Idoia

2017-08-10

The global pandemic of obesity has led to an increased risk for prediabetes and type-2 diabetes (T2D). The aims of the current project are: (1) to evaluate the effect of a 22-week family based intervention program, including supervised exercise, on insulin resistance syndrome (IRS) risk in children with a high risk of developing T2D and (2) to identify the profile of microRNA in circulating exosomes and in peripheral blood mononuclear cells in children with a high risk of developing T2D and its response to a multidisciplinary intervention program including exercise. A total of 84 children, aged 8-12 years, with a high risk of T2D will be included and randomly assigned to control (N = 42) or intervention (N = 42) groups. The control group will receive a family based lifestyle education and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week, 90 min per session including warm-up, moderate to vigorous aerobic activities, and strength exercises). The following measurements will be evaluated at baseline prior to randomization and after the intervention: fasting insulin, glucose and hemoglobin A1c; body composition (dual-energy X-ray absorptiometry); ectopic fat (magnetic resonance imaging); microRNA expression in circulating exosomes and in peripheral blood mononuclear cells (MiSeq; Illumina); cardiorespiratory fitness (cardiopulmonary exercise testing); dietary habits and physical activity (accelerometry). Prevention and identification of children with a high risk of developing T2D could help to improve their cardiovascular health and to reduce the comorbidities associated with obesity. ClinicalTrials.gov, ID: NCT03027726 . Registered on 16 January 2017.

Lex-SVM: exploring the potential of exon expression profiling for disease classification.

PubMed

Yuan, Xiongying; Zhao, Yi; Liu, Changning; Bu, Dongbo

2011-04-01

Exon expression profiling technologies, including exon arrays and RNA-Seq, measure the abundance of every exon in a gene. Compared with gene expression profiling technologies like 3' array, exon expression profiling technologies could detect alterations in both transcription and alternative splicing, therefore they are expected to be more sensitive in diagnosis. However, exon expression profiling also brings higher dimension, more redundancy, and significant correlation among features. Ignoring the correlation structure among exons of a gene, a popular classification method like L1-SVM selects exons individually from each gene and thus is vulnerable to noise. To overcome this limitation, we present in this paper a new variant of SVM named Lex-SVM to incorporate correlation structure among exons and known splicing patterns to promote classification performance. Specifically, we construct a new norm, ex-norm, including our prior knowledge on exon correlation structure to regularize the coefficients of a linear SVM. Lex-SVM can be solved efficiently using standard linear programming techniques. The advantage of Lex-SVM is that it can select features group-wisely, force features in a subgroup to take equal weihts and exclude the features that contradict the majority in the subgroup. Experimental results suggest that on exon expression profile, Lex-SVM is more accurate than existing methods. Lex-SVM also generates a more compact model and selects genes more consistently in cross-validation. Unlike L1-SVM selecting only one exon in a gene, Lex-SVM assigns equal weights to as many exons in a gene as possible, lending itself easier for further interpretation.

Tissue-specific mismatch repair protein expression: MSH3 is higher than MSH6 in multiple mouse tissues.

PubMed

Tomé, Stéphanie; Simard, Jodie P; Slean, Meghan M; Holt, Ian; Morris, Glenn E; Wojciechowicz, Kamila; te Riele, Hein; Pearson, Christopher E

2013-01-01

Mismatch repair (MMR) proteins have critical roles in the maintenance of genomic stability, both class-switch recombination and somatic hypermutation of immunoglobulin genes and disease-associated trinucleotide repeat expansions. In the genetic absence of MMR, certain tissues are predisposed to mutations and cancer. MMR proteins are involved in various functions including protection from replication-associated and non-mitotic mutations, as well as driving programmed and deleterious mutations, including disease-causing trinucleotide repeat expansions. Here we have assessed the levels of MSH2, MSH3, and MSH6 expression in a large number of murine tissues by transcript analysis and simultaneous Western blotting. We observed that MMR expression patterns varied widely between 14 different tissue types, but did not vary with age (13-84 weeks). MMR protein expression is highest in testis, thymus and spleen and lowest in pancreas, quadriceps and heart, with intermediate levels in liver, kidney, intestine, colon, cortex, striatum and cerebellum. By equalizing antibody signal intensity to represent levels found in mMutSα and mMutSβ purified proteins, we observed that mMSH3 protein levels are greater than mMSH6 levels in the multiple tissues analyzed, with more MSH6 in proliferating tissues. In the intestinal epithelium MSH3 and MSH6 are more highly expressed in the proliferative undifferentiated cells of the crypts than in the differentiated villi cells, as reported for MSH2. This finding correlates with the higher level of MMR expression in highly proliferative mouse tissues such as the spleen and thymus. The relative MMR protein expression levels may explain the functional and tissue-specific reliance upon the roles of each MMR protein. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

The effectiveness of a trauma-focused psycho-educational secondary prevention program for children exposed to interparental violence: study protocol for a randomized controlled trial.

PubMed

Overbeek, Mathilde M; de Schipper, J Clasien; Lamers-Winkelman, Francien; Schuengel, Carlo

2012-02-06

Children who witness interparental violence are at a heightened risk for developing psychosocial, behavioral and cognitive problems, as well as posttraumatic stress symptoms. For these children the psycho-educational secondary prevention program 'En nu ik...!' ('It's my turn now!') has been developed. This program includes specific therapeutic factors focused on emotion awareness and expression, increasing feelings of emotional security, teaching specific coping strategies, developing a trauma narrative, improving parent-child interaction and psycho-education. The main study aim is to evaluate the effectiveness of the specific therapeutic factors in the program. A secondary objective is to study mediating and moderating factors. This study is a prospective multicenter randomized controlled trial across cities in the Netherlands. Participants (N = 140) are referred to the secondary preventive intervention program by police, social work, women shelters and youth (mental health) care. Children, aged 6-12 years, and their parents, who experienced interparental violence are randomly assigned to either the intervention program or the control program. The control program is comparable on nonspecific factors by offering positive attention, positive expectations, recreation, distraction, warmth and empathy of the therapist, and social support among group participants, in ways that are similar to the intervention program. Primary outcome measures are posttraumatic stress symptoms and emotional and behavioral problems of the child. Mediators tested are the ability to differentiate and express emotions, emotional security, coping strategies, feelings of guilt and parent-child interaction. Mental health of the parent, parenting stress, disturbances in parent-child attachment, duration and severity of the domestic violence and demographics are examined for their moderating effect. Data are collected one week before the program starts (T1), and one week (T2) and six months (T3) after finishing the program. Both intention-to-treat and completer analyses will be done. Adverse outcomes after witnessing interparental violence are highly diverse and may be explained by multiple risk factors. An important question for prevention programs is therefore to what extent a specific focus on potential psychotrauma is useful. This trial may point to several directions for optimizing public health response to children's exposure to interparental violence.

Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis.

PubMed

Qu, Hai-Xia; Zhao, Li-Ping; Zhan, Shu-Hui; Geng, Chang-Xin; Xu, Lin; Xin, Yong-Ning; Jiang, Xiang-Jun

2016-11-01

The clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. To investigate this question, we conducted a meta-analysis. A comprehensive literature search of electronic databases (up to July 10, 2016) was performed for relevant studies using multiple search strategies. Correlation between PD-L1 expression and clinicopathological features/overall survival (OS) was analyzed. A total of 1,350 ESCC patients from eight studies were included. The pooled odds ratios (ORs) indicated that none of the clinicopathological characteristics was correlated with PD-L1 expression, including gender [OR =0.84; 95% confidence interval (CI): 0.59-1.18; P=0.31], histological differentiation (OR =1.33; 95% CI: 0.95-1.85; P=0.09), tumor depth (OR =0.66; 95% CI: 0.33-1.35; P=0.26), status of lymph node metastasis (OR =0.67; 95% CI: 0.30-1.52; P=0.34), distal metastasis (OR =0.66; 95% CI: 0.40-1.09; P=0.10) and tumor node metastasis (TNM) stage (OR =0.93; 95% CI: 0.49-1.75; P=0.82). The combined hazard ratio (HR) for OS showed a trend that overexpression of PD-L1 might be associated with the survival outcome of ESCC, though the difference was not statistically significant (HR =1.65; 95% CI 0.95-2.85; P=0.07). Based on the published studies, PD-L1 overexpression in ESCC was not associated with common clinicopathological characteristics. PD-L1 might be a poor prognostic biomarker for ESCC. Further large-scale research should be performed to reveal the precise clinicopathological and prognostic significance of PD-L1 in ESCC by unified testing standard.

Epigenomics, gestational programming and risk of metabolic syndrome.

PubMed

Desai, M; Jellyman, J K; Ross, M G

2015-04-01

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis.

PubMed

Zhuan-Sun, Yongxun; Huang, Fengting; Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43-2.17, P <0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25-1.98, P =0.0001) and neural invasion (RR =1.30, 95% CI: 1.03-1.64, P =0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics.

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

PubMed Central

Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43–2.17, P<0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25–1.98, P=0.0001) and neural invasion (RR =1.30, 95% CI: 1.03–1.64, P=0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics. PMID:29081663

Cherokee Choices: a diabetes prevention program for American Indians.

PubMed

Bachar, Jeffrey J; Lefler, Lisa J; Reed, Lori; McCoy, Tara; Bailey, Robin; Bell, Ronny

2006-07-01

In 1999, the Centers for Disease Control and Prevention (CDC) provided Racial and Ethnic Approaches to Community Health 2010 (REACH 2010) funds to the Eastern Band of Cherokee Indians to develop a community-based intervention to improve the health of this rural, mountainous community in North Carolina. During the first year of the Cherokee Choices program, team members conducted formative research, formed coalitions, and developed a culturally appropriate community action plan for the prevention of type 2 diabetes, particularly among children. The Eastern Band of Cherokee Indians has higher rates of obesity and type 2 diabetes than the U.S. and North Carolina general populations. The Cherokee Choices program includes three main components: elementary school mentoring, worksite wellness for adults, and church-based health promotion. A social marketing strategy, including television advertisements and a television documentary series, supports the three components. School policy was altered to allow Cherokee Choices to have class time and after-school time devoted to health promotion activities. School staff have shown an interest in improving their health through attendance at fitness sessions. The credibility of the program has been validated through multiple invitations to participate in school events. Participants in the worksite wellness program have met dietary and physical activity goals, had reductions in body fat, and expressed enthusiasm for the program. A subcoalition has been formed to expand the worksite wellness component and link prevention efforts to health care cost reduction. Participants in the church program have walked more than 31,600 miles collectively.

76 FR 22412 - Fellowship Placement Pilot Program Requests for Expressions of Interests To Administer Pilot...

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2011-04-21

... Program Requests for Expressions of Interests To Administer Pilot Contact Information Correction AGENCY...). The April 13, 2011, notice had an incorrect telephone number for the contact person. This notice corrects the Contact Information section of the notice. All other information remains correct as published...

Quantification of indium in steel using PIXE

NASA Astrophysics Data System (ADS)

Oliver, A.; Miranda, J.; Rickards, J.; Cheang, J. C.

1989-04-01

The quantitative analysis of steel for endodontics tools was carried out using low-energy protons (≤ 700 keV). A computer program for a thick-target analysis which includes enhancement due to secondary fluorescence was used. In this experiment the L-lines of indium are enhanced due to the proximity of other elements' K-lines to the indium absorption edge. The results show that the ionization cross section expression employed to evaluate this magnitude is important.

Nuclear Resonance Fluorescence and Isotopic Mapping of Containers

NASA Astrophysics Data System (ADS)

Johnson, Micah S.; McNabb, Dennis P.

2009-03-01

National security programs have expressed interest in developing systems to isotopically map shipping containers, fuel assemblies, and waste barrels for various materials including special nuclear material (SNM). Current radiographic systems offer little more than an ambiguous density silhouette of a container's contents. In this paper we will present a system being developed at LLNL to isotopically map containers using the nuclear resonance fluorescence (NRF) method. Recent experimental measurements on NRF strengths in SNM are discussed.

Emotion-based preventive intervention: Effectively promoting emotion knowledge and adaptive behavior among at-risk preschoolers.

PubMed

Finlon, Kristy J; Izard, Carroll E; Seidenfeld, Adina; Johnson, Stacy R; Cavadel, Elizabeth Woodburn; Ewing, E Stephanie Krauthamer; Morgan, Judith K

2015-11-01

Effectiveness studies of preschool social-emotional programs are needed in low-income, diverse populations to help promote the well-being of at-risk children. Following an initial program efficacy study 2 years prior, 248 culturally diverse Head Start preschool children participated in the current effectiveness trial and received either the Emotion-Based Prevention Program (EBP) or the I Can Problem Solve (ICPS) intervention. Pre- and postdata collection included direct child assessment, teacher report, parent interview, and independent observations. Teachers implementing the EBP intervention demonstrated good and consistent fidelity to the program. Overall, children in EBP classrooms gained more emotion knowledge and displayed greater decreases in negative emotion expressions and internalizing behaviors across the implementation period as compared to children in ICPS classrooms. In addition, cumulative risk, parental depressive symptoms, and classroom climate significantly moderated treatment effects. For children experiencing more stress or less support, EBP produced more successful outcomes than did ICPS. These results provide evidence of EBP sustainability and program effectiveness, as did previous findings that demonstrated EBP improvements in emotion knowledge, regulation skills, and behavior problems replicated under unsupervised program conditions.

TraceContract

NASA Technical Reports Server (NTRS)

Kavelund, Klaus; Barringer, Howard

2012-01-01

TraceContract is an API (Application Programming Interface) for trace analysis. A trace is a sequence of events, and can, for example, be generated by a running program, instrumented appropriately to generate events. An event can be any data object. An example of a trace is a log file containing events that a programmer has found important to record during a program execution. Trace - Contract takes as input such a trace together with a specification formulated using the API and reports on any violations of the specification, potentially calling code (reactions) to be executed when violations are detected. The software is developed as an internal DSL (Domain Specific Language) in the Scala programming language. Scala is a relatively new programming language that is specifically convenient for defining such internal DSLs due to a number of language characteristics. This includes Scala s elegant combination of object-oriented and functional programming, a succinct notation, and an advanced type system. The DSL offers a combination of data-parameterized state machines and temporal logic, which is novel. As an extension of Scala, it is a very expressive and convenient log file analysis framework.

Androgen receptor agonism promotes an osteogenic gene program in preadipocytes

PubMed Central

Hartig, Sean M.; Feng, Qin; Ochsner, Scott A.; Xiao, Rui; McKenna, Neil J.; McGuire, Sean E.; He, Bin

2013-01-01

Androgens regulate body composition by interacting with the androgen receptor (AR) to control gene expression in a tissue-specific manner. To identify novel regulatory roles for AR in preadipocytes, we created a 3T3-L1 cell line stably expressing human AR. We found AR expression is required for androgen-mediated inhibition of 3T3-L1 adipogenesis. This inhibition is characterized by decreased lipid accumulation, reduced expression of adipogenic genes, and induction of genes associated with osteoblast differentiation. Collectively, our results suggest androgens promote an osteogenic gene program at the expense of adipocyte differentiation. PMID:23567971

Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death

PubMed Central

1996-01-01

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point. PMID:8642331

Reassessing apoptosis in plants.

PubMed

Dickman, Martin; Williams, Brett; Li, Yurong; de Figueiredo, Paul; Wolpert, Thomas

2017-10-01

Cell death can be driven by a genetically programmed signalling pathway known as programmed cell death (PCD). In plants, PCD occurs during development as well as in response to environmental and biotic stimuli. Our understanding of PCD regulation in plants has advanced significantly over the past two decades; however, the molecular machinery responsible for driving the system remains elusive. Thus, whether conserved PCD regulatory mechanisms include plant apoptosis remains enigmatic. Animal apoptotic regulators, including Bcl-2 family members, have not been identified in plants but expression of such regulators can trigger or suppress plant PCD. Moreover, plants exhibit nearly all of the biochemical and morphological features of apoptosis. One difference between plant and animal PCD is the absence of phagocytosis in plants. Evidence is emerging that the vacuole may be key to removal of unwanted plant cells, and may carry out functions that are analogous to animal phagocytosis. Here, we provide context for the argument that apoptotic-like cell death occurs in plants.

Maternal Diets Trigger Sex-Specific Divergent Trajectories of Gene Expression and Epigenetic Systems in Mouse Placenta

PubMed Central

Gabory, Anne; Ferry, Laure; Fajardy, Isabelle; Jouneau, Luc; Gothié, Jean-David; Vigé, Alexandre; Fleur, Cécile; Mayeur, Sylvain; Gallou-Kabani, Catherine; Gross, Marie-Sylvie; Attig, Linda; Vambergue, Anne; Lesage, Jean; Reusens, Brigitte; Vieau, Didier; Remacle, Claude; Jais, Jean-Philippe; Junien, Claudine

2012-01-01

Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols. PMID:23144842

Stability of Reference Gene Expression After Porcine Sapelovirus Infection in Porcine Intestinal Epithelial Cells.

PubMed

Huang, Yong; Chen, Yabing; Sun, Huan; Lan, Daoliang

2016-01-01

Intestinal epithelial cells, which serve as the first physical barrier to protect intestinal tract from external antigens, have an important role in the local innate immunity. Screening of reference genes that have stable expression levels after viral infection in porcine intestinal epithelial cells is critical for ensuring the reliability of the expression analysis on anti-infection genes in porcine intestinal epithelial cells. In this study, nine common reference genes in pigs, including ACTB, B2M, GAPDH, HMBS, SDHA, HPRT1, TBP, YWHAZ, and RPL32, were chosen as the candidate reference genes. Porcine sapelovirus (PSV) was used as a model virus to infect porcine intestinal epithelial cell line (IPEC-J2). The expression stability of the nine genes was assessed by the geNorm, NormFinder, and BestKeeper software. Moreover, RefFinder program was used to evaluate the analytical results of above three softwares, and a relative expression experiment of selected target gene was used to verify the analysis results. The comprehensive results indicated that the gene combination of TBP and RPL32 has the most stable expression, which could be considered as an appropriate reference gene for research on gene expression after PSV infection in IPEC-J2cells. The results provided essential data for expression analysis of anti-infection genes in porcine intestinal epithelial cells.

snoSeeker: an advanced computational package for screening of guide and orphan snoRNA genes in the human genome.

PubMed

Yang, Jian-Hua; Zhang, Xiao-Chen; Huang, Zhan-Peng; Zhou, Hui; Huang, Mian-Bo; Zhang, Shu; Chen, Yue-Qin; Qu, Liang-Hu

2006-01-01

Small nucleolar RNAs (snoRNAs) represent an abundant group of non-coding RNAs in eukaryotes. They can be divided into guide and orphan snoRNAs according to the presence or absence of antisense sequence to rRNAs or snRNAs. Current snoRNA-searching programs, which are essentially based on sequence complementarity to rRNAs or snRNAs, exist only for the screening of guide snoRNAs. In this study, we have developed an advanced computational package, snoSeeker, which includes CDseeker and ACAseeker programs, for the highly efficient and specific screening of both guide and orphan snoRNA genes in mammalian genomes. By using these programs, we have systematically scanned four human-mammal whole-genome alignment (WGA) sequences and identified 54 novel candidates including 26 orphan candidates as well as 266 known snoRNA genes. Eighteen novel snoRNAs were further experimentally confirmed with four snoRNAs exhibiting a tissue-specific or restricted expression pattern. The results of this study provide the most comprehensive listing of two families of snoRNA genes in the human genome till date.

Divergence between motoneurons: gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons

PubMed Central

Cui, Dapeng; Dougherty, Kimberly J.; Machacek, David W.; Sawchuk, Michael; Hochman, Shawn; Baro, Deborah J.

2009-01-01

Studies in the developing spinal cord suggest that different motoneuron (MN) cell types express very different genetic programs, but the degree to which adult programs differ is unknown. To compare genetic programs between adult MN columnar cell types, we used laser capture micro-dissection (LCM) and Affymetrix microarrays to create expression profiles for three columnar cell types: lateral and medial MNs from lumbar segments and sympathetic preganglionic motoneurons located in the thoracic intermediolateral nucleus. A comparison of the three expression profiles indicated that ~7% (813/11,552) of the genes showed significant differences in their expression levels. The largest differences were observed between sympathetic preganglionic MNs and the lateral motor column, with 6% (706/11,552) of the genes being differentially expressed. Significant differences in expression were observed for 1.8% (207/11,552) of the genes when comparing sympathetic preganglionic MNs with the medial motor column. Lateral and medial MNs showed the least divergence, with 1.3% (150/11,552) of the genes being differentially expressed. These data indicate that the amount of divergence in expression profiles between identified columnar MNs does not strictly correlate with divergence of function as defined by innervation patterns (somatic/muscle vs. autonomic/viscera). Classification of the differentially expressed genes with regard to function showed that they underpin all fundamental cell systems and processes, although most differentially expressed genes encode proteins involved in signal transduction. Mining the expression profiles to examine transcription factors essential for MN development suggested that many of the same transcription factors participatein combinatorial codes in embryonic and adult neurons, but patterns of expression change significantly. PMID:16317082

Maple procedures for the coupling of angular momenta. IX. Wigner D-functions and rotation matrices

NASA Astrophysics Data System (ADS)

Pagaran, J.; Fritzsche, S.; Gaigalas, G.

2006-04-01

The Wigner D-functions, Dpqj(α,β,γ), are known for their frequent use in quantum mechanics. Defined as the matrix elements of the rotation operator Rˆ(α,β,γ) in R and parametrized in terms of the three Euler angles α, β, and γ, these functions arise not only in the transformation of tensor components under the rotation of the coordinates, but also as the eigenfunctions of the spherical top. In practice, however, the use of the Wigner D-functions is not always that simple, in particular, if expressions in terms of these and other functions from the theory of angular momentum need to be simplified before some computations can be carried out in detail. To facilitate the manipulation of such Racah expressions, here we present an extension to the RACAH program [S. Fritzsche, Comput. Phys. Comm. 103 (1997) 51] in which the properties and the algebraic rules of the Wigner D-functions and reduced rotation matrices are implemented. Care has been taken to combine the standard knowledge about the rotation matrices with the previously implemented rules for the Clebsch-Gordan coefficients, Wigner n-j symbols, and the spherical harmonics. Moreover, the application of the program has been illustrated below by means of three examples. Program summaryTitle of program:RACAH Catalogue identifier:ADFv_9_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADFv_9_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Catalogue identifier of previous version: ADFW, ADHW, title RACAH Journal reference of previous version(s): S. Fritzsche, Comput. Phys. Comm. 103 (1997) 51; S. Fritzsche, S. Varga, D. Geschke, B. Fricke, Comput. Phys. Comm. 111 (1998) 167; S. Fritzsche, T. Inghoff, M. Tomaselli, Comput. Phys. Comm. 153 (2003) 424. Does the new version supersede the previous one: Yes, in addition to the spherical harmonics and recoupling coefficients, the program now supports also the occurrence of the Wigner rotation matrices in the algebraic expressions to be evaluated. Licensing provisions:None Computer for which the program is designed and others on which it is operable: All computers with a license for the computer algebra package Maple [Maple is a registered trademark of Waterloo Maple Inc.] Installations:University of Kassel (Germany) Operating systems under which the program has been tested: Linux 8.2+ Program language used:MAPLE, Release 8 and 9 Memory required to execute with typical data:10-50 MB No. of lines in distributed program, including test data, etc.:52 653 No. of bytes in distributed program, including test data, etc.:1 195 346 Distribution format:tar.gzip Nature of the physical problem: The Wigner D-functions and (reduced) rotation matrices occur very frequently in physical applications. They are known not only as the (infinite) representation of the rotation group but also to obey a number of integral and summation rules, including those for their orthogonality and completeness. Instead of the direct computation of these matrices, therefore, one first often wishes to find algebraic simplifications before the computations can be carried out in practice. Reasons for new version: The RACAH program has been found an efficient tool during recent years, in order to evaluate and simplify expressions from Racah's algebra. Apart from the Wigner n-j symbols ( j=3,6,9) and spherical harmonics, we now extended the code to allow for Wigner rotation matrices. This extension will support the study of those quantum processes especially where different axis of quantization occurs in course of the theoretical deviations. Summary of revisions: In a revised version of the RACAH program [S. Fritzsche, Comput. Phys. Comm. 103 (1997) 51; S. Fritzsche, T. Inghoff, M. Tomaselli, Comput. Phys. Comm. 153 (2003) 424], we now also support the occurrence of the Wigner D-functions and reduced rotation matrices. By following our previous design, the (algebraic) properties of these rotation matrices as well as a number of summation and integration rules are implemented to facilitate the algebraic simplification of expressions from the theories of angular momentum and the spherical tensor operators. Restrictions onto the complexity of the problem: The definition as well as the properties of the rotation matrices, as used in our implementation, are based mainly on the book of Varshalovich et al. [D.A. Varshalovich, A.N. Moskalev, V.K. Khersonskii, Quantum Theory of Angular Momentum, World Scientific, Singapore, 1988], Chapter 4. From this monograph, most of the relations involving the Wigner D-functions and rotation matrices are taken into account although, in practice, only a rather selected set was needed to be implemented explicitly owing to the symmetries of these functions. In the integration over the rotation matrices, products of up to three Wigner D-functions or reduced matrices (with the same angular arguments) are recognized and simplified properly; for the integration over a solid angle, however, the domain of integration must be specified for the Euler angles α and γ. This restriction arose because MAPLE does not generate a constant of integration when the limits in the integral are omitted. For any integration over the angle β the range of the integration, if omitted, is always taken from 0 to π. Unusual features of the program: The RACAH program is designed for interactive use that allows a quick and algebraic evaluation of (complex) expression from Racah's algebra. It is based on a number of well-defined data structures that are now extended to incorporate the Wigner rotation matrices. For these matrices, the transformation properties, sum rules, recursion relations, as well as a variety of special function expansions have been added to the previous functionality of the RACAH program. Moreover, the knowledge about the orthogonality as well as the completeness of the Wigner D-functions is also implemented. Typical running time:All the examples presented in Section 4 take only a few seconds on a 1.5 GHz Pentium Pro computer.

Barriers and Facilitators to Tobacco Cessation in a Nationwide Sample of Addiction Treatment Programs.

PubMed

Pagano, Anna; Tajima, Barbara; Guydish, Joseph

2016-08-01

Smoking rates among addiction treatment clients are 3-4 times higher than those of the general population. Recent studies indicate that ceasing tobacco use during treatment may improve recovery outcomes. Across the United States, publicly funded addiction treatment programs vary widely in terms of their tobacco policies and tobacco cessation services offered to clients. The study reported here is the qualitative component of a larger study. Twenty-four programs were recruited from a random sample of publicly funded programs participating in the NIDA Clinical Trials Network. Semi-structured interviews were administered by phone to program directors. ATLAS.ti software was used to facilitate thematic analysis of interview transcripts. While all directors expressed interest in helping clients to quit smoking, they cited numerous barriers to implementing tobacco policies and services. These included smoking culture, client resistance, lack of resources, staff smoking, and environmental barriers. Directors also cited several factors that they believed would support tobacco cessation. These included financial support, enhanced leadership, and state mandates against smoking in addiction treatment programs. Addiction treatment programs are beginning to place more emphasis on tobacco cessation during treatment. However, furthering this goal requires substantial infrastructural and cultural change. These qualitative study findings may help to inform Single State Agencies (SSAs) to support publicly funded addiction treatment programs in their tobacco cessation efforts. In order to maximize effectiveness, state-level policies regarding tobacco cessation during treatment should be informed by ongoing dialogue between service providers and SSAs. Copyright © 2016 Elsevier Inc. All rights reserved.

Engaging partners to initiate evaluation efforts: tactics used and lessons learned from the prevention research centers program.

PubMed

Wright, Demia Sundra; Anderson, Lynda A; Brownson, Ross C; Gwaltney, Margaret K; Scherer, Jennifer; Cross, Alan W; Goodman, Robert M; Schwartz, Randy; Sims, Tom; White, Carol R

2008-01-01

The Centers for Disease Control and Prevention's (CDC's) Prevention Research Centers (PRC) Program underwent a 2-year evaluation planning project using a participatory process that allowed perspectives from the national community of PRC partners to be expressed and reflected in a national logic model. The PRC Program recognized the challenge in developing a feasible, useable, and relevant evaluation process for a large, diverse program. To address the challenge, participatory and utilization-focused evaluation models were used. Four tactics guided the evaluation planning process: 1) assessing stakeholders' communication needs and existing communication mechanisms and infrastructure; 2) using existing mechanisms and establishing others as needed to inform, educate, and request feedback; 3) listening to and using feedback received; and 4) obtaining adequate resources and building flexibility into the project plan to support multifaceted mechanisms for data collection. Participatory methods resulted in buy-in from stakeholders and the development of a national logic model. Benefits included CDC's use of the logic model for program planning and development of a national evaluation protocol and increased expectations among PRC partners for involvement. Challenges included the time, effort, and investment of program resources required for the participatory approach and the identification of whom to engage and when to engage them for feedback on project decisions. By using a participatory and utilization-focused model, program partners positively influenced how CDC developed an evaluation plan. The tactics we used can guide the involvement of program stakeholders and help with decisions on appropriate methods and approaches for engaging partners.

A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae

DOE PAGES

Reider Apel, Amanda; d'Espaux, Leo; Wehrs, Maren; ...

2016-11-28

Despite the extensive use of Saccharomyces cerevisiae as a platform for synthetic biology, strain engineering remains slow and laborious. Here, we employ CRISPR/Cas9 technology to build a cloning-free toolkit that addresses commonly encountered obstacles in metabolic engineering, including chromosomal integration locus and promoter selection, as well as protein localization and solubility. The toolkit includes 23 Cas9-sgRNA plasmids, 37 promoters of various strengths and temporal expression profiles, and 10 protein-localization, degradation and solubility tags. We facilitated the use of these parts via a web-based tool, that automates the generation of DNA fragments for integration. Our system builds upon existing gene editingmore » methods in the thoroughness with which the parts are standardized and characterized, the types and number of parts available and the ease with which our methodology can be used to perform genetic edits in yeast. We demonstrated the applicability of this toolkit by optimizing the expression of a challenging but industrially important enzyme, taxadiene synthase (TXS). This approach enabled us to diagnose an issue with TXS solubility, the resolution of which yielded a 25-fold improvement in taxadiene production.« less

A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae

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

Reider Apel, Amanda; d'Espaux, Leo; Wehrs, Maren

Despite the extensive use of Saccharomyces cerevisiae as a platform for synthetic biology, strain engineering remains slow and laborious. Here, we employ CRISPR/Cas9 technology to build a cloning-free toolkit that addresses commonly encountered obstacles in metabolic engineering, including chromosomal integration locus and promoter selection, as well as protein localization and solubility. The toolkit includes 23 Cas9-sgRNA plasmids, 37 promoters of various strengths and temporal expression profiles, and 10 protein-localization, degradation and solubility tags. We facilitated the use of these parts via a web-based tool, that automates the generation of DNA fragments for integration. Our system builds upon existing gene editingmore » methods in the thoroughness with which the parts are standardized and characterized, the types and number of parts available and the ease with which our methodology can be used to perform genetic edits in yeast. We demonstrated the applicability of this toolkit by optimizing the expression of a challenging but industrially important enzyme, taxadiene synthase (TXS). This approach enabled us to diagnose an issue with TXS solubility, the resolution of which yielded a 25-fold improvement in taxadiene production.« less

The calculation of sparticle and Higgs decays in the minimal and next-to-minimal supersymmetric standard models: SOFTSUSY4.0

NASA Astrophysics Data System (ADS)

Allanach, B. C.; Cridge, T.

2017-11-01

We describe a major extension of the SOFTSUSY spectrum calculator to include the calculation of the decays, branching ratios and lifetimes of sparticles into lighter sparticles, covering the next-to-minimal supersymmetric standard model (NMSSM) as well as the minimal supersymmetric standard model (MSSM). This document acts as a manual for the new version of SOFTSUSY, which includes the calculation of sparticle decays. We present a comprehensive collection of explicit expressions used by the program for the various partial widths of the different decay modes in the appendix. Program Files doi:http://dx.doi.org/10.17632/5hhwwmp43g.1 Licensing provisions: GPLv3 Programming language:C++, fortran Nature of problem: Calculating supersymmetric particle partial decay widths in the MSSM or the NMSSM, given the parameters and spectrum which have already been calculated by SOFTSUSY. Solution method: Analytic expressions for tree-level 2 body decays and loop-level decays and one-dimensional numerical integration for 3 body decays. Restrictions: Decays are calculated in the real R -parity conserving MSSM or the real R -parity conserving NMSSM only. No additional charge-parity violation (CPV) relative to the Standard Model (SM). Sfermion mixing has only been accounted for in the third generation of sfermions in the decay calculation. Decays in the MSSM are 2-body and 3-body, whereas decays in the NMSSM are 2-body only. Does the new version supersede the previous version?: Yes. Reasons for the new version: Significantly extended functionality. The decay rates and branching ratios of sparticles are particularly useful for collider searches. Decays calculated in the NMSSM will be a particularly useful check of the other programs in the literature, of which there are few. Summary of revisions: Addition of the calculation of sparticle and Higgs decays. All 2-body and important 3-body tree-level decays, including phenomenologically important loop-level decays (notably, Higgs decays to gg, γγ and Zγ). Next-to-leading order corrections are added to neutral Higgs decays to q q ¯ for quarks q of any flavour and to the neutral Higgs decays to gg. Additional comments: Program obtainable from: http://softsusy.hepforge.org/

Real-Time MENTAT programming language and architecture

NASA Technical Reports Server (NTRS)

Grimshaw, Andrew S.; Silberman, Ami; Liu, Jane W. S.

1989-01-01

Real-time MENTAT, a programming environment designed to simplify the task of programming real-time applications in distributed and parallel environments, is described. It is based on the same data-driven computation model and object-oriented programming paradigm as MENTAT. It provides an easy-to-use mechanism to exploit parallelism, language constructs for the expression and enforcement of timing constraints, and run-time support for scheduling and exciting real-time programs. The real-time MENTAT programming language is an extended C++. The extensions are added to facilitate automatic detection of data flow and generation of data flow graphs, to express the timing constraints of individual granules of computation, and to provide scheduling directives for the runtime system. A high-level view of the real-time MENTAT system architecture and programming language constructs is provided.

Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila.

PubMed

Brüggemann, Holger; Hagman, Arne; Jules, Matthieu; Sismeiro, Odile; Dillies, Marie-Agnès; Gouyette, Catherine; Kunst, Frank; Steinert, Michael; Heuner, Klaus; Coppée, Jean-Yves; Buchrieser, Carmen

2006-08-01

Adaptation to the host environment and exploitation of host cell functions are critical to the success of intracellular pathogens. Here, insight to these virulence mechanisms was obtained for the first time from the transcriptional program of the human pathogen Legionella pneumophila during infection of its natural host, Acanthamoeba castellanii. The biphasic life cycle of L. pneumophila was reflected by a major shift in gene expression from replicative to transmissive phase, concerning nearly half of the genes predicted in the genome. However, three different L. pneumophila strains showed similar in vivo gene expression patterns, indicating that common regulatory mechanisms govern the Legionella life cycle, despite the plasticity of its genome. During the replicative phase, in addition to components of aerobic metabolism and amino acid catabolism, the Entner-Doudoroff pathway, a NADPH producing mechanism used for sugar and/or gluconate assimilation, was expressed, suggesting for the first time that intracellular L. pneumophila may also scavenge host carbohydrates as nutrients and not only proteins. Identification of genes only upregulated in vivo but not in vitro, may explain higher virulence of in vivo grown L. pneumophila. Late in the life cycle, L. pneumophila upregulates genes predicted to promote transmission and manipulation of a new host cell, therewith priming it for the next attack. These including substrates of the Dot/Icm secretion system, other factors associated previously with invasion and virulence, the motility and the type IV pilus machineries, and > 90 proteins not characterized so far. Analysis of a fliA (sigma28) deletion mutant identified genes coregulated with the flagellar regulon, including GGDEF/EAL regulators and factors that promote host cell entry and survival.

Heterologous expression of anti-apoptotic human 14-3-3β/α enhances iron-mediated programmed cell death in yeast

PubMed Central

Eid, Rawan; Zhou, David R.; Arab, Nagla T. T.; Boucher, Eric; Young, Paul G.; Mandato, Craig A.

2017-01-01

The induction of Programmed Cell Death (PCD) requires the activation of complex responses involving the interplay of a variety of different cellular proteins, pathways, and processes. Uncovering the mechanisms regulating PCD requires an understanding of the different processes that both positively and negatively regulate cell death. Here we have examined the response of normal as well as PCD resistant yeast cells to different PCD inducing stresses. As expected cells expressing the pro-survival human 14-3-3β/α sequence show increased resistance to numerous stresses including copper and rapamycin. In contrast, other stresses including iron were more lethal in PCD resistant 14-3-3β/α expressing cells. The increased sensitivity to PCD was not iron and 14-3-3β/α specific since it was also observed with other stresses (hydroxyurea and zinc) and other pro-survival sequences (human TC-1 and H-ferritin). Although microscopical examination revealed little differences in morphology with iron or copper stresses, cells undergoing PCD in response to high levels of prolonged copper treatment were reduced in size. This supports the interaction some forms of PCD have with the mechanisms regulating cell growth. Analysis of iron-mediated effects in yeast mutant strains lacking key regulators suggests that a functional vacuole is required to mediate the synergistic effects of iron and 14-3-3β/α on yeast PCD. Finally, mild sub-lethal levels of copper were found to attenuate the observed inhibitory effects of iron. Taken together, we propose a model in which a subset of stresses like iron induces a complex process that requires the cross-talk of two different PCD inducing pathways. PMID:28854230

Simulation of n-qubit quantum systems. III. Quantum operations

NASA Astrophysics Data System (ADS)

Radtke, T.; Fritzsche, S.

2007-05-01

During the last decade, several quantum information protocols, such as quantum key distribution, teleportation or quantum computation, have attracted a lot of interest. Despite the recent success and research efforts in quantum information processing, however, we are just at the beginning of understanding the role of entanglement and the behavior of quantum systems in noisy environments, i.e. for nonideal implementations. Therefore, in order to facilitate the investigation of entanglement and decoherence in n-qubit quantum registers, here we present a revised version of the FEYNMAN program for working with quantum operations and their associated (Jamiołkowski) dual states. Based on the implementation of several popular decoherence models, we provide tools especially for the quantitative analysis of quantum operations. Apart from the implementation of different noise models, the current program extension may help investigate the fragility of many quantum states, one of the main obstacles in realizing quantum information protocols today. Program summaryTitle of program: Feynman Catalogue identifier: ADWE_v3_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADWE_v3_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions: None Operating systems: Any system that supports MAPLE; tested under Microsoft Windows XP, SuSe Linux 10 Program language used:MAPLE 10 Typical time and memory requirements: Most commands that act upon quantum registers with five or less qubits take ⩽10 seconds of processor time (on a Pentium 4 processor with ⩾2 GHz or equivalent) and 5-20 MB of memory. Especially when working with symbolic expressions, however, the memory and time requirements critically depend on the number of qubits in the quantum registers, owing to the exponential dimension growth of the associated Hilbert space. For example, complex (symbolic) noise models (with several Kraus operators) for multi-qubit systems often result in very large symbolic expressions that dramatically slow down the evaluation of measures or other quantities. In these cases, MAPLE's assume facility sometimes helps to reduce the complexity of symbolic expressions, but often only numerical evaluation is possible. Since the complexity of the FEYNMAN commands is very different, no general scaling law for the CPU time and memory usage can be given. No. of bytes in distributed program including test data, etc.: 799 265 No. of lines in distributed program including test data, etc.: 18 589 Distribution format: tar.gz Reasons for new version: While the previous program versions were designed mainly to create and manipulate the state of quantum registers, the present extension aims to support quantum operations as the essential ingredient for studying the effects of noisy environments. Does this version supersede the previous version: Yes Nature of the physical problem: Today, entanglement is identified as the essential resource in virtually all aspects of quantum information theory. In most practical implementations of quantum information protocols, however, decoherence typically limits the lifetime of entanglement. It is therefore necessary and highly desirable to understand the evolution of entanglement in noisy environments. Method of solution: Using the computer algebra system MAPLE, we have developed a set of procedures that support the definition and manipulation of n-qubit quantum registers as well as (unitary) logic gates and (nonunitary) quantum operations that act on the quantum registers. The provided hierarchy of commands can be used interactively in order to simulate and analyze the evolution of n-qubit quantum systems in ideal and nonideal quantum circuits.

Expressive Writing: Enhancing the Emotional Intelligence of Human Services Majors

ERIC Educational Resources Information Center

Castillo, Yuleinys; Fischer, Jerome M.

2017-01-01

The skills and tasks in the human services field are highly connected to emotional intelligence abilities. The purpose of the study was to investigate the effect of an expressive writing program involving human service students in an undergraduate rehabilitation services course. The program was developed to enhance their emotional intelligence.…

A Conversion Tool for Mathematical Expressions in Web XML Files.

ERIC Educational Resources Information Center

Ohtake, Nobuyuki; Kanahori, Toshihiro

2003-01-01

This article discusses the conversion of mathematical equations into Extensible Markup Language (XML) on the World Wide Web for individuals with visual impairments. A program is described that converts the presentation markup style to the content markup style in MathML to allow browsers to render mathematical expressions without other programs.…

Attitudes of Jordanian Adolescent Students Toward Overweight and Obesity

PubMed Central

Abu Baker, Nesrin N.; Al-Ali, Nahla; Al-Ajlouni, Ranyah

2018-01-01

Background: Obesity is a serious public health problem especially among adolescents. Understanding adolescents’ attitudes toward obesity and healthy lifestyle is a crucial step to develop effective health programs to treat and prevent obesity. Objectives: To examine the attitudes toward overweight and obesity among Jordanian adolescent students and to identify the components of obesity prevention program that the students perceive as important. Methods: A sample of 1000 students in 8th to 10th grades was randomly selected from 16 schools in Irbid, Jordan. A self-reported questionnaire including attitude related questions was used in a descriptive, cross-sectional study. Results: Generally, the students expressed positive attitudes toward obesity; which means that their attitudes were consistent with societal norms in terms of health and social functioning (mean= 3.5, SD=0.39). Furthermore, the students expressed positive attitudes toward lifestyle; which means that their attitudes were consistent with healthy behaviors (mean=3.7, SD=0.58). However, boys had significantly more positive attitudes than girls (p=0.04). The prevalence of overweight and obesity was 23.8%, while obese and non-obese students had similar attitudes toward lifestyle and obesity. Finally, around 20% to 30% of students desired a prevention program out of school time shared with their families and friends and involves eating healthy food and getting more exercise. Conclusion: More efforts are needed to build effective obesity prevention programs that focus on eating healthy diet and getting more exercise considering gender differences. PMID:29456780

Creative musical expression as a catalyst for quality-of-life improvement in inner-city adolescents placed in a court-referred residential treatment program.

PubMed

Bittman, Barry; Dickson, Larry; Coddington, Kim

2009-01-01

Obstacles to effectively rehabilitate inner-city adolescents in staff-secure residential treatment centers should not be underestimated. Effective evidence-based protocols are lacking to help juveniles who are often angry, detached, frustrated, and in direct conflict with their peers. Facing a myriad of issues ranging from youth delinquency offenses to trauma, abuse, drug/alcohol use, peer pressure/gang-related activities, lack of structure in home environments, mental health diagnoses, and cognitive functioning difficulties, these adolescents present extraordinary challenges to an over-stressed juvenile justice system. A randomized controlled crossover study is utilized to comprehensively evaluate the effectiveness of a novel creative musical expression protocol as a catalyst for nonverbal and verbal disclosure leading to improvements in quality of life for inner-city youth in a court-referred residential treatment program. A total of 52 (30 females and 22 males) African-American, Asian, Caucasian, and Puerto Rican subjects ranging in age from 12 to 18 (mean age 14.5) completed the study. Dependent variable measures included the Child and Adolescent Functional Assessment Scale (CAFAS), the Adolescent Psychopathology Scale (APS), the Adolescent Anger Rating Scale (AARS), the Reynolds Adolescent Depression Scale, 2nd edition (RADS 2), and the Adolescent Visual-Analog Recreational Music Making Assessment (A-VARMMA). Statistically significant (experimental vs control) improvements in multiple parameters include school/work role performance, total depression, anhedonia/negative affect, negative self-evaluation, and instrumental anger. In addition, extended impact (experimental vs control) is characterized by statistically significant improvements 6 weeks after completion of the protocol, for school/work role performance, behavior toward others, anhedonia/negative affect, total anger, instrumental anger, anger, and interpersonal problems. The primary limitations of this study include an extended follow-up period of only 6 weeks post completion of the protocol, and the inability to blind the counselors performing standardized assessments. This study is the first of its kind to test a replicable creative musical expression protocol as a catalyst for nonverbal and verbal disclosure leading to improved quality of life for inner-city youth in a court-referred residential treatment program. With substantial potential for widespread dissemination, this innovative protocol for adolescents can be readily utilized by behavioral health professionals without prior musical experience.

NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

PubMed

Singh-Taylor, A; Molet, J; Jiang, S; Korosi, A; Bolton, J L; Noam, Y; Simeone, K; Cope, J; Chen, Y; Mortazavi, A; Baram, T Z

2018-03-01

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies

PubMed Central

Ilcus, Cristina; Bagacean, Cristina; Tempescul, Adrian; Popescu, Cristian; Parvu, Andrada; Cenariu, Mihai; Bocsan, Corina; Zdrenghea, Mihnea

2017-01-01

The co-inhibitory receptor programmed cell death (PD)-1, expressed by immune effector cells, is credited with a protective role for normal tissue during immune responses, by limiting the extent of effector activation. Its presently known ligands, programmed death ligands (PD-Ls) 1 and 2, are expressed by a variety of cells including cancer cells, suggesting a role for these molecules as an immune evasion mechanism. Blocking of the PD-1-PD-L signaling axis has recently been shown to be effective and was clinically approved in relapsed/refractory tumors such as malignant melanoma and lung cancer, but also classical Hodgkin’s lymphoma. A plethora of trials exploring PD-1 blockade in cancer are ongoing. Here, we review the role of PD-1 signaling in lymphoid malignancies, and the latest results of trials investigating PD-1 or PD-L1 blocking agents in this group of diseases. Early phase studies proved very promising, leading to the clinical approval of a PD-1 blocking agent in Hodgkin’s lymphoma, and Phase III clinical studies are either planned or ongoing in most lymphoid malignancies. PMID:28496333

Transcriptional analysis of product-concentration driven changes in cellular programs of recombinant Clostridium acetobutylicumstrains.

PubMed

Tummala, Seshu B; Junne, Stefan G; Paredes, Carlos J; Papoutsakis, Eleftherios T

2003-12-30

Antisense RNA (asRNA) downregulation alters protein expression without changing the regulation of gene expression. Downregulation of primary metabolic enzymes possibly combined with overexpression of other metabolic enzymes may result in profound changes in product formation, and this may alter the large-scale transcriptional program of the cells. DNA-array based large-scale transcriptional analysis has the potential to elucidate factors that control cellular fluxes even in the absence of proteome data. These themes are explored in the study of large-scale transcriptional analysis programs and the in vivo primary-metabolism fluxes of several related recombinant C. acetobutylicum strains: C. acetobutylicum ATCC 824(pSOS95del) (plasmid control; produces high levels of butanol snd acetone), 824(pCTFB1AS) (expresses antisense RNA against CoA transferase (ctfb1-asRNA); produces very low levels of butanol and acetone), and 824(pAADB1) (expresses ctfb1-asRNA and the alcohol-aldehyde dahydrogenase gene (aad); produce high alcohol and low acetone levels). DNA-array based transcriptional analysis revealed that the large changes in product concentrations (snd notably butanol concentration) due to ctfb1-asRNA expression alone and in combination with aad overexpression resulted in dramatic changes of the cellular transcriptome. Cluster analysis and gene expression patterns of established and putative operons involved in stress response, motility, sporulation, and fatty-acid biosynthesis indicate that these simple genetic changes dramatically alter the cellular programs of C. acetobutylicum. Comparison of gene expression and flux analysis data may point to possible flux-controling steps and suggest unknown regulatory mechanisms. Copyright 2003; Wiley Periodicals, Inc.

Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients.

PubMed

Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan; Mora-Jensen, Helena; Krogh, Anders; Kohlmann, Alexander; Thiede, Christian; Borregaard, Niels; Bullinger, Lars; Winther, Ole; Theilgaard-Mönch, Kim; Porse, Bo T

2014-02-06

Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.

Defining the Transcriptional Landscape during Cytomegalovirus Latency with Single-Cell RNA Sequencing

PubMed Central

2018-01-01

ABSTRACT Primary infection with human cytomegalovirus (HCMV) results in a lifelong infection due to its ability to establish latent infection, with one characterized viral reservoir being hematopoietic cells. Although reactivation from latency causes serious disease in immunocompromised individuals, our molecular understanding of latency is limited. Here, we delineate viral gene expression during natural HCMV persistent infection by analyzing the massive transcriptome RNA sequencing (RNA-seq) atlas generated by the Genotype-Tissue Expression (GTEx) project. This systematic analysis reveals that HCMV persistence in vivo is prevalent in diverse tissues. Notably, we find only viral transcripts that resemble gene expression during various stages of lytic infection with no evidence of any highly restricted latency-associated viral gene expression program. To further define the transcriptional landscape during HCMV latent infection, we also used single-cell RNA-seq and a tractable experimental latency model. In contrast to some current views on latency, we also find no evidence for any highly restricted latency-associated viral gene expression program. Instead, we reveal that latency-associated gene expression largely mirrors a late lytic viral program, albeit at much lower levels of expression. Overall, our work has the potential to revolutionize our understanding of HCMV persistence and suggests that latency is governed mainly by quantitative changes, with a limited number of qualitative changes, in viral gene expression. PMID:29535194

Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, and Pax7 genes during myogenesis

PubMed Central

Demmerle, Justin; Koch, Adam J.; Holaska, James M.

2016-01-01

The spatial organization of chromatin is critical in establishing cell-type dependent gene expression programs. The inner nuclear membrane protein emerin has been implicated in regulating global chromatin architecture. We show emerin associates with genomic loci of muscle differentiation promoting factors in murine myogenic progenitors, including Myf5 and MyoD. Prior to their transcriptional activation Myf5 and MyoD loci localized to the nuclear lamina in proliferating progenitors and moved to the nucleoplasm upon transcriptional activation during differentiation. The Pax7 locus, which is transcribed in proliferating progenitors, localized to the nucleoplasm and Pax7 moved to the nuclear lamina upon repression during differentiation. Localization of Myf5, MyoD, and Pax7 to the nuclear lamina and proper temporal expression of these genes required emerin and HDAC3. Interestingly, activation of HDAC3 catalytic activity rescued both Myf5 localization to the nuclear lamina and its expression. Collectively, these data support a model whereby emerin facilitates repressive chromatin formation at the nuclear lamina by activating the catalytic activity of HDAC3 to regulate the coordinated spatiotemporal expression of myogenic differentiation genes. PMID:24062260

Integrating Language, Pragmatics, and Social Intervention in a Single-Subject Case Study of a Child With a Developmental Social Communication Disorder.

PubMed

Adams, Catherine; Gaile, Jacqueline; Lockton, Elaine; Freed, Jenny

2015-10-01

This clinical focus article presents an illustration of a complex communication intervention, the Social Communication Intervention Programme (SCIP), as delivered to a child who has a social communication disorder (SCD). The SCIP intervention combined language processing and pragmatic and social understanding therapies in a program of individualized therapy activities and in close liaison with families. The study used an enhanced AB single-subject design in which an 8-year-old child with an SCD participated in 20 therapy sessions with a specialist speech-language pathologist. A procedure of matching assessment findings to intervention choices was followed to construct an individualized treatment program. Examples of intervention content and the embedded structure of SCIP are illustrated. Observational and formal measurements of receptive and expressive language, conversation, and parent-teacher ratings of social communication were completed before therapy, after therapy, and at a 6-month follow-up session. Outcomes revealed change in total and receptive language scores but not in expressive language. Conversation showed marked improvement in responsiveness, appreciation of listener knowledge, turn taking, and adaptation of discourse style. Teacher-reported outcomes included improved classroom behavior and enhanced literacy skills. Parent-reported outcomes included improved verbal interactions with family members and personal narratives. This clinical focus article demonstrates the complexity of needs in a child with an SCD and how these can be addressed in individualized intervention. Findings are discussed in relation to the essential nature of language support including pragmatic therapy for children with SCDs. Discussion of the role of formal and functional outcome measurement as well as the proximity of chosen outcomes to the intervention is included.

CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

PubMed Central

Hu, Shimin; Xu-Monette, Zijun Y.; Balasubramanyam, Aarthi; Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexander; Liu, Wei-min; Miranda, Roberto N.; Zhang, Li; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W. L.; Han van Krieken, J.; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Zhao, Xiaoying; Winter, Jane N.; Zhang, Mingzhi; Li, Ling; Møller, Michael B.; Piris, Miguel A.; Li, Yong; Go, Ronald S.; Wu, Lin; Medeiros, L. Jeffrey; Young, Ken H.

2013-01-01

CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+, 79% vs CD30–, 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30+ DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30+ DLBCL as a distinct subgroup of DLBCL. PMID:23343832

Research in advanced formal theorem-proving techniques. [design and implementation of computer languages

NASA Technical Reports Server (NTRS)

Raphael, B.; Fikes, R.; Waldinger, R.

1973-01-01

The results are summarised of a project aimed at the design and implementation of computer languages to aid in expressing problem solving procedures in several areas of artificial intelligence including automatic programming, theorem proving, and robot planning. The principal results of the project were the design and implementation of two complete systems, QA4 and QLISP, and their preliminary experimental use. The various applications of both QA4 and QLISP are given.

A Seasonal Time-Series Model Based on Gene Expression Programming for Predicting Financial Distress

PubMed Central

2018-01-01

The issue of financial distress prediction plays an important and challenging research topic in the financial field. Currently, there have been many methods for predicting firm bankruptcy and financial crisis, including the artificial intelligence and the traditional statistical methods, and the past studies have shown that the prediction result of the artificial intelligence method is better than the traditional statistical method. Financial statements are quarterly reports; hence, the financial crisis of companies is seasonal time-series data, and the attribute data affecting the financial distress of companies is nonlinear and nonstationary time-series data with fluctuations. Therefore, this study employed the nonlinear attribute selection method to build a nonlinear financial distress prediction model: that is, this paper proposed a novel seasonal time-series gene expression programming model for predicting the financial distress of companies. The proposed model has several advantages including the following: (i) the proposed model is different from the previous models lacking the concept of time series; (ii) the proposed integrated attribute selection method can find the core attributes and reduce high dimensional data; and (iii) the proposed model can generate the rules and mathematical formulas of financial distress for providing references to the investors and decision makers. The result shows that the proposed method is better than the listing classifiers under three criteria; hence, the proposed model has competitive advantages in predicting the financial distress of companies. PMID:29765399

A Seasonal Time-Series Model Based on Gene Expression Programming for Predicting Financial Distress.

PubMed

Cheng, Ching-Hsue; Chan, Chia-Pang; Yang, Jun-He

2018-01-01

The issue of financial distress prediction plays an important and challenging research topic in the financial field. Currently, there have been many methods for predicting firm bankruptcy and financial crisis, including the artificial intelligence and the traditional statistical methods, and the past studies have shown that the prediction result of the artificial intelligence method is better than the traditional statistical method. Financial statements are quarterly reports; hence, the financial crisis of companies is seasonal time-series data, and the attribute data affecting the financial distress of companies is nonlinear and nonstationary time-series data with fluctuations. Therefore, this study employed the nonlinear attribute selection method to build a nonlinear financial distress prediction model: that is, this paper proposed a novel seasonal time-series gene expression programming model for predicting the financial distress of companies. The proposed model has several advantages including the following: (i) the proposed model is different from the previous models lacking the concept of time series; (ii) the proposed integrated attribute selection method can find the core attributes and reduce high dimensional data; and (iii) the proposed model can generate the rules and mathematical formulas of financial distress for providing references to the investors and decision makers. The result shows that the proposed method is better than the listing classifiers under three criteria; hence, the proposed model has competitive advantages in predicting the financial distress of companies.

Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.

PubMed

Rund, Samuel S C; Hou, Tim Y; Ward, Sarah M; Collins, Frank H; Duffield, Giles E

2011-08-09

Anopheles gambiae, the primary African vector of malaria parasites, exhibits numerous rhythmic behaviors including flight activity, swarming, mating, host seeking, egg laying, and sugar feeding. However, little work has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is regulated globally by diel and circadian mechanisms, we have undertaken a DNA microarray analysis of An. gambiae under light/dark cycle (LD) and constant dark (DD) conditions. Adult mated, non-blood-fed female mosquitoes were collected every 4 h for 48 h, and samples were processed with DNA microarrays. Using a cosine wave-fitting algorithm, we identified 1,293 and 600 rhythmic genes with a period length of 20-28 h in the head and body, respectively, under LD conditions, representing 9.7 and 4.5% of the An. gambiae gene set. A majority of these genes was specific to heads or bodies. Examination of mosquitoes under DD conditions revealed that rhythmic programming of the transcriptome is dependent on an interaction between the endogenous clock and extrinsic regulation by the LD cycle. A subset of genes, including the canonical clock components, was expressed rhythmically under both environmental conditions. A majority of genes had peak expression clustered around the day/night transitions, anticipating dawn and dusk. Genes cover diverse biological processes such as transcription/translation, metabolism, detoxification, olfaction, vision, cuticle regulation, and immunity, and include rate-limiting steps in the pathways. This study highlights the fundamental roles that both the circadian clock and light play in the physiology of this important insect vector and suggests targets for intervention.

Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring

PubMed Central

Ramírez-López, María Teresa; Arco, Raquel; Decara, Juan; Vázquez, Mariam; Noemí Blanco, Rosario; Alén, Francisco; Suárez, Juan; Gómez de Heras, Raquel

2016-01-01

Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS). In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a) the adult expression of endocannabinoid-related behaviors, b) the metabolic profile of adult offspring and c) the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a) sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b) features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c) tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed. PMID:27806128

Factors influencing perceived sustainability of Dutch community health programs.

PubMed

Vermeer, A J M; Van Assema, P; Hesdahl, B; Harting, J; De Vries, N K

2015-09-01

We assessed the perceived sustainability of community health programs organized by local intersectoral coalitions, as well as the factors that collaborating partners think might influence sustainability. Semi-structured interviews were conducted among 31 collaborating partners of 5 community health programs in deprived neighborhoods in the southern part of the Netherlands. The interview guide was based on a conceptual framework that includes factors related to the context, the leading organization, leadership, the coalition, collaborating partners, interventions and outcomes. Interviews were recorded, transcribed and content analyzed using NVivo 8.0. Participants in each of the programs varied in their perceptions of the sustainability of the program, but those people collaborating in pre-existing neighborhood structures expressed relatively high faith in their continuation. The participating citizens in particular believed that these structures would continue to address the health of the community in the future. We found factors from all categories of the conceptual framework that were perceived to influence sustainability. The program leaders appeared to be crucial to the programs, as they were frequently mentioned in close interaction with other factors. Program leaders should use a motivating and supportive leadership style and should act as 'program champions'. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CHESS (CgHExpreSS): a comprehensive analysis tool for the analysis of genomic alterations and their effects on the expression profile of the genome.

PubMed

Lee, Mikyung; Kim, Yangseok

2009-12-16

Genomic alterations frequently occur in many cancer patients and play important mechanistic roles in the pathogenesis of cancer. Furthermore, they can modify the expression level of genes due to altered copy number in the corresponding region of the chromosome. An accumulating body of evidence supports the possibility that strong genome-wide correlation exists between DNA content and gene expression. Therefore, more comprehensive analysis is needed to quantify the relationship between genomic alteration and gene expression. A well-designed bioinformatics tool is essential to perform this kind of integrative analysis. A few programs have already been introduced for integrative analysis. However, there are many limitations in their performance of comprehensive integrated analysis using published software because of limitations in implemented algorithms and visualization modules. To address this issue, we have implemented the Java-based program CHESS to allow integrative analysis of two experimental data sets: genomic alteration and genome-wide expression profile. CHESS is composed of a genomic alteration analysis module and an integrative analysis module. The genomic alteration analysis module detects genomic alteration by applying a threshold based method or SW-ARRAY algorithm and investigates whether the detected alteration is phenotype specific or not. On the other hand, the integrative analysis module measures the genomic alteration's influence on gene expression. It is divided into two separate parts. The first part calculates overall correlation between comparative genomic hybridization ratio and gene expression level by applying following three statistical methods: simple linear regression, Spearman rank correlation and Pearson's correlation. In the second part, CHESS detects the genes that are differentially expressed according to the genomic alteration pattern with three alternative statistical approaches: Student's t-test, Fisher's exact test and Chi square test. By successive operations of two modules, users can clarify how gene expression levels are affected by the phenotype specific genomic alterations. As CHESS was developed in both Java application and web environments, it can be run on a web browser or a local machine. It also supports all experimental platforms if a properly formatted text file is provided to include the chromosomal position of probes and their gene identifiers. CHESS is a user-friendly tool for investigating disease specific genomic alterations and quantitative relationships between those genomic alterations and genome-wide gene expression profiling.

Abstinence-based programs for prevention of adolescent pregnancies. A review.

PubMed

Thomas, M H

2000-01-01

This article assesses the abstinence-based programs developed by family life educators and the factors associated with positive results through a review of abstinence promotion programs of the federal government. In 1996, Section 510 was added to Title V of the Social Security Act allocating US$50 million annually from 1998-2000 to fund abstinence education programs, while in 1997, a National Strategy to Prevent Teen Pregnancy was launched by the Office of Adolescent Pregnancy Prevention to provide teen pregnancy programs to at least 25% of the communities. Presented in this paper is a discussion of the Abstinence Only programs, which focus on the prevention of pregnancy and sexually transmitted disease among adolescents, and the Abstinence Plus programs, which emphasize other prevention methods as well as abstinence. Evaluation of Abstinence Only programs include Success Express, Project Taking Charge, Sex Respect, Teen Aid, Values and Choices and Facts and Feelings. Moreover, programs such as Reducing the Risk, Postponing Sexual Involvement, Project Education Now, and Babies Later were evaluated under the Abstinence Plus programs. Several programs evaluated have shown to have a positive effect on attitudes among adolescents, but are not proven to have a significant effect on sexual behavior. In conclusion, this article encourages exploration of new approaches to address teen pregnancy and the increasing incidence of sexually transmitted diseases among adolescents, while the federal government must utilize the implementation of existing programs with positive effects.

Identification of cancer genes that are independent of dominant proliferation and lineage programs

PubMed Central

Selfors, Laura M.; Stover, Daniel G.; Harris, Isaac S.; Brugge, Joan S.; Coloff, Jonathan L.

2017-01-01

Large, multidimensional cancer datasets provide a resource that can be mined to identify candidate therapeutic targets for specific subgroups of tumors. Here, we analyzed human breast cancer data to identify transcriptional programs associated with tumors bearing specific genetic driver alterations. Using an unbiased approach, we identified thousands of genes whose expression was enriched in tumors with specific genetic alterations. However, expression of the vast majority of these genes was not enriched if associations were analyzed within individual breast tumor molecular subtypes, across multiple tumor types, or after gene expression was normalized to account for differences in proliferation or tumor lineage. Together with linear modeling results, these findings suggest that most transcriptional programs associated with specific genetic alterations in oncogenes and tumor suppressors are highly context-dependent and are predominantly linked to differences in proliferation programs between distinct breast cancer subtypes. We demonstrate that such proliferation-dependent gene expression dominates tumor transcriptional programs relative to matched normal tissues. However, we also identified a relatively small group of cancer-associated genes that are both proliferation- and lineage-independent. A subset of these genes are attractive candidate targets for combination therapy because they are essential in breast cancer cell lines, druggable, enriched in stem-like breast cancer cells, and resistant to chemotherapy-induced down-regulation. PMID:29229826

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein-Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines.

PubMed

Chang, Ann Margaret V; Chiosea, Simion I; Altman, Alexey; Pagdanganan, Hester A; Ma, Changqing

2017-06-01

Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry. One case with MMR deficiency was also assessed for microsatellite instability (MSI) by polymerase chain reaction. EBV and human papillomavirus (HPV) status were tested by in situ hybridization. All NPCs were p16 negative. Three of the 56 NPCs (5%) were EBV negative (EBV-) and HPV negative, while one NPC (1/56, 2%) was EBV positive and showed MSI (EBV+/MSI). Positive PD-L1 expression (PD-L1+), defined as membranous staining in ≥1% tumor cells, was seen in 64% (36/56) of NPCs. All three EBV- NPCs were PD-L1+ as was the EBV+/MSI NPC. PD-L1+ was seen significantly more often in NPCs from non-smokers than those from smokers (23/28, 82% vs 9/18, 50%; P = 0.047). PD-L1+ was not associated with pT, pN, distant metastasis, or clinical stage (P > 0.05). PD-L1+ was not associated with overall survival (P = 0.473). In summary, our results show frequent PD-L1 expression in NPCs regardless of EBV status and a preferential PD-L1 expression in non-smokers. MSI and HPV positivity are exceedingly rare in NPCs.

Pathway activity inference for multiclass disease classification through a mathematical programming optimisation framework.

PubMed

Yang, Lingjian; Ainali, Chrysanthi; Tsoka, Sophia; Papageorgiou, Lazaros G

2014-12-05

Applying machine learning methods on microarray gene expression profiles for disease classification problems is a popular method to derive biomarkers, i.e. sets of genes that can predict disease state or outcome. Traditional approaches where expression of genes were treated independently suffer from low prediction accuracy and difficulty of biological interpretation. Current research efforts focus on integrating information on protein interactions through biochemical pathway datasets with expression profiles to propose pathway-based classifiers that can enhance disease diagnosis and prognosis. As most of the pathway activity inference methods in literature are either unsupervised or applied on two-class datasets, there is good scope to address such limitations by proposing novel methodologies. A supervised multiclass pathway activity inference method using optimisation techniques is reported. For each pathway expression dataset, patterns of its constituent genes are summarised into one composite feature, termed pathway activity, and a novel mathematical programming model is proposed to infer this feature as a weighted linear summation of expression of its constituent genes. Gene weights are determined by the optimisation model, in a way that the resulting pathway activity has the optimal discriminative power with regards to disease phenotypes. Classification is then performed on the resulting low-dimensional pathway activity profile. The model was evaluated through a variety of published gene expression profiles that cover different types of disease. We show that not only does it improve classification accuracy, but it can also perform well in multiclass disease datasets, a limitation of other approaches from the literature. Desirable features of the model include the ability to control the maximum number of genes that may participate in determining pathway activity, which may be pre-specified by the user. Overall, this work highlights the potential of building pathway-based multi-phenotype classifiers for accurate disease diagnosis and prognosis problems.

Focus group responses of potential participants in a nutrition education program for individuals with limited literacy skills.

PubMed

Hartman, T J; McCarthy, P R; Park, R J; Schuster, E; Kushi, L H

1994-07-01

To obtain information to direct the design and development of a nutrition intervention program targeted at a low-literacy audience. Thirty-nine female and two male clients of the Expanded Food and Nutrition Education Program (EFNEP) participated in five focus-group discussions. The focus groups included 23 African American, 9 white, 4 Southeast Asian, 1 American Indian, 2 Hispanic American, and 2 Middle Eastern EFNEP participants. All focus groups were moderated and co-moderated by University of Minnesota staff members. The focus groups were tape-recorded and transcribed. A written report was generated based on the independent evaluation of two staff members. We learned that EFNEP participants thought they would be motivated to change their eating habits for health concerns, including weight loss, and to help their families develop healthful eating habits. They mentioned several barriers to making changes, including extra time and money needed to purchase and prepare healthful foods, food preferences of family members, lack of interest and skills in cooking, and insufficient knowledge about which foods are healthful. Participants shared ideas for program content and delivery. Clients with limited literacy skills have valuable opinions and insights that program developers targeting this hard-to-reach group should hear. The EFNEP participants wanted simple, practical, and relevant information about what foods to eat and how to prepare them. They considered lectures an ineffective way to receive nutrition information, and they expressed a preference for hands-on activities that were enjoyable and allowed participants to share ideas and experiences.

Implementing Immediate Postpartum Long-Acting Reversible Contraception Programs.

PubMed

Hofler, Lisa G; Cordes, Sarah; Cwiak, Carrie A; Goedken, Peggy; Jamieson, Denise J; Kottke, Melissa

2017-01-01

To understand the most important steps required to implement immediate postpartum long-acting reversible contraception (LARC) programs in different Georgia hospitals and the barriers to implementing such a program. This was a qualitative study. We interviewed 32 key personnel from 10 Georgia hospitals working to establish immediate postpartum LARC programs. Data were analyzed using directed qualitative content analysis principles. We used the Stages of Implementation to organize participant-identified key steps for immediate postpartum LARC into an implementation guide. We compared this guide to hospitals' implementation experiences. At the completion of the study, LARC was available for immediate postpartum placement at 7 of 10 study hospitals. Participants identified common themes for the implementation experience: team member identification and ongoing communication, payer preparedness challenges, interdependent department-specific tasks, and piloting with continuing improvements. Participants expressed a need for anticipatory guidance throughout the process. Key first steps to immediate postpartum LARC program implementation were identifying project champions, creating an implementation team that included all relevant departments, obtaining financial reassurance, and ensuring hospital administration awareness of the project. Potential barriers included lack of knowledge about immediate postpartum LARC, financial concerns, and competing clinical and administrative priorities. Hospitals that were successful at implementing immediate postpartum LARC programs did so by prioritizing clear communication and multidisciplinary teamwork. Although the implementation guide reflects a comprehensive assessment of the steps to implementing immediate postpartum LARC programs, not all hospitals required every step to succeed. Hospital teams report that implementing immediate postpartum LARC programs involves multiple departments and a number of important steps to consider. A stage-based approach to implementation, and a standardized guide detailing these steps, may provide the necessary structure for the complex process of implementing immediate postpartum LARC programs in the hospital setting.

Stakeholder Perspectives on Workplace Health Promotion: A Qualitative Study of Midsized Employers in Low-Wage Industries

PubMed Central

Hannon, Peggy A.; Hammerback, Kristen; Garson, Gayle; Harris, Jeffrey R.; Sopher, Carrie J.

2014-01-01

Purpose Study goals were to (1) describe stakeholder perceptions of workplace health promotion (WHP) appropriateness, (2) describe barriers and facilitators to implementing WHP, (3) learn the extent to which WHP programs are offered to workers’ spouses and partners and assess attitudes toward including partners in WHP programs, and (4) describe willingness to collaborate with nonprofit agencies to offer WHP. Design Five 1.5-hour focus groups. Setting The focus groups were conducted with representatives of midsized (100–999 workers) workplaces in the Seattle metropolitan area, Washington state. Subjects Thirty-four human resources professionals in charge of WHP programs and policies from five low-wage industries: accommodation/food services, manufacturing, health care/social assistance, education, and retail trade. Measures A semistructured discussion guide. Analysis Qualitative analysis of focus group transcripts using grounded theory to identify themes. Results Most participants viewed WHP as appropriate, but many expressed reservations about intruding in workers’ personal lives. Barriers to implementing WHP included cost, time, logistical challenges, and unsupportive culture. Participants saw value in extending WHP programs to workers’ partners, but were unsure how to do so. Most were willing to work with nonprofit agencies to offer WHP. Conclusion Midsized, low-wage employers face significant barriers to implementing WHP; to reach these employers and their workers, nonprofit agencies and WHP vendors need to offer WHP programs that are inexpensive, turnkey, and easy to adapt. PMID:23113780

Stakeholder perspectives on workplace health promotion: a qualitative study of midsized employers in low-wage industries.

PubMed

Hannon, Peggy A; Hammerback, Kristen; Garson, Gayle; Harris, Jeffrey R; Sopher, Carrie J

2012-01-01

Study goals were to (1) describe stakeholder perceptions of workplace health promotion (WHP) appropriateness, (2) describe barriers and facilitators to implementing WHP, (3) learn the extent to which WHP programs are offered to workers' spouses and partners and assess attitudes toward including partners in WHP programs, and (4) describe willingness to collaborate with nonprofit agencies to offer WHP. Five 1.5-hour focus groups. The focus groups were conducted with representatives of midsized (100-999 workers) workplaces in the Seattle metropolitan area, Washington state. Thirty-four human resources professionals in charge of WHP programs and policies from five low-wage industries: accommodation/food services, manufacturing, health care/social assistance, education, and retail trade. A semistructured discussion guide. Qualitative analysis of focus group transcripts using grounded theory to identify themes. Most participants viewed WHP as appropriate, but many expressed reservations about intruding in workers' personal lives. Barriers to implementing WHP included cost, time, logistical challenges, and unsupportive culture. Participants saw value in extending WHP programs to workers' partners, but were unsure how to do so. Most were willing to work with nonprofit agencies to offer WHP. Midsized, low-wage employers face significant barriers to implementing WHP; to reach these employers and their workers, nonprofit agencies and WHP vendors need to offer WHP programs that are inexpensive, turnkey, and easy to adapt.

A Novel Persistence Associated EBV miRNA Expression Profile Is Disrupted in Neoplasia

PubMed Central

Qiu, Jin; Cosmopoulos, Katherine; Pegtel, Michiel; Hopmans, Erik; Murray, Paul; Middeldorp, Jaap; Shapiro, Michael; Thorley-Lawson, David A.

2011-01-01

We have performed the first extensive profiling of Epstein-Barr virus (EBV) miRNAs on in vivo derived normal and neoplastic infected tissues. We describe a unique pattern of viral miRNA expression by normal infected cells in vivo expressing restricted viral latency programs (germinal center: Latency II and memory B: Latency I/0). This includes the complete absence of 15 of the 34 miRNAs profiled. These consist of 12 BART miRNAs (including approximately half of Cluster 2) and 3 of the 4 BHRF1 miRNAs. All but 2 of these absent miRNAs become expressed during EBV driven growth (Latency III). Furthermore, EBV driven growth is accompanied by a 5–10 fold down regulation in the level of the BART miRNAs expressed in germinal center and memory B cells. Therefore, Latency III also expresses a unique pattern of viral miRNAs. We refer to the miRNAs that are specifically expressed in EBV driven growth as the Latency III associated miRNAs. In EBV associated tumors that employ Latency I or II (Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma and gastric carcinoma), the Latency III associated BART but not BHRF1 miRNAs are up regulated. Thus BART miRNA expression is deregulated in the EBV associated tumors. This is the first demonstration that Latency III specific genes (the Latency III associated BARTs) can be expressed in these tumors. The EBV associated tumors demonstrate very similar patterns of miRNA expression yet were readily distinguished when the expression data were analyzed either by heat-map/clustering or principal component analysis. Systematic analysis revealed that the information distinguishing the tumor types was redundant and distributed across all the miRNAs. This resembles “secret sharing” algorithms where information can be distributed among a large number of recipients in such a way that any combination of a small number of recipients is able to understand the message. Biologically, this may be a consequence of functional redundancy between the miRNAs. PMID:21901094

PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.

PubMed

Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying

2018-04-01

The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined. We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls. Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-γ-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the brachyury gene regulatory network.

PubMed

José-Edwards, Diana S; Kerner, Pierre; Kugler, Jamie E; Deng, Wei; Jiang, Di; Di Gregorio, Anna

2011-07-01

The notochord is the distinctive characteristic of chordates; however, the knowledge of the complement of transcription factors governing the development of this structure is still incomplete. Here we present the expression patterns of seven transcription factor genes detected in the notochord of the ascidian Ciona intestinalis at various stages of embryonic development. Four of these transcription factors, Fos-a, NFAT5, AFF and Klf15, have not been directly associated with the notochord in previous studies, while the others, including Spalt-like-a, Lmx-like, and STAT5/6-b, display evolutionarily conserved expression in this structure as well as in other domains. We examined the hierarchical relationships between these genes and the transcription factor Brachyury, which is necessary for notochord development in all chordates. We found that Ciona Brachyury regulates the expression of most, although not all, of these genes. These results shed light on the genetic regulatory program underlying notochord formation in Ciona and possibly other chordates. Copyright © 2011 Wiley-Liss, Inc.

Retinal Determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by Master Regulators

PubMed Central

Baker, Nicholas E.; Firth, Lucy C.

2015-01-01

It is thought that Retinal Determination gene products define the response made to cell-cell signals within the eye developmental field by binding to enhancers of genes that are also regulated by cell-cell signaling pathways. In Drosophila, Retinal Determination genes including Eyeless, teashirt, eyes absent, dachsous and sine oculis, are required for normal eye development and can induce ectopic eyes when mis-expressed. Characterization of the enhancers responsible for eye expression of the hedgehog, shaven, and atonal genes, as well as the dynamics of Retinal Determination gene expression themselves, now suggest a multilayered network whereby transcriptional regulation by either Retinal Determination genes or cell-cell signaling pathways can sometimes be indirect and mediated by other transcription factor intermediates. In this updated view of the interaction between extracellular information and cell intrinsic programs during development, regulation of individual genes might sometimes be several steps removed from either the Retinal Determination genes or cell-cell signaling pathways that nevertheless govern their expression. PMID:21607995

A Single-Cell Approach to the Elusive Latent Human Cytomegalovirus Transcriptome.

PubMed

Goodrum, Felicia; McWeeney, Shannon

2018-06-12

Herpesvirus latency has been difficult to understand molecularly due to low levels of viral genomes and gene expression. In the case of the betaherpesvirus human cytomegalovirus (HCMV), this is further complicated by the heterogeneity inherent to hematopoietic subpopulations harboring genomes and, as a consequence, the various patterns of infection that simultaneously exist in a host, ranging from latent to lytic. Single-cell RNA sequencing (scRNA-seq) provides tremendous potential in measuring the gene expression profiles of heterogeneous cell populations for a wide range of applications, including in studies of cancer, immunology, and infectious disease. A recent study by Shnayder et al. (mBio 9:e00013-18, 2018, https://doi.org/10.1128/mBio.00013-18) utilized scRNA-seq to define transcriptomal characteristics of HCMV latency. They conclude that latency-associated gene expression is similar to the late lytic viral program but at lower levels of expression. The study highlights the numerous challenges, from the definition of latency to the analysis of scRNA-seq, that exist in defining a latent transcriptome. Copyright © 2018 Goodrum and McWeeney.

[Identification of educational needs among patients with HIV and their health care providers].

PubMed

Araya G, Alejandra; Carrasco A, Paola; Loayza G, Carla; Fernández S, Ana María; Pérez C, Carlos; Lasso B, Martín

2013-05-01

The success of educational interventions depends on the integration of educational programs into clinical practice. To determine the educational needs and perceived barriers of people living with HIV (PHIV) and their health care providers (HCP). Qualitative study conducted in 60 PHIV and 10 HCP. For data collection, a semi-structured in-depth interview was applied, addressing the educational needs (content, methodology, person, time, physical location) and identified barriers to implement an educational program for PHIV Content analysis technique was used for data analysis. PHIV and their HCP identified the same educational needs as the following: general-related content, psychological, sexual and secondary prevention aspects of the disease. Individual sessions with written material and web pages were identified as important resources to support education. Both PHIV and professionals expressed their willingness to participate in educational programs, but the most commonly identified barrier was lack of time. This study identifies the key elements to include in an educational program for Chilean PHIV from the user and professional perspective.

Combating Obesity at Community Health Centers (COACH): A Quality Improvement Collaborative for Weight Management Programs

PubMed Central

Wilkes, Abigail E.; John, Priya M.; Vable, Anusha M.; Campbell, Amanda; Heuer, Loretta; Schaefer, Cynthia; Vinci, Lisa; Drum, Melinda L.; Chin, Marshall H.; Quinn, Michael T.; Burnet, Deborah L.

2013-01-01

Community health centers (CHCs) seek effective strategies to address obesity. MidWest Clinicians’ Network partnered with [an academic medical center] to test feasibility of a weight management quality improvement (QI) collaborative. MidWest Clinicians’ Network members expressed interest in an obesity QI program. This pilot study aimed to determine whether the QI model can be feasibly implemented with limited resources at CHCs to improve weight management programs. Five health centers with weight management programs enrolled with CHC staff as primary study participants; this study did not attempt to measure patient outcomes. Participants attended learning sessions and monthly conference calls to build QI skills and share best practices. Tailored coaching addressed local needs. Topics rated most valuable were patient recruitment/retention strategies, QI techniques, evidence-based weight management, motivational interviewing. Challenges included garnering provider support, high staff turnover, and difficulty tracking patient-level data. This paper reports practical lessons about implementing a weight management QI collaborative in CHCs. PMID:23727964

Programming an interim report on the SETL project. Part I: generalities. Part II: the SETL language and examples of its use

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

Schwartz, J T

1975-06-01

A summary of work during the past several years on SETL, a new programming language drawing its dictions and basic concepts from the mathematical theory of sets, is presented. The work was started with the idea that a programming language modeled after an appropriate version of the formal language of mathematics might allow a programming style with some of the succinctness of mathematics, and that this might ultimately enable one to express and experiment with more complex algorithms than are now within reach. Part I discusses the general approach followed in the work. Part II focuses directly on the detailsmore » of the SETL language as it is now defined. It describes the facilities of SETL, includes short libraries of miscellaneous and of code optimization algorithms illustrating the use of SETL, and gives a detailed description of the manner in which the set-theoretic primitives provided by SETL are currently implemented. (RWR)« less

African American perspectives: A qualitative study of an informal science enrichment program

NASA Astrophysics Data System (ADS)

Simpson, Jamila Rashida

The purposes of this study were to determine what program characteristics African American parents consider when they enroll their children into an informal science education enrichment program, the parents' evaluation of a program called Jordan Academy in which they enrolled their children, and the alignment of the parents' perspectives with Black Cultural Ethos (BCE). BCE refers to nine dimensions posited by Wade Boykin, a psychologist, as comprising African American culture. Participants were parents of students that attended Jordan Academy, an informal science enrichment program designed for third through sixth grade students from underserved populations. Qualitative methodologies were utilized to perform a thorough assessment of parents' perspectives. Data sources included classroom observations, student surveys, academy curriculum, photos and video-taped class sessions. Data included teachers and parents' responses to semi-structured, audio recorded interviews and students' written responses to open-ended items on the program's evaluation instrument. The data were analyzed for themes and the findings compared to Black Cultural Ethos. Findings revealed that the participants believed that informal science education offered their children opportunities not realized in the formal school setting - a means of impacting their children holistically. The parents expressed the academic, cultural, and personal development of their children in their characterizations of the ideal informal science education experience and in their evaluations of Jordan Academy. Overall, the parents' views emphasized the BCE values of harmony, affect, verve, movement, orality and communalism. The study has important implications for practices within and research on informal science education.

Ectopic expression of Msx-2 in posterior limb bud mesoderm impairs limb morphogenesis while inducing BMP-4 expression, inhibiting cell proliferation, and promoting apoptosis.

PubMed

Ferrari, D; Lichtler, A C; Pan, Z Z; Dealy, C N; Upholt, W B; Kosher, R A

1998-05-01

During early stages of chick limb development, the homeobox-containing gene Msx-2 is expressed in the mesoderm at the anterior margin of the limb bud and in a discrete group of mesodermal cells at the midproximal posterior margin. These domains of Msx-2 expression roughly demarcate the anterior and posterior boundaries of the progress zone, the highly proliferating posterior mesodermal cells underneath the apical ectodermal ridge (AER) that give rise to the skeletal elements of the limb and associated structures. Later in development as the AER loses its activity, Msx-2 expression expands into the distal mesoderm and subsequently into the interdigital mesenchyme which demarcates the developing digits. The domains of Msx-2 expression exhibit considerably less proliferation than the cells of the progress zone and also encompass several regions of programmed cell death including the anterior and posterior necrotic zones and interdigital mesenchyme. We have thus suggested that Msx-2 may be in a regulatory network that delimits the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed. In the present study we show that ectopic expression of Msx-2 via a retroviral expression vector in the posterior mesoderm of the progress zone from the time of initial formation of the limb bud severely impairs limb morphogenesis. Msx-2-infected limbs are typically very narrow along the anteroposterior axis, are occasionally truncated, and exhibit alterations in the pattern of formation of skeletal elements, indicating that as a consequence of ectopic Msx-2 expression the morphogenesis of large portions of the posterior mesoderm has been suppressed. We further show that Msx-2 impairs limb morphogenesis by reducing cell proliferation and promoting apoptosis in the regions of the posterior mesoderm in which it is ectopically expressed. The domains of ectopic Msx-2 expression in the posterior mesoderm also exhibit ectopic expression of BMP-4, a secreted signaling molecule that is coexpressed with Msx-2 during normal limb development in the anterior limb mesoderm, the posterior necrotic zone, and interdigital mesenchyme. This indicates that Msx-2 regulates BMP-4 expression and that the suppressive effects of Msx-2 on limb morphogenesis might be mediated in part by BMP-4. These studies indicate that during normal limb development Msx-2 is a key component of a regulatory network that delimits the boundaries of the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed, thus restricting the outgrowth and formation of skeletal elements and associated structures to the progress zone. We also report that rather large numbers of apoptotic cells as well as proliferating cells are present throughout the AER during all stages of normal limb development we have examined, indicating that many of the cells of the AER are continuously undergoing programmed cell death at the same time that new AER cells are being generated by cell proliferation. Thus, a balance between cell proliferation and programmed cell death may play a very important role in maintaining the activity of the AER. Copyright 1998 Academic Press.

A new animal model for modulating myosin isoform expression by altered mechanical activity

NASA Technical Reports Server (NTRS)

Caiozzo, V. J.; Ma, E.; McCue, S. A.; Smith, E.; Herrick, R. E.; Baldwin, K. M.

1992-01-01

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.

Gene therapy for prostate cancer: where are we now?

PubMed

Steiner, M S; Gingrich, J R

2000-10-01

The ability to recombine specifically and alter DNA sequences followed by techniques to transfer these sequences or even whole genes into normal and diseased cells has revolutionized medical research and ushered the clinicians of today into the age of gene therapy. We provide urologists a review of relevant background information, outline current treatment strategies and clinical trials, and delineate current challenges facing the field of gene therapy for advanced prostate cancer. We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. We selected for review literature representative of the principal scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials. Current prostate cancer gene therapy strategies include correcting aberrant gene expression, exploiting programmed cell death pathways, targeting critical cell biological functions, introducing toxic or cell lytic suicide genes, enhancing the immune system antitumor response and combining treatment with conventional cytotoxic chemotherapy or radiation therapy. Many challenges lie ahead for gene therapy, including improving DNA transfer efficiency to cells locally and at distant sites, enhancing levels of gene expression and overcoming immune responses that limit the time that genes are expressed. Nevertheless, despite these current challenges it is almost certain that gene therapy will be part of the urological armamentarium against prostate cancer in this century.

A Systematic Review of Satisfaction and Pediatric Obesity Treatment: New Avenues for Addressing Attrition

PubMed Central

Skelton, Joseph A.; Irby, Megan Bennett; Geiger, Ann M.

2014-01-01

Pediatric obesity treatment programs report high attrition rates, but it is unknown if family experience and satisfaction contributes. This review surveys the literature regarding satisfaction in pediatric obesity and questions used in measurement. A systematic review of the literature was conducted using Med-line, PsychINFO, and CINAHL. Studies of satisfaction in pediatric weight management were reviewed, and related studies of obesity were included. Satisfaction survey questions were obtained from the articles or from the authors. Eighteen studies were included; 14 quantitative and 4 qualitative. Only one study linked satisfaction to attrition, and none investigated the association of satisfaction and weight outcomes. Most investigations included satisfaction as a secondary aim or used single-item questions of overall satisfaction; only one assessed satisfaction in noncompleters. Overall, participants expressed high levels of satisfaction with obesity treatment or prevention programs. Surveys focused predominantly on overall satisfaction or specific components of the program. Few in-depth studies of satisfaction with pediatric obesity treatment have been conducted. Increased focus on family satisfaction with obesity treatment may provide an avenue to lower attrition rates and improve outcomes. Enhancing measurement of satisfaction to yield actionable responses could positively influence outcomes, and a framework, via patient-centered care principles, is provided. PMID:23414547

A systematic review of satisfaction and pediatric obesity treatment: new avenues for addressing attrition.

PubMed

Skelton, Joseph A; Irby, Megan Bennett; Geiger, Ann M

2014-01-01

Pediatric obesity treatment programs report high attrition rates, but it is unknown if family experience and satisfaction contributes. This review surveys the literature regarding satisfaction in pediatric obesity and questions used in measurement. A systematic review of the literature was conducted using Medline, PsychINFO, and CINAHL. Studies of satisfaction in pediatric weight management were reviewed, and related studies of obesity were included. Satisfaction survey questions were obtained from the articles or from the authors. Eighteen studies were included; 14 quantitative and 4 qualitative. Only one study linked satisfaction to attrition, and none investigated the association of satisfaction and weight outcomes. Most investigations included satisfaction as a secondary aim or used single-item questions of overall satisfaction; only one assessed satisfaction in noncompleters. Overall, participants expressed high levels of satisfaction with obesity treatment or prevention programs. Surveys focused predominantly on overall satisfaction or specific components of the program. Few in-depth studies of satisfaction with pediatric obesity treatment have been conducted. Increased focus on family satisfaction with obesity treatment may provide an avenue to lower attrition rates and improve outcomes. Enhancing measurement of satisfaction to yield actionable responses could positively influence outcomes, and a framework, via patient-centered care principles, is provided. © 2013 National Association for Healthcare Quality.

The Temporal Program of Peripheral Blood Gene Expression in the Response of Nonhuman Primates to Ebola Hemorrhagic Fever

DTIC Science & Technology

2007-08-28

the family Filoviridae. The EBOV genus consists of four distinct species: Ivory Coast Ebola virus, Reston Ebola virus, Sudan Ebola virus, and Zaire...S, Liu CL, Belcher CE, Botstein D, Staudt LM, Brown PO, Relman DA: Stereotyped and specific gene expression programs in human innate immune responses

Improving Written Expression of Seventh Grade Mildly Intellectually Disabled Students Utilizing a Basal Reading Program, Journal Writing and Computer Applications.

ERIC Educational Resources Information Center

Wimberly, Sabrenai R.

A practicum was designed to increase mildly intellectually disabled students' written communication skills by demonstrating functional written expression skills in daily assignments and in social communication. A sequenced reading and language program with the integration of journal writing and computer applications was utilized. Seventh- and…

SARANA: language, compiler and run-time system support for spatially aware and resource-aware mobile computing.

PubMed

Hari, Pradip; Ko, Kevin; Koukoumidis, Emmanouil; Kremer, Ulrich; Martonosi, Margaret; Ottoni, Desiree; Peh, Li-Shiuan; Zhang, Pei

2008-10-28

Increasingly, spatial awareness plays a central role in many distributed and mobile computing applications. Spatially aware applications rely on information about the geographical position of compute devices and their supported services in order to support novel functionality. While many spatial application drivers already exist in mobile and distributed computing, very little systems research has explored how best to program these applications, to express their spatial and temporal constraints, and to allow efficient implementations on highly dynamic real-world platforms. This paper proposes the SARANA system architecture, which includes language and run-time system support for spatially aware and resource-aware applications. SARANA allows users to express spatial regions of interest, as well as trade-offs between quality of result (QoR), latency and cost. The goal is to produce applications that use resources efficiently and that can be run on diverse resource-constrained platforms ranging from laptops to personal digital assistants and to smart phones. SARANA's run-time system manages QoR and cost trade-offs dynamically by tracking resource availability and locations, brokering usage/pricing agreements and migrating programs to nodes accordingly. A resource cost model permeates the SARANA system layers, permitting users to express their resource needs and QoR expectations in units that make sense to them. Although we are still early in the system development, initial versions have been demonstrated on a nine-node system prototype.

Determination of Duty Cycle for Energy Storage Systems in a PV Smoothing Application

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

Schoenwald, David A.; Ellison, James

This report supplements the document, "Protocol for Uniformly Measuring and Expressing the Performance of Energy Storage Systems," issued in a revised version in April 2016 (see [4]), which will include the photovoltaic (PV) smoothing application for an energy storage system (ESS). This report provides the background and documentation associated with the determination of a duty cycle for an ESS operated in a PV smoothing application for the purpose of measuring and expressing ESS performance in accordance with the ESS performance protocol. ACKNOWLEDGEMENTS The authors gratefully acknowledge the support of Dr. Imre Gyuk, program manager for the DOE Energy Storage Systemsmore » Program. The authors would also like to express their appreciation to all the stakeholders who participated as members of the PV Smoothing Subgroup. Without their thoughtful input and recommendations, the definitions, metrics, and duty cycle provided in this report would not have been possible. A complete listing of members of the PV Smoothing Subgroup appears in the first chapter of this report. Special recognition should go to the staffs at Pacific Northwest National Laboratory (PNNL) and Sandia National Laboratories (SNL) in collaborating on this effort. In particular, Mr. David Conover and Dr. Vish Viswanathan of PNNL and Dr. Summer Ferreira of SNL were especially helpful in their suggestions for the determination of a duty cycle for the PV Smoothing application.« less

SMARCA4/Brg1 coordinates genetic and epigenetic networks underlying Shh-type medulloblastoma development.

PubMed

Shi, X; Wang, Q; Gu, J; Xuan, Z; Wu, J I

2016-11-03

Recent large-scale genomic studies have classified medulloblastoma into four subtypes: Wnt, Shh, Group 3 and Group 4. Each is characterized by specific mutations and distinct epigenetic states. Previously, we showed that a chromatin regulator SMARCA4/Brg1 is required for Gli-mediated transcription activation in Sonic hedgehog (Shh) signaling. We report here that Brg1 controls a transcriptional program that specifically regulates Shh-type medulloblastoma growth. Using a mouse model of Shh-type medulloblastoma, we deleted Brg1 in precancerous progenitors and primary or transplanted tumors. Brg1 deletion significantly inhibited tumor formation and progression. Genome-wide expression analyses and binding experiments indicate that Brg1 specifically coordinates with key transcription factors including Gli1, Atoh1 and REST to regulate the expression of both oncogenes and tumor suppressors that are required for medulloblastoma identity and proliferation. Shh-type medulloblastoma displays distinct H3K27me3 properties. We demonstrate that Brg1 modulates activities of H3K27me3 modifiers to regulate the expression of medulloblastoma genes. Brg1-regulated pathways are conserved in human Shh-type medulloblastoma, and Brg1 is important for the growth of a human medulloblastoma cell line. Thus, Brg1 coordinates a genetic and epigenetic network that regulates the transcriptional program underlying the Shh-type medulloblastoma development.

Effect of long real space flight on the whole genome mRNA expression properties in medaka Oryzias latipes

NASA Astrophysics Data System (ADS)

Kozlova, Olga; Gusev, Oleg; Levinskikh, Margarita; Sychev, Vladimir; Poddubko, Svetlana

The current study is addressed to the complex analysis of whole genome mRNA expression profile and properties of splicing variants formation in different organs of medaka fish exposed to prolonged space flight in the frame of joint Russia-Japan research program “Aquarium-AQH”. The fish were kept in the AQH joint-aquariums system in October-December 2013, followed by fixation in RNA-preserving buffers and freezing during the space flight. The samples we returned to the Earth frozen in March 2013 and mRNAs from four fish were sequenced in organ-specific manner using HiSeq Illumina sequencing platform. The ground group fish treated in the same way was used as a control. The comparison between the groups revealed space group-specific specific mRNA expression pattern. More than 50 genes (including several types of myosins) were down-regulated in the space group. Moreover, we found an evidence for formation of space group-specific splicing variants of mRNA. Taking together, the data suggest that in spite of aquatic environment, space flight-associated factors have a strong effect on the activity of fish genome. This work was supported in part by subsidy of the Russian Government to support the Program of competitive growth of Kazan Federal University among world class academic centres and universities.

Nuclear Calcium Signaling Controls Expression of a Large Gene Pool: Identification of a Gene Program for Acquired Neuroprotection Induced by Synaptic Activity

PubMed Central

Zhang, Sheng-Jia; Zou, Ming; Lu, Li; Lau, David; Ditzel, Désirée A. W.; Delucinge-Vivier, Celine; Aso, Yoshinori; Descombes, Patrick; Bading, Hilmar

2009-01-01

Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling. The nuclear calcium-regulated gene pool contains a genomic program that mediates synaptic activity-induced, acquired neuroprotection. The core set of neuroprotective genes consists of 9 principal components, termed Activity-regulated Inhibitor of Death (AID) genes, and includes Atf3, Btg2, GADD45β, GADD45γ, Inhibin β-A, Interferon activated gene 202B, Npas4, Nr4a1, and Serpinb2, which strongly promote survival of cultured hippocampal neurons. Several AID genes provide neuroprotection through a common process that renders mitochondria more resistant to cellular stress and toxic insults. Stereotaxic delivery of AID gene-expressing recombinant adeno-associated viruses to the hippocampus confers protection in vivo against seizure-induced brain damage. Thus, treatments that enhance nuclear calcium signaling or supplement AID genes represent novel therapies to combat neurodegenerative conditions and neuronal cell loss caused by synaptic dysfunction, which may be accompanied by a deregulation of calcium signal initiation and/or propagation to the cell nucleus. PMID:19680447

Environmental, policy, and cultural factors related to physical activity in sedentary American Indian women.

PubMed

Thompson, Janice L; Allen, Peg; Cunningham-Sabo, Leslie; Yazzie, Dedra A; Curtis, Michelle; Davis, Sally M

2002-01-01

Focus group interviews were conducted to explore sociocultural, environmental, and policy-related determinants of physical activity among sedentary American Indian women. Thirty women aged 20 to 50 years (mean = 37.4 +/- 10.6 years) participated. Three sessions were conducted with women aged 20 to 34 years and three with women aged 35 to 50 to evaluate response differences by age. Because no obvious age differences were observed, data were pooled. Barriers to physical activity included inadequate support for household and child care responsibilities and difficulties balancing home-related and societal expectations with physical activity. In addition, women reported little support from their communities and work sites to be physically active. Environmental barriers included lack of safe outdoor areas and accessible walking trails. Weather and stray dogs were also commonly mentioned. Sociocultural barriers included giving family obligations priority above all other things, being expected to eat large portions of high-fat foods, and failing to follow a traditionally active lifestyle. Enablers of physical activity included support from family and coworkers and participation in traditional community events. Suggested intervention approaches included accessible and affordable programs and facilities, community emphasis on physical activity, and programs that incorporated the needs of larger women and of families. Participants emphasized a preference for programs that were compatible with the role expectations of their families and communities, and they expressed the desire for acceptance and encouragement to be physically active from the family, the community, the worksite, and their tribal leaders.

Why Providers Participate in Clinical Trials: Considering the National Cancer Institute’s Community Clinical Oncology Program

PubMed Central

McAlearney, Ann Scheck; Song, Paula H.; Reiter, Kristin L.

2012-01-01

Background The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute’s Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. Objectives This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. Research Methods We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Results Interviewees expressed both “altruistic” and “self-interested” motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. Conclusion The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. PMID:22925970

Why providers participate in clinical trials: considering the National Cancer Institute's Community Clinical Oncology Program.

PubMed

McAlearney, Ann Scheck; Song, Paula H; Reiter, Kristin L

2012-11-01

The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute's Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Interviewees expressed both "altruistic" and "self-interested" motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. Copyright © 2012 Elsevier Inc. All rights reserved.

Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

PubMed Central

2017-01-01

Real-time quantitative PCR (qPCR) is the most reliable and accurate technique for analyses of gene expression. Endogenous reference genes are being used to normalize qPCR data even though their expression may vary under different conditions and in different tissues. Nonetheless, verification of expression of reference genes in selected studied tissue is essential in order to accurately assess the level of expression of target genes of interest. Therefore, in this study, we attempted to examine six commonly used reference genes in order to identify the gene being expressed most constantly under the influence of testosterone in the kidneys and hypothalamus. The reference genes include glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin beta (ACTB), beta-2 microglobulin (B2m), hypoxanthine phosphoribosyltransferase 1 (HPRT), peptidylprolylisomerase A (Ppia) and hydroxymethylbilane synthase (Hmbs). The cycle threshold (Ct) value for each gene was determined and data obtained were analyzed using the software programs NormFinder, geNorm, BestKeeper, and rank aggregation. Results showed that Hmbs and Ppia genes were the most stably expressed in the hypothalamus. Meanwhile, in kidneys, Hmbs and GAPDH appeared to be the most constant genes. In conclusion, variations in expression levels of reference genes occur in kidneys and hypothalamus under similar conditions; thus, it is important to verify reference gene levels in these tissues prior to commencing any studies. PMID:28591185

GeneMesh: a web-based microarray analysis tool for relating differentially expressed genes to MeSH terms.

PubMed

Jani, Saurin D; Argraves, Gary L; Barth, Jeremy L; Argraves, W Scott

2010-04-01

An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases. Here we describe GeneMesh, a web-based program that facilitates analysis of DNA microarray gene expression data. GeneMesh relates genes in a query set to categories available in the Medical Subject Headings (MeSH) hierarchical index. The interface enables hypothesis driven relational analysis to a specific MeSH subcategory (e.g., Cardiovascular System, Genetic Processes, Immune System Diseases etc.) or unbiased relational analysis to broader MeSH categories (e.g., Anatomy, Biological Sciences, Disease etc.). Genes found associated with a given MeSH category are dynamically linked to facilitate tabular and graphical depiction of Entrez Gene information, Gene Ontology information, KEGG metabolic pathway diagrams and intermolecular interaction information. Expression intensity values of groups of genes that cluster in relation to a given MeSH category, gene ontology or pathway can be displayed as heat maps of Z score-normalized values. GeneMesh operates on gene expression data derived from a number of commercial microarray platforms including Affymetrix, Agilent and Illumina. GeneMesh is a versatile web-based tool for testing and developing new hypotheses through relating genes in a query set (e.g., differentially expressed genes from a DNA microarray experiment) to descriptors making up the hierarchical structure of the National Library of Medicine controlled vocabulary thesaurus, MeSH. The system further enhances the discovery process by providing links between sets of genes associated with a given MeSH category to a rich set of html linked tabular and graphic information including Entrez Gene summaries, gene ontologies, intermolecular interactions, overlays of genes onto KEGG pathway diagrams and heatmaps of expression intensity values. GeneMesh is freely available online at http://proteogenomics.musc.edu/genemesh/.

Down-Regulation of MicroRNA-210 Confers Sensitivity towards 1’S-1’-Acetoxychavicol Acetate (ACA) in Cervical Cancer Cells by Targeting SMAD4

PubMed Central

Phuah, Neoh Hun; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

2017-01-01

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1’S-1’-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3′UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer. PMID:28401751

Down-Regulation of MicroRNA-210 Confers Sensitivity towards 1'S-1'-Acetoxychavicol Acetate (ACA) in Cervical Cancer Cells by Targeting SMAD4.

PubMed

Phuah, Neoh Hun; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

2017-04-01

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.

Gravity-regulated gene expression in Arabidopsis thaliana

NASA Astrophysics Data System (ADS)

Sederoff, Heike; Brown, Christopher S.; Heber, Steffen; Kajla, Jyoti D.; Kumar, Sandeep; Lomax, Terri L.; Wheeler, Benjamin; Yalamanchili, Roopa

Plant growth and development is regulated by changes in environmental signals. Plants sense environmental changes and respond to them by modifying gene expression programs to ad-just cell growth, differentiation, and metabolism. Functional expression of genes comprises many different processes including transcription, translation, post-transcriptional and post-translational modifications, as well as the degradation of RNA and proteins. Recently, it was discovered that small RNAs (sRNA, 18-24 nucleotides long), which are heritable and systemic, are key elements in regulating gene expression in response to biotic and abiotic changes. Sev-eral different classes of sRNAs have been identified that are part of a non-cell autonomous and phloem-mobile network of regulators affecting transcript stability, translational kinetics, and DNA methylation patterns responsible for heritable transcriptional silencing (epigenetics). Our research has focused on gene expression changes in response to gravistimulation of Arabidopsis roots. Using high-throughput technologies including microarrays and 454 sequencing, we iden-tified rapid changes in transcript abundance of genes as well as differential expression of small RNA in Arabidopsis root apices after minutes of reorientation. Some of the differentially regu-lated transcripts are encoded by genes that are important for the bending response. Functional mutants of those genes respond faster to reorientation than the respective wild type plants, indicating that these proteins are repressors of differential cell elongation. We compared the gravity responsive sRNAs to the changes in transcript abundances of their putative targets and identified several potential miRNA: target pairs. Currently, we are using mutant and transgenic Arabidopsis plants to characterize the function of those miRNAs and their putative targets in gravitropic and phototropic responses in Arabidopsis.

Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma

PubMed Central

Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

2016-01-01

Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.

PubMed

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

2016-03-15

Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis.

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

PubMed Central

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

2016-01-01

Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis. PMID:26918453

Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.

PubMed

Umemoto, Yuichiroh; Okano, Shinji; Matsumoto, Yoshihiro; Nakagawara, Hidekazu; Matono, Rumi; Yoshiya, Shohei; Yamashita, Yo-Ichi; Yoshizumi, Tomoharu; Ikegami, Toru; Soejima, Yuji; Harada, Mamoru; Aishima, Shinichi; Oda, Yoshinao; Shirabe, Ken; Maehara, Yoshihiko

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined. We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis. High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS. PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

Review of the algal biology program within the National Alliance for Advanced Biofuels and Bioproducts

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

Unkefer, Clifford J.; Sayre, Richard T.; Magnuson, Jon K.

In 2010,when the National Alliance for Advanced Biofuels and Bioproducts (NAABB) consortiumbegan, littlewas known about themolecular basis of algal biomass or oil production. Very fewalgal genome sequenceswere available and efforts to identify the best-producing wild species through bioprospecting approaches had largely stalled after the U.S. Department of Energy's Aquatic Species Program. This lack of knowledge included how reduced carbon was partitioned into storage products like triglycerides or starch and the role played bymetabolite remodeling in the accumulation of energy-dense storage products. Furthermore, genetic transformation and metabolic engineering approaches to improve algal biomass and oil yields were in their infancy. Genomemore » sequencing and transcriptional profiling were becoming less expensive, however; and the tools to annotate gene expression profiles under various growth and engineered conditions were just starting to be developed for algae. It was in this context that an integrated algal biology program was introduced in the NAABB to address the greatest constraints limiting algal biomass yield. This review describes the NAABB algal biology program, including hypotheses, research objectives, and strategies to move algal biology research into the twenty-first century and to realize the greatest potential of algae biomass systems to produce biofuels.« less

Review of the algal biology program within the National Alliance for Advanced Biofuels and Bioproducts

DOE PAGES

Unkefer, Clifford Jay; Sayre, Richard Thomas; Magnuson, Jon K.; ...

2016-06-21

In 2010,when the National Alliance for Advanced Biofuels and Bioproducts (NAABB) consortium began, little was known about the molecular basis of algal biomass or oil production. Very few algal genome sequences were available and efforts to identify the best-producing wild species through bioprospecting approaches had largely stalled after the U.S. Department of Energy's Aquatic Species Program. This lack of knowledge included how reduced carbon was partitioned into storage products like triglycerides or starch and the role played by metabolite remodeling in the accumulation of energy-dense storage products. Furthermore, genetic transformation and metabolic engineering approaches to improve algal biomass and oilmore » yields were in their infancy. Genome sequencing and transcriptional profiling were becoming less expensive, however; and the tools to annotate gene expression profiles under various growth and engineered conditions were just starting to be developed for algae. It was in this context that an integrated algal biology program was introduced in the NAABB to address the greatest constraints limiting algal biomass yield. Our review describes the NAABB algal biology program, including hypotheses, research objectives, and strategies to move algal biology research into the twenty-first century and to realize the greatest potential of algae biomass systems to produce biofuels.« less

Review of the algal biology program within the National Alliance for Advanced Biofuels and Bioproducts

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

Unkefer, Clifford Jay; Sayre, Richard Thomas; Magnuson, Jon K.

In 2010,when the National Alliance for Advanced Biofuels and Bioproducts (NAABB) consortium began, little was known about the molecular basis of algal biomass or oil production. Very few algal genome sequences were available and efforts to identify the best-producing wild species through bioprospecting approaches had largely stalled after the U.S. Department of Energy's Aquatic Species Program. This lack of knowledge included how reduced carbon was partitioned into storage products like triglycerides or starch and the role played by metabolite remodeling in the accumulation of energy-dense storage products. Furthermore, genetic transformation and metabolic engineering approaches to improve algal biomass and oilmore » yields were in their infancy. Genome sequencing and transcriptional profiling were becoming less expensive, however; and the tools to annotate gene expression profiles under various growth and engineered conditions were just starting to be developed for algae. It was in this context that an integrated algal biology program was introduced in the NAABB to address the greatest constraints limiting algal biomass yield. Our review describes the NAABB algal biology program, including hypotheses, research objectives, and strategies to move algal biology research into the twenty-first century and to realize the greatest potential of algae biomass systems to produce biofuels.« less

Impact of the ‘Artful Moments’ Intervention on Persons with Dementia and Their Care Partners: a Pilot Study

PubMed Central

Hazzan, Afeez Abiola; Humphrey, Janis; Kilgour-Walsh, Laurie; Moros, Katherine L.; Murray, Carmen; Stanners, Shannon; Montemuro, Maureen; Giangregorio, Aidan; Papaioannou, Alexandra

2016-01-01

Background Engaging with art can be valuable for persons living with dementia. ‘Artful Moments’ was a collaborative project undertaken by the Art Gallery of Hamilton and the Behavioural Health Program at Hamilton Health Sciences that sought to develop and implement a program of arts-based activities for persons in the middle-to-late stages of dementia who exhibit behavioural symptoms and for their accompanying care partners. Methods This pilot study employed a qualitative descriptive design. Eight participants were observed during multiple art sessions to evaluate their level of engagement in the program. Care partners also completed a questionnaire describing their experience. Qualitative content analysis was used to identify themes. Results For program participants, factors that promoted continued interest and engagement in art included: care partner involvement, group activities, opportunities to share opinions, validation of their personhood, and increased engagement over time. Care partners observed improvements in participants’ creativity, communication, relationship forming, and task accomplishment, and some reported reduced stress. Conclusions ‘Artful Moments’ promoted engagement and expression in persons in the middle-to-late stages of dementia, as well as having benefits for their care partners. Limitations of the study included a small convenience sample drawn from one hospital setting. PMID:27403209

Minority recruitment and retention in dietetics: issues and interventions.

PubMed

Greenwald, H P; Davis, R A

2000-08-01

To better understand the reasons why minorities and males are underrepresented among registered dietitians (RDs) and dietetic technicians, registered, (DTRs) and to develop focuses for intervention, the investigators performed a telephone survey of newly credentialed RDs and DTRs and directors of RD and DTR education programs. Using lists of students recruited by the American Dietetic Association for participation in the survey, the investigators interviewed 83 RDs and DTRs and 20 education program directors. RDs and DTRs attributed minority underrepresentation primarily to the field's lack of visibility and underrepresentation of men to the traditional association with women. Education program directors attributed minority underrepresentation to educational disadvantages, particularly in scientific subjects. Findings from this study support program-level interventions such as increasing program flexibility, initiating outreach to K-12 schools and lower-division college students, providing tutoring in a nondemeaning atmosphere, and visibly expressing commitment to minority representation. More fundamental changes in the profession itself appear necessary for large-scale increases in minority representation. These include increasing internship opportunities; raising the profession's level of remuneration, prestige, and independence; increasing scholarship support; and advertising nationally through channels capable of reaching minorities.

Improving oncology nurses' communication skills for difficult conversations.

PubMed

Baer, Linda; Weinstein, Elizabeth

2013-06-01

When oncology nurses have strong communication skills, they play a pivotal role in influencing patient satisfaction, adherence to plans of care, and overall clinical outcomes. However, research studies indicate that nurses tend to keep communication with patients and families at a superficial, nontherapeutic level. Processes for teaching goals-of-care communication skills and for implementing skills into clinical practice are not clearly defined. Nurses at a large comprehensive cancer center recognized the need for help with this skill set and sought out communication experts to assist in providing the needed education. An educational project was developed to improve therapeutic communication skills in oncology nurses during goals-of-care discussions and giving bad news. The program was tailored to nurses and social workers providing care to patients in a busy, urban, academic, outpatient oncology setting. Program topics included exploring the patient's world, eliciting hopes and concerns, and dealing with conflict about goals. Sharing and discussing specific difficult questions and scenarios were encouraged throughout the program. The program was well attended and well received by oncology nurses and social workers. Participants expressed interest in the continuation of communication programs to further enhance skills.

Using Answer Set Programming to Integrate RNA Expression with Signalling Pathway Information to Infer How Mutations Affect Ageing

PubMed Central

Papatheodorou, Irene; Ziehm, Matthias; Wieser, Daniela; Alic, Nazif; Partridge, Linda; Thornton, Janet M.

2012-01-01

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects. PMID:23251396

Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing.

PubMed

Papatheodorou, Irene; Ziehm, Matthias; Wieser, Daniela; Alic, Nazif; Partridge, Linda; Thornton, Janet M

2012-01-01

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects.

Obesity impairs apoptotic cell clearance in asthma

PubMed Central

Fernandez-Boyanapalli, Ruby; Goleva, Elena; Kolakowski, Christena; Min, Elysia; Day, Brian; Leung, Donald Y. M.; Riches, David W. H.; Bratton, Donna L.; Sutherland, E. Rand

2014-01-01

Background Asthma in obese adults is typically more severe and less responsive to glucocorticoids than asthma in nonobese adults. Objective We sought to determine whether the clearance of apoptotic inflammatory cells (efferocytosis) by airway macrophages was associated with altered inflammation and reduced glucocorticoid sensitivity in obese asthmatic patients. Methods We investigated the relationship of efferocytosis by airway (induced sputum) macrophages and blood monocytes to markers of monocyte programming, in vitro glucocorticoid response, and systemic oxidative stress in a cohort of adults with persistent asthma. Results Efferocytosis by airway macrophages was assessed in obese (n = 14) and nonobese (n = 19) asthmatic patients. Efferocytosis by macrophages was 40% lower in obese than nonobese subjects, with a mean efferocytic index of 1.77 (SD, 1.07) versus 3.00 (SD, 1.25; P < .01). A similar reduction of efferocytic function was observed in blood monocytes of obese participants. In these monocytes there was also a relative decrease in expression of markers of alternative (M2) programming associated with efferocytosis, including peroxisome proliferator-activated receptor δ and CX3 chemokine receptor 1. Macrophage efferocytic index was significantly correlated with dexamethasone-induced mitogen-activated protein kinase phosphatase 1 expression (ρ = 0.46, P < .02) and baseline glucocorticoid receptor α expression (ρ = 0.44, P < .02) in PBMCs. Plasma 4-hydroxynonenal levels were increased in obese asthmatic patients at 0.33 ng/mL (SD, 0.15 ng/mL) versus 0.16 ng/mL (SD, 0.08 ng/mL) in nonobese patients (P = .006) and was inversely correlated with macrophage efferocytic index (ρ = −0.67, P = .02). Conclusions Asthma in obese adults is associated with impaired macrophage/monocyte efferocytosis. Impairment of this anti-inflammatory process is associated with altered monocyte/macrophage programming, reduced glucocorticoid responsiveness, and systemic oxidative stress. PMID:23154082

Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program

PubMed Central

Hindi, Sajedah M.; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M.; Ogura, Yuji; Yan, Zhen; Burkly, Linda C.; Zheng, Timothy S.; Kumar, Ashok

2014-01-01

Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.—Hindi, S. M., Mishra, V., Bhatnagar, S., Tajrishi, M. M., Ogura, Y., Yan, Z., Burkly, L. C., Zheng, T. S., Kumar, A. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program. PMID:24327607

Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

PubMed

Jonscher, Karen R; Stewart, Michael S; Alfonso-Garcia, Alba; DeFelice, Brian C; Wang, Xiaoxin X; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J R; Janssen, Rachel C; de la Houssaye, Becky A; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L; Potma, Eric O; Fiehn, Oliver; Friedman, Jacob E

2017-04-01

Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes ( Nos2 , Nlrp3 , Il6 , and Ptgs2 ), were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. © FASEB.

Emotions, Ideas and Experiences of Caregivers of Patients With Schizophrenia About "Family to Family Support Program".

PubMed

Bademli, Kerime; Duman, Zekiye Çetinkaya

2016-06-01

"Family to Family Support Program" is a significant intervention program to assist families by informing them about treatment procedures and coping strategies, increasing their functionality, helping them to overcome the challenges of the disease. This study was particularly designed to investigate the emotions, thoughts, and experiences of caregivers of schizophrenia patients who participated in "Family to Family Support Program." The study was conducted with one of the qualitative research methods, phenomenological method. The study sample included caregivers who care for schizophrenia patients and participated in the "Family to Family Support Program". Twenty caregivers were included in the sample. The study was carried out in İzmir Schizophrenia Support Association. The study data were collected with four open ended questions. The average age of the participants was 56,77 ± 72,89, 10 male caregivers and 10 female caregivers, 9 caregivers were fathers, 6 caregivers were mothers, and 5 of them were siblings. The thematic analysis indicated that the emotions, thoughts and experiences of caregivers can be categorized in four groups: "I learned to deal with my problems", "I am conscious in my interaction with the patient and I know and I am not alone", "I feel much better", and "Schizophrenia is not the end of the road, knowledge sorts things out." Caregivers who participated in "Family to Family Support Program" expressed their satisfaction that they were benefited from the program, their coping skills were improved, they experienced less challenges when providing care, they understood the disease better, and it felt comfortable. Copyright © 2015 Elsevier Inc. All rights reserved.

Center for Prostate Disease Research

MedlinePlus

... 2017 Cancer Statistics programs Clinical Research Program Synopsis Leadership Multi-Disciplinary Clinic Staff Listing 2017 Cancer Statistics Basic Science Research Program Synopsis Leadership Gene Expression Data Research Achievements Staff Listing Lab ...

Influence of precracked specimen configuration and starting stress intensity on the stress corrosion cracking of 4340 steel

NASA Technical Reports Server (NTRS)

Lisagor, W. B.

1984-01-01

Since the pioneer work of Brown (1966), precracked specimens and related fracture mechanics analyses have been extensively used to study stress corrosion cracking. Certain questions arose in connection with initial attempts to prepare standardized recommended practices by ASTM Committee G-1 on Corrosion of Metals. These questions were related to adequacy of test control as it pertains to acceptable limits of variability, and to validity of expressions for stress intensity and crack-surface displacements for both specimen configurations. An interlaboratory test program, was, therefore, planned with the objective to examine the validity of KIscc testing for selected specimen configurations, materials,and environmental systems. The results reported in the present paper include details of a single laboratory test program. The program was conducted to determine if the threshold value of stress intensity for onset and arrest of stress corrosion cracking was independent for the two specimen configurations examined.

Medical Student Education in State Psychiatric Hospitals: A Survey of US State Hospitals.

PubMed

Nurenberg, Jeffry R; Schleifer, Steven J; Kennedy, Cheryl; Walker, Mary O; Mayerhoff, David

2016-04-01

State hospitals may be underutilized in medical education. US state psychiatric hospitals were surveyed on current and potential psychiatry medical student education. A 10-item questionnaire, with multiple response formats, was sent to identified hospitals in late 2012. Ninety-seven of 221 hospitals contacted responded. Fifty-three (55%) reported current medical student education programs, including 27 clinical clerkship rotations. Education and training in other disciplines was prevalent in hospitals both with and without medical students. The large majority of responders expressed enthusiasm about medical education. The most frequent reported barrier to new programs was geographic distance from the school. Limited resources were limiting factors for hospitals with and without current programs. Only a minority of US state hospitals may be involved in medical student education. While barriers such as geographic distance may be difficult to overcome, responses suggest opportunities for expanding medical education in the state psychiatric hospitals.

PASCAL/48 reference manual

NASA Technical Reports Server (NTRS)

Knight, J. C.; Hamm, R. W.

1984-01-01

PASCAL/48 is a programming language for the Intel MCS-48 series of microcomputers. In particular, it can be used with the Intel 8748. It is designed to allow the programmer to control most of the instructions being generated and the allocation of storage. The language can be used instead of ASSEMBLY language in most applications while allowing the user the necessary degree of control over hardware resources. Although it is called PASCAL/48, the language differs in many ways from PASCAL. The program structure and statements of the two languages are similar, but the expression mechanism and data types are different. The PASCAL/48 cross-compiler is written in PASCAL and runs on the CDC CYBER NOS system. It generates object code in Intel hexadecimal format that can be used to program the MCS-48 series of microcomputers. This reference manual defines the language, describes the predeclared procedures, lists error messages, illustrates use, and includes language syntax diagrams.

DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1

PubMed Central

de Bruin, R. A. M.; Kalashnikova, T. I.; Aslanian, A.; Wohlschlegel, J.; Chahwan, C.; Yates, J. R.; Russell, P.; Wittenberg, C.

2008-01-01

The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G1 to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication. PMID:18682565

Interleukin-1 and Interferon-γ Orchestrate β-Glucan-Activated Human Dendritic Cell Programming via IκB-ζ Modulation

PubMed Central

Cardone, Marco; Dzutsev, Amiran K.; Li, Hongchuan; Riteau, Nicolas; Gerosa, Franca; Shenderov, Kevin; Winkler-Pickett, Robin; Provezza, Lisa; Riboldi, Elena; Leighty, Robert M.; Orr, Selinda J.; Steinhagen, Folkert; Wewers, Mark D.; Sher, Alan; Anderson, Stephen K.; Goldszmid, Romina; McVicar, Daniel W.

2014-01-01

Recognition of microbial components via innate receptors including the C-type lectin receptor Dectin-1, together with the inflammatory environment, programs dendritic cells (DCs) to orchestrate the magnitude and type of adaptive immune responses. The exposure to β-glucan, a known Dectin-1 agonist and component of fungi, yeasts, and certain immune support supplements, activates DCs to induce T helper (Th)17 cells that are essential against fungal pathogens and extracellular bacteria but may trigger inflammatory pathology or autoimmune diseases. However, the exact mechanisms of DC programming by β-glucan have not yet been fully elucidated. Using a gene expression/perturbation approach, we demonstrate that in human DCs β-glucan transcriptionally activates via an interleukin (IL)-1- and inflammasome-mediated positive feedback late-induced genes that bridge innate and adaptive immunity. We report that in addition to its known ability to directly prime T cells toward the Th17 lineage, IL-1 by promoting the transcriptional cofactor inhibitor of κB-ζ (IκB-ζ) also programs β-glucan-exposed DCs to express cell adhesion and migration mediators, antimicrobial molecules, and Th17-polarizing factors. Interferon (IFN)-γ interferes with the IL-1/IκB-ζ axis in β-glucan-activated DCs and promotes T cell-mediated immune responses with increased release of IFN-γ and IL-22, and diminished production of IL-17. Thus, our results identify IL-1 and IFN-γ as regulators of DC programming by β-glucan. These molecular networks provide new insights into the regulation of the Th17 response as well as new targets for the modulation of immune responses to β-glucan-containing microorganisms. PMID:25474109

Tools to minimize interlaboratory variability in vitellogenin gene expression monitoring programs

USGS Publications Warehouse

Jastrow, Aaron; Gordon, Denise A.; Auger, Kasie M.; Punska, Elizabeth C.; Arcaro, Kathleen F.; Keteles, Kristen; Winkelman, Dana L.; Lattier, David; Biales, Adam; Lazorchak, James M.

2017-01-01

The egg yolk precursor protein vitellogenin is widely used as a biomarker of estrogen exposure in male fish. However, standardized methodology is lacking and little is known regarding the reproducibility of results among laboratories using different equipment, reagents, protocols, and data analysis programs. To address this data gap we tested the reproducibility across laboratories to evaluate vitellogenin gene (vtg) expression and assessed the value of using a freely available software data analysis program. Samples collected from studies of male fathead minnows (Pimephales promelas) exposed to 17α-ethinylestradiol (EE2) and minnows exposed to processed wastewater effluent were evaluated for vtg expression in 4 laboratories. Our results indicate reasonable consistency among laboratories if the free software for expression analysis LinRegPCR is used, with 3 of 4 laboratories detecting vtg in fish exposed to 5 ng/L EE2 (n = 5). All 4 laboratories detected significantly increased vtg levels in 15 male fish exposed to wastewater effluent compared with 15 male fish held in a control stream. Finally, we were able to determine that the source of high interlaboratory variability from complementary deoxyribonucleic acid (cDNA) to quantitative polymerase chain reaction (qPCR) analyses was the expression analysis software unique to each real-time qPCR machine. We successfully eliminated the interlaboratory variability by reanalyzing raw fluorescence data with independent freeware, which yielded cycle thresholds and polymerase chain reaction (PCR) efficiencies that calculated results independently of proprietary software. Our results suggest that laboratories engaged in monitoring programs should validate their PCR protocols and analyze their gene expression data following the guidelines established in the present study for all gene expression biomarkers. 

The Voyager spacecraft /James Watt International Gold Medal Lecture/

NASA Technical Reports Server (NTRS)

Heacock, R. L.

1980-01-01

The Voyager Project background is reviewed with emphasis on selected features of the Voyager spacecraft. Investigations by the Thermo-electric Outer Planets Spacecraft Project are discussed, including trajectories, design requirements, and the development of a Self Test and Repair computer, and a Computer Accessed Telemetry System. The design and configuration of the spacecraft are described, including long range communications, attitude control, solar independent power, sequencing and control data handling, and spacecraft propulsion. The development program, maintained by JPL, experienced a variety of problems such as design deficiencies, and process control and manufacturing problems. Finally, the spacecraft encounter with Jupiter is discussed, and expectations for the Saturn encounter are expressed.

An EXPRESS Rack Overview and Support for Microgravity Research on the International Space Station (ISS)

NASA Technical Reports Server (NTRS)

Pelfrey, Joseph J.; Jordan, Lee P.

2008-01-01

The EXpedite the PRocessing of Experiments to Space Station or EXPRESS Rack System has provided accommodations and facilitated operations for microgravity-based research payloads for over 6 years on the International Space Station (ISS). The EXPRESS Rack accepts Space Shuttle middeck type lockers and International Subrack Interface Standard (ISIS) drawers, providing a modular-type interface on the ISS. The EXPRESS Rack provides 28Vdc power, Ethernet and RS-422 data interfaces, thermal conditioning, vacuum exhaust, and Nitrogen supply for payload use. The EXPRESS Rack system also includes payload checkout capability with a flight rack or flight rack emulator prior to launch, providing a high degree of confidence in successful operations once an-orbit. In addition, EXPRESS trainer racks are provided to support crew training of both rack systems and subrack operations. Standard hardware and software interfaces provided by the EXPRESS Rack simplify the integration processes for ISS payload development. The EXPRESS Rack is designed to accommodate multidiscipline research, allowing for the independent operation of each subrack payload within a single rack. On-orbit operations began for the EXPRESS Rack Project on April 24, 2001, with one rack operating continuously to support high-priority payloads. The other on-orbit EXPRESS Racks operate based on payload need and resource availability. Over 50 multi-discipline payloads have now been supported on-orbit by the EXPRESS Rack Program. Sustaining engineering, logistics, and maintenance functions are in place to maintain hardware, operations and provide software upgrades. Additional EXPRESS Racks are planned for launch prior to ISS completion in support of long-term operations and the planned transition of the U.S. Segment to a National Laboratory.

Understanding Barriers to Participation in Cost-Share Programs For Pollinator Conservation by Wisconsin (USA) Cranberry Growers.

PubMed

Gaines-Day, Hannah R; Gratton, Claudio

2017-08-01

The expansion of modern agriculture has led to the loss and fragmentation of natural habitat, resulting in a global decline in biodiversity, including bees. In many countries, farmers can participate in cost-share programs to create natural habitat on their farms for the conservation of beneficial insects, such as bees. Despite their dependence on bee pollinators and the demonstrated commitment to environmental stewardship, participation in such programs by Wisconsin cranberry growers has been low. The objective of this study was to understand the barriers that prevent participation by Wisconsin cranberry growers in cost-share programs for on-farm conservation of native bees. We conducted a survey of cranberry growers (n = 250) regarding farming practices, pollinators, and conservation. Although only 10% of growers were aware of federal pollinator cost-share programs, one third of them were managing habitat for pollinators without federal aid. Once informed of the programs, 50% of growers expressed interest in participating. Fifty-seven percent of growers manage habitat for other wildlife, although none receive cost-share funding to do so. Participation in cost-share programs could benefit from outreach activities that promote the programs, a reduction of bureaucratic hurdles to participate, and technical support for growers on how to manage habitat for wild bees.

Understanding Barriers to Participation in Cost-Share Programs For Pollinator Conservation by Wisconsin (USA) Cranberry Growers

PubMed Central

Gratton, Claudio

2017-01-01

The expansion of modern agriculture has led to the loss and fragmentation of natural habitat, resulting in a global decline in biodiversity, including bees. In many countries, farmers can participate in cost-share programs to create natural habitat on their farms for the conservation of beneficial insects, such as bees. Despite their dependence on bee pollinators and the demonstrated commitment to environmental stewardship, participation in such programs by Wisconsin cranberry growers has been low. The objective of this study was to understand the barriers that prevent participation by Wisconsin cranberry growers in cost-share programs for on-farm conservation of native bees. We conducted a survey of cranberry growers (n = 250) regarding farming practices, pollinators, and conservation. Although only 10% of growers were aware of federal pollinator cost-share programs, one third of them were managing habitat for pollinators without federal aid. Once informed of the programs, 50% of growers expressed interest in participating. Fifty-seven percent of growers manage habitat for other wildlife, although none receive cost-share funding to do so. Participation in cost-share programs could benefit from outreach activities that promote the programs, a reduction of bureaucratic hurdles to participate, and technical support for growers on how to manage habitat for wild bees. PMID:28763038

Exocarp Properties and Transcriptomic Analysis of Cucumber (Cucumis sativus) Fruit Expressing Age-Related Resistance to Phytophthora capsici

PubMed Central

Ando, Kaori; Carr, Kevin M.; Colle, Marivi; Mansfeld, Ben N.; Grumet, Rebecca

2015-01-01

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10–12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size. PMID:26528543

Exocarp Properties and Transcriptomic Analysis of Cucumber (Cucumis sativus) Fruit Expressing Age-Related Resistance to Phytophthora capsici.

PubMed

Ando, Kaori; Carr, Kevin M; Colle, Marivi; Mansfeld, Ben N; Grumet, Rebecca

2015-01-01

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10-12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size.

Implementation of density functional theory method on object-oriented programming (C++) to calculate energy band structure using the projector augmented wave (PAW)

NASA Astrophysics Data System (ADS)

Alfianto, E.; Rusydi, F.; Aisyah, N. D.; Fadilla, R. N.; Dipojono, H. K.; Martoprawiro, M. A.

2017-05-01

This study implemented DFT method into the C++ programming language with object-oriented programming rules (expressive software). The use of expressive software results in getting a simple programming structure, which is similar to mathematical formula. This will facilitate the scientific community to develop the software. We validate our software by calculating the energy band structure of Silica, Carbon, and Germanium with FCC structure using the Projector Augmented Wave (PAW) method then compare the results to Quantum Espresso calculation’s results. This study shows that the accuracy of the software is 85% compared to Quantum Espresso.

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

PubMed Central

2014-01-01

Background The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin. Methods Cell death/viability was measured by flow cytometry/determination of intracellular ATP levels/crystal violet staining. Cell surface expression of TRAIL receptors was detected by flow cytometry, expression of proteins by Western blot. Ceramide levels were quantified by high-performance thin layer chromatography and densitometric analysis, clonogenic survival of cells was determined by crystal violet staining or by soft agarose cloning. Results TRAIL-induced programmed necrosis killed eight out of 14 tumor cell lines. Clonogenic survival was reduced in all sensitive and even one resistant cell lines tested. TRAIL synergized with chemotherapeutics in killing tumor cell lines by programmed necrosis, enhancing their effect in eight out of 10 tested tumor cell lines and in 41 out of 80 chemotherapeutic/TRAIL combinations. Susceptibility/resistance of the investigated tumor cell lines to programmed necrosis seems to primarily depend on expression of the pro-necrotic kinase RIPK3 rather than the related kinase RIPK1 or cell surface expression of TRAIL receptors. Furthermore, interference with production of the lipid ceramide protected all tested tumor cell lines. Conclusions Our study provides evidence that TRAIL-induced programmed necrosis represents a feasible approach for the elimination of tumor cells, and that this treatment may represent a promising new option for the future development of combination therapies. Our data also suggest that RIPK3 expression may serve as a potential predictive marker for the sensitivity of tumor cells to programmed necrosis and extend the previously established role of ceramide as a key mediator of death receptor-induced programmed necrosis (and thus as a potential target for future therapies) also to the tumor cell lines examined here. PMID:24507727

Computer program for calculation of real gas turbulent boundary layers with variable edge entropy

NASA Technical Reports Server (NTRS)

Boney, L. R.

1974-01-01

A user's manual for a computer program which calculates real gas turbulent boundary layers with variable edge entropy on a blunt cone or flat plate at zero angle of attack is presented. An integral method is used. The method includes the effect of real gas in thermodynamic equilibrium and variable edge entropy. A modified Crocco enthalpy velocity relationship is used for the enthalpy profiles and an empirical correlation of the N-power law profile is used for the velocity profile. The skin-friction-coefficient expressions of Spalding and Chi and Van Driest are used in the solution of the momentum equation and in the heat-transfer predictions that use several modified forms of Reynolds analogy.

SEL-Focused After-School Programs

ERIC Educational Resources Information Center

Hurd, Noelle; Deutsch, Nancy

2017-01-01

After-school programs offer young people opportunities for self-expression, exploring their talents, and forming relationships with supportive adults. That is, after-school programs promote young people's social and emotional learning (SEL) skills--whether the programs use that term or not. Despite these programs' potential, Noelle Hurd and Nancy…

NURD: an implementation of a new method to estimate isoform expression from non-uniform RNA-seq data

PubMed Central

2013-01-01

Background RNA-Seq technology has been used widely in transcriptome study, and one of the most important applications is to estimate the expression level of genes and their alternative splicing isoforms. There have been several algorithms published to estimate the expression based on different models. Recently Wu et al. published a method that can accurately estimate isoform level expression by considering position-related sequencing biases using nonparametric models. The method has advantages in handling different read distributions, but there hasn’t been an efficient program to implement this algorithm. Results We developed an efficient implementation of the algorithm in the program NURD. It uses a binary interval search algorithm. The program can correct both the global tendency of sequencing bias in the data and local sequencing bias specific to each gene. The correction makes the isoform expression estimation more reliable under various read distributions. And the implementation is computationally efficient in both the memory cost and running time and can be readily scaled up for huge datasets. Conclusion NURD is an efficient and reliable tool for estimating the isoform expression level. Given the reads mapping result and gene annotation file, NURD will output the expression estimation result. The package is freely available for academic use at http://bioinfo.au.tsinghua.edu.cn/software/NURD/. PMID:23837734

Parameter optimization for constructing competing endogenous RNA regulatory network in glioblastoma multiforme and other cancers.

PubMed

Chiu, Yu-Chiao; Hsiao, Tzu-Hung; Chen, Yidong; Chuang, Eric Y

2015-01-01

In addition to direct targeting and repressing mRNAs, recent studies reported that microRNAs (miRNAs) can bridge up an alternative layer of post-transcriptional gene regulatory networks. The competing endogenous RNA (ceRNA) regulation depicts the scenario where pairs of genes (ceRNAs) sharing, fully or partially, common binding miRNAs (miRNA program) can establish coexpression through competition for a limited pool of the miRNA program. While the dynamics of ceRNA regulation among cellular conditions have been verified based on in silico and in vitro experiments, comprehensive investigation into the strength of ceRNA regulation in human datasets remains largely unexplored. Furthermore, pan-cancer analysis of ceRNA regulation, to our knowledge, has not been systematically investigated. In the present study we explored optimal conditions for ceRNA regulation, investigated functions governed by ceRNA regulation, and evaluated pan-cancer effects. We started by investigating how essential factors, such as the size of miRNA programs, the number of miRNA program binding sites, and expression levels of miRNA programs and ceRNAs affect the ceRNA regulation capacity in tumors derived from glioblastoma multiforme patients captured by The Cancer Genome Atlas (TCGA). We demonstrated that increased numbers of common targeting miRNAs as well as the abundance of binding sites enhance ceRNA regulation and strengthen coexpression of ceRNA pairs. Also, our investigation revealed that the strength of ceRNA regulation is dependent on expression levels of both miRNA programs and ceRNAs. Through functional annotation analysis, our results indicated that ceRNA regulation is highly associated with essential cellular functions and diseases including cancer. Furthermore, the highly intertwined ceRNA regulatory relationship enables constitutive and effective intra-function regulation of genes in diverse types of cancer. Using gene and microRNA expression datasets from TCGA, we successfully quantified the optimal conditions for ceRNA regulation, which hinge on four essential parameters of ceRNAs. Our analysis suggests optimized ceRNA regulation is related to disease pathways and essential cellular functions. Furthermore, although the strength of ceRNA regulation is dynamic among cancers, its governing functions are stably maintained. The findings of this report contribute to better understanding of ceRNA dynamics and its crucial roles in cancers.

mr: A C++ library for the matching and running of the Standard Model parameters

NASA Astrophysics Data System (ADS)

Kniehl, Bernd A.; Pikelner, Andrey F.; Veretin, Oleg L.

2016-09-01

We present the C++ program library mr that allows us to reliably calculate the values of the running parameters in the Standard Model at high energy scales. The initial conditions are obtained by relating the running parameters in the MS bar renormalization scheme to observables at lower energies with full two-loop precision. The evolution is then performed in accordance with the renormalization group equations with full three-loop precision. Pure QCD corrections to the matching and running are included through four loops. We also provide a Mathematica interface for this program library. Catalogue identifier: AFAI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AFAI_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 517613 No. of bytes in distributed program, including test data, etc.: 2358729 Distribution format: tar.gz Programming language: C++. Computer: IBM PC. Operating system: Linux, Mac OS X. RAM: 1 GB Classification: 11.1. External routines: TSIL [1], OdeInt [2], boost [3] Nature of problem: The running parameters of the Standard Model renormalized in the MS bar scheme at some high renormalization scale, which is chosen by the user, are evaluated in perturbation theory as precisely as possible in two steps. First, the initial conditions at the electroweak energy scale are evaluated from the Fermi constant GF and the pole masses of the W, Z, and Higgs bosons and the bottom and top quarks including the full two-loop threshold corrections. Second, the evolution to the high energy scale is performed by numerically solving the renormalization group evolution equations through three loops. Pure QCD corrections to the matching and running are included through four loops. Solution method: Numerical integration of analytic expressions Additional comments: Available for download from URL: http://apik.github.io/mr/. The MathLink interface is tested to work with Mathematica 7-9 and, with an additional flag, also with Mathematica 10 under Linux and with Mathematica 10 under Mac OS X. Running time: less than 1 second References: [1] S. P. Martin and D. G. Robertson, Comput. Phys. Commun. 174 (2006) 133-151 [hep-ph/0501132]. [2] K. Ahnert and M. Mulansky, AIP Conf. Proc. 1389 (2011) 1586-1589 [arxiv:1110.3397 [cs.MS

I-35w incident management and impact of incidents on freeway operations. Final report, 1976-1979

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

Lari, A.; Christianson, D.; Porter, S.

1982-01-01

I-35W and I-94 Traffic Management System have been in operation since 1974. As of December 1979, the TMS operation included six principal functional subsystems. These are (1) a 24 camera closed circuit television network (2) 38 ramp meter signals, (3) eleven express bus and/or carpool meter bypass ramps, (4) a motorist information program including changeable message signs, lane control signals, highway advisory radio and a traffic grade information sign, (5) the Traffic Management Center and (6) an incident detection and response program. The purpose of this study was twofold: first, available incident records accumulated on the TMS were analyzed tomore » develop a comprehensive view of the types and quantities of incidents that have occurred. Second, the incident data base and companion volume and occupancy data was used to determine the impact of 'typical' incidents and the impact of the total incident problem. Included in the report is an analysis of incident types detected, mode of incident detection, duration of incidents, and incident response activities.« less

Expressing the sense of the House of Representatives that specialty crops are a vital part of agriculture in the United States, that the Committee on Agriculture should propose funding for programs that support specialty crops priorities, and that legislation should be passed that includes funding reflecting specialty crops as a growing and important part of United States agriculture.

THOMAS, 113th Congress

Rep. DelBene, Suzan K. [D-WA-1

2013-04-25

House - 05/03/2013 Referred to the Subcommittee on Horticulture, Research, Biotechnology, and Foreign Agriculture. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Aerospace applications of integer and combinatorial optimization

NASA Technical Reports Server (NTRS)

Padula, S. L.; Kincaid, R. K.

1995-01-01

Research supported by NASA Langley Research Center includes many applications of aerospace design optimization and is conducted by teams of applied mathematicians and aerospace engineers. This paper investigates the benefits from this combined expertise in solving combinatorial optimization problems. Applications range from the design of large space antennas to interior noise control. A typical problem, for example, seeks the optimal locations for vibration-damping devices on a large space structure and is expressed as a mixed/integer linear programming problem with more than 1500 design variables.

Development and Implementation of a Combined Master of Science and PGY1/PGY2 Health-System Pharmacy Administration Residency Program at a Large Community Teaching Hospital.

PubMed

Gazda, Nicholas P; Griffin, Emily; Hamrick, Kasey; Baskett, Jordan; Mellon, Meghan M; Eckel, Stephen F; Granko, Robert P

2018-04-01

Purpose: The purpose of this article is to share experiences after the development of a health-system pharmacy administration residency with a MS degree and express the need for additional programs in nonacademic medical center health-system settings. Summary: Experiences with the development and implementation of a health-system pharmacy administration residency at a large community teaching hospital are described. Resident candidates benefit from collaborations with other health-systems through master's degree programs and visibility to leaders at your health-system. Programs benefit from building a pipeline of future pharmacy administrators and by leveraging the skills of residents to contribute to projects and department-wide initiatives. Tools to assist in the implementation of a new pharmacy administration program are also described and include rotation and preceptor development, marketing and recruiting, financial evaluation, and steps to prepare for accreditation. Conclusion: Health-system pharmacy administration residents provide the opportunity to build a pipeline of high-quality leaders, provide high-level project involvement, and produce a positive return on investment (ROI) for health-systems. These programs should be explored in academic and nonacademic-based health-systems.

Residency Training: The need for an integrated diversity curriculum for neurology residency.

PubMed

Rosendale, Nicole; Josephson, S Andrew

2017-12-12

Providing culturally responsive care to an increasingly multicultural population is essential and requires formal cultural humility training for residents. We sought to understand the current prevalence and need for this type of training within neurology programs and to pilot an integrated curriculum locally. We surveyed via email all program directors of academic neurology programs nationally regarding the prevalence of and need for formal cultural responsiveness training. Forty-seven program directors (36%) responded to the survey. The majority of respondents did not have a formalized diversity curriculum in their program (65%), but most (85%) believed that training in cultural responsiveness was important. We developed locally an integrated diversity curriculum as a proof of concept. The curriculum covered topics of diversity in language, religion, sexual orientation, gender identity/expression, and socioeconomic status designed to focus on the needs of the local community. Program evaluation included a pre and post survey of the learner attitudes toward cultural diversity. There is an unmet need for cultural responsiveness training within neurology residencies, and integrating this curriculum is both feasible and efficacious. When adapted to address cultural issues of the local community, this curriculum can be generalizable to both academic and community organizations. © 2017 American Academy of Neurology.

Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.

PubMed

Rodriguez, Ramon M; Suarez-Alvarez, Beatriz; Lavín, José L; Mosén-Ansorena, David; Baragaño Raneros, Aroa; Márquez-Kisinousky, Leonardo; Aransay, Ana M; Lopez-Larrea, Carlos

2017-01-15

Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8 + T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8 + T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8 + T cell maintenance and T cell terminal differentiation. Copyright © 2017 by The American Association of Immunologists, Inc.

A Participatory Design Approach to Develop a Web-Based Self-Care Program Supporting Early Rehabilitation among Patients after Total Laryngectomy.

PubMed

Cnossen, Ingrid C; van Uden-Kraan, Cornelia F; Eerenstein, Simone E J; Rinkel, Rico N P M; Aalders, Ijke J; van den Berg, Klaske; de Goede, Cees J T; van Stijgeren, Ans J; Cruijff-Bijl, Yvonne; de Bree, Remco; Leemans, C René; Verdonck-de Leeuw, Irma M

2015-01-01

To develop a Web-based self-care program for patients after total laryngectomy according to a participatory design approach. We conducted a needs assessment with laryngectomees (n = 9) and their partners (n = 3) by means of a focus group interview. In 4 focus group sessions, a requirement plan was formulated by a team of health care professionals (n = 10) and translated into a prototype. An e-health application was built including illustrated information on functional changes after total laryngectomy as well as video demonstrations of skills and exercises. Usability of the prototype was tested by end users (n = 4) and expert users (n = 10). Interviews were held to elicit the intention to use and the desired implementation strategy. Six main self-care topics were identified: (1) nutrition, (2) tracheostomy care, (3) voice prosthesis care, (4) speech rehabilitation, (5) smell rehabilitation, and (6) mobility of head, neck, and shoulder muscles. Expert users expressed concerns regarding tailored exercises, indicated a positive intent to implement the intervention in routine care, and expressed a need for guidance when implementing the intervention. End users and expert users appreciated the content completeness and multimedia-based information built into the application. The participatory design is a valuable approach to develop a self-care program to help meet users' needs. © 2016 S. Karger AG, Basel.

Use of gene-expression programming to estimate Manning’s roughness coefficient for high gradient streams

USGS Publications Warehouse

Azamathulla, H. Md.; Jarrett, Robert D.

2013-01-01

Manning’s roughness coefficient (n) has been widely used in the estimation of flood discharges or depths of flow in natural channels. Therefore, the selection of appropriate Manning’s nvalues is of paramount importance for hydraulic engineers and hydrologists and requires considerable experience, although extensive guidelines are available. Generally, the largest source of error in post-flood estimates (termed indirect measurements) is due to estimates of Manning’s n values, particularly when there has been minimal field verification of flow resistance. This emphasizes the need to improve methods for estimating n values. The objective of this study was to develop a soft computing model in the estimation of the Manning’s n values using 75 discharge measurements on 21 high gradient streams in Colorado, USA. The data are from high gradient (S > 0.002 m/m), cobble- and boulder-bed streams for within bank flows. This study presents Gene-Expression Programming (GEP), an extension of Genetic Programming (GP), as an improved approach to estimate Manning’s roughness coefficient for high gradient streams. This study uses field data and assessed the potential of gene-expression programming (GEP) to estimate Manning’s n values. GEP is a search technique that automatically simplifies genetic programs during an evolutionary processes (or evolves) to obtain the most robust computer program (e.g., simplify mathematical expressions, decision trees, polynomial constructs, and logical expressions). Field measurements collected by Jarrett (J Hydraulic Eng ASCE 110: 1519–1539, 1984) were used to train the GEP network and evolve programs. The developed network and evolved programs were validated by using observations that were not involved in training. GEP and ANN-RBF (artificial neural network-radial basis function) models were found to be substantially more effective (e.g., R2 for testing/validation of GEP and RBF-ANN is 0.745 and 0.65, respectively) than Jarrett’s (J Hydraulic Eng ASCE 110: 1519–1539, 1984) equation (R2 for testing/validation equals 0.58) in predicting the Manning’s n.

Effects of Lifestyle Modification on Telomerase Gene Expression in Hypertensive Patients: A Pilot Trial of Stress Reduction and Health Education Programs in African Americans.

PubMed

Duraimani, Shanthi; Schneider, Robert H; Randall, Otelio S; Nidich, Sanford I; Xu, Shichen; Ketete, Muluemebet; Rainforth, Maxwell A; Gaylord-King, Carolyn; Salerno, John W; Fagan, John

2015-01-01

African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans. Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes. Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors. In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP observed in this high-risk population suggest hypotheses that telomerase gene expression may either be a biomarker for reduced BP or a mechanism by which stress reduction and lifestyle modification reduces BP. ClinicalTrials.gov NCT00681200.

Effects of Lifestyle Modification on Telomerase Gene Expression in Hypertensive Patients: A Pilot Trial of Stress Reduction and Health Education Programs in African Americans

PubMed Central

Duraimani, Shanthi; Schneider, Robert H.; Randall, Otelio S.; Nidich, Sanford I.; Xu, Shichen; Ketete, Muluemebet; Rainforth, Maxwell A.; Gaylord-King, Carolyn; Salerno, John W.; Fagan, John

2015-01-01

Background African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans. Methods Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes. Results Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors. Conclusion In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP observed in this high-risk population suggest hypotheses that telomerase gene expression may either be a biomarker for reduced BP or a mechanism by which stress reduction and lifestyle modification reduces BP. Trial Registration ClinicalTrials.gov NCT00681200 PMID:26571023

Tumor-associated myeloid cells as guiding forces of cancer cell stemness.

PubMed

Sica, Antonio; Porta, Chiara; Amadori, Alberto; Pastò, Anna

2017-08-01

Due to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, including tumor angiogenesis, immunosuppression, tissue remodeling and metastasis formation. In addition, these myeloid populations support cancer cell stemness, favoring tumor maintenance and progression, as well as resistance to anticancer treatments. Here, we discuss inflammatory circuits and molecules expressed by TAMs and MDSCs as guiding forces of cancer cell stemness.