Differences in the Processing of Prefixes and Suffixes Revealed by a Letter-Search Task

ERIC Educational Resources Information Center

Beyersmann, Elisabeth; Ziegler, Johannes C.; Grainger, Jonathan

2015-01-01

A letter-search task was used to test the hypothesis that affixes are chunked during morphological processing and that such chunking might operate differently for prefixes and suffixes. Participants had to detect a letter target that was embedded either in a prefix or suffix (e.g., "R" in "propoint" or "filmure") or…

Past participle formation in specific language impairment.

PubMed

Kauschke, Christina; Renner, Lena F; Domahs, Ulrike

2017-03-01

German participles are formed by a co-occurrence of prefixation and suffixation. While the acquisition of regular and irregular suffixation has been investigated exhaustively, it is still unclear how German children master the prosodically determined prefixation rule (prefix ge-). Findings reported in the literature are inconsistent on this point. In particular, it is unclear whether participle formation is vulnerable in German children with specific language impairment (SLI). To compare children with and without SLI in their abilities to form German participles correctly, and to determine their relative sensitivities to the morphophonological regularities of prefixation. The performance of 14 German-speaking children with SLI (mean age = 7;5) in a participle formation task was compared with that of age-matched and younger typically developing controls. The materials included 60 regular verbs and 20 pseudo-verbs, half of them requiring the prefix ge-. Overall, children with SLI performed poorly compared with both groups of typically developing children. Children with SLI tended either to avoid participle markings or choose inappropriate affixes. However, while such children showed marked impairment at the morphological level, they were generally successful in applying the morphoprosodic rules governing prefixation. In contrast to earlier findings, the present results demonstrate that regular participle formation is problematic for German children with SLI. © 2016 Royal College of Speech and Language Therapists.

Toward Large-Graph Comparison Measures to Understand Internet Topology Dynamics

DTIC Science & Technology

2013-09-01

continuously from randomly selected vantage points in these monitors to destination IP addresses . From each IPv4 /24 prefix on the Internet, a destination is...expected to be more similar. This was verified when the esd and vsd measures applied to this dataset gave a low reading 5 An IPv4 address is a 32-bit...integer value. /24 is the prefix of the IPv4 network starting at a given address , having 24 bits allocated for the network prefix. 6 This utility

The comparative metabolism of 2,6-dichlorothiobenzamide (prefix) and 2,6-dichlorobenzonitrile in the dog and rat

PubMed Central

Griffiths, M. H.; Moss, J. A.; Rose, J. A.; Hathway, D. E.

1966-01-01

1. A single oral dose of either [14C]Prefix or 2,6-dichlorobenzo[14C]nitrile to rats is almost entirely eliminated in 4 days: 84·8–100·5% of 14C from [14C]Prefix is excreted, 67·3–79·7% in the urine, and 85·8–97·2% of 14C from 2,6-dichlorobenzo-[14C]nitrile is excreted, 72·3–80·7% in the urine. Only 0·37±0·03% of the dose of [14C]Prefix and 0·25±0·03% of the dose of 2,6-dichlorobenzo[14C]nitrile are present in the carcass plus viscera after removal of the gut. Rats do not show sex differences in the pattern of elimination of the respective metabolites of the two herbicides. The rates of elimination of 14C from the two compounds in the 24hr. and 48hr. urines are not significantly different (P >0·05) from one another. 2. After oral administration to dogs, 85·9–106·1% of 14C from [14C]Prefix is excreted, 66·6–80·9% in the urine, and 86·8–92·5% of 14C from 2,6-dichlorobenzo[14C]nitrile is excreted, 60·0–70·1% in the urine. Dogs do not show sex differences in the pattern of eliminating the metabolites of either Prefix or 2,6-dichlorobenzonitrile. 3. Dogs and rats do not show species differences in the patterns of elimination of the two herbicides. 4. Prefix and 2,6-dichlorobenzonitrile are completely metabolized; unchanged Prefix and 2,6-dichlorobenzonitrile are absent from the urine and faeces, and from the carcasses when elimination is complete. In the hydrolysed urine of rats dosed with either [14C]Prefix or 2,6-dichlorobenzo[14C]nitrile, 2,6-dichloro-3-hydroxybenzonitrile accounts for approx. 42% of the 14C, a further 10–11% is accounted for by 2,6-dichlorobenzamide, 2,6-dichlorobenzoic acid, 2,6-dichloro-3- and -4-hydroxybenzoic acid and 2,6-dichloro-4-hydroxybenzonitrile collectively, and 25–30% by six polar constituents, of which two are sulphur-containing amino acids. 5. In the unhydrolysed urines of rats dosed with either [14C]Prefix or 2,6-dichlorobenzo[14C]nitrile, there are present free 2,6-dichloro-3- and -4-hydroxybenzonitrile, their glucuronide conjugates, ester glucuronides of the principal aromatic acids that are present in the hydrolysed urines, and two sulphur-containing metabolites analogous to mercapturic acids or premercapturic acids. 6. Prefix is thus extensively transformed into 2,6-dichlorobenzonitrile: R·CS·NH2→R·CN+H2S, where R=C6H3Cl2. However, the competitive reaction: R·CS·NH2+H2O→R·CO·NH2+H2S takes place to a very limited extent. PMID:5911525

49 CFR 821.3 - Description of docket numbering system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... handled by the Board will receive a letter prefix. These letter prefixes reflect the case type: “SE” for... of civil penalties; “NA” for cases in which a petition for review or appeal is not accepted because...

14 CFR 1260.15 - Format and numbering.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Fiscal Year 2004 would be NNC04AA01H and NNC04AA02H. (7) The Catalog of Federal Domestic Assistance (CFDA... will be applied as follows: (1) Agency prefix. NASA's agency prefix shall be represented by the...

Vocabulary: A Major Factor in Reading Comprehension.

ERIC Educational Resources Information Center

Stotsky, Sandra L.

The major purpose of this research was to show how specific theoretical principles and criteria could be integrated and supported by empirical data to provide a rationale for more systematic introduction of vocabulary in middle-grade reading-instruction material. Research was limited to the teaching of prefixes and the use of prefixed words. A…

Vowel Harmony in Palestinian Arabic: A Metrical Perspective.

ERIC Educational Resources Information Center

Abu-Salim, I. M.

1987-01-01

The autosegmental rule of vowel harmony (VH) in Palestinian Arabic is shown to be constrained simultaneously by metrical and segmental boundaries. The indicative prefix bi- is no longer an exception to VH if a structure is assumed that disallows the prefix from sharing a foot with the stem, consequently blocking VH. (Author/LMO)

Common Medical Abbreviations and Terminology: Modularized Instruction for Nurses.

ERIC Educational Resources Information Center

Moseley, James L.

A learning module to introduce nurses to the main medical abbreviations and often-used prefixes and suffixes is presented. Learning objectives of the module are: to provide the definitions of often-used suffixes and prefixes, and to identify definitions of medical abbreviations. The following materials are presented: a pretest consisting of 30…

48 CFR 246.710-70 - Warranty attachment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Enterprise Identifier Code Type 0-9—GS1 Company Prefix. D—CAGE. LB—ATIS-0322000. LH—EHIBCC. RH—HIBCC. UN—DUNS... Guarantor Enterprise Identifier Code Type 0-9—GS1 Company Prefix. D—CAGE. LB—ATIS-0322000. LH—EHIBCC. RH... returns Name ** Address line 1 ** Address line 2 ** City/county ** State/province ** Postal code...

Algorithmic and user study of an autocompletion algorithm on a large medical vocabulary.

PubMed

Sevenster, Merlijn; van Ommering, Rob; Qian, Yuechen

2012-02-01

Autocompletion supports human-computer interaction in software applications that let users enter textual data. We will be inspired by the use case in which medical professionals enter ontology concepts, catering the ongoing demand for structured and standardized data in medicine. Goal is to give an algorithmic analysis of one particular autocompletion algorithm, called multi-prefix matching algorithm, which suggests terms whose words' prefixes contain all words in the string typed by the user, e.g., in this sense, opt ner me matches optic nerve meningioma. Second we aim to investigate how well it supports users entering concepts from a large and comprehensive medical vocabulary (snomed ct). We give a concise description of the multi-prefix algorithm, and sketch how it can be optimized to meet required response time. Performance will be compared to a baseline algorithm, which gives suggestions that extend the string typed by the user to the right, e.g. optic nerve m gives optic nerve meningioma, but opt ner me does not. We conduct a user experiment in which 12 participants are invited to complete 40 snomed ct terms with the baseline algorithm and another set of 40 snomed ct terms with the multi-prefix algorithm. Our results show that users need significantly fewer keystrokes when supported by the multi-prefix algorithm than when supported by the baseline algorithm. The proposed algorithm is a competitive candidate for searching and retrieving terms from a large medical ontology. Copyright © 2011 Elsevier Inc. All rights reserved.

Zebra finches are able to learn affixation-like patterns.

PubMed

Chen, Jiani; Jansen, Naomi; ten Cate, Carel

2016-01-01

Adding an affix to transform a word is common across the world languages, with the edges of words more likely to carry out such a function. However, detecting affixation patterns is also observed in learning tasks outside the domain of language, suggesting that the underlying mechanism from which affixation patterns have arisen may not be language or even human specific. We addressed whether a songbird, the zebra finch, is able to discriminate between, and generalize, affixation-like patterns. Zebra finches were trained and tested in a Go/Nogo paradigm to discriminate artificial song element sequences resembling prefixed and suffixed 'words.' The 'stems' of the 'words,' consisted of different combinations of a triplet of song elements, to which a fourth element was added as either a 'prefix' or a 'suffix.' After training, the birds were tested with novel stems, consisting of either rearranged familiar element types or novel element types. The birds were able to generalize the affixation patterns to novel stems with both familiar and novel element types. Hence, the discrimination resulting from the training was not based on memorization of individual stimuli, but on a shared property among Go or Nogo stimuli, i.e., affixation patterns. Remarkably, birds trained with suffixation as Go pattern showed clear evidence of using both prefix and suffix, while those trained with the prefix as the Go stimulus used primarily the prefix. This finding illustrates that an asymmetry in attending to different affixations is not restricted to human languages.

Lessons Learned from the Soviet Withdrawal from Afghanistan: Examples for U.S. Policy Concerning Central Asia and Afghanistan after 2014

DTIC Science & Technology

2014-12-01

7. 248 A great deal of uncertainty surrounds the incident as the government suppressed media reporting and blocked all forms of communication ... A Post-2014 Strategy for Central Asia. Carlisle, PA: Army War College , 2012. http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html...Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the

Decomposing Slavic Aspect: The Role of Aspectual Morphology in Polish and Other Slavic Languages

ERIC Educational Resources Information Center

Lazorczyk, Agnieszka Agata

2010-01-01

This dissertation considers the problem of the semantic function of verbal aspectual morphology in Polish and other Slavic languages in the framework of generative syntax and semantics. Three kinds of such morphology are examined: (i) prefixes attaching directly to the root, (ii) "secondary imperfective" suffixes, and (iii) three prefixes that…

Prefix Identification in the Reading of Dutch Bisyllabic Words

ERIC Educational Resources Information Center

Verhoeven, Ludo; Schreuder, Robert; Haarman, Vera

2006-01-01

Two experiments were conducted in order to explore the role of prefix identification in the reading of Dutch bisyllabic words. Although Dutch orthography is highly regular, several deviations from a one-to-one correspondence exist. A case in point is the grapheme E which can represent the vowels epsilon, e and oe in polysyllabic words. In…

Medical Terminology: Using Some Common Prefixes, Suffixes, and Roots. Health Occupations Education Module.

ERIC Educational Resources Information Center

Temple Univ., Philadelphia, PA. Div. of Vocational Education.

This module on medical terminology (using common prefixes, suffixes, and root words) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three learning…

Enhancing a Web Crawler with Arabic Search Capability

DTIC Science & Technology

2010-09-01

7 Figure 2. Monolingual 11-point precision results. From [14]...........................................8 Figure 3. Lucene...libraries (prefixes dictionary , stems dictionary and suffixes dictionary ). If all the word elements (prefix, stem, suffix) are found in their...stemmer improved over 90% in average precision from raw retrieval. The authors concluded that stemming is very effective on Arabic IR. For monolingual

Contrastive Analysis between English and Indonesian Prefixes and Suffixes (A Narative Text Analysis of Legends in Perspective of Morphology)

ERIC Educational Resources Information Center

Pauzan

2016-01-01

This research deals with finding the similarities and differences, and describing the types of the English and Indonesian prefixes and suffixes for the narrative text of Legends. In this research, writer used descriptive qualitative research and contrastive methodology to find out the valid data. After investigating the data, writer found some…

Learning about Science Graphs and Word Games. Superific Science Book V. A Good Apple Science Activity Book for Grades 5-8+.

ERIC Educational Resources Information Center

Conway, Lorraine

This packet of student materials contains a variety of worksheet activities dealing with science graphs and science word games. These reproducible materials deal with: (1) bar graphs; (2) line graphs; (3) circle graphs; (4) pictographs; (5) histograms; (6) artgraphs; (7) designing your own graphs; (8) medical prefixes; (9) color prefixes; (10)…

Entropy-Based Bounds On Redundancies Of Huffman Codes

NASA Technical Reports Server (NTRS)

Smyth, Padhraic J.

1992-01-01

Report presents extension of theory of redundancy of binary prefix code of Huffman type which includes derivation of variety of bounds expressed in terms of entropy of source and size of alphabet. Recent developments yielded bounds on redundancy of Huffman code in terms of probabilities of various components in source alphabet. In practice, redundancies of optimal prefix codes often closer to 0 than to 1.

Symbolic Dynamics and Grammatical Complexity

NASA Astrophysics Data System (ADS)

Hao, Bai-Lin; Zheng, Wei-Mou

The following sections are included: * Formal Languages and Their Complexity * Formal Language * Chomsky Hierarchy of Grammatical Complexity * The L-System * Regular Language and Finite Automaton * Finite Automaton * Regular Language * Stefan Matrix as Transfer Function for Automaton * Beyond Regular Languages * Feigenbaum and Generalized Feigenbaum Limiting Sets * Even and Odd Fibonacci Sequences * Odd Maximal Primitive Prefixes and Kneading Map * Even Maximal Primitive Prefixes and Distinct Excluded Blocks * Summary of Results

Index of NASA prefixed forms

NASA Technical Reports Server (NTRS)

1992-01-01

This Handbook sets forth information for the guidance of all users of the NASA Forms Management Program System. It is issued in accordance with the Federal Information Resources Management Regulation (FIRMR), Subpart 201-9.1. This Handbook sets forth an alpha-functional index of NASA-prefixed forms by title, identifying number, and unit of issue. The automated processing two-letter code (NF) has been substituted for the spelling out of the NASA form-prefix preceding the form number. To indicate a description in lieu of a distinct title, the entire reference under the Form Title/Description column has been enclosed in parentheses. A list of current forms, shown by number and page, is included for cross-reference and to preclude the ordering of those forms which have been deleted from the system. This Handbook will be updated, as appropriate. NHB 1420.2H dated July 1986, is cancelled.

Sorting permutations by prefix and suffix rearrangements.

PubMed

Lintzmayer, Carla Negri; Fertin, Guillaume; Dias, Zanoni

2017-02-01

Some interesting combinatorial problems have been motivated by genome rearrangements, which are mutations that affect large portions of a genome. When we represent genomes as permutations, the goal is to transform a given permutation into the identity permutation with the minimum number of rearrangements. When they affect segments from the beginning (respectively end) of the permutation, they are called prefix (respectively suffix) rearrangements. This paper presents results for rearrangement problems that involve prefix and suffix versions of reversals and transpositions considering unsigned and signed permutations. We give 2-approximation and ([Formula: see text])-approximation algorithms for these problems, where [Formula: see text] is a constant divided by the number of breakpoints (pairs of consecutive elements that should not be consecutive in the identity permutation) in the input permutation. We also give bounds for the diameters concerning these problems and provide ways of improving the practical results of our algorithms.

Structural Analysis via Generalized Interactive Graphics - STAGING. Volume III. System Manual.

DTIC Science & Technology

1979-09-01

DISTRIBUTION UNLIMITED 17 DISTRIBUTION ST ATEMENT (of the abnsrct entered in Block 20. it different from, Report) IS SJPPLEMENTARY NOTES I9 KEY WORDS ILCI-lue on...prefixMENUDRIVER and the menu data base itself is cataloged as prefixMENU. The maintanance of the STAGING Material Property Data Base (MPDB...Property Data Base System, and conversion routines as describe,: -n Section 1.2 through 1.6. If any difficulties arise due to differences in operatire

Department of Defense Dictionary Of Military and Associated Terms

DTIC Science & Technology

2010-12-31

designated United States Naval Ships and use the prefix “USNS” with the ship name and the letter “T” as a prefix to the ship classification (e.g., T- AKR ...T- AKR ). See also Military Sealift Command; United States Naval Ship. (JP 3-02.2) gradient — The rate of inclination to horizontal expressed as a ...Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a

The Effect of Knowledge Management Systems on Organizational Performance. Do Soldier and Unit Counterinsurgency Knowledge and Performance Improve Following ’Push’ or ’Adaptive-Push’ Training

DTIC Science & Technology

2009-01-01

theory ...................24 Table 3.1 Five techniques of pretest - posttest analysis (from Bonate, 2000) ....................34 Table 3.2 Main Effects...Davenport, 1998). In a pretest / posttest design study by Schlomer, Anderson, and Shaw (1997) no statistically significant differences in KR outcomes were... Pretest / posttest design overview ____________ 54 Question numbers ranged from 1 to 55. The prefix a represents a pretest question and the prefix b

FloCon 2008 Proceedings

DTIC Science & Technology

2008-01-01

anomalous traffic of the node ÷ total anomalous traffic – Make parent nodes by merging child node information. prefix/length coverage/collateral...A T A U P L O A D F L O W S E N S O R 5. DATA DOWNLOAD FLOW SENSOR 1. RECON SNORT: KICKASS_PORN DRAGON: PORN HARDCORE SOURCEDEST SOURCE SOURCE...traffic • Make parent nodes by merging child node information. prefix/length coverage/collateral 0.0.0.0/0 100/100 depth=0 non divided 0.0.0.0/1 50/30

Refining search terms for nanotechnology

NASA Astrophysics Data System (ADS)

Porter, Alan L.; Youtie, Jan; Shapira, Philip; Schoeneck, David J.

2008-05-01

The ability to delineate the boundaries of an emerging technology is central to obtaining an understanding of the technology's research paths and commercialization prospects. Nowhere is this more relevant than in the case of nanotechnology (hereafter identified as "nano") given its current rapid growth and multidisciplinary nature. (Under the rubric of nanotechnology, we also include nanoscience and nanoengineering.) Past efforts have utilized several strategies, including simple term search for the prefix nano, complex lexical and citation-based approaches, and bootstrapping techniques. This research introduces a modularized Boolean approach to defining nanotechnology which has been applied to several research and patenting databases. We explain our approach to downloading and cleaning data, and report initial results. Comparisons of this approach with other nanotechnology search formulations are presented. Implications for search strategy development and profiling of the nanotechnology field are discussed.

An adverse event screening tool based on routinely collected hospital-acquired diagnoses.

PubMed

Brand, Caroline; Tropea, Joanne; Gorelik, Alexandra; Jolley, Damien; Scott, Ian; Sundararajan, Vijaya

2012-06-01

The aim was to develop an electronic adverse event (AE) screening tool applicable to acute care hospital episodes for patients admitted with chronic heart failure (CHF) and pneumonia. Consensus building using a modified Delphi method and descriptive analysis of hospital discharge data. Consultant physicians in general medicine (n = 38). In-hospital acquired (C-prefix) diagnoses associated with CHF and pneumonia admissions to 230 hospitals in Victoria, Australia, were extracted from the Victorian Admitted Episodes Data Set between July 2004 and June 2007. A 9-point rating scale was used to prioritize diagnoses acquired during hospitalization (routinely coded as a 'C-prefix' diagnosis to distinguish from diagnoses present on admission) for inclusion within an AE screening tool. Diagnoses rated a group median score between 7 and 9 by the physician panel were included. Selection of C-prefix diagnoses with a group median rating of 7-9 in a screening tool, and the level of physician agreement, as assessed using the Interpercentile Range Adjusted for Symmetry. Of 697 initial C-prefix diagnoses, there were high levels of agreement to include 113 (16.2%) in the AE screening tool. Using these selected diagnoses, a potential AE was flagged in 14% of all admissions for the two index conditions. Intra-rater reliability for each clinician ranged from kappa 0.482 to 1.0. A high level of physician agreement was obtained in selecting in-hospital diagnoses for inclusion in an AE screening tool based on routinely collected data. These results support further tool validation.

Willingness to pay for a 4% chlorhexidine (7.1% chlorhexidine digluconate) product for umbilical cord care in rural Bangladesh: a contingency valuation study

PubMed Central

2013-01-01

Background Recent trials in Bangladesh, Nepal, and Pakistan have shown that chlorhexidine is an effective antiseptic for umbilical cord care compared to existing community-based cord care practices. Because of the aggregate reduction in neonatal mortality in these trials, interest is high in introducing a 7.1% chlorhexidine digluconate liquid or gel that delivers 4% chlorhexidine for umbilical cord care in Bangladesh and elsewhere. Methods In 2010, we conducted a household survey applying a contingent valuation method with 1717 eligible couples (pregnant women or women with a first child younger than 6 months old, and their husbands) in the rural subdistricts of Abhoynagar and Mirsarai in Bangladesh to assess their willingness to pay for three types of umbilical cord care products at different price points. Each respondent was asked about willingness to pay prefixed prices for any one of three 7.1% chlorhexidine digluconate products: 1) a single-dose liquid, 2) a multi-dose liquid, or 3) a gel formulation. Each also reported the maximum price they were independently willing to pay for their selected product. We compared participant willingness-to-pay responses to the prefixed prices with their independently reported maximum prices for each type of the product separately. The comparison identified to what extent the respondents’ positive responses to the prefixed prices matched their independently reported maximum prices. Results This cross matching revealed that willingness to pay the prefixed prices was 41% for the single-dose liquid, 33% for the multi-dose liquid, and 31% for the gel formulation. Although the majority of the respondents were unwilling to pay the prefixed prices, all were willing to pay some amount and reported they could borrow money if necessary. Subsequent analysis of responses to the multi-dose liquid showed borrowing money would not be required if the unit price was Bangladeshi taka 15–25. Conclusions A unit price of Bangladeshi taka 15–25 (US$0.21–0.35) for multi-dose 7.1% chlorhexidine digluconate liquid would be affordable to the primary target population in Bangladesh. Although a large market demand could be generated if the product were available at this price point, subsidization may be required to achieve optimal coverage, especially among poorer families. PMID:24139384

Willingness to pay for a 4% chlorhexidine (7.1% chlorhexidine digluconate) product for umbilical cord care in rural Bangladesh: a contingency valuation study.

PubMed

Coffey, Patricia S; Metzler, Mutsumi; Islam, Ziaul; Koehlmoos, Tracey P

2013-10-18

Recent trials in Bangladesh, Nepal, and Pakistan have shown that chlorhexidine is an effective antiseptic for umbilical cord care compared to existing community-based cord care practices. Because of the aggregate reduction in neonatal mortality in these trials, interest is high in introducing a 7.1% chlorhexidine digluconate liquid or gel that delivers 4% chlorhexidine for umbilical cord care in Bangladesh and elsewhere. In 2010, we conducted a household survey applying a contingent valuation method with 1717 eligible couples (pregnant women or women with a first child younger than 6 months old, and their husbands) in the rural subdistricts of Abhoynagar and Mirsarai in Bangladesh to assess their willingness to pay for three types of umbilical cord care products at different price points. Each respondent was asked about willingness to pay prefixed prices for any one of three 7.1% chlorhexidine digluconate products: 1) a single-dose liquid, 2) a multi-dose liquid, or 3) a gel formulation. Each also reported the maximum price they were independently willing to pay for their selected product. We compared participant willingness-to-pay responses to the prefixed prices with their independently reported maximum prices for each type of the product separately. The comparison identified to what extent the respondents' positive responses to the prefixed prices matched their independently reported maximum prices. This cross matching revealed that willingness to pay the prefixed prices was 41% for the single-dose liquid, 33% for the multi-dose liquid, and 31% for the gel formulation. Although the majority of the respondents were unwilling to pay the prefixed prices, all were willing to pay some amount and reported they could borrow money if necessary. Subsequent analysis of responses to the multi-dose liquid showed borrowing money would not be required if the unit price was Bangladeshi taka 15-25. A unit price of Bangladeshi taka 15-25 (US$0.21-0.35) for multi-dose 7.1% chlorhexidine digluconate liquid would be affordable to the primary target population in Bangladesh. Although a large market demand could be generated if the product were available at this price point, subsidization may be required to achieve optimal coverage, especially among poorer families.

Replication of urban innovations - prioritization of strategies for the replication of Dhaka's community-based decentralized composting model.

PubMed

Yedla, Sudhakar

2012-01-01

Dhaka's community-based decentralized composting (DCDC) is a successful demonstration of solid waste management by adopting low-cost technology, local resources community participation and partnerships among the various actors involved. This paper attempts to understand the model, necessary conditions, strategies and their priorities to replicate DCDC in the other developing cities of Asia. Thirteen strategies required for its replication are identified and assessed based on various criteria, namely transferability, longevity, economic viability, adaptation and also overall replication. Priority setting by multi-criteria analysis by applying analytic hierarchy process revealed that immediate transferability without long-term and economic viability consideration is not advisable as this would result in unsustainable replication of DCDC. Based on the analysis, measures to ensure the product quality control; partnership among stakeholders (public-private-community); strategies to achieve better involvement of the private sector in solid waste management (entrepreneurship in approach); simple and low-cost technology; and strategies to provide an effective interface among the complementing sectors are identified as important strategies for its replication.

Alerting prefixes for speech warning messages. [in helicopters

NASA Technical Reports Server (NTRS)

Bucher, N. M.; Voorhees, J. W.; Karl, R. L.; Werner, E.

1984-01-01

A major question posed by the design of an integrated voice information display/warning system for next-generation helicopter cockpits is whether an alerting prefix should precede voice warning messages; if so, the characteristics desirable in such a cue must also be addressed. Attention is presently given to the results of a study which ascertained pilot response time and response accuracy to messages preceded by either neutral cues or the cognitively appropriate semantic cues. Both verbal cues and messages were spoken in direct, phoneme-synthesized speech, and a training manipulation was included to determine the extent to which previous exposure to speech thus produced facilitates these messages' comprehension. Results are discussed in terms of the importance of human factors research in cockpit display design.

How Do Children Restrict Their Linguistic Generalizations? An (Un-)Grammaticality Judgment Study

PubMed Central

Ambridge, Ben

2013-01-01

A paradox at the heart of language acquisition research is that, to achieve adult-like competence, children must acquire the ability to generalize verbs into non-attested structures, while avoiding utterances that are deemed ungrammatical by native speakers. For example, children must learn that, to denote the reversal of an action, un- can be added to many verbs, but not all (e.g., roll/unroll; close/*unclose). This study compared theoretical accounts of how this is done. Children aged 5–6 (N = 18), 9–10 (N = 18), and adults (N = 18) rated the acceptability of un- prefixed forms of 48 verbs (and, as a control, bare forms). Across verbs, a negative correlation was observed between the acceptability of ungrammatical un- prefixed forms (e.g., *unclose) and the frequency of (a) the bare form and (b) alternative forms (e.g., open), supporting the entrenchment and pre-emption hypotheses, respectively. Independent ratings of the extent to which verbs instantiate the semantic properties characteristic of a hypothesized semantic cryptotype for un- prefixation were a significant positive predictor of acceptability, for all age groups. The relative importance of each factor differed for attested and unattested un- forms and also varied with age. The findings are interpreted in the context of a new hybrid account designed to incorporate the three factors of entrenchment, pre-emption, and verb semantics. PMID:23252958

Anatomical study of prefixed versus postfixed brachial plexuses in adult human cadaver.

PubMed

Guday, Edengenet; Bekele, Asegedech; Muche, Abebe

2017-05-01

The brachial plexus is usually formed by the fusion of anterior primary rami of the fifth to eighth cervical and the first thoracic spinal nerves. Variations in the formation of the brachial plexus may occur. Variations in brachial plexus anatomy are important to radiologists, surgeons and anaesthesiologists performing surgical procedures in the neck, axilla and upper limb regions. These variations may lead to deviation from the expected dermatome distribution as well as differences in the motor innervation of muscles of the upper limb. This study is aimed to describe the anatomical variations of brachial plexus in its formation among 20 Ethiopian cadavers. Observational based study was conducted by using 20 cadavers obtained from the Department of Human Anatomy at University of Gondar, Bahir Dar, Addis Ababa, Hawasa, Hayat Medical College and St Paul Hospital Millennium Medical College. Data analysis was conducted using thematic approaches. A total of 20 cadavers examined bilaterally for the formation of brachial plexus. Of the 40 sides, 30 sides (75%) were found normal, seven sides (17.5%) prefixed, three sides (7.5%) postfixed and one side of the cadaver lacks cord formation. The brachial plexus formation in most subjects is found to be normal. Among the variants, the numbers of the prefixed brachial plexuses are greater than the postfixed brachial plexuses. © 2016 Royal Australasian College of Surgeons.

FPS-RAM: Fast Prefix Search RAM-Based Hardware for Forwarding Engine

NASA Astrophysics Data System (ADS)

Zaitsu, Kazuya; Yamamoto, Koji; Kuroda, Yasuto; Inoue, Kazunari; Ata, Shingo; Oka, Ikuo

Ternary content addressable memory (TCAM) is becoming very popular for designing high-throughput forwarding engines on routers. However, TCAM has potential problems in terms of hardware and power costs, which limits its ability to deploy large amounts of capacity in IP routers. In this paper, we propose new hardware architecture for fast forwarding engines, called fast prefix search RAM-based hardware (FPS-RAM). We designed FPS-RAM hardware with the intent of maintaining the same search performance and physical user interface as TCAM because our objective is to replace the TCAM in the market. Our RAM-based hardware architecture is completely different from that of TCAM and has dramatically reduced the costs and power consumption to 62% and 52%, respectively. We implemented FPS-RAM on an FPGA to examine its lookup operation.

Development of Defective and Persistent Sendai Virus Vector

PubMed Central

Nishimura, Ken; Sano, Masayuki; Ohtaka, Manami; Furuta, Birei; Umemura, Yoko; Nakajima, Yoshiro; Ikehara, Yuzuru; Kobayashi, Toshihiro; Segawa, Hiroaki; Takayasu, Satoko; Sato, Hideyuki; Motomura, Kaori; Uchida, Eriko; Kanayasu-Toyoda, Toshie; Asashima, Makoto; Nakauchi, Hiromitsu; Yamaguchi, Teruhide; Nakanishi, Mahito

2011-01-01

The ectopic expression of transcription factors can reprogram differentiated tissue cells into induced pluripotent stem cells. However, this is a slow and inefficient process, depending on the simultaneous delivery of multiple genes encoding essential reprogramming factors and on their sustained expression in target cells. Moreover, once cell reprogramming is accomplished, these exogenous reprogramming factors should be replaced with their endogenous counterparts for establishing autoregulated pluripotency. Complete and designed removal of the exogenous genes from the reprogrammed cells would be an ideal option for satisfying this latter requisite as well as for minimizing the risk of malignant cell transformation. However, no single gene delivery/expression system has ever been equipped with these contradictory characteristics. Here we report the development of a novel replication-defective and persistent Sendai virus (SeVdp) vector based on a noncytopathic variant virus, which fulfills all of these requirements for cell reprogramming. The SeVdp vector could accommodate up to four exogenous genes, deliver them efficiently into various mammalian cells (including primary tissue cells and human hematopoietic stem cells) and express them stably in the cytoplasm at a prefixed balance. Furthermore, interfering with viral transcription/replication using siRNA could erase the genomic RNA of SeVdp vector from the target cells quickly and thoroughly. A SeVdp vector installed with Oct4/Sox2/Klf4/c-Myc could reprogram mouse primary fibroblasts quite efficiently; ∼1% of the cells were reprogrammed to Nanog-positive induced pluripotent stem cells without chromosomal gene integration. Thus, this SeVdp vector has potential as a tool for advanced cell reprogramming and for stem cell research. PMID:21138846

Genetics Home Reference: schizoaffective disorder

MedlinePlus

... mental health condition that includes features of both schizophrenia and a mood disorder such as bipolar disorder ... prefix "schizo-" refers to the psychotic symptoms of schizophrenia that affect a person's thinking, sense of self, ...

Fixation, transient landscape, and diffusion dilemma in stochastic evolutionary game dynamics

NASA Astrophysics Data System (ADS)

Zhou, Da; Qian, Hong

2011-09-01

Agent-based stochastic models for finite populations have recently received much attention in the game theory of evolutionary dynamics. Both the ultimate fixation and the pre-fixation transient behavior are important to a full understanding of the dynamics. In this paper, we study the transient dynamics of the well-mixed Moran process through constructing a landscape function. It is shown that the landscape playing a central theoretical “device” that integrates several lines of inquiries: the stable behavior of the replicator dynamics, the long-time fixation, and continuous diffusion approximation associated with asymptotically large population. Several issues relating to the transient dynamics are discussed: (i) multiple time scales phenomenon associated with intra- and inter-attractoral dynamics; (ii) discontinuous transition in stochastically stationary process akin to Maxwell construction in equilibrium statistical physics; and (iii) the dilemma diffusion approximation facing as a continuous approximation of the discrete evolutionary dynamics. It is found that rare events with exponentially small probabilities, corresponding to the uphill movements and barrier crossing in the landscape with multiple wells that are made possible by strong nonlinear dynamics, plays an important role in understanding the origin of the complexity in evolutionary, nonlinear biological systems.

Reconsidering Replication: New Perspectives on Large-Scale School Improvement

ERIC Educational Resources Information Center

Peurach, Donald J.; Glazer, Joshua L.

2012-01-01

The purpose of this analysis is to reconsider organizational replication as a strategy for large-scale school improvement: a strategy that features a "hub" organization collaborating with "outlet" schools to enact school-wide designs for improvement. To do so, we synthesize a leading line of research on commercial replication to construct a…

9 CFR 71.1 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... subchapter, for conducting an active State scrapie program involving the identification of scrapie in sheep... which contains or displays an AIN with an 840 prefix must bear the U.S. shield. The design, size, shape...

9 CFR 71.1 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... subchapter, for conducting an active State scrapie program involving the identification of scrapie in sheep... which contains or displays an AIN with an 840 prefix must bear the U.S. shield. The design, size, shape...

Strategic Use of Random Subsample Replication and a Coefficient of Factor Replicability

ERIC Educational Resources Information Center

Katzenmeyer, William G.; Stenner, A. Jackson

1975-01-01

The problem of demonstrating replicability of factor structure across random variables is addressed. Procedures are outlined which combine the use of random subsample replication strategies with the correlations between factor score estimates across replicate pairs to generate a coefficient of replicability and confidence intervals associated with…

Replicating Social Programmes: Approaches, Strategies and Conceptual Issues. Management of Social Transformations (MOST) Discussion Paper Series, No. 18.

ERIC Educational Resources Information Center

van Oudenhoven, Nico; Wazir, Rekha

This paper reviews the key issues and methodologies involved in the replication of social programs, as they pertain to non-profit sector development in the United States and in international development. The related process of knowledge transfer and dissemination, as well as the more specific strategies involved in replication and going-to-scale…

Life and dynamic capacity modeling for aircraft transmissions

NASA Technical Reports Server (NTRS)

Savage, Michael

1991-01-01

A computer program to simulate the dynamic capacity and life of parallel shaft aircraft transmissions is presented. Five basic configurations can be analyzed: single mesh, compound, parallel, reverted, and single plane reductions. In execution, the program prompts the user for the data file prefix name, takes input from a ASCII file, and writes its output to a second ASCII file with the same prefix name. The input data file includes the transmission configuration, the input shaft torque and speed, and descriptions of the transmission geometry and the component gears and bearings. The program output file describes the transmission, its components, their capabilities, locations, and loads. It also lists the dynamic capability, ninety percent reliability, and mean life of each component and the transmission as a system. Here, the program, its input and output files, and the theory behind the operation of the program are described.

HNP renumbering support in PMIPv6

NASA Astrophysics Data System (ADS)

Yan, Zhiwei; Geng, Guanggang; Lee, Xiaodong

2015-12-01

In the basic PMIPv6 (Proxy Mobile IPv6), the MN (Mobile Node) is assigned with a 64-bit HNP (Home Network Prefix) during the initial attachment for the HoA (Home Address) configuration. During the movements of MN, this prefix is assumed to be unchanged and then the upper layer applications do not have to use the reconfigured HoA and then the handover is transparent at the IP and above layers. However, the current protocol does not specify the related operation to support the MN to timely receive the new HNP and configure the new HoA when its HNP is renumbered. In this paper, this problem is discussed and a possible solution is proposed based on some simple extensions of the basic PMIPv6. Our analysis demonstrates that the proposed scheme can effectively discover the HNP renumbering and keep lower signaling cost, compared with the basic PMIPv6.

Effect of pre-fixation delay and freezing on mink testicular endpoints for environmental research.

PubMed

Spörndly-Nees, Ellinor; Ekstedt, Elisabeth; Magnusson, Ulf; Fakhrzadeh, Azadeh; Luengo Hendriks, Cris L; Holm, Lena

2015-01-01

There is growing interest in using wild animals to monitor the real-life cocktail effect of environmental chemicals on male reproduction. However, practical difficulties, such as long distances to the laboratory, generally prolong the time between euthanisation and specimen handling. For instance, tissue fixation is often performed on frozen material or on material where deterioration has started, which may affect tissue morphology. This study examined the effect of pre-fixation delay and freezing on mink testicular endpoints in order to determine robust endpoints in suboptimally handled specimens. Sexually mature farmed mink (n=30) selected at culling were divided into six groups and subjected to different time intervals between euthanisation and fixation or freezing: 0 hours (fixed immediately post mortem), 6 hours, 18 hours, 30 hours, 42 hours, or frozen 6 hours post mortem and thawed overnight. Unaffected endpoints when pre-fixation storage was extended to 30 hours included: area and diameter of the seminiferous tubules, length and weight of the testes, and acrosomes marked with Gata-4. Epithelial height, Sertoli cells marked with Gata-4 and cell morphology were affected endpoints after 6 hours of storage. Freezing the tissue prior to fixation severely altered cell morphology and reduced testicular weight, tubular diameter and area. Morphological changes seen after 6 hours included shredded germ cells and excess cytoplasm in seminiferous tubular lumen, chromatin rearrangements and increased germ cell death. Extended delay before fixation and freezing affected many endpoints in the mink testicular tissue. Some of these endpoints may mimic chemically induced effects, which is important to consider when evaluating specimens from wild animals for environmental toxicity.

Education Policy and the 'Inter'-Regnum

ERIC Educational Resources Information Center

Hartley, David

2007-01-01

In the UK, the vocabulary of public services is becoming infused with the prefixes "inter"-, "multi-" and "co-". Public-sector agencies are being encouraged to adopt"'multi"- or "inter-agency" configurations; "workforce reform" seeks to dissolve once-impermeable professional boundaries;…

Flexible Data Link

DTIC Science & Technology

2015-04-01

DDC ) results in more complicated digital (FPGA) processing, yet simplifies the analog design significantly while improving the quality of the...Interleaved CP Cyclic Prefix DAC Digital to Analog Converter DDC Digital Down Converter DDR Double Data Rate DUC Digital Up Converter ENOB Effective

Rosetta Stones for Energy Problems.

ERIC Educational Resources Information Center

Hayden, Howard C.

1981-01-01

Demonstrates, using specific problems, how various energy units can be converted to joules and power units to watts. Conversion tables are provided for power, energy, generation values, thermal insulation, consumption values, sunlight, with tables also on metric prefixes and time conversions. (SK)

Multiplex CRISPR/Cas9 system impairs HCMV replication by excising an essential viral gene.

PubMed

Gergen, Janina; Coulon, Flora; Creneguy, Alison; Elain-Duret, Nathan; Gutierrez, Alejandra; Pinkenburg, Olaf; Verhoeyen, Els; Anegon, Ignacio; Nguyen, Tuan Huy; Halary, Franck Albert; Haspot, Fabienne

2018-01-01

Anti-HCMV treatments used in immunosuppressed patients reduce viral replication, but resistant viral strains can emerge. Moreover, these drugs do not target latently infected cells. We designed two anti-viral CRISPR/Cas9 strategies to target the UL122/123 gene, a key regulator of lytic replication and reactivation from latency. The singleplex strategy contains one gRNA to target the start codon. The multiplex strategy contains three gRNAs to excise the complete UL122/123 gene. Primary fibroblasts and U-251 MG cells were transduced with lentiviral vectors encoding Cas9 and one or three gRNAs. Both strategies induced mutations in the target gene and a concomitant reduction of immediate early (IE) protein expression in primary fibroblasts. Further detailed analysis in U-251 MG cells showed that the singleplex strategy induced 50% of indels in the viral genome, leading to a reduction in IE protein expression. The multiplex strategy excised the IE gene in 90% of all viral genomes and thus led to the inhibition of IE protein expression. Consequently, viral genome replication and late protein expression were reduced by 90%. Finally, the production of new viral particles was nearly abrogated. In conclusion, the multiplex anti-UL122/123 CRISPR/Cas9 system can target the viral genome efficiently enough to significantly prevent viral replication.

How Soon Will We Measure in Metric?

ERIC Educational Resources Information Center

Weaver, Kenneth F.

1977-01-01

A brief history of measurement systems beginning with the Egyptians and Babylonians is given, ending with a discussion of the metric system and its adoption by the United States. Tables of metric prefixes, metric units, and common metric conversions are included. (MN)

Common conversion factors.

PubMed

2001-05-01

This appendix presents tables of some of the more common conversion factors for units of measure used throughout Current Protocols manuals, as well as prefixes indicating powers of ten for SI units. Another table gives conversions between temperatures on the Celsius (Centigrade) and Fahrenheit scales.

morphogen: Translation into Morphologically Rich Languages with Synthetic Phrases

DTIC Science & Technology

2013-10-01

specific trans - lation phrases. These “synthetic phrases” augment the standard translation grammars and decoding proceeds normally with a standard...Genitive case grandparent(poss) Hebrew Suffix ים ( masculine plural) parent=NNS after=NNS Prefix א (first person sing. + future) child(nsubj)=I child(aux

TESL Reporter, Vol. 10, No. 4.

ERIC Educational Resources Information Center

Pack, Alice C., Ed.

This issue contains the following articles: "Providing Practice Teaching through Peer Teaching: A Realistic Approach," by Ted Plaister; "Repetition within a Fun Context," by Emilio G. Cortez; "Sector Analysis and Working Sentences," by Lynn Henrichsen; "The TESL Teacher and English Prefixes," by Mohammed Ali…

MISR Level 3 Radiance Versioning

Atmospheric Science Data Center

2016-11-04

... ESDT Product File Name Prefix Current Quality Designations MIL3DRD, MIL3MRD, MIL3QRD, and MIL3YRD ... Data Product Specification Rev K  (PDF). Update to work with new format of the input PGE 1 files.   F02_0007 ...

What's in a name? Atopic dermatitis or atopic eczema, but not eczema alone.

PubMed

Silverberg, J I; Thyssen, J P; Paller, A S; Drucker, A M; Wollenberg, A; Lee, K H; Kabashima, K; Todd, G; Schmid-Grendelmeier, P; Bieber, T

2017-12-01

The ideal nomenclature of atopic dermatitis (AD) / atopic eczema (AE) has long been contested. However, it is becoming increasingly clear that the disparate nomenclature of this disease may have important deleterious ramifications for clinical care and research. An electronic questionnaire regarding the preferred nomenclature for AD was sent to councilors of the International Eczema Council (IEC) (n=77), an international group of clinicians and researchers with expertise in AD/AE. The survey consisted of 2 questions for consensus regarding the preference for an atopic prefix, and preference for the term AD or AE, and an exploratory question about the acceptability of the terms AD, AE or eczema. Consensus was defined a priori as at least 90% agreement for each question with a response rate of at least 90%. Seventy-one of 77 (92.2%) IEC councilors and associates responded to the survey, with all respondents completing the entire survey. Consensus was reached for question 1, with 69 of 71 respondents (97.2%) preferring the atopic prefix. However, consensus was not reached for question 2, with 40 respondents (58.0%) preferring the term AD and 30 (43,5%) preferring AE. Sixty-three respondents (88.7%) and 55 (77.5%) felt that the terms AD and AE were acceptable, whereas only 11 (15.5%) felt that eczema was acceptable. The IEC noted that the term eczema is imprecise, and its use is confusing. The consensus of the IEC was to recommend use of the prefix "atopic" (i.e., AD or AE) in all publications, presentations and discussions about the disorder. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

The effect of selective attention and a stimulus prefix on the output order of immediate free recall of short and long lists.

PubMed

Grenfell-Essam, Rachel; Ward, Geoff

2015-03-01

Participants tend to initiate immediate free recall (IFR) of short lists of words with the first word in the list (Serial Position 1 [SP1]) and then proceed in forward serial order. Two potential explanations for this finding were examined: that the first items have increased selective attention (Experiment 1A and 1B) and enhanced temporal distinctiveness (Experiment 2) relative to subsequent list items. In Experiments 1A and 1B, participants were presented with lists of colored words for IFR. The experimental group was told that some trials would contain a red word and that when this occurred, they should output this word first in recall before recalling as many other words as they could. This instruction was designed to shift attention away from SP1 and toward the red item. The control group participants received identical stimuli but were unaware of the importance of the colored words and had no output order constraints. The overall recall of SP1 was not greatly affected in either experiment. In Experiment 2, participants were presented with lists containing between 2 and 12 words. Half of the trials contained a triple word stimulus prefix. For short lists in IFR, the overall recall of SP1 and the tendency to initiate recall with SP1 were reduced but far from eliminated by the stimulus prefix. We argue that our findings may be explained within a grouping interpretation in which the tendency to initiate recall with the first to-be-remembered item may reflect participants' tendency to output the first word in a highly salient participant-determined group. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

MISR Level 1A CCD, 1B1, 1B2, and Browse Products

Atmospheric Science Data Center

2013-04-01

... ESDT Product File Name Prefix Current Quality Designations MI1B2E MISR_AM1_GRP_ELLIPSOID_GM, ... should be used. All calibration files for the life of the mission have been reprocessed using the best available calibration. ...

Planning Programs for Transescents.

ERIC Educational Resources Information Center

Eichhorn, Donald H.

"Transescents" -- the prefix "trans" meaning "to go across" and the suffix "escent" meaning "to become something" -- are young people in transition from childhood to adolescence. The middle school organization presents educators with an opportunity for improved educational processes uniquely suited to students of this age group. Transescents are…

System International d'Unites: Metric Measurement in Water Resources Engineering.

ERIC Educational Resources Information Center

Klingeman, Peter C.

This pamphlet gives definitions and symbols for the basic and derived metric units, prefixes, and conversion factors for units frequently used in water resources. Included are conversion factors for units of area, work, heat, power, pressure, viscosity, flow rate, and others. (BB)

Medical Information for the Vocational Rehabilitation Counselor--A Training Guide.

ERIC Educational Resources Information Center

Phelps, William R.

This paper presents information helpful to the vocational rehabilitation counselor and can be utilized in training programs for the newly employed untrained vocational rehabilitation practitioner. Areas covered include medical terminology, common prefixes and suffixes, speciality boards; paramedic professions, and medical education. Undergraduate…

ML Frame Synchronization for OFDM Systems Using a Known Pilot and Cyclic Prefixes

NASA Astrophysics Data System (ADS)

Huh, Heon

Orthogonal frequency-division multiplexing (OFDM) is a popular air interface technology that is adopted as a standard modulation scheme for 4G communication systems owing to its excellent spectral efficiency. For OFDM systems, synchronization problems have received much attention along with peak-to-average power ratio (PAPR) reduction. In addition to frequency offset estimation, frame synchronization is a challenging problem that must be solved to achieve optimal system performance. In this paper, we present a maximum likelihood (ML) frame synchronizer for OFDM systems. The synchronizer exploits a synchronization word and cyclic prefixes together to improve the synchronization performance. Numerical results show that the performance of the proposed frame synchronizer is better than that of conventional schemes. The proposed synchronizer can be used as a reference for evaluating the performance of other suboptimal frame synchronizers. We also modify the proposed frame synchronizer to reduce the implementation complexity and propose a near-ML synchronizer for time-varying fading channels.

Ancient Greek Terminology in Hepatopancreatobiliary Anatomy and Surgery.

PubMed

Papoulas, Michail; Douvetzemis, Stergios

2015-08-01

Most of the terminology in medicine originates from Greek or Latin, revealing the impact of the ancient Greeks on modern medicine. However, the literature on the etymology of Greek words used routinely in medical practice is sparse. We provide a short guide to the etymology and meaning of Greek words currently used in the field of hepatopancreatobiliary (HPB) anatomy and surgery. Focusing on HPB medical literature, the etymology and origin of Greek words including suffixes and prefixes are shown and analyzed. For example, anatomy (anatomia) is a Greek word derived from the prefix ana- (on, upon) and the suffix -tomy from the verb temno meaning to cut. Surgery, however, is not a Greek word. The corresponding Greek word is chirourgiki derived from cheir (hand) and ergon (action, work) meaning the action made by hands. Understanding the root of Greek terminology leads to an accurate, precise and comprehensive scientific medical language, reflecting the need for a universal medical language as a standardized means of communication within the health care sector.

Laying a Solid Foundation: Strategies for Effective Program Replication

ERIC Educational Resources Information Center

Summerville, Geri

2009-01-01

The replication of proven social programs is a cost-effective and efficient way to achieve large-scale, positive social change. Yet there has been little guidance available about how to approach program replication and limited development of systems--at local, state or federal levels--to support replication efforts. "Laying a Solid Foundation:…

31 CFR 589.201 - Prohibited transactions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Register and incorporated into OFAC's Specially Designated Nationals and Blocked Persons List (“SDN List”) and appear with the prefix “UKRAINE” in the program tag associated with each listing. The SDN List is accessible through the following page on OFAC's Web site: www.treasury.gov/sdn. Additional information...

All You Need to Know About Metric

ERIC Educational Resources Information Center

American Metric Journal, 1974

1974-01-01

Information found necessary for South Africa's citizens to learn during their recent conversion to the metric system is presented. Twelve terms and prefixes are suggested that satisfy practically all ordinary needs. Tables are given for the most commonly used measures, with relationships between different units indicated. (LS)

Synthesis of Efficient Structures for Concurrent Computation.

DTIC Science & Technology

1983-10-01

formal presentation of these techniques, called virtualisation and aggregation, can be found n [King-83$. 113.2 Census Functions Trees perform broadcast... Functions .. .. .. .. ... .... ... ... .... ... ... ....... 6 4 User-Assisted Aggregation .. .. .. .. ... ... ... .... ... .. .......... 6 5 Parallel...6. Simple Parallel Structure for Broadcasting .. .. .. .. .. . ... .. . .. . .... 4 Figure 7. Internal Structure of a Prefix Computation Network

2017 Louisiana “Ho” nursery variety trials

USDA-ARS?s Scientific Manuscript database

In the USDA Sugarcane Research Unit’s sugarcane variety program, promising experimental varieties are assigned permanent numbers three years after selection in the seedling stage. Varieties where both the cross and selection were done in Houma were assigned a prefix of “Ho”. Varieties where a cross...

RUN LENGTH SYNCHRONIZATION TECHNIQUES

DTIC Science & Technology

An important aspect of digital communications is the problem of determining efficient methods for acquiring block synchronization . In this paper we...utilizes an N-digit sync sequence as prefix to the data blocks. The results of this study show that this technique is a practical method for acquiring block synchronization .

The ESS and replicator equation in matrix games under time constraints.

PubMed

Garay, József; Cressman, Ross; Móri, Tamás F; Varga, Tamás

2018-06-01

Recently, we introduced the class of matrix games under time constraints and characterized the concept of (monomorphic) evolutionarily stable strategy (ESS) in them. We are now interested in how the ESS is related to the existence and stability of equilibria for polymorphic populations. We point out that, although the ESS may no longer be a polymorphic equilibrium, there is a connection between them. Specifically, the polymorphic state at which the average strategy of the active individuals in the population is equal to the ESS is an equilibrium of the polymorphic model. Moreover, in the case when there are only two pure strategies, a polymorphic equilibrium is locally asymptotically stable under the replicator equation for the pure-strategy polymorphic model if and only if it corresponds to an ESS. Finally, we prove that a strict Nash equilibrium is a pure-strategy ESS that is a locally asymptotically stable equilibrium of the replicator equation in n-strategy time-constrained matrix games.

Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

PubMed

Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

2017-11-30

Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

Weight of fitness deviation governs strict physical chaos in replicator dynamics

NASA Astrophysics Data System (ADS)

Pandit, Varun; Mukhopadhyay, Archan; Chakraborty, Sagar

2018-03-01

Replicator equation—a paradigm equation in evolutionary game dynamics—mathematizes the frequency dependent selection of competing strategies vying to enhance their fitness (quantified by the average payoffs) with respect to the average fitnesses of the evolving population under consideration. In this paper, we deal with two discrete versions of the replicator equation employed to study evolution in a population where any two players' interaction is modelled by a two-strategy symmetric normal-form game. There are twelve distinct classes of such games, each typified by a particular ordinal relationship among the elements of the corresponding payoff matrix. Here, we find the sufficient conditions for the existence of asymptotic solutions of the replicator equations such that the solutions—fixed points, periodic orbits, and chaotic trajectories—are all strictly physical, meaning that the frequency of any strategy lies inside the closed interval zero to one at all times. Thus, we elaborate on which of the twelve types of games are capable of showing meaningful physical solutions and for which of the two types of replicator equation. Subsequently, we introduce the concept of the weight of fitness deviation that is the scaling factor in a positive affine transformation connecting two payoff matrices such that the corresponding one-shot games have exactly same Nash equilibria and evolutionary stable states. The weight also quantifies how much the excess of fitness of a strategy over the average fitness of the population affects the per capita change in the frequency of the strategy. Intriguingly, the weight's variation is capable of making the Nash equilibria and the evolutionary stable states, useless by introducing strict physical chaos in the replicator dynamics based on the normal-form game.

Weight of fitness deviation governs strict physical chaos in replicator dynamics.

PubMed

Pandit, Varun; Mukhopadhyay, Archan; Chakraborty, Sagar

2018-03-01

Replicator equation-a paradigm equation in evolutionary game dynamics-mathematizes the frequency dependent selection of competing strategies vying to enhance their fitness (quantified by the average payoffs) with respect to the average fitnesses of the evolving population under consideration. In this paper, we deal with two discrete versions of the replicator equation employed to study evolution in a population where any two players' interaction is modelled by a two-strategy symmetric normal-form game. There are twelve distinct classes of such games, each typified by a particular ordinal relationship among the elements of the corresponding payoff matrix. Here, we find the sufficient conditions for the existence of asymptotic solutions of the replicator equations such that the solutions-fixed points, periodic orbits, and chaotic trajectories-are all strictly physical, meaning that the frequency of any strategy lies inside the closed interval zero to one at all times. Thus, we elaborate on which of the twelve types of games are capable of showing meaningful physical solutions and for which of the two types of replicator equation. Subsequently, we introduce the concept of the weight of fitness deviation that is the scaling factor in a positive affine transformation connecting two payoff matrices such that the corresponding one-shot games have exactly same Nash equilibria and evolutionary stable states. The weight also quantifies how much the excess of fitness of a strategy over the average fitness of the population affects the per capita change in the frequency of the strategy. Intriguingly, the weight's variation is capable of making the Nash equilibria and the evolutionary stable states, useless by introducing strict physical chaos in the replicator dynamics based on the normal-form game.

Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

PubMed Central

Mühlberger, Elke; Weik, Michael; Volchkov, Viktor E.; Klenk, Hans-Dieter; Becker, Stephan

1999-01-01

The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses. PMID:9971816

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

46 CFR Sec. 2 - Voyage numbers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... voyage No. 1 having the prefixed designation NSA and followed by the General Agents' abbreviated designation and voyage number, as NSA-1/ABC-1. (b) The continuity of NSA voyage numbers shall not change with... General Agent shall affix his abbreviated designation and initial voyage numbers, as NSA-13/XYZ-1. ...

Neuroscience and Education: Blind Spots in a Strange Relationship

ERIC Educational Resources Information Center

Kraft, Volker

2012-01-01

This article--mainly referring to the situation in Germany--consists of three parts. In a first section the current presence of neurosciences in the public discourse will be described in order to illuminate the background which is relevant for contemporary educational thinking. The prefix "neuro-" is ubiquitous today and therefore…

How to Achieve Competence in English: A Quick Reference Handbook.

ERIC Educational Resources Information Center

Johnson, Eric W.

Written to provide a quick, simple, practical reference, this handbook contains explanations and examples of the use of English. Entries, arranged alphabetically, may be as specific as "bibliography,""colons,""dashes,""footnotes," and "prefixes" or as general as articles on cliches, books, figurative language, frame tests, grammar, and plagiarism.…

An Outline of English Spelling. Technical Report 55.

ERIC Educational Resources Information Center

Russell, Paula

The purpose of this booklet is to provide a definition of phonological and morphological principles governing the English spelling system. Included in the discussion are an exhaustive list of sound-to-spelling correspondences, lists of common prefixes and suffixes, and rules for combining affixes with base morphemes. Charts provided outline…

Changing to the Metric System.

ERIC Educational Resources Information Center

Chambers, Donald L.; Dowling, Kenneth W.

This report examines educational aspects of the conversion to the metric system of measurement in the United States. Statements of positions on metrication and basic mathematical skills are given from various groups. Base units, symbols, prefixes, and style of the metric system are outlined. Guidelines for teaching metric concepts are given,…

40 CFR 156.212 - Personal protective equipment statements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... respirator with MSHA/NIOSH/ approval number prefix TC-21C; or (ii) Respirator with an organic-vapor-removing... unnecessarily. (ii) Gases applied outdoors. For products that are formulated or applied as a gas (space and soil... activities outdoors, use either a respirator with an organic-vapor-removing cartridge with a prefilter...

40 CFR 156.212 - Personal protective equipment statements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... respirator with MSHA/NIOSH/ approval number prefix TC-21C; or (ii) Respirator with an organic-vapor-removing... unnecessarily. (ii) Gases applied outdoors. For products that are formulated or applied as a gas (space and soil... activities outdoors, use either a respirator with an organic-vapor-removing cartridge with a prefilter...

40 CFR 156.212 - Personal protective equipment statements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... respirator with MSHA/NIOSH/ approval number prefix TC-21C; or (ii) Respirator with an organic-vapor-removing... unnecessarily. (ii) Gases applied outdoors. For products that are formulated or applied as a gas (space and soil... activities outdoors, use either a respirator with an organic-vapor-removing cartridge with a prefilter...

40 CFR 156.212 - Personal protective equipment statements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... respirator with MSHA/NIOSH/ approval number prefix TC-21C; or (ii) Respirator with an organic-vapor-removing... unnecessarily. (ii) Gases applied outdoors. For products that are formulated or applied as a gas (space and soil... activities outdoors, use either a respirator with an organic-vapor-removing cartridge with a prefilter...

40 CFR 156.212 - Personal protective equipment statements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... respirator with MSHA/NIOSH/ approval number prefix TC-21C; or (ii) Respirator with an organic-vapor-removing... unnecessarily. (ii) Gases applied outdoors. For products that are formulated or applied as a gas (space and soil... activities outdoors, use either a respirator with an organic-vapor-removing cartridge with a prefilter...

9 CFR 79.2 - Identification of sheep and goats in interstate commerce.

Code of Federal Regulations, 2014 CFR

2014-01-01

... prefix that has been linked in the National Scrapie Database with the assigned premises identification... official identification method or device approved by the Administrator. (3) The owner of the flock of... premises identification if they are linked to the premises in the National Scrapie Database) will be...

9 CFR 79.2 - Identification of sheep and goats in interstate commerce.

Code of Federal Regulations, 2013 CFR

2013-01-01

... prefix that has been linked in the National Scrapie Database with the assigned premises identification... official identification method or device approved by the Administrator. (3) The owner of the flock of... premises identification if they are linked to the premises in the National Scrapie Database) will be...

9 CFR 79.2 - Identification of sheep and goats in interstate commerce.

Code of Federal Regulations, 2012 CFR

2012-01-01

... prefix that has been linked in the National Scrapie Database with the assigned premises identification... official identification method or device approved by the Administrator. (3) The owner of the flock of... premises identification if they are linked to the premises in the National Scrapie Database) will be...

Au-HKUST-1 Composite Nanocapsules: Synthesis with a Coordination Replication Strategy and Catalysis on CO Oxidation.

PubMed

Liu, Yongxin; Zhang, Jiali; Song, Lingxiao; Xu, Wenyuan; Guo, Zanru; Yang, Xiaomin; Wu, Xiaoxin; Chen, Xi

2016-09-07

A novel coordination replication of Cu2O redox-template strategy is reported to efficiently fabricate Au-HKUST-1 composite nanocapsule, with a HKUST-1 sandwich shell and an embedded Au nanoparticles layer. The novel synthesis procedure involves forming Au nanoparticles on the surface of Cu2O, transforming partial Cu2O into HKUST-1 shell via coordination replication, and removing the residual Cu2O by acid. The as-prepared Au-HKUST-1 composite nanocapsules displayed high catalytic activity on CO oxidation.

Verbal Self-Guidance as a Treatment Approach for Children with Developmental Coordination Disorder: A Systematic Replication Study.

ERIC Educational Resources Information Center

Martini, Rose; Polatajko, Helene J.

1998-01-01

Replicating a 1994 study, four children with developmental coordination disorder (DCD) were taught a verbal self-guidance strategy (Goal, Plan, Do, Check) by an occupational therapist. All four improved performance in attaining their occupational goals, supporting the possible use of a cognitive strategy with children with DCD. (SK)

Growing What Works: Lessons Learned Replicating Promising Practices for Latino Student Success

ERIC Educational Resources Information Center

Santiago, Deborah A.; Lopez, Estela

2013-01-01

How does the country accelerate Latino student success in higher education? The U.S. has to find programs and strategies that improve the success of Latino students, and then replicate or scale up those programs and strategies to serve more students. Those are the basic principles behind "Excelencia" in Education's Growing What Works (GWW)…

A dynamic replication management strategy in distributed GIS

NASA Astrophysics Data System (ADS)

Pan, Shaoming; Xiong, Lian; Xu, Zhengquan; Chong, Yanwen; Meng, Qingxiang

2018-03-01

Replication strategy is one of effective solutions to meet the requirement of service response time by preparing data in advance to avoid the delay of reading data from disks. This paper presents a brand-new method to create copies considering the selection of replicas set, the number of copies for each replica and the placement strategy of all copies. First, the popularities of all data are computed considering both the historical access records and the timeliness of the records. Then, replica set can be selected based on their recent popularities. Also, an enhanced Q-value scheme is proposed to assign the number of copies for each replica. Finally, a reasonable copies placement strategy is designed to meet the requirement of load balance. In addition, we present several experiments that compare the proposed method with techniques that use other replication management strategies. The results show that the proposed model has better performance than other algorithms in all respects. Moreover, the experiments based on different parameters also demonstrated the effectiveness and adaptability of the proposed algorithm.

From Discovery to Justification: Outline of an Ideal Research Program in Empirical Psychology

PubMed Central

Witte, Erich H.; Zenker, Frank

2017-01-01

The gold standard for an empirical science is the replicability of its research results. But the estimated average replicability rate of key-effects that top-tier psychology journals report falls between 36 and 39% (objective vs. subjective rate; Open Science Collaboration, 2015). So the standard mode of applying null-hypothesis significance testing (NHST) fails to adequately separate stable from random effects. Therefore, NHST does not fully convince as a statistical inference strategy. We argue that the replicability crisis is “home-made” because more sophisticated strategies can deliver results the successful replication of which is sufficiently probable. Thus, we can overcome the replicability crisis by integrating empirical results into genuine research programs. Instead of continuing to narrowly evaluate only the stability of data against random fluctuations (discovery context), such programs evaluate rival hypotheses against stable data (justification context). PMID:29163256

Putting "Meta" Terms in Context: Constructing a Developmental Picture and Exploring Philosophical Implications.

ERIC Educational Resources Information Center

Zolliker, Susan

Exploring the use of the prefix "meta" and the use of "meta" terms in the context of Lev S. Vygotsky's theories demonstrates that students need to use language to learn about language. "Writing about writing" is already part of many classrooms, but by establishing a connection between metadiscourse written informally…

Pronunciation Training Facilitates the Learning and Retention of L2 Grammatical Structures

ERIC Educational Resources Information Center

Martin, Ines A.; Jackson, Carrie N.

2016-01-01

The present study investigated the impact of pronunciation training on the learning and retention of second language (L2) grammatical structures. By drawing on the phonological saliency of stress placement in German separable- and inseparable-prefix verbs, the study explored whether enhancing explicit instruction through pronunciation training can…

What's in a Title? Gender Micro-Inequities in a University Human Resources Database

ERIC Educational Resources Information Center

Saporu, Darlene F.; Herbers, Joan M.

2015-01-01

Men and women are perceived differently, and those perceptions can be damaging in a professional context. Unconscious bias expressed within work environments can introduce "micro-inequities" that impede career progression for women compared to men. This study examines title prefixes for faculty in the human resources database of a large…

Amphibians

Treesearch

Harold E. Basey; David A. Sinclear

1980-01-01

This chapter offers the most recent information available on the habitat relations of teh 26 speicies of amphibians and 27 species of reptiles know to occur in the west slope of the Sierra Nevada. nomenclature used follows that in the most recent literature for each species. the species are arrange in phylogenetic order and numbered in sequence, with prefix "A...

Metric Measurement. A Course to Reduce Math Anxiety and Sex-Role Stereotyping in Elementary Education.

ERIC Educational Resources Information Center

City Univ. of New York, Flushing, NY. Queens Coll.

This Teacher Education and Mathematics (TEAM) content module focuses on metric measurement. Topics addressed include decimal structure and prefixes, precision in measurement, reference measures, United States customary and metric systems, volume, area, and conversion. The module consists of: (1) an instructor's text; (2) an instructor's guide and…

What About Metric? 1977 Edition.

ERIC Educational Resources Information Center

Barbrow, Louis E.

The conversion to the metric system of measurement and resulting advantages over the English system are discussed. Names of metric units are listed along with the multiplication factors indicated by their prefixes. A comparison of the major units of both systems using everyday quantities and sizes is made and a guide for estimating the most common…

Reporting of Inpatient Data

DTIC Science & Technology

1988-04-06

of flexion, extremity-- see Contracture motion joint-- see Ankylosis muscle -- see Paralysis nerve-- see Paralysis Loss of. absence bladder (urinary...Outer space -----------XX (Omit from screen) REGISTER NUMBER ( 7 FAMILY MEMBER PREFIX 2 01-69--Family members 01-19--Child of sponsor 20--SPONSOR 30-39...K Navigator--------------------------------------------- L Chief flight surgeon---------------------------------- P Senior flight surgeon

Classical Sanskrit Preverb Ordering: A Diachronic Study

ERIC Educational Resources Information Center

Papke, Julia Kay Porter

2010-01-01

The Indo-European language family contains many "small words" with various adverbial meanings and functions, including preverbs. The term "preverb" is used to label any of a variety of modifying morphemes that form a close semantic unit with a verb, including both words and prefixes (Booij and Kemenade 2003). Some Indo-European languages not only…

Zur Wortbildung in wissenschaftlichen Texten (Word Formation in Scientific Texts)

ERIC Educational Resources Information Center

Rogalla, Hanna; Rogalla, Willy

1976-01-01

Discusses a German frequency list of 1,500 to 2,000 scientific words, which is being developed, and the importance of learning word-building principles. Substantive and adjective suffixes are listed according to frequency, followed by remarks on copulative compounds, with examples and frequency ranking, and, finally, prefixes. (Text is in German.)…

Effects of Cyclic Prefix Jamming Versus Noise Jamming in OFDM Signals

DTIC Science & Technology

2011-03-01

is even found in the Bluetooth technology used in something as common as videogame con- trollers. It is now a more universally-accepted standard for...Dec 2009. [Online]. Avail- able: http://www.brighthub.com/electronics/gps/articles/60598.aspx. 8. LTE Product Design, “LTE Benefits v 3.3,” May

47 CFR 74.791 - Digital call signs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Booster Stations § 74.791 Digital call signs. (a) Digital low power stations. Call signs for digital low power stations will be made up of a prefix consisting of the initial letter K or W followed by the channel number assigned to the station and two additional letters and a suffix consisting of the letters...

47 CFR 74.791 - Digital call signs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Booster Stations § 74.791 Digital call signs. (a) Digital low power stations. Call signs for digital low power stations will be made up of a prefix consisting of the initial letter K or W followed by the channel number assigned to the station and two additional letters and a suffix consisting of the letters...

47 CFR 74.791 - Digital call signs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Booster Stations § 74.791 Digital call signs. (a) Digital low power stations. Call signs for digital low power stations will be made up of a prefix consisting of the initial letter K or W followed by the channel number assigned to the station and two additional letters and a suffix consisting of the letters...

47 CFR 74.791 - Digital call signs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Booster Stations § 74.791 Digital call signs. (a) Digital low power stations. Call signs for digital low power stations will be made up of a prefix consisting of the initial letter K or W followed by the channel number assigned to the station and two additional letters and a suffix consisting of the letters...

Career Goal-Based E-Learning Recommendation Using Enhanced Collaborative Filtering and PrefixSpan

ERIC Educational Resources Information Center

Ma, Xueying; Ye, Lu

2018-01-01

This article describes how e-learning recommender systems nowadays have applied different kinds of techniques to recommend personalized learning content for users based on their preference, goals, interests and background information. However, the cold-start problem which exists in traditional recommendation algorithms are still left over in…

23 CFR 140.603 - Programs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Bond Issue Projects § 140.603 Programs. Programs covering projects to be financed from the proceeds of bonds shall be prepared and submitted to FHWA. Project designations shall be the same as for regular Federal-aid projects except that the prefix letter “B” for bond issue shall be used as the first letter of...

27 CFR 19.752 - Marks.

Code of Federal Regulations, 2012 CFR

2012-04-01

... alphabetical prefix or suffix to the series; and (iii) When there is a change in proprietorship or a change in the individual, firm, corporate name, or trade name, the series in use at the time of the change may...: (1) Quantity in wine gallons; (2) Proof of the spirits; (3) Name, address, and permit number of the...

27 CFR 19.752 - Marks.

Code of Federal Regulations, 2011 CFR

2011-04-01

... alphabetical prefix or suffix to the series; and (iii) When there is a change in proprietorship or a change in the individual, firm, corporate name, or trade name, the series in use at the time of the change may...: (1) Quantity in wine gallons; (2) Proof of the spirits; (3) Name, address, and permit number of the...

27 CFR 19.752 - Marks.

Code of Federal Regulations, 2013 CFR

2013-04-01

... alphabetical prefix or suffix to the series; and (iii) When there is a change in proprietorship or a change in the individual, firm, corporate name, or trade name, the series in use at the time of the change may...: (1) Quantity in wine gallons; (2) Proof of the spirits; (3) Name, address, and permit number of the...

Units for quantities of dimension one

NASA Astrophysics Data System (ADS)

Dybkaer, René

2004-02-01

All quantities of dimension one are said to have the SI coherent derived unit "one" with the symbol '1'. (Single quotation marks are used here sometimes to indicate a quote, name, term or symbol; double quotation marks flag a concept when necessary.) Conventionally, the term and symbol may not be combined with the SI prefixes (except for the special terms and symbols for one and 1: radian, rad, and steradian, sr). This restriction is understandable, but leads to correct yet impractical alternatives and ISO deprecated symbols such as ppm or in some cases redundant combinations of units, such as mg/kg. "Number of entities" is dimensionally independent of the current base quantities and should take its rightful place among them. The corresponding base unit is "one". A working definition is given. Other quantities of dimension one are derived as fraction, ratio, efficiency, relative quantity, relative increment or characteristic number and may also use the unit "one", whether considered to be base or derived. The special term 'uno' and symbol 'u' in either case are proposed, allowing combination with SI prefixes.

Terminator Detection by Support Vector Machine Utilizing aStochastic Context-Free Grammar

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

Francis-Lyon, Patricia; Cristianini, Nello; Holbrook, Stephen

2006-12-30

A 2-stage detector was designed to find rho-independent transcription terminators in the Escherichia coli genome. The detector includes a Stochastic Context Free Grammar (SCFG) component and a Support Vector Machine (SVM) component. To find terminators, the SCFG searches the intergenic regions of nucleotide sequence for local matches to a terminator grammar that was designed and trained utilizing examples of known terminators. The grammar selects sequences that are the best candidates for terminators and assigns them a prefix, stem-loop, suffix structure using the Cocke-Younger-Kasaami (CYK) algorithm, modified to incorporate energy affects of base pairing. The parameters from this inferred structure aremore » passed to the SVM classifier, which distinguishes terminators from non-terminators that score high according to the terminator grammar. The SVM was trained with negative examples drawn from intergenic sequences that include both featureless and RNA gene regions (which were assigned prefix, stem-loop, suffix structure by the SCFG), so that it successfully distinguishes terminators from either of these. The classifier was found to be 96.4% successful during testing.« less

Uniform resolution of compact identifiers for biomedical data

PubMed Central

Wimalaratne, Sarala M.; Juty, Nick; Kunze, John; Janée, Greg; McMurry, Julie A.; Beard, Niall; Jimenez, Rafael; Grethe, Jeffrey S.; Hermjakob, Henning; Martone, Maryann E.; Clark, Tim

2018-01-01

Most biomedical data repositories issue locally-unique accessions numbers, but do not provide globally unique, machine-resolvable, persistent identifiers for their datasets, as required by publishers wishing to implement data citation in accordance with widely accepted principles. Local accessions may however be prefixed with a namespace identifier, providing global uniqueness. Such “compact identifiers” have been widely used in biomedical informatics to support global resource identification with local identifier assignment. We report here on our project to provide robust support for machine-resolvable, persistent compact identifiers in biomedical data citation, by harmonizing the Identifiers.org and N2T.net (Name-To-Thing) meta-resolvers and extending their capabilities. Identifiers.org services hosted at the European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL-EBI), and N2T.net services hosted at the California Digital Library (CDL), can now resolve any given identifier from over 600 source databases to its original source on the Web, using a common registry of prefix-based redirection rules. We believe these services will be of significant help to publishers and others implementing persistent, machine-resolvable citation of research data. PMID:29737976

Digital Object Identifiers for NASA's Earth Observing System Products

NASA Astrophysics Data System (ADS)

Moses, J. F.; James, N.

2012-12-01

The science community has long recognized the importance of citing data in published literature to encourage replication of experiments and verification of results. Authors that try to cite their data often find that publishers will not accept Internet addresses because they are viewed as transient references, frequently changed by the data provider after the paper is published. Digital Object Identifiers (DOIs) and the DOI® System were created to avoid this problem by providing a unique and persistent identifier scheme and an online resolution service. DOIs and the Internet service provided by the DOI System have emerged as the most acceptable scheme for publishers. NASA's Earth Science Data and Information System (ESDIS) Project, in cooperation with several Earth Observing System (EOS) instrument teams and data providers, has developed methods for assigning DOIs to EOS products. By assigning DOIs we are enabling authors and publishers to find it easier and more compelling to cite EOS data products. DOIs are unique alphanumeric strings that consist of a prefix and suffix. The prefix is assigned by a registration agency for the DOI System. The suffix must be unique, but is otherwise free to be constructed by the publisher, in this case NASA ESDIS Project. A strategy was needed for constructing DOI suffix names that corresponds to each EOS product. Since the onset of the DOI System, publishers have developed conventions to suit their own purposes. These range from random generation to complex, formally controlled vocabularies. An overarching ESDIS goal has been for the DOI names to be attractive for researchers to use in publication applications. Keeping them short and simple is paramount. When adding meaning to the string, it is also important that the name only refer to the data and not to the publisher, so that the DOI can be accepted as persistent even if the data is moved to a new publisher. Most users download EOS product files to their local facilities when they want to use the data for analysis or applications. By imbedding DOIs in the file metadata, users have access to the DOI value long after the product has left the source data center. This enables users to find documentation about the product in the future - long after it has left the contextual environment of the data provider. Existing HDF and netCDF metadata structures have been adapted to accommodate the addition of DOIs. In addition, associated EOSDIS core metadata will also contain a product specific attribute for DOIs. Advances in computer science and Internet brought about a host of data identification schemes designed to solve problems inherent in developing advanced provenance models. Lessons from trying to use early satellite observations in climate studies today point to the importance of providing links in data archives to documentation and publications about the data. Data system engineers link data records to standard product documentation prepared at the time of the mission and archive with the data, but will need to add links to the whole range of information needed to support future research and long-term climate studies. DOIs can serve this need if referenced by developers when preparing technical data and reports, as well as when publishing research results.

Environmental stress speeds up DNA replication in Pseudomonas putida in chemostat cultivations.

PubMed

Lieder, Sarah; Jahn, Michael; Koepff, Joachim; Müller, Susann; Takors, Ralf

2016-01-01

Cellular response to different types of stress is the hallmark of the cell's strategy for survival. How organisms adjust their cell cycle dynamics to compensate for changes in environmental conditions is an important unanswered question in bacterial physiology. A cell using binary fission for reproduction passes through three stages during its cell cycle: a stage from cell birth to initiation of replication, a DNA replication phase and a period of cell division. We present a detailed analysis of durations of cell cycle phases, investigating their dynamics under environmental stress conditions. Applying continuous steady state cultivations (chemostats), the DNA content of a Pseudomonas putida KT2440 population was quantified with flow cytometry at distinct growth rates. Data-driven modeling revealed that under stress conditions, such as oxygen deprivation, solvent exposure and decreased iron availability, DNA replication was accelerated correlated to the severity of the imposed stress (up to 1.9-fold). Cells maintained constant growth rates by balancing the shortened replication phase with extended cell cycle phases before and after replication. Transcriptome data underpin the transcriptional upregulation of crucial genes of the replication machinery. Hence adaption of DNA replication speed appears to be an important strategy to withstand environmental stress. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring the Replicability of a Study's Results: Bootstrap Statistics for the Multivariate Case.

ERIC Educational Resources Information Center

Thompson, Bruce

Conventional statistical significance tests do not inform the researcher regarding the likelihood that results will replicate. One strategy for evaluating result replication is to use a "bootstrap" resampling of a study's data so that the stability of results across numerous configurations of the subjects can be explored. This paper…

Charter School Replication. Policy Guide

ERIC Educational Resources Information Center

Rhim, Lauren Morando

2009-01-01

"Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…

MicroRNA regulation of human protease genes essential for influenza virus replication.

PubMed

Meliopoulos, Victoria A; Andersen, Lauren E; Brooks, Paula; Yan, Xiuzhen; Bakre, Abhijeet; Coleman, J Keegan; Tompkins, S Mark; Tripp, Ralph A

2012-01-01

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies.

Replication Origins and Timing of Temporal Replication in Budding Yeast: How to Solve the Conundrum?

PubMed Central

Barberis, Matteo; Spiesser, Thomas W.; Klipp, Edda

2010-01-01

Similarly to metazoans, the budding yeast Saccharomyces cereviasiae replicates its genome with a defined timing. In this organism, well-defined, site-specific origins, are efficient and fire in almost every round of DNA replication. However, this strategy is neither conserved in the fission yeast Saccharomyces pombe, nor in Xenopus or Drosophila embryos, nor in higher eukaryotes, in which DNA replication initiates asynchronously throughout S phase at random sites. Temporal and spatial controls can contribute to the timing of replication such as Cdk activity, origin localization, epigenetic status or gene expression. However, a debate is going on to answer the question how individual origins are selected to fire in budding yeast. Two opposing theories were proposed: the “replicon paradigm” or “temporal program” vs. the “stochastic firing”. Recent data support the temporal regulation of origin activation, clustering origins into temporal blocks of early and late replication. Contrarily, strong evidences suggest that stochastic processes acting on origins can generate the observed kinetics of replication without requiring a temporal order. In mammalian cells, a spatiotemporal model that accounts for a partially deterministic and partially stochastic order of DNA replication has been proposed. Is this strategy the solution to reconcile the conundrum of having both organized replication timing and stochastic origin firing also for budding yeast? In this review we discuss this possibility in the light of our recent study on the origin activation, suggesting that there might be a stochastic component in the temporal activation of the replication origins, especially under perturbed conditions. PMID:21037857

ROOTing Out Meaning: More Morphemic Analysis for Primary Pupils

ERIC Educational Resources Information Center

Mountain, Lee

2005-01-01

In an elementary-school professional development program, a group of primary teachers and a university consultant reviewed the research on morphemic analysis and then explored ways to give pupils in grades 1, 2, and 3 an early start on using prefixes, suffixes, and roots to construct word meaning. The teachers examined some middle-grade strategies…

Star Trek with Latin. Teacher's Guide. Tentative Edition.

ERIC Educational Resources Information Center

Masciantonio, Rudolph; And Others

The purpose of this guide is to assist Latin and English teachers with some background in Latin to expand the English vocabulary and reading skills of students through the study of Latin roots, prefixes, and suffixes. The introductory material in the guide provides general notes on the teaching of Latin in the Philadelphia School District,…

What Is So Difficult about Telicity Marking in L2 Russian?

ERIC Educational Resources Information Center

Slabakova, Roumyana

2005-01-01

Two major mechanisms of encoding telicity across languages are either marking the object as exhaustively countable or measurable, or utilizing a specific prefix on the verbal form. English predominantly uses the first mechanism, while Russian mostly utilizes the second. The learning task of an English speaker acquiring Russian, then, is two-fold:…

Recurrent Prefixes, Roots, and Suffixes: A Morphemic Approach to Disciplinary Literacy

ERIC Educational Resources Information Center

Mountain, Lee

2015-01-01

Students in a content-area reading course examined the vocabulary of each of their disciplines, focusing on recurrent roots and affixes. They wanted to become teachers of math, science, English, music, and history; therefore, they needed to learn discipline-specific morphemes so they could help their future students figure out new words in their…

Promoting Morphological Awareness in Children with Language Needs: Do the Common Core State Standards Pave the Way?

ERIC Educational Resources Information Center

Gabig, Cheryl Smith; Zaretsky, Elena

2013-01-01

Recent research has acknowledged the importance of morphological awareness, beyond phonological awareness, to literacy achievement in both reading and writing for children, adolescents, and adults. Morphological awareness is the ability to recognize, reflect on, and manipulate the sublexical structure of words--the roots, prefixes, and suffixes.…

The Contribution of Morphological Awareness to the Spelling of Morphemes and Morphologically Complex Words in French

ERIC Educational Resources Information Center

Fejzo, Anila

2016-01-01

The goal of this study was to explore the relationship between morphological awareness and the spelling of morphemes and morphologically complex words among 75 third- and fourth-grade Francophone students of low socio-economic status. To reach this objective, we administered a dictation comprised of morphologically complex words with prefixes,…

75 FR 72686 - Express Mail Open and Distribute and Priority Mail Open and Distribute

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... POSTAL SERVICE 39 CFR Part 111 Express Mail Open and Distribute and Priority Mail Open and... ``DB'' prefix along with new Tag 257, Tag 267, or Label 257S, on all Express Mail[supreg] Open and Distribute containers. The Postal Service is also revising the service commitment for Express Mail Open and...

Building English Vocabulary through Roots, Prefixes and Suffixes

ERIC Educational Resources Information Center

Yurtbasi, Metin

2015-01-01

Semantics, the study of the meaning of words, is the sum of the basic elements of four skills, namely, reading, writing, speaking and listening effectively. The knowledge of vocabulary words in lexico-semantics, on the other hand, is essential in every grade level, subject area and assessment for every student. In order to improve students'…

Metrics. A Basic Core Curriculum for Teaching Metrics to Vocational Students.

ERIC Educational Resources Information Center

Albracht, James; Simmons, A. D.

This core curriculum contains five units for use in teaching metrics to vocational students. Included in the first unit are a series of learning activities to familiarize students with the terminology of metrics, including the prefixes and their values. Measures of distance and speed are covered. Discussed next are measures of volume used with…

27 CFR 19.752 - Marks.

Code of Federal Regulations, 2014 CFR

2014-04-01

... numbering system of any series reaches “1,000,000” the proprietor may begin the series again by adding an alphabetical prefix or suffix to the series; and (iii) When there is a change in proprietorship or a change in the individual, firm, corporate name, or trade name, the series in use at the time of the change may...

Viral precursor protein P3 and its processed products perform discrete and essential functions in the poliovirus RNA replication complex

USDA-ARS?s Scientific Manuscript database

The differential use of protein precursors and their products is a key strategy used during poliovirus replication. To characterize the role of protein precursors during replication, we examined the complementation profiles of mutants that inhibited 3D polymerase or 3C-RNA binding activity. We showe...

Addressing the "Replication Crisis": Using Original Studies to Design Replication Studies with Appropriate Statistical Power.

PubMed

Anderson, Samantha F; Maxwell, Scott E

2017-01-01

Psychology is undergoing a replication crisis. The discussion surrounding this crisis has centered on mistrust of previous findings. Researchers planning replication studies often use the original study sample effect size as the basis for sample size planning. However, this strategy ignores uncertainty and publication bias in estimated effect sizes, resulting in overly optimistic calculations. A psychologist who intends to obtain power of .80 in the replication study, and performs calculations accordingly, may have an actual power lower than .80. We performed simulations to reveal the magnitude of the difference between actual and intended power based on common sample size planning strategies and assessed the performance of methods that aim to correct for effect size uncertainty and/or bias. Our results imply that even if original studies reflect actual phenomena and were conducted in the absence of questionable research practices, popular approaches to designing replication studies may result in a low success rate, especially if the original study is underpowered. Methods correcting for bias and/or uncertainty generally had higher actual power, but were not a panacea for an underpowered original study. Thus, it becomes imperative that 1) original studies are adequately powered and 2) replication studies are designed with methods that are more likely to yield the intended level of power.

Molecular Studies of HTLV-1 Replication: An Update

PubMed Central

Martin, Jessica L.; Maldonado, José O.; Mueller, Joachim D.; Zhang, Wei; Mansky, Louis M.

2016-01-01

Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus. Virus replication initiates host antiviral immunity and the checkpoint control of cell proliferation, but HTLV-1 has evolved elegant strategies to counteract these host defense mechanisms to allow for virus persistence. The study of the molecular biology of HTLV-1 replication has provided crucial information for understanding HTLV-1 replication as well as aspects of viral replication that are shared between HTLV-1 and human immunodeficiency virus type 1 (HIV-1). Here in this review, we discuss the various stages of the virus replication cycle—both foundational knowledge as well as current updates of ongoing research that is important for understanding HTLV-1 molecular pathogenesis as well as in developing novel therapeutic strategies. PMID:26828513

Get on Board the Cost Effective Way: A Tech Prep Replication Process.

ERIC Educational Resources Information Center

Moore, Wayne A.; Szul, Linda F.; Rivosecchi, Karen

1997-01-01

The Northwestern Pennsylvania Tech Prep Consortium model for replicating tech prep programs includes these steps: fact finding, local industry analysis, curriculum development, detailed description, marketing strategies, implementation, and program evaluation. (SK)

Asexual and sexual replication in sporulating organisms

NASA Astrophysics Data System (ADS)

Lee, Bohyun; Tannenbaum, Emmanuel

2007-08-01

Replication via sporulation is the replication strategy for all multicellular life, and may even be observed in unicellular life (such as with budding yeast). We consider diploid populations replicating via one of two possible sporulation mechanisms. (1) Asexual sporulation, whereby adult organisms produce single-celled diploid spores that grow into adults themselves. (2) Sexual sporulation, whereby adult organisms produce single-celled diploid spores that divide into haploid gametes. The haploid gametes enter a haploid “pool,” where they may recombine with other haploids to form a diploid spore that then grows into an adult. We consider a haploid fusion rate given by second-order reaction kinetics. We work with a simplified model where the diploid genome consists of only two chromosomes, each of which may be rendered defective with a single point mutation of the wild-type. We find that the asexual strategy is favored when the rate of spore production is high compared to the characteristic growth rate from a spore to a reproducing adult. Conversely, the sexual strategy is favored when the rate of spore production is low compared to the characteristic growth rate from a spore to a reproducing adult. As the characteristic growth time increases, or as the population density increases, the critical ratio of spore production rate to organism growth rate at which the asexual strategy overtakes the sexual one is pushed to higher values. Therefore, the results of this model suggest that, for complex multicellular organisms, sexual replication is favored at high population densities and low growth and sporulation rates.

Replication Research in L2 Listening Comprehension: A Conceptual Replication of Graham & Macaro (2008) and an Approximate Replication of Vandergrift & Tafaghodtari (2010) and Brett (1997)

ERIC Educational Resources Information Center

Vandergrift, Larry; Cross, Jeremy

2017-01-01

Most recent publications related to listening comprehension research deal with listening strategy instruction, metacognitive instruction or multimedia applications. This paper discusses one study from each of these three domains--Graham & Macaro (2008), Vandergrift & Tafaghodtari (2010) and Brett (1997)--and presents the need and…

MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication

PubMed Central

Meliopoulos, Victoria A.; Andersen, Lauren E.; Brooks, Paula; Yan, Xiuzhen; Bakre, Abhijeet; Coleman, J. Keegan; Tompkins, S. Mark; Tripp, Ralph A.

2012-01-01

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies. PMID:22606348

Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence1

PubMed Central

Davis, Michael J.; Eastman, Alison J.; Qiu, Yafeng; Gregorka, Brian; Kozel, Thomas R.; Osterholzer, John J.; Curtis, Jeffrey L.; Swanson, Joel A.; Olszewski, Michal A.

2015-01-01

Upon ingestion by macrophages, Cryptococcus neoformans (Cn) can survive and replicate intracellularly unless the macrophages become classically activated. The mechanism enabling intracellular replication is not fully understood; neither are the mechanisms which allow classical activation to counteract replication. Cn-induced lysosome damage was observed in infected murine bone marrow-derived macrophages, increased with time and required yeast viability. To demonstrate lysosome damage in the infected host, we developed a novel flow-cytometric method for measuring lysosome damage. Increased lysosome damage was found in Cn-containing lung cells compared to Cn–free cells. Among Cn-containing myeloid cells, recently recruited cells displayed lower damage than resident cells, consistent with the protective role of recruited macrophages. The magnitude of lysosome damage correlated with increased Cn replication. Experimental induction of lysosome damage increased Cn replication. Activation of macrophages with IFN-γ abolished macrophage lysosome damage and enabled increased killing of Cn. We conclude that induction of lysosome damage is an important Cn survival strategy and that classical activation of host macrophages counters replication by preventing damage. Thus, therapeutic strategies which decrease lysosomal damage, or increase resistance to such damage, could be valuable in treating cryptococcal infections. PMID:25637026

Replication Strategy for Spatiotemporal Data Based on Distributed Caching System

PubMed Central

Xiong, Lian; Tao, Yang; Xu, Juan; Zhao, Lun

2018-01-01

The replica strategy in distributed cache can effectively reduce user access delay and improve system performance. However, developing a replica strategy suitable for varied application scenarios is still quite challenging, owing to differences in user access behavior and preferences. In this paper, a replication strategy for spatiotemporal data (RSSD) based on a distributed caching system is proposed. By taking advantage of the spatiotemporal locality and correlation of user access, RSSD mines high popularity and associated files from historical user access information, and then generates replicas and selects appropriate cache node for placement. Experimental results show that the RSSD algorithm is simple and efficient, and succeeds in significantly reducing user access delay. PMID:29342897

Differentiated strategies for improving streaming service quality

NASA Astrophysics Data System (ADS)

An, Hui; Chen, Xin-Meng

2005-02-01

With the explosive growth of streaming services, users are becoming more and more sensitive to its quality of service. To handle these problems, the research community focuses of the application of caching and replication techniques. But most approaches try to find specific strategies of caching of replication that suit for streaming service characteristics and to design some kind of universal policy to deal with all streaming objects. This paper explores the combination of caching and replication for improving streaming service quality and demonstrates that it makes sense to incorporate two technologies. It provides a system model and discusses some related issues of how to determining a refreshable streaming object and which refreshment policies a refreshable object should use.

Porcine Endogenous Retrovirus (PERV) – Molecular Structure and Replication Strategy in the Context of Retroviral Infection Risk of Human Cells

PubMed Central

Łopata, Krzysztof; Wojdas, Emilia; Nowak, Roman; Łopata, Paweł; Mazurek, Urszula

2018-01-01

The xenotransplantation of porcine tissues may help overcome the shortage of human organs for transplantation. However, there are some concerns about recipient safety because the risk of porcine endogenous retrovirus (PERV) transmission to human cells remains unknown. Although, to date, no PERV infections have been noted in vivo, the possibility of such infections has been confirmed in vitro. Better understanding of the structure and replication cycle of PERVs is a prerequisite for determining the risk of infection and planning PERV-detection strategies. This review presents the current state of knowledge about the structure and replication cycle of PERVs in the context of retroviral infection risk. PMID:29755422

National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module II. Human Systems and Patient Assessment.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

This instructor's lesson plan guide on human systems and patient assessment is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Four units are presented: (1) medical terminology, which covers some common prefixes and suffixes and the use of the medical dictionary; (2) an overview of the…

NASA education briefs for the classroom. Metrics in space

NASA Technical Reports Server (NTRS)

1982-01-01

The use of metric measurement in space is summarized for classroom use. Advantages of the metric system over the English measurement system are described. Some common metric units are defined, as are special units for astronomical study. International system unit prefixes and a conversion table of metric/English units are presented. Questions and activities for the classroom are recommended.

The Effects of Morphemic Vocabulary Instruction on Prefix Vocabulary and Sentence Comprehension for Middle School Students with Learning Disabilities

ERIC Educational Resources Information Center

Brown, Shannon Harris; Lignugaris-Kraft, Benjamin; Forbush, David E.

2016-01-01

A limited vocabulary is a substantial obstacle to success in reading comprehension (Graves, 2004). A morphemic approach to vocabulary instruction may be an effective method for increasing student outcomes in both word knowledge and reading comprehension (Kuo & Anderson, 2006; Reed, 2008). The purpose of this research was to examine the effects…

Self-Instructional Manual for Tumor Registrars: Book 3, Tumor Registrar Vocabulary - The Composition of Medical Terms.

ERIC Educational Resources Information Center

Shambaugh, Evelyn M., Ed.

Book 3 of the self-instructional manual for tumor registrars deals with tumor registrar vocabulary. It is designed to teach tumor registrars to recognize diagnostic terms versus treatment terms, terms that refer to anatomical sites, terms that refer to patient symptoms. The first three parts of the book are concerned with word roots, prefixes and…

The ROSS Language Manual.

DTIC Science & Technology

1982-09-01

when receiving (Mary requests meeting) (tell Mary meet for lunch at Superfood ) (tell Eunice bring stock reports) (tell Secretary cancel other lunch...someone requests meeting) (if (equal ’stockbroker (ask !someone recall your occupation)) then (tell ?someone meet for lunch at Superfood ) (tell...meet for lunch at Superfood ). Several other prefixes commonly used when writing ROSS code, either to control evaluation or to dictate variables in

NASA education briefs for the classroom. Metrics in space

NASA Astrophysics Data System (ADS)

The use of metric measurement in space is summarized for classroom use. Advantages of the metric system over the English measurement system are described. Some common metric units are defined, as are special units for astronomical study. International system unit prefixes and a conversion table of metric/English units are presented. Questions and activities for the classroom are recommended.

Conditionally replicative adenovirus for gastrointestinal cancers.

PubMed

Yamamoto, Masato

2004-08-01

The clinical outcome of advanced gastrointestinal (GI) cancers (especially pancreatic and oesophageal cancers) is dismal, despite the advance of conventional therapeutic strategies. Cancer gene therapy is a category of new therapeutics, among which conditionally replicative adenovirus (CRAd) is one promising strategy to overcome existing obstacles of cancer gene therapy. Various CRAds have been developed for GI cancer treatment by taking advantage of the replication biology of adenovirus. Some CRAds have already been tested in clinical trials, but have fallen short of initial expectations. Concerns for clinical applicability include therapeutic potency, replication selectivity and interval end points in clinical trials. In addition, improvement of experimental animal models is needed for a deeper understanding of CRAd biology. Despite these obstacles, CRAds continue to be an exciting area of investigation with great potential for clinical utility. Further virological and oncological research will eventually lead to full realisation of the therapeutic potential of CRAds in the field of GI cancers.

Identification of rep-associated factors in herpes simplex virus type 1-induced adeno-associated virus type 2 replication compartments.

PubMed

Nicolas, Armel; Alazard-Dany, Nathalie; Biollay, Coline; Arata, Loredana; Jolinon, Nelly; Kuhn, Lauriane; Ferro, Myriam; Weller, Sandra K; Epstein, Alberto L; Salvetti, Anna; Greco, Anna

2010-09-01

Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase delta was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus.

Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy

PubMed Central

Jang, Sang-Min; Redon, Christophe E.; Aladjem, Mirit I.

2018-01-01

Cullin-RING (Really Interesting New Gene) E3 ubiquitin ligases (CRLs), the largest family of E3 ubiquitin ligases, are functional multi-subunit complexes including substrate receptors, adaptors, cullin scaffolds, and RING-box proteins. CRLs are responsible for ubiquitination of ~20% of cellular proteins and are involved in diverse biological processes including cell cycle progression, genome stability, and oncogenesis. Not surprisingly, cullins are deregulated in many diseases and instances of cancer. Recent studies have highlighted the importance of CRL-mediated ubiquitination in the regulation of DNA replication/repair, including specific roles in chromatin assembly and disassembly of the replication machinery. The development of novel therapeutics targeting the CRLs that regulate the replication machinery and chromatin in cancer is now an attractive therapeutic strategy. In this review, we summarize the structure and assembly of CRLs and outline their cellular functions and their diverse roles in cancer, emphasizing the regulatory functions of nuclear CRLs in modulating the DNA replication machinery. Finally, we discuss the current strategies for targeting CRLs against cancer in the clinic. PMID:29594129

Reproducibility of R-fMRI metrics on the impact of different strategies for multiple comparison correction and sample sizes.

PubMed

Chen, Xiao; Lu, Bin; Yan, Chao-Gan

2018-01-01

Concerns regarding reproducibility of resting-state functional magnetic resonance imaging (R-fMRI) findings have been raised. Little is known about how to operationally define R-fMRI reproducibility and to what extent it is affected by multiple comparison correction strategies and sample size. We comprehensively assessed two aspects of reproducibility, test-retest reliability and replicability, on widely used R-fMRI metrics in both between-subject contrasts of sex differences and within-subject comparisons of eyes-open and eyes-closed (EOEC) conditions. We noted permutation test with Threshold-Free Cluster Enhancement (TFCE), a strict multiple comparison correction strategy, reached the best balance between family-wise error rate (under 5%) and test-retest reliability/replicability (e.g., 0.68 for test-retest reliability and 0.25 for replicability of amplitude of low-frequency fluctuations (ALFF) for between-subject sex differences, 0.49 for replicability of ALFF for within-subject EOEC differences). Although R-fMRI indices attained moderate reliabilities, they replicated poorly in distinct datasets (replicability < 0.3 for between-subject sex differences, < 0.5 for within-subject EOEC differences). By randomly drawing different sample sizes from a single site, we found reliability, sensitivity and positive predictive value (PPV) rose as sample size increased. Small sample sizes (e.g., < 80 [40 per group]) not only minimized power (sensitivity < 2%), but also decreased the likelihood that significant results reflect "true" effects (PPV < 0.26) in sex differences. Our findings have implications for how to select multiple comparison correction strategies and highlight the importance of sufficiently large sample sizes in R-fMRI studies to enhance reproducibility. Hum Brain Mapp 39:300-318, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Linguistic Models, Acquisition Theories, and Learner Corpora: Morphological Productivity in SLA Research Exemplified by Complex Verbs in German

ERIC Educational Resources Information Center

Lüdeling, Anke; Hirschmann, Hagen; Shadrova, Anna

2017-01-01

The present study analyzes morphological productivity for complex verbs in second language acquisition by analyzing a corpus of German as a Foreign Language (GFL). It shows that advanced learners of GFL use prefix and particle verbs relatively frequently and productively but less so than native speakers do and discusses these findings in the light…

Ermittlung von Wortstaemmen in russischen wissenschaftlichen Fachsprachen mit Hilfe des Computers (Establishing Word Stems in Scientific Russian With the Aid of a Computer)

ERIC Educational Resources Information Center

Halbauer, Siegfried

1976-01-01

It was considered that students of intensive scientific Russian courses could learn vocabulary more efficiently if they were taught word stems and how to combine them with prefixes and suffixes to form scientific words. The computer programs developed to identify the most important stems is discussed. (Text is in German.) (FB)

Language-Specific and Language-General Factors in Text Reading in Arabic: Evidence from the Missing Letter Effect

ERIC Educational Resources Information Center

Saady, Amany; Ibrahim, Raphiq; Eviatar, Zohar

2015-01-01

The goal of the present study was to extend the models explaining the missing-letter effect (MLE) to an additional language and orthography, and to test the role of phonology in silent reading in Arabic. We also examined orthographic effects such as letter position and letter shape, morphological effects such as pseudo-prefixes, and phonological…

An Introduction to the Black Sea Ecology

DTIC Science & Technology

2001-01-01

the marine environment ( abiotic factors). For indicating the attitude of organisms toward environmental factors, the prefixes eury- (meaning wide...are important for explanations of various biological features of the marine organisms as well as of the ecological processes that occurr in this... features which are determined by the specific conditions of this marine basin. So far, not so many attempts of integrated exposition of ecological

Introduction to Medical Terminology for Claretian Medical Center Worker Education Program of Northeastern Illinois University's Chicago Teachers' Center in Partnership with the Union of Needletrades, Industrial, Textile Employers (UNITE).

ERIC Educational Resources Information Center

Essex Community Coll., MD.

This manual consists of glossaries and descriptions of medical terminology for use in a workplace literacy program for hospital workers. The sections are as follows: hospital patient care areas; hospital departments; medical specialists; word elements (root, prefix, suffix, combining vowel, compound word); surgical procedures; diseases and…

Bridging from Replication to Translation with a Thermal, Autonomous Replicator Made from Transfer RNA

NASA Astrophysics Data System (ADS)

Braun, Dieter; Möller, Friederike M.; Krammer, Hubert

2013-03-01

Central to the understanding of living systems is the interplay between DNA/RNA and proteins. Known as Eigen paradox, proteins require genetic information while proteins are needed for the replication of genes. RNA world scenarios focus on a base by base replication disconnected from translation. Here we used strategies from DNA machines to demonstrate a tight connection between a basic replication mechanism and translation. A pool of hairpin molecules replicate a two-letter code. The replication is thermally driven: the energy and negative entropy to drive replication is initially stored in metastable hairpins by kinetic cooling. Both are released by a highly specific and exponential replication reaction that is solely implemented by base hybridization. The duplication time is 30s. The reaction is monitored by fluorescence and described by a detailed kinetic model. The RNA hairpins usetransfer RNA sequences and the replication is driven by the simple disequilibrium setting of a thermal gradient The experiments propose a physical rather than a chemical scenario for the autonomous replication of protein encoding information. Supported by the NanoSystems Initiative Munich and ERC.

Insight into HIV-2 latency may disclose strategies for a cure for HIV-1 infection.

PubMed

Saleh, Suha; Vranckx, Lenard; Gijsbers, Rik; Christ, Frauke; Debyser, Zeger

2017-01-01

HIV-1 and HIV-2 originate from two distinct zoonotic transmissions of simian immunodeficiency viruses from primate to human. Although both share similar modes of transmission and can result in the development of AIDS with similar clinical manifestations, HIV-2 infection is generally milder and less likely to progress to AIDS. HIV is currently incurable due to the presence of HIV provirus integrated into the host DNA of long-lived memory cells of the immune system without active replication. As such, the latent virus is immunologically inert and remains insensitive to the administered antiviral drugs targeting active viral replication steps. Recent evidence suggests that persistent HIV replication may occur in anatomical sanctuaries such as the lymphoid tissue due to low drug penetration. At present, different strategies are being evaluated either to completely eradicate the virus from the patient (sterilising cure) or to allow treatment interruption without viral rebound (functional cure). Because HIV-2 is naturally less pathogenic and displays a more latent phenotype than HIV-1, it may represent a valuable model that provides elementary information to cure HIV-1 infection. Insight into the viral and cellular determinants of HIV-2 replication may therefore pave the way for alternative strategies to eradicate HIV-1 or promote viral remission.

55 Nitinol Alloys

DTIC Science & Technology

1967-01-01

Urn 1~I.tion of-heat (courtesy of Goodyear C.2 Aerospace Corporation) Name derived from N i-Ti.NOL. Prefix numerical value (e.g., 55. Nitinol ... Nitinol plastically deformed below its critical, temperature (A5) will recover its original’ shape-when heated above its critical temperature, THIS...of Nitinol and other high damping materials is given in Reference 11. f WORKING CHARACTERISTICS: May be hot worked directly from the arc-melted ingot

Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

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

Nelson, O.D.

1998-07-25

This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used.

AGILE: Autonomous Global Integrated Language Exploitation

DTIC Science & Technology

2008-04-01

training is extending the pronunciation dictionary to cover any additional words. For many languages this is relatively straightforward via grapheme-to...into one or more word sequences and look up the constituent parts in the Master dictionary or apply Buckwalter to them. The Buckwalter prefix table was...errors involve the article ’Al’. As a result of this analysis, the pronunciation dictionary was extended to add alternate pronunciations for the

Fuel Price Effects on Readiness

DTIC Science & Technology

2014-05-01

While fuel purchases represent only about 2.5 percent of the Department’s budget, there is large variation among the Services. In Fiscal Year (FY...Training pillar were used as the primary quantitative measures of readiness in this paper. Level of training can be measured using operating tempo (OPTEMPO...CA: Naval Post Graduate School, 1989), http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier =ADA219807; Lawrence Goldberg

Inner ear tissue preservation by rapid freezing: Improving fixation by high-pressure freezing and hybrid methods

PubMed Central

Bullen, A.; Taylor, R.R.; Kachar, B.; Moores, C.; Fleck, R.A.; Forge, A.

2014-01-01

In the preservation of tissues in as ‘close to life’ state as possible, rapid freeze fixation has many benefits over conventional chemical fixation. One technique by which rapid freeze-fixation can be achieved, high pressure freezing (HPF), has been shown to enable ice crystal artefact-free freezing and tissue preservation to greater depths (more than 40 μm) than other quick-freezing methods. Despite increasingly becoming routine in electron microscopy, the use of HPF for the fixation of inner ear tissue has been limited. Assessment of the quality of preservation showed routine HPF techniques were suitable for preparation of inner ear tissues in a variety of species. Good preservation throughout the depth of sensory epithelia was achievable. Comparison to chemically fixed tissue indicated that fresh frozen preparations exhibited overall superior structural preservation of cells. However, HPF fixation caused characteristic artefacts in stereocilia that suggested poor quality freezing of the actin bundles. The hybrid technique of pre-fixation and high pressure freezing was shown to produce cellular preservation throughout the tissue, similar to that seen in HPF alone. Pre-fixation HPF produced consistent high quality preservation of stereociliary actin bundles. Optimising the preparation of samples with minimal artefact formation allows analysis of the links between ultrastructure and function in inner ear tissues. PMID:25016142

A Mnemonic for the Inositols

NASA Astrophysics Data System (ADS)

Painter, Terence J.

1996-10-01

The mnemonic derives from the mythical tale of Scylla and Charybdis in Homer's Odyssey (chapter 12). It takes the form of an imaginary headline in a newspaper: SCYLLA MEETS CHARYBDIS - EPIC NEWS MUCH ALARMS SICILY. The first two or three letters in each of these eight words remind the user that the nine configurational prefixes are scyllo-, meso-, (or myo-), chiro- [(+) and (-)], epi-, neo-, muco-, allo-, and cis-, respectively. The mnemonic also arranges the prefixes in an order that allows the configurations to be derived in a logical manner by performing a defined sequence of imaginary configurational inversions (epimerizations) around a cyclohexane ring. The all-equatorial, chair conformation of scyllo-inositol is selected as the starting point, and the sequence of inversions is defined by a systematic permutation of possibilities for performing one, two or three inversions in succession (1; 1 and 2; 1 and 3; 1 and 4; 1, 2 and 3; 1, 2 and 4; and finally 1, 3 and 5). In the case of the two chiro-inositols, the enantiomeric form is determined simply by the direction (clockwise or counterclockwise) around the ring in which the imaginary inversions are performed. This also applies formally to allo-inositol, but in that case the two optical enantiomers are isoenergetic chair conformers in rapid equilibrium.

Low template STR typing: effect of replicate number and consensus method on genotyping reliability and DNA database search results.

PubMed

Benschop, Corina C G; van der Beek, Cornelis P; Meiland, Hugo C; van Gorp, Ankie G M; Westen, Antoinette A; Sijen, Titia

2011-08-01

To analyze DNA samples with very low DNA concentrations, various methods have been developed that sensitize short tandem repeat (STR) typing. Sensitized DNA typing is accompanied by stochastic amplification effects, such as allele drop-outs and drop-ins. Therefore low template (LT) DNA profiles are interpreted with care. One can either try to infer the genotype by a consensus method that uses alleles confirmed in replicate analyses, or one can use a statistical model to evaluate the strength of the evidence in a direct comparison with a known DNA profile. In this study we focused on the first strategy and we show that the procedure by which the consensus profile is assembled will affect genotyping reliability. In order to gain insight in the roles of replicate number and requested level of reproducibility, we generated six independent amplifications of samples of known donors. The LT methods included both increased cycling and enhanced capillary electrophoresis (CE) injection [1]. Consensus profiles were assembled from two to six of the replications using four methods: composite (include all alleles), n-1 (include alleles detected in all but one replicate), n/2 (include alleles detected in at least half of the replicates) and 2× (include alleles detected twice). We compared the consensus DNA profiles with the DNA profile of the known donor, studied the stochastic amplification effects and examined the effect of the consensus procedure on DNA database search results. From all these analyses we conclude that the accuracy of LT DNA typing and the efficiency of database searching improve when the number of replicates is increased and the consensus method is n/2. The most functional number of replicates within this n/2 method is four (although a replicate number of three suffices for samples showing >25% of the alleles in standard STR typing). This approach was also the optimal strategy for the analysis of 2-person mixtures, although modified search strategies may be needed to retrieve the minor component in database searches. From the database searches follows the recommendation to specifically mark LT DNA profiles when entering them into the DNA database. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The replicator equation and other game dynamics

PubMed Central

Cressman, Ross; Tao, Yi

2014-01-01

The replicator equation is the first and most important game dynamics studied in connection with evolutionary game theory. It was originally developed for symmetric games with finitely many strategies. Properties of these dynamics are briefly summarized for this case, including the convergence to and stability of the Nash equilibria and evolutionarily stable strategies. The theory is then extended to other game dynamics for symmetric games (e.g., the best response dynamics and adaptive dynamics) and illustrated by examples taken from the literature. It is also extended to multiplayer, population, and asymmetric games. PMID:25024202

Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

2017-07-15

Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

School Readiness and Later Achievement: A French Canadian Replication and Extension

ERIC Educational Resources Information Center

Pagani, Linda S.; Fitzpatrick, Caroline; Archambault, Isabelle; Janosz, Michel

2010-01-01

We first replicated the data analytic strategy used in Duncan et al. (2007) with a population-based data set of French-speaking children from Quebec (Canada). Prospective associations were examined between cognitive, attention, and socioemotional characteristics underlying kindergarten school readiness and second grade math, reading, and general…

77 FR 53941 - Emerging Global Advisors, LLC, et al.;

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-04

... sampling strategy to track its Underlying Index. A Fund using a replication strategy will invest in the.... A Fund using a representative sampling strategy will hold some, but not necessarily all, of the... strategy, a Fund is not expected to track the performance of its Underlying Index with the same degree of...

Regulating DNA Replication in Plants

PubMed Central

Sanchez, Maria de la Paz; Costas, Celina; Sequeira-Mendes, Joana; Gutierrez, Crisanto

2012-01-01

Chromosomal DNA replication in plants has requirements and constraints similar to those in other eukaryotes. However, some aspects are plant-specific. Studies of DNA replication control in plants, which have unique developmental strategies, can offer unparalleled opportunities of comparing regulatory processes with yeast and, particularly, metazoa to identify common trends and basic rules. In addition to the comparative molecular and biochemical studies, genomic studies in plants that started with Arabidopsis thaliana in the year 2000 have now expanded to several dozens of species. This, together with the applicability of genomic approaches and the availability of a large collection of mutants, underscores the enormous potential to study DNA replication control in a whole developing organism. Recent advances in this field with particular focus on the DNA replication proteins, the nature of replication origins and their epigenetic landscape, and the control of endoreplication will be reviewed. PMID:23209151

Novel Chromosome Organization Pattern in Actinomycetales—Overlapping Replication Cycles Combined with Diploidy

PubMed Central

Böhm, Kati; Meyer, Fabian; Rhomberg, Agata; Kalinowski, Jörn; Donovan, Catriona

2017-01-01

ABSTRACT Bacteria regulate chromosome replication and segregation tightly with cell division to ensure faithful segregation of DNA to daughter generations. The underlying mechanisms have been addressed in several model species. It became apparent that bacteria have evolved quite different strategies to regulate DNA segregation and chromosomal organization. We have investigated here how the actinobacterium Corynebacterium glutamicum organizes chromosome segregation and DNA replication. Unexpectedly, we found that C. glutamicum cells are at least diploid under all of the conditions tested and that these organisms have overlapping C periods during replication, with both origins initiating replication simultaneously. On the basis of experimental data, we propose growth rate-dependent cell cycle models for C. glutamicum. PMID:28588128

Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase.

PubMed

Watashi, Koichi; Ishii, Naoto; Hijikata, Makoto; Inoue, Daisuke; Murata, Takayuki; Miyanari, Yusuke; Shimotohno, Kunitada

2005-07-01

Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus (HCV) genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.

Treating hepatitis C: can you teach old dogs new tricks?

PubMed

Rice, Charles M; You, Shihyun

2005-12-01

Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.

Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.

PubMed

de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

2015-05-01

HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.

MSR 2.0: Language Definition and Programming Environment

DTIC Science & Technology

2011-11-01

this version, was also used in foundational studies for crypto - protocols [14, 19]. An implementation of MSR 2.0 which adheres to the definition...describing non-standard ways to parse oc- currences of this symbol. A unary constant f can be declared either prefixed or postfixed by means of the...Information Technology — MFCSIT’00, pages 1–43, Cork, Ireland, 2000. Elsevier ENTCS 40. [6] Iliano Cervesato. A Specification Language for Crypto

Inhibition of herpesvirus and influenza virus replication by blocking polymerase subunit interactions.

PubMed

Palù, Giorgio; Loregian, Arianna

2013-09-01

Protein-protein interactions (PPIs) play a key role in many biological processes, including virus replication in the host cell. Since most of the PPIs are functionally essential, a possible strategy to inhibit virus replication is based on the disruption of viral protein complexes by peptides or small molecules that interfere with subunit interactions. In particular, an attractive target for antiviral drugs is the binding between the subunits of essential viral enzymes. This review describes the development of new antiviral compounds that inhibit herpesvirus and influenza virus replication by blocking interactions between subunit proteins of their polymerase complexes. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

PubMed

Kumar, S; Peng, X; Daley, J; Yang, L; Shen, J; Nguyen, N; Bae, G; Niu, H; Peng, Y; Hsieh, H-J; Wang, L; Rao, C; Stephan, C C; Sung, P; Ira, G; Peng, G

2017-04-17

Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in replication and HR repair. Here we demonstrate that DNA2 is overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90-95% of cases. In addition, depletion of DNA2 significantly reduces pancreatic cancer cell survival and xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition. Finally, we develop a robust high-throughput biochemistry assay to screen for inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion, including decreased DNA double strand break end resection and attenuation of HR repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2 selectively attenuates the growth of various cancer cells with oncogene-induced replication stress. Taken together, our findings open a new avenue to develop a new class of anticancer drugs by targeting druggable nuclease DNA2. We propose DNA2 inhibition as new strategy in cancer therapy by targeting replication stress, a molecular property of cancer cells that is acquired as a result of oncogene activation instead of targeting currently undruggable oncoprotein itself such as KRAS.

Teacher Perceptions of School Consultant Social Influence Strategies: Replication and Expansion

ERIC Educational Resources Information Center

Owens, Julie Sarno; Schwartz, Madeline E.; Erchul, William P.; Himawan, Lina; Evans, Steven W.; Coles, Erika K.; Schulte, Ann C.

2017-01-01

The goals were to (a) replicate the findings of Erchul, Raven, and Whichard (2001) with regard to the Consultee/Teacher Version of the Interpersonal Power Inventory (IPI; Raven, Schwarzwald, & Koslowsky, 1998), and (b) advance the literature by examining IPI scores about a current consultation relationship. Sample 1 included 99 elementary…

Spatial pattern dynamics due to the fitness gradient flux in evolutionary games.

PubMed

deForest, Russ; Belmonte, Andrew

2013-06-01

We introduce a nondiffusive spatial coupling term into the replicator equation of evolutionary game theory. The spatial flux is based on motion due to local gradients in the relative fitness of each strategy, providing a game-dependent alternative to diffusive coupling. We study numerically the development of patterns in one dimension (1D) for two-strategy games including the coordination game and the prisoner's dilemma, and in two dimensions (2D) for the rock-paper-scissors game. In 1D we observe modified traveling wave solutions in the presence of diffusion, and asymptotic attracting states under a frozen-strategy assumption without diffusion. In 2D we observe spiral formation and breakup in the frozen-strategy rock-paper-scissors game without diffusion. A change of variables appropriate to replicator dynamics is shown to correctly capture the 1D asymptotic steady state via a nonlinear diffusion equation.

Spatial pattern dynamics due to the fitness gradient flux in evolutionary games

NASA Astrophysics Data System (ADS)

deForest, Russ; Belmonte, Andrew

2013-06-01

We introduce a nondiffusive spatial coupling term into the replicator equation of evolutionary game theory. The spatial flux is based on motion due to local gradients in the relative fitness of each strategy, providing a game-dependent alternative to diffusive coupling. We study numerically the development of patterns in one dimension (1D) for two-strategy games including the coordination game and the prisoner's dilemma, and in two dimensions (2D) for the rock-paper-scissors game. In 1D we observe modified traveling wave solutions in the presence of diffusion, and asymptotic attracting states under a frozen-strategy assumption without diffusion. In 2D we observe spiral formation and breakup in the frozen-strategy rock-paper-scissors game without diffusion. A change of variables appropriate to replicator dynamics is shown to correctly capture the 1D asymptotic steady state via a nonlinear diffusion equation.

Therapies based on targeting EBV lytic replication for EBV-associated malignancies.

PubMed

Li, Hongde; Hu, Jianmin; Luo, Xiangjian; Bode, Ann M; Dong, Zigang; Cao, Ya

2018-05-11

In recent years, EBV lytic infection has been shown to significantly contribute to carcinogenesis. Thus, therapies aimed at targeting the EBV lytic cycle have been developed as novel strategies for treatment of EBV-associated diseases malignancies. In this review, focusing on the viral lytic proteins, we describe recent advances regarding the involvement of the EBV lytic cycle in carcinogenesis. Moreover, we further discuss two distinct EBV lytic cycle-targeted therapeutic strategies against EBV-induced malignancies: One of the strategies involves inhibition of the EBV lytic cycle by natural compounds known to have anti-EBV properties; another one is to intentionally induce EBV lytic replication in combination with nucleotide analogues. Recent advances in EBV lytic-based strategies are beginning to show promise in the treatment and/or prevention of EBV-related tumors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

PubMed

Shayestehpour, Mohammad; Moghim, Sharareh; Salimi, Vahid; Jalilvand, Somayeh; Yavarian, Jila; Romani, Bizhan; Mokhtari-Azad, Talat

2017-08-15

MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID 50 . No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells. Copyright © 2017. Published by Elsevier B.V.

Distinct sperm nucleus behaviors between genotypic and temperature-dependent sex determination males are associated with replication and expression-related pathways in a gynogenetic fish.

PubMed

Zhu, Yao-Jun; Li, Xi-Yin; Zhang, Jun; Li, Zhi; Ding, Miao; Zhang, Xiao-Juan; Zhou, Li; Gui, Jian-Fang

2018-06-05

Coexistence and transition of diverse sex determination strategies have been revealed in some ectothermic species, but the variation between males caused by different sex determination strategies and the underlying mechanism remain unclear. Here, we used the gynogenetic gibel carp (Carassius gibelio) with both genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) strategies to illustrate this issue. We found out that males of GSD and TSD in gibel carp had similar morphology, testicular histology, sperm structure and sperm vitality. However, when maternal individuals were mated with males of GSD, sperm nucleus swelling and fusing with the female pronucleus were observed in the fertilized eggs. On the contrary, when maternal individuals were mated with males of TSD, sperm nucleus remained in the condensed status throughout the whole process. Subsequently, semen proteomics analysis unveiled that DNA replication and gene expression-related pathways were inhibited in the sperm from males of TSD compared to males of GSD, and most differentially expressed proteins associated with DNA replication, transcription and translation were down-regulated. Moreover, via BrdU incorporation and immunofluorescence detection, male nucleus replication was revealed to be present in the fertilized eggs by the sperm from males of GSD, but absent in the fertilized eggs by the sperm from males of TSD. These findings indicate that DNA replication and gene expression-related pathways are associated with the distinct sperm nucleus development behaviors in fertilized eggs in response to the sperm from males of GSD and TSD. And this study is the first attempt to screen the differences between males determined via GSD and TSD in gynogenetic species, which might give a hint for understanding evolutionary adaption of diverse sex determination mechanisms in unisexual vertebrates.

The babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction

USDA-ARS?s Scientific Manuscript database

Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission o...

Teacher Perceptions of School Consultant Social Influence Strategies: Replication and Expansion

ERIC Educational Resources Information Center

Owens, Julie Sarno; Schwartz, Madeleine E.; Erchul, William P.; Himawan, Lina K.; Evans, Steven W.; Coles, Erika K.; Schulte, Ann C.

2017-01-01

The goals were to (a) replicate the findings of previous research with regard to the Consultee/Teacher Version of the Interpersonal Power Inventory (IPI), and (b) advance the literature by examining IPI scores about a current consultation relationship. Sample 1 included 99 elementary school teachers (44.4% Hispanic) who completed the IPI. Results…

Surface-Water Quality-Assurance Plan for the USGS Georgia Water Science Center

DTIC Science & Technology

2005-01-01

data-collection activi- ties through offices in Atlanta, Albany, Savannah, and Tifton . A Field Office Chief Technician, under the supervision of the...Roswell, GA (02335450) on May 19, 2004, will have the file- name 040519_02335450_555.txt and will be placed in the /sw/edldata/02335450/555/WY2004...letters of the stream and the first three letters of the nearest location. EXAMPLE: The transect prefix for Chattahoochee River near Norcross, GA

Inner ear tissue preservation by rapid freezing: improving fixation by high-pressure freezing and hybrid methods.

PubMed

Bullen, A; Taylor, R R; Kachar, B; Moores, C; Fleck, R A; Forge, A

2014-09-01

In the preservation of tissues in as 'close to life' state as possible, rapid freeze fixation has many benefits over conventional chemical fixation. One technique by which rapid freeze-fixation can be achieved, high pressure freezing (HPF), has been shown to enable ice crystal artefact-free freezing and tissue preservation to greater depths (more than 40 μm) than other quick-freezing methods. Despite increasingly becoming routine in electron microscopy, the use of HPF for the fixation of inner ear tissue has been limited. Assessment of the quality of preservation showed routine HPF techniques were suitable for preparation of inner ear tissues in a variety of species. Good preservation throughout the depth of sensory epithelia was achievable. Comparison to chemically fixed tissue indicated that fresh frozen preparations exhibited overall superior structural preservation of cells. However, HPF fixation caused characteristic artefacts in stereocilia that suggested poor quality freezing of the actin bundles. The hybrid technique of pre-fixation and high pressure freezing was shown to produce cellular preservation throughout the tissue, similar to that seen in HPF alone. Pre-fixation HPF produced consistent high quality preservation of stereociliary actin bundles. Optimising the preparation of samples with minimal artefact formation allows analysis of the links between ultrastructure and function in inner ear tissues. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Parallel design of JPEG-LS encoder on graphics processing units

NASA Astrophysics Data System (ADS)

Duan, Hao; Fang, Yong; Huang, Bormin

2012-01-01

With recent technical advances in graphic processing units (GPUs), GPUs have outperformed CPUs in terms of compute capability and memory bandwidth. Many successful GPU applications to high performance computing have been reported. JPEG-LS is an ISO/IEC standard for lossless image compression which utilizes adaptive context modeling and run-length coding to improve compression ratio. However, adaptive context modeling causes data dependency among adjacent pixels and the run-length coding has to be performed in a sequential way. Hence, using JPEG-LS to compress large-volume hyperspectral image data is quite time-consuming. We implement an efficient parallel JPEG-LS encoder for lossless hyperspectral compression on a NVIDIA GPU using the computer unified device architecture (CUDA) programming technology. We use the block parallel strategy, as well as such CUDA techniques as coalesced global memory access, parallel prefix sum, and asynchronous data transfer. We also show the relation between GPU speedup and AVIRIS block size, as well as the relation between compression ratio and AVIRIS block size. When AVIRIS images are divided into blocks, each with 64×64 pixels, we gain the best GPU performance with 26.3x speedup over its original CPU code.

The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription▿

PubMed Central

Dutta, Chaitali; Patel, Prasanta K.; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

2008-01-01

The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G1/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes. PMID:18662996

A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles

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

Meador, Lydia R.

Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viralmore » vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. - Highlights: • We devised a prime/boost anti HIV-1 vaccination strategy modeled after RV144. • We used plant-derived virus-like particles (VLPs) consisting of Gag and dgp41. • We used attenuated, replicating vaccinia virus vectors expressing the same antigens. • The immunogens elicited strong cellular and humoral immune responses.« less

Kill: boosting HIV-specific immune responses.

PubMed

Trautmann, Lydie

2016-07-01

Increasing evidence suggests that purging the latent HIV reservoir in virally suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV-infected cells ('Shock and Kill' strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in-vivo and in-silico models to accelerate the design of new clinical trials. New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment.

Engineering T Cells to Functionally Cure HIV-1 Infection.

PubMed

Leibman, Rachel S; Riley, James L

2015-07-01

Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure.

HMGB1 Protein Binds to Influenza Virus Nucleoprotein and Promotes Viral Replication

PubMed Central

Moisy, Dorothée; Avilov, Sergiy V.; Jacob, Yves; Laoide, Brid M.; Ge, Xingyi; Baudin, Florence; Jestin, Jean-Luc

2012-01-01

Influenza virus has evolved replication strategies that hijack host cell pathways. To uncover interactions between viral macromolecules and host proteins, we applied a phage display strategy. A library of human cDNA expression products displayed on filamentous phages was submitted to affinity selection for influenza viral ribonucleoproteins (vRNPs). High-mobility-group box (HMGB) proteins were found to bind to the nucleoprotein (NP) component of vRNPs. HMGB1 and HMGB2 bind directly to the purified NP in the absence of viral RNA, and the HMG box A domain is sufficient to bind the NP. We show that HMGB1 associates with the viral NP in the nuclei of infected cells, promotes viral growth, and enhances the activity of the viral polymerase. The presence of a functional HMGB1 DNA-binding site is required to enhance influenza virus replication. Glycyrrhizin, which reduces HMGB1 binding to DNA, inhibits influenza virus polymerase activity. Our data show that the HMGB1 protein can play a significant role in intranuclear replication of influenza viruses, thus extending previous findings on the bornavirus and on a number of DNA viruses. PMID:22696656

A Thousand Frames in Just a Few Words: Lingual Description of Videos through Latent Topics and Sparse Object Stitching (Open Access)

DTIC Science & Technology

2013-10-03

the Stanford NLP Suite∗ to create an- notated dictionaries based on word morphologies ; the human descriptions provide the input. The predicted...keywords from the low level topic models are labeled through these dictionaries. For more than two POS for the same morphology , we prefer verbs, but other...redundancy particularly retaining subjects like “man,” “woman” etc. and verb morphologies (which otherwise stem to the same prefix) as proxies for ten

Biocorrosion vs. erosion: the 21st century and a time to change.

PubMed

Grippo, John O

2012-02-01

The author's objective is to precisely define the term "erosion" as a physical mechanism and to establish the mechanism of biocorrosion in the lexicon of dental terms. Using the prefix "bio" before corrosion differentiates it from corrosion, because it designates the chemical, biochemical, and electrochemical actions on enamel and dentin. Biocorrosion encompasses endogenous and exogenous acidic and proteolytic chemical degradation of enamel and dentin, as well as the piezoelectric electrochemical action on the collagen in dentin.

Implementation of the Diabetes Practice Guideline in the Army Medical Department: Final Evaluation

DTIC Science & Technology

2005-01-01

Diabetes Quality Improvement Project DRG Diagnosis-Related Group ER Emergency room FMP Family Member Prefix HBA1c Hemoglobin A1c HCSR Health-Care Service...glycemic control by assessing and managing glycosylated hemoglobin, reported as hemoglobin A1c ( HbA1c ) lev- els. Assess HbA1c levels relative to target...frequency involved in adjusting insulin dosages Increase in the percentage of noninsulin patients who fill prescribed medications to control HbA1c

Da Vinci's codex and the anatomy of healthcare.

PubMed

Stephens-Borg, Keith

2012-08-01

We usually display a laid-back approach to medical jargon throughout our theatre work. The word 'perioperative' is built from the Greek word 'peri' (around) and the Latin 'operari' (to work). Latin and Greek became the prefixed language of choice for Leonardo da Vinci, and his research was pivotal in determining the way in which surgical procedures are documented. Ancient manuscripts aided the unfolding of the secrets of anatomy, and Leonardo revealed that art was the key in expressive detailed explanation.

Self-replication with magnetic dipolar colloids

NASA Astrophysics Data System (ADS)

Dempster, Joshua M.; Zhang, Rui; Olvera de la Cruz, Monica

2015-10-01

Colloidal self-replication represents an exciting research frontier in soft matter physics. Currently, all reported self-replication schemes involve coating colloidal particles with stimuli-responsive molecules to allow switchable interactions. In this paper, we introduce a scheme using ferromagnetic dipolar colloids and preprogrammed external magnetic fields to create an autonomous self-replication system. Interparticle dipole-dipole forces and periodically varying weak-strong magnetic fields cooperate to drive colloid monomers from the solute onto templates, bind them into replicas, and dissolve template complexes. We present three general design principles for autonomous linear replicators, derived from a focused study of a minimalist sphere-dimer magnetic system in which single binding sites allow formation of dimeric templates. We show via statistical models and computer simulations that our system exhibits nonlinear growth of templates and produces nearly exponential growth (low error rate) upon adding an optimized competing electrostatic potential. We devise experimental strategies for constructing the required magnetic colloids based on documented laboratory techniques. We also present qualitative ideas about building more complex self-replicating structures utilizing magnetic colloids.

Network structures between strategies in iterated prisoners' dilemma games

NASA Astrophysics Data System (ADS)

Kim, Young Jin; Roh, Myungkyoon; Son, Seung-Woo

2014-02-01

We use replicator dynamics to study an iterated prisoners' dilemma game with memory. In this study, we investigate the characteristics of all 32 possible strategies with a single-step memory by observing the results when each strategy encounters another one. Based on these results, we define similarity measures between the 32 strategies and perform a network analysis of the relationship between the strategies by constructing a strategies network. Interestingly, we find that a win-lose circulation, like rock-paper-scissors, exists between strategies and that the circulation results from one unusual strategy.

Category cued recall evokes a generate-recognize retrieval process.

PubMed

Hunt, R Reed; Smith, Rebekah E; Toth, Jeffrey P

2016-03-01

The experiments reported here were designed to replicate and extend McCabe, Roediger, and Karpicke's (2011) finding that retrieval in category cued recall involves both controlled and automatic processes. The extension entailed identifying whether distinctive encoding affected 1 or both of these 2 processes. The first experiment successfully replicated McCabe et al., but the second, which added a critical baseline condition, produced data inconsistent with a 2 independent process model of recall. The third experiment provided evidence that retrieval in category cued recall reflects a generate-recognize strategy, with the effect of distinctive processing being localized to recognition. Overall, the data suggest that category cued recall evokes a generate-recognize retrieval strategy and that the subprocesses underlying this strategy can be dissociated as a function of distinctive versus relational encoding processes. (c) 2016 APA, all rights reserved).

Category Cued Recall Evokes a Generate-Recognize Retrieval Process

PubMed Central

Hunt, R. Reed; Smith, Rebekah E.; Toth, Jeffrey P.

2015-01-01

The experiments reported here were designed to replicate and extend McCabe, Roediger, and Karpicke’s (2011) finding that retrieval in category cued recall involves both controlled and automatic processes. The extension entailed identifying whether distinctive encoding affected one or both of these two processes. The first experiment successfully replicated McCabe et al., but the second, which added a critical baseline condition, produced data inconsistent with a two independent process model of recall. The third experiment provided evidence that retrieval in category cued recall reflects a generate-recognize strategy, with the effect of distinctive processing being localized to recognition. Overall, the data suggest that category cued recall evokes a generate-recognize retrieval strategy and that the sub-processes underlying this strategy can be dissociated as a function of distinctive versus relational encoding processes. PMID:26280355

Pathways for maintenance of telomeres and common fragile sites during DNA replication stress

PubMed Central

Özer, Özgün

2018-01-01

Oncogene activation during tumour development leads to changes in the DNA replication programme that enhance DNA replication stress. Certain regions of the human genome, such as common fragile sites and telomeres, are particularly sensitive to DNA replication stress due to their inherently ‘difficult-to-replicate’ nature. Indeed, it appears that these regions sometimes fail to complete DNA replication within the period of interphase when cells are exposed to DNA replication stress. Under these conditions, cells use a salvage pathway, termed ‘mitotic DNA repair synthesis (MiDAS)’, to complete DNA synthesis in the early stages of mitosis. If MiDAS fails, the ensuing mitotic errors threaten genome integrity and cell viability. Recent studies have provided an insight into how MiDAS helps cells to counteract DNA replication stress. However, our understanding of the molecular mechanisms and regulation of MiDAS remain poorly defined. Here, we provide an overview of how DNA replication stress triggers MiDAS, with an emphasis on how common fragile sites and telomeres are maintained. Furthermore, we discuss how a better understanding of MiDAS might reveal novel strategies to target cancer cells that maintain viability in the face of chronic oncogene-induced DNA replication stress. PMID:29695617

Brief Report: Use of an Antecedent Procedure to Decrease Night Awakening in an Infant--A Replication

ERIC Educational Resources Information Center

Cautilli, Joseph

2005-01-01

Borowski, Hunter, and Johnson (2001) found that an antecedent strategy such as white noise could decrease sleep awakenings for infants in the natural home environment. This study attempts to replicate the findings using an ABAB reversal design. A five month and one week old child, who had difficulty with waking an average of four times per night,…

New Therapeutic Strategies for Antibiotic-Resistant Select Agents

DTIC Science & Technology

2007-12-31

activity possibly due to inherent differences between mesophilic versus thermophilic replication enzymes (Figure 7A). E. coli helicase stimulated Y...primase activity possibly due to inherent differences between mesophilic versus thermophilic replication enzymes (Figure 7A). B E. coli...either lower the enzyme and template to 20 nM, or use higher compound concentrations that are the same as the enzyme and template. A series of

The Relationship between Language Learning Strategies, Proficiency, Age and Self-Efficacy Beliefs: A Study of Language Learners in Botswana

ERIC Educational Resources Information Center

Magogwe, Joel Mokuedi; Oliver, Rhonda

2007-01-01

This research seeks to extend our current knowledge by exploring the relationship between preferred language strategies, age, proficiency, and self-efficacy beliefs. Responding to the call for more replication of strategy research and for research in different cultural contexts, this research was undertaken in Botswana between 2002 and 2005. The…

Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation

PubMed Central

Vincent, Heather A.; Ziehr, Benjamin; Moorman, Nathaniel J.

2016-01-01

mRNA translation requires the ordered assembly of translation initiation factors and ribosomal subunits on a transcript. Host signaling pathways regulate each step in this process to match levels of protein synthesis to environmental cues. In response to infection, cells activate multiple defenses that limit viral protein synthesis, which viruses must counteract to successfully replicate. Human cytomegalovirus (HCMV) inhibits host defenses that limit viral protein expression and manipulates host signaling pathways to promote the expression of both host and viral proteins necessary for virus replication. Here we review key regulatory steps in mRNA translation, and the strategies used by HCMV to maintain protein synthesis in infected cells. PMID:27089357

Understanding HIV infection for the design of a therapeutic vaccine. Part I: Epidemiology and pathogenesis of HIV infection.

PubMed

de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

2015-03-01

HIV infection leads to a gradual loss CD4+ T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive life-long adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

SMC1-Mediated Intra-S-Phase Arrest Facilitates Bocavirus DNA Replication

PubMed Central

Luo, Yong; Deng, Xuefeng; Cheng, Fang; Li, Yi

2013-01-01

Activation of a host DNA damage response (DDR) is essential for DNA replication of minute virus of canines (MVC), a member of the genus Bocavirus of the Parvoviridae family; however, the mechanism by which DDR contributes to viral DNA replication is unknown. In the current study, we demonstrate that MVC infection triggers the intra-S-phase arrest to slow down host cellular DNA replication and to recruit cellular DNA replication factors for viral DNA replication. The intra-S-phase arrest is regulated by ATM (ataxia telangiectasia-mutated kinase) signaling in a p53-independent manner. Moreover, we demonstrate that SMC1 (structural maintenance of chromosomes 1) is the key regulator of the intra-S-phase arrest induced during infection. Either knockdown of SMC1 or complementation with a dominant negative SMC1 mutant blocks both the intra-S-phase arrest and viral DNA replication. Finally, we show that the intra-S-phase arrest induced during MVC infection was caused neither by damaged host cellular DNA nor by viral proteins but by replicating viral genomes physically associated with the DNA damage sensor, the Mre11-Rad50-Nbs1 (MRN) complex. In conclusion, the feedback loop between MVC DNA replication and the intra-S-phase arrest is mediated by ATM-SMC1 signaling and plays a critical role in MVC DNA replication. Thus, our findings unravel the mechanism underlying DDR signaling-facilitated MVC DNA replication and demonstrate a novel strategy of DNA virus-host interaction. PMID:23365434

EVALUATION OF BIOREMEDIATION STRATEGIES OF A CONTROLLED OIL RELEASE IN A WETLAND

EPA Science Inventory

A controlled petroleum release was conducted to evaluate bioremediation in a wetland near Houston, Texas. The 140-day study was conducted using a randomized, complete block design to test three treatments with six replicates per treatment. The three treatment strategies were in...

Minority Teacher Recruitment and Retention Strategies

ERIC Educational Resources Information Center

Kearney-Gissendaner, Janet E.

2010-01-01

The tools and resources in this book help school leaders seamlessly incorporate minority teacher recruitment and retention programs into current human-resources activities. With details about exemplary minority teacher recruitment and retention programs, this book also showcases strategies for how to replicate such programs in your own school or…

Back to basics: pBR322 and protein expression systems in E. coli.

PubMed

Balbás, Paulina; Bolívar, Francisco

2004-01-01

The extensive variety of plasmid-based expression systems in E. coli resulted from the fact that there is no single strategy for achieving maximal expression of every cloned gene. Although a number of strategies have been implemented to deal with problems associated to gene transcription and translation, protein folding, secretion, location, posttranslational modifications, particularities of different strains, and the like and more integrated processes have been developed, the basic plasmid-borne elements and their interaction with the particular host strain will influence the overall expression system and final productivity. Plasmid vector pBR322 is a well-established multipurpose cloning vector in laboratories worldwide, and a large number of derivatives have been created for specific applications and research purposes, including gene expression in its natural host, E. coli, and few other bacteria. The early characterization of the molecule, including its nucleotide sequence, replication and maintenance mechanisms, and determination of its coding regions, accounted for its success, not only as a universal cloning vector, but also as a provider of genes and an origin of replication for other intraspecies vectors. Since the publication of the aforementioned reviews, novel discoveries pertaining to these issues have appeared in the literature that deepen the understanding of the plasmid's features, behavior, and impact in gene expression systems, as well as some important strain characteristics that affect plasmid replication and stability. The objectives of this review include updating and discussing the new information about (1) the replication and maintenance of pBR322; (2) the host-related modulation mechanisms of plasmid replication; (3) the effects of growth rate on replication control, stability, and recombinant gene expression; (4) ways for plasmid amplification and elimination. Finally, (5) a summary of novel ancillary studies about pBR322 is presented.

Proactive replica checking to assure reliability of data in cloud storage with minimum replication

NASA Astrophysics Data System (ADS)

Murarka, Damini; Maheswari, G. Uma

2017-11-01

The two major issues for cloud storage systems are data reliability and storage costs. For data reliability protection, multi-replica replication strategy which is used mostly in current clouds acquires huge storage consumption, leading to a large storage cost for applications within the loud specifically. This paper presents a cost-efficient data reliability mechanism named PRCR to cut back the cloud storage consumption. PRCR ensures data reliability of large cloud information with the replication that might conjointly function as a price effective benchmark for replication. The duplication shows that when resembled to the standard three-replica approach, PRCR will scale back to consume only a simple fraction of the cloud storage from one-third of the storage, thence considerably minimizing the cloud storage price.

Hypothesis-Testing Demands Trustworthy Data—A Simulation Approach to Inferential Statistics Advocating the Research Program Strategy

PubMed Central

Krefeld-Schwalb, Antonia; Witte, Erich H.; Zenker, Frank

2018-01-01

In psychology as elsewhere, the main statistical inference strategy to establish empirical effects is null-hypothesis significance testing (NHST). The recent failure to replicate allegedly well-established NHST-results, however, implies that such results lack sufficient statistical power, and thus feature unacceptably high error-rates. Using data-simulation to estimate the error-rates of NHST-results, we advocate the research program strategy (RPS) as a superior methodology. RPS integrates Frequentist with Bayesian inference elements, and leads from a preliminary discovery against a (random) H0-hypothesis to a statistical H1-verification. Not only do RPS-results feature significantly lower error-rates than NHST-results, RPS also addresses key-deficits of a “pure” Frequentist and a standard Bayesian approach. In particular, RPS aggregates underpowered results safely. RPS therefore provides a tool to regain the trust the discipline had lost during the ongoing replicability-crisis. PMID:29740363

Hypothesis-Testing Demands Trustworthy Data-A Simulation Approach to Inferential Statistics Advocating the Research Program Strategy.

PubMed

Krefeld-Schwalb, Antonia; Witte, Erich H; Zenker, Frank

2018-01-01

In psychology as elsewhere, the main statistical inference strategy to establish empirical effects is null-hypothesis significance testing (NHST). The recent failure to replicate allegedly well-established NHST-results, however, implies that such results lack sufficient statistical power, and thus feature unacceptably high error-rates. Using data-simulation to estimate the error-rates of NHST-results, we advocate the research program strategy (RPS) as a superior methodology. RPS integrates Frequentist with Bayesian inference elements, and leads from a preliminary discovery against a (random) H 0 -hypothesis to a statistical H 1 -verification. Not only do RPS-results feature significantly lower error-rates than NHST-results, RPS also addresses key-deficits of a "pure" Frequentist and a standard Bayesian approach. In particular, RPS aggregates underpowered results safely. RPS therefore provides a tool to regain the trust the discipline had lost during the ongoing replicability-crisis.

Bridging research and practice: community-researcher partnerships for replicating effective interventions.

PubMed

Rotheram-Borus, M J; Rebchook, G M; Kelly, J A; Adams, J; Neumann, M S

2000-01-01

Long-term collaborations among researchers, staff and volunteers in community-based agencies, staff in institutional settings, and health advocates present challenges. Each group has different missions, procedures, attributes, and rewards. This article reviews areas of potential conflict and suggests strategies for coping with these challenges. During the replication of five effective HIV prevention interventions, strategies for maintaining mutually beneficial collaborations included selecting agencies with infrastructures that could support research-based interventions; obtaining letters of understanding that clarified roles, responsibilities, and time frames; and setting training schedules with opportunities for observing, practicing, becoming invested in, and repeatedly implementing the intervention. The process of implementing interventions highlighted educating funders of research and public health services about (a) the costs of disseminating interventions, (b) the need for innovation to new modalities and theories for delivering effective interventions, and (c) adopting strategies of marketing research and quality engineering when designing interventions.

Immunological Prediction of Cytomegalovirus (CMV) Replication Risk in Solid Organ Transplantation Recipients: Approaches for Regulating the Targeted Anti-CMV Prevention Strategies

PubMed Central

2017-01-01

The current cytomegalovirus (CMV) prevention strategies in solid organ transplantation (SOT) recipients have contributed towards overcoming the detrimental effects caused by CMV lytic infection, and improving the long-term success rate of graft survival. Although the quantification of CMV in peripheral blood is the standard method, and an excellent end-point for diagnosing CMV replication and modulating the anti-CMV prevention strategies in SOT recipients, a novel biomarker mimicking the CMV control mechanism is required. CMV-specific immune monitoring can be employed as a basic tool predicting CMV infection or disease after SOT, since uncontrolled CMV replication mostly originates from the impairment of immune responses against CMV under immunosuppressive conditions in SOT recipients. Several studies conducted during the past few decades have indicated the possibility of measuring the CMV-specific cell-mediated immune response in clinical situations. Among several analytical assays, the most advancing standardized tool is the QuantiFERON®-CMV assay. The T-Track® CMV kit that uses the standardized enzyme-linked immunospot assay is also widely employed. In addition to these assays, immunophenotyping and intracellular cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal antibodies or peptide-major histocompatibility complex multimers) needs to be adequately standardized and validated for potential clinical applications. PMID:29027383

Kill: Boosting HIV-specific immune responses

PubMed Central

Trautmann, Lydie

2016-01-01

Purpose of review Increasing evidences suggest that purging the latent HIV reservoir in virally-suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV infected cells (“Shock and Kill” strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent findings Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in vivo and in silico models to accelerate the design of new clinical trials. Summary New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment. PMID:27054280

A Queueing Approach to Optimal Resource Replication in Wireless Sensor Networks

DTIC Science & Technology

2009-04-29

network (an energy- centric approach) or to ensure the proportion of query failures does not exceed a predetermined threshold (a failure- centric ...replication strategies in wireless sensor networks. The model can be used to minimize either the total transmission rate of the network (an energy- centric ...approach) or to ensure the proportion of query failures does not exceed a predetermined threshold (a failure- centric approach). The model explicitly

Modulation of ColE1-like Plasmid Replication for Recombinant Gene Expression

PubMed Central

Camps, Manel

2010-01-01

ColE1-like plasmids constitute the most popular vectors for recombinant protein expression. ColE1 plasmid replication is tightly controlled by an antisense RNA mechanism that is highly dynamic, tuning plasmid metabolic burden to the physiological state of the host. Plasmid homeostasis is upset upon induction of recombinant protein expression because of non-physiological levels of expression and because of the frequently biased amino acid composition of recombinant proteins. Disregulation of plasmid replication is the main cause of collapse of plasmid-based expression systems because of a simultaneous increase in the metabolic burden (due to increased average copy number) and in the probability of generation of plasmid-free cells (due to increased copy number variation). Interference between regulatory elements of co-resident plasmids causes comparable effects on plasmid stability (plasmid incompatibility). Modulating plasmid copy number for recombinant gene expression aims at achieving a high gene dosage while preserving the stability of the expression system. Here I present strategies targeting plasmid replication for optimizing recombinant gene expression. Specifically, I review approaches aimed at modulating the antisense regulatory system (as well as their implications for plasmid incompatibility) and innovative strategies involving modulation of host factors, of R-loop formation, and of the timing of recombinant gene expression. PMID:20218961

The importance of imaging strategies for pre-clinical and clinical in vivo distribution of oncolytic viruses

PubMed Central

Pelin, Adrian; Wang, Jiahu; Bell, John; Le Boeuf, Fabrice

2017-01-01

Oncolytic viruses (OVs) are an emergent and unique therapy for cancer patients. Similar to chemo- and radiation therapy, OV can lyse (kill) cancer cell directly. In general, the advantages of OVs over other treatments are primarily: a higher safety profile (as shown by less adverse effects), ability to replicate, transgene(s) delivery, and stimulation of a host’s immune system against cancer. The latter has prompted successful use of OVs with other immunotherapeutic strategies in a synergistic manner. In spite of extended testing in pre-clinical and clinical setting, using biologically derived therapeutics like virus always raises potential concerns about safety (replication at non-intended locations) and bio-availability of the product. Recent advent in in vivo imaging techniques dramatically improves the convenience of use, quality of pictures, and amount of information acquired. Easy assessing of safety/localization of the biotherapeutics like OVs became a new potential weapon in the physician’s arsenal to improve treatment outcome. Given that OVs are typically replicating, in vivo imaging can also track virus replication and persistence as well as precisely mapping tumor tissues presence. This review discusses the importance of imaging in vivo in evaluating OV efficacy, as well as currently available tools and techniques. PMID:29637059

Suppressor Effects of Coping Strategies on Resilience

ERIC Educational Resources Information Center

Yoon, Jae ho; Lee, Ji hae; Lee, Chae Yeon; Cho, Minhee; Lee, Sang Min

2014-01-01

The purpose of the current study is to demonstrate a significant suppressor effect among coping strategies on resilience. Two different samples were used to replicate the suppressor effect. Participants in the first example were 391 adolescents (middle school students) in Korea, and participants in the second example were 282 young adults…

78 FR 24392 - Agency Information Collection Activities; Comment Request; Evaluation and Accountability Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... effectiveness of Title II, Part D formula and competitive grant-funded projects, activities and strategies in... and strategies that effectively infuse technology with curriculum and instruction, show evidence of positive impacts for student learning, and can be widely replicated by other State educational agencies and...

Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question

PubMed Central

Koonin, Eugene V.; Starokadomskyy, Petro

2016-01-01

The question whether or not “viruses are alive” has caused considerable debate over many years. Yet, the question is effectively without substance because the answer depends entirely on the definition of life or the state of “being alive” that is bound to be arbitrary. In contrast, the status of viruses among biological entities is readily defined within the replicator paradigm. All biological replicators form a continuum along the selfishness-cooperativity axis, from the completely selfish to fully cooperative forms. Within this range, typical, lytic viruses represent the selfish extreme whereas temperate viruses and various mobile elements occupy positions closer to the middle of the range. Selfish replicators not only belong to the biological realm but are intrinsic to any evolving system of replicators. No such system can evolve without the emergence of parasites, and moreover, parasites drive the evolution of biological complexity at multiple levels. The history of life is a story of parasite-host coevolution that includes both the incessant arms race and various forms of cooperation. All organisms are communities of interacting, coevolving replicators of different classes. A complete theory of replicator coevolution remains to be developed, but it appears likely that not only the differentiation between selfish and cooperative replicators but the emergence of the entire range of replication strategies, from selfish to cooperative, is intrinsic to biological evolution. PMID:26965225

Compartmentalized self-replication: a novel method for the directed evolution of polymerases and other enzymes.

PubMed

Ghadessy, Farid J; Holliger, Philipp

2007-01-01

Compartmentalized self-replication (CSR) is a novel method for the directed evolution of enzymes and, in particular, polymerases. In its simplest form, CSR consists of a simple feedback loop involving a polymerase that replicates only its own encoding gene (self-replication). Self-replication occurs in discrete, spatially separate, noncommunicating compartments formed by a heat-stable water-in-oil emulsion. Compartmentalization ensures the linkage of phenotype and genotype (i.e., it ensures that each polymerase replicates only its own encoding gene to the exclusion of those in the other compartments). As a result, adaptive gains by the polymerase directly (and proportionally) translate into genetic amplification of the encoding polymerase gene. CSR has proven to be a useful strategy for the directed evolution of polymerases directly from diverse repertoires of polymerase genes. In this chapter, we describe some of the CSR protocols used successfully to evolve variants of T. aquaticus Pol I (Taq) polymerase with novel and useful properties, such as increased thermostability or resistance to the potent inhibitor, heparin, from a repertoire of randomly mutated Taq polymerase genes.

A Hybrid Analysis for Security Protocols with State

DTIC Science & Technology

2014-07-16

Approved for Public Release; Distribution Unlimited. 14-1013. A Hybrid Analysis for Security Protocols with State∗ John D. Ramsdell Daniel J ...their consequences in the anno - tated protocol theory Tannot(Π, ) use only the limited vocabulary of Tbnd(Π); we call them bridge lemmas. Lemma 3 is a...and we proved it using pvs. Lemma 1 (Prefix Boot Extend). ∀π ∈ path, t :>, i, k ∈ N. i ≤ k ∧ π(k) has t ⊃ subterm(π(i), π(k)) ∨ ∃ j ∈ N. i ≤ j < k ∧ π

Parallel Algorithms and Patterns

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

Robey, Robert W.

2016-06-16

This is a powerpoint presentation on parallel algorithms and patterns. A parallel algorithm is a well-defined, step-by-step computational procedure that emphasizes concurrency to solve a problem. Examples of problems include: Sorting, searching, optimization, matrix operations. A parallel pattern is a computational step in a sequence of independent, potentially concurrent operations that occurs in diverse scenarios with some frequency. Examples are: Reductions, prefix scans, ghost cell updates. We only touch on parallel patterns in this presentation. It really deserves its own detailed discussion which Gabe Rockefeller would like to develop.

A Simulation Testbed for Adaptive Modulation and Coding in Airborne Telemetry (Brief)

DTIC Science & Technology

2014-10-01

SOQPSK 0.0085924 us 0.015231 kH2 10 1/2 20 Time Modulation/ Coding State ... .. . . D - 2/3 3/4 4/5 GTRI_B-‹#› MATLAB GUI Interface 8...802.11a) • Modulations: BPSK, QPSK, 16 QAM, 64 QAM • Cyclic Prefix Lengths • Number of Subcarriers • Coding • LDPC • Rates: 1/2, 2/3, 3/4, 4/5...and Coding in Airborne Telemetry (Brief) October 2014 DISTRIBUTION STATEMENT A. Approved for public release: distribution unlimited. Test

SI (Metric) handbook

NASA Technical Reports Server (NTRS)

Artusa, Elisa A.

1994-01-01

This guide provides information for an understanding of SI units, symbols, and prefixes; style and usage in documentation in both the US and in the international business community; conversion techniques; limits, fits, and tolerance data; and drawing and technical writing guidelines. Also provided is information of SI usage for specialized applications like data processing and computer programming, science, engineering, and construction. Related information in the appendixes include legislative documents, historical and biographical data, a list of metric documentation, rules for determining significant digits and rounding, conversion factors, shorthand notation, and a unit index.

Absence of MutSbeta leads to the formation of slipped-DNA for CTG/CAG contractions at primate replication forks

PubMed Central

Slean, Meghan M.; Panigrahi, Gagan B.; Castel, Arturo López; Pearson, August B.; Tomkinson, Alan E.; Pearson, Christopher E.

2016-01-01

Typically disease-causing CAG/CTG repeats expand, but rare affected families can display high levels of contraction of the expanded repeat amongst offspring. Understanding instability is important since arresting expansions or enhancing contractions could be clinically beneficial. The MutSβ mismatch repair complex is required for CAG/CTG expansions in mice and patients. Oddly, by unknown mechanisms MutSβ-deficient mice incur contractions instead of expansions. Replication using CTG or CAG as the lagging strand template is known to cause contractions or expansions respectively; however, the interplay between replication and repair leading to this instability remains unclear. Towards understanding how repeat contractions may arise, we performed in vitro SV40-mediated replication of repeat-containing plasmids in the presence or absence of mismatch repair. Specifically, we separated repair from replication: Replication mediated by MutSβ- and MutSα-deficient human cells or cell extracts produced slipped-DNA heteroduplexes in the contraction- but not expansion-biased replication direction. Replication in the presence of MutSβ disfavoured the retention of replication products harbouring slipped-DNA heteroduplexes. Post-replication repair of slipped-DNAs by MutSβ-proficient extracts eliminated slipped-DNAs. Thus, a MutSβ-deficiency likely enhances repeat contractions because MutSβ protects against contractions by repairing template strand slip-outs. Replication deficient in LigaseI or PCNA-interaction mutant LigaseI revealed slipped-DNA formation at lagging strands. Our results reveal that distinct mechanisms lead to expansions or contractions and support inhibition of MutSβ as a therapeutic strategy to enhance the contraction of expanded repeats. PMID:27155933

Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes.

PubMed

Gu, Jijin; Al-Bayati, Karam; Ho, Emmanuel A

2017-08-01

RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands. In this study, chitosan nanoparticles (CS-NPs) were prepared by a complex coacervation method in the presence of siRNA, and antibody was chemically conjugated to the nanoparticles. The antibody-modified chitosan nanoparticles (Ab-CS-NPs) were spherical in shape, with an average particle size of 235.7 ± 10.2 nm and a zeta potential of 22.88 ± 1.78 mV. The therapeutic potential of the nanoparticles was evaluated based on their cellular uptake and gene silencing efficiency. Cellular accumulation and gene silencing efficiency of Ab-CS-NPs in astrocytes were significantly improved compared to non-modified CS-NPs and single-antibody-modified CS-NPs. These results suggest that the combination of anti-Tf antibody and anti-B2 antibody significantly increased the knockdown effect of siRNA-loaded nanoparticles. Thus, antibody-mediated dual-targeting nanoparticles are an efficient and promising delivery strategy for inhibiting HIV replication in astrocytes. Graphical abstract Graphic representation of dual-antibody-conjugated chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier (BBB) for inhibiting HIV replication in astrocytes. a Nanoparticle delivery to the BBB and penetration. b TfR-mediated transcytosis of nanoparticles across the epithelial cells. c B2R-mediated endocytosis of nanoparticles in astrocytes. d The molecular interactions between HIV-1 Tat protein and Cyclin T1 and Tip110 cellular proteins. e A schematic representation of chitosan nanoparticles with its components. RNAPII RNA polymerase II, TAR transactivation response RNA element, LTR long terminal repeat, Ab antibody, CS chitosan, TPP tripolyphosphate.

Human Metapneumovirus Induces Formation of Inclusion Bodies for Efficient Genome Replication and Transcription

PubMed Central

Cifuentes-Muñoz, Nicolás; Branttie, Jean; Slaughter, Kerri Beth

2017-01-01

ABSTRACT Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA subpopulations in infected cells. The FISH probes were specific for detection of HMPV positive-sense RNA (+RNA) and viral genomic RNA (vRNA). Time course analysis of human bronchial epithelial BEAS-2B cells infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection. HMPV IBs were shown to be cytoplasmic sites of active transcription and replication, with the translation of viral proteins being closely associated. Inclusion body formation was consistent with an actin-dependent coalescence of multiple early replicative sites. Time course quantitative reverse transcription-PCR analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate and transcribe the viral genome. These results provide a better understanding of the steps following HMPV entry and have important clinical implications. IMPORTANCE Human metapneumovirus (HMPV) is a recently discovered pathogen that affects human populations of all ages worldwide. Reinfections are common throughout life, but no vaccines or antiviral treatments are currently available. In this work, a spatiotemporal analysis of HMPV replication and transcription in bronchial epithelial cell-derived immortal cells was performed. HMPV was shown to induce the formation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcription. Unlike other cytoplasmic structures, such as stress granules and processing bodies, inclusion bodies are exclusively present in infected cells and contain HMPV RNA and proteins to more efficiently transcribe and replicate the viral genome. Though inclusion body formation is nuanced, it corresponds to a more generalized strategy used by different viruses, including filoviruses and rhabdoviruses, for genome transcription and replication. Thus, an understanding of inclusion body formation is crucial for the discovery of innovative therapeutic targets. PMID:28978704

Human Metapneumovirus Induces Formation of Inclusion Bodies for Efficient Genome Replication and Transcription.

PubMed

Cifuentes-Muñoz, Nicolás; Branttie, Jean; Slaughter, Kerri Beth; Dutch, Rebecca Ellis

2017-12-15

Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA subpopulations in infected cells. The FISH probes were specific for detection of HMPV positive-sense RNA (+RNA) and viral genomic RNA (vRNA). Time course analysis of human bronchial epithelial BEAS-2B cells infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection. HMPV IBs were shown to be cytoplasmic sites of active transcription and replication, with the translation of viral proteins being closely associated. Inclusion body formation was consistent with an actin-dependent coalescence of multiple early replicative sites. Time course quantitative reverse transcription-PCR analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate and transcribe the viral genome. These results provide a better understanding of the steps following HMPV entry and have important clinical implications. IMPORTANCE Human metapneumovirus (HMPV) is a recently discovered pathogen that affects human populations of all ages worldwide. Reinfections are common throughout life, but no vaccines or antiviral treatments are currently available. In this work, a spatiotemporal analysis of HMPV replication and transcription in bronchial epithelial cell-derived immortal cells was performed. HMPV was shown to induce the formation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcription. Unlike other cytoplasmic structures, such as stress granules and processing bodies, inclusion bodies are exclusively present in infected cells and contain HMPV RNA and proteins to more efficiently transcribe and replicate the viral genome. Though inclusion body formation is nuanced, it corresponds to a more generalized strategy used by different viruses, including filoviruses and rhabdoviruses, for genome transcription and replication. Thus, an understanding of inclusion body formation is crucial for the discovery of innovative therapeutic targets. Copyright © 2017 American Society for Microbiology.

Construction of green fluorescent protein-tagged recombinant iridovirus to assess viral replication.

PubMed

Huang, Youhua; Huang, Xiaohong; Cai, Jia; Ye, Fuzhou; Guan, Liya; Liu, Hong; Qin, Qiwei

2011-09-01

Green fluorescent protein-tagged recombinant virus has been successfully applied to observing the infective dynamics and evaluating viral replication. Here, we identified soft-shelled turtle iridovirus (STIV) ORF55 as an envelope protein (VP55), and developed a recombinant STIV expressing an enhanced green fluorescent protein (EGFP) fused to VP55 (EGFP-STIV). Recombinant EGFP-STIV shared similar single-step growth curves and ultrastructural morphology with wild type STIV (wt-STIV). The green fluorescence distribution during EGFP-STIV infection was consistent with the intracellular distribution of VP55 which was mostly co-localized with virus assembly sites. Furthermore, EGFP-STIV could be used to evaluate viral replication conveniently under drug treatment, and the result showed that STIV replication was significantly inhibited after the addition of antioxidant pyrrolidine dithiocarbamate (PDTC). Thus, the EGFP-tagged recombinant iridovirus will not only be useful for further investigations on the viral replicative dynamics, but also provide an alternative simple strategy to screen for antiviral substances. Copyright © 2011 Elsevier B.V. All rights reserved.

SEE locomotor behavior test discriminates C57BL/6J and DBA/2J mouse inbred strains across laboratories and protocol conditions.

PubMed

Kafkafi, Neri; Lipkind, Dina; Benjamini, Yoav; Mayo, Cheryl L; Elmer, Gregory I; Golani, Ilan

2003-06-01

Conventional tests of behavioral phenotyping frequently have difficulties differentiating certain genotypes and replicating these differences across laboratories and protocol conditions. This study explores the hypothesis that automated tests can be designed to quantify ethologically relevant behavior patterns that more readily characterize heritable and replicable phenotypes. It used SEE (Strategy for the Exploration of Exploration) to phenotype the locomotor behavior of the C57BL/6 and DBA/2 mouse inbred strains across 3 laboratories. The 2 genotypes differed in 15 different measures of behavior, none of which had a significant genotype-laboratory interaction. Within the same laboratory, most of these differences were replicated in additional experiments despite the test photoperiod phase being changed and saline being injected. Results suggest that well-designed tests may considerably enhance replicability across laboratories.

Prospects for Oral Replicating Adenovirus-Vectored Vaccines

PubMed Central

Deal, Cailin; Pekosz, Andrew; Ketner, Gary

2013-01-01

Orally delivered replicating adenovirus (Ad) vaccines have been used for decades to prevent adenovirus serotype 4 and 7 respiratory illness in military recruits, demonstrating exemplary safety and high efficacy. That experience suggests that oral administration of live recombinant Ads (rAds) holds promise for immunization against other infectious diseases, including those that have been refractory to traditional vaccination methods. Live rAds can express intact antigens from free-standing transgenes during replication in infected cells. Alternatively, antigenic epitopes can be displayed on the rAd capsid itself, allowing presentation of the epitope to the immune system both prior to and during replication of the virus. Such capsid-display rAds offer a novel vaccine approach that could be used either independently of or in combination with transgene expression strategies to provide a new tool in the search for protection from infectious disease. PMID:23707160

Increased T cell trafficking as adjunct therapy for HIV-1

PubMed Central

Wolinsky, Steven M.; McLean, Angela R.

2018-01-01

Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical model to illustrate a new approach to eliminating the part of the reservoir attributable to persistent replication in drug sanctuaries. Reducing the residency time of CD4 T cells in drug sanctuaries renders ongoing replication unsustainable in those sanctuaries. We hypothesize that, in combination with antiretroviral drugs, a strategy to orchestrate CD4 T cell trafficking could contribute to a functional cure for HIV-1 infection. PMID:29499057

Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission.

PubMed

Ren, Yuwei; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Zhang, Shujun

2017-01-01

Preventing pathogen transmission to a new host is of major interest to the immunologist and could benefit from a detailed investigation of pathogen immune evasion strategies. The first line of defense against pathogen invasion is provided by macrophages. When they sense pathogens, macrophages initiate signals to inflammatory and pro-inflammatory cytokines through pattern recognition receptors (PRRs) subsequently mediating phagocytosis and inflammation. The macrophage immune machinery classically includes two subsets: the activated M1 and the activated M2 that respond accordingly in diverse immune challenges. The lipid and glycogen metabolic pathways work together with the lysosome to help the mature phagosome to degrade and eliminate intracellular pathogens in macrophages. The viral evasion strategies are even more complex due to the interplay between autophagy and apoptosis. However, pathogens evolve several strategies to camouflage themselves against immune responses in order to ensure their survival, replication and transmission. These strategies include the muting of PRRs initiated inflammatory responses, attenuation of M1 and/or induction of M2 macrophages, suppression of autophago-lysosomal formation, interference with lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis cross-talk to enhance viral replication. This review focuses on pathogen immune evasion methods and on the strategies used by the host against camouflaged pathogens.

Concentrated Language Encounter Approach in Practice for Global Teaching of Literacy: Lighthouse Strategy Implementation

ERIC Educational Resources Information Center

Rattanavich, Saowalak

2015-01-01

This article presents the lighthouse literacy strategies model using the concentrated language encounter (CLE) approach that has been successfully replicated in many countries in different languages and cultures. A review of CLE research studies and the project implementation in Thailand showed highly significant results in students' literacy…

A Rapid Assessment of Instructional Strategies to Teach Auditory-Visual Conditional Discriminations to Children with Autism

ERIC Educational Resources Information Center

Kodak, Tiffany; Clements, Andrea; LeBlanc, Brittany

2013-01-01

The purpose of the present investigation was to evaluate a rapid assessment procedure to identify effective instructional strategies to teach auditory-visual conditional discriminations to children diagnosed with autism. We replicated and extended previous rapid skills assessments (Lerman, Vorndran, Addison, & Kuhn, 2004) by evaluating the effects…

Lymph Node Cellular and Viral Dynamics in Natural Hosts and Impact for HIV Cure Strategies.

PubMed

Huot, Nicolas; Bosinger, Steven E; Paiardini, Mirko; Reeves, R Keith; Müller-Trutwin, Michaela

2018-01-01

Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells. Natural hosts of SIV, such as African green monkeys and sooty mangabeys, generally do not progress to disease although displaying persistently high viremia. Strikingly, these hosts mount a strong control of viral replication in LN follicles shortly after peak viremia that lasts throughout infection. Herein, we discuss the potential interplay between viral control in LNs and the resolution of inflammation, which is characteristic for natural hosts. We furthermore detail the differences that exist between non-pathogenic SIV infection in natural hosts and pathogenic HIV/SIV infection in humans and macaques regarding virus target cells and replication dynamics in LNs. Several mechanisms have been proposed to be implicated in the strong control of viral replication in natural host's LNs, such as NK cell-mediated control, that will be reviewed here, together with lessons and limitations of in vivo cell depletion studies that have been performed in natural hosts. Finally, we discuss the impact that these insights on viral dynamics and host responses in LNs of natural hosts have for the development of strategies toward HIV cure.

Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology.

PubMed

Letellier, Carine; Boxus, Mathieu; Rosar, Laurent; Toussaint, Jean-François; Walravens, Karl; Roels, Stefan; Meyer, Gilles; Letesson, Jean-Jacques; Kerkhofs, Pierre

2008-09-02

Respiratory syncytial virus (RSV) is a major cause of respiratory disease in both cattle and young children. Despite the development of vaccines against bovine (B)RSV, incomplete protection and exacerbation of subsequent RSV disease have occurred. In order to circumvent these problems, calves were vaccinated with the nucleocapsid protein, known to be a major target of CD8(+) T cells in cattle. This was performed according to a DNA prime-protein boost strategy. The results showed that DNA vaccination primed a specific T-cell-mediated response, as indicated by both a lymphoproliferative response and IFN-gamma production. These responses were enhanced after protein boost. After challenge, mock-vaccinated calves displayed gross pneumonic lesions and viral replication in the lungs. In contrast, calves vaccinated by successive administrations of plasmid DNA and protein exhibited protection against the development of pneumonic lesions and the viral replication in the BAL fluids and the lungs. The protection correlated to the cell-mediated immunity and not to the antibody response.

Directed evolution of polymerase function by compartmentalized self-replication.

PubMed

Ghadessy, F J; Ong, J L; Holliger, P

2001-04-10

We describe compartmentalized self-replication (CSR), a strategy for the directed evolution of enzymes, especially polymerases. CSR is based on a simple feedback loop consisting of a polymerase that replicates only its own encoding gene. Compartmentalization serves to isolate individual self-replication reactions from each other. In such a system, adaptive gains directly (and proportionally) translate into genetic amplification of the encoding gene. CSR has applications in the evolution of polymerases with novel and useful properties. By using three cycles of CSR, we obtained variants of Taq DNA polymerase with 11-fold higher thermostability than the wild-type enzyme or with a >130-fold increased resistance to the potent inhibitor heparin. Insertion of an extra stage into the CSR cycle before the polymerase reaction allows its application to enzymes other than polymerases. We show that nucleoside diphosphate kinase and Taq polymerase can form such a cooperative CSR cycle based on reciprocal catalysis, whereby nucleoside diphosphate kinase produces the substrates required for the replication of its own gene. We also find that in CSR the polymerase genes themselves evolve toward more efficient replication. Thus, polymerase genes and their encoded polypeptides cooperate to maximize postselection copy number. CSR should prove useful for the directed evolution of enzymes, particularly DNA or RNA polymerases, as well as for the design and study of in vitro self-replicating systems mimicking prebiotic evolution and viral replication.

Role of the Polymerase ϵ sub-unit DPB2 in DNA replication, cell cycle regulation and DNA damage response in Arabidopsis.

PubMed

Pedroza-Garcia, José Antonio; Domenichini, Séverine; Mazubert, Christelle; Bourge, Mickael; White, Charles; Hudik, Elodie; Bounon, Rémi; Tariq, Zakia; Delannoy, Etienne; Del Olmo, Ivan; Piñeiro, Manuel; Jarillo, Jose Antonio; Bergounioux, Catherine; Benhamed, Moussa; Raynaud, Cécile

2016-09-06

Faithful DNA replication maintains genome stability in dividing cells and from one generation to the next. This is particularly important in plants because the whole plant body and reproductive cells originate from meristematic cells that retain their proliferative capacity throughout the life cycle of the organism. DNA replication involves large sets of proteins whose activity is strictly regulated, and is tightly linked to the DNA damage response to detect and respond to replication errors or defects. Central to this interconnection is the replicative polymerase DNA Polymerase ϵ (Pol ϵ) which participates in DNA replication per se, as well as replication stress response in animals and in yeast. Surprisingly, its function has to date been little explored in plants, and notably its relationship with DNA Damage Response (DDR) has not been investigated. Here, we have studied the role of the largest regulatory sub-unit of Arabidopsis DNA Pol ϵ: DPB2, using an over-expression strategy. We demonstrate that excess accumulation of the protein impairs DNA replication and causes endogenous DNA stress. Furthermore, we show that Pol ϵ dysfunction has contrasting outcomes in vegetative and reproductive cells and leads to the activation of distinct DDR pathways in the two cell types. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Endonuclease G promotes mitochondrial genome cleavage and replication

PubMed Central

Wiehe, Rahel Stefanie; Gole, Boris; Chatre, Laurent; Walther, Paul; Calzia, Enrico; Ricchetti, Miria; Wiesmüller, Lisa

2018-01-01

Endonuclease G (EndoG) is a nuclear-encoded endonuclease, mostly localised in mitochondria. In the nucleus EndoG participates in site-specific cleavage during replication stress and genome-wide DNA degradation during apoptosis. However, the impact of EndoG on mitochondrial DNA (mtDNA) metabolism is poorly understood. Here, we investigated whether EndoG is involved in the regulation of mtDNA replication and removal of aberrant copies. We applied the single-cell mitochondrial Transcription and Replication Imaging Protocol (mTRIP) and PCR-based strategies on human cells after knockdown/knockout and re-expression of EndoG. Our analysis revealed that EndoG stimulates both mtDNA replication initiation and mtDNA depletion, the two events being interlinked and dependent on EndoG's nuclease activity. Stimulation of mtDNA replication by EndoG was independent of 7S DNA processing at the replication origin. Importantly, both mtDNA-directed activities of EndoG were promoted by oxidative stress. Inhibition of base excision repair (BER) that repairs oxidative stress-induced DNA damage unveiled a pronounced effect of EndoG on mtDNA removal, reminiscent of recently discovered links between EndoG and BER in the nucleus. Altogether with the downstream effects on mitochondrial transcription, protein expression, redox status and morphology, this study demonstrates that removal of damaged mtDNA by EndoG and compensatory replication play a critical role in mitochondria homeostasis. PMID:29719607

Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements

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

Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex

Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatiblemore » with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.« less

Immunological Prediction of Cytomegalovirus (CMV) Replication Risk in Solid Organ Transplantation Recipients: Approaches for Regulating the Targeted Anti-CMV Prevention Strategies.

PubMed

Han, Sang Hoon

2017-09-01

The current cytomegalovirus (CMV) prevention strategies in solid organ transplantation (SOT) recipients have contributed towards overcoming the detrimental effects caused by CMV lytic infection, and improving the long-term success rate of graft survival. Although the quantification of CMV in peripheral blood is the standard method, and an excellent end-point for diagnosing CMV replication and modulating the anti-CMV prevention strategies in SOT recipients, a novel biomarker mimicking the CMV control mechanism is required. CMV-specific immune monitoring can be employed as a basic tool predicting CMV infection or disease after SOT, since uncontrolled CMV replication mostly originates from the impairment of immune responses against CMV under immunosuppressive conditions in SOT recipients. Several studies conducted during the past few decades have indicated the possibility of measuring the CMV-specific cell-mediated immune response in clinical situations. Among several analytical assays, the most advancing standardized tool is the QuantiFERON®-CMV assay. The T-Track® CMV kit that uses the standardized enzyme-linked immunospot assay is also widely employed. In addition to these assays, immunophenotyping and intracellular cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal antibodies or peptide-major histocompatibility complex multimers) needs to be adequately standardized and validated for potential clinical applications. Copyright © 2017 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy.

Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens

PubMed Central

Meliopoulos, Victoria A.; Andersen, Lauren E.; Birrer, Katherine F.; Simpson, Kaylene J.; Lowenthal, John W.; Bean, Andrew G. D.; Stambas, John; Stewart, Cameron R.; Tompkins, S. Mark; van Beusechem, Victor W.; Fraser, Iain; Mhlanga, Musa; Barichievy, Samantha; Smith, Queta; Leake, Devin; Karpilow, Jon; Buck, Amy; Jona, Ghil; Tripp, Ralph A.

2012-01-01

Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.—Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. PMID:22247330

Verification of immune response optimality through cybernetic modeling.

PubMed

Batt, B C; Kompala, D S

1990-02-09

An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included.

Improvement and Optimization of Two Engineered Phage Resistance Mechanisms in Lactococcus lactis

PubMed Central

McGrath, Stephen; Fitzgerald, Gerald F.; van Sinderen, Douwe

2001-01-01

Homologous replication module genes were identified for four P335 type phages. DNA sequence analysis revealed that all four phages exhibited more than 90% DNA homology for at least two genes, designated rep2009 and orf17. One of these genes, rep2009, codes for a putative replisome organizer protein and contains an assumed origin of phage DNA replication (ori2009), which was identical for all four phages. DNA fragments representing the ori2009 sequence confer a phage-encoded resistance (Per) phenotype on lactococcal hosts when they are supplied on a high-copy-number vector. Furthermore, cloning multiple copies of the ori2009 sequence was found to increase the effectiveness of the Per phenotype conferred. A number of antisense plasmids targeting specific genes of the replication module were constructed. Two separate plasmids targeting rep2009 and orf17 were found to efficiently inhibit proliferation of all four phages by interfering with intracellular phage DNA replication. These results represent two highly effective strategies for inhibiting bacteriophage proliferation, and they also identify a novel gene, orf17, which appears to be important for phage DNA replication. Furthermore, these results indicate that although the actual mechanisms of DNA replication are very similar, if not identical, for all four phages, expression of the replication genes is significantly different in each case. PMID:11157223

The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

PubMed

Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

2013-12-01

Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

Narrative-compression coding for a channel with errors. Professional paper for period ending June 1987

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

Bond, J.W.

1988-01-01

Data-compression codes offer the possibility of improving the thruput of existing communication systems in the near term. This study was undertaken to determine if data-compression codes could be utilized to provide message compression in a channel with up to a 0.10-bit error rate. The data-compression capabilities of codes were investigated by estimating the average number of bits-per-character required to transmit narrative files. The performance of the codes in a channel with errors (a noisy channel) was investigated in terms of the average numbers of characters-decoded-in-error and of characters-printed-in-error-per-bit-error. Results were obtained by encoding four narrative files, which were resident onmore » an IBM-PC and use a 58-character set. The study focused on Huffman codes and suffix/prefix comma-free codes. Other data-compression codes, in particular, block codes and some simple variants of block codes, are briefly discussed to place the study results in context. Comma-free codes were found to have the most-promising data compression because error propagation due to bit errors are limited to a few characters for these codes. A technique was found to identify a suffix/prefix comma-free code giving nearly the same data compressions as a Huffman code with much less error propagation than the Huffman codes. Greater data compression can be achieved through the use of this comma-free code word assignments based on conditioned probabilities of character occurrence.« less

Morphological and ultrastructural characterization of ionoregulatory cells in the teleost Oreochromis niloticus following salinity challenge combining complementary confocal scanning laser microscopy and transmission electron microscopy using a novel prefixation immunogold labeling technique.

PubMed

Fridman, Sophie; Rana, Krishen J; Bron, James E

2013-10-01

Aspects of ionoregulatory or mitochondria-rich cell (MRC) differentiation and adaptation in Nile tilapia yolk-sac larvae following transfer from freshwater to elevated salinities, that is, 12.5 and 20 ppt are described. Investigations using immunohistochemistry on whole-mount Nile tilapia larvae using anti- Na⁺/K⁺-ATPase as a primary antibody and Fluoronanogold™ (Nanoprobes) as a secondary immunoprobe allowed fluorescent labeling with the high resolution of confocal scanning laser microscopy combined with the detection of immunolabeled target molecules at an ultrastructural level using transmission electron microscopy (TEM). It reports, for the first time, various developmental stages of MRCs within the epithelial layer of the tail of yolk-sac larvae, corresponding to immature, developing, and mature MRCs, identifiable by their own characteristic ultrastructure and form. Following transfer to hyperosmotic salinities the density of immunogold particles and well as the intricacy of the tubular system appeared to increase. In addition, complementary confocal scanning laser microscopy allowed identification of immunopositive ramifying extensions that appeared to emanate from the basolateral portion of the cell that appeared to be correlated with the localization of subsurface tubular areas displaying immunogold labeled Na⁺/K⁺-ATPase. This integrated approach describes a reliable and repeatable prefixation immunogold labeling technique allowing precise visualization of NaK within target cells combined with a 3D imaging that offers valuable insights into MRC dynamics at an ultrastructural level. Copyright © 2013 Wiley Periodicals, Inc.

The role of technical assistance in the replication of effective HIV interventions.

PubMed

O'Donnell, L; Scattergood, P; Adler, M; Doval, A S; Barker, M; Kelly, J A; Kegeles, S M; Rebchook, G M; Adams, J; Terry, M A; Neumann, M S

2000-01-01

This article examines the role of technical assistance (TA) in supporting the replication of proven HIV interventions. A case study of the replication of the VOICES/VOCES intervention elucidates the level and types of TA provided to support new users through the adoption process. TA included help in garnering administrative support, identifying target audiences, recruiting groups for sessions, maintaining fidelity to the intervention's core elements, tailoring the intervention to meet clients' needs, strengthening staff members' facilitation skills, troubleshooting challenges, and devising strategies to sustain the intervention. Two to four hours per month of TA were provided to each agency adopting the intervention, at an estimated monthly cost of $206 to $412. Findings illustrate how TA supports replication by establishing a conversation between the researcher TA providers experienced with the intervention and new users. This communication helps preserve key program elements and contributes to ongoing refinement of the intervention.

The plant cell cycle: Pre-Replication complex formation and controls

PubMed Central

Brasil, Juliana Nogueira; Costa, Carinne N. Monteiro; Cabral, Luiz Mors; Ferreira, Paulo C. G.; Hemerly, Adriana S.

2017-01-01

Abstract The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes. PMID:28304073

The right half of the Escherichia coli replication origin is not essential for viability, but facilitates multi-forked replication

PubMed Central

Stepankiw, Nicholas; Kaidow, Akihiro; Boye, Erik; Bates, David

2010-01-01

Summary Replication initiation is a key event in the cell cycle of all organisms and oriC, the replication origin in Escherichia coli, serves as the prototypical model for this process. The minimal sequence required for oriC function was originally determined entirely from plasmid studies using cloned origin fragments, which have previously been shown to differ dramatically in sequence requirement from the chromosome. Using an in vivo recombineering strategy to exchange wt oriCs for mutated ones regardless of whether they are functional origins or not, we have determined the minimal origin sequence that will support chromosome replication. Nearly the entire right half of oriC could be deleted without loss of origin function, demanding a reassessment of existing models for initiation. Cells carrying the new DnaA box-depleted 163 bp minimal oriC exhibited little or no loss of fitness under slow-growth conditions, but were sensitive to rich medium, suggesting that the dense packing of initiator binding sites that is a hallmark of prokaryotic origins, has likely evolved to support the increased demands of multi-forked replication. PMID:19737351

Empowering Teachers with Low-Intensity Strategies to Support Instruction: Self-Monitoring in an Elementary Resource Classroom

ERIC Educational Resources Information Center

Ennis, Robin Parks; Lane, Kathleen Lynne; Oakes, Wendy Peia

2018-01-01

Self-monitoring is a low-intensity strategy teachers can use to support instruction in classrooms across the grade span in various instructional settings and content areas. This study extended the knowledge base by examining the effectiveness of self-monitoring through a systematic replication with three students with specific learning…

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing

PubMed Central

2012-01-01

Background RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Results Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. Conclusions This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates. PMID:22985019

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing.

PubMed

Robles, José A; Qureshi, Sumaira E; Stephen, Stuart J; Wilson, Susan R; Burden, Conrad J; Taylor, Jennifer M

2012-09-17

RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates.

Novel host restriction factors implicated in HIV-1 replication.

PubMed

Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

2018-04-01

Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

Role of DNA Repair Factor Xeroderma Pigmentosum Protein Group C in Response to Replication Stress As Revealed by DNA Fragile Site Affinity Chromatography and Quantitative Proteomics.

PubMed

Beresova, Lucie; Vesela, Eva; Chamrad, Ivo; Voller, Jiri; Yamada, Masayuki; Furst, Tomas; Lenobel, Rene; Chroma, Katarina; Gursky, Jan; Krizova, Katerina; Mistrik, Martin; Bartek, Jiri

2016-12-02

Replication stress (RS) fuels genomic instability and cancer development and may contribute to aging, raising the need to identify factors involved in cellular responses to such stress. Here, we present a strategy for identification of factors affecting the maintenance of common fragile sites (CFSs), which are genomic loci that are particularly sensitive to RS and suffer from increased breakage and rearrangements in tumors. A DNA probe designed to match the high flexibility island sequence typical for the commonly expressed CFS (FRA16D) was used as specific DNA affinity bait. Proteins significantly enriched at the FRA16D fragment under normal and replication stress conditions were identified using stable isotope labeling of amino acids in cell culture-based quantitative mass spectrometry. The identified proteins interacting with the FRA16D fragment included some known CFS stabilizers, thereby validating this screening approach. Among the hits from our screen so far not implicated in CFS maintenance, we chose Xeroderma pigmentosum protein group C (XPC) for further characterization. XPC is a key factor in the DNA repair pathway known as global genomic nucleotide excision repair (GG-NER), a mechanism whose several components were enriched at the FRA16D fragment in our screen. Functional experiments revealed defective checkpoint signaling and escape of DNA replication intermediates into mitosis and the next generation of XPC-depleted cells exposed to RS. Overall, our results provide insights into an unexpected biological role of XPC in response to replication stress and document the power of proteomics-based screening strategies to elucidate mechanisms of pathophysiological significance.

34 CFR 611.11 - What are the program's general selection criteria?

Code of Federal Regulations, 2011 CFR

2011-07-01

...; (ii) Project outcomes lead directly to improvements in teaching quality and student achievement as... after federal funding ends; and (iv) Project strategies, methods, and accomplishments are replicable...

Sleeping Beauty transposon-based system for rapid generation of HBV-replicating stable cell lines.

PubMed

Wu, Yong; Zhang, Tian-Ying; Fang, Lin-Lin; Chen, Zi-Xuan; Song, Liu-Wei; Cao, Jia-Li; Yang, Lin; Yuan, Quan; Xia, Ning-Shao

2016-08-01

The stable HBV-replicating cell lines, which carry replication-competent HBV genome stably integrated into the genome of host cell, are widely used to evaluate the effects of antiviral agents. However, current methods to generate HBV-replicating cell lines, which are mostly dependent on random integration of foreign DNA via plasmid transfection, are less-efficient and time-consuming. To address this issue, we constructed an all-in-one Sleeping Beauty transposon system (denoted pTSMP-HBV vector) for robust generation of stable cell lines carrying replication-competent HBV genome of different genotype. This vector contains a Sleeping Beauty transposon containing HBV 1.3-copy genome with an expression cassette of the SV40 promoter driving red fluorescent protein (mCherry) and self-cleaving P2A peptide linked puromycin resistance gene (PuroR). In addition, a PGK promoter-driven SB100X hyperactive transposase cassette is placed in the outside of the transposon in the same plasmid.The HBV-replicating stable cells could be obtained from pTSMP-HBV transfected HepG2 cells by red fluorescence-activated cell sorting and puromycin resistant cell selection within 4-week. Using this system, we successfully constructed four cell lines carrying replication-competent HBV genome of genotypes A-D. The replication and viral protein expression profiles of these cells were systematically characterized. In conclusion, our study provides a high-efficiency strategy to generate HBV-replicating stable cell lines, which may facilitate HBV-related virological study. Copyright © 2016. Published by Elsevier B.V.

Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

PubMed

Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

2017-05-09

Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

A replacement name for Thomasella Santos-Silva, Bezark Martins (Coleoptera, Cerambycidae, Cerambycinae).

PubMed

Santos-Silva, Antonio; Bezark, Larry G

2018-03-14

        Santos-Silva et al. (2012) described Thomasella as a new genus of Rhinotragini to include a single species from Panama: Ommata (Eclipta) igniventris Giesbert, 1991. However, Thomasella is a junior homonym of Thomasella Fredericks, 1928 (Brachiopoda). To resolve this homonym, in accordance with the International Code of Zoological Nomenclature, we are proposing Neothomasella as a new replacement name (nomen novum) for Thomasella Santos-Silva et al. (2012). The new name is a compound of the prefix "neo-" (from Greek νεο-, meaning "new") + Thomasella; feminine gender.

Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation Machinery as a Strategy for Co-opting Host Cell Protein Synthesis.

PubMed

Reid, David W; Campos, Rafael K; Child, Jessica R; Zheng, Tianli; Chan, Kitti Wing Ki; Bradrick, Shelton S; Vasudevan, Subhash G; Garcia-Blanco, Mariano A; Nicchitta, Christopher V

2018-04-01

A primary question in dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here, we combined cell fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation. DENV infection was accompanied by an ER compartment-specific remodeling of translation, where ER translation capacity was subverted from host transcripts to DENV plus-strand RNA, particularly at late stages of infection. Remarkably, translation levels and patterns in the cytosol compartment were only modestly affected throughout the experimental time course of infection. Comparisons of ribosome footprinting densities of the DENV plus-strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely loaded with ribosomes. Combined, these observations suggest a mechanism where ER-localized translation and translational control mechanisms, likely cis encoded, are used to repurpose the ER for DENV virion production. Consistent with this view, we found ER-linked cellular stress response pathways commonly associated with viral infection, namely, the interferon response and unfolded protein response, to be only modestly activated during DENV infection. These data support a model where DENV reprograms the ER protein synthesis and processing environment to promote viral survival and replication while minimizing the activation of antiviral and proteostatic stress response pathways. IMPORTANCE DENV, a prominent human health threat with no broadly effective or specific treatment, depends on host cell translation machinery for viral replication, immune evasion, and virion biogenesis. The molecular mechanism by which DENV commandeers the host cell protein synthesis machinery and the subcellular organization of DENV replication and viral protein synthesis is poorly understood. Here, we report that DENV has an almost exclusively ER-localized life cycle, with viral replication and translation largely restricted to the ER. Surprisingly, DENV infection largely affects only ER-associated translation, with relatively modest effects on host cell translation in the cytosol. DENV RNA translation is very inefficient, likely representing a strategy to minimize disruption of ER proteostasis. Overall these findings demonstrate that DENV has evolved an ER-compartmentalized life cycle; thus, targeting the molecular signatures and regulation of the DENV-ER interaction landscape may reveal strategies for therapeutic intervention. Copyright © 2018 American Society for Microbiology.

How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery

PubMed Central

Bordignon, Valentina; Trento, Elisabetta; D’Agosto, Giovanna; Cavallo, Ilaria; Pontone, Martina; Pimpinelli, Fulvia; Mariani, Luciano; Ensoli, Fabrizio

2017-01-01

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM- and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)–STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses. PMID:29257060

Enterovirus 3A Facilitates Viral Replication by Promoting Phosphatidylinositol 4-Kinase IIIβ–ACBD3 Interaction

PubMed Central

Xiao, Xia; Lei, Xiaobo; Zhang, Zhenzhen; Ma, Yijie; Qi, Jianli; Wu, Chao; Xiao, Yan; Li, Li

2017-01-01

ABSTRACT Like other enteroviruses, enterovirus 71 (EV71) relies on phosphatidylinositol 4-kinase IIIβ (PI4KB) for genome RNA replication. However, how PI4KB is recruited to the genome replication sites of EV71 remains elusive. Recently, we reported that a host factor, ACBD3, is needed for EV71 replication by interacting with viral 3A protein. Here, we show that ACBD3 is required for the recruitment of PI4KB to RNA replication sites. Overexpression of viral 3A or EV71 infection stimulates the interaction of PI4KB and ACBD3. Consistently, EV71 infection induces the production of phosphatidylinositol-4-phosphate (PI4P). Furthermore, PI4KB, ACBD3, and 3A are all localized to the viral-RNA replication sites. Accordingly, PI4KB or ACBD3 depletion by small interfering RNA (siRNA) leads to a reduction in PI4P production after EV71 infection. I44A or H54Y substitution in 3A interrupts the stimulation of PI4KB and ACBD3. Further analysis suggests that stimulation of ACBD3-PI4KB interaction is also important for the replication of enterovirus 68 but disadvantageous to human rhinovirus 16. These results reveal a mechanism of enterovirus replication that involves a selective strategy for recruitment of PI4KB to the RNA replication sites. IMPORTANCE Enterovirus 71, like other human enteroviruses, replicates its genome within host cells, where viral proteins efficiently utilize cellular machineries. While multiple factors are involved, it is largely unclear how viral replication is controlled. We show that the 3A protein of enterovirus 71 recruits an enzyme, phosphatidylinositol 4-kinase IIIβ, by interacting with ACBD3, which alters cellular membranes through the production of a lipid, PI4P. Consequently, the viral and host proteins form a large complex that is necessary for RNA synthesis at replication sites. Notably, PI4KB-ACBD3 interaction also differentially mediates the replication of enterovirus 68 and rhinovirus 16. These results provide new insight into the molecular network of enterovirus replication. PMID:28701404

Economic Evaluation of Pharmacologic Pre- and Postconditioning With Sevoflurane Compared With Total Intravenous Anesthesia in Liver Surgery: A Cost Analysis.

PubMed

Eichler, Klaus; Urner, Martin; Twerenbold, Claudia; Kern, Sabine; Brügger, Urs; Spahn, Donat R; Beck-Schimmer, Beatrice; Ganter, Michael T

2017-03-01

Pharmacologic pre- and postconditioning with sevoflurane compared with total IV anesthesia in patients undergoing liver surgery reduced complication rates as shown in 2 recent randomized controlled trials. However, the potential health economic consequences of these different anesthesia regimens have not yet been assessed. An expostcost analysis of these 2 trials in 129 patients treated between 2006 and 2010 was performed. We analyzed direct medical costs for in-hospital stay and compared pharmacologic pre- and postconditioning with sevoflurane (intervention) with total IV anesthesia (control) from the perspective of a Swiss university hospital. Year 2015 costs, converted to US dollars, were derived from hospital cost accounting data and compared with a multivariable regression analysis adjusting for relevant covariables. Costs with negative prefix indicate savings and costs with positive prefix represent higher spending in our analysis. Treatment-related costs per patient showed a nonsignificant change by -12,697 US dollars (95% confidence interval [CI], 10,956 to -36,352; P = .29) with preconditioning and by -6139 US dollars (95% CI, 6723 to -19,000; P = .35) with postconditioning compared with the control group. Results were robust in our sensitivity analysis. For both procedures (control and intervention) together, major complications led to a significant increase in costs by 86,018 US dollars (95% CI, 13,839-158,198; P = .02) per patient compared with patients with no major complications. In this cost analysis, reduced in-hospital costs by pharmacologic conditioning with sevoflurane in patients undergoing liver surgery are suggested. This possible difference in costs compared with total IV anesthesia is the result of reduced complication rates with pharmacologic conditioning, because major complications have significant cost implications.

Economic Evaluation of Pharmacologic Pre- and Postconditioning With Sevoflurane Compared With Total Intravenous Anesthesia in Liver Surgery: A Cost Analysis

PubMed Central

Urner, Martin; Twerenbold, Claudia; Kern, Sabine; Brügger, Urs; Spahn, Donat R.; Beck-Schimmer, Beatrice; Ganter, Michael T.

2017-01-01

BACKGROUND: Pharmacologic pre- and postconditioning with sevoflurane compared with total IV anesthesia in patients undergoing liver surgery reduced complication rates as shown in 2 recent randomized controlled trials. However, the potential health economic consequences of these different anesthesia regimens have not yet been assessed. METHODS: An expostcost analysis of these 2 trials in 129 patients treated between 2006 and 2010 was performed. We analyzed direct medical costs for in-hospital stay and compared pharmacologic pre- and postconditioning with sevoflurane (intervention) with total IV anesthesia (control) from the perspective of a Swiss university hospital. Year 2015 costs, converted to US dollars, were derived from hospital cost accounting data and compared with a multivariable regression analysis adjusting for relevant covariables. Costs with negative prefix indicate savings and costs with positive prefix represent higher spending in our analysis. RESULTS: Treatment-related costs per patient showed a nonsignificant change by −12,697 US dollars (95% confidence interval [CI], 10,956 to −36,352; P = .29) with preconditioning and by −6139 US dollars (95% CI, 6723 to −19,000; P = .35) with postconditioning compared with the control group. Results were robust in our sensitivity analysis. For both procedures (control and intervention) together, major complications led to a significant increase in costs by 86,018 US dollars (95% CI, 13,839-158,198; P = .02) per patient compared with patients with no major complications. CONCLUSIONS: In this cost analysis, reduced in-hospital costs by pharmacologic conditioning with sevoflurane in patients undergoing liver surgery are suggested. This possible difference in costs compared with total IV anesthesia is the result of reduced complication rates with pharmacologic conditioning, because major complications have significant cost implications. PMID:28067701

RNA N6-adenosine methylation (m6A) steers epitranscriptomic control of herpesvirus replication

PubMed Central

Ye, Fengchun

2017-01-01

Latency is a hallmark of all herpesviruses, during which the viral genomes are silenced through DNA methylation and suppressive histone modifications. When latent herpesviruses reactivate to undergo productive lytic replication, the suppressive epigenetic marks are replaced with active ones to allow for transcription of viral genes. Interestingly, by using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model, we recently demonstrated that the newly transcribed viral RNAs are also subjected to post-transcriptional N6-adenosine methylation (m6A). Blockade of this post-transcriptional event abolishes viral protein expression and halts virion production. We found that m6A modification controls RNA splicing, stability, and protein translation to regulate viral lytic gene expression and replication. Thus, our finding for the first time reveals a critical role of this epitranscriptomic mechanism in the control of herpesviral replication, which shall shed lights on development of novel strategies for the control of herpesviral infection. PMID:29082271

Genome Cyclization as Strategy for Flavivirus RNA Replication

PubMed Central

Villordo, Sergio M.; Gamarnik, Andrea V.

2017-01-01

Long-range and local RNA-RNA contacts in viral RNA genomes result in tertiary structures that modulate the function of enhancers, promoters, and silencers during translation, RNA replication, and encapsidation. In the case of flaviviruses, the presence of inverted complementary sequences at the 5′ and 3′ ends of the genome mediate long-range RNA interactions and RNA cyclization. The circular conformation of flavivirus genomes was demonstrated to be essential for RNA amplification. New ideas about the mechanisms by which circular genomes participate in flavivirus replication have emerged in the last few years. Here, we will describe the latest information about cis-acting elements involved in flavivirus genome cyclization, RNA promoter elements required for viral polymerase recognition, and how these elements together coordinate viral RNA synthesis. PMID:18703097

Ferret airway epithelial cell cultures support efficient replication of influenza B virus but not mumps virus.

PubMed

Elderfield, Ruth A; Parker, Lauren; Stilwell, Peter; Roberts, Kim L; Schepelmann, Silke; Barclay, Wendy S

2015-08-01

Ferrets have become the model animal of choice for influenza pathology and transmission experiments as they are permissive and susceptible to human influenza A viruses. However, inoculation of ferrets with mumps virus (MuV) did not lead to successful infections. We evaluated the use of highly differentiated ferret tracheal epithelium cell cultures, FTE, for predicting the potential of ferrets to support respiratory viral infections. FTE cultures supported productive replication of human influenza A and B viruses but not of MuV, whereas analogous cells generated from human airways supported replication of all three viruses. We propose that in vitro strategies using these cultures might serve as a method of triaging viruses and potentially reducing the use of ferrets in viral studies.

Novel Chromosome Organization Pattern in Actinomycetales-Overlapping Replication Cycles Combined with Diploidy.

PubMed

Böhm, Kati; Meyer, Fabian; Rhomberg, Agata; Kalinowski, Jörn; Donovan, Catriona; Bramkamp, Marc

2017-06-06

Bacteria regulate chromosome replication and segregation tightly with cell division to ensure faithful segregation of DNA to daughter generations. The underlying mechanisms have been addressed in several model species. It became apparent that bacteria have evolved quite different strategies to regulate DNA segregation and chromosomal organization. We have investigated here how the actinobacterium Corynebacterium glutamicum organizes chromosome segregation and DNA replication. Unexpectedly, we found that C. glutamicum cells are at least diploid under all of the conditions tested and that these organisms have overlapping C periods during replication, with both origins initiating replication simultaneously. On the basis of experimental data, we propose growth rate-dependent cell cycle models for C. glutamicum IMPORTANCE Bacterial cell cycles are known for few model organisms and can vary significantly between species. Here, we studied the cell cycle of Corynebacterium glutamicum , an emerging cell biological model organism for mycolic acid-containing bacteria, including mycobacteria. Our data suggest that C. glutamicum carries two pole-attached chromosomes that replicate with overlapping C periods, thus initiating a new round of DNA replication before the previous one is terminated. The newly replicated origins segregate to midcell positions, where cell division occurs between the two new origins. Even after long starvation or under extremely slow-growth conditions, C. glutamicum cells are at least diploid, likely as an adaptation to environmental stress that may cause DNA damage. The cell cycle of C. glutamicum combines features of slow-growing organisms, such as polar origin localization, and fast-growing organisms, such as overlapping C periods. Copyright © 2017 Böhm et al.

Theoretical models for the regulation of DNA replication in fast-growing bacteria

NASA Astrophysics Data System (ADS)

Creutziger, Martin; Schmidt, Mischa; Lenz, Peter

2012-09-01

Growing in always changing environments, Escherichia coli cells are challenged by the task to coordinate growth and division. In particular, adaption of their growth program to the surrounding medium has to guarantee that the daughter cells obtain fully replicated chromosomes. Replication is therefore to be initiated at the right time, which is particularly challenging in media that support fast growth. Here, the mother cell initiates replication not only for the daughter but also for the granddaughter cells. This is possible only if replication occurs from several replication forks that all need to be correctly initiated. Despite considerable efforts during the last 40 years, regulation of this process is still unknown. Part of the difficulty arises from the fact that many details of the relevant molecular processes are not known. Here, we develop a novel theoretical strategy for dealing with this general problem: instead of analyzing a single model, we introduce a wide variety of 128 different models that make different assumptions about the unknown processes. By comparing the predictions of these models we are able to identify the key quantities that allow the experimental discrimination of the different models. Analysis of these quantities yields that out of the 128 models 94 are not consistent with available experimental data. From the remaining 34 models we are able to conclude that mass growth and DNA replication need either to be truly coupled, by coupling DNA replication initiation to the event of cell division, or to the amount of accumulated mass. Finally, we make suggestions for experiments to further reduce the number of possible regulation scenarios.

Targeting eukaryotic Rab proteins: a smart strategy for chlamydial survival and replication.

PubMed

Damiani, María Teresa; Gambarte Tudela, Julián; Capmany, Anahí

2014-09-01

Chlamydia, an obligate intracellular bacterium which passes its entire lifecycle within a membrane-bound vacuole called the inclusion, has evolved a variety of unique strategies to establish an advantageous intracellular niche for survival. This review highlights the mechanisms by which Chlamydia subverts vesicular transport in host cells, particularly by hijacking the master controllers of eukaryotic trafficking, the Rab proteins. A subset of Rabs and Rab interacting proteins that control the recycling pathway or the biosynthetic route are selectively recruited to the chlamydial inclusion membrane. By interfering with Rab-controlled transport steps, this intracellular pathogen not only prevents its own degradation in the phagocytic pathway, but also creates a favourable intracellular environment for growth and replication. Chlamydia, a highly adapted and successful intracellular pathogen, has several redundant strategies to re-direct vesicles emerging from biosynthetic compartments that carry host molecules essential for bacterial development. Although current knowledge is limited, the latest findings have shed light on the role of Rab proteins in the course of chlamydial infections and could open novel opportunities for anti-chlamydial therapy. © 2014 John Wiley & Sons Ltd.

Shifts in growth strategies reflect tradeoffs in cellular economics

PubMed Central

Molenaar, Douwe; van Berlo, Rogier; de Ridder, Dick; Teusink, Bas

2009-01-01

The growth rate-dependent regulation of cell size, ribosomal content, and metabolic efficiency follows a common pattern in unicellular organisms: with increasing growth rates, cell size and ribosomal content increase and a shift to energetically inefficient metabolism takes place. The latter two phenomena are also observed in fast growing tumour cells and cell lines. These patterns suggest a fundamental principle of design. In biology such designs can often be understood as the result of the optimization of fitness. Here we show that in basic models of self-replicating systems these patterns are the consequence of maximizing the growth rate. Whereas most models of cellular growth consider a part of physiology, for instance only metabolism, the approach presented here integrates several subsystems to a complete self-replicating system. Such models can yield fundamentally different optimal strategies. In particular, it is shown how the shift in metabolic efficiency originates from a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The models elucidate how the optimization of growth by natural selection shapes growth strategies. PMID:19888218

Minority games, evolving capitals and replicator dynamics

NASA Astrophysics Data System (ADS)

Galla, Tobias; Zhang, Yi-Cheng

2009-11-01

We discuss a simple version of the minority game (MG) in which agents hold only one strategy each, but in which their capitals evolve dynamically according to their success and in which the total trading volume varies in time accordingly. This feature is known to be crucial for MGs to reproduce stylized facts of real market data. The stationary states and phase diagram of the model can be computed, and we show that the ergodicity breaking phase transition common for MGs, and marked by a divergence of the integrated response, is present also in this simplified model. An analogous majority game turns out to be relatively void of interesting features, and the total capital is found to diverge in time. Introducing a restraining force leads to a model akin to the replicator dynamics of evolutionary game theory, and we demonstrate that here a different type of phase transition is observed. Finally we briefly discuss the relation of this model with one strategy per player to more sophisticated minority games with dynamical capitals and several trading strategies per agent.

Mask replication using jet and flash imprint lithography

NASA Astrophysics Data System (ADS)

Selinidis, Kosta S.; Jones, Chris; Doyle, Gary F.; Brown, Laura; Imhof, Joseph; LaBrake, Dwayne L.; Resnick, Douglas J.; Sreenivasan, S. V.

2011-11-01

The Jet and Flash Imprint Lithography (J-FILTM) process uses drop dispensing of UV curable resists to assist high resolution patterning for subsequent dry etch pattern transfer. The technology is actively being used to develop solutions for memory markets including Flash memory and patterned media for hard disk drives. It is anticipated that the lifetime of a single template (for patterned media) or mask (for semiconductor) will be on the order of 104 - 105imprints. This suggests that tens of thousands of templates/masks will be required to satisfy the needs of a manufacturing environment. Electron-beam patterning is too slow to feasibly deliver these volumes, but instead can provide a high quality "master" mask which can be replicated many times with an imprint lithography tool. This strategy has the capability to produce the required supply of "working" templates/masks. In this paper, we review the development of the mask form factor, imprint replication tools and the semiconductor mask replication process. A PerfectaTM MR5000 mask replication tool has been developed specifically to pattern replica masks from an ebeam written master. Performance results, including image placement, critical dimension uniformity, and pattern transfer are covered in detail.

Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

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

Huang, Hanxia; Falgout, Barry; Takeda, Kazuyo

We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retardingmore » ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. - Highlights: •Hemin treatment protected monocyte-derived macrophages against Zika virus (ZIKV) infection. •Innate cellular protection against ZIKV infection correlated with Nrf2-dependent HO-1 expression. •Stimulation of innate cellular responses may provide a therapeutic strategy against ZIKV infection.« less

How MCM loading and spreading specify eukaryotic DNA replication initiation sites.

PubMed

Hyrien, Olivier

2016-01-01

DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb) non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs), the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC), they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes.

FAMILY TYMOVIRIDAE

USDA-ARS?s Scientific Manuscript database

This article provides a brief review of the taxonomic structure, virion properties, genome organization and replication strategy, antigenic properties, and biological properties of viruses in the family Tymoviridae. Criteria for demarcation of genus and species are provided. A brief review of each...

Single-stranded DNA and RNA origami.

PubMed

Han, Dongran; Qi, Xiaodong; Myhrvold, Cameron; Wang, Bei; Dai, Mingjie; Jiang, Shuoxing; Bates, Maxwell; Liu, Yan; An, Byoungkwon; Zhang, Fei; Yan, Hao; Yin, Peng

2017-12-15

Self-folding of an information-carrying polymer into a defined structure is foundational to biology and offers attractive potential as a synthetic strategy. Although multicomponent self-assembly has produced complex synthetic nanostructures, unimolecular folding has seen limited progress. We describe a framework to design and synthesize a single DNA or RNA strand to self-fold into a complex yet unknotted structure that approximates an arbitrary user-prescribed shape. We experimentally construct diverse multikilobase single-stranded structures, including a ~10,000-nucleotide (nt) DNA structure and a ~6000-nt RNA structure. We demonstrate facile replication of the strand in vitro and in living cells. The work here thus establishes unimolecular folding as a general strategy for constructing complex and replicable nucleic acid nanostructures, and expands the design space and material scalability for bottom-up nanotechnology. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A Rab-centric perspective of bacterial pathogen-occupied vacuoles.

PubMed

Sherwood, Racquel Kim; Roy, Craig R

2013-09-11

The ability to create and maintain a specialized organelle that supports bacterial replication is an important virulence property for many intracellular pathogens. Living in a membrane-bound vacuole presents inherent challenges, including the need to remodel a plasma membrane-derived organelle into a novel structure that will expand and provide essential nutrients to support replication, while also having the vacuole avoid membrane transport pathways that target bacteria for destruction in lysosomes. It is clear that pathogenic bacteria use different strategies to accomplish these tasks. The dynamics by which host Rab GTPases associate with pathogen-occupied vacuoles provide insight into the mechanisms used by different bacteria to manipulate host membrane transport. In this review we highlight some of the strategies bacteria use to maintain a pathogen-occupied vacuole by focusing on the Rab proteins involved in biogenesis and maintenance of these novel organelles. Copyright © 2013 Elsevier Inc. All rights reserved.

A systematic approach to the development of a safe live attenuated Zika vaccine.

PubMed

Kwek, Swee Sen; Watanabe, Satoru; Chan, Kuan Rong; Ong, Eugenia Z; Tan, Hwee Cheng; Ng, Wy Ching; Nguyen, Mien T X; Gan, Esther S; Zhang, Summer L; Chan, Kitti W K; Tan, Jun Hao; Sessions, October M; Manuel, Menchie; Pompon, Julien; Chua, Camillus; Hazirah, Sharifah; Tryggvason, Karl; Vasudevan, Subhash G; Ooi, Eng Eong

2018-03-12

Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.

Point of a space experiment proposal.

PubMed

Fukui, Keiji; Shimazu, Toru; Higashibata, Akira; Fujimoto, Nobuyoshi; Ishioka, Noriaki

2003-10-01

JAXA will solicit research proposals for space flight experiments that would be conducted for less than three years after the selection. In principle, available samples will be limited to Arabidopsis and C. elegans and flight hardware and protocol of space flight experiment will be pre-fixed. Proposals using different combinations of species and flight hardware will not be acceptable. Besides scientific issues, it is very important for proposer to write an impressive proposal. Hypothesis basis research proposal is the accepted standard. Reviewers will dislike a descriptive and unfocused research proposal without hypothesis. Ground preparation experiments, which are not related directly to space experiments, should not be included in the solicitation.

Etymology as an Aid to Understanding Chemistry Concepts

NASA Astrophysics Data System (ADS)

Sarma, Nittala S.

2004-10-01

Recognition of word roots and the pattern of evolution of scientific terms can be helpful in understanding chemistry concepts (gaining knowledge of new concepts represented by related terms). The meaning and significance of various etymological roots, occurring as prefixes and suffixes in technical terms particularly of organic chemistry, are explained in a unified manner in order to show the connection of various concepts vis à vis the terms in currency. The meanings of some special words and many examples are provided. The interesting aspects of history and culture often involved in the evolution of terms will help sustain an abiding engagement in the study of chemistry.

Zadoff-Chu sequence-based hitless ranging scheme for OFDMA-PON configured 5G fronthaul uplinks

NASA Astrophysics Data System (ADS)

Reza, Ahmed Galib; Rhee, June-Koo Kevin

2017-05-01

A Zadoff-Chu (ZC) sequence-based low-complexity hitless upstream time synchronization scheme is proposed for an orthogonal frequency division multiple access passive optical network configured cloud radio access network fronthaul. The algorithm is based on gradual loading of the ZC sequences, where the phase discontinuity due to the cyclic prefix is alleviated by a frequency domain phase precoder, eliminating the requirements of guard bands to mitigate intersymbol interference and inter-carrier interference. Simulation results for uncontrolled-wavelength asynchronous transmissions from four concurrent transmitting optical network units are presented to demonstrate the effectiveness of the proposed scheme.

The Building Assets-Reducing Risks Program: Replication and Expansion of an Effective Strategy to Turn Around Low-Achieving Schools. i3 Development Grant. Final Report

ERIC Educational Resources Information Center

Corsello, Maryann; Sharma, Anu

2015-01-01

The Building Assets Reducing Risks (BARR) Model BARR is a comprehensive model that addresses the challenges that are part of the 9th grade transition year. BARR employs eight different school-wide and individual strategies that are built on positive relationships and ongoing monitoring of student data. In 2010, BARR received an Investing in…

Checkpoint independence of most DNA replication origins in fission yeast

PubMed Central

Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A

2007-01-01

Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in checkpoint-mutant cells. Conclusion The fact that ~97% of fission yeast replication origins – both early and late – are not significantly affected by replication checkpoint mutations in HU-treated cells suggests that (i) most late-firing origins are restrained from firing in HU-treated cells by at least one checkpoint-independent mechanism, and (ii) checkpoint-dependent slowing of S phase in fission yeast when DNA is damaged may be accomplished primarily by the slowing of replication forks. PMID:18093330

Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.

PubMed

Morohashi, Kengo; Sahara, Hiroeki; Watashi, Koichi; Iwabata, Kazuki; Sunoki, Takashi; Kuramochi, Kouji; Takakusagi, Kaori; Miyashita, Hiroki; Sato, Noriyuki; Tanabe, Atsushi; Shimotohno, Kunitada; Kobayashi, Susumu; Sakaguchi, Kengo; Sugawara, Fumio

2011-04-29

Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However, the regulation mechanisms of HCV replication governed by CsA target proteins have not been fully understood. Here we show a chemical biology approach that elucidates a novel mechanism of HCV replication. We developed a phage display screening to investigate compound-peptide interaction and identified a novel cellular target molecule of CsA. This protein, named CsA associated helicase-like protein (CAHL), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. The downregulation of CAHL in the cells resulted in a decrease of HCV genome replication. CAHL formed a complex with HCV-derived RNA polymerase NS5B and host-derived cyclophilin B (CyPB), known as a cellular cofactor for HCV replication, to regulate NS5B-CyPB interaction. We found a cellular factor, CAHL, as CsA associated helicase-like protein, which would form trimer complex with CyPB and NS5B of HCV. The strategy using a chemical compound and identifying its target molecule by our phage display analysis is useful to reveal a novel mechanism underlying cellular and viral physiology.

HSV Recombinant Vectors for Gene Therapy

PubMed Central

Manservigi, Roberto; Argnani, Rafaela; Marconi, Peggy

2010-01-01

The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges. PMID:20835362

Paying a price: culture, trust, and negotiation consequences.

PubMed

Gunia, Brian C; Brett, Jeanne M; Nandkeolyar, Amit K; Kamdar, Dishan

2011-07-01

Three studies contrasting Indian and American negotiators tested hypotheses derived from theory proposing why there are cultural differences in trust and how cultural differences in trust influence negotiation strategy. Study 1 (a survey) documented that Indian negotiators trust their counterparts less than American negotiators. Study 2 (a negotiation simulation) linked American and Indian negotiators' self-reported trust and strategy to their insight and joint gains. Study 3 replicated and extended Study 2 using independently coded negotiation strategy data, allowing for stronger causal inference. Overall, the strategy associated with Indian negotiators' reluctance to extend interpersonal (as opposed to institutional) trust produced relatively poor outcomes. Our data support an expanded theoretical model of negotiation, linking culture to trust, strategies, and outcomes.

Intelligent tit-for-tat in the iterated prisoner's dilemma game

NASA Astrophysics Data System (ADS)

Baek, Seung Ki; Kim, Beom Jun

2008-07-01

We seek a route to the equilibrium where all the agents cooperate in the iterated prisoner’s dilemma game on a two-dimensional plane, focusing on the role of tit-for-tat strategy. When a time horizon, within which a strategy can recall the past, is one time step, an equilibrium can be achieved as cooperating strategies dominate the whole population via proliferation of tit-for-tat. Extending the time horizon, we filter out poor strategies by simplified replicator dynamics and observe a similar evolutionary pattern to reach the cooperating equilibrium. In particular, the rise of a modified tit-for-tat strategy plays a central role, which implies how a robust strategy is adopted when provided with an enhanced memory capacity.

Adaptive strategies for cumulative cultural learning.

PubMed

Ehn, Micael; Laland, Kevin

2012-05-21

The demographic and ecological success of our species is frequently attributed to our capacity for cumulative culture. However, it is not yet known how humans combine social and asocial learning to generate effective strategies for learning in a cumulative cultural context. Here we explore how cumulative culture influences the relative merits of various pure and conditional learning strategies, including pure asocial and social learning, critical social learning, conditional social learning and individual refiner strategies. We replicate the Rogers' paradox in the cumulative setting. However, our analysis suggests that strategies that resolved Rogers' paradox in a non-cumulative setting may not necessarily evolve in a cumulative setting, thus different strategies will optimize cumulative and non-cumulative cultural learning. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prevention strategies differentially modulate the impact of cytomegalovirus replication on CD8(+) T-cell differentiation in high-risk solid organ transplant patients.

PubMed

Cantisán, Sara; Páez-Vega, Aurora; Pérez-Romero, Pilar; Montejo, Miguel; Cordero, Elisa; Gracia-Ahufinger, Irene; Martín-Gandul, Cecilia; Maruri, Naroa; Aguado, Rocío; Solana, Rafael; Torre-Cisneros, Julián

2016-08-01

The present study aimed to determine whether antiviral prevention strategies against cytomegalovirus (CMV) infection used in high-risk D+R- solid organ transplanted patients can modulate the impact of CMV replication on CD8(+) T-cell differentiation. The different CD8(+) T-cell subpopulations were measured at a single point when at least one year had elapsed since transplantation. A total of 68 D+R- patients were included, of which 33 underwent pre-emptive therapy and 35 received prophylaxis. Multivariate analysis showed that CMV replication was associated with the expansion of CD28־ EMRA CD8(+) T cells in patients managed pre-emptively but not in patients under prophylaxis (21.4% vs. 3.6%). This finding is likely related to the higher frequency of CMV recurrence observed in patients under pre-emptive therapy compared to those under prophylaxis (75% vs. 14.3%; p < 0.001). In fact, multivariate analysis showed that having more than one replication episode was associated with a 17.2% increase (p = 0.001) in the percentage of CD28־ EMRA CD8(+) T cells compared to "no episode" and with a 10.9% increase with respect to "single episodes" (p = 0.025). Additionally, patients with IFNγ response to CMV (QuantiFERON-CMV Reactive) had a higher percentage of late-differentiated CD8(+) T cells than patients lacking this response. In summary, recurrent CMV replication in D+R- patients under pre-emptive therapy was associated with the expansion of CD28־ EMRA CD8(+) T cells, which might have a short-term beneficial effect related to the high functionality of this T-cell subpopulation. Nevertheless, we cannot rule out that this accumulation might have a long-term detrimental effect related to immunosenescence and inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

The eROSITA X-ray mirrors: technology and qualification aspects of the production of mandrels, shells and mirror modules

NASA Astrophysics Data System (ADS)

Arcangeli, L.; Borghi, G.; Bräuninger, H.; Citterio, O.; Ferrario, I.; Friedrich, P.; Grisoni, G.; Marioni, F.; Predehl, P.; Rossi, M.; Ritucci, A.; Valsecchi, G.; Vernani, D.

2017-11-01

The name "eROSITA" stands for extended Roentgen Survey with an Imaging Telescope Array. The general design of the eROSITA X-ray telescope is derived from that of ABRIXAS. A bundle of 7 mirror modules with short focal lengths make up a compact telescope which is ideal for survey observations. Similar designs had been proposed for the missions DUO and ROSITA but were not realized due to programmatic shortfall. Compared to those, however, the effective area in the soft X-ray band has now much increased by adding 27 additional outer mirror shells to the original 27 ones of each mirror module. The requirement on the on-axis resolution has also been confined, namely to 15 arc seconds HEW. For these reasons the prefix "extended" was added to the original name "ROSITA". The scientific motivation for this extension is founded in the ambitious goal to detect about 100,000 clusters of galaxies which trace the large scale structure of the Universe in space and time. The X-ray telescope of eROSITA will consist of 7 identical and co-aligned mirror modules, each with 54 nested Wolter-1 mirror shells. The mirror shells are glued onto a spider wheel which is screwed to the mirror interface structure making a rigid mechanical unit. The assembly of 7 modules forms a compact hexagonal configuration with 1300 mm diameter (see Fig. 1) and will be attached to the telescope structure which connects to the 7 separate CCD cameras in the focal planes. The co-alignment of the mirror module enables eROSITA to perform also pointed observations. The replication process described in chapter III allows the manufacturing in one single piece and at the same time of both the parabola and hyperbola parts of the Wolter 1 mirror.

Two Proline-Rich Nuclear Localization Signals in the Amino- and Carboxyl-Terminal Regions of the Borna Disease Virus Phosphoprotein

PubMed Central

Shoya, Yuko; Kobayashi, Takeshi; Koda, Toshiaki; Ikuta, Kazuyoshi; Kakinuma, Mitsuaki; Kishi, Masahiko

1998-01-01

Borna disease virus (BDV) uses a unique strategy of replication and transcription which takes place in the nucleus, unlike other known, nonsegmented, negative-stranded RNA viruses of animal origin. In this process, viral constituents necessary for replication must be transported to the nucleus from the cytoplasm. We report here the evidence that BDV P protein, which may play an important role in viral replication and transcription, is transported into the nucleus in the absence of other viral constituents. This transportation is accomplished by its own nuclear localization signals (NLSs), which are present in both N-terminal (29PRPRKIPR36) and C-terminal (181PPRIYPQLPSAPT193) regions of the protein. These two NLSs can function independently and both have several Pro residues as key amino acids. PMID:9811710

SeMet attenuates OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR signaling pathway.

PubMed

Qian, Gang; Liu, Dandan; Hu, Junfa; Gan, Fang; Hou, Lili; Zhai, Nianhui; Chen, Xingxiang; Huang, Kehe

2018-02-13

Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.

Viruses within the Flaviviridae Decrease CD4 Expression and Inhibit HIV Replication in Human CD4+ Cells1

PubMed Central

Xiang, Jinhua; McLinden, James H.; Rydze, Robert A.; Chang, Qing; Kaufman, Thomas M.; Klinzman, Donna; Stapleton, Jack T.

2013-01-01

Viral infections alter host cell homeostasis and this may lead to immune evasion and/or interfere with the replication of other microbes in coinfected hosts. Two flaviviruses are associated with a reduction in HIV replication or improved survival in HIV-infected people (dengue virus (DV) and GB virus type C (GBV-C)). GBV-C infection and expression of the GBV-C nonstructural protein 5A (NS5A) and the DV NS5 protein in CD4+ T cells inhibit HIV replication in vitro. To determine whether the inhibitory effect on HIV replication is conserved among other flaviviruses and to characterize mechanism(s) of HIV inhibition, the NS5 proteins of GBV-C, DV, hepatitis C virus, West Nile virus, and yellow fever virus (YFV; vaccine strain 17D) were expressed in CD4+ T cells. All NS5 proteins inhibited HIV replication. This correlated with decreased steady-state CD4 mRNA levels and reduced cell surface CD4 protein expression. Infection of CD4+ T cells and macrophages with YFV (17D vaccine strain) also inhibited HIV replication and decreased CD4 gene expression. In contrast, mumps virus was not inhibited by the expression of flavivirus NS5 protein or by YFV infection, and mumps infection did not alter CD4 mRNA or protein levels. In summary, CD4 gene expression is decreased by all human flavivirus NS5 proteins studied. CD4 regulation by flaviviruses may interfere with innate and adaptive immunity and contribute to in vitro HIV replication inhibition. Characterization of the mechanisms by which flaviviruses regulate CD4 expression may lead to novel therapeutic strategies for HIV and immunological diseases. PMID:19923460

The IFITMs Inhibit Zika Virus Replication.

PubMed

Savidis, George; Perreira, Jill M; Portmann, Jocelyn M; Meraner, Paul; Guo, Zhiru; Green, Sharone; Brass, Abraham L

2016-06-14

Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses. Copyright © 2016. Published by Elsevier Inc.

Machiavellian Beliefs and Social Influence.

ERIC Educational Resources Information Center

O'Hair, Dan; Cody, Michael J.

1987-01-01

Replicates previous findings of separate Machiavellian belief constructs (Deceit, Flatter, Immorality, and Cynicism). Indicates that different constructs predict selection of compliance-gaining strategies; for example, actors who scored high on Immorality used more referent influence on superiors. Discusses implications of this study concerning a…

DNA hypomethylation induces a DNA replication-associated cell cycle arrest to block hepatic outgrowth in uhrf1 mutant zebrafish embryos

PubMed Central

Jacob, Vinitha; Chernyavskaya, Yelena; Chen, Xintong; Tan, Poh Seng; Kent, Brandon; Hoshida, Yujin; Sadler, Kirsten C.

2015-01-01

UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 to hemimethylated DNA during replication and is essential for maintaining DNA methylation. uhrf1 mutant zebrafish have global DNA hypomethylation and display embryonic defects, including a small liver, and they die as larvae. We make the surprising finding that, despite their reduced organ size, uhrf1 mutants express high levels of genes controlling S-phase and have many more cells undergoing DNA replication, as measured by BrdU incorporation. In contrast to wild-type hepatocytes, which are continually dividing during hepatic outgrowth and thus dilute the BrdU label, uhrf1 mutant hepatocytes retain BrdU throughout outgrowth, reflecting cell cycle arrest. Pulse-chase-pulse experiments with BrdU and EdU, and DNA content analysis indicate that uhrf1 mutant cells undergo DNA re-replication and that apoptosis is the fate of many of the re-replicating and arrested hepatocytes. Importantly, the DNA re-replication phenotype and hepatic outgrowth failure are preceded by global loss of DNA methylation. Moreover, uhrf1 mutants are phenocopied by mutation of dnmt1, and Dnmt1 knockdown in uhrf1 mutants enhances their small liver phenotype. Together, these data indicate that unscheduled DNA replication and failed cell cycle progression leading to apoptosis are the mechanisms by which DNA hypomethylation prevents organ expansion in uhrf1 mutants. We propose that cell cycle arrest leading to apoptosis is a strategy that restricts propagation of epigenetically damaged cells during embryogenesis. PMID:25564650

DNA hypomethylation induces a DNA replication-associated cell cycle arrest to block hepatic outgrowth in uhrf1 mutant zebrafish embryos.

PubMed

Jacob, Vinitha; Chernyavskaya, Yelena; Chen, Xintong; Tan, Poh Seng; Kent, Brandon; Hoshida, Yujin; Sadler, Kirsten C

2015-02-01

UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 to hemimethylated DNA during replication and is essential for maintaining DNA methylation. uhrf1 mutant zebrafish have global DNA hypomethylation and display embryonic defects, including a small liver, and they die as larvae. We make the surprising finding that, despite their reduced organ size, uhrf1 mutants express high levels of genes controlling S-phase and have many more cells undergoing DNA replication, as measured by BrdU incorporation. In contrast to wild-type hepatocytes, which are continually dividing during hepatic outgrowth and thus dilute the BrdU label, uhrf1 mutant hepatocytes retain BrdU throughout outgrowth, reflecting cell cycle arrest. Pulse-chase-pulse experiments with BrdU and EdU, and DNA content analysis indicate that uhrf1 mutant cells undergo DNA re-replication and that apoptosis is the fate of many of the re-replicating and arrested hepatocytes. Importantly, the DNA re-replication phenotype and hepatic outgrowth failure are preceded by global loss of DNA methylation. Moreover, uhrf1 mutants are phenocopied by mutation of dnmt1, and Dnmt1 knockdown in uhrf1 mutants enhances their small liver phenotype. Together, these data indicate that unscheduled DNA replication and failed cell cycle progression leading to apoptosis are the mechanisms by which DNA hypomethylation prevents organ expansion in uhrf1 mutants. We propose that cell cycle arrest leading to apoptosis is a strategy that restricts propagation of epigenetically damaged cells during embryogenesis. © 2015. Published by The Company of Biologists Ltd.

How MCM loading and spreading specify eukaryotic DNA replication initiation sites

PubMed Central

Hyrien, Olivier

2016-01-01

DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb) non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs), the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC), they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes. PMID:27635237

Analysis of IAV Replication and Co-infection Dynamics by a Versatile RNA Viral Genome Labeling Method.

PubMed

Dou, Dan; Hernández-Neuta, Iván; Wang, Hao; Östbye, Henrik; Qian, Xiaoyan; Thiele, Swantje; Resa-Infante, Patricia; Kouassi, Nancy Mounogou; Sender, Vicky; Hentrich, Karina; Mellroth, Peter; Henriques-Normark, Birgitta; Gabriel, Gülsah; Nilsson, Mats; Daniels, Robert

2017-07-05

Genome delivery to the proper cellular compartment for transcription and replication is a primary goal of viruses. However, methods for analyzing viral genome localization and differentiating genomes with high identity are lacking, making it difficult to investigate entry-related processes and co-examine heterogeneous RNA viral populations. Here, we present an RNA labeling approach for single-cell analysis of RNA viral replication and co-infection dynamics in situ, which uses the versatility of padlock probes. We applied this method to identify influenza A virus (IAV) infections in cells and lung tissue with single-nucleotide specificity and to classify entry and replication stages by gene segment localization. Extending the classification strategy to co-infections of IAVs with single-nucleotide variations, we found that the dependence on intracellular trafficking places a time restriction on secondary co-infections necessary for genome reassortment. Altogether, these data demonstrate how RNA viral genome labeling can help dissect entry and co-infections. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Automatic detection and measurement of viral replication compartments by ellipse adjustment

PubMed Central

Garcés, Yasel; Guerrero, Adán; Hidalgo, Paloma; López, Raul Eduardo; Wood, Christopher D.; Gonzalez, Ramón A.; Rendón-Mancha, Juan Manuel

2016-01-01

Viruses employ a variety of strategies to hijack cellular activities through the orchestrated recruitment of macromolecules to specific virus-induced cellular micro-environments. Adenoviruses (Ad) and other DNA viruses induce extensive reorganization of the cell nucleus and formation of nuclear Replication Compartments (RCs), where the viral genome is replicated and expressed. In this work an automatic algorithm designed for detection and segmentation of RCs using ellipses is presented. Unlike algorithms available in the literature, this approach is deterministic, automatic, and can adjust multiple RCs using ellipses. The proposed algorithm is non iterative, computationally efficient and is invariant to affine transformations. The method was validated over both synthetic images and more than 400 real images of Ad-infected cells at various timepoints of the viral replication cycle obtaining relevant information about the biogenesis of adenoviral RCs. As proof of concept the algorithm was then used to quantitatively compare RCs in cells infected with the adenovirus wild type or an adenovirus mutant that is null for expression of a viral protein that is known to affect activities associated with RCs that result in deficient viral progeny production. PMID:27819325

Automatic detection and measurement of viral replication compartments by ellipse adjustment

NASA Astrophysics Data System (ADS)

Garcés, Yasel; Guerrero, Adán; Hidalgo, Paloma; López, Raul Eduardo; Wood, Christopher D.; Gonzalez, Ramón A.; Rendón-Mancha, Juan Manuel

2016-11-01

Viruses employ a variety of strategies to hijack cellular activities through the orchestrated recruitment of macromolecules to specific virus-induced cellular micro-environments. Adenoviruses (Ad) and other DNA viruses induce extensive reorganization of the cell nucleus and formation of nuclear Replication Compartments (RCs), where the viral genome is replicated and expressed. In this work an automatic algorithm designed for detection and segmentation of RCs using ellipses is presented. Unlike algorithms available in the literature, this approach is deterministic, automatic, and can adjust multiple RCs using ellipses. The proposed algorithm is non iterative, computationally efficient and is invariant to affine transformations. The method was validated over both synthetic images and more than 400 real images of Ad-infected cells at various timepoints of the viral replication cycle obtaining relevant information about the biogenesis of adenoviral RCs. As proof of concept the algorithm was then used to quantitatively compare RCs in cells infected with the adenovirus wild type or an adenovirus mutant that is null for expression of a viral protein that is known to affect activities associated with RCs that result in deficient viral progeny production.

Evolutionary game theory: Temporal and spatial effects beyond replicator dynamics

NASA Astrophysics Data System (ADS)

Roca, Carlos P.; Cuesta, José A.; Sánchez, Angel

2009-12-01

Evolutionary game dynamics is one of the most fruitful frameworks for studying evolution in different disciplines, from Biology to Economics. Within this context, the approach of choice for many researchers is the so-called replicator equation, that describes mathematically the idea that those individuals performing better have more offspring and thus their frequency in the population grows. While very many interesting results have been obtained with this equation in the three decades elapsed since it was first proposed, it is important to realize the limits of its applicability. One particularly relevant issue in this respect is that of non-mean-field effects, that may arise from temporal fluctuations or from spatial correlations, both neglected in the replicator equation. This review discusses these temporal and spatial effects focusing on the non-trivial modifications they induce when compared to the outcome of replicator dynamics. Alongside this question, the hypothesis of linearity and its relation to the choice of the rule for strategy update is also analyzed. The discussion is presented in terms of the emergence of cooperation, as one of the current key problems in Biology and in other disciplines.

Therapeutic vaccines in HBV: lessons from HCV.

PubMed

Barnes, Eleanor

2015-02-01

Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control.

Analysis of host response to bacterial infection using error model based gene expression microarray experiments

PubMed Central

Stekel, Dov J.; Sarti, Donatella; Trevino, Victor; Zhang, Lihong; Salmon, Mike; Buckley, Chris D.; Stevens, Mark; Pallen, Mark J.; Penn, Charles; Falciani, Francesco

2005-01-01

A key step in the analysis of microarray data is the selection of genes that are differentially expressed. Ideally, such experiments should be properly replicated in order to infer both technical and biological variability, and the data should be subjected to rigorous hypothesis tests to identify the differentially expressed genes. However, in microarray experiments involving the analysis of very large numbers of biological samples, replication is not always practical. Therefore, there is a need for a method to select differentially expressed genes in a rational way from insufficiently replicated data. In this paper, we describe a simple method that uses bootstrapping to generate an error model from a replicated pilot study that can be used to identify differentially expressed genes in subsequent large-scale studies on the same platform, but in which there may be no replicated arrays. The method builds a stratified error model that includes array-to-array variability, feature-to-feature variability and the dependence of error on signal intensity. We apply this model to the characterization of the host response in a model of bacterial infection of human intestinal epithelial cells. We demonstrate the effectiveness of error model based microarray experiments and propose this as a general strategy for a microarray-based screening of large collections of biological samples. PMID:15800204

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

PubMed

Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

2004-09-15

The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC.

Why do people reject unintended inequity? Responders' rejection in a truncated ultimatum game.

PubMed

Ohmura, Yu; Yamagishi, Toshio

2005-04-01

Rejection of an inequitable and yet unintended outcome in a truncated ultimatum game was examined in an experiment with 46 undergraduate students (27 men and 19 women) from a large national university in Japan. In an ultimatum game, one of two players, the proposer, makes an offer to divide a fixed-sum of money. The other player, the responder, decides whether to accept or reject the offer. When the responder rejects the proposer's offer, neither of the two players receives a reward. Previous work examining the behavior of participants in the truncated ultimatum game employed strategy method in their experimental design. We examined whether these previous findings would be replicated in an experimental design that did not use the strategy method and instead used the standard one-shot game. Seven out of 46 responders given an inequitable offer rejected it, replicating prior results with the strategy method. We further found that subjects who rejected an offer that was involuntary and yet inequitable did not over-attribute intentions to the proposer's involuntary behavior more strongly than did acceptors. These findings strongly suggest that aversion to inequity is the explanation for the subjects' rejection of the inequitable offer.

The Replicator Equation on Graphs

PubMed Central

Ohtsuki, Hisashi; Nowak, Martin A.

2008-01-01

We study evolutionary games on graphs. Each player is represented by a vertex of the graph. The edges denote who meets whom. A player can use any one of n strategies. Players obtain a payoff from interaction with all their immediate neighbors. We consider three different update rules, called ‘birth-death’, ‘death-birth’ and ‘imitation’. A fourth update rule, ‘pairwise comparison’, is shown to be equivalent to birth-death updating in our model. We use pair-approximation to describe the evolutionary game dynamics on regular graphs of degree k. In the limit of weak selection, we can derive a differential equation which describes how the average frequency of each strategy on the graph changes over time. Remarkably, this equation is a replicator equation with a transformed payoff matrix. Therefore, moving a game from a well-mixed population (the complete graph) onto a regular graph simply results in a transformation of the payoff matrix. The new payoff matrix is the sum of the original payoff matrix plus another matrix, which describes the local competition of strategies. We discuss the application of our theory to four particular examples, the Prisoner’s Dilemma, the Snow-Drift game, a coordination game and the Rock-Scissors-Paper game. PMID:16860343

Overcoming the positive-capture strategy in young children: learning about indeterminacy.

PubMed

Klahr, David; Chen, Zhe

2003-01-01

Two experiments were conducted to examine whether and how 4- and 5-year-olds learn to distinguish determinate from indeterminate evidence. Children were asked to decide whether various patterns of evidence were sufficient to reach unambiguous conclusions. This study replicated the finding that young children tend to use a strategy that, although generally successful, fails on evidence patterns in which a single positive instance co-occurs with an unexplored source of evidence. Experiment 1 demonstrated that this positive-capture strategy is deeply entrenched, even in a meaningful, pragmatic context. With a microgenetic design, Experiment 2 revealed that young children are capable of replacing the positive-capture strategy with a correct strategy when they are exposed to various analogous tasks in several training sessions.

Genome Dynamics in Legionella: The Basis of Versatility and Adaptation to Intracellular Replication

PubMed Central

Gomez-Valero, Laura; Buchrieser, Carmen

2013-01-01

Legionella pneumophila is a bacterial pathogen present in aquatic environments that can cause a severe pneumonia called Legionnaires’ disease. Soon after its recognition, it was shown that Legionella replicates inside amoeba, suggesting that bacteria replicating in environmental protozoa are able to exploit conserved signaling pathways in human phagocytic cells. Comparative, evolutionary, and functional genomics suggests that the Legionella–amoeba interaction has shaped this pathogen more than previously thought. A complex evolutionary scenario involving mobile genetic elements, type IV secretion systems, and horizontal gene transfer among Legionella, amoeba, and other organisms seems to take place. This long-lasting coevolution led to the development of very sophisticated virulence strategies and a high level of temporal and spatial fine-tuning of bacteria host–cell interactions. We will discuss current knowledge of the evolution of virulence of Legionella from a genomics perspective and propose our vision of the emergence of this human pathogen from the environment. PMID:23732852

Dedicated education unit: implementing an innovation in replication sites.

PubMed

Moscato, Susan R; Nishioka, Vicki M; Coe, Michael T

2013-05-01

An important measure of an innovation is the ease of replication and achievement of the same positive outcomes. The dedicated education unit (DEU) clinical education model uses a collaborative academic-service partnership to develop an optimal learning environment for students. The University of Portland adapted this model from Flinders University, Australia, to increase the teaching capacity and quality of nursing education. This article identifies DEU implementation essentials and reports on the outcomes of two replication sites that received consultation support from the University of Portland. Program operation information, including education requirements for clinician instructors, types of patient care units, and clinical faculty-to-student ratios is presented. Case studies of the three programs suggest the DEU model is adaptable to a range of different clinical settings and continues to show promise as one strategy for addressing the nurse faculty shortage and strengthening academic-clinical collaborations while maintaining quality clinical education for students. Copyright 2013, SLACK Incorporated.

Experimentally guided models reveal replication principles that shape the mutation distribution of RNA viruses

PubMed Central

Schulte, Michael B; Draghi, Jeremy A; Plotkin, Joshua B; Andino, Raul

2015-01-01

Life history theory posits that the sequence and timing of events in an organism's lifespan are fine-tuned by evolution to maximize the production of viable offspring. In a virus, a life history strategy is largely manifested in its replication mode. Here, we develop a stochastic mathematical model to infer the replication mode shaping the structure and mutation distribution of a poliovirus population in an intact single infected cell. We measure production of RNA and poliovirus particles through the infection cycle, and use these data to infer the parameters of our model. We find that on average the viral progeny produced from each cell are approximately five generations removed from the infecting virus. Multiple generations within a single cell infection provide opportunities for significant accumulation of mutations per viral genome and for intracellular selection. DOI: http://dx.doi.org/10.7554/eLife.03753.001 PMID:25635405

Hepatitis A Virus Genome Organization and Replication Strategy.

PubMed

McKnight, Kevin L; Lemon, Stanley M

2018-04-02

Hepatitis A virus (HAV) is a positive-strand RNA virus classified in the genus Hepatovirus of the family Picornaviridae It is an ancient virus with a long evolutionary history and multiple features of its capsid structure, genome organization, and replication cycle that distinguish it from other mammalian picornaviruses. HAV proteins are produced by cap-independent translation of a single, long open reading frame under direction of an inefficient, upstream internal ribosome entry site (IRES). Genome replication occurs slowly and is noncytopathic, with transcription likely primed by a uridylated protein primer as in other picornaviruses. Newly produced quasi-enveloped virions (eHAV) are released from cells in a nonlytic fashion in a unique process mediated by interactions of capsid proteins with components of the host cell endosomal sorting complexes required for transport (ESCRT) system. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Genome dynamics in Legionella: the basis of versatility and adaptation to intracellular replication.

PubMed

Gomez-Valero, Laura; Buchrieser, Carmen

2013-06-01

Legionella pneumophila is a bacterial pathogen present in aquatic environments that can cause a severe pneumonia called Legionnaires' disease. Soon after its recognition, it was shown that Legionella replicates inside amoeba, suggesting that bacteria replicating in environmental protozoa are able to exploit conserved signaling pathways in human phagocytic cells. Comparative, evolutionary, and functional genomics suggests that the Legionella-amoeba interaction has shaped this pathogen more than previously thought. A complex evolutionary scenario involving mobile genetic elements, type IV secretion systems, and horizontal gene transfer among Legionella, amoeba, and other organisms seems to take place. This long-lasting coevolution led to the development of very sophisticated virulence strategies and a high level of temporal and spatial fine-tuning of bacteria host-cell interactions. We will discuss current knowledge of the evolution of virulence of Legionella from a genomics perspective and propose our vision of the emergence of this human pathogen from the environment.

Modes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence

PubMed Central

Carpentier, Alexandre; Barez, Pierre-Yves; Hamaidia, Malik; Gazon, Hélène; de Brogniez, Alix; Perike, Srikanth; Gillet, Nicolas; Willems, Luc

2015-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV-associated myelopathy—tropical spastic paraparesis, HAM/TSP). Since virions are particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying an integrated provirus. After transcription, the viral genomic RNA undergoes reverse transcription and integration into the chromosomal DNA of a cell from the newly infected host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus budding and infection of new targets and (ii) mitotic division of cells harboring an integrated provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to counteract these defense mechanisms allowing continuous persistence in humans. PMID:26198240

Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection.

PubMed

Ling, Binhua; Rogers, Linda; Johnson, Ann-Marie; Piatak, Michael; Lifson, Jeffrey; Veazey, Ronald S

2013-11-01

Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (<30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to <30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5(+)CD4(+) mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to <30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

Cyclosporin A Associated Helicase-Like Protein Facilitates the Association of Hepatitis C Virus RNA Polymerase with Its Cellular Cyclophilin B

PubMed Central

Sahara, Hiroeki; Iwabata, Kazuki; Sunoki, Takashi; Kuramochi, Kouji; Takakusagi, Kaori; Miyashita, Hiroki; Sato, Noriyuki; Tanabe, Atsushi; Shimotohno, Kunitada; Kobayashi, Susumu; Sakaguchi, Kengo; Sugawara, Fumio

2011-01-01

Background Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However, the regulation mechanisms of HCV replication governed by CsA target proteins have not been fully understood. Principal Findings Here we show a chemical biology approach that elucidates a novel mechanism of HCV replication. We developed a phage display screening to investigate compound-peptide interaction and identified a novel cellular target molecule of CsA. This protein, named CsA associated helicase-like protein (CAHL), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. The downregulation of CAHL in the cells resulted in a decrease of HCV genome replication. CAHL formed a complex with HCV-derived RNA polymerase NS5B and host-derived cyclophilin B (CyPB), known as a cellular cofactor for HCV replication, to regulate NS5B-CyPB interaction. Conclusions We found a cellular factor, CAHL, as CsA associated helicase-like protein, which would form trimer complex with CyPB and NS5B of HCV. The strategy using a chemical compound and identifying its target molecule by our phage display analysis is useful to reveal a novel mechanism underlying cellular and viral physiology. PMID:21559518

Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

PubMed

Simões, Margarida; Martins, Carlos; Ferreira, Fernando

2015-12-02

Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

PubMed

Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

2018-02-15

Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this concept needs expansion as the functions are more diverse. We showed that capsid protein VI regulates the antiviral response by modulation of the transcription factor Daxx during infection. Moreover, core protein VII interacts with SPOC1 restriction factor, which is beneficial for efficient viral gene expression. Here, we were able to show that core protein V also represents a novel substrate of the host SUMOylation machinery and contains several conserved SCMs; mutation of these consensus motifs reduced SUMOylation of the protein. Unexpectedly, we observed that introducing these mutations into HAdV promotes adenoviral replication. In conclusion, we offer novel insights into adenovirus core proteins and provide evidence that SUMOylation of HAdV factors regulates replication efficiency. Copyright © 2018 American Society for Microbiology.

Occurrence analysis of daily rainfalls through non-homogeneous Poissonian processes

NASA Astrophysics Data System (ADS)

Sirangelo, B.; Ferrari, E.; de Luca, D. L.

2011-06-01

A stochastic model based on a non-homogeneous Poisson process, characterised by a time-dependent intensity of rainfall occurrence, is employed to explain seasonal effects of daily rainfalls exceeding prefixed threshold values. The data modelling has been performed with a partition of observed daily rainfall data into a calibration period for parameter estimation and a validation period for checking on occurrence process changes. The model has been applied to a set of rain gauges located in different geographical areas of Southern Italy. The results show a good fit for time-varying intensity of rainfall occurrence process by 2-harmonic Fourier law and no statistically significant evidence of changes in the validation period for different threshold values.

Combinatorics of the Breakage-Fusion-Bridge Mechanism

PubMed Central

Bafna, Vineet

2012-01-01

Abstract The breakage-fusion-bridge (BFB) mechanism was proposed over seven decades ago and is a source of genomic variability and gene amplification in cancer. Here we formally model and analyze the BFB mechanism, to our knowledge the first time this has been undertaken. We show that BFB can be modeled as successive inverted prefix duplications of a string. Using this model, we show that BFB can achieve a surprisingly broad range of amplification patterns. We find that a sequence of BFB operations can be found that nearly fits most patterns of copy number increases along a chromosome. We conclude that this limits the usefulness of methods like array CGH for detecting BFB. PMID:22506505

Tapered enlarged ends in multimode optical fibers.

PubMed

Brenci, M; Falciai, R; Scheggi, A M

1982-01-15

Radiation characteristics of multimode fibers with enlarged tapers were investigated on a number of samples obtained by varying the fiber drawing speed with a given law corresponding to a prefixed taper profile. The characterization of the fibers was made by near- and far-field intensity pattern measurements as well as by measuring the losses introduced by the taper. With a suitable choice of parameters the taper constitutes a reasonable low-loss component useful, for example, for either efficient coupling to large-spot high-power density sources or connecting fibers of different sizes. Conversely at the exit of the fiber the taper can be used for beam shaping which is of interest for mechanical or surgical applications.

Redesigning Technology Integration into World Language Education

ERIC Educational Resources Information Center

Rodríguez, Julio C.

2018-01-01

This article describes how a multi-institutional, proficiency-based program engages stakeholders in design thinking to discover and explore solutions to perennial problems in technology integration into world language education (WLE). Examples of replicable activities illustrate the strategies used to fuel innovation efforts, including fostering…

A Study of Authoring Alternatives for Training-Oriented Videodiscs.

ERIC Educational Resources Information Center

Bunderson, C. Victor; And Others

This study examined eight areas that are related to the problems of authoring and producing training-oriented videodiscs: the delivery system itself; media selection during instructional systems development; instructional strategies; author mock-up and simulation prior to premastering; premastering; mastering and replication; composition of…

Pond Crash Forensics: Presumptive identification of pond crash agents by next generation sequencing in replicate raceway mass cultures of Nannochloropsis salina

DOE PAGES

Carney, Laura T.; Wilkenfeld, Joshua S.; Lane, Pam D.; ...

2016-06-02

Productivity of algal mass culture can be severely reduced by contaminating organisms. It is, therefore, important to identify contaminants, determine their effect on productivity and, ultimately, develop countermeasures against such contamination. In this paper, we utilized microbiome analysis by second-generation sequencing of small subunit rRNA genes to characterize the predator and pathogen burden of open raceway cultures of Nannochloropsis salina. Samples were analyzed from replicate raceways before and after crashes. In one culture cycle, we identified two algivorous species, the rotifer Brachionus and gastrotrich Chaetonotus, the presence of which may have contributed to the loss of algal biomass. In themore » second culture cycle, the raceways were treated with hypochlorite in an unsuccessful attempt to interdict the crash. Finally, our analyses were shown to be an effective strategy for the identification of the biological contaminants and the characterization of intervention strategies.« less

Understanding DNA Repair in Hyperthermophilic Archaea: Persistent Gaps and Other Reasons to Focus on the Fork

PubMed Central

Grogan, Dennis W.

2015-01-01

Although hyperthermophilic archaea arguably have a great need for efficient DNA repair, they lack members of several DNA repair protein families broadly conserved among bacteria and eukaryotes. Conversely, the putative DNA repair genes that do occur in these archaea often do not generate the expected phenotype when deleted. The prospect that hyperthermophilic archaea have some unique strategies for coping with DNA damage and replication errors has intellectual and technological appeal, but resolving this question will require alternative coping mechanisms to be proposed and tested experimentally. This review evaluates a combination of four enigmatic properties that distinguishes the hyperthermophilic archaea from all other organisms: DNA polymerase stalling at dU, apparent lack of conventional NER, lack of MutSL homologs, and apparent essentiality of homologous recombination proteins. Hypothetical damage-coping strategies that could explain this set of properties may provide new starting points for efforts to define how archaea differ from conventional models of DNA repair and replication fidelity. PMID:26146487

Pathogen trafficking pathways and host phosphoinositide metabolism.

PubMed

Weber, Stefan S; Ragaz, Curdin; Hilbi, Hubert

2009-03-01

Phosphoinositide (PI) glycerolipids are key regulators of eukaryotic signal transduction, cytoskeleton architecture and membrane dynamics. The host cell PI metabolism is targeted by intracellular bacterial pathogens, which evolved intricate strategies to modulate uptake processes and vesicle trafficking pathways. Upon entering eukaryotic host cells, pathogenic bacteria replicate in distinct vacuoles or in the host cytoplasm. Vacuolar pathogens manipulate PI levels to mimic or modify membranes of subcellular compartments and thereby establish their replicative niche. Legionella pneumophila, Brucella abortus, Mycobacterium tuberculosis and Salmonella enterica translocate effector proteins into the host cell, some of which anchor to the vacuolar membrane via PIs or enzymatically turnover PIs. Cytoplasmic pathogens target PI metabolism at the plasma membrane, thus modulating their uptake and antiapoptotic signalling pathways. Employing this strategy, Shigella flexneri directly injects a PI-modifying effector protein, while Listeria monocytogenes exploits PI metabolism indirectly by binding to transmembrane receptors. Thus, regardless of the intracellular lifestyle of the pathogen, PI metabolism is critically involved in the interactions with host cells.

A Brief Review of West Nile Virus Biology.

PubMed

Londono-Renteria, Berlin; Colpitts, Tonya M

2016-01-01

West Nile virus (WNV) is an arbovirus with increased global incidence in the last decade. It is also a major cause of human encephalitis in the USA. WNV is an arthropod-transmitted virus that mainly affects birds but humans become infected as incidental dead-end hosts which can cause outbreaks in naïve populations. The main vectors of WNV are mosquitoes of the genus Culex, which preferentially feed on birds. As in many other arboviruses, the characteristics that allow Flaviviruses like WNV to replicate and transmit to different hosts are encrypted in their genome, which also contains information for the production of structural and nonstructural proteins needed for host cell infection. WNV and other Flaviviruses have developed different strategies to establish infection, replication, and successful transmission. Most of these strategies include the diversion of the host's immune responses away from the virus. In this review, we describe the molecular structure and protein function of WNV with emphasis on protein involvement in the modulation of antiviral immune responses.

Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation.

PubMed

Fisher, Chris

2015-01-01

Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR) and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.

Building Blocks for Peer Success: Lessons Learned from a Train-the-Trainer Program

PubMed Central

Downes, Alicia; Eddens, Shalini; Ruiz, John

2012-01-01

Abstract The National HIV/AIDS Strategy (NHAS) calls for a reduction in health disparities, a reduction in new HIV infections, and improved retention in HIV care and treatment. It acknowledges that HIV-positive peers can play an important role in supporting these aims. However, peer training must be comprehensive enough to equip peers with the knowledge and skills needed for this work. This article describes the development of a national train the trainer (TTT) model for HIV peer educators, and the results of its implementation and replication. A mixed methods evaluation identified who was trained locally as a result of TTT implementation, what aspects of the TTT were most useful to trainers in implementing local training sessions, and areas for improvement. Over the course of 1 year, 91 individuals were trained at 1 of 6 TTT sessions. These individuals then conducted 26 local training sessions for 272 peers. Factors that facilitated local replication training included the teach-back/feedback model, faculty modeling of facilitation styles, financial support for training logistics, and faculty support in designing and implementing the training. The model could be improved by providing instruction on how to incorporate peers as part of the training team. TTT programs that are easily replicable in the community will be an important asset in developing a peer workforce that can help implement the National AIDS Strategy. PMID:22103430

Performance of Lempel-Ziv compressors with deferred innovation

NASA Technical Reports Server (NTRS)

Cohn, Martin

1989-01-01

The noiseless data-compression algorithms introduced by Lempel and Ziv (LZ) parse an input data string into successive substrings each consisting of two parts: The citation, which is the longest prefix that has appeared earlier in the input, and the innovation, which is the symbol immediately following the citation. In extremal versions of the LZ algorithm the citation may have begun anywhere in the input; in incremental versions it must have begun at a previous parse position. Originally the citation and the innovation were encoded, either individually or jointly, into an output word to be transmitted or stored. Subsequently, it was speculated that the cost of this encoding may be excessively high because the innovation contributes roughly 1g(A) bits, where A is the size of the input alphabet, regardless of the compressibility of the source. To remedy this excess, it was suggested to store the parsed substring as usual, but encoding for output only the citation, leaving the innovation to be encoded as the first symbol of the next substring. Being thus included in the next substring, the innovation can participate in whatever compression that substring enjoys. This strategy is called deferred innovation. It is exemplified in the algorithm described by Welch and implemented in the C program compress that has widely displaced adaptive Huffman coding (compact) as a UNIX system utility. The excessive expansion is explained, an implicit warning is given against using the deferred innovation compressors on nearly incompressible data.

Generalized enhanced suffix array construction in external memory.

PubMed

Louza, Felipe A; Telles, Guilherme P; Hoffmann, Steve; Ciferri, Cristina D A

2017-01-01

Suffix arrays, augmented by additional data structures, allow solving efficiently many string processing problems. The external memory construction of the generalized suffix array for a string collection is a fundamental task when the size of the input collection or the data structure exceeds the available internal memory. In this article we present and analyze [Formula: see text] [introduced in CPM (External memory generalized suffix and [Formula: see text] arrays construction. In: Proceedings of CPM. pp 201-10, 2013)], the first external memory algorithm to construct generalized suffix arrays augmented with the longest common prefix array for a string collection. Our algorithm relies on a combination of buffers, induced sorting and a heap to avoid direct string comparisons. We performed experiments that covered different aspects of our algorithm, including running time, efficiency, external memory access, internal phases and the influence of different optimization strategies. On real datasets of size up to 24 GB and using 2 GB of internal memory, [Formula: see text] showed a competitive performance when compared to [Formula: see text] and [Formula: see text], which are efficient algorithms for a single string according to the related literature. We also show the effect of disk caching managed by the operating system on our algorithm. The proposed algorithm was validated through performance tests using real datasets from different domains, in various combinations, and showed a competitive performance. Our algorithm can also construct the generalized Burrows-Wheeler transform of a string collection with no additional cost except by the output time.

Insensitivity of chromosome I and the cell cycle to blockage of replication and segregation of Vibrio cholerae chromosome II.

PubMed

Kadoya, Ryosuke; Chattoraj, Dhruba K

2012-01-01

Vibrio cholerae has two chromosomes (chrI and chrII) whose replication and segregation are under different genetic controls. The region covering the replication origin of chrI resembles that of the Escherichia coli chromosome, and both origins are under control of the highly conserved initiator, DnaA. The origin region of chrII resembles that of plasmids that have iterated initiator-binding sites (iterons) and is under control of the chrII-specific initiator, RctB. Both chrI and chrII encode chromosome-specific orthologs of plasmid partitioning proteins, ParA and ParB. Here, we have interfered with chrII replication, segregation, or both, using extra copies of sites that titrate RctB or ParB. Under these conditions, replication and segregation of chrI remain unaffected for at least 1 cell cycle. In this respect, chrI behaves similarly to the E. coli chromosome when plasmid maintenance is disturbed in the same cell. Apparently, no checkpoint exists to block cell division before the crippled chromosome is lost by a failure to replicate or to segregate. Whether blocking chrI replication can affect chrII replication remains to be tested. Chromosome replication, chromosome segregation, and cell division are the three main events of the cell cycle. They occur in an orderly fashion once per cell cycle. How the sequence of events is controlled is only beginning to be answered in bacteria. The finding of bacteria that possess more than one chromosome raises the important question: how are different chromosomes coordinated in their replication and segregation? It appears that in the evolution of the two-chromosome genome of V. cholerae, either the secondary chromosome adapted to the main chromosome to ensure its maintenance or it is maintained independently, as are bacterial plasmids. An understanding of chromosome coordination is expected to bear on the evolutionary process of chromosome acquisition and on the efficacy of possible strategies for selective elimination of a pathogen by targeting a specific chromosome.

Rv0004 is a new essential member of the mycobacterial DNA replication machinery

PubMed Central

Hooppaw, Anna J.; Richardson, Kirill; Lee, Hark Joon; Kimmey, Jacqueline M.; Aldridge, Bree B.

2017-01-01

DNA replication is fundamental for life, yet a detailed understanding of bacterial DNA replication is limited outside the organisms Escherichia coli and Bacillus subtilis. Many bacteria, including mycobacteria, encode no identified homologs of helicase loaders or regulators of the initiator protein DnaA, despite these factors being essential for DNA replication in E. coli and B. subtilis. In this study we discover that a previously uncharacterized protein, Rv0004, from the human pathogen Mycobacterium tuberculosis is essential for bacterial viability and that depletion of Rv0004 leads to a block in cell cycle progression. Using a combination of genetic and biochemical approaches, we found that Rv0004 has a role in DNA replication, interacts with DNA and the replicative helicase DnaB, and affects DnaB-DnaA complex formation. We also identify a conserved domain in Rv0004 that is predicted to structurally resemble the N-terminal protein-protein interaction domain of DnaA. Mutation of a single conserved tryptophan within Rv0004’s DnaA N-terminal-like domain leads to phenotypes similar to those observed upon Rv0004 depletion and can affect the association of Rv0004 with DnaB. In addition, using live cell imaging during depletion of Rv0004, we have uncovered a previously unappreciated role for DNA replication in coordinating mycobacterial cell division and cell size. Together, our data support that Rv0004 encodes a homolog of the recently identified DciA family of proteins found in most bacteria that lack the DnaC-DnaI helicase loaders in E. coli and B. subtilis. Therefore, the mechanisms of Rv0004 elucidated here likely apply to other DciA homologs and reveal insight into the diversity of bacterial strategies in even the most conserved biological processes. PMID:29176877

Rv0004 is a new essential member of the mycobacterial DNA replication machinery.

PubMed

Mann, Katherine M; Huang, Deborah L; Hooppaw, Anna J; Logsdon, Michelle M; Richardson, Kirill; Lee, Hark Joon; Kimmey, Jacqueline M; Aldridge, Bree B; Stallings, Christina L

2017-11-01

DNA replication is fundamental for life, yet a detailed understanding of bacterial DNA replication is limited outside the organisms Escherichia coli and Bacillus subtilis. Many bacteria, including mycobacteria, encode no identified homologs of helicase loaders or regulators of the initiator protein DnaA, despite these factors being essential for DNA replication in E. coli and B. subtilis. In this study we discover that a previously uncharacterized protein, Rv0004, from the human pathogen Mycobacterium tuberculosis is essential for bacterial viability and that depletion of Rv0004 leads to a block in cell cycle progression. Using a combination of genetic and biochemical approaches, we found that Rv0004 has a role in DNA replication, interacts with DNA and the replicative helicase DnaB, and affects DnaB-DnaA complex formation. We also identify a conserved domain in Rv0004 that is predicted to structurally resemble the N-terminal protein-protein interaction domain of DnaA. Mutation of a single conserved tryptophan within Rv0004's DnaA N-terminal-like domain leads to phenotypes similar to those observed upon Rv0004 depletion and can affect the association of Rv0004 with DnaB. In addition, using live cell imaging during depletion of Rv0004, we have uncovered a previously unappreciated role for DNA replication in coordinating mycobacterial cell division and cell size. Together, our data support that Rv0004 encodes a homolog of the recently identified DciA family of proteins found in most bacteria that lack the DnaC-DnaI helicase loaders in E. coli and B. subtilis. Therefore, the mechanisms of Rv0004 elucidated here likely apply to other DciA homologs and reveal insight into the diversity of bacterial strategies in even the most conserved biological processes.

Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

PubMed

Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

2009-05-01

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

Churn-Resilient Replication Strategy for Peer-to-Peer Distributed Hash-Tables

NASA Astrophysics Data System (ADS)

Legtchenko, Sergey; Monnet, Sébastien; Sens, Pierre; Muller, Gilles

DHT-based P2P systems provide a fault-tolerant and scalable mean to store data blocks in a fully distributed way. Unfortunately, recent studies have shown that if connection/disconnection frequency is too high, data blocks may be lost. This is true for most current DHT-based system's implementations. To avoid this problem, it is necessary to build really efficient replication and maintenance mechanisms. In this paper, we study the effect of churn on an existing DHT-based P2P system such as DHash or PAST. We then propose solutions to enhance churn tolerance and evaluate them through discrete event simulations.

What Information Theory Says about Bounded Rational Best Response

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2005-01-01

Probability Collectives (PC) provides the information-theoretic extension of conventional full-rationality game theory to bounded rational games. Here an explicit solution to the equations giving the bounded rationality equilibrium of a game is presented. Then PC is used to investigate games in which the players use bounded rational best-response strategies. Next it is shown that in the continuum-time limit, bounded rational best response games result in a variant of the replicator dynamics of evolutionary game theory. It is then shown that for team (shared-payoff) games, this variant of replicator dynamics is identical to Newton-Raphson iterative optimization of the shared utility function.

HSPA5 is an essential host factor for Ebola virus infection.

PubMed

Reid, St Patrick; Shurtleff, Amy C; Costantino, Julie A; Tritsch, Sarah R; Retterer, Cary; Spurgers, Kevin B; Bavari, Sina

2014-09-01

Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures. Published by Elsevier B.V.

"Scaling Up" Good Practices in Girls' Education

ERIC Educational Resources Information Center

Subrahmanian, Ramya

2005-01-01

This publication focuses on strategies for meeting international targets and national goals for universalizing girls' access to, retention in and completion of quality education. This will be done through "scaling up" successful interventions, or components of interventions that can be replicated. UNESCO published this book within the…

Special Education Teachers Integrating Reading with 8th Grade U.S. History Content

ERIC Educational Resources Information Center

O'Connor, Rollanda E.; Sanchez, Victoria; Beach, Kristen D.; Bocian, Kathleen M.

2017-01-01

This research replicates an earlier study (O'Connor, Beach, Sanchez, Bocian, & Flynn, 2015) and extends it by shifting instructional responsibility from researchers to special education teachers, who implemented reading instruction that included multisyllabic word decoding, academic vocabulary, and three comprehension strategies (generating…

STRATEGIES FOR INSTRUCTIONAL CHANGE--PROMISING IDEAS AND PERPLEXING PROBLEMS.

ERIC Educational Resources Information Center

HARRIS, BEN M.

SUPERVISION, BECAUSE IT COVERS A MULTIPLICITY OF TASKS PERFORMED IN NO FIXED LOCUS, ITS ALMOST IMMUNE TO SYSTEMATIC EVALUATION. ELABORATE DESCRIPTIVE STUDIES ARE NEEDED (POSSIBLY REPLICATIONS OF EDUCATIONAL ADMINISTRATION STUDIES) ON SUCH TOPICS AS RESISTANCE TO CHANGE AND SUPERVISOR-SUPERVISOR RELATIONSHIPS. THEORETICAL MODELS AND CONCEPTS WHICH…

Herpes simplex virus mutant generation and dual-detection methods for gaining insight into latent/lytic cycles in vivo.

PubMed

Sawtell, Nancy M; Thompson, Richard L

2014-01-01

Two important components to a useful strategy to examine viral gene regulation in vivo are (1) a highly efficient protocol to generate viral mutants that limits undesired mutation and retains full replication competency in vivo and (2) an efficient system to detect and quantify viral promoter activity in rare cells in vivo. Our strategy and protocols for generating, characterizing, and employing HSV viral promoter/reporter mutants in vivo are provided in this two-part chapter.

Strategies for Providing Low-Cost Water Immersion Therapy With Limited Resources.

PubMed

Brickhouse, Brenda; Isaacs, Christine; Batten, Meghann; Price, Amber

At our university-affiliated medical center, a major renovation of the women's health and birthing unit resulted in the temporary loss of the permanent tub used for water immersion therapy during labor. Because 40 percent of the women in the nurse-midwifery practice utilize hydrotherapy, we undertook a rigorous search for an interim solution. We developed a safe and cost-effective strategy that can be easily replicated and utilized by others to provide hydrotherapy for laboring women. © 2015 AWHONN.

Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

PubMed

Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P; Shields, Christopher B

2013-04-01

Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice. A focal demyelination model was created by stereotaxically injecting lysolecithin into the bilateral ventrolateral funiculus (VLF) of T8 and T9 mouse spinal cords. Immediately after lysolecithin injection mice were treated with COG112, prefix peptide control or vehicle control for 21 days. The locomotor function of the mice was measured by the beam walking test and Basso Mouse Scale (BMS) assessment. The nerve transmission of the VLF of mice was assessed in vivo by transcranial magnetic motor evoked potentials (tcMMEPs). The histological changes were also examined by by eriochrome cyanine staining, immunohistochemistry staining and electron microscopy (EM) method. The area of demyelination in the spinal cord was significantly reduced in the COG112 group. EM examination showed that treatment with COG112 increased the thickness of myelin sheaths and the numbers of surviving axons in the lesion epicenter. Locomotor function was improved in COG112 treated animals when measured by the beam walking test and BMS assessment compared to controls. TcMMEPs also demonstrated the COG112-mediated enhancement of amplitude of evoked responses. The apoE-mimetic COG112 demonstrates a favorable combination of activities in suppressing inflammatory response, mitigating demyelination and in promoting remyelination and associated functional recovery in animal model of CNS demyelination. These data support that apoE-mimetic strategy may represent a promising therapy for MS and other demyelination disorders.

Mother-to-Child HIV Transmission Bottleneck Selects for Consensus Virus with Lower Gag-Protease-Driven Replication Capacity

PubMed Central

Naidoo, Vanessa L.; Mann, Jaclyn K.; Noble, Christie; Adland, Emily; Carlson, Jonathan M.; Thomas, Jake; Brumme, Chanson J.; Thobakgale-Tshabalala, Christina F.; Brumme, Zabrina L.; Goulder, Philip J. R.

2017-01-01

ABSTRACT In the large majority of cases, HIV infection is established by a single variant, and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease-driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma-derived Gag-protease from 53 nontransmitter mothers, 48 transmitter mothers, and 47 infected infants were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. All study participants were infected with HIV-1 subtype C. There was no significant difference in replication capacities between the nontransmitter (n = 53) and transmitter (n = 44) mothers (P = 0.48). Infant-derived Gag-protease NL4-3 recombinant viruses (n = 41) were found to have a significantly lower Gag-protease-driven replication capacity than that of viruses derived from the mothers (P < 0.0001 by a paired t test). High percent similarities to consensus subtype C Gag, p17, p24, and protease sequences were also found in the infants (n = 28) in comparison to their mothers (P = 0.07, P = 0.002, P = 0.03, and P = 0.02, respectively, as determined by a paired t test). These data suggest that of the viral quasispecies found in mothers, the HIV mother-to-child transmission bottleneck favors the transmission of consensus-like viruses with lower viral replication capacities. IMPORTANCE Understanding the characteristics of successfully transmitted HIV variants has important implications for preventative interventions. Little is known about the viral determinants of HIV mother-to-child transmission (MTCT). We addressed the role of viral replication capacity driven by Gag, a major structural protein that is a significant determinant of overall viral replicative ability and an important target of the host immune response, in the MTCT bottleneck. This study advances our understanding of the genetic bottleneck in MTCT by revealing that viruses transmitted to infants have a lower replicative ability as well as a higher similarity to the population consensus (in this case HIV subtype C) than those of their mothers. Furthermore, the observation that “consensus-like” virus sequences correspond to lower in vitro replication abilities yet appear to be preferentially transmitted suggests that viral characteristics favoring transmission are decoupled from those that enhance replicative capacity. PMID:28637761

Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

PubMed

Prowse, Thomas A A; Cassey, Phillip; Ross, Joshua V; Pfitzner, Chandran; Wittmann, Talia A; Thomas, Paul

2017-08-16

Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial 'silver bullet' for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous end-joining (NHEJ)-mediated DNA repair. We used stochastic individual-based models to identify realistic gene-drive strategies capable of eradicating vertebrate pest populations (mice, rats and rabbits) on islands. One popular strategy, a sex-reversing drive that converts heterozygous females into sterile males, failed to spread and required the ongoing deployment of gene-drive carriers to achieve eradication. Under alternative strategies, multiplexed gRNAs could overcome inherent polymorphic resistance and were required for eradication success even when the probability of NHEJ was low. Strategies causing homozygotic embryonic non-viability or homozygotic female sterility produced high probabilities of eradication and were robust to NHEJ-mediated deletion of the DNA sequence between multiplexed endonuclease recognition sites. The latter two strategies also purged the gene drive when eradication failed, therefore posing lower long-term risk should animals escape beyond target islands. Multiplexing gRNAs will be necessary if this technology is to be useful for insular extirpation attempts; however, precise knowledge of homing rates will be required to design low-risk gene drives with high probabilities of eradication success. © 2017 The Author(s).

Barriers to Participation in a Community-Based Program to Control Transmission of Taenia solium in Peru.

PubMed

Beam, Michelle; Spencer, Angela; Fernandez, Lauralee; Atto, Ruth; Muro, Claudio; Vilchez, Percy; Gamboa, Ricardo; Olaya, Sandra; Ayvar, Viterbo; Gonzalez, Armando E; Garcia, Hector H; O'Neal, Seth E; For The Cysticercosis Working Group In Peru

2018-04-16

Infection of the brain with Taenia solium larvae (neurocysticercosis) is a leading cause of preventable epilepsy worldwide. Effective and sustainable strategies to control parasite transmission in rural endemic communities are needed to prevent the disease. Surveillance and targeted intervention around infected pigs (ring control strategy) have been shown to be effective when carried out by research teams. However, this strategy has not been implemented or tested as a community-based program. In this small trial in northern Peru, eight villages were randomly assigned to community-led surveillance and treatment (five villages, 997 residents) or control (three villages, 1,192 residents). In intervention villages, community-led surveillance and reporting were promoted by community health workers, radio advertisement, and school and household education. Each suspected pig infection was verified, with confirmed cases resulting in treatment with niclosamide for taeniasis and oxfendazole for pigs in clusters of homes nearby. No incentives beyond human and pig treatment were offered. Control villages received basic disease education but no treatment intervention in response to reports. Despite 14 case reports, community-based replication of ring control strategy did not replicate prior results. After 12 months, there was no change in seroincidence in intervention villages between the baseline and study end, and no difference compared with control villages. There was no difference in prevalence of taeniasis or porcine cysticercosis at study end. Community members described lack of knowledge as the main reason for not reporting infected pigs. Further exploration of methods to transfer ring strategy and other control interventions for cysticercosis to the community is needed.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus).

PubMed

Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-12-13

Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia ( Niloticus oreochromis ) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.

Stable isotope deltas: Tiny, yet robust signatures in nature

USGS Publications Warehouse

Brand, Willi A.; Coplen, Tyler B.

2012-01-01

Although most of them are relatively small, stable isotope deltas of naturally occurring substances are robust and enable workers in anthropology, atmospheric sciences, biology, chemistry, environmental sciences, food and drug authentication, forensic science, geochemistry, geology, oceanography, and paleoclimatology to study a variety of topics. Two fundamental processes explain the stable isotope deltas measured in most terrestrial systems: isotopic fractionation and isotope mixing. Isotopic fractionation is the result of equilibrium or kinetic physicochemical processes that fractionate isotopes because of small differences in physical or chemical properties of molecular species having different isotopes. It is shown that the mixing of radioactive and stable isotope end members can be modelled to provide information on many natural processes, including 14C abundances in the modern atmosphere and the stable hydrogen and oxygen isotopic compositions of the oceans during glacial and interglacial times. The calculation of mixing fractions using isotope balance equations with isotope deltas can be substantially in error when substances with high concentrations of heavy isotopes (e.g. 13C, 2H, and 18O ) are mixed. In such cases, calculations using mole fractions are preferred as they produce accurate mixing fractions. Isotope deltas are dimensionless quantities. In the International System of Units (SI), these quantities have the unit 1 and the usual list of prefixes is not applicable. To overcome traditional limitations with expressing orders of magnitude differences in isotope deltas, we propose the term urey (symbol Ur), after Harold C. Urey, for the unit 1. In such a manner, an isotope delta value expressed traditionally as−25 per mil can be written as−25 mUr (or−2.5 cUr or−0.25 dUr; the use of any SI prefix is possible). Likewise, very small isotopic differences often expressed in per meg ‘units’ are easily included (e.g. either+0.015 ‰ or+15 per meg can be written as+15 μUr.

Characterizing Bacteriophage PR772 as a Potential Surrogate for Adenovirus in Water Disinfection: A Comparative Analysis of Inactivation Kinetics and Replication Cycle Inhibition by Free Chlorine.

PubMed

Gall, Aimee M; Shisler, Joanna L; Mariñas, Benito J

2016-03-01

Elucidating mechanisms by which pathogenic waterborne viruses become inactivated by drinking water disinfectants would facilitate the development of sensors to detect infectious viruses and novel disinfection strategies to provide safe water. Using bacteriophages as surrogates for human pathogenic viruses could assist in elucidating these mechanisms; however, an appropriate viral surrogate for human adenovirus (HAdV), a medium-sized virus with a double-stranded DNA genome, needs to be identified. Here, we characterized the inactivation kinetics of bacteriophage PR772, a member of the Tectiviridae family with many similarities in structure and replication to HAdV. The inactivation of PR772 and HAdV by free chlorine had similar kinetics that could be represented with a model previously developed for HAdV type 2 (HAdV-2). We developed and tested a quantitative assay to analyze several steps in the PR772 replication cycle to determine if both viruses being inactivated at similar rates resulted from similar replication cycle events being inhibited. Like HAdV-2, we observed that PR772 inactivated by free chlorine still attached to host cells, and viral DNA synthesis and early and late gene transcription were inhibited. Consequently, free chlorine exposure inhibited a replication cycle event that was post-binding but took place prior to early gene synthesis for both PR772 and HAdV-2.

Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor.

PubMed

Goto, Kaku; Watashi, Koichi; Inoue, Daisuke; Hijikata, Makoto; Shimotohno, Kunitada

2009-10-01

We have so far reported that an immunosuppressant cyclosporin A (CsA), a well-known cyclophilin (CyP) inhibitor (CPI), strongly suppressed hepatitis C virus (HCV) replication in cell culture, and that CyPB was a cellular cofactor for viral replication. To further investigate antiviral mechanisms of CPI, we here developed cells carrying CsA-resistant HCV replicons, by culturing the HCV subgenomic replicon cells for 4 weeks in the presence of CsA with G418. Transfection of total RNA from the isolated CsA-resistant cells to naïve Huh7 cells conferred CsA resistance, suggesting that the replicon RNA itself was responsible for the resistant phenotype. Of the identified amino acid mutations, D320E in NS5A conferred the CsA resistance. The replicon carrying the D320E mutation was sensitive to interferon-alpha, but was resistant to CsA and other CPIs including NIM811 and sanglifehrin A. Knockdown of individual CyP subtypes revealed CyP40, in addition to CyPA and CyPB, contributed to viral replication, and CsA-resistant replicons acquired independence from CyPA for efficient replication. These data provide important evidence on the mechanisms underlying the regulation of HCV replication by CyP and for designing novel and specific anti-HCV strategies with CPIs.

Monkey Viperin Restricts Porcine Reproductive and Respiratory Syndrome Virus Replication.

PubMed

Fang, Jianyu; Wang, Haiyan; Bai, Juan; Zhang, Qiaoya; Li, Yufeng; Liu, Fei; Jiang, Ping

2016-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen which causes huge economic damage globally in the swine industry. Current vaccination strategies provide only limited protection against PRRSV infection. Viperin is an interferon (IFN) stimulated protein that inhibits some virus infections via IFN-dependent or IFN-independent pathways. However, the role of viperin in PRRSV infection is not well understood. In this study, we cloned the full-length monkey viperin (mViperin) complementary DNA (cDNA) from IFN-α-treated African green monkey Marc-145 cells. It was found that the mViperin is up-regulated following PRRSV infection in Marc-145 cells along with elevated IRF-1 gene levels. IFN-α induced mViperin expression in a dose- and time-dependent manner and strongly inhibits PRRSV replication in Marc-145 cells. Overexpression of mViperin suppresses PRRSV replication by blocking the early steps of PRRSV entry and genome replication and translation but not inhibiting assembly and release. And mViperin co-localized with PRRSV GP5 and N protein, but only interacted with N protein in distinct cytoplasmic loci. Furthermore, it was found that the 13-16 amino acids of mViperin were essential for inhibiting PRRSV replication, by disrupting the distribution of mViperin protein from the granular distribution to a homogeneous distribution in the cytoplasm. These results could be helpful in the future development of novel antiviral therapies against PRRSV infection.

Enquire within: cultural evolution and cognitive science.

PubMed

Heyes, Cecilia

2018-04-05

Cultural evolution and cognitive science need each other. Cultural evolution needs cognitive science to find out whether the conditions necessary for Darwinian evolution are met in the cultural domain. Cognitive science needs cultural evolution to explain the origins of distinctively human cognitive processes. Focusing on the first question, I argue that cultural evolutionists can get empirical traction on third-way cultural selection by rooting the distinction between replication and reconstruction, two modes of cultural inheritance, in the distinction between System 1 and System 2 cognitive processes. This move suggests that cultural epidemiologists are right in thinking that replication has higher fidelity than reconstruction, and replication processes are not genetic adaptations for culture, but wrong to assume that replication is rare. If replication is not rare, an important requirement for third-way cultural selection, one-shot fidelity , is likely to be met. However, there are other requirements, overlooked by dual-inheritance theorists when they conflate strong (Darwinian) and weak (choice) senses of 'cultural selection', including dumb choices and recurrent fidelity In a second excursion into cognitive science, I argue that these requirements can be met by metacognitive social learning strategies , and trace the origins of these distinctively human cognitive processes to cultural evolution. Like other forms of cultural learning, they are not cognitive instincts but cognitive gadgets.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'. © 2018 The Author(s).

Design of experiments on 135 cloned poplar trees to map environmental influence in greenhouse.

PubMed

Pinto, Rui Climaco; Stenlund, Hans; Hertzberg, Magnus; Lundstedt, Torbjörn; Johansson, Erik; Trygg, Johan

2011-01-31

To find and ascertain phenotypic differences, minimal variation between biological replicates is always desired. Variation between the replicates can originate from genetic transformation but also from environmental effects in the greenhouse. Design of experiments (DoE) has been used in field trials for many years and proven its value but is underused within functional genomics including greenhouse experiments. We propose a strategy to estimate the effect of environmental factors with the ultimate goal of minimizing variation between biological replicates, based on DoE. DoE can be analyzed in many ways. We present a graphical solution together with solutions based on classical statistics as well as the newly developed OPLS methodology. In this study, we used DoE to evaluate the influence of plant specific factors (plant size, shoot type, plant quality, and amount of fertilizer) and rotation of plant positions on height and section area of 135 cloned wild type poplar trees grown in the greenhouse. Statistical analysis revealed that plant position was the main contributor to variability among biological replicates and applying a plant rotation scheme could reduce this variation. Copyright © 2010 Elsevier B.V. All rights reserved.

Flaviviral NS4b, chameleon and jack-in-the-box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention.

PubMed

Zmurko, Joanna; Neyts, Johan; Dallmeier, Kai

2015-07-01

Dengue virus and other flaviviruses such as the yellow fever, West Nile, and Japanese encephalitis viruses are emerging vector-borne human pathogens that affect annually more than 100 million individuals and that may cause debilitating and potentially fatal hemorrhagic and encephalitic diseases. Currently, there are no specific antiviral drugs for the treatment of flavivirus-associated disease. A better understanding of the flavivirus-host interactions during the different events of the flaviviral life cycle may be essential when developing novel antiviral strategies. The flaviviral non-structural protein 4b (NS4b) appears to play an important role in flaviviral replication by facilitating the formation of the viral replication complexes and in counteracting innate immune responses such as the following: (i) type I IFN signaling; (ii) RNA interference; (iii) formation of stress granules; and (iv) the unfolded protein response. Intriguingly, NS4b has recently been shown to constitute an excellent target for the selective inhibition of flavivirus replication. We here review the current knowledge on NS4b. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.

Flaviviral NS4b, chameleon and jack‐in‐the‐box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention

PubMed Central

Zmurko, Joanna; Dallmeier, Kai

2015-01-01

Summary Dengue virus and other flaviviruses such as the yellow fever, West Nile, and Japanese encephalitis viruses are emerging vector‐borne human pathogens that affect annually more than 100 million individuals and that may cause debilitating and potentially fatal hemorrhagic and encephalitic diseases. Currently, there are no specific antiviral drugs for the treatment of flavivirus‐associated disease. A better understanding of the flavivirus–host interactions during the different events of the flaviviral life cycle may be essential when developing novel antiviral strategies. The flaviviral non‐structural protein 4b (NS4b) appears to play an important role in flaviviral replication by facilitating the formation of the viral replication complexes and in counteracting innate immune responses such as the following: (i) type I IFN signaling; (ii) RNA interference; (iii) formation of stress granules; and (iv) the unfolded protein response. Intriguingly, NS4b has recently been shown to constitute an excellent target for the selective inhibition of flavivirus replication. We here review the current knowledge on NS4b. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:25828437

Cytomegalovirus and polyomavirus BK posttransplant.

PubMed

Egli, Adrian; Binggeli, Simone; Bodaghi, Sohrab; Dumoulin, Alexis; Funk, Georg A; Khanna, Nina; Leuenberger, David; Gosert, Rainer; Hirsch, Hans H

2007-09-01

Virus replication and progression to disease in transplant patients is determined by patient-, graft- and virus-specific factors. This complex interaction is modulated by the net state of immunosuppression and its impact on virus-specific cellular immunity. Due to the increasing potency of immunosuppressive regimens, graft rejections have decreased, but susceptibility to infections has increased. Therefore, cytomegalovirus (CMV) remains the most important viral pathogen posttransplant despite availability of effective antiviral drugs and validated strategies for prophylactic, preemptive and therapeutic intervention. CMV replication can affect almost every organ system, with frequent recurrences and increasing rates of antiviral resistance. Together with indirect long-term effects, CMV significantly reduces graft and patient survival after solid organ and hematopoietic stem cell transplantation. The human polyomavirus called BK virus (BKV), on the other hand, only recently surfaced as pathogen with organ tropism largely limited to the reno-urinary tract, manifesting as polyomavirus-associated nephropathy in kidney transplant and hemorrhagic cystitis in hematopoetic stem cell transplant patients. No licensed anti-polyoma viral drugs are available, and treatment relies mainly on improving immune functions to regain control over BKV replication. In this review, we discuss diagnostic and therapeutic aspects of CMV and BKV replication and disease posttransplantation.

Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System.

PubMed

Bertrand, Luc; Nair, Madhavan; Toborek, Michal

2016-01-01

Recent decades mark a great progress in the treatment of HIV infection. What was once a deadly disease is now a chronic infection. However, HIV-infected patients are prone to develop comorbidities, which severely affect their daily functions. For example, a large population of patients develop a variety of neurological and cognitive complications, called HIV associated neurological disorders (HAND). Despite efficient repression of viral replication in the periphery, evidence shows that the virus can remain active in the central nervous system (CNS). This low level of replication is believed to result in a progression of neurocognitive dysfunction in infected individuals. Insufficient viral inhibition in the brain results from the inability of several treatment drugs in crossing the blood-brain barrier (BBB) and reaching therapeutic concentrations in the CNS. The current manuscript discusses several strategies that are being developed to enable therapeutics to cross the BBB, including bypassing BBB, inhibition of efflux transporters, the use of active transporters present at the BBB, and nanotechnology. The increased concentration of therapeutics in the CNS is desirable to prevent viral replication; however, potential side effects of anti-retroviral drugs need also to be taken into consideration.

The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot-and-Mouth Disease Virus Replication

PubMed Central

Xue, Qiao

2017-01-01

Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180–214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies. PMID:29226127

An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

PubMed

Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

2017-12-01

Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

PubMed

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

AR-12 suppresses dengue virus replication by down-regulation of PI3K/AKT and GRP78.

PubMed

Chen, Hsin-Hsin; Chen, Chien-Chin; Lin, Yee-Shin; Chang, Po-Chun; Lu, Zi-Yi; Lin, Chiou-Feng; Chen, Chia-Ling; Chang, Chih-Peng

2017-06-01

Dengue virus (DENV) infection has become a public health issue of worldwide concern and is a serious health problem in Taiwan, yet there are no approved effective antiviral drugs to treat DENV. The replication of DENV requires both viral and cellular factors. Targeting host factors may provide a potential antiviral strategy. It has been known that up-regulation of PI3K/AKT signaling and GRP78 by DENV infection supports its replication. AR-12, a celecoxib derivative with no inhibiting activity on cyclooxygenase, shows potent inhibitory activities on both PI3K/AKT signaling and GRP78 expression levels, and recently has been found to block the replication of several hemorrhagic fever viruses. However the efficacy of AR-12 in treating DENV infection is still unclear. Here, we provide evidence to show that AR-12 is able to suppress DENV replication before or after virus infection in cell culture and mice. The antiviral activities of AR-12 are positive against infection of the four different DENV serotypes. AR-12 significantly down-regulates the PI3K/AKT activity and GRP78 expression in DENV infected cells whereas AKT and GRP78 rescue are able to attenuate anti-DENV effect of AR-12. Using a DENV-infected suckling mice model, we further demonstrate that treatment of AR-12 before or after DENV infection reduces virus replication and mice mortality. In conclusion, we uncover the potential efficacy of AR-12 as a novel drug for treating dengue. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

PubMed Central

Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

Silencing honey bee naked cuticle (nkd) reduces Nosema ceranae replication and disease levels

USDA-ARS?s Scientific Manuscript database

Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera that has been implicated in alarming colony losses worldwide. RNA interference (RNAi), a post-transcriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling in...

Applying Questioning or Reading Strategy to Review Technology Enhanced Coedited Notes of Elementary School Students

ERIC Educational Resources Information Center

Chiu, Chiung-Hui; Cheng, Hsiao-Wei; Wu, Chiu-Yi

2016-01-01

The authors examined whether applying questioning review better enhances elementary level students' learning from technology-enhanced coediting-based note taking than does traditional reading review. A nonequivalent comparison group quasi-experimental design was implemented and replicated on four independent units. Two sixth grade elementary…

Application of GPS and Near-Surface Geophysical Methods to Evaluate Agricultural Test Plot Differences

USDA-ARS?s Scientific Manuscript database

A field research facility with two pairs of replicated agricultural test plots (four total) was established at a location in northwest Ohio during 2005 for the purpose of studying water table management strategies. Initial efforts at this field research facility were devoted to evaluating difference...

Thinking Routines: Replicating Classroom Practices within Museum Settings

ERIC Educational Resources Information Center

Wolberg, Rochelle Ibanez; Goff, Allison

2012-01-01

This article describes thinking routines as tools to guide and support young children's thinking. These learning strategies, developed by Harvard University's Project Zero Classroom, actively engage students in constructing meaning while also understanding their own thinking process. The authors discuss how thinking routines can be used in both…

Origins of Teachers' Selection of Aversive Interventions.

ERIC Educational Resources Information Center

Lee, Steven W.; Weis, Glenna

This study was designed to replicate and improve upon Kaplan's 1992 study of the possible link between teachers' past experiences and use of aversive disciplinary strategies. The current study examines the possible effect of past home and school experience on both preservice and practicing teachers' choices of intervention. The first study…

Special Education Teachers Integrating Reading with Eighth Grade U.S. History Content

ERIC Educational Resources Information Center

O'Connor, Rollanda E.; Sanchez, Victoria; Beach, Kristen D.; Bocian, Kathleen M.

2017-01-01

This research replicates an earlier study and extends it by shifting instructional responsibility from researchers to special education teachers, who implemented reading instruction that included multisyllabic word decoding, academic vocabulary, and three comprehension strategies (generating main ideas, comparing and contrasting people and events,…

The Management of Large-Scale Change in Pakistani Education

ERIC Educational Resources Information Center

Razzaq, Jamila; Forde, Christine

2014-01-01

This article argues that although there are increasing similarities in priorities across different national education systems, contextual differences raise questions about the replication of sets of change strategies based on particular understandings of the nature of educational change across these different systems. This article begins with an…

Community in Online Higher Education: Challenges and Opportunities

ERIC Educational Resources Information Center

Arasaratnam-Smith, Lily A.; Northcote, Maria

2017-01-01

Exploring the challenges and opportunities associated with the concepts of community and communication in online higher education, this paper reconsiders the intention to replicate face-to-face learning and teaching strategies in online learning environments. Rather than beginning with the assumption that face-to-face education is the prototype…

Understanding the Etiology of Complex Traits: Symbiotic Relationships between Psychology and Genetics

ERIC Educational Resources Information Center

Grigorenko, Elena L.

2007-01-01

The present article offers comments on the infusion of methodologies, approaches, reasoning strategies, and findings from the fields of genetics and genomics into studies of complex human behaviors (hereafter, complex phenotypes). Specifically, I discuss issues of generality and specificity, causality, and replicability as they pertain to…

The Warm-Cold Study: A Classroom Demonstration of Impression Formation.

ERIC Educational Resources Information Center

Symbaluk, Diane G.; Cameron, Judy

1998-01-01

Describes a procedure for teaching experimental design to students in the social sciences. Argues that by replicating Solomon Asch's and H. Kelley's classic studies on impression formation, students learn how to conduct experiments, analyze data, and evaluate the significance of research. Provides instructions for implementing the strategy. (DSK)

Successive Research: A Strategy for Building on Previous Research.

ERIC Educational Resources Information Center

Noble, Mary Anne

1979-01-01

Describes an approach to clinical research used by the author in teaching graduate nursing students, involving replication and expansion of a primary study of hospital intensive care units. This approach provided valuable experience as well as validated data about clinical practice. Discusses advantages and disadvantages in the approach. (MF)

Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome

PubMed Central

Shen, Weiran; Deng, Xuefeng; Zou, Wei; Engelhardt, John F.; Yan, Ziying

2016-01-01

ABSTRACT Parvoviruses are single-stranded DNA viruses that use the palindromic structures at the ends of the viral genome for their replication. The mechanism of parvovirus replication has been studied mostly in the dependoparvovirus adeno-associated virus 2 (AAV2) and the protoparvovirus minute virus of mice (MVM). Here, we used human bocavirus 1 (HBoV1) to understand the replication mechanism of bocaparvovirus. HBoV1 is pathogenic to humans, causing acute respiratory tract infections, especially in young children under 2 years old. By using the duplex replicative form of the HBoV1 genome in human embryonic kidney 293 (HEK293) cells, we identified the HBoV1 minimal replication origin at the right-end hairpin (OriR). Mutagenesis analyses confirmed the putative NS1 binding and nicking sites within the OriR. Of note, unlike the large nonstructural protein (Rep78/68 or NS1) of other parvoviruses, HBoV1 NS1 did not specifically bind OriR in vitro, indicating that other viral and cellular components or the oligomerization of NS1 is required for NS1 binding to the OriR. In vivo studies demonstrated that residues responsible for NS1 binding and nicking are within the origin-binding domain. Further analysis identified that the small nonstructural protein NP1 is required for HBoV1 DNA replication at OriR. NP1 and other viral nonstructural proteins (NS1 to NS4) colocalized within the viral DNA replication centers in both OriR-transfected cells and virus-infected cells, highlighting a direct involvement of NP1 in viral DNA replication at OriR. Overall, our study revealed the characteristics of HBoV1 DNA replication at OriR, suggesting novel characteristics of autonomous parvovirus DNA replication. IMPORTANCE Human bocavirus 1 (HBoV1) causes acute respiratory tract infections in young children. The duplex HBoV1 genome replicates in HEK293 cells and produces progeny virions that are infectious in well-differentiated airway epithelial cells. A recombinant AAV2 vector pseudotyped with an HBoV1 capsid has been developed to efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to human airway epithelia. Here, we identified both cis-acting elements and trans-acting proteins that are required for HBoV1 DNA replication at the right-end hairpin in HEK293 cells. We localized the minimal replication origin, which contains both NS1 nicking and binding sites, to a 46-nucleotide sequence in the right-end hairpin. The identification of these essential elements of HBoV1 DNA replication acting both in cis and in trans will provide guidance to develop antiviral strategies targeting viral DNA replication at the right-end hairpin and to design next-generation recombinant HBoV1 vectors, a promising tool for gene therapy of lung diseases. PMID:27334591

Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome.

PubMed

Shen, Weiran; Deng, Xuefeng; Zou, Wei; Engelhardt, John F; Yan, Ziying; Qiu, Jianming

2016-09-01

Parvoviruses are single-stranded DNA viruses that use the palindromic structures at the ends of the viral genome for their replication. The mechanism of parvovirus replication has been studied mostly in the dependoparvovirus adeno-associated virus 2 (AAV2) and the protoparvovirus minute virus of mice (MVM). Here, we used human bocavirus 1 (HBoV1) to understand the replication mechanism of bocaparvovirus. HBoV1 is pathogenic to humans, causing acute respiratory tract infections, especially in young children under 2 years old. By using the duplex replicative form of the HBoV1 genome in human embryonic kidney 293 (HEK293) cells, we identified the HBoV1 minimal replication origin at the right-end hairpin (OriR). Mutagenesis analyses confirmed the putative NS1 binding and nicking sites within the OriR. Of note, unlike the large nonstructural protein (Rep78/68 or NS1) of other parvoviruses, HBoV1 NS1 did not specifically bind OriR in vitro, indicating that other viral and cellular components or the oligomerization of NS1 is required for NS1 binding to the OriR. In vivo studies demonstrated that residues responsible for NS1 binding and nicking are within the origin-binding domain. Further analysis identified that the small nonstructural protein NP1 is required for HBoV1 DNA replication at OriR. NP1 and other viral nonstructural proteins (NS1 to NS4) colocalized within the viral DNA replication centers in both OriR-transfected cells and virus-infected cells, highlighting a direct involvement of NP1 in viral DNA replication at OriR. Overall, our study revealed the characteristics of HBoV1 DNA replication at OriR, suggesting novel characteristics of autonomous parvovirus DNA replication. Human bocavirus 1 (HBoV1) causes acute respiratory tract infections in young children. The duplex HBoV1 genome replicates in HEK293 cells and produces progeny virions that are infectious in well-differentiated airway epithelial cells. A recombinant AAV2 vector pseudotyped with an HBoV1 capsid has been developed to efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to human airway epithelia. Here, we identified both cis-acting elements and trans-acting proteins that are required for HBoV1 DNA replication at the right-end hairpin in HEK293 cells. We localized the minimal replication origin, which contains both NS1 nicking and binding sites, to a 46-nucleotide sequence in the right-end hairpin. The identification of these essential elements of HBoV1 DNA replication acting both in cis and in trans will provide guidance to develop antiviral strategies targeting viral DNA replication at the right-end hairpin and to design next-generation recombinant HBoV1 vectors, a promising tool for gene therapy of lung diseases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Fight fire with fire: Gene therapy strategies to cure HIV.

PubMed

Huyghe, Jon; Magdalena, Sips; Vandekerckhove, Linos

2017-08-01

Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive. Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART. Nevertheless, this latent HIV reservoir is fully capable to refuel viral replication when treatment is stopped, creating a major obstacle towards a cure for HIV. Several gene therapy approaches ranging from the generation of HIV resistant CD4 + T cells to the eradication of HIV infected cells by immune cell engineering are currently under pre-clinical and clinical investigation and may present a promising road to a cure. In this review, we focus on the status and the prospects of gene therapy strategies to cure/eradicate HIV. Expert commentary: Recent advances in gene therapy for oncology and infectious diseases indicate that gene therapy may be a feasible and very potent cure strategy, and therefore a potential game changer in the search for an effective HIV cure.

TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

PubMed

Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

2015-05-01

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts

PubMed Central

Bernstein, Diana L.; Le Lay, John E.; Ruano, Elena G.; Kaestner, Klaus H.

2015-01-01

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator–like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics. PMID:25866970

Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases.

PubMed

Al-Bari, Md Abdul Alim

2017-02-01

Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated. Since the analogs have interesting biochemical properties, these drugs are found to be effective against a wide variety of viral infections. As antiviral action, the analogs have been shown to inhibit acidification of endosome during the events of replication and infection. Moreover, immunomodulatory effects of analogs have been beneficial to patients with severe inflammatory complications of several viral diseases. Interestingly, one of the successful targeting strategies is the inhibition of HIV replication by the analogs in vitro which are being tested in several clinical trials. This review focuses on the potentialities of chloroquine analogs for the treatment of endosomal low pH dependent emerging viral diseases.

TCC: an R package for comparing tag count data with robust normalization strategies

PubMed Central

2013-01-01

Background Differential expression analysis based on “next-generation” sequencing technologies is a fundamental means of studying RNA expression. We recently developed a multi-step normalization method (called TbT) for two-group RNA-seq data with replicates and demonstrated that the statistical methods available in four R packages (edgeR, DESeq, baySeq, and NBPSeq) together with TbT can produce a well-ranked gene list in which true differentially expressed genes (DEGs) are top-ranked and non-DEGs are bottom ranked. However, the advantages of the current TbT method come at the cost of a huge computation time. Moreover, the R packages did not have normalization methods based on such a multi-step strategy. Results TCC (an acronym for Tag Count Comparison) is an R package that provides a series of functions for differential expression analysis of tag count data. The package incorporates multi-step normalization methods, whose strategy is to remove potential DEGs before performing the data normalization. The normalization function based on this DEG elimination strategy (DEGES) includes (i) the original TbT method based on DEGES for two-group data with or without replicates, (ii) much faster methods for two-group data with or without replicates, and (iii) methods for multi-group comparison. TCC provides a simple unified interface to perform such analyses with combinations of functions provided by edgeR, DESeq, and baySeq. Additionally, a function for generating simulation data under various conditions and alternative DEGES procedures consisting of functions in the existing packages are provided. Bioinformatics scientists can use TCC to evaluate their methods, and biologists familiar with other R packages can easily learn what is done in TCC. Conclusion DEGES in TCC is essential for accurate normalization of tag count data, especially when up- and down-regulated DEGs in one of the samples are extremely biased in their number. TCC is useful for analyzing tag count data in various scenarios ranging from unbiased to extremely biased differential expression. TCC is available at http://www.iu.a.u-tokyo.ac.jp/~kadota/TCC/ and will appear in Bioconductor (http://bioconductor.org/) from ver. 2.13. PMID:23837715

Innate immunity against HIV: a priority target for HIV prevention research.

PubMed

Borrow, Persephone; Shattock, Robin J; Vyakarnam, Annapurna

2010-10-11

This review summarizes recent advances and current gaps in understanding of innate immunity to human immunodeficiency virus (HIV) infection, and identifies key scientific priorities to enable application of this knowledge to the development of novel prevention strategies (vaccines and microbicides). It builds on productive discussion and new data arising out of a workshop on innate immunity against HIV held at the European Commission in Brussels, together with recent observations from the literature.Increasing evidence suggests that innate responses are key determinants of the outcome of HIV infection, influencing critical events in the earliest stages of infection including the efficiency of mucosal HIV transmission, establishment of initial foci of infection and local virus replication/spread as well as virus dissemination, the ensuing acute burst of viral replication, and the persisting viral load established. They also impact on the subsequent level of ongoing viral replication and rate of disease progression. Modulation of innate immunity thus has the potential to constitute a powerful effector strategy to complement traditional approaches to HIV prophylaxis and therapy. Importantly, there is increasing evidence to suggest that many arms of the innate response play both protective and pathogenic roles in HIV infection. Consequently, understanding the contributions made by components of the host innate response to HIV acquisition/spread versus control is a critical pre-requisite for the employment of innate immunity in vaccine or microbicide design, so that appropriate responses can be targeted for up- or down-modulation. There is also an important need to understand the mechanisms via which innate responses are triggered and mediate their activity, and to define the structure-function relationships of individual innate factors, so that they can be selectively exploited or inhibited. Finally, strategies for achieving modulation of innate functions need to be developed and subjected to rigorous testing to ensure that they achieve the desired level of protection without stimulation of immunopathological effects. Priority areas are identified where there are opportunities to accelerate the translation of recent gains in understanding of innate immunity into the design of improved or novel vaccine and microbicide strategies against HIV infection.

Replicator dynamics with turnover of players

NASA Astrophysics Data System (ADS)

Juul, Jeppe; Kianercy, Ardeshir; Bernhardsson, Sebastian; Pigolotti, Simone

2013-08-01

We study adaptive dynamics in games where players abandon the population at a given rate and are replaced by naive players characterized by a prior distribution over the admitted strategies. We demonstrate how such a process leads macroscopically to a variant of the replicator equation, with an additional term accounting for player turnover. We study how Nash equilibria and the dynamics of the system are modified by this additional term for prototypical examples such as the rock-paper-scissors game and different classes of two-action games played between two distinct populations. We conclude by showing how player turnover can account for nontrivial departures from Nash equilibria observed in data from lowest unique bid auctions.

Interplay between Herpesvirus Infection and Host Defense by PML Nuclear Bodies.

PubMed

Tavalai, Nina; Stamminger, Thomas

2009-12-01

In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication at different stages. The antiviral function of ND10, however, is antagonized by viral regulatory proteins (e.g., ICP0 of herpes simplex virus; IE1 of human cytomegalovirus) which induce either a modification or disruption of ND10. This review will summarize the current knowledge on how viral replication is inhibited by ND10 proteins. Furthermore, herpesviral strategies to defeat this host defense mechanism are discussed.

Origin, History, and Meanings of the Word Transmission.

PubMed

Villalba, Joaquín; Navarro, Fernando A; Cortés, Francisco

2017-12-01

The origin of the words transmit and transmission and their derivatives can be traced to the Latin transmittere , in turn formed by prefixing the preposition trans ("across or beyond") to the verb mittere ("to let go or to send"). From the times of Ancient Rome in the 3rd century b.c.e., the Latin word transmissio has been "transmitted" (through Romance languages such as French, Italian, Spanish, and Portuguese) to all the major languages of culture, English among them. And through English, the international language of biomedical science in the 21st century, the term transmission is increasingly present today in some of the most dynamic disciplines of modern natural science, including genomics, molecular microbiology, hospital epidemiology, molecular genetics, biotechnology, evolutionary biology, and systems biology.

Internet and Advertisement.

PubMed

Moustafa, Khaled

2016-02-01

The Internet has revolutionized the way knowledge is currently produced, stored and disseminated. A few finger clicks on a keyboard can save time and many hours of search in libraries or shopping in stores. Online trademarks with an (e-) prefix such as e-library, e-business, e-health etc., are increasingly part of our daily professional vocabularies. However, the Internet has also produced multiple negative side effects, ranging from an unhealthy dependency to a dehumanization of human relationships. Fraudulent, unethical and scam practices are also flourishing through for example misleading online advertising methods. Some social and professional networks gather users' profiles for selling and advertising purposes, sometimes by making it technically difficult to unsubscribe. Here, I discuss some of these unethical aspects and propose some potential solutions to reduce them.

[Efficacy of mental health prevention and promotion strategies in higher education].

PubMed

Martineau, Marc; Beauchamp, Guy; Marcotte, Diane

Recent studies inform of increases in reported mental health problems in higher education students worldwide, with suicide and homicide being the most dramatic outcomes. Improving first-hand intervention and implementing mental health prevention and promotion strategies in colleges and universities are amongst the most commonly mentioned means of addressing these concerns. While institutions increasingly favor mental health promotion, most programs have not been properly evaluated and most strategies cannot be replicated. The article analyses results obtained from literature reviews and meta-analysis focusing on mental health prevention and promotion strategies targeting college and university students. Mindfulness, cognitive-behavioral and relaxation strategies, as well as social ability training, appeared to be the most effective if they were practiced under supervision. The implementation of supervised mental health prevention strategies within a setting-based systematic and multifactorial promotion frame could significantly decrease mental health problems in higher education students.

Costly Advertising and the Evolution of Cooperation

PubMed Central

Brede, Markus

2013-01-01

In this paper, I investigate the co-evolution of fast and slow strategy spread and game strategies in populations of spatially distributed agents engaged in a one off evolutionary dilemma game. Agents are characterized by a pair of traits, a game strategy (cooperate or defect) and a binary ‘advertising’ strategy (advertise or don’t advertise). Advertising, which comes at a cost , allows investment into faster propagation of the agents’ traits to adjacent individuals. Importantly, game strategy and advertising strategy are subject to the same evolutionary mechanism. Via analytical reasoning and numerical simulations I demonstrate that a range of advertising costs exists, such that the prevalence of cooperation is significantly enhanced through co-evolution. Linking costly replication to the success of cooperators exposes a novel co-evolutionary mechanism that might contribute towards a better understanding of the origins of cooperation-supporting heterogeneity in agent populations. PMID:23861752

Costly advertising and the evolution of cooperation.

PubMed

Brede, Markus

2013-01-01

In this paper, I investigate the co-evolution of fast and slow strategy spread and game strategies in populations of spatially distributed agents engaged in a one off evolutionary dilemma game. Agents are characterized by a pair of traits, a game strategy (cooperate or defect) and a binary 'advertising' strategy (advertise or don't advertise). Advertising, which comes at a cost [Formula: see text], allows investment into faster propagation of the agents' traits to adjacent individuals. Importantly, game strategy and advertising strategy are subject to the same evolutionary mechanism. Via analytical reasoning and numerical simulations I demonstrate that a range of advertising costs exists, such that the prevalence of cooperation is significantly enhanced through co-evolution. Linking costly replication to the success of cooperators exposes a novel co-evolutionary mechanism that might contribute towards a better understanding of the origins of cooperation-supporting heterogeneity in agent populations.

Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor

PubMed Central

Richardson, Max W.; Ellebrecht, Christoph T.; Glover, Joshua A.; Secreto, Anthony J.; Kulikovskaya, Irina; Yi, Yanjie; Wang, Jianbin; Dufendach, Keith A.; Holmes, Michael C.; Collman, Ronald G.

2017-01-01

HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy. PMID:29023549

A human fecal contamination score for ranking recreational sites using the HF183/BacR287 quantitative real-time PCR method.

PubMed

Cao, Yiping; Sivaganesan, Mano; Kelty, Catherine A; Wang, Dan; Boehm, Alexandria B; Griffith, John F; Weisberg, Stephen B; Shanks, Orin C

2018-01-01

Human fecal pollution of recreational waters remains a public health concern worldwide. As a result, there is a growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for water quality research and management. However, there are currently no standardized approaches for field implementation and interpretation of qPCR data. In this study, a standardized HF183/BacR287 qPCR method was combined with a water sampling strategy and a novel Bayesian weighted average approach to establish a human fecal contamination score (HFS) that can be used to prioritize sampling sites for remediation based on measured human waste levels. The HFS was then used to investigate 975 study design scenarios utilizing different combinations of sites with varying sampling intensities (daily to once per week) and number of qPCR replicates per sample (2-14 replicates). Findings demonstrate that site prioritization with HFS is feasible and that both sampling intensity and number of qPCR replicates influence reliability of HFS estimates. The novel data analysis strategy presented here provides a prescribed approach for the implementation and interpretation of human-associated HF183/BacR287 qPCR data with the goal of site prioritization based on human fecal pollution levels. In addition, information is provided for future users to customize study designs for optimal HFS performance. Published by Elsevier Ltd.

Self-Replication of Localized Vegetation Patches in Scarce Environments

NASA Astrophysics Data System (ADS)

Bordeu, Ignacio; Clerc, Marcel G.; Couteron, Piere; Lefever, René; Tlidi, Mustapha

2016-09-01

Desertification due to climate change and increasing drought periods is a worldwide problem for both ecology and economy. Our ability to understand how vegetation manages to survive and propagate through arid and semiarid ecosystems may be useful in the development of future strategies to prevent desertification, preserve flora—and fauna within—or even make use of scarce resources soils. In this paper, we study a robust phenomena observed in semi-arid ecosystems, by which localized vegetation patches split in a process called self-replication. Localized patches of vegetation are visible in nature at various spatial scales. Even though they have been described in literature, their growth mechanisms remain largely unexplored. Here, we develop an innovative statistical analysis based on real field observations to show that patches may exhibit deformation and splitting. This growth mechanism is opposite to the desertification since it allows to repopulate territories devoid of vegetation. We investigate these aspects by characterizing quantitatively, with a simple mathematical model, a new class of instabilities that lead to the self-replication phenomenon observed.

3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV

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

Aly, Hussein Hassan; Shimotohno, Kunitada; Hijikata, Makoto

2009-02-06

Due to the high polymorphism of natural hepatitis C virus (HCV) variants, existing recombinant HCV replication models have failed to be effective in developing effective anti-HCV agents. In the current study, we describe an in vitro system that supports the infection and replication of natural HCV from patient blood using an immortalized primary human hepatocyte cell line cultured in a three-dimensional (3D) culture system. Comparison of the gene expression profile of cells cultured in the 3D system to those cultured in the existing 2D system demonstrated an up-regulation of several genes activated by peroxisome proliferator-activated receptor alpha (PPAR{alpha}) signaling. Furthermore,more » using PPAR{alpha} agonists and antagonists, we also analyzed the effect of PPAR{alpha} signaling on the modulation of HCV replication using this system. The 3D in vitro system described in this study provides significant insight into the search for novel anti-HCV strategies that are specific to various strains of HCV.« less

Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.

PubMed

Bray, Mike; Geisbert, Thomas W

2005-08-01

Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression of interferon responses. Infected dendritic cells also secrete proinflammatory mediators, but cannot initiate antigen-specific responses. In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic shock. Massive "bystander" apoptosis of natural killer and T cells further impairs immunity. These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival.

Canonical and Non-Canonical Autophagy in HIV-1 Replication Cycle

PubMed Central

Leymarie, Olivier; Lepont, Leslie; Berlioz-Torrent, Clarisse

2017-01-01

Autophagy is a lysosomal-dependent degradative process essential for maintaining cellular homeostasis, and is a key player in innate and adaptive immune responses to intracellular pathogens such as human immunodeficiency virus type 1 (HIV-1). In HIV-1 target cells, autophagy mechanisms can (i) selectively direct viral proteins and viruses for degradation; (ii) participate in the processing and presentation of viral-derived antigens through major histocompatibility complexes; and (iii) contribute to interferon production in response to HIV-1 infection. As a consequence, HIV-1 has evolved different strategies to finely regulate the autophagy pathway to favor its replication and dissemination. HIV-1 notably encodes accessory genes encoding Tat, Nef and Vpu proteins, which are able to perturb and hijack canonical and non-canonical autophagy mechanisms. This review outlines the current knowledge on the complex interplay between autophagy and HIV-1 replication cycle, providing an overview of the autophagy-mediated molecular processes deployed both by infected cells to combat the virus and by HIV-1 to evade antiviral response. PMID:28946621

Selective Entrapment of Extrachromosomally Amplified DNA by Nuclear Budding and Micronucleation during S Phase

PubMed Central

Shimizu, Noriaki; Itoh, Nobuo; Utiyama, Hiroyasu; Wahl, Geoffrey M.

1998-01-01

Acentric, autonomously replicating extrachromosomal structures called double-minute chromosomes (DMs) frequently mediate oncogene amplification in human tumors. We show that DMs can be removed from the nucleus by a novel micronucleation mechanism that is initiated by budding of the nuclear membrane during S phase. DMs containing c-myc oncogenes in a colon cancer cell line localized to and replicated at the nuclear periphery. Replication inhibitors increased micronucleation; cell synchronization and bromodeoxyuridine–pulse labeling demonstrated de novo formation of buds and micronuclei during S phase. The frequencies of S-phase nuclear budding and micronucleation were increased dramatically in normal human cells by inactivating p53, suggesting that an S-phase function of p53 minimizes the probability of producing the broken chromosome fragments that induce budding and micronucleation. These data have implications for understanding the behavior of acentric DNA in interphase nuclei and for developing chemotherapeutic strategies based on this new mechanism for DM elimination. PMID:9508765

Viperin restricts chikungunya virus replication and pathology

PubMed Central

Teng, Terk-Shin; Foo, Suan-Sin; Simamarta, Diane; Lum, Fok-Moon; Teo, Teck-Hui; Lulla, Aleksei; Yeo, Nicholas K.W.; Koh, Esther G.L.; Chow, Angela; Leo, Yee-Sin; Merits, Andres; Chin, Keh-Chuang; Ng, Lisa F.P.

2012-01-01

Chikungunya virus (CHIKV) is a mosquito-borne arthralgia arbovirus that is reemergent in sub-Saharan Africa and Southeast Asia. CHIKV infection has been shown to be self-limiting, but the molecular mechanisms of the innate immune response that control CHIKV replication remain undefined. Here, longitudinal transcriptional analyses of PBMCs from a cohort of CHIKV-infected patients revealed that type I IFNs controlled CHIKV infection via RSAD2 (which encodes viperin), an enigmatic multifunctional IFN-stimulated gene (ISG). Viperin was highly induced in monocytes, the major target cell of CHIKV in blood. Anti-CHIKV functions of viperin were dependent on its localization in the ER, and the N-terminal amphipathic α-helical domain was crucial for its antiviral activity in controlling CHIKV replication. Furthermore, mice lacking Rsad2 had higher viremia and severe joint inflammation compared with wild-type mice. Our data demonstrate that viperin is a critical antiviral host protein that controls CHIKV infection and provide a preclinical basis for the design of effective control strategies against CHIKV and other reemerging arthrogenic alphaviruses. PMID:23160199

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

PubMed

Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

2016-08-01

The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. Copyright © 2016 Herod et al.

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

PubMed Central

Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.

2016-01-01

ABSTRACT The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. PMID:27194768

A Language Training Strategy for Teaching Young Language-Delayed Children a Functional Syntactical Form.

ERIC Educational Resources Information Center

Hester, Peggy; Hendrickson, Jo

A modeling procedure involving dynamic interactions was used to train three language-delayed preschool children to emit five-element syntactic responses. A single-subject multiple baseline design using within- and across-subject replication was employed to study the acquisition of expanded "agent-action-object" sentences and the…

Application of GPS and Near-Surface Geophysical Methods to Evaluate Differences Between Agricultural Test Plots

USDA-ARS?s Scientific Manuscript database

A field research facility with two pairs of replicated agricultural test plots (four total) was established at a location in northwest Ohio during 2005 for the purpose of studying water table management strategies. Initial efforts at this field research facility were devoted to evaluating difference...

SELF (Supports for Early Learning Foundations): A Non-Directed Model Demonstration Project. Final Report.

ERIC Educational Resources Information Center

Harrison, Holly

This final report describes achievements and activities of Project SELF (Supports for Early Learning Foundations), a federally funded project in New Mexico which developed, evaluated, and replicated an innovative model that provides strategies for early interventionists and families to support early learning foundations. The project identified…

Crossing the Divide: An Emerging Typology of Postsecondary Bridging for Opportunity Youth

ERIC Educational Resources Information Center

Almeida, Cheryl; Allen, Lili

2016-01-01

Through Job For the Future's (JFF's) work with communities around the country on the Back on Track model, postsecondary bridging strategies have emerged as a particularly critical and especially replicable component of programming for vulnerable youth. This issue brief offers a typology of evidence-informed bridge programming, drawing on…

Effects of thinning on drought vulnerability and climate response in north temperate forest ecosystems

Treesearch

Anthony W. D' Amato; John B. Bradford; Shawn Fraver; Brian J. Palik

2013-01-01

Reducing tree densities through silvicultural thinning has been widely advocated as a strategy for enhancing resistance and resilience to drought, yet few empirical evaluations of this approach exist. We examined detailed dendrochronological data from a long-term (>50 years) replicated thinning experiment to determine if density reductions conferred greater...

The People’s Liberation Army Navy, A Modern Navy With Chinese Characteristics

DTIC Science & Technology

2009-04-01

strategy that does not advocate replicating U.S. or Soviet " blue -water" naval capabilities. Instead, it calls for naval capabilities suited for...strength in 2009 consists of approximately 26 destroyers, 48 fugates , more than 80 missile-armed patrol craft, 58 amphibious ships, 40 mine warfare

Inclusive Education: Identifying Teachers' Strategies for Coping with Perceived Stressors in Inclusive Classrooms

ERIC Educational Resources Information Center

Brackenreed, Darlene

2011-01-01

This research replicates the study conducted by Forlin (2001) in Churchlands, Western Australia. Forlin's Inclusive Education "Teacher Stress and Coping Questionnaire" was adapted from the original questionnaire to more accurately reflect the language and practice of inclusion in Ontario. The purpose of this portion of the study was to…

Effects of Explicit Subtraction Instruction on Fifth Grade Students with Learning Disabilities

ERIC Educational Resources Information Center

Ferreira, Danielle

2009-01-01

This study involved an investigation of the effects of strategy instruction integrated with the concrete-representational-abstract teaching sequence on students with learning disabilities. A multiple probe design across subjects with one replication was used in this study. Two sets of data were analyzed to determine effectiveness of the…

Exploring the Psycho-Social Therapies Through the Personalities of Effective Therapists.

ERIC Educational Resources Information Center

Dent, James K.; Furse, George A.

Several specific research approaches are compared with regard to cost-effectiveness, types of disorders to which they best respond, general strategies, and therapist personality. Replicated findings include: (1) support for both the functional reversal and semantic reversal of the "A-B Scale;" (2) characterization of therapists who are effective…

The Aggregation of Single-Case Results Using Hierarchical Linear Models

ERIC Educational Resources Information Center

Van den Noortgate, Wim; Onghena, Patrick

2007-01-01

To investigate the generalizability of the results of single-case experimental studies, evaluating the effect of one or more treatments, in applied research various simultaneous and sequential replication strategies are used. We discuss one approach for aggregating the results for single-cases: the use of hierarchical linear models. This approach…

Taking the "de" Out of Demotivation.

ERIC Educational Resources Information Center

Chambers, Gary

1993-01-01

Examines ways to motivate students who do not want to learn a foreign language. Questionnaires were completed by 191 year 9 pupils and 7 teachers. The responses of the teachers offered simple strategies that could be replicated without great addition to workload or financial outlay. Responses of a disgruntled minority of students are presented.…

Effects of Two Interventions on Solving Basic Fact Problems by Second Graders with Mathematics Learning Disabilities

ERIC Educational Resources Information Center

Dennis, Minyi Shih; Sorrells, Audrey McCray; Falcomata, Terry S.

2016-01-01

This study used a multiple probe across participants design, replicated across two interventions and counterbalanced across participant groups to examine the effects of number sense intervention and extensive practice intervention on strategy transformation when students with mathematics learning disabilities (MLD) solved basic fact problems. In…

Maximizing Teaching through Brain Research

ERIC Educational Resources Information Center

Pattridge, Gregory C.

2009-01-01

Teachers and parents who read about the brain on the Internet should do so critically to determine fact from opinion. Are the assertions real about certain methods/strategies that claim to be based on brain research? Will they make a difference in their teaching and in achievement levels? Turning theory into fact take time and replication of solid…

Role Play and Simulation: Returning to Teaching for Understanding

ERIC Educational Resources Information Center

Clapper, Timothy C.

2010-01-01

This article describes how simulation and role play can be important learning strategies that will create long-lasting understanding. Simulation involves participating in a very real learning experience that closely resembles an actual setting. These actual settings may be replicated by either employing models or mannequins or in the case of role…

A Randomized Evaluation of the Success for All Middle School Reading Program

ERIC Educational Resources Information Center

Chamberlain, Anne; Daniels, Cecelia; Madden, Nancy A.; Slavin, Robert E.

2007-01-01

This article describes a randomized evaluation of The Reading Edge, a reading program for middle school students. The Reading Edge was designed to integrate findings of research on cooperative learning and metacognitive reading strategies into a replicable reading instructional package that could be implemented effectively in Title I middle…

[Anti-influenza vaccination in animals].

PubMed

Bublot, M

2009-01-01

Until recently, Influenza was considered as a veterinary problem in avian, swine and horse only. New influenza strains able to infect and cause a disease in dogs and cats emerged these last six years. The most widely used influenza veterinary vaccines are the inactivated adjuvanted vaccines which are based on whole or split virus. New technologies have allowed the development of new generation vaccines including modified-live and vector vaccines. Modified-live influenza vaccines are available for horses only but they are in development in other species. Vector vaccines are already in use in chickens (replicative fowlpox vector) and in horses (non-replicative canarypox vector). These vaccines induce a rapid cellular and humoral immunity. Experimental studies have also shown that these vector vaccines are protective in other domestic species. These vector vaccines are compatible with the "DIVA" strategy which consists in differentiating infected from vaccinated animals and which allows disease eradication. The successive use of vector and inactivated vaccines (heterologous "prime-boost") induces a superior protective immunity in domestic poultry and constitutes a promising strategy for the control of H5N1 infection.

How do walkers behave when crossing the way of a mobile robot that replicates human interaction rules?

PubMed

Vassallo, Christian; Olivier, Anne-Hélène; Souères, Philippe; Crétual, Armel; Stasse, Olivier; Pettré, Julien

2018-02-01

Previous studies showed the existence of implicit interaction rules shared by human walkers when crossing each other. Especially, each walker contributes to the collision avoidance task and the crossing order, as set at the beginning, is preserved along the interaction. This order determines the adaptation strategy: the first arrived increases his/her advance by slightly accelerating and changing his/her heading, whereas the second one slows down and moves in the opposite direction. In this study, we analyzed the behavior of human walkers crossing the trajectory of a mobile robot that was programmed to reproduce this human avoidance strategy. In contrast with a previous study, which showed that humans mostly prefer to give the way to a non-reactive robot, we observed similar behaviors between human-human avoidance and human-robot avoidance when the robot replicates the human interaction rules. We discuss this result in relation with the importance of controlling robots in a human-like way in order to ease their cohabitation with humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular mimicry: an important virulence strategy employed by Legionella pneumophila to subvert host functions.

PubMed

Nora, Tamara; Lomma, Mariella; Gomez-Valero, Laura; Buchrieser, Carmen

2009-08-01

It is 32 years since Legionella pneumophila was identified and recognized as a human pathogen, causing the severe form of pneumonia termed Legionnaires' disease, or legionellosis. This bacterium is found in freshwater reservoirs where it replicates in aquatic protozoa and can invade man-made water distribution systems. Although the disease can be treated by antibiotherapy and prevented through surveillance and control measures, reported cases of Legionnaires' disease continue to rise across Europe and outbreaks of major public health significance still occur. Genome sequencing and analyses led to a giant step forward by suggesting new ways by which this intracellular bacterium might subvert host functions. One particular feature revealed was the presence of many eukaryotic-like proteins, possibly mimicking host proteins to allow intracellular replication of Legionella. Here, we describe the identification and analysis of these proteins and report on recent advances detailing the mechanisms by which these proteins function. Finally, comparative and evolutionary genomic aspects regarding the eukaryotic-like proteins are presented. Collectively, these data have shed new light on the virulence strategies of L. pneumophila, a major aspect of which is molecular mimicry.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

PubMed Central

Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-01-01

Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591

Game theory and reciprocity in some extensive form experimental games.

PubMed

McCabe, K A; Rassenti, S J; Smith, V L

1996-11-12

We examine decision making in two-person extensive form game trees using nine treatments that vary matching protocol, payoffs, and payoff information. Our objective is to establish replicable principles of cooperative versus noncooperative behavior that involve the use of signaling, reciprocity, and backward induction strategies, depending on the availability of dominated direct punishing strategies and the probability of repeated interaction with the same partner. Contrary to the predictions of game theory, we find substantial support for cooperation under complete information even in various single-play treatments.

Introduction to Cost Control Strategies for Zero Energy Buildings: High-Performance Design and Construction on a Budget (Fact Sheet)

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

Not Available

2014-09-01

Momentum behind zero energy building design and construction is increasing, presenting a tremendous opportunity for advancing energy performance in the commercial building industry. At the same time, there is a lingering perception that zero energy buildings must be cost prohibitive or limited to showcase projects. Fortunately, an increasing number of projects are demonstrating that high performance can be achieved within typical budgets. This factsheet highlights replicable, recommended strategies for achieving high performance on a budget, based on experiences from past projects.

Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication.

PubMed

Schultz, M J; Tan, A L; Gray, C N; Isern, S; Michael, S F; Frydman, H M; Connor, J H

2018-05-22

Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia w Stri, isolated from Laodelphax striatellus , was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that w Stri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. w Stri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by w Stri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into w Stri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia -infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in w Stri-infected cells. This study's findings increase the potential for application of w Stri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection. IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, Wolbachia w Stri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of Wolbachia w Stri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy. Copyright © 2018 Schultz et al.

The Proximity of Ribosomal Protein Genes to oriC Enhances Vibrio cholerae Fitness in the Absence of Multifork Replication.

PubMed

Soler-Bistué, Alfonso; Timmermans, Michaël; Mazel, Didier

2017-02-28

Recent works suggest that bacterial gene order links chromosome structure to cell homeostasis. Comparative genomics showed that, in fast-growing bacteria, ribosomal protein genes (RP) locate near the replication origin ( oriC ). We recently showed that Vibrio cholerae employs this positional bias as a growth optimization strategy: under fast-growth conditions, multifork replication increases RP dosage and expression. However, RP location may provide advantages in a dosage-independent manner: for example, the physical proximity of the many ribosomal components, in the context of a crowded cytoplasm, may favor ribosome biogenesis. To uncover putative dosage-independent effects, we studied isogenic V. cholerae derivatives in which the major RP locus, S10-spc-α (S10), was relocated to alternative genomic positions. When bacteria grew fast, bacterial fitness was reduced according to the S10 relative distance to oriC The growth of wild-type V. cholerae could not be improved by additional copies of the locus, suggesting a physiologically optimized genomic location. Slow growth is expected to uncouple RP position from dosage, since multifork replication does not occur. Under these conditions, we detected a fitness impairment when S10 was far from oriC Deep sequencing followed by marker frequency analysis in the absence of multifork replication revealed an up to 30% S10 dosage reduction associated with its relocation that closely correlated with fitness alterations. Hence, the impact of S10 location goes beyond a growth optimization strategy during feast periods. RP location may be important during the whole life cycle of this pathogen. IMPORTANCE The role of gene order within the bacterial chromosome is poorly understood. In fast growers, the location of genes linked with the expression of genetic information (i.e., transcription and translation) is biased toward oriC It was proposed that the location of these genes helps to maximize their expression by recruiting multifork replication during fast growth. Our results show that such genomic positioning impacts cell fitness beyond fast-growth conditions, probably across the whole life cycle of fast growers. Thus, the genomic position of key highly expressed genes, such as RP, was finely tuned during the evolution of fast-growing bacteria and may also be important in slow growers. In the near future, many more genes whose genomic position impacts bacterial phenotype will be described. These studies will contribute to discovery the rules of genome organization and application of them for the design of synthetic chromosomes and the creation of artificial life forms. Copyright © 2017 Soler-Bistué et al.

Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release.

PubMed

Chan, Renee W Y; Chan, Louisa L Y; Mok, Chris K P; Lai, Jimmy; Tao, Kin P; Obadan, Adebimpe; Chan, Michael C W; Perez, Daniel R; Peiris, J S Malik; Nicholls, John M

2017-07-24

H9N2 viruses are the most widespread influenza viruses in poultry in Asia. We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung. This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures. The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract. The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.

Separation of replication and transcription domains in nucleoli.

PubMed

Smirnov, E; Borkovec, J; Kováčik, L; Svidenská, S; Schröfel, A; Skalníková, M; Švindrych, Z; Křížek, P; Ovesný, M; Hagen, G M; Juda, P; Michalová, K; Cardoso, M C; Cmarko, D; Raška, I

2014-12-01

In mammalian cells, active ribosomal genes produce the 18S, 5.8S and 28S RNAs of ribosomal particles. Transcription levels of these genes are very high throughout interphase, and the cell needs a special strategy to avoid collision of the DNA polymerase and RNA polymerase machineries. To investigate this problem, we measured the correlation of various replication and transcription signals in the nucleoli of HeLa, HT-1080 and NIH 3T3 cells using a specially devised software for analysis of confocal images. Additionally, to follow the relationship between nucleolar replication and transcription in living cells, we produced a stable cell line expressing GFP-RPA43 (subunit of RNA polymerase I, pol I) and RFP-PCNA (the sliding clamp protein) based on human fibrosarcoma HT-1080 cells. We found that replication and transcription signals are more efficiently separated in nucleoli than in the nucleoplasm. In the course of S phase, separation of PCNA and pol I signals gradually increased. During the same period, separation of pol I and incorporated Cy5-dUTP signals decreased. Analysis of single molecule localization microscopy (SMLM) images indicated that transcriptionally active FC/DFC units (i.e. fibrillar centers with adjacent dense fibrillar components) did not incorporate DNA nucleotides. Taken together, our data show that replication of the ribosomal genes is spatially separated from their transcription, and FC/DFC units may provide a structural basis for that separation. Copyright © 2014 Elsevier Inc. All rights reserved.

Production of pseudoinfectious yellow fever virus with a two-component genome.

PubMed

Shustov, Alexandr V; Mason, Peter W; Frolov, Ilya

2007-11-01

Application of genetically modified, deficient-in-replication flaviviruses that are incapable of developing productive, spreading infection is a promising means of designing safe and effective vaccines. Here we describe a two-component genome yellow fever virus (YFV) replication system in which each of the genomes encodes complete sets of nonstructural proteins that form the replication complex but expresses either only capsid or prM/E instead of the entire structural polyprotein. Upon delivery to the same cell, these genomes produce together all of the viral structural proteins, and cells release a combination of virions with both types of genomes packaged into separate particles. In tissue culture, this modified YFV can be further passaged at an escalating scale by using a high multiplicity of infection (MOI). However, at a low MOI, only one of the genomes is delivered into the cells, and infection cannot spread. The replicating prM/E-encoding genome produces extracellular E protein in the form of secreted subviral particles that are known to be an effective immunogen. The presented strategy of developing viruses defective in replication might be applied to other flaviviruses, and these two-component genome viruses can be useful for diagnostic or vaccine applications, including the delivery and expression of heterologous genes. In addition, the achieved separation of the capsid-coding sequence and the cyclization signal in the YFV genome provides a new means for studying the mechanism of the flavivirus packaging process.

Jointly determining significance levels of primary and replication studies by controlling the false discovery rate in two-stage genome-wide association studies.

PubMed

Jiang, Wei; Yu, Weichuan

2017-01-01

In genome-wide association studies, we normally discover associations between genetic variants and diseases/traits in primary studies, and validate the findings in replication studies. We consider the associations identified in both primary and replication studies as true findings. An important question under this two-stage setting is how to determine significance levels in both studies. In traditional methods, significance levels of the primary and replication studies are determined separately. We argue that the separate determination strategy reduces the power in the overall two-stage study. Therefore, we propose a novel method to determine significance levels jointly. Our method is a reanalysis method that needs summary statistics from both studies. We find the most powerful significance levels when controlling the false discovery rate in the two-stage study. To enjoy the power improvement from the joint determination method, we need to select single nucleotide polymorphisms for replication at a less stringent significance level. This is a common practice in studies designed for discovery purpose. We suggest this practice is also suitable in studies with validation purpose in order to identify more true findings. Simulation experiments show that our method can provide more power than traditional methods and that the false discovery rate is well-controlled. Empirical experiments on datasets of five diseases/traits demonstrate that our method can help identify more associations. The R-package is available at: http://bioinformatics.ust.hk/RFdr.html .

Drawing ability in typical and atypical development; colour cues and the effect of oblique lines.

PubMed

Farran, E K; Dodd, G F

2015-06-01

Individuals with Williams syndrome (WS) have poor drawing ability. Here, we investigated whether colour could be used as a facilitation cue during a drawing task. Participants with WS and non-verbal ability matched typically developing (TD) children were shown line figures presented on a 3 by 3 dot matrix, and asked to replicate the figures by drawing on an empty dot matrix. The dots of the matrix were either all black (control condition), or nine different coloured dots (colour condition). In a third condition, which also used coloured dots, participants were additionally asked to verbalise the colours of the dots prior to replicating the line drawings (colour-verbal condition). Performance was stronger in both WS and TD groups on the two coloured conditions, compared with the control condition. However, the facilitation effect of colour was significantly weaker in the WS group than in the TD group. Replication of oblique line segments was less successful than replication of non-oblique line segments for both groups; this effect was reduced by colour facilitation in the TD group only. Verbalising the colours had no additional impact on performance in either group. We suggest that colour acted as a cue to individuate the dots, thus enabling participants to better ascertain the spatial relationships between the parts of each figure, to determine the start and end points of component lines, and to determine the correspondence between the model and their replication. The reduced facilitation in the WS group is discussed in relation to the effect of oblique versus non-oblique lines, the use of atypical drawing strategies, and reduced attention to the model when drawing the replication. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

PubMed

Foxman, Ellen F; Storer, James A; Vanaja, Kiran; Levchenko, Andre; Iwasaki, Akiko

2016-07-26

Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33-35 °C) than at lung temperature (37 °C). Recent studies found that although 37 °C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication at 37 °C, we studied RV infection in human bronchial epithelial cells and H1-HeLa cells. During the single replication cycle, RV exhibited temperature-dependent replication in both cell types in the absence of IFN induction. At 37 °C, earlier signs of apoptosis in RV-infected cells were accompanied by reduced virus production. Furthermore, apoptosis of epithelial cells was enhanced at 37 °C in response to diverse stimuli. Dynamic mathematical modeling and B cell lymphoma 2 (BCL2) overexpression revealed that temperature-dependent host cell death could partially account for the temperature-dependent growth observed during RV amplification, but also suggested additional mechanisms of virus control. In search of a redundant antiviral pathway, we identified a role for the RNA-degrading enzyme RNAseL. Simultaneous antagonism of apoptosis and RNAseL increased viral replication and dramatically reduced temperature dependence. These findings reveal two IFN-independent mechanisms active in innate defense against RV, and demonstrate that even in the absence of IFNs, temperature-dependent RV amplification is largely a result of host cell antiviral restriction mechanisms operating more effectively at 37 °C than at 33 °C.

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

PubMed Central

Müller, Christian; Schillert, Arne; Röthemeier, Caroline; Trégouët, David-Alexandre; Proust, Carole; Binder, Harald; Pfeiffer, Norbert; Beutel, Manfred; Lackner, Karl J.; Schnabel, Renate B.; Tiret, Laurence; Wild, Philipp S.; Blankenberg, Stefan

2016-01-01

Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data. PMID:27272489

A risk hedging strategy under the nonparallel-shift yield curve

NASA Astrophysics Data System (ADS)

Gong, Pu; He, Xubiao

2005-08-01

Under the assumption of the movement of rigid, a nonparallel-shift model in the term structure of interest rates is developed by introducing Fisher & Weil duration which is a well-known concept in the area of interest risk management. This paper has studied the hedge and replication for portfolio immunization to minimize the risk exposure. Throughout the experiment of numerical simulation, the risk exposures of the portfolio under the different risk hedging strategies are quantitatively evaluated by the method of value at risk (VaR) order statistics (OS) estimation. The results show that the risk hedging strategy proposed in this paper is very effective for the interest risk management of the default-free bond.

Immunization against Small Ruminant Lentiviruses

PubMed Central

Reina, Ramsés; de Andrés, Damián; Amorena, Beatriz

2013-01-01

Multisystemic disease caused by Small Ruminant Lentiviruses (SRLV) in sheep and goats leads to production losses, to the detriment of animal health and welfare. This, together with the lack of treatments, has triggered interest in exploring different strategies of immunization to control the widely spread SRLV infection and, also, to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding viral proteins in the presence or absence of plasmids encoding immunological adjuvants and naturally or artificially attenuated viruses. In this review, we revisit, comprehensively, the immunization strategies against SRLV and analyze this double edged tool individually, as it may contribute to either controlling or enhancing virus replication and/or disease. PMID:23917352

Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update

PubMed Central

Aneja, Kawalpreet K.; Yuan, Yan

2017-01-01

The life cycle of Kaposi’s sarcoma-associated herpesvirus (KSHV) consists of two phases, latent and lytic. The virus establishes latency as a strategy for avoiding host immune surveillance and fusing symbiotically with the host for lifetime persistent infection. However, latency can be disrupted and KSHV is reactivated for entry into the lytic replication. Viral lytic replication is crucial for efficient dissemination from its long-term reservoir to the sites of disease and for the spread of the virus to new hosts. The balance of these two phases in the KSHV life cycle is important for both the virus and the host and control of the switch between these two phases is extremely complex. Various environmental factors such as oxidative stress, hypoxia, and certain chemicals have been shown to switch KSHV from latency to lytic reactivation. Immunosuppression, unbalanced inflammatory cytokines, and other viral co-infections also lead to the reactivation of KSHV. This review article summarizes the current understanding of the initiation and regulation of KSHV reactivation and the mechanisms underlying the process of viral lytic replication. In particular, the central role of an immediate-early gene product RTA in KSHV reactivation has been extensively investigated. These studies revealed multiple layers of regulation in activation of RTA as well as the multifunctional roles of RTA in the lytic replication cascade. Epigenetic regulation is known as a critical layer of control for the switch of KSHV between latency and lytic replication. The viral non-coding RNA, PAN, was demonstrated to play a central role in the epigenetic regulation by serving as a guide RNA that brought chromatin remodeling enzymes to the promoters of RTA and other lytic genes. In addition, a novel dimension of regulation by microPeptides emerged and has been shown to regulate RTA expression at the protein level. Overall, extensive investigation of KSHV reactivation and lytic replication has revealed a sophisticated regulation network that controls the important events in KSHV life cycle. PMID:28473805

Selection Bias, Vote Counting, and Money-Priming Effects: A Comment on Rohrer, Pashler, and Harris (2015) and Vohs (2015)

PubMed Central

2016-01-01

When a series of studies fails to replicate a well-documented effect, researchers might be tempted to use a “vote counting” approach to decide whether the effect is reliable—that is, simply comparing the number of successful and unsuccessful replications. Vohs’s (2015) response to the absence of money priming effects reported by Rohrer, Pashler, and Harris (2015) provides an example of this approach. Unfortunately, vote counting is a poor strategy to assess the reliability of psychological findings because it neglects the impact of selection bias and questionable research practices. In the present comment, we show that a range of meta-analytic tools indicate irregularities in the money priming literature discussed by Rohrer et al. and Vohs, which all point to the conclusion that these effects are distorted by selection bias, reporting biases, or p-hacking. This could help to explain why money-priming effects have proven unreliable in a number of direct replication attempts in which biases have been minimized through preregistration or transparent reporting. Our major conclusion is that the simple proportion of significant findings is a poor guide to the reliability of research and that preregistered replications are an essential means to assess the reliability of money-priming effects. PMID:27077759

Selection bias, vote counting, and money-priming effects: A comment on Rohrer, Pashler, and Harris (2015) and Vohs (2015).

PubMed

Vadillo, Miguel A; Hardwicke, Tom E; Shanks, David R

2016-05-01

When a series of studies fails to replicate a well-documented effect, researchers might be tempted to use a "vote counting" approach to decide whether the effect is reliable-that is, simply comparing the number of successful and unsuccessful replications. Vohs's (2015) response to the absence of money priming effects reported by Rohrer, Pashler, and Harris (2015) provides an example of this approach. Unfortunately, vote counting is a poor strategy to assess the reliability of psychological findings because it neglects the impact of selection bias and questionable research practices. In the present comment, we show that a range of meta-analytic tools indicate irregularities in the money priming literature discussed by Rohrer et al. and Vohs, which all point to the conclusion that these effects are distorted by selection bias, reporting biases, or p-hacking. This could help to explain why money-priming effects have proven unreliable in a number of direct replication attempts in which biases have been minimized through preregistration or transparent reporting. Our major conclusion is that the simple proportion of significant findings is a poor guide to the reliability of research and that preregistered replications are an essential means to assess the reliability of money-priming effects. (c) 2016 APA, all rights reserved).

Recent Progress in Understanding Coxsackievirus Replication, Dissemination, and Pathogenesis

PubMed Central

Sin, Jon; Mangale, Vrushali; Thienphrapa, Wdee; Gottlieb, Roberta A.; Feuer, Ralph

2015-01-01

Coxsackieviruses (CVs) are relatively common viruses associated with a number of serious human diseases, including myocarditis and meningo-encephalitis. These viruses are considered cytolytic yet can persist for extended periods of time within certain host tissues requiring evasion from the host immune response and a greatly reduced rate of replication. A member of Picornaviridae family, CVs have been historically considered non-enveloped viruses – although recent evidence suggest that CV and other picornaviruses hijack host membranes and acquire an envelope. Acquisition of an envelope might provide distinct benefits to CV virions, such as resistance to neutralizing antibodies and efficient nonlytic viral spread. CV exhibits a unique tropism for progenitor cells in the host which may help to explain the susceptibility of the young host to infection and the establishment of chronic disease in adults. CVs have also been shown to exploit autophagy to maximize viral replication and assist in unconventional release from target cells. In this article, we review recent progress in clarifying virus replication and dissemination within the host cell, identifying determinants of tropism, and defining strategies utilized by the virus to evade the host immune response. Also, we will highlight unanswered questions and provide future perspectives regarding the potential mechanisms of CV pathogenesis. PMID:26142496

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

PubMed

See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

2008-09-01

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

Healthcare information systems: data mining methods in the creation of a clinical recommender system

NASA Astrophysics Data System (ADS)

Duan, L.; Street, W. N.; Xu, E.

2011-05-01

Recommender systems have been extensively studied to present items, such as movies, music and books that are likely of interest to the user. Researchers have indicated that integrated medical information systems are becoming an essential part of the modern healthcare systems. Such systems have evolved to an integrated enterprise-wide system. In particular, such systems are considered as a type of enterprise information systems or ERP system addressing healthcare industry sector needs. As part of efforts, nursing care plan recommender systems can provide clinical decision support, nursing education, clinical quality control, and serve as a complement to existing practice guidelines. We propose to use correlations among nursing diagnoses, outcomes and interventions to create a recommender system for constructing nursing care plans. In the current study, we used nursing diagnosis data to develop the methodology. Our system utilises a prefix-tree structure common in itemset mining to construct a ranked list of suggested care plan items based on previously-entered items. Unlike common commercial systems, our system makes sequential recommendations based on user interaction, modifying a ranked list of suggested items at each step in care plan construction. We rank items based on traditional association-rule measures such as support and confidence, as well as a novel measure that anticipates which selections might improve the quality of future rankings. Since the multi-step nature of our recommendations presents problems for traditional evaluation measures, we also present a new evaluation method based on average ranking position and use it to test the effectiveness of different recommendation strategies.

Negative Feedback Regulation of HIV-1 by Gene Editing Strategy.

PubMed

Kaminski, Rafal; Chen, Yilan; Salkind, Julian; Bella, Ramona; Young, Won-Bin; Ferrante, Pasquale; Karn, Jonathan; Malcolm, Thomas; Hu, Wenhui; Khalili, Kamel

2016-08-16

The CRISPR/Cas9 gene editing method is comprised of the guide RNA (gRNA) to target a specific DNA sequence for cleavage and the Cas9 endonuclease for introducing breaks in the double-stranded DNA identified by the gRNA. Co-expression of both a multiplex of HIV-1-specific gRNAs and Cas9 in cells results in the modification and/or excision of the segment of viral DNA, leading to replication-defective virus. In this study, we have personalized the activity of CRISPR/Cas9 by placing the gene encoding Cas9 under the control of a minimal promoter of HIV-1 that is activated by the HIV-1 Tat protein. We demonstrate that functional activation of CRISPR/Cas9 by Tat during the course of viral infection excises the designated segment of the integrated viral DNA and consequently suppresses viral expression. This strategy was also used in a latently infected CD4+ T-cell model after treatment with a variety of HIV-1 stimulating agents including PMA and TSA. Controlled expression of Cas9 by Tat offers a new strategy for safe implementation of the Cas9 technology for ablation of HIV-1 at a very early stage of HIV-1 replication during the course of the acute phase of infection and the reactivation of silent proviral DNA in latently infected cells.

The Benefits of Peer Collaboration: A Replication with a Delayed Posttest.

PubMed

Fleming, Victoria Manion; Alexander, Joyce M.

2001-10-01

The benefits of peer collaboration on strategy use, metacognitive causal attribution, and recall were supported in an earlier study (Manion & Alexander, 1997). Following that study two primary questions remained: Would the observed benefits last beyond an immediate posttest, and would they last regardless of which strategy the children chose to use? The current investigation explores those questions. Thirty-one fourth-grade students from two public schools in Sydney, Australia, experienced either a peer-collaborative treatment condition or an individual task (control condition). A posttest was conducted 5.5 weeks later. As was the case in the original study, children in the treatment condition outperformed children in the control condition in strategy use, metacognitive understanding of strategy chosen, and recall gain. Benefits also sustained regardless of the strategy children chose to implement on the task. Most importantly, the benefits lasted after a period of over a month. Implications for future research are discussed. Copyright 2001 Academic Press.

Chimpanzees Immunized with Recombinant Soluble CD4 Develop Anti-Self CD4 Antibody Responses with Anti-Human Immunodeficiency Virus Activity

NASA Astrophysics Data System (ADS)

Watanabe, Mamoru; Boyson, Jonathan E.; Lord, Carol I.; Letvin, Norman L.

1992-06-01

In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

PubMed Central

Li, Haoyang; Hua, Chen; Zhang, Hanzhen

2017-01-01

Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4+ T cells. Currently, two types of HIV cures are in development: a “sterilizing cure” and a “functional cure.” A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment. Based on these concepts, significant progress has been made in different areas. This review focuses on recent advancements and future prospects for HIV cures. PMID:28529952

Multifarious immunotherapeutic approaches to cure HIV-1 infection.

PubMed

Imami, Nesrina; Herasimtschuk, Anna A

2015-01-01

Immunotherapy in the context of treated HIV-1 infection aims to improve immune responses to achieve better control of the virus. To date, multifaceted immunotherapeutic approaches have been shown to reduce immune activation and increase CD4 T-lymphocyte counts, further to the effects of antiretroviral therapy alone, in addition to improving HIV-1-specific T-cell responses. While sterilizing cure of HIV-1 would involve elimination of all replication-competent virus, a functional cure in which the host has long-lasting control of viral replication may be more feasible. In this commentary, we discuss novel strategies aimed at targeting the latent viral reservoir with cure of HIV-1 infection being the ultimate goal, an achievement that would have considerable impact on worldwide HIV-1 infection.

Immediate response strategy and shift to place strategy in submerged T-maze.

PubMed

Asem, Judith S A; Holland, Peter C

2013-12-01

A considerable amount of research has demonstrated that animals can use different strategies when learning about, and navigating within, their environment. Since the influential research of Packard and McGaugh (1996), it has been widely accepted that, early in learning, rats use a flexible dorsal hippocampal-dependent place strategy. As learning progresses, they switch to a less effortful and more automatic dorsolateral caudate-dependent response strategy. However, supporting literature is dominated by the use of appetitively motivated tasks, using food reward. Because motivation often plays a crucial role in guiding learning, memory, and behavior, we examined spatial learning strategies of rats in an escape-motivated submerged T-maze. In Experiment 1, we observed rapid learning and the opposite pattern as that reported in appetitively motivated tasks. Rats exhibited a response strategy early in learning before switching to a place strategy, which persisted over extensive training. In Experiment 2, we replicated Packard and McGaugh's (1996) observations, using the apparatus and procedures as in Experiment 1, but with food reward instead of water escape. Mechanisms for, and implications of, this motivational modulation of spatial learning strategy are considered.

Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

PubMed Central

Zhu, Shimao; Guo, Caiping

2016-01-01

Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies. PMID:27801824

An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006–2015 data for China’s 22 provinces

PubMed Central

Pang, Jinbo; Deng, Lingfei

2017-01-01

Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a “buy” strategy and speculators adopt a “do not speculate” strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies. PMID:28241024

An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006-2015 data for China's 22 provinces.

PubMed

Pang, Jinbo; Deng, Lingfei; Wang, Gangyi

2017-01-01

Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a "buy" strategy and speculators adopt a "do not speculate" strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies.

Protection Against Dengue Virus by Non-Replicating and Live Attenuated Vaccines Used Together in a Prime Boost Vaccination Strategy

DTIC Science & Technology

2010-01-01

vaccines primed rhesus maca - ques for an immune response to a tetravalent live attenuated virus (TLAV) vaccine. An initial experiment was performed in 16...and 4 and no measurable increase for DENV 1. These two experiments clearly demonstrated that rhesus maca - ques could be successfully immunized and

NSW Executive Enhancements

DTIC Science & Technology

1981-06-01

independently on the same network. Given this reduction in scale, the projected impl widely distributed, fully replicated, synchronized dat design...Manager that "owns" other resources. This strategy requires minimum synchronization while providing advantages in reliability and robustness. 2 3...interactive tools on TENEX, transparent file motion and translation, and a primitive set of project management functions. This demonstration confirmed that

Implementation Guide of Suggested School-to-Work Career Guidance Strategies for School Personnel and Students.

ERIC Educational Resources Information Center

Vocational Curriculum Resource Center of Maine, Fairfield.

This guide, which is intended to help practitioners replicate two model career guidance programs developed at Portland Arts and Technology High School in Portland, Maine, contains materials for conducting a course titled "Exploring Industry" and a career fair. The first half of the guide begins with coordinator instructions and logistics…

Comprehensive Evaluation Report for the Canadian Replication of the Families and Schools Together (FAST) Program.

ERIC Educational Resources Information Center

Sass, James S.

Families and Schools Together (FAST) is a 2-year program beginning with 8 weeks of multiple family meetings and transitioning into a long-term follow-up segment called FASTWORKS. FAST uses tested family therapy principles, delinquency and substance-abuse strategies, psychiatric techniques, family systems theory, and group dynamics to give parents…

Leadership's Influence: A Case Study of an Elementary Principal's "Indirect" Impact on Student Achievement

ERIC Educational Resources Information Center

Brown, Goldy, III

2016-01-01

This study investigated leadership supports provided by an elementary principal of 15 years in a high performing diverse school. Employing document analysis and interviews, the researcher gathered and analyzed data in an effort to identify those leadership strategies that could be replicated at other school sites. The study identified the…

Replicating Peer-Led Team Learning in Cyberspace: Research, Opportunities, and Challenges

ERIC Educational Resources Information Center

Smith, Joshua; Wilson, Sarah Beth; Banks, Julianna; Zhu, Lin; Varma-Nelson, Pratibha

2014-01-01

This quasi-experimental, mixed methods study examined the transfer of a well-established pedagogical strategy, Peer-Led Team Learning (PLTL), to an online workshop environment (cPLTL) in a general chemistry course at a research university in the Midwest. The null hypothesis guiding the study was that no substantive differences would emerge between…

Integrated corridor management : stage 3A analysis, modeling, and simulation for the I-15 corridor in San Diego, California, pre-deployment AMS assessment.

DOT National Transportation Integrated Search

2012-08-01

The objective of the Stage 3A AMS efforts is to ensure that the Stage 2 models and methodologies can sufficiently replicate and evaluate corridor conditions and the proposed ICM strategies prior to deployment. In Stage 3A, the AMS contractor and the ...

Reducing Achievement Gaps in Academic Writing for Latinos and English Learners in Grades 7-12

ERIC Educational Resources Information Center

Olson, Carol Booth; Matuchniak, Tina; Chung, Huy Q.; Stumpf, Rachel; Farkas, George

2017-01-01

This study reports 2 years of findings from a randomized controlled trial designed to replicate and demonstrate the efficacy of an existing, successful professional development program, the Pathway Project, that uses a cognitive strategies approach to text-based analytical writing. Building on an earlier randomized field trial in a large, urban,…

Distance Video-Teleconferencing in Early Intervention: Pilot Study of a Naturalistic Parent-Implemented Language Intervention

ERIC Educational Resources Information Center

McDuffie, Andrea; Machalicek, Wendy; Oakes, Ashley; Haebig, Eileen; Weismer, Susan Ellis; Abbeduto, Leonard

2013-01-01

Maternal verbal responsiveness in naturally occurring interactions is known to facilitate language development for children with neurodevelopmental disorders. The present study used a series of A-B replications to examine proximal effects of a naturalistic language intervention on the use of specific language support strategies by mothers of eight…

DNA Replication and Transcription: An Innovative Teaching Strategy

ERIC Educational Resources Information Center

Fossey, Annabel; Hancock, Carolyn

2005-01-01

First-year students in genetics at the University of KwaZulu-Natal, South Africa, attend two general biology modules, one in each semester. Teaching involves four formal lectures per week of 45 min each, one 3-h practical, and one lecture period tutorial. These students, graduating from secondary education, are well schooled in rote learning but…

A Comparison of Prompting Strategies to Teach Intraverbals to an Adolescent with Down Syndrome

ERIC Educational Resources Information Center

Wallace, Abigail M.; Bechtel, D. Reed; Heatter, Sue; Barry, Leasha M.

2016-01-01

Ingvarsson and Hollobaugh (2011) investigated tact- or echoic-to-intraverbal transfer of stimulus control to "wh" questions for three preschool-aged boys with autism. The current study was a systematic replication of this study with an adolescent girl with Down syndrome. A multi-element design was used to compare the effectiveness and…

Economic Development and Maryland Community Colleges: An Identification and Comparison of Stakeholders' Perception

ERIC Educational Resources Information Center

Lee, Carolyn S.

2010-01-01

The purpose of this exploratory survey research was to replicate a study designed to examine the perception of community college administrators and local stakeholders regarding the economic development strategies, but applied to Maryland community colleges. A Web-based survey was directed to community college leaders (32) and local leaders (100).…

Establishing a Eucalyptus energy plantation on the central coast of California

Treesearch

Norman H. Pillsbury; Nelson L. Ayers

1983-01-01

A 17.5-acre non-irrigated biomass energy plantation has been established near San Luis Obispo. This joint California Polytechnic State University - California Department of Forestry project is measuring plot growth response of seven eucalyptus species for three spacing trials and for the effect of fertilization. All study plots are replicated. Site preparation strategy...

New Evidence on Self-Affirmation Effects and Theorized Sources of Heterogeneity from Large-Scale Replications

ERIC Educational Resources Information Center

Hanselman, Paul; Rozek, Christopher S.; Grigg, Jeffrey; Borman, Geoffrey D.

2017-01-01

Brief, targeted self-affirmation writing exercises have recently been offered as a way to reduce racial achievement gaps, but evidence about their effects in educational settings is mixed, leaving ambiguity about the likely benefits of these strategies if implemented broadly. A key limitation in interpreting these mixed results is that they come…

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

Biology doesn't waste energy: that's really smart

NASA Astrophysics Data System (ADS)

Vincent, Julian F. V.; Bogatyreva, Olga; Bogatyrev, Nikolaj

2006-03-01

Biology presents us with answers to design problems that we suspect would be very useful if only we could implement them successfully. We use the Russian theory of problem solving - TRIZ - in a novel way to provide a system for analysis and technology transfer. The analysis shows that whereas technology uses energy as the main means of solving technical problems, biology uses information and structure. Biology is also strongly hierarchical. The suggestion is that smart technology in hierarchical structures can help us to design much more efficient technology. TRIZ also suggests that biological design is autonomous and can be defined by the prefix "self-" with any function. This autonomy extends to the control system, so that the sensor is commonly also the actuator, resulting in simpler systems and greater reliability.

Long frame sync words for binary PSK telemetry

NASA Technical Reports Server (NTRS)

Levitt, B. K.

1975-01-01

Correlation criteria have previously been established for identifying whether a given binary sequence would be a good frame sync word for phase-shift keyed telemetry. In the past, the search for a good K-bit sync word has involved the application of these criteria to the entire set of 2 exponent K binary K-tuples. It is shown that restricting this search to a much smaller subset consisting of K-bit prefixes of pseudonoise sequences results in sync words of comparable quality, with greatly reduced computer search times for larger values of K. As an example, this procedure is used to find good sync words of length 16-63; from a storage viewpoint, each of these sequences can be generated by a 5- or 6-bit linear feedback shift register.

Route Flap Damping Made Usable

NASA Astrophysics Data System (ADS)

Pelsser, Cristel; Maennel, Olaf; Mohapatra, Pradosh; Bush, Randy; Patel, Keyur

The Border Gateway Protocol (BGP), the de facto inter-domain routing protocol of the Internet, is known to be noisy. The protocol has two main mechanisms to ameliorate this, MinRouteAdvertisementInterval (MRAI), and Route Flap Damping (RFD). MRAI deals with very short bursts on the order of a few to 30 seconds. RFD deals with longer bursts, minutes to hours. Unfortunately, RFD was found to severely penalize sites for being well-connected because topological richness amplifies the number of update messages exchanged. So most operators have disabled it. Through measurement, this paper explores the avenue of absolutely minimal change to code, and shows that a few RFD algorithmic constants and limits can be trivially modified, with the result being damping a non-trivial amount of long term churn without penalizing well-behaved prefixes' normal convergence process.

Optimistic barrier synchronization

NASA Technical Reports Server (NTRS)

Nicol, David M.

1992-01-01

Barrier synchronization is fundamental operation in parallel computation. In many contexts, at the point a processor enters a barrier it knows that it has already processed all the work required of it prior to synchronization. The alternative case, when a processor cannot enter a barrier with the assurance that it has already performed all the necessary pre-synchronization computation, is treated. The problem arises when the number of pre-sychronization messages to be received by a processor is unkown, for example, in a parallel discrete simulation or any other computation that is largely driven by an unpredictable exchange of messages. We describe an optimistic O(log sup 2 P) barrier algorithm for such problems, study its performance on a large-scale parallel system, and consider extensions to general associative reductions as well as associative parallel prefix computations.

Phonology without universal grammar

PubMed Central

Archangeli, Diana; Pulleyblank, Douglas

2015-01-01

The question of identifying the properties of language that are specific human linguistic abilities, i.e., Universal Grammar, lies at the center of linguistic research. This paper argues for a largely Emergent Grammar in phonology, taking as the starting point that memory, categorization, attention to frequency, and the creation of symbolic systems are all nonlinguistic characteristics of the human mind. The articulation patterns of American English rhotics illustrate categorization and systems; the distribution of vowels in Bantu vowel harmony uses frequencies of particular sequences to argue against Universal Grammar and in favor of Emergent Grammar; prefix allomorphy in Esimbi illustrates the Emergent symbolic system integrating phonological and morphological generalizations. The Esimbi case has been treated as an example of phonological opacity in a Universal Grammar account; the Emergent analysis resolves the pattern without opacity concerns. PMID:26388791

Hexon modification to improve the activity of oncolytic adenovirus vectors against neoplastic and stromal cells in pancreatic cancer.

PubMed

Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q; Schmidt, Christoph Q Andreas; Wortmann, Andreas; Bachem, Max G; Simmet, Thomas; Kochanek, Stefan

2015-01-01

Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety.

MicroRNA reduction of neuronal West Nile virus replication attenuates and affords a protective immune response in mice

PubMed Central

Brostoff, Terza; Pesavento, Patricia A.; Barker, Christopher M.; Kenney, Joan L.; Dietrich, Elizabeth A.; Duggal, Nisha K.; Bosco-Lauth, Angela M.; Brault, Aaron C.

2017-01-01

West Nile virus (WNV) is an important agent of human encephalitis that has quickly become endemic across much of the United States since its identification in North America in 1999. While the majority (~75%) of infections are subclinical, neurologic disease can occur in a subset of cases, with outcomes including permanent neurologic damage and death. Currently, there are no WNV vaccines approved for use in humans. This study introduces a novel vaccine platform for WNV to reduce viral replication in the central nervous system while maintaining peripheral replication to elicit strong neutralizing antibody titers. Vaccine candidates were engineered to incorporate microRNA (miRNA) target sequences for a cognate miRNA expressed only in neurons, allowing the host miRNAs to target viral transcription through endogenous RNA silencing. To maintain stability, these targets were incorporated in multiple locations within the 3′-untranslated region, flanking sequences essential for viral replication without affecting the viral open reading frame. All candidates replicated comparably to wild type WNV in vitro within cells that did not express the cognate miRNA. Insertional control viruses were also capable of neuroinvasion and neurovirulence in vivo in CD-1 mice. Vaccine viruses were safe at all doses tested and did not demonstrate mutations associated with a reversion to virulence when serially passaged in mice. All vaccine constructs were protective from lethal challenge in mice, producing 93–100% protection at the highest dose tested. Overall, this is a safe and effective attenuation strategy with broad potential application for vaccine development. PMID:27637937

MicroRNA reduction of neuronal West Nile virus replication attenuates and affords a protective immune response in mice.

PubMed

Brostoff, Terza; Pesavento, Patricia A; Barker, Christopher M; Kenney, Joan L; Dietrich, Elizabeth A; Duggal, Nisha K; Bosco-Lauth, Angela M; Brault, Aaron C

2016-10-17

West Nile virus (WNV) is an important agent of human encephalitis that has quickly become endemic across much of the United States since its identification in North America in 1999. While the majority (∼75%) of infections are subclinical, neurologic disease can occur in a subset of cases, with outcomes including permanent neurologic damage and death. Currently, there are no WNV vaccines approved for use in humans. This study introduces a novel vaccine platform for WNV to reduce viral replication in the central nervous system while maintaining peripheral replication to elicit strong neutralizing antibody titers. Vaccine candidates were engineered to incorporate microRNA (miRNA) target sequences for a cognate miRNA expressed only in neurons, allowing the host miRNAs to target viral transcription through endogenous RNA silencing. To maintain stability, these targets were incorporated in multiple locations within the 3'-untranslated region, flanking sequences essential for viral replication without affecting the viral open reading frame. All candidates replicated comparably to wild type WNV in vitro within cells that did not express the cognate miRNA. Insertional control viruses were also capable of neuroinvasion and neurovirulence in vivo in CD-1 mice. Vaccine viruses were safe at all doses tested and did not demonstrate mutations associated with a reversion to virulence when serially passaged in mice. All vaccine constructs were protective from lethal challenge in mice, producing 93-100% protection at the highest dose tested. Overall, this is a safe and effective attenuation strategy with broad potential application for vaccine development. Published by Elsevier Ltd.