TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation

PubMed Central

Tauseef, Mohammad; Knezevic, Nebojsa; Chava, Koteswara R.; Smith, Monica; Sukriti, Sukriti; Gianaris, Nicholas; Obukhov, Alexander G.; Vogel, Stephen M.; Schraufnagel, Dean E.; Dietrich, Alexander; Birnbaumer, Lutz; Malik, Asrar B.

2012-01-01

Lung vascular endothelial barrier disruption and the accompanying inflammation are primary pathogenic features of acute lung injury (ALI); however, the basis for the development of both remains unclear. Studies have shown that activation of transient receptor potential canonical (TRPC) channels induces Ca2+ entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca2+ signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca2+ entry in ECs in a TLR4-dependent manner. Moreover, deletion of TRPC6 renders mice resistant to endotoxin-induced barrier dysfunction and inflammation, and protects against sepsis-induced lethality. TRPC6 induces Ca2+ entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca2+ entry mediated by TRPC6, in turn, activates the nonmuscle myosin light chain kinase (MYLK), which not only increases lung vascular permeability but also serves as a scaffold to promote the interaction of myeloid differentiation factor 88 and IL-1R–associated kinase 4, which are required for NF-κB activation and lung inflammation. Our findings suggest that TRPC6-dependent Ca2+ entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin. PMID:23045603

A 16 kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne's disease.

PubMed

Castellanos, Elena; Aranaz, Alicia; de Juan, Lucia; Dominguez, Lucas; Linedale, Richard; Bull, Tim J

2012-09-14

In this study we characterise the genomic and transcriptomic variability of a natural deletion strain of Mycobacterium avium subspecies paratuberculosis (MAP) prevalent in Spanish Guadarrama goats. Using a pan-genome microarray including MAP and M. avium subspecies hominissuis 104 genomes (MAPAC) we demonstrate the genotype to be MAP Type II with a single deletion of 19 contiguous ORFs (16 kb) including a complete mammalian cell entry (mce7_1) operon and adjacent proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) genes. A deletion specific PCR test was developed and a subsequent screening identified four goat herds infected with the variant strain. Each was located in central Spain and showed epidemiological links suggestive of transmission between herds. A majority of animals infected with the variant manifested a paucibacillary form of the disease. Comparisons between virulent complete genome compliment strains isolated from multibacillary diseased goats and the MAP variant strain during entry into activated macrophages demonstrated an increased sensitivity in the variant to intracellular killing in human and ovine macrophages. As PPE and mce genes are associated with mycobacterial virulence and pathogenesis we investigated the interplay of these gene sets during cell entry using the MAPAC array. This showed significant differential transcriptome profiles compared to full genome complement MAP controls that included changes in other undeleted mce operons and PE/PPE genes, esx-like signalling operons and stress response/fatty acid metabolism pathways. This strain represents the first report of a MAP Type II genotype with significant natural genomic deletions which remains able to cause disease and is transmissible in goats. Copyright © 2012 Elsevier B.V. All rights reserved.

Virulence Phenotypes of Legionella pneumophila Associated with Noncoding RNA lpr0035

PubMed Central

Jayakumar, Deepak; Early, Julie V.

2012-01-01

The Philadelphia-1 strain of Legionella pneumophila, the causative organism of Legionnaires' disease, contains a recently discovered noncoding RNA, lpr0035. lpr0035 straddles the 5′ chromosomal junction of a 45-kbp mobile genetic element, pLP45, which can exist as an episome or integrated in the bacterial chromosome. A 121-bp deletion was introduced in strain JR32, a Philadelphia-1 derivative. The deletion inactivated lpr0035, removed the 49-bp direct repeat at the 5′ junction of pLP45, and locked pLP45 in the chromosome. Intracellular multiplication of the deletion mutant was decreased by nearly 3 orders of magnitude in Acanthamoeba castellanii amoebae and nearly 2 orders of magnitude in J774 mouse macrophages. Entry of the deletion mutant into amoebae and macrophages was decreased by >70%. The level of entry in both hosts was restored to that in strain JR32 by plasmid copies of two open reading frames immediately downstream of the 5′ junction and plasmid lpr0035 driven by its endogenous promoter. When induced from a tac promoter, plasmid lpr0035 completely reversed the intracellular multiplication defect in macrophages but was without effect in amoebae. These data are the first evidence of a role for noncoding RNA lpr0035, which has homologs in six other Legionella genomes, in entry of L. pneumophila into amoebae and macrophages and in host-specific intracellular multiplication. The data also demonstrate that deletion of a direct-repeat sequence restricts the mobility of pLP45 and is a means of studying the role of pLP45 mobility in Legionella virulence phenotypes. PMID:22966048

76 FR 2598 - Final Theft Data; Motor Vehicle Theft Prevention Standard

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2011-01-14

... ``Quattro'' and ``Avant'' should be deleted from the Volkswagen and Audi vehicle line nomenclature. The..., Quattro and Avant have been deleted from the vehicle line nomenclature for the Volkswagen and Audi vehicle lines. Therefore, the entry for the Audi A6/A6 Quattro/S6/ S6 Avant has been changed to the Audi A6 and...

Contributions of herpes simplex virus type 1 envelope proteins to entry by endocytosis

USDA-ARS?s Scientific Manuscript database

Herpes simplex virus (HSV) proteins specifically required for endocytic entry but not direct penetration have not been identified. HSVs deleted of gE, gG, gI, gJ, gM, UL45, or Us9 entered cells via either pH-dependent or pH-independent endocytosis and were inactivated by mildly acidic pH. Thus, the ...

Neutrophil Activation of Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration and Vascular Injury.

PubMed

Mittal, Manish; Nepal, Saroj; Tsukasaki, Yoshikazu; Hecquet, Claudie M; Soni, Dheeraj; Rehman, Jalees; Tiruppathi, Chinnaswamy; Malik, Asrar B

2017-10-13

TRPM2 (transient receptor potential melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca 2+ entry in response to intracellular generation of adenosine diphosphoribose-the TRPM2 ligand. Because polymorphonuclear neutrophils (PMN) interaction with ECs generates reactive oxygen species, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. We observed defective PMN transmigration in response to lipopolysaccharide challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted ( Trpm2 iΔEC ). PMN interaction with ECs induced the entry of Ca 2+ in ECs via the EC-expressed TRPM2. Prevention of generation of adenosine diphosphoribose in ECs significantly reduced Ca 2+ entry in response to PMN activation of TRPM2 in ECs. PMNs isolated from gp91phox -/- mice significantly reduced Ca 2+ entry in ECs via TRPM2 as compared with wild-type PMNs and failed to induce PMN transmigration. Overexpression of the adenosine diphosphoribose insensitive TRPM2 mutant channel (C1008→A) in ECs suppressed the Ca 2+ entry response. Further, the forced expression of TRPM2 mutant channel (C1008→A) or silencing of poly ADP-ribose polymerase in ECs of mice prevented PMN transmigration. Thus, endotoxin-induced transmigration of PMNs was secondary to TRPM2-activated Ca 2+ signaling and VE-cadherin phosphorylation resulting in the disassembly of adherens junctions and opening of the paracellular pathways. These results suggest blocking TRPM2 activation in ECs is a potentially important means of therapeutically modifying PMN-mediated vascular inflammation. © 2017 American Heart Association, Inc.

Using natural language processing to analyze physician modifications to data entry templates.

PubMed Central

Wilcox, Adam B.; Narus, Scott P.; Bowes, Watson A.

2002-01-01

Efficient data entry by clinicians remains a significant challenge for electronic medical records. Current approaches have largely focused on either structured data entry, which can be limiting in expressive power, or free-text entry, which restricts the use of the data for automated decision support. Text-based templates are a semi-structured data entry method that has been used to assist physicians in manually entering clinical notes, by allowing them to edit predefined example notes. We analyzed changes made to 18,726 sentences from text templates, using a natural language processor. The most common changes were addition or deletion of normal observations, or changes in certainty. We identified common modifications that could be captured in structured form by a graphical user interface. PMID:12463955

78 FR 17384 - Privacy Act of 1974; System of Records

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MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice

PubMed Central

Risal, Sanjiv; Zhang, Jingjing; Adhikari, Deepak; Liu, Xiaoman; Shao, Jingchen; Hu, Mengwen; Busayavalasa, Kiran; Tu, Zhaowei; Chen, Zijiang; Kaldis, Philipp; Liu, Kui

2017-01-01

In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75–8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death of Mastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl-null PGCs was rescued by simultaneous deletion of Ppp2r1a (α subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis. PMID:28224044

75 FR 9185 - Privacy Act of 1974; System of Records

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75 FR 74019 - Privacy Act of 1974; System of Records

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Deletions of 9p and the quest for a conserved mechanism of sex determination.

PubMed

Ottolenghi, C; McElreavey, K

2000-01-01

Distal chromosome 9p contains a locus that, when deleted, is a cause of 46,XY gonadal dysgenesis in the absence of extragenital anomalies. This locus might account for the frequently observed cases of 46,XY pure gonadal dysgenesis who do not harbor mutations in SRY, the sex master regulator gene found in mammalian species. The genomic organization of 9p positional candidate genes is currently being studied and mutational screens are ongoing. Among other positional candidates, including two additional doublesex-related genes, the evidence to support a role for the gene DMRT1 in vertebrate male sexual development is accumulating. Although formal proof of the requirement of DMRT1 in gonadal sex fate choice has not been obtained so far, the particular interest in this gene and perhaps other doublesex-related genes identified in vertebrates lies in that they may provide an entry point to a conserved mechanism of sex determination across animal phyla. We discuss recent results and emerging views on the genetics of sex determination, while stressing that the majority of cases of 46,XY gonadal dysgenesis remain unexplained. The latter is likely to be efficiently addressed by positional cloning efforts, particularly by considering the wealth of sequence data provided by the Human Genome Project. Copyright 2000 Academic Press.

77 FR 69443 - Privacy Act of 1974; System of Records

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77 FR 38608 - Privacy Act of 1974; System of Records

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78 FR 65620 - Privacy Act of 1974; System of Records

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75 FR 19622 - Privacy Act of 1974; System of Records

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77 FR 9902 - Privacy Act of 1974; System of Records

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76 FR 3115 - Privacy Act of 1974; System of Records

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76 FR 38119 - Privacy Act of 1974; System of Records

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Alanine substitution of conserved residues in the cytoplasmic tail of herpes simplex virus gB can enhance or abolish cell fusion activity and viral entry

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

Ruel, Nancy; Zago, Anna; Spear, Patricia G.

2006-03-01

Herpes simplex virus (HSV) glycoprotein B (gB) is one of the four viral glycoproteins required for viral entry and cell fusion and is highly conserved among herpesviruses. Mutants of HSV type 2 gB were generated by substituting conserved residues in the cytoplasmic tail with alanine or by deleting 41 amino acids from the C-terminus. Some of the mutations abolished cell fusion activity and also prevented transport of gB to the cell surface, identifying residues in the gB cytoplasmic tail that are critical for intracellular transport of this glycoprotein. These mutations also prevented production of infectious virus, possibly because the mutantmore » forms of gB were not transported to the site of envelopment. Other mutations, particularly the deletion, significantly enhanced cell fusion activity. These mutations, as well as others described previously, identify regions of the gB cytoplasmic domain that modulate cell fusion activity.« less

Performance analysis of different database in new internet mapping system

NASA Astrophysics Data System (ADS)

Yao, Xing; Su, Wei; Gao, Shuai

2017-03-01

In the Mapping System of New Internet, Massive mapping entries between AID and RID need to be stored, added, updated, and deleted. In order to better deal with the problem when facing a large number of mapping entries update and query request, the Mapping System of New Internet must use high-performance database. In this paper, we focus on the performance of Redis, SQLite, and MySQL these three typical databases, and the results show that the Mapping System based on different databases can adapt to different needs according to the actual situation.

76 FR 18195 - Privacy Act of 1974; System of Records

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78 FR 73515 - Privacy Act of 1974; System of Records

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75 FR 17908 - Privacy Act of 1974; System of Records

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75 FR 6000 - Privacy Act of 1974; Systems of Records

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2010-02-05

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75 FR 17906 - Privacy Act of 1974; Systems of Records

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75 FR 19946 - Privacy Act of 1974; System of Records

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78 FR 73512 - Privacy Act of 1974; System of Records

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.... This system will be used to evaluate and settle Admiralty tort claims asserted for and against the..., citizenship, race/ethnicity, physically descriptive characteristics, birth date, personal cell telephone....'' Purpose(s): Delete entry and replace with ``To evaluate and settle Admiralty tort claims asserted for and...

75 FR 49482 - Privacy Act of 1974; System of Records

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75 FR 70760 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing and...

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2010-11-18

...'' and ``Economic indicators'' are added. Delivery Detail under this topic (``Book-entry only;'' ``Bearer... at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the... certain product knowledge and MSRB rules and eliminate redundancy; delete dated references to certain...

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2011-05-19

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The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K (gK) Is Required for gB Binding to Akt, Release of Intracellular Calcium, and Fusion of the Viral Envelope with Plasma Membranes.

PubMed

Musarrat, Farhana; Jambunathan, Nithya; Rider, Paul J F; Chouljenko, V N; Kousoulas, K G

2018-03-15

Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino-terminal 38 amino acids of gK prevents herpes simplex virus 1 (HSV-1) infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 phosphorylated at S473 [Akt-1(S473)] confirmed that HSV-1(McKrae) gB interacted with Akt-1(S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced the release of intracellular calcium. In contrast, the gB specified by HSV-1(McKrae) gKΔ31-68, lacking the amino-terminal 38 amino acids of gK, failed to interact with Akt-1(S473) and induce intracellular calcium release. The Akt inhibitor miltefosine inhibited the entry of McKrae but not the gKΔ31-68 mutant into SK-N-SH cells. Importantly, the entry of the gKΔ31-68 mutant but not McKrae into SK-N-SH cells treated with the endocytosis inhibitors pitstop-2 and dynasore hydrate was significantly inhibited, indicating that McKrae gKΔ31-68 entered via endocytosis. These results suggest that the amino terminus of gK functions to regulate the fusion of the viral envelope with cellular plasma membranes. IMPORTANCE HSV-1 glycoprotein B (gB) functions in the fusion of the viral envelope with cellular membranes during virus entry. Herein, we show that a deletion in the amino terminus of glycoprotein K (gK) inhibits gB binding to Akt-1(S473), the release of intracellular calcium, and virus entry via fusion of the viral envelope with cellular plasma membranes. Copyright © 2018 American Society for Microbiology.

Direct access inter-process shared memory

DOEpatents

Brightwell, Ronald B; Pedretti, Kevin; Hudson, Trammell B

2013-10-22

A technique for directly sharing physical memory between processes executing on processor cores is described. The technique includes loading a plurality of processes into the physical memory for execution on a corresponding plurality of processor cores sharing the physical memory. An address space is mapped to each of the processes by populating a first entry in a top level virtual address table for each of the processes. The address space of each of the processes is cross-mapped into each of the processes by populating one or more subsequent entries of the top level virtual address table with the first entry in the top level virtual address table from other processes.

Address entry while driving: speech recognition versus a touch-screen keyboard.

PubMed

Tsimhoni, Omer; Smith, Daniel; Green, Paul

2004-01-01

A driving simulator experiment was conducted to determine the effects of entering addresses into a navigation system during driving. Participants drove on roads of varying visual demand while entering addresses. Three address entry methods were explored: word-based speech recognition, character-based speech recognition, and typing on a touch-screen keyboard. For each method, vehicle control and task measures, glance timing, and subjective ratings were examined. During driving, word-based speech recognition yielded the shortest total task time (15.3 s), followed by character-based speech recognition (41.0 s) and touch-screen keyboard (86.0 s). The standard deviation of lateral position when performing keyboard entry (0.21 m) was 60% higher than that for all other address entry methods (0.13 m). Degradation of vehicle control associated with address entry using a touch screen suggests that the use of speech recognition is favorable. Speech recognition systems with visual feedback, however, even with excellent accuracy, are not without performance consequences. Applications of this research include the design of in-vehicle navigation systems as well as other systems requiring significant driver input, such as E-mail, the Internet, and text messaging.

Optimizing TLB entries for mixed page size storage in contiguous memory

DOEpatents

Chen, Dong; Gara, Alan; Giampapa, Mark E.; Heidelberger, Philip; Kriegel, Jon K.; Ohmacht, Martin; Steinmacher-Burow, Burkhard

2013-04-30

A system and method for accessing memory are provided. The system comprises a lookup buffer for storing one or more page table entries, wherein each of the one or more page table entries comprises at least a virtual page number and a physical page number; a logic circuit for receiving a virtual address from said processor, said logic circuit for matching the virtual address to the virtual page number in one of the page table entries to select the physical page number in the same page table entry, said page table entry having one or more bits set to exclude a memory range from a page.

Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry

PubMed Central

Moller-Tank, Sven; Albritton, Lorraine M.; Rennert, Paul D.

2014-01-01

ABSTRACT T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members were recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance entry of Ebola virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. The PtdSer-binding activity of the immunoglobulin-like variable (IgV) domain is essential for both virus binding and internalization by TIM-1. However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indicating that other domains of TIM proteins are functionally important. Here, we investigate the domains supporting enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. IMPORTANCE T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance virus entry by binding the phospholipid, PtdSer, present on the viral membrane. While it is known that the PtdSer binding is essential for the PVEER function of TIM-1, TIM-3 shares this binding activity but does not enhance virus entry. No comprehensive studies have been done to characterize the other domains of TIM-1. In this study, using a variety of chimeric proteins and deletion mutants, we define the features necessary for a functional PVEER. With these features in mind, we generated a TIM-1 mimic using functionally similar domains from other proteins. This mimic, like TIM-1, effectively enhanced transduction. These studies provide insight into the key features necessary for PVEERs and will allow for more effective identification of unknown PVEERs. PMID:24696470

75 FR 2118 - Privacy Act of 1974; System of Records

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2010-01-14

...: Maintained on computer and electronic storage media. RETRIEVABILITY: Retrieved by name and Social Security... proposed action will be effective without further notice on February 16, 2010 unless comments are received....'' * * * * * CATEGORIES OF RECORDS IN THE SYSTEM: Delete entry and replace with ``Name, Social Security Number (SSN...

75 FR 77853 - Privacy Act of 1974; System of Records

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2010-12-14

... action will be effective without further notice on January 13, 2011 unless comments are received which...: * * * * * Categories of records in the system: Delete entry and replace with ``Name, Social Security Number (SSN... school. Categories of records in the system: Name, Social Security Number (SSN), course data to include...

75 FR 10474 - Privacy Act of 1974; Systems of Records

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2010-03-08

... storage media. RETRIEVABILITY: Retrieved by last name and Social Security Number (SSN). SAFEGUARDS... proposed action will be effective without further notice on April 7, 2010 unless comments are received... RECORDS IN THE SYSTEM: Delete entry and replace with ``The files contain full name, grade, Social Security...

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

... system: Storage: Electronic storage media. Retrievability: Name and last four digits of the Social... be effective without further notice on April 19, 2010 unless comments are received which result in a...: Delete entry and replace with ``INDIVIDUAL PROFILE DATA: Full name of the individual; Social Security...

77 FR 21973 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-12

... location: Delete entry and replace with ``Amazon Web Services, LLC 13461 Sunrise Valley Drive, Herndon, VA.../JS Privacy Office, Freedom of Information Directorate, Washington Headquarters Services, 1155 Defense..., protocols and/or in briefings of the consequences of improper access or use of the data. The web-based files...

77 FR 56632 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-13

...) through Chief Master Sergeant (E-9). Air National Guard and Air Force Reserve personnel grades Staff Sergeant (E-5) through Chief Master Sergeant (E- 9).'' * * * * * Retrievability: Delete entry and replace.... Electronic files are only accessed by authorized personnel with a Secure Common Access Card (CAC) and need...

78 FR 74122 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-10

... drive government owned or leased vehicles that exceed 10,000 pounds gross vehicle weight and are used... vehicle operator identification card. DATES: This proposed action will be effective on January 10, 2014... license.'' Authority for maintenance of the system: Delete entry and replace with ``10 U.S.C. 8013...

76 FR 18191 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

... action would be effective without further notice on May 2, 2011 unless comments are received which result... replace with ``DMDC 10 DoD.'' * * * * * System location: Delete entry and replace with ``Defense Manpower... facilities or using facilities interfacing with Defense Manpower Data Center Physical Access Control Systems...

76 FR 3111 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

.... Storage: Maintained in paper and electronic storage media. Retrievability: Retrieved by name and or Social... Program.'' Categories of records in the system: Delete entry and replace with ``Individual's name, Social..., and award records. Statement of good standing before the bar and other State Bar records, law school...

78 FR 14292 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

.... SUPPLEMENTARY INFORMATION: The Department of the Air Force's notices for systems of records subject to the... system: Delete entry and replace with ``10 U.S.C. 105, Armed Forces Health Professionals Financial Assistance Programs; 10 U.S.C. 9301, Members of Air Force: detail as students, observers, and investigators...

75 FR 64711 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... without change, including any personal identifiers or contact information. FOR FURTHER INFORMATION CONTACT.../ detachment, and Social Security Number (SSN).'' Authority for Maintenance of the System: Delete entry and... Acquisition Technology and Logistics; DoD 4525.6-M, DoD Postal Manual; and E.O. 9397 (SSN), as amended...

75 FR 29728 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

.... NM01754-3 SYSTEM NAME: DON Child and Youth Program (December 6, 2007; 72 FR 68867). CHANGES: * * * * * SYSTEM LOCATION: Delete entry and replace with ``Navy: Navy Child and Youth Program or Family Service... or Department of Defense personnel receiving services under the Navy Child and Youth Program or the...

78 FR 68823 - Procurement List Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the...: Effective 12/16/2013. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely Disabled, 1401...

78 FR 77106 - Procurement List; Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the...: Effective Date: 1/20/2014. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely Disabled...

78 FR 52080 - Potato Research and Promotion Plan; Amend the Administrative Committee Structure and Delete the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-22

...-13-0027] Potato Research and Promotion Plan; Amend the Administrative Committee Structure and Delete... (Board) and deletes the Board's mailing address from the Potato Research and Promotion Plan. The Plan is... FURTHER INFORMATION CONTACT: Patricia A. Petrella, Marketing Specialist, Promotion and Economics Division...

The Deceptive Mean: Conceptual Scoring of Cloze Entries Differentially Advantages More Able Readers

ERIC Educational Resources Information Center

O'Toole, J. M.; King, R. A. R.

2011-01-01

The "cloze" test is one possible investigative instrument for predicting text comprehensibility. Conceptual coding of student replacement of deleted words has been considered to be more valid than exact coding, partly because conceptual coding seemed fairer to poorer readers. This paper reports a quantitative study of 447 Australian…

75 FR 63824 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

.... 922, Brady Handgun Violence Prevention Act; 28 U.S.C. 534, Uniform Federal Crime Reporting Act; 42 U.S....'' * * * * * Storage: Delete entry and replace with ``Paper records and electronic storage media.'' Retrievability... (DIBRS); 18 U.S.C. 922, Brady Handgun Violence Prevention Act; 28 U.S.C. 534, Uniform Federal Crime...

76 FR 3618 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

...; System of Records AGENCY: U.S. Marine Corps, DoD. ACTION: Notice to Delete Four Systems of Records. SUMMARY: The U.S. Marine Corps is deleting four systems of records notices from its existing inventory of... FOR FURTHER INFORMATION CONTACT address above. The U.S. Marine Corps proposes to delete four systems...

78 FR 66283 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... is the contaminant source. The laboratory found no organic contaminants in the soil samples taken... Register informing the public that the deletion will not take effect. ADDRESSES: Submit your comments... of the deletion, and the deletion will not take effect. EPA will, as appropriate, prepare a response...

Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system.

PubMed

Suda, Yuto; Fukushi, Shuetsu; Tani, Hideki; Murakami, Shin; Saijo, Masayuki; Horimoto, Taisuke; Shimojima, Masayuki

2016-06-01

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.

2nd International Planetary Probe Workshop

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Martinez, Ed; Arcadi, Marla

2005-01-01

Included are presentations from the 2nd International Planetary Probe Workshop. The purpose of the second workshop was to continue to unite the community of planetary scientists, spacecraft engineers and mission designers and planners; whose expertise, experience and interests are in the areas of entry probe trajectory and attitude determination, and the aerodynamics/aerothermodynamics of planetary entry vehicles. Mars lander missions and the first probe mission to Titan made 2004 an exciting year for planetary exploration. The Workshop addressed entry probe science, engineering challenges, mission design and instruments, along with the challenges of reconstruction of the entry, descent and landing or the aerocapture phases. Topics addressed included methods, technologies, and algorithms currently employed; techniques and results from the rich history of entry probe science such as PAET, Venera/Vega, Pioneer Venus, Viking, Galileo, Mars Pathfinder and Mars MER; upcoming missions such as the imminent entry of Huygens and future Mars entry probes; and new and novel instrumentation and methodologies.

78 FR 35610 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... Defense. NM05720-1 System name: FOIA Request/Appeal Files and Tracking System (April 2, 2008, 73 FR 17961...: Delete entry and replace with ``Records are accessed by custodian of the record system and by persons... cabinets or rooms, which are not viewable by individuals who do not have a need to know. Computerized...

NASA Thesaurus Supplement: A three part cumulative supplement to the 1982 edition of the NASA Thesaurus (supplement 3)

NASA Technical Reports Server (NTRS)

1985-01-01

The three part cumulative NASA Thesaurus Supplement to the 1982 edition of the NASA Thesaurus includes Part 1, Hierarchical Listing, Part 2, Access Vocabulary, and Part 3, Deletions. The semiannual supplement gives complete hierarchies for new terms and includes new term indications for entries new to this supplement.

76 FR 11213 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

...: The Department of the Air Force's notices for systems of records subject to the Privacy Act of 1974 (5... the Air Force's compilation of systems of records notices.'' * * * * * Categories of records in the... maintenance of the system: Delete entry and replace with ``10 U.S.C. 8013, Secretary of the Air Force; 10 U.S...

78 FR 14293 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

.... SUPPLEMENTARY INFORMATION: The Department of the Air Force's notices for systems of records subject to the...: Delete entry and replace with ``10 U.S.C. 8013, Secretary of the Air Force; 10 U.S.C. 8032, The Air Staff... system interfaces. The interfaces are the Air Force Logistics Module, Air Force Military Personnel Data...

Herpes simplex virus type 2 glycoprotein H interacts with integrin αvβ3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells.

PubMed

Cheshenko, Natalia; Trepanier, Janie B; González, Pablo A; Eugenin, Eliseo A; Jacobs, William R; Herold, Betsy C

2014-09-01

Herpes simplex virus (HSV) entry requires multiple interactions at the cell surface and activation of a complex calcium signaling cascade. Previous studies demonstrated that integrins participate in this process, but their precise role has not been determined. These studies were designed to test the hypothesis that integrin αvβ3 signaling promotes the release of intracellular calcium (Ca2+) stores and contributes to viral entry and cell-to-cell spread. Transfection of cells with small interfering RNA (siRNA) targeting integrin αvβ3, but not other integrin subunits, or treatment with cilengitide, an Arg-Gly-Asp (RGD) mimetic, impaired HSV-induced Ca2+ release, viral entry, plaque formation, and cell-to-cell spread of HSV-1 and HSV-2 in human cervical and primary genital tract epithelial cells. Coimmunoprecipitation studies and proximity ligation assays indicated that integrin αvβ3 interacts with glycoprotein H (gH). An HSV-2 gH-null virus was engineered to further assess the role of gH in the virus-induced signaling cascade. The gH-2-null virus bound to cells and activated Akt to induce a small Ca2+ response at the plasma membrane, but it failed to trigger the release of cytoplasmic Ca2+ stores and was impaired for entry and cell-to-cell spread. Silencing of integrin αvβ3 and deletion of gH prevented phosphorylation of focal adhesion kinase (FAK) and the transport of viral capsids to the nuclear pore. Together, these findings demonstrate that integrin signaling is activated downstream of virus-induced Akt signaling and facilitates viral entry through interactions with gH by activating the release of intracellular Ca2+ and FAK phosphorylation. These findings suggest a new target for HSV treatment and suppression. Herpes simplex viruses are the leading cause of genital disease worldwide, the most common infection associated with neonatal encephalitis, and a major cofactor for HIV acquisition and transmission. There is no effective vaccine. These epidemiological findings underscore the urgency to develop novel HSV treatment or prevention strategies. This study addresses this gap by further defining the signaling pathways the virus usurps to enter human genital tract epithelial cells. Specifically, the study defines the role played by integrins and by the viral envelope glycoprotein H in entry and cell-to-cell spread. This knowledge will facilitate the identification of new targets for the development of treatment and prevention. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

CLT and CLS job responsibilities: current distinctions and updates.

PubMed

Doig, K; Beck, S J; Kolenc, K

2001-01-01

This study was undertaken to address the following questions: 1. What tasks distinguish the job of a clinical laboratory scientist (CLS) from that of a clinical laboratory technician (CLT)? 2. What changes in role distinctions, have occurred for entry-level CLS and CLT practitioners over the five-year period 1993-98? 3. What tasks have been deleted from the CLT and CLS content outlines because they were not frequently performed or not considered entry-level? 4. What changes in practice are reflected in the current job analyses? A national job analysis of tasks constituting the job of clinical laboratory scientists (CLSs) and clinical laboratory technicians (CLTs) was conducted in 1998-99 as part of a standard setting process for the certifying examinations of the National Credentialing Agency for Laboratory Personnel (NCA). The job analyses relied upon mail surveys to 1200 individuals for each job level asking respondents to identify tasks significant to effective practice at job entry. The task lists resulting from statistical analysis of those surveys were examined to answer the study questions. The sample for each survey included 1200 practitioners, educators and laboratory managers selected at random from membership in professional organizations or from NCA certificant lists. Sampling was stratified to insure adequate practitioner representation. The mean rating on a four point scale for each item on the surveys was evaluated for overall significance as well as significance across geographic regions. The tasks meeting specified criteria were retained in the final task lists. Tasks were counted and their content evaluated to compare CLS and CLT job tasks. The response rates to the surveys were 33% for CLT and 21% for CLS. Reliability was judged based on average intraclass correlation coefficients of .86 and .82 for the CLT and CLS surveys, respectively. There were 952 tasks retained on the CLS content outline and 725 retained on the CLT content outline of the 1151 tasks on the original survey. Seven hundred and twenty two tasks were found on content outlines of both job levels, representing a 76% overlap. Tasks found only on the CLS outline included advanced technical tasks, a few management tasks, and more communication tasks. The jobs of CLS and CLT practitioners are distinct at job entry level with CLSs performing a broader array of technical and communication tasks as well as some management tasks. Though CLS staff uses few management skills at job entry, those tasks are performed by CLS staff in the laboratory and curricula must help prepare graduates for these tasks expected of experienced staff. CLTs perform tasks requiring problem solving and high level reasoning. CLT curricula must address the need for CLTs to perform these tasks.

Developing Formulas by Skipping Rows in Pascal's Triangle

ERIC Educational Resources Information Center

Buonpastore, Robert J.; Osler, Thomas J.

2007-01-01

A table showing the first thirteen rows of Pascal's triangle, where the rows are, as usual numbered from 0 to 12 is presented. The entries in the table are called binomial coefficients. In this note, the authors systematically delete rows from Pascal's triangle and, by trial and error, try to find a formula that allows them to add new rows to the…

Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry

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

Stiles, Katie M., E-mail: stileskm@mail.med.upenn.ed; Krummenacher, Claude

2010-03-30

Entry of herpes simplex virus (HSV) occurs either by fusion at the plasma membrane or by endocytosis and fusion with an endosome. Binding of glycoprotein D (gD) to a receptor such as nectin-1 is essential in both cases. We show that virion gD triggered the rapid down-regulation of nectin-1 with kinetics similar to those of virus entry. In contrast, nectin-1 was not constitutively recycled from the surface of uninfected cells. Both the nectin-1alpha and beta isoforms were internalized in response to gD despite having different cytoplasmic tails. However, deletion of the nectin-1 cytoplasmic tail slowed down-regulation of nectin-1 and internalizationmore » of virions. These data suggest that nectin-1 interaction with a cytoplasmic protein is not required for its down-regulation. Overall, this study shows that gD binding actively induces the rapid internalization of various forms of nectin-1. We suggest that HSV activates a nectin-1 internalization pathway to use for endocytic entry.« less

Exploratory Study of the Potential Effects of Exposure to Sonic Boom on Human Health. Volume 2. Epidemiological Study.

DTIC Science & Technology

1986-06-01

were retained from the original source. The undesired data lines in both shortened population files were then manually deleted through full-screen...Prenatal Visits 00-99 00-blank 88-not on certificate 99-unknown Apgar Score: 161-162 1 min. 00-10, 88, 99 99-entry >10 88-not on record 00=blank 163

76 FR 32145 - Procurement List Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION... such agencies. DATES: Effective Date: 7/4/2011. ADDRESSES: Committee for Purchase From People Who Are...

76 FR 27999 - Procurement List; Addition and Deletion

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION...: Effective Date: June 13, 2011. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely...

75 FR 7451 - Procurement List Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION... disabilities. DATES: Effective Date: March 22, 2010. ADDRESSES: Committee for Purchase From People Who Are...

75 FR 16755 - Procurement List Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-02

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION.... DATES: Effective Date: May 3, 2010. ADDRESSES: Committee for Purchase From People Who Are Blind or...

78 FR 54870 - Procurement List; Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION...: Effective: October 7, 2013. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely Disabled...

75 FR 60739 - Procurement List; Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION.... DATES: Effective Date: 11/1/2010. ADDRESSES: Committee for Purchase From People Who Are Blind or...

76 FR 21335 - Procurement List Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION... such agencies. DATES: Effective Date: May 16, 2011. ADDRESSES: Committee for Purchase From People Who...

78 FR 65618 - Procurement List; Proposed Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed.... Comments Must Be Received on or Before: 12/2/2013. ADDRESSES: Committee for Purchase From People Who Are...

78 FR 20622 - Procurement List, Proposed Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List, Proposed Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled... agencies. Comments Must Be Received On or Before: 5/6/2013. ADDRESSES: Committee for Purchase From People...

76 FR 41768 - Procurement List; Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-15

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION...: Effective Date: 8/15/2011. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely Disabled...

76 FR 13361 - Procurement List; Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION...: Effective Date: 4/11/2011. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely Disabled...

78 FR 67129 - Procurement List; Proposed Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled... agencies. Comments Must Be Received on or Before: 12/9/2013. ADDRESSES: Committee for Purchase From People...

PAX ECONOPACK Economic Analysis Package. User’s Manual.

DTIC Science & Technology

1986-01-01

35807-4301 ______________ I I CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Commander US Army Corns of Fneineers January 1936 ATTN: TOAP-ZCP-"B...20 Mass. Ave. , NW 3 NUMBER OF PAGES ..ILI;I DC 20314-10G-0 253 14. MONITRING AGENCY NAME & ADDRESSIl dlierent [min Controlling Office) IS. SECURITY...PROMPT. EXANPLE: C>QED (1) QED EDITOR = CONTROL A - FOR CHARACTER DELETION = CONTROL W - FOR WORD DELETION = CONTROL Q - FOR L[NE DELETION = CONTROL R

78 FR 25970 - Procurement List; Proposed Additions and Deletion

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION.... DATES: Comments Must Be Received On or Before: 6/3/2013. ADDRESSES: Committee for Purchase From People...

76 FR 23998 - Procurement List; Proposed Additions and Deletion

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION... such agency. Comments Must be Received On or Before: 5/30/2011. ADDRESSES: Committee for Purchase From...

75 FR 29994 - Procurement List Proposed Additions and Deletion

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION... MUST BE RECEIVED ON OR BEFORE: 6/28/2010. ADDRESSES: Committee for Purchase From People Who Are Blind...

77 FR 6562 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-08

... name and address 264 Bayer CropScience, P.O. Box 12014, 2. T.W. Alexander Drive, Research Triangle Park... these products who desire continued use on crops or sites being deleted should contact the applicable... BXN Cotton. [[Page 6563

Contribution of Interstitial Deletion of 21q22.2-3 per se to Prostate Cancer Progression in Tumors Harboring TMPRSS2-ERG Translocations

DTIC Science & Technology

2015-12-01

harboring TMPRSS2-ERG translocations PRINCIPAL INVESTIGATOR: Yan Dong CONTRACTING ORGANIZATION: Tulane University New Orleans , LA 70112...AND ADDRESS(ES) Tulane University AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER 6823 Saint Charles Ave New Orleans , LA 70118-5665 9

76 FR 77388 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... in the Federal Register, informing the public that the deletion will not take effect. ADDRESSES... will not take effect. EPA will, if appropriate, prepare a response to comments and continue with the... discusses the Site and demonstrates how it meets the deletion criteria. Section V discusses EPA's action to...

38 CFR 21.9520 - Basic eligibility.

Code of Federal Regulations, 2010 CFR

2010-07-01

... excluding entry level and skill training (to determine when entry level and skill training may be included..., social security number, and address); (ii) If applicable, an election to receive benefits under chapter...

Predictors of student success in entry-level science courses

NASA Astrophysics Data System (ADS)

Singh, Mamta K.

Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and their relationships to student achievement. However, the literature contains little information that specifically addresses student biology content knowledge skills (basics and higher order thinking skills) and identifies factors that affect students' success in entry-level college science courses. These gate-keeping courses require detailed evaluation if the goal of an institution is to increase students' performance and success in these courses. These factors are, in fact, a stepping stone for increasing the number of graduates in Science, Technology, Engineering, and Mathematics (STEM) majors. The present study measured students' biology content knowledge and investigated students' performance and success in college biology, chemistry, and physics entry-level courses. Seven variables---gender, ethnicity, high school Grade Point Average (GPA), high school science, college major, school financial aid support, and work hours were used as independent variables and course final performance as a dichotomous dependent variable. The sample comprised voluntary student participants in entry-level science courses. The study attempted to explore eight research questions. Content knowledge assessments, demographic information analysis, multiple regression analysis, and binary logistic regression analysis were used to address research questions. The results suggested that high school GPA was a consistently good predictor of students' performance and success in entry-level science courses. Additionally, high school chemistry was a significant predictor variable for student success in entry-level biology and chemistry courses. Similarly, students' performance and success in entry-level physics courses were influenced by high school physics. Finally, the study developed student success equation with high school GAP and high school chemistry as good predictors of students' success in entry-level science courses.

Security of patient data when decommissioning ultrasound systems.

PubMed

Moggridge, James

2017-02-01

Although ultrasound systems generally archive to Picture Archiving and Communication Systems (PACS), their archiving workflow typically involves storage to an internal hard disk before data are transferred onwards. Deleting records from the local system will delete entries in the database and from the file allocation table or equivalent but, as with a PC, files can be recovered. Great care is taken with disposal of media from a healthcare organisation to prevent data breaches, but ultrasound systems are routinely returned to lease companies, sold on or donated to third parties without such controls. In this project, five methods of hard disk erasure were tested on nine ultrasound systems being decommissioned: the system's own delete function; full reinstallation of system software; the manufacturer's own disk wiping service; open source disk wiping software for full and just blank space erasure. Attempts were then made to recover data using open source recovery tools. All methods deleted patient data as viewable from the ultrasound system and from browsing the disk from a PC. However, patient identifiable data (PID) could be recovered following the system's own deletion and the reinstallation methods. No PID could be recovered after using the manufacturer's wiping service or the open source wiping software. The typical method of reinstalling an ultrasound system's software may not prevent PID from being recovered. When transferring ownership, care should be taken that an ultrasound system's hard disk has been wiped to a sufficient level, particularly if the scanner is to be returned with approved parts and in a fully working state.

Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

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

Mahmoud, Nora F.; Faculty of Pharmacy, Suez Canal University, Ismailia; Jasirwan, Chyntia

2016-03-15

Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highlymore » conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.« less

Base flow investigation of the Apollo AS-202 Command Module

NASA Astrophysics Data System (ADS)

Walpot, Louis M. G.; Wright, Michael J.; Noeding, Peter; Schrijer, Ferry

2012-01-01

A major contributor to the overall vehicle mass of re-entry vehicles is the afterbody thermal protection system. This is due to the large acreage (equal or bigger than that of the forebody) to be protected. The present predictive capabilities for base flows are comparatively lower than those for windward flowfields and offer therefore a substantial potential for improving the design of future re-entry vehicles. To that end, it is essential to address the accuracy of high fidelity CFD tools exercised in the US and EU, which motivates a thorough investigation of the present status of hypersonic flight afterbody heating. This paper addresses the predictive capabilities of afterbody flow fields of re-entry vehicles investigated in the frame of the NATO/RTO-RTG-043 task group. First, the verification of base flow topologies on the basis of available wind-tunnel results performed under controlled supersonic conditions (i.e. cold flows devoid of reactive effects) is performed. Such tests address the detailed characterization of the base flow with particular emphasis on separation/reattachment and their relation to Mach number effects. The tests have been performed on an Apollo-like re-entry capsule configuration. Second, the tools validated in the frame of the previous effort are exercised and appraised against flight-test data collected during the Apollo AS-202 re-entry.

Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins

PubMed Central

Hyun, Seong-In; Weisberg, Andrea

2017-01-01

ABSTRACT The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes. IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights into many aspects of cell biology. The I2 protein is conserved in all poxviruses that infect vertebrates, suggesting an important role. The present study revealed that this protein is essential for vaccinia virus morphogenesis and that its absence results in an accumulation of deformed virus particles retaining the scaffold protein and deficient in surface proteins needed for cell entry. PMID:28490596

Challenges to Computational Aerothermodynamic Simulation and Validation for Planetary Entry Vehicle Analysis

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.; Johnston, Christopher O.; Kleb, Bil

2010-01-01

Challenges to computational aerothermodynamic (CA) simulation and validation of hypersonic flow over planetary entry vehicles are discussed. Entry, descent, and landing (EDL) of high mass to Mars is a significant driver of new simulation requirements. These requirements include simulation of large deployable, flexible structures and interactions with reaction control system (RCS) and retro-thruster jets. Simulation of radiation and ablation coupled to the flow solver continues to be a high priority for planetary entry analyses, especially for return to Earth and outer planet missions. Three research areas addressing these challenges are emphasized. The first addresses the need to obtain accurate heating on unstructured tetrahedral grid systems to take advantage of flexibility in grid generation and grid adaptation. A multi-dimensional inviscid flux reconstruction algorithm is defined that is oriented with local flow topology as opposed to grid. The second addresses coupling of radiation and ablation to the hypersonic flow solver - flight- and ground-based data are used to provide limited validation of these multi-physics simulations. The third addresses the challenges of retro-propulsion simulation and the criticality of grid adaptation in this application. The evolution of CA to become a tool for innovation of EDL systems requires a successful resolution of these challenges.

Using Competencies to Assess Entry-Level Knowledge of Students Graduating from Parks and Recreation Academic Programs

ERIC Educational Resources Information Center

Hurd, Amy R.; Elkins, Daniel J.; Beggs, Brent A.

2014-01-01

To address the Council on Accreditation of Parks, Recreation, Tourism, and Related Professions accreditation standard 7.01.01, the Entry Level Competency Assessment was developed to measure 46 competencies in four categories needed by entry level professionals. Students rated their competence prior to beginning their senior internship. The results…

The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast.

PubMed

Li, Liangtao; Kaplan, Jerry; Ward, Diane M

2017-09-15

The budding yeast Saccharomyces cerevisiae stores iron in the vacuole, which is a major resistance mechanism against iron toxicity. One key protein involved in vacuolar iron storage is the iron importer Ccc1, which facilitates iron entry into the vacuole. Transcription of the CCC1 gene is largely regulated by the binding of iron-sulfur clusters to the activator domain of the transcriptional activator Yap5. Additional evidence, however, suggests that Yap5-independent transcriptional activation of CCC1 also contributes to iron resistance. Here, we demonstrate that components of the signaling pathway involving the low-glucose sensor Snf1 regulate CCC1 transcription and iron resistance. We found that SNF1 deletion acts synergistically with YAP5 deletion to regulate CCC1 transcription and iron resistance. A kinase-dead mutation of Snf1 lowered iron resistance as did deletion of SNF4 , which encodes a partner protein of Snf1. Deletion of all three alternative partners of Snf1 encoded by SIT1 , SIT2 , and GAL83 decreased both CCC1 transcription and iron resistance. The Snf1 complex is known to activate the general stress transcription factors Msn2 and Msn4. We show that Msn2 and Msn4 contribute to Snf1-mediated CCC1 transcription. Of note, SNF1 deletion in combination with MSN2 and MSN4 deletion resulted in additive effects on CCC1 transcription, suggesting that other activators contribute to the regulation of CCC1 transcription. In conclusion, we show that yeast have developed multiple transcriptional mechanisms to regulate Ccc1 expression and to protect against high cytosolic iron toxicity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

An efficient procedure for marker-free mutagenesis of S. coelicolor by site-specific recombination for secondary metabolite overproduction.

PubMed

Zhang, Bo; Zhang, Lin; Dai, Ruixue; Yu, Meiying; Zhao, Guoping; Ding, Xiaoming

2013-01-01

Streptomyces bacteria are known for producing important natural compounds by secondary metabolism, especially antibiotics with novel biological activities. Functional studies of antibiotic-biosynthesizing gene clusters are generally through homologous genomic recombination by gene-targeting vectors. Here, we present a rapid and efficient method for construction of gene-targeting vectors. This approach is based on Streptomyces phage φBT1 integrase-mediated multisite in vitro site-specific recombination. Four 'entry clones' were assembled into a circular plasmid to generate the destination gene-targeting vector by a one-step reaction. The four 'entry clones' contained two clones of the upstream and downstream flanks of the target gene, a selectable marker and an E. coli-Streptomyces shuttle vector. After targeted modification of the genome, the selectable markers were removed by φC31 integrase-mediated in vivo site-specific recombination between pre-placed attB and attP sites. Using this method, part of the calcium-dependent antibiotic (CDA) and actinorhodin (Act) biosynthetic gene clusters were deleted, and the rrdA encoding RrdA, a negative regulator of Red production, was also deleted. The final prodiginine production of the engineered strain was over five times that of the wild-type strain. This straightforward φBT1 and φC31 integrase-based strategy provides an alternative approach for rapid gene-targeting vector construction and marker removal in streptomycetes.

76 FR 33809 - Amendment and Update to the Entry for an Individual Named in the Annex to Executive Order 13219...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

... Specially Designated Nationals and Blocked Persons (``SDN List''). The individual's date of birth has been amended and two addresses and an alternate place of birth have been added to the SDN List entry. The... entry of this individual on the SDN List is effective May 26, 2011. FOR FURTHER INFORMATION CONTACT...

Entry Risk into the Juvenile Justice System: African American, American Indian, Asian American, European American, and Hispanic Children and Adolescents

ERIC Educational Resources Information Center

Vazsonyi, Alexander T.; Chen, Pan

2010-01-01

Background: Findings on disproportionate minority contact remain mixed. Few empirical studies have examined to what extent entry risk into juvenile justice varies across ethnic/racial groups, and to what extent childhood aggressive behaviors foretell later deviance and entry risk. In the current study, we sought to address these shortcomings by…

U.S. Army Delayed Entry Program Optimization Model

DTIC Science & Technology

2004-08-01

United States Military Academy West Point, New York 10996 OPERATIONS RESEARCH CENTER OF EXCELLENCE TECHNICAL REPORT No. DSE-TR- 0428 DTIC #: ADAXXXXX...following entries: Author(s) Department of Systems Engineering 2 Mahan Hall West Point, NY 10996 Client USAAC CAR 4 1307 Third Ave., Fort Knox, KY 40121...Wolter, LTC Michael J. Kwinn, Jr., LTC John Halstead DSE-R- 0428 5S. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8

Porcine, murine and human sialoadhesin (Sn/Siglec-1/CD169): portals for porcine reproductive and respiratory syndrome virus entry into target cells.

PubMed

Van Breedam, Wander; Verbeeck, Mieke; Christiaens, Isaura; Van Gorp, Hanne; Nauwynck, Hans J

2013-09-01

Porcine sialoadhesin (pSn; a sialic acid-binding lectin) and porcine CD163 (pCD163) are molecules that facilitate infectious entry of porcine reproductive and respiratory syndrome virus (PRRSV) into alveolar macrophages. In this study, it was shown that murine Sn (mSn) and human Sn (hSn), like pSn, can promote PRRSV infection of pCD163-expressing cells. Intact sialic acid-binding domains are crucial, since non-sialic acid-binding mutants of pSn, mSn and hSn did not promote infection. Endodomain-deletion mutants of pSn, mSn and hSn promoted PRRSV infection less efficiently, but also showed markedly reduced expression levels, making further research into the potential role of the Sn endodomain in PRRSV receptor activity necessary. These data further complement our knowledge on Sn as an important PRRSV receptor, and suggest - in combination with other published data - that species differences in the main PRRSV entry mediators Sn and CD163 do not account for the strict host species specificity displayed by the virus.

Security of patient data when decommissioning ultrasound systems

PubMed Central

2017-01-01

Background Although ultrasound systems generally archive to Picture Archiving and Communication Systems (PACS), their archiving workflow typically involves storage to an internal hard disk before data are transferred onwards. Deleting records from the local system will delete entries in the database and from the file allocation table or equivalent but, as with a PC, files can be recovered. Great care is taken with disposal of media from a healthcare organisation to prevent data breaches, but ultrasound systems are routinely returned to lease companies, sold on or donated to third parties without such controls. Methods In this project, five methods of hard disk erasure were tested on nine ultrasound systems being decommissioned: the system’s own delete function; full reinstallation of system software; the manufacturer’s own disk wiping service; open source disk wiping software for full and just blank space erasure. Attempts were then made to recover data using open source recovery tools. Results All methods deleted patient data as viewable from the ultrasound system and from browsing the disk from a PC. However, patient identifiable data (PID) could be recovered following the system’s own deletion and the reinstallation methods. No PID could be recovered after using the manufacturer’s wiping service or the open source wiping software. Conclusion The typical method of reinstalling an ultrasound system’s software may not prevent PID from being recovered. When transferring ownership, care should be taken that an ultrasound system’s hard disk has been wiped to a sufficient level, particularly if the scanner is to be returned with approved parts and in a fully working state. PMID:28228821

The NSO FTS database program and archive (FTSDBM)

NASA Technical Reports Server (NTRS)

Lytle, D. M.

1992-01-01

Data from the NSO Fourier transform spectrometer is being re-archived from half inch tape onto write-once compact disk. In the process, information about each spectrum and a low resolution copy of each spectrum is being saved into an on-line database. FTSDBM is a simple database management program in the NSO external package for IRAF. A command language allows the FTSDBM user to add entries to the database, delete entries, select subsets from the database based on keyword values including ranges of values, create new database files based on these subsets, make keyword lists, examine low resolution spectra graphically, and make disk number/file number lists. Once the archive is complete, FTSDBM will allow the database to be efficiently searched for data of interest to the user and the compact disk format will allow random access to that data.

The Rewarding Challenge: Welcoming Re-Entry Women Students to the Small College.

ERIC Educational Resources Information Center

Midland Lutheran Coll., Fremont, NE.

This handbook was designed to offer a low-cost, local, and practical approach to working with re-entry women college students. It is intended for use by staff in small colleges (under 1,000 students) where women's centers and on-campus child care are rare and where the needs of re-entry students have not been adequately addressed. The information…

Gain-of-function mutant p53 but not p53 deletion promotes head and neck cancer progression in response to oncogenic K-ras

PubMed Central

Acin, Sergio; Li, Zhongyou; Mejia, Olga; Roop, Dennis R; El-Naggar, Adel K; Caulin, Carlos

2015-01-01

Mutations in p53 occur in over 50% of the human head and neck squamous cell carcinomas (SCCHN). The majority of these mutations result in the expression of mutant forms of p53, rather than deletions in the p53 gene. Some p53 mutants are associated with poor prognosis in SCCHN patients. However, the molecular mechanisms that determine the poor outcome of cancers carrying p53 mutations are unknown. Here, we generated a mouse model for SCCHN and found that activation of the endogenous p53 gain-of-function mutation p53R172H, but not deletion of p53, cooperates with oncogenic K-ras during SCCHN initiation, accelerates oral tumour growth, and promotes progression to carcinoma. Mechanistically, expression profiling of the tumours that developed in these mice and studies using cell lines derived from these tumours determined that mutant p53 induces the expression of genes involved in mitosis, including cyclin B1 and cyclin A, and accelerates entry in mitosis. Additionally, we discovered that this oncogenic function of mutant p53 was dependent on K-ras because the expression of cyclin B1 and cyclin A decreased, and entry in mitosis was delayed, after suppressing K-ras expression in oral tumour cells that express p53R172H. The presence of double-strand breaks in the tumours suggests that oncogene-dependent DNA damage resulting from K-ras activation promotes the oncogenic function of mutant p53. Accordingly, DNA damage induced by doxorubicin also induced increased expression of cyclin B1 and cyclin A in cells that express p53R172H. These findings represent strong in vivo evidence for an oncogenic function of endogenous p53 gain-of-function mutations in SCCHN and provide a mechanistic explanation for the genetic interaction between oncogenic K-ras and mutant p53. PMID:21952947

76 FR 60028 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... provides that a registrant of a pesticide product may at any time request that any of its pesticide... later than October 28, 2011 for the deletion in Table 1. Users of these products who desire continued..., 2012 for the products in Table 2, or October 28, 2011 for the product in Table 1. ADDRESSES: Submit...

Sex Differences in Ethanol's Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice with a Null Mutation of the 5α-Reductase Type 1 Gene.

PubMed

Tanchuck-Nipper, Michelle A; Ford, Matthew M; Hertzberg, Anna; Beadles-Bohling, Amy; Cozzoli, Debra K; Finn, Deborah A

2015-05-01

Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5α-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5α-reductase-1 gene (Srd5a1). The present studies examined the impact of Srd5a1 deletion in male and female mice on several acute effects of ethanol and on chronic ethanol withdrawal severity. Genotype and sex did not differentially alter ethanol-induced hypothermia, ataxia, hypnosis, or metabolism, but ethanol withdrawal was significantly lower in female versus male mice. On the elevated plus maze, deletion of the Srd5a1 gene significantly decreased ethanol's effect on total entries versus wildtype (WT) mice and significantly decreased ethanol's anxiolytic effect in female knockout (KO) versus WT mice. The limited sex differences in the ability of Srd5a1 genotype to modulate select ethanol effects may reflect an interaction between developmental compensations to deletion of the Srd5a1 gene with sex hormones and levels of endogenous neurosteroids.

Sex Differences in Ethanol’s Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice With a Null Mutation of the 5α-Reductase Type 1 Gene

PubMed Central

Tanchuck-Nipper, Michelle A.; Ford, Matthew M.; Hertzberg, Anna; Beadles-Bohling, Amy; Cozzoli, Debra K.; Finn, Deborah A.

2015-01-01

Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5α-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5α-reductase-1 gene (Srd5a1). The present studies examined the impact of Srd5a1 deletion in male and female mice on several acute effects of ethanol and on chronic ethanol withdrawal severity. Genotype and sex did not differentially alter ethanol-induced hypothermia, ataxia, hypnosis, or metabolism, but ethanol withdrawal was significantly lower in female versus male mice. On the elevated plus maze, deletion of the Srd5a1 gene significantly decreased ethanol’s effect on total entries versus wildtype (WT) mice and significantly decreased ethanol’s anxiolytic effect in female knockout (KO) versus WT mice. The limited sex differences in the ability of Srd5a1 genotype to modulate select ethanol effects may reflect an interaction between developmental compensations to deletion of the Srd5a1 gene with sex hormones and levels of endogenous neurosteroids. PMID:25355320

Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins.

PubMed

Hyun, Seong-In; Weisberg, Andrea; Moss, Bernard

2017-08-01

The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes. IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights into many aspects of cell biology. The I2 protein is conserved in all poxviruses that infect vertebrates, suggesting an important role. The present study revealed that this protein is essential for vaccinia virus morphogenesis and that its absence results in an accumulation of deformed virus particles retaining the scaffold protein and deficient in surface proteins needed for cell entry. Copyright © 2017 American Society for Microbiology.

Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons.

PubMed

Fukui, Hirokazu; Moraes, Carlos T

2009-03-15

Age-dependent accumulation of partially deleted mitochondrial DNA (DeltamtDNA) has been suggested to contribute to aging and the development of age-associated diseases including Parkinson's disease. However, the molecular mechanisms underlying the generation and accumulation of DeltamtDNA have not been addressed in vivo. In this study, we have developed a mouse model expressing an inducible mitochondria-targeted restriction endonuclease (PstI). Using this system, we could trigger mtDNA double-strand breaks (DSBs) in adult neurons. We found that this transient event leads to the generation of a family of DeltamtDNA with features that closely resemble naturally-occurring mtDNA deletions. The formation of these deleted species is likely to be mediated by yet uncharacterized DNA repairing machineries that participate in homologous recombination and non-homologous end-joining. Furthermore, we obtained in vivo evidence that DeltamtDNAs with larger deletions accumulate faster than those with smaller deletions, implying a replicative advantage of smaller mtDNAs. These findings identify DSB, DNA repair systems and replicative advantage as likely mechanisms underlying the generation and age-associated accumulation of DeltamtDNA in mammalian neurons.

RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry

PubMed Central

Siddiqui, Mohammad Adnan; Dayal, Shubham; Naji, Merna; Ezelle, Heather J.; Zeng, Chun; Zhou, Aimin; Hassel, Bret A.

2014-01-01

ABSTRACT The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents. PMID:25352621

Attenuated Response to Methamphetamine Sensitization and Deficits in Motor Learning and Memory after Selective Deletion of [beta]-Catenin in Dopamine Neurons

ERIC Educational Resources Information Center

Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R.; Tagliaferro, Adriana; Brusco, Alicia; Backman, Cristina M.

2012-01-01

In the present study, we analyzed mice with a targeted deletion of [beta]-catenin in DA neurons (DA-[beta]cat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-[beta]cat KO mice showed significant…

MM/T Program for Three Color Light Emitting Diode Display Modules.

DTIC Science & Technology

1981-10-01

DAVID, G W LEWIS DARKAS AG -C 0566 UNCLASSIFIED DELET-TR-RO 0566 1 ML 1.0 ______ 220 1.25 _ 1 .r DELET-TR- 80-0566-1 Research and Development Technical...is transmitted, followed by the "Literal" address of the pixel LA I16170 Sit 1034373S U~ T I I TABLE I SHIFTED ASCU CHAR. BINARY DEC. ASCU 3fHARY DEC

“Black holes” and bacterial pathogenicity: A large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli

PubMed Central

Maurelli, Anthony T.; Fernández, Reinaldo E.; Bloch, Craig A.; Rode, Christopher K.; Fasano, Alessio

1998-01-01

Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in ≈90% of E. coli strains but is uniformly absent in Shigella strains. When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella. Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA. Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these “black holes,” deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases. PMID:9520472

``Black Holes" and Bacterial Pathogenicity: A Large Genomic Deletion that Enhances the Virulence of Shigella spp. and Enteroinvasive Escherichia coli

NASA Astrophysics Data System (ADS)

Maurelli, Anthony T.; Fernandez, Reinaldo E.; Bloch, Craig A.; Rode, Christopher K.; Fasano, Alessio

1998-03-01

Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylate (LDC) activity is present in ≈ 90% of E. coli strains but is uniformly absent in Shigella strains. When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella. Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA. Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these ``black holes,'' deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.

Natural Infection of a Homozygous Δ24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus

PubMed Central

Chen, Zhiwei; Kwon, Douglas; Jin, Zhanqun; Monard, Simon; Telfer, Paul; Jones, Morris S.; Lu, Chang Y.; Aguilar, Roberto F.; Ho, David D.; Marx, Preston A.

1998-01-01

A homozygous 24-bp deletion (Δ24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Δ24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpectedly, RCM-009, one of 11 homozygotes (Δ24CCR5/ Δ24CCR5), was found to be naturally infected with a divergent simian immunodeficiency virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as its major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other divergent SIVs tested. Cells transfected with the Δ24 CCR5 did not support entry of R5-tropic SIVmac, SIVcpz, SIVmne, HIV-2, or HIV-1, and were also inactive in signal transduction mediated by β-chemokines. At 86.6%, the Δ24 allelic frequency was significantly higher than that of the 32-bp deletion found in humans. The Δ24 frequency was 4.1% in 34 sooty mangabeys (SMs), a geographically isolated subspecies that was naturally infected with R5-tropic SIV. Finding identical deletions in two mangabey subspecies separated for 10,000 years or more dates the Δ24 CCR5 deletion as ancient. However, the source of the selective pressure for the high rate of CCR5 deletion in RCMs remains to be determined. The high allelic frequency of the Δ24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 genetic defects appeared in its host. PMID:9841919

Entry and Competition in the U.S. Transit Bus Manufacturing Industry

DOT National Transportation Integrated Search

1982-03-01

This report is an analytic paper addressing the trend toward entry into the U.S. transit bus market by new foreign manufacturers. The purpose of this study is to provide an explanation, and outline the implications of why so many companies are intere...

Directory of Child Advocacy Programs.

ERIC Educational Resources Information Center

Administration for Children, Youth, and Families (DHEW), Washington, DC.

This directory lists 107 child advocacy programs in 37 states, the District of Columbia and the Virgin Islands. Each entry includes project title, address, telephone number, contact person, a statement of purpose and a summary of current advocacy activities. Entries are indexed under the following terms: adolescent parenthood,…

NF1 Microdeletion Syndrome: Refined FISH Characterization of Sporadic and Familial Deletions with Locus-Specific Probes

PubMed Central

Riva, Paola; Corrado, Lucia; Natacci, Federica; Castorina, Pierangela; Wu, Bai-Li; Schneider, Gretchen H.; Clementi, Maurizio; Tenconi, Romano; Korf, Bruce R.; Larizza, Lidia

2000-01-01

Summary Two familial and seven sporadic patients with neurofibromatosis 1—who showed dysmorphism, learning disabilities/mental retardation, and additional signs and carried deletions of the NF1 gene—were investigated by use of a two-step FISH approach to characterize the deletions. With FISH of YAC clones belonging to a 7-Mb 17q11.2 contig, we estimated the extension of all of the deletions and identified the genomic regions harboring the breakpoints. Mosaicism accounted for the mild phenotype in two patients. In subsequent FISH experiments, performed with locus-specific probes generated from the same YACs by means of a novel procedure, we identified the smallest region of overlapping (SRO), mapped the deletion breakpoints, and identified the genes that map to each deletion interval. From centromere to telomere, the ∼0.8-Mb SRO includes sequence-tagged site 64381, the SUPT6H gene (encoding a transcription factor involved in chromatin structure), and NF1. Extending telomerically from the SRO, two additional genes—BLMH, encoding a hydrolase involved in bleomycin resistance, and ACCN1, encoding an amiloride-sensitive cation channel expressed in the CNS—were located in the deleted intervals of seven and three patients, respectively. An apparently common centromeric deletion breakpoint was shared by all of the patients, whereas a different telomeric breakpoint defined a deletion interval of 0.8–3 Mb. There was no apparent correlation between the extent of the deletion and the phenotype. This characterization of gross NF1 deletions provides the premise for addressing correctly any genotype-phenotype correlation in the subset of patients with NF1 deletions. PMID:10631140

Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging.

PubMed

Boutier, Maxime; Ronsmans, Maygane; Ouyang, Ping; Fournier, Guillaume; Reschner, Anca; Rakus, Krzysztof; Wilkie, Gavin S; Farnir, Frédéric; Bayrou, Calixte; Lieffrig, François; Li, Hong; Desmecht, Daniel; Davison, Andrew J; Vanderplasschen, Alain

2015-02-01

Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open reading frame 134 (ORF134), we unexpectedly obtained a clone with additional deletion of ORF56 and ORF57. This triple deleted recombinant replicated efficiently in vitro and expressed an in vivo safety/efficacy profile compatible with use as an attenuated vaccine. To determine the role of the double ORF56-57 deletion in the phenotype and to improve further the quality of the vaccine candidate, a series of deleted recombinants was produced and tested in vivo. These experiments led to the selection of a double deleted recombinant lacking ORF56 and ORF57 as a vaccine candidate. The safety and efficacy of this strain were studied using an in vivo bioluminescent imaging system (IVIS), qPCR, and histopathological examination, which demonstrated that it enters fish via skin infection similar to the wild type strain. However, compared to the parental wild type strain, the vaccine candidate replicated at lower levels and spread less efficiently to secondary sites of infection. Transmission experiments allowing water contamination with or without additional physical contact between fish demonstrated that the vaccine candidate has a reduced ability to spread from vaccinated fish to naïve sentinel cohabitants. Finally, IVIS analyses demonstrated that the vaccine candidate induces a protective mucosal immune response at the portal of entry. Thus, the present study is the first to report the rational development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. We also demonstrated the relevance of the CyHV 3 carp model for studying alloherpesvirus transmission and mucosal immunity in teleost skin.

75 FR 82565 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-48; Introduction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-30

... delete the requirement for submission of full social security numbers and home addresses of individual... subcontractors to maintain the full social security number and current address of each covered worker, and... Department of Labor for purposes of an investigation or audit of compliance with prevailing wage requirements...

Yes, Michael: Reflections on How Inclusion Can Build Social Skills.

ERIC Educational Resources Information Center

Anderson, Genan T.

2003-01-01

Describes a teacher's and preschool students' experiences with the classroom inclusion of an autistic child. Specifically addresses: (1) how social skills affect academic skills; (2) teaching social competency; (3) coaching group entry; (4) successful group entry and sustained social interaction; and (5) lessons learned from inclusion of a special…

77 FR 5768 - Application(s) for Duty-Free Entry of Scientific Instruments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... DEPARTMENT OF COMMERCE International Trade Administration Application(s) for Duty-Free Entry of... before February 27, 2012. Address written comments to Statutory Import Programs Staff, Room 3720, U.S... the U.S. Department of Commerce in Room 3720. Docket Number: 11-072. Applicant: University of...

The PEN&PAD data entry system: from prototype to practical system.

PubMed Central

Kirby, J.; Rector, A. L.

1996-01-01

This paper describes some of the issues addressed in the transition of the PEN&PAD from prototype clinical workstation to practical data entry system for use by general practitioners in the UK. Background and motivation of the PEN&PAD and GALEN projects are presented before the operation of the PEN&PAD user interface is described. A number of issues which have arisen in the development of the PEN&PAD Data Entry System are discussed. PMID:8947757

Orion Entry Handling Qualities Assessments

NASA Technical Reports Server (NTRS)

Bihari, B.; Tiggers, M.; Strahan, A.; Gonzalez, R.; Sullivan, K.; Stephens, J. P.; Hart, J.; Law, H., III; Bilimoria, K.; Bailey, R.

2011-01-01

The Orion Command Module (CM) is a capsule designed to bring crew back from the International Space Station (ISS), the moon and beyond. The atmospheric entry portion of the flight is deigned to be flown in autopilot mode for nominal situations. However, there exists the possibility for the crew to take over manual control in off-nominal situations. In these instances, the spacecraft must meet specific handling qualities criteria. To address these criteria two separate assessments of the Orion CM s entry Handling Qualities (HQ) were conducted at NASA s Johnson Space Center (JSC) using the Cooper-Harper scale (Cooper & Harper, 1969). These assessments were conducted in the summers of 2008 and 2010 using the Advanced NASA Technology Architecture for Exploration Studies (ANTARES) six degree of freedom, high fidelity Guidance, Navigation, and Control (GN&C) simulation. This paper will address the specifics of the handling qualities criteria, the vehicle configuration, the scenarios flown, the simulation background and setup, crew interfaces and displays, piloting techniques, ratings and crew comments, pre- and post-fight briefings, lessons learned and changes made to improve the overall system performance. The data collection tools, methods, data reduction and output reports will also be discussed. The objective of the 2008 entry HQ assessment was to evaluate the handling qualities of the CM during a lunar skip return. A lunar skip entry case was selected because it was considered the most demanding of all bank control scenarios. Even though skip entry is not planned to be flown manually, it was hypothesized that if a pilot could fly the harder skip entry case, then they could also fly a simpler loads managed or ballistic (constant bank rate command) entry scenario. In addition, with the evaluation set-up of multiple tasks within the entry case, handling qualities ratings collected in the evaluation could be used to assess other scenarios such as the constant bank angle maintenance case. The 2008 entry assessment was divided into two sections (see Figure 1). Entry I was the first, high speed portion of a lunar return and Entry II was the second, lower speed portion of a lunar return, which is similar (but not identical) to a typical ISS return.

A Novel CCR5 Mutation Common in Sooty Mangabeys Reveals SIVsmm Infection of CCR5-Null Natural Hosts and Efficient Alternative Coreceptor Use In Vivo

PubMed Central

Riddick, Nadeene E.; Hermann, Emilia A.; Loftin, Lamorris M.; Elliott, Sarah T.; Wey, Winston C.; Cervasi, Barbara; Taaffe, Jessica; Engram, Jessica C.; Li, Bing; Else, James G.; Li, Yingying; Hahn, Beatrice H.; Derdeyn, Cynthia A.; Sodora, Donald L.; Apetrei, Cristian; Paiardini, Mirko; Silvestri, Guido; Collman, Ronald G.

2010-01-01

In contrast to HIV infection in humans and SIV in macaques, SIV infection of natural hosts including sooty mangabeys (SM) is non-pathogenic despite robust virus replication. We identified a novel SM CCR5 allele containing a two base pair deletion (Δ2) encoding a truncated molecule that is not expressed on the cell surface and does not support SIV entry in vitro. The allele was present at a 26% frequency in a large SM colony, along with 3% for a CCR5Δ24 deletion allele that also abrogates surface expression. Overall, 8% of animals were homozygous for defective CCR5 alleles and 41% were heterozygous. The mutant allele was also present in wild SM in West Africa. CD8+ and CD4+ T cells displayed a gradient of CCR5 expression across genotype groups, which was highly significant for CD8+ cells. Remarkably, the prevalence of natural SIVsmm infection was not significantly different in animals lacking functional CCR5 compared to heterozygous and homozygous wild-type animals. Furthermore, animals lacking functional CCR5 had robust plasma viral loads, which were only modestly lower than wild-type animals. SIVsmm primary isolates infected both homozygous mutant and wild-type PBMC in a CCR5-independent manner in vitro, and Envs from both CCR5-null and wild-type infected animals used CXCR6, GPR15 and GPR1 in addition to CCR5 in transfected cells. These data clearly indicate that SIVsmm relies on CCR5-independent entry pathways in SM that are homozygous for defective CCR5 alleles and, while the extent of alternative coreceptor use in SM with CCR5 wild type alleles is uncertain, strongly suggest that SIVsmm tropism and host cell targeting in vivo is defined by the distribution and use of alternative entry pathways in addition to CCR5. SIVsmm entry through alternative pathways in vivo raises the possibility of novel CCR5-negative target cells that may be more expendable than CCR5+ cells and enable the virus to replicate efficiently without causing disease in the face of extremely restricted CCR5 expression seen in SM and several other natural host species. PMID:20865163

A novel CCR5 mutation common in sooty mangabeys reveals SIVsmm infection of CCR5-null natural hosts and efficient alternative coreceptor use in vivo.

PubMed

Riddick, Nadeene E; Hermann, Emilia A; Loftin, Lamorris M; Elliott, Sarah T; Wey, Winston C; Cervasi, Barbara; Taaffe, Jessica; Engram, Jessica C; Li, Bing; Else, James G; Li, Yingying; Hahn, Beatrice H; Derdeyn, Cynthia A; Sodora, Donald L; Apetrei, Cristian; Paiardini, Mirko; Silvestri, Guido; Collman, Ronald G

2010-08-26

In contrast to HIV infection in humans and SIV in macaques, SIV infection of natural hosts including sooty mangabeys (SM) is non-pathogenic despite robust virus replication. We identified a novel SM CCR5 allele containing a two base pair deletion (Δ2) encoding a truncated molecule that is not expressed on the cell surface and does not support SIV entry in vitro. The allele was present at a 26% frequency in a large SM colony, along with 3% for a CCR5Δ24 deletion allele that also abrogates surface expression. Overall, 8% of animals were homozygous for defective CCR5 alleles and 41% were heterozygous. The mutant allele was also present in wild SM in West Africa. CD8+ and CD4+ T cells displayed a gradient of CCR5 expression across genotype groups, which was highly significant for CD8+ cells. Remarkably, the prevalence of natural SIVsmm infection was not significantly different in animals lacking functional CCR5 compared to heterozygous and homozygous wild-type animals. Furthermore, animals lacking functional CCR5 had robust plasma viral loads, which were only modestly lower than wild-type animals. SIVsmm primary isolates infected both homozygous mutant and wild-type PBMC in a CCR5-independent manner in vitro, and Envs from both CCR5-null and wild-type infected animals used CXCR6, GPR15 and GPR1 in addition to CCR5 in transfected cells. These data clearly indicate that SIVsmm relies on CCR5-independent entry pathways in SM that are homozygous for defective CCR5 alleles and, while the extent of alternative coreceptor use in SM with CCR5 wild type alleles is uncertain, strongly suggest that SIVsmm tropism and host cell targeting in vivo is defined by the distribution and use of alternative entry pathways in addition to CCR5. SIVsmm entry through alternative pathways in vivo raises the possibility of novel CCR5-negative target cells that may be more expendable than CCR5+ cells and enable the virus to replicate efficiently without causing disease in the face of extremely restricted CCR5 expression seen in SM and several other natural host species.

Mediator can regulate mitotic entry and direct periodic transcription in fission yeast.

PubMed

Banyai, Gabor; Lopez, Marcela Davila; Szilagyi, Zsolt; Gustafsson, Claes M

2014-11-01

Cdk8 is required for correct timing of mitotic progression in fission yeast. How the activity of Cdk8 is regulated is unclear, since the kinase is not activated by T-loop phosphorylation and its partner, CycC, does not oscillate. Cdk8 is, however, a component of the multiprotein Mediator complex, a conserved coregulator of eukaryotic transcription that is connected to a number of intracellular signaling pathways. We demonstrate here that other Mediator components regulate the activity of Cdk8 in vivo and thereby direct the timing of mitotic entry. Deletion of Mediator components Med12 and Med13 leads to higher cellular Cdk8 protein levels, premature phosphorylation of the Cdk8 target Fkh2, and earlier entry into mitosis. We also demonstrate that Mediator is recruited to clusters of mitotic genes in a periodic fashion and that the complex is required for the transcription of these genes. We suggest that Mediator functions as a hub for coordinated regulation of mitotic progression and cell cycle-dependent transcription. The many signaling pathways and activator proteins shown to function via Mediator may influence the timing of these cell cycle events. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene.

PubMed

Vaughn, Cecily P; Baker, Christine L; Samowitz, Wade S; Swensen, Jeffrey J

2013-01-01

Lynch syndrome is characterized by mutations in one of four mismatch repair genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in PMS2 has previously been confined to Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method that permits detection of deletions of PMS2 Exons 12-15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3' deletions in 58 samples that were reported to be negative for PMS2 mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3' region of PMS2, including three previously reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15. Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through Alu-mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a PMS2 mutation based on immunohistochemical staining, for which mutations have not yet been identified, would benefit from testing using the new methodology. Copyright © 2012 Wiley Periodicals, Inc.

Arginine-glycine-aspartic acid motif is critical for human parechovirus 1 entry.

PubMed

Boonyakiat, Y; Hughes, P J; Ghazi, F; Stanway, G

2001-10-01

The human parechovirus 1 RGD motif in VP1 was studied by mutagenesis. An RGD-to-RGE change gave only revertant viruses with a restored RGD, while deletion of GD was lethal and nonrevertable. Mutations at the +1 and +2 positions had some effect on growth properties and a +1 M-to-P change was lethal. These studies indicate that the RGD motif plays a critical role in infectivity, presumably by interacting with integrins, and that downstream amino acids can have an influence on function.

Nearest Neighbor Classification of Stationary Time Series: An Application to Anesthesia Level Classification by EEG Analysis.

DTIC Science & Technology

1980-12-05

classification procedures that are common in speech processing. The anesthesia level classification by EEG time series population screening problem example is in...formance. The use of the KL number type metric in NN rule classification, in a delete-one subj ect ’s EE-at-a-time KL-NN and KL- kNN classification of the...17 individual labeled EEG sample population using KL-NN and KL- kNN rules. The results obtained are shown in Table 1. The entries in the table indicate

The feasibility study based on e-commerce instructions-focuses on detection and deletion of illegal content

NASA Astrophysics Data System (ADS)

Guo, Tianze; Bi, Siyu; Liu, Jiaming

2018-04-01

This essay legally restrains the illegal content based on the e-commerce directive and introduces that the European countries detect and notify illegal content through the instructions of competent authorities, notification of credible flaggers, user reports and technical tools. The illegal content should be deleted through the service terms and transparency report basing on prevent excessive deletions system. At the same time, use filters to detect and filter to against the recurrence of illegal content. By analyzing the advantages of China under the environment of cracking down on illegal content, this essay concludes that the success of China in cracking down on illegal content lies in all-round collaborative management model of countries, governments, enterprises and individuals. At the end of the essay, one is to build a training corpus that can automatically update the ability to identify the illegal content. And it proposes an optimization scheme that establish a complete set of address resolution procedures and classify IP address data according to big data analysis and DNS protection module to prevent hackers from spreading illegal content by tampering with DNS segments.

An Entry Flight Controls Analysis for a Reusable Launch Vehicle

NASA Technical Reports Server (NTRS)

Calhoun, Philip

2000-01-01

The NASA Langley Research Center has been performing studies to address the feasibility of various single-stage to orbit concepts for use by NASA and the commercial launch industry to provide a lower cost access to space. Some work on the conceptual design of a typical lifting body concept vehicle, designated VentureStar(sup TM) has been conducted in cooperation with the Lockheed Martin Skunk Works. This paper will address the results of a preliminary flight controls assessment of this vehicle concept during the atmospheric entry phase of flight. The work includes control analysis from hypersonic flight at the atmospheric entry through supersonic speeds to final approach and landing at subsonic conditions. The requirements of the flight control effectors are determined over the full range of entry vehicle Mach number conditions. The analysis was performed for a typical maximum crossrange entry trajectory utilizing angle of attack to limit entry heating and providing for energy management, and bank angle to modulation of the lift vector to provide downrange and crossrange capability to fly the vehicle to a specified landing site. Sensitivity of the vehicle open and closed loop characteristics to CG location, control surface mixing strategy and wind gusts are included in the results. An alternative control surface mixing strategy utilizing a reverse aileron technique demonstrated a significant reduction in RCS torque and fuel required to perform bank maneuvers during entry. The results of the control analysis revealed challenges for an early vehicle configuration in the areas of hypersonic pitch trim and subsonic longitudinal controllability.

75 FR 20850 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

... in the efforts to make system changes. Grantees will complete systems web-based data entry on goals... grantee and key staff-partner interview 249 2 1.60 797 guide EBHV grantee systems web-based data entry... prevent child maltreatment. An evaluation study will address four domains: (1) Systems change to develop...

Predictors of Student Success in Entry-Level Science Courses

ERIC Educational Resources Information Center

Singh, Mamta K.

2009-01-01

Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and…

Energy Education Resources: Kindergarten through 12th Grade.

ERIC Educational Resources Information Center

Energy Information Administration (DOE), Washington, DC.

This guide is aimed at educators, students, and other information users and lists free or low cost energy education materials. Each entry includes the address, telephone number, internet address, e-mail address, description of the providing organization, and a synopsis of the item available. The organizations represented take policy positions on…

Implementing asyncronous collective operations in a multi-node processing system

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

Chen, Dong; Eisley, Noel A.; Heidelberger, Philip

A method, system, and computer program product are disclosed for implementing an asynchronous collective operation in a multi-node data processing system. In one embodiment, the method comprises sending data to a plurality of nodes in the data processing system, broadcasting a remote get to the plurality of nodes, and using this remote get to implement asynchronous collective operations on the data by the plurality of nodes. In one embodiment, each of the nodes performs only one task in the asynchronous operations, and each nodes sets up a base address table with an entry for a base address of a memorymore » buffer associated with said each node. In another embodiment, each of the nodes performs a plurality of tasks in said collective operations, and each task of each node sets up a base address table with an entry for a base address of a memory buffer associated with the task.« less

Pleiotropy in microdeletion syndromes: Neurologic and spermatogenic abnormalities in mice homozygous for the p{sup 6H} deletion are likely due to dysfunction of a single gene

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

Rinchik, E.M.; Carpenter, D.A.; Handel, M.A.

1995-07-03

Variability and complexity of phenotypes observed in microdeletion syndromes can be due to deletion of a single gene whose product participates in several aspects of development or can be due to the deletion of a number of tightly linked genes, each adding its own effect to the syndrome. The p{sup 6H} deletion in mouse chromosome 7 presents a good model with which to address this question of multigene vs. single-gene pleiotropy. Mice homozygous for the p{sup 6H} deletion are diluted in pigmentation, are smaller than their littermates, and manifest a nervous jerky-gait phenotype. Male homozygotes are sterile and exhibit profoundmore » abnormalities in spermiogenesis. By using N-ethyl-N-nitrosourea (EtNU) mutagenesis and a breeding protocol designed to recover recessive mutations expressed hemizygously opposite a large p-locus deletion, we have generated three noncomplementing mutations that map to the p{sup 6H} deletion. Each of these EtNU-induced mutations has adverse effects on the size, nervous behavior, and progression of spermiogenesis that characterize p{sup 6H} deletion homozygotes. Because etNU is thought to induce primarily intragenic (point) mutations in mouse stem-cell spermatogonia, we propose that the trio of phenotypes (runtiness, nervous jerky gait, and male sterility) expressed in p{sup 6H} deletion homozygotes is the result of deletion of a single highly pleiotropic gene. We also predict that a homologous single locus, quite possibly tightly linked and distal to the D15S12 (P) locus in human chromosome 15q11-q13, may be associated with similar developmental abnormalities in humans. 29 refs., 3 figs., 1 tab.« less

Low levels of LTR retrotransposon deletion by ectopic recombination in the gigantic genomes of salamanders.

PubMed

Frahry, Matthew Blake; Sun, Cheng; Chong, Rebecca A; Mueller, Rachel Lockridge

2015-02-01

Across the tree of life, species vary dramatically in nuclear genome size. Mutations that add or remove sequences from genomes-insertions or deletions, or indels-are the ultimate source of this variation. Differences in the tempo and mode of insertion and deletion across taxa have been proposed to contribute to evolutionary diversity in genome size. Among vertebrates, most of the largest genomes are found within the salamanders, an amphibian clade with genome sizes ranging from ~14 to ~120 Gb. Salamander genomes have been shown to experience slower rates of DNA loss through small (i.e., <30 bp) deletions than do other vertebrate genomes. However, no studies have addressed DNA loss from salamander genomes resulting from larger deletions. Here, we focus on one type of large deletion-ectopic-recombination-mediated removal of LTR retrotransposon sequences. In ectopic recombination, double-strand breaks are repaired using a "wrong" (i.e., ectopic, or non-allelic) template sequence-typically another locus of similar sequence. When breaks occur within the LTR portions of LTR retrotransposons, ectopic-recombination-mediated repair can produce deletions that remove the internal transposon sequence and the equivalent of one of the two LTR sequences. These deletions leave a signature in the genome-a solo LTR sequence. We compared levels of solo LTRs in the genomes of four salamander species with levels present in five vertebrates with smaller genomes. Our results demonstrate that salamanders have low levels of solo LTRs, suggesting that ectopic-recombination-mediated deletion of LTR retrotransposons occurs more slowly than in other vertebrates with smaller genomes.

Cross-cultural re-entry for missionaries: a new application for the Dual Process Model.

PubMed

Selby, Susan; Clark, Sheila; Braunack-Mayer, Annette; Jones, Alison; Moulding, Nicole; Beilby, Justin

Nearly half a million foreign aid workers currently work worldwide, including over 140,000 missionaries. During re-entry these workers may experience significant psychological distress. This article positions previous research about psychological distress during re-entry, emphasizing loss and grief. At present there is no identifiable theoretical framework to provide a basis for assessment, management, and prevention of re-entry distress in the clinical setting. The development of theoretical concepts and frameworks surrounding loss and grief including the Dual Process Model (DPM) are discussed. All the parameters of the DPM have been shown to be appropriate for the proposed re-entry model, the Dual Process Model applied to Re-entry (DPMR). It is proposed that the DPMR is an appropriate framework to address the processes and strategies of managing re-entry loss and grief. Possible future clinical applications and limitations of the proposed model are discussed. The DPMR is offered for further validation and use in clinical practice.

Involvement of Escherichia coli K1 ibeT in bacterial adhesion that is associated with the entry into human brain microvascular endothelial cells.

PubMed

Zou, Yanming; He, Lina; Chi, Feng; Jong, Ambrose; Huang, Sheng-He

2008-12-01

IbeT is a downstream gene of the invasion determinant ibeA in the chromosome of a clinical isolate of Escherichia coli K1 strain RS218 (serotype 018:K1:H7). Both ibeT and ibeA are in the same operon. Our previous mutagenesis and complementation studies suggested that ibeT may coordinately contribute to E. coli K1 invasion with ibeA. An isogenic in-frame deletion mutant of ibeT has been made by chromosomal gene replacement with a recombinant suicide vector carrying a fragment with an ibeT internal deletion. The characteristics of the mutant in meningitic E. coli infection were examined in vitro [cell culture of human brain microvascular endothelial cells (HBMEC)] and in vivo (infant rat model of E. coli meningitis) in comparison with the parent strain. The ibeT deletion mutant was significantly less adhesive and invasive than its parent strain E. coli E44 in vitro, and the adhesion- and invasion-deficient phenotypes of the mutant can be complemented by the ibeT gene. Recombinant IbeT protein is able to block E. coli E44 invasion of HBMEC. Furthermore, the ibeT deletion mutant is less capable of colonizing intestine and less virulent in bacterial translocation across the blood-brain barrier (BBB) than its parent E. coli E44 in vivo. These data suggest that ibeT-mediated E. coli K1 adhesion is associated with the bacterial invasion process.

A Linear Kernel for Co-Path/Cycle Packing

NASA Astrophysics Data System (ADS)

Chen, Zhi-Zhong; Fellows, Michael; Fu, Bin; Jiang, Haitao; Liu, Yang; Wang, Lusheng; Zhu, Binhai

Bounded-Degree Vertex Deletion is a fundamental problem in graph theory that has new applications in computational biology. In this paper, we address a special case of Bounded-Degree Vertex Deletion, the Co-Path/Cycle Packing problem, which asks to delete as few vertices as possible such that the graph of the remaining (residual) vertices is composed of disjoint paths and simple cycles. The problem falls into the well-known class of 'node-deletion problems with hereditary properties', is hence NP-complete and unlikely to admit a polynomial time approximation algorithm with approximation factor smaller than 2. In the framework of parameterized complexity, we present a kernelization algorithm that produces a kernel with at most 37k vertices, improving on the super-linear kernel of Fellows et al.'s general theorem for Bounded-Degree Vertex Deletion. Using this kernel,and the method of bounded search trees, we devise an FPT algorithm that runs in time O *(3.24 k ). On the negative side, we show that the problem is APX-hard and unlikely to have a kernel smaller than 2k by a reduction from Vertex Cover.

75 FR 12250 - Notification of the Imposition of Conditions of Entry for Certain Vessels Arriving to the United...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... Republic of Timor-Leste. DATES: The requirements announced in this notice will become effective March 29, 2010. ADDRESSES: This notice will be available for inspection and copying at the Docket Management... arriving from ports that are not maintaining effective anti- terrorism measures and to deny entry into the...

A Guide to Internet Resources in Language Arts.

ERIC Educational Resources Information Center

Homme, John, Comp.; And Others

This paper presents a list of 154 Internet resources (listservs, freenets, telnet sites, gophers, etc.) dealing with language arts. Each entry in the list includes the name of the resource, and subscription and electronic mail addresses. Some of the entries in the list include a brief description of the resource. The paper lists 17 language arts…

9 CFR 98.34 - Import permits for poultry semen and animal semen.

Code of Federal Regulations, 2010 CFR

2010-01-01

... eartag; the region of origin; the name and address of the exporter; the port of embarkation in the foreign region; the mode of transportation, route of travel, and the port of entry in the United States... delivery will be made from the port of entry. Additional information may be required in the form of...

9 CFR 98.34 - Import permits for poultry semen and animal semen.

Code of Federal Regulations, 2011 CFR

2011-01-01

... eartag; the region of origin; the name and address of the exporter; the port of embarkation in the foreign region; the mode of transportation, route of travel, and the port of entry in the United States... delivery will be made from the port of entry. Additional information may be required in the form of...

Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis.

PubMed Central

Percy, N; Belsham, G J; Brangwyn, J K; Sullivan, M; Stone, D M; Almond, J W

1992-01-01

A series of genetic deletions based partly on two RNA secondary structure models (M. A. Skinner, V. R. Racaniello, G. Dunn, J. Cooper, P. D. Minor, and J. W. Almond, J. Mol. Biol. 207:379-392, 1989; E. V. Pilipenko, V. M. Blinov, L. I. Romanova, A. N. Sinyakov, S. V. Maslova, and V. I. Agol, Virology 168:201-209, 1989) was made in the cDNA encoding the 5' noncoding region (5' NCR) of the poliovirus genome in order to study the sequences that direct the internal entry of ribosomes. The modified cDNAs were placed between two open reading frames in a single transcriptional unit and used to transfect cells in culture. Internal entry of ribosomes was detected by measuring translation from the second open reading frame in the bicistronic mRNA. When assayed alone, a large proportion of the poliovirus 5' NCR superstructure including several well-defined stem-loops was required for ribosome entry and efficient translation. However, in cells cotransfected with a complete infectious poliovirus cDNA, the requirement for the stem-loops in this large superstructure was reduced. The results suggest that virus infection modifies the cellular translational machinery, so that shortened forms of the 5' NCR are sufficient for cap-independent translation, and that the internal entry of ribosomes occurs by two distinct modes during the virus replication cycle. Images PMID:1310772

Methods for Determining Likelihood of Tweet Deletion

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

Few works exist that attempt to build predictive models for tweet deletion. Zhou et al. (2015) focus on a subset of deleted tweets – regrettable tweets. These are tweets that the authors believe to contain inappropriate content. Inappropriate can range from vulgar language to sharing private content such as a personal email address. The presence of inappropriate content doesn’t guarantee that a tweet will be deleted, however intuition dictates it can be in an important factor in the tweet being deleted. In their work, the authors create a predictive model for identifying regrettable tweets. It is important to note themore » authors focus on predicting regrettable tweets that are distinctly not spam and only written in English. Through manual investigation, the authors identify ten major topics including negative sentiment, cursing, and relationships that are prevalent in regrettable tweets. The authors then exploit WordNet and UrbanDictionary to create keyword lists related to the ten topics. Finally, using a combination of existing lexica and the topic keywords as features, the authors build classifiers to test the accuracy of their model. The authors complement 700 manually labeled regrettable tweets with 700 normal tweets to create their evaluation dataset. The authors’ best performance from 10-fold cross-validation was an f1 score of 0.85 using a J48 classifier on a balanced dataset of deleted and non-deleted tweets.« less

77 FR 10791 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... Deleting NYSE Amex Equities Rule 319, Which Addresses Fidelity Bond Requirements, and Adopt New Rule Text... 319, which addresses fidelity bond requirements, and adopt new rule text that is substantially similar to FINRA Rule 4360. The text of the proposed rule change is available at the Exchange, the Commission...

Mammalian cell entry genes in Streptomyces may provide clues to the evolution of bacterial virulence

PubMed Central

Clark, Laura C.; Seipke, Ryan F.; Prieto, Pilar; Willemse, Joost; van Wezel, Gilles P.; Hutchings, Matthew I.; Hoskisson, Paul A.

2013-01-01

Understanding the evolution of virulence is key to appreciating the role specific loci play in pathogenicity. Streptomyces species are generally non-pathogenic soil saprophytes, yet within their genome we can find homologues of virulence loci. One example of this is the mammalian cell entry (mce) locus, which has been characterised in Mycobacterium tuberculosis. To investigate the role in Streptomyces we deleted the mce locus and studied its impact on cell survival, morphology and interaction with other soil organisms. Disruption of the mce cluster resulted in virulence towards amoebae (Acanthamoeba polyphaga) and reduced colonization of plant (Arabidopsis) models, indicating these genes may play an important role in Streptomyces survival in the environment. Our data suggest that loss of mce in Streptomyces spp. may have profound effects on survival in a competitive soil environment, and provides insight in to the evolution and selection of these genes as virulence factors in related pathogenic organisms. PMID:23346366

Genomic alterations in Warthin tumors of the parotid gland.

PubMed

Wemmert, Silke; Willnecker, Vivienne; Sauter, Birgit; Schuh, Sebastian; Brunner, Christian; Bohle, Rainer Maria; Urbschat, Steffi; Schick, Bernhard

2014-04-01

Despite the fact that Warthin tumors are the second most common type of benign salivary gland tumors, information regarding genetic alterations is extremely limited, and the tumorigenesis of these tumors has not been elucidated. The present results of the largest series of 30 tumors analyzed by comparative genomic hybridization (CGH) to date confirmed previous genetic findings and identified significant new candidate regions. The most commonly observed alterations were deletions of the short arm of chromosome 8, followed by deletions on 9p. Further representative changes were deletions on 16p and 22q with the minimal overlapping region at 16p12p13.1 and 22q12.1q12.3. Moreover, we indicated two different patterns of chromosomal aberrations. One group harbors deletions on 8p partly apparent with deletions on 9q, 11q 15q, 16p and 22. The second group shows gains on 22, partly apparent with gains on 1p and 20q and deletions on 9p. This leads to the assumption that Warthin tumors, in particular those with a high number of alterations, can be divided into two different genetic groups based on the pattern of numerical chromosomal aberrations. Further studies should address whether these subgroups also reflect a different clinical presentation.

Addressing childhood obesity at school entry: Qualitative experiences of school health professionals.

PubMed

Turner, Gillian L; Owen, Stephanie; Watson, Paula M

2016-09-01

School entry provides an opportune moment for health professionals to intervene with children who are overweight, yet identification and management of childhood obesity presents challenges in practice. This multi-method qualitative study explored the experiences of 26 school health professionals in addressing childhood obesity at school entry. Methods included semi-structured interviews with service managers (n = 3); focus groups with school nurses (n = 12) and child health practitioners (n = 6); and open-ended questionnaires with school nurses (n = 4) and child health practitioners (n = 1) who were unable to attend the focus groups. A thematic analysis revealed agreement between service managers, school nurses and child health practitioners. Whilst it was felt school health professionals have an important role to play in managing childhood obesity, efforts to address child weight were limited by a lack of capacity, lack of clear protocols, challenges of engaging parents and insufficient training in childhood obesity and related lifestyle issues. School health policymakers need to recognize childhood obesity as a serious public health issue, allocate appropriate resources to nurse training and development and ensure clear pathways are established to ensure consistency of care. © The Author(s) 2015.

Cellular receptor traffic is essential for productive duck hepatitis B virus infection.

PubMed

Breiner, K M; Schaller, H

2000-03-01

We have investigated the mechanism of duck hepatitis B virus (DHBV) entry into susceptible primary duck hepatocytes (PDHs), using mutants of carboxypeptidase D (gp180), a transmembrane protein shown to act as the primary cellular receptor for avian hepatitis B virus uptake. The variant proteins were abundantly produced from recombinant adenoviruses and tested for the potential to functionally outcompete the endogenous wild-type receptor. Overexpression of wild-type gp180 significantly enhanced the efficiency of DHBV infection in PDHs but did not affect ongoing DHBV replication, an observation further supporting gp180 receptor function. A gp180 mutant deficient for endocytosis abolished DHBV infection, indicating endocytosis to be the route of hepadnaviral entry. With further gp180 variants, carrying mutations in the cytoplasmic domain and characterized by an accelerated turnover, the ability of gp180 to function as a DHBV receptor was found to depend on a wild-type-like sorting phenotype which largely avoids transport toward the endolysosomal compartment. Based on these data, we propose a model in which a distinct intracellular DHBV traffic to the endosome, but not beyond, is a prerequisite for completion of viral entry, i.e., for fusion and capsid release. Furthermore, the deletion of the two enzymatically active carboxypeptidase domains of gp180 did not lead to a loss of receptor function.

A Guide to Alternative Education In the Bay Area. Second Edition.

ERIC Educational Resources Information Center

McCausland, Leigh; Rockbottom, Gwendolyn

More than 150 schools that offer alternatives to traditional education in San Francisco and the Bay Area are listed in this 60-page catalog. Each entry lists the name, address, phone number and name of the director of each school. Many entries include a 20-200 word description of the school's philosophy, cost, student teacher ratio, total…

BOOK REVIEW: The Complete A-Z Physics Handbook, Second Edition

NASA Astrophysics Data System (ADS)

Breithaupt, Jim

2000-11-01

The first edition of this book was published in 1997 and reviewed in Physics Education in March 1988. This second edition is 13 pages longer and contains a significant number of new entries, mostly in particle physics and astrophysics, to match the latest AS/A-level specifications. Some entries on topics such as surface tension that were removed from previous AS/A-level syllabuses have now been deleted. The revised book thus provides an effective alphabetical guide to key terms used in the latest AS/A-level specifications as most AS/A-level core terms are included, apart from terms for some of the new topics such as image processing in the new IOP AS/A-level specification. The style of the second edition is the same as the first, each entry commencing with the key term in bold print followed by an explanation of the term, accompanied by the relevant equation and/or a simple diagram where appropriate. Cross-references are given in italics. For example, the entry under quarks (which is one of the new entries) lists the six quarks and their characteristic properties in bullet point format then follows up with the information about the quark composition of baryons and mesons, giving the composition of the proton, the neutron and the pions as examples. The change of quark composition due to beta decay is mentioned with a cross-reference to beta decay. Other cross-references link to entries on the proton, the neutron and the four fundamental interactions. Lengthy entries such as the photoelectric effect each cover several pages, thus providing opportunities for in-depth revision. Useful theme entries provided in the first edition have been retained and referred to in a new two-page appendix on preparing for synoptic questions. Some proofs are provided such as the proof of the kinetic theory equation. Some experiments are described, each under an appropriate entry. Technically, the entries are reasonably accurate and usually expressed in appropriate and familiar language. The book ends with the same appendices as in the first edition (units, formulae, physical constants, examiners' terms, a suggested revision list and notes on examination preparation) plus the two-page synoptic appendix. The second edition with its additional entries on particle physics and astrophysics should prove useful as a study guide to supplement a textbook or as a revision guide as AS or A2 examinations approach. In addition, the concise nature of many of the entries could be valuable in helping physics students sharpen their written communication skills, thereby securing marks which all too often they lose on account of inadequate answers to descriptive questions.

Genome-Wide Estimates of Transposable Element Insertion and Deletion Rates in Drosophila Melanogaster

PubMed Central

Adrion, Jeffrey R.; Song, Michael J.; Schrider, Daniel R.; Hahn, Matthew W.

2017-01-01

Abstract Knowing the rate at which transposable elements (TEs) insert and delete is critical for understanding their role in genome evolution. We estimated spontaneous rates of insertion and deletion for all known, active TE superfamilies present in a set of Drosophila melanogaster mutation-accumulation (MA) lines using whole genome sequence data. Our results demonstrate that TE insertions far outpace TE deletions in D. melanogaster. We found a significant effect of background genotype on TE activity, with higher rates of insertions in one MA line. We also found significant rate heterogeneity between the chromosomes, with both insertion and deletion rates elevated on the X relative to the autosomes. Further, we identified significant associations between TE activity and chromatin state, and tested for associations between TE activity and other features of the local genomic environment such as TE content, exon content, GC content, and recombination rate. Our results provide the most detailed assessment of TE mobility in any organism to date, and provide a useful benchmark for both addressing theoretical predictions of TE dynamics and for exploring large-scale patterns of TE movement in D. melanogaster and other species. PMID:28338986

Sliding mode control for Mars entry based on extended state observer

NASA Astrophysics Data System (ADS)

Lu, Kunfeng; Xia, Yuanqing; Shen, Ganghui; Yu, Chunmei; Zhou, Liuyu; Zhang, Lijun

2017-11-01

This paper addresses high-precision Mars entry guidance and control approach via sliding mode control (SMC) and Extended State Observer (ESO). First, differential flatness (DF) approach is applied to the dynamic equations of the entry vehicle to represent the state variables more conveniently. Then, the presented SMC law can guarantee the property of finite-time convergence of tracking error, which requires no information on high uncertainties that are estimated by ESO, and the rigorous proof of tracking error convergence is given. Finally, Monte Carlo simulation results are presented to demonstrate the effectiveness of the suggested approach.

Analysis of Mars Pathfinder Entry Data, Aerothermal Heating, and Heat Shield Material Response

NASA Technical Reports Server (NTRS)

Milos, Frank; Chen, Y. K.; Tran, H. K.; Rasky, Daniel J. (Technical Monitor)

1997-01-01

The Mars Pathfinder heatshield contained several thermocouples and resistance thermometers. A description of the experiment, the entry data, and analysis of the entry environment and material response is presented. In particular, the analysis addresses uncertainties of the data and the fluid dynamics and material response models. The calculations use the latest trajectory and atmosphere reconstructions for the Pathfinder entry. A modified version of the GIANTS code is used for CFD (computational fluid dynamics) analyses, and FIAT is used for material response. The material response and flowfield are coupled appropriately. Three different material response models are considered. The analysis of Pathfinder entry data for validation of aerothermal heating and material response models is complicated by model uncertainties and unanticipated data-acquisition and processing problems. We will discuss these issues as well as ramifications of the data and analysis for future Mars missions.

The state-of-the-art port of entry workshop

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

Godfrey, B.

1995-05-01

The increased demand for freight movements through international ports of entry and the signing of the North American Free Trade Agreement (NAFTA) have increased freight traffic at border ports of entry. The State-of-the-Art Port of Entry Workshop initiated a dialogue among technologists and stakeholders to explore the potential uses of technology at border crossings and to set development priorities. International ports of entry are both information and labor intensive, and there are many promising technologies that could be used to provide timely information and optimize inspection resources. Participants universally held that integration of technologies and operations is critical to improvingmore » port services. A series of Next Steps was developed to address stakeholder issues and national priorities, such as the National Transportation Policy and National Drug Policy. This report documents the views of the various stakeholders and technologists present at the workshop and outlines future directions of study.« less

Addressing Personal Issues in Supervision: Impact of Counselors' Experience Level on Various Aspects of the Supervisory Relationship.

ERIC Educational Resources Information Center

Sumerel, Marie B.; Borders, L. Dianne

1996-01-01

In this study, entry-level and advanced counselors (N=40) rated videotaped supervision sessions in which either the counselor's personal issues or skills deficits were addressed. The study's goal was to determine the impact that addressing counselors' personal issues in supervision has on relationship, quality of the session, postsession mood, and…

NBCe1 expression is required for normal renal ammonia metabolism

PubMed Central

Handlogten, Mary E.; Osis, Gunars; Lee, Hyun-Wook; Romero, Michael F.; Verlander, Jill W.

2015-01-01

The mechanisms regulating proximal tubule ammonia metabolism are incompletely understood. The present study addressed the role of the proximal tubule basolateral electrogenic Na+-coupled bicarbonate cotransporter (NBCe1; Slc4a4) in renal ammonia metabolism. We used mice with heterozygous and homozygous NBCe1 gene deletion and compared these mice with their wild-type littermates. Because homozygous NBCe1 gene deletion causes 100% mortality before day 25, we studied mice at day 8 (±1 day). Both heterozygous and homozygous gene deletion caused a gene dose-related decrease in serum bicarbonate. The ability to lower urinary pH was intact, and even accentuated, with NBCe1 deletion. However, in contrast to the well-known effect of metabolic acidosis to increase urinary ammonia excretion, NBCe1 deletion caused a gene dose-related decrease in ammonia excretion. There was no identifiable change in proximal tubule structure by light microscopy. Examination of proteins involved in renal ammonia metabolism showed decreased expression of phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase, key enzymes in proximal tubule ammonia generation, and increased expression of glutamine synthetase, which recycles intrarenal ammonia and regenerates glutamine. Expression of key proteins involved in ammonia transport outside of the proximal tubule (rhesus B glycoprotein and rhesus C glycoprotein) was not significantly changed by NBCe1 deletion. We conclude from these findings that NBCe1 expression is necessary for normal proximal tubule ammonia metabolism. PMID:26224717

Avoidance of pseudogene interference in the detection of 3' deletions in PMS2.

PubMed

Vaughn, Cecily P; Hart, Kimberly J; Samowitz, Wade S; Swensen, Jeffrey J

2011-09-01

Lynch syndrome is characterized by mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. In PMS2, detection of mutations is confounded by numerous pseudogenes. Detection of 3' deletions is particularly complicated by the pseudogene PMS2CL, which has strong similarity to PMS2 exons 9 and 11-15, due to extensive gene conversion. A newly designed multiplex ligation-dependent probe amplification (MLPA) kit incorporates probes for variants found in both PMS2 and PMS2CL. This provides detection of deletions, but does not allow localization of deletions to the gene or pseudogene. To address this, we have developed a methodology incorporating reference samples with known copy numbers of variants, and paired MLPA results with sequencing of PMS2 and PMS2CL. We tested a subset of clinically indicated samples for which mutations were either unidentified or not fully characterized using existing methods. We identified eight unrelated patients with deletions encompassing exons 9-15, 11-15, 13-15, 14-15, and 15. By incorporating specific, characterized reference samples and sequencing the gene and pseudogene it is possible to identify deletions in this region of PMS2 and provide clinically relevant results. This methodology represents a significant advance in the diagnosis of patients with Lynch syndrome caused by PMS2 mutations. © 2011 Wiley-Liss, Inc.

The low density lipoprotein receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies

PubMed Central

Lillis, Anna P.; Van Duyn, Lauren B.; Murphy-Ullrich, Joanne E.; Strickland, Dudley K.

2008-01-01

The low-density lipoprotein (LDL) receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor family that plays diverse roles in various biological processes including lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a critical, but as of yet, undefined role in development. Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, in macrophages and in adipocytes. Three important properties of LRP1 dictate its diverse role in physiology: first, its ability to recognize more than thirty distinct ligands; second, its ability to bind a large number of cytoplasmic adaptor proteins via determinants located on its cytoplasmic domain in a phosphorylation-specific manner; and third, its ability to associate with and modulate the activity of other transmembrane receptors such as integrins and receptor tyrosine kinases. PMID:18626063

Increased resistance to ionizing and ultraviolet radiation in Escherichia coli JM83 is associated with a chromosomal rearrangement.

PubMed

McLean, K M; Gutman, P D; Minton, K W; Clark, E P

1992-06-01

Cells cope with radiation damage through several mechanisms: (1) increased DNA repair activity, (2) scavenging and inactivation of radiation-induced radical molecules, and (3) entry into a G0-like quiescent state. We have investigated a chromosomal rearrangement to elucidate further the molecular and genetic mechanisms underlying these phenomena. A mutant of Escherichia coli JM83 (phi 80dlacZ delta M15) was isolated that demonstrated significantly increased resistance to both ionizing and ultraviolet radiation. Surviving fractions of mutant and wild-type cells were measured following exposure to standardized doses of radiation. Increased radioresistance was directly related to a chromosomal alteration near the bacteriophage phi 80 attachment site (attB), as initially detected by the LacZ- phenotype of the isolate. Southern hybridization of chromosomal DNA from the mutant and wild-type E. coli JM83 strains indicated that a deletion had occurred. We propose that the deletion near the attB locus produces the radioresistant phenotype of the E. coli JM83 LacZ- mutant, perhaps through the alteration or inactivation of a gene or its controlling element(s).

Managed Entry Agreements for Pharmaceuticals in the Context of Adaptive Pathways in Europe.

PubMed

Bouvy, Jacoline C; Sapede, Claudine; Garner, Sarah

2018-01-01

As per the EMA definition, adaptive pathways is a scientific concept for the development of medicines which seeks to facilitate patient access to promising medicines addressing high unmet need through a prospectively planned approach in a sustainable way. This review reports the findings of activities undertaken by the ADAPT-SMART consortium to identify enablers and explore the suitability of managed entry agreements for adaptive pathways products in Europe. We found that during 2006-2016 outcomes-based managed entry agreements were not commonly used for products with a conditional marketing authorization or authorized under exceptional circumstances. The barriers and enablers to develop workable managed entry agreements models for adaptive pathways products were discussed through interviews and a multi-stakeholder workshop with a number of recommendations made in this paper.

Population Education Accessions List. January-April 1997.

ERIC Educational Resources Information Center

United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

This bibliography addresses the subject of population education. Entries are categorized into three parts. Part 1, "Population Education," consists of titles of books and other documents addressing various aspects of population education arranged by country in the first section and general materials in the second section. Part 2,…

Cargo Movement Operations Systems (CMOS). Revised Draft Software Test Plan

DTIC Science & Technology

1990-05-17

NO [ ] COMMENT DISPOSITION: ACCEPT [ ] REJECT [ ] COMMENT STATUS: OPEN [ ] CLOSED [ ] Cmnt Page Paragraph No. No. Number Comment 1. 1 1 Delete the period following this and all other single digit paragraph numbers in order to comply with the format used in the DID. 2. 9 3.1.3 Replace "Z-248" with "PC Workstation" in the second line of the paragraph. 3. 10 3.2.1 Change the "?" to a "" in the second entry of Table 3.2.1. 10 3.2.2 rut parentheses around the phrase bounded by commas in the second and third lines, i.e.,

STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction.

PubMed

Legrand, Julien M D; Roy, Edwige; Ellis, Jonathan J; Francois, Mathias; Brooks, Andrew J; Khosrotehrani, Kiarash

2016-09-01

Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

PubMed

Soh, Sheila X; Siddiqui, Fahad J; Allen, John C; Kim, Go Woon; Lee, Jae Cheol; Yatabe, Yasushi; Soda, Manabu; Mano, Hiroyuki; Soo, Ross A; Chin, Tan-Min; Ebi, Hiromichi; Yano, Seiji; Matsuo, Keitaro; Niu, Xiaomin; Lu, Shun; Isobe, Kazutoshi; Lee, Jih-Hsiang; Yang, James C; Zhao, Mingchuan; Zhou, Caicun; Lee, June-Koo; Lee, Se-Hoon; Lee, Ji Yun; Ahn, Myung-Ju; Tan, Tira J; Tan, Daniel S; Tan, Eng-Huat; Ong, S Tiong; Lim, Wan-Teck

2017-06-20

A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.

Overview of the MEDLI Project

NASA Technical Reports Server (NTRS)

Gazarik, Michael J.; Hwang, Helen; Little, Alan; Cheatwood, Neil; Wright, Michael; Herath, Jeff

2007-01-01

The Mars Science Laboratory Entry, Descent, and Landing Instrumentation (MEDLI) Project's objectives are to measure aerothermal environments, sub-surface heatshield material response, vehicle orientation, and atmospheric density for the atmospheric entry and descent phases of the Mars Science Laboratory (MSL) entry vehicle. The flight science objectives of MEDLI directly address the largest uncertainties in the ability to design and validate a robust Mars entry system, including aerothermal, aerodynamic and atmosphere models, and thermal protection system (TPS) design. The instrumentation suite will be installed in the heatshield of the MSL entry vehicle. The acquired data will support future Mars entry and aerocapture missions by providing measured atmospheric data to validate Mars atmosphere models and clarify the design margins for future Mars missions. MEDLI thermocouple and recession sensor data will significantly improve the understanding of aeroheating and TPS performance uncertainties for future missions. MEDLI pressure data will permit more accurate trajectory reconstruction, as well as separation of aerodynamic and atmospheric uncertainties in the hypersonic and supersonic regimes. This paper provides an overview of the project including the instrumentation design, system architecture, and expected measurement response.

Overview of the MEDLI Project

NASA Technical Reports Server (NTRS)

Gazarik, Michael J.; Little, Alan; Cheatwood, F. Neil; Wright, Michael J.; Herath, Jeff A.; Martinez, Edward R.; Munk, Michelle; Novak, Frank J.; Wright, Henry S.

2008-01-01

The Mars Science Laboratory Entry, Descent, and Landing Instrumentation (MEDLI) Project s objectives are to measure aerothermal environments, sub-surface heatshield material response, vehicle orientation, and atmospheric density for the atmospheric entry and descent phases of the Mars Science Laboratory (MSL) entry vehicle. The flight science objectives of MEDLI directly address the largest uncertainties in the ability to design and validate a robust Mars entry system, including aerothermal, aerodynamic and atmosphere models, and thermal protection system (TPS) design. The instrumentation suite will be installed in the heatshield of the MSL entry vehicle. The acquired data will support future Mars entry and aerocapture missions by providing measured atmospheric data to validate Mars atmosphere models and clarify the design margins for future Mars missions. MEDLI thermocouple and recession sensor data will significantly improve the understanding of aeroheating and TPS performance uncertainties for future missions. MEDLI pressure data will permit more accurate trajectory reconstruction, as well as separation of aerodynamic and atmospheric uncertainties in the hypersonic and supersonic regimes. This paper provides an overview of the project including the instrumentation design, system architecture, and expected measurement response.

Heatshield for Extreme Entry Environment Technology (HEEET)

NASA Technical Reports Server (NTRS)

Venkatapathy, E.; Ellerby, D.; Stackpoole, M..; Peterson, K.; Gage, P.; Beerman, A.; Blosser, M.; Chinnapongse, R.; Dillman, R.; Feldman, J.;

NASA's Advanced TPS Materials and Technology Development: Multi-Functional Materials and Systems for Space Exploration

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Feldman, Jay; Ellerby, Donald T.; Wercinski, Paul F.; Beck, Robin A S.

2017-01-01

NASA's future missions will be more demanding. They require materials to be mass efficient, robust, multi-functional, scalable and able to be integrated with other subsystems to enable innovative missions to accomplish future science missions. Thermal protection systems and materials (TPSM) are critical for the robotic and human exploration of the solar system when it involves entry. TPSM is a single string system with no back-up. Mass efficiency and robustness are required. Integration of TPSM with the aeroshell is both a challenge and an opportunity. Since 2010, NASA's Space Technology Mission Directorate has invested in innovative new materials and systems across a spectrum of game changing technologies. In this keynote address, we plan to highlight and present our successful approaches utilized in developing four different materials and system technologies that use innovative new manufacturing techniques to meet mission needs. 3-D weaving and felt manufacturing allowed us to successfully propose new ways of addressing TPSM challenges. In the 3-D MAT project, we developed and delivered a multi-functional TPS materials solution, in under three years that is an enabler for Lunar Capable Orion Spacecraft. Under the HEEET project, we are developing a robust heat-shield that can withstand extreme entry conditions, both thermally and mechanically, for entry at Venus, Saturn or higher speed sample return missions. The improved efficiency of HEEET allows science missions entry at much reduced G'loads enabling delicate science instruments to be used. The ADEPT concept is a foldable and deployable entry system and the critical component is a multi-functional fabric that is foldable and deployable and also functions as a mechanical aeroshell and a TPS. The fourth technology we will highlight involves felt to address integration challenges of rigid ablative system such as PICA that was used on MSL. The felt technology allows us to develop a compliant TPS for easy integration. The above four technology developments have focused on mission infusion as the success criteria. These technologies are in different stages of mission infusion. These innovations have led to new mission concepts to be proposed in the future. In our keynote address we will present approaches we have employed throughout the project to create the bridge to transition from low TRL to mission infusion and to overcome the traditional TRL valley of death.

Semi-Formal Description of KVM/370 Trusted Processes

DTIC Science & Technology

1977-12-09

OF KVM/370 TRUSTED PROCESSES 9I OTICD. H. THOMPSON SELECTEU JAN 5 IM8 , 9 DECEMBER 1977 D CLEARED FOR OPEN...Record Process TM-6062/111/00 OP15a: Start (Re der) given: Raddr: DeviceAddress NewClasses: set of Class entry: for some (R:ReaderEmtry) In Readers...Corporatio PRPU1: Process request for output spooling device assignment given: Process : ProcessName RequestedClassest set of Class entry: true error on for

Utilization of RNA polymerase I promoter and terminator sequences to develop a DNA transfection system for the study of hepatitis C virus internal ribosomal entry site-dependent translation.

PubMed

Oem, Jae-Ku; Xiang, Zhonghua; Zhou, Yan; Babiuk, Lorne A; Liu, Qiang

2007-09-01

Hepatitis C virus (HCV) causes severe liver diseases in a large population worldwide. HCV protein translation is controlled by an internal ribosomal entry site (IRES) within the 5'-untranslated region (UTR). HCV IRES-dependent translation is critical for HCV-associated pathogenesis. To develop a plasmid DNA transfection system by using RNA polymerase I promoter and terminator sequences for studying HCV IRES-dependent translation. A gene cassette containing HCV 5'-UTR, Renilla luciferase reporter gene, and HCV 3'-UTR was inserted between RNA polymerase I promoter and terminator sequences. HCV IRES-directed translation was determined by luciferase assay after transfection. Transfection of the RNA polymerase I-HCV IRES plasmid into human hepatoma Huh-7 and HepG2 cells resulted in luciferase gene expression. Deletion of the IIIf domain in HCV IRES dramatically reduced luciferase activity. Our results indicated that the plasmid vector system-based on RNA polymerase I promoter and terminator sequences represents an effective approach for the study of HCV IRES-dependent translation.

Radiometric age map of Aleutian Islands

USGS Publications Warehouse

Wilson, Frederic H.; Turner, D.L.

1975-01-01

This map includes published, thesis, and open-file radiometric data available to us as of June, 1975. Some dates are not plotted because of inadequate location data in the original references.The map is divided into five sections, based on 1:1,000,000 scale enlargements of the National Atlas maps of Alaska. Within each section (e.g., southeastern Alaska), radiometric dates are plotted and keyed to 1:250,000 scale quadrangles. Accompanying each map section is table 1, listing map numbers and the sample identification numbers used in DGGS Special Report 10: Radiometric Dates from Alaska-A 1975 Compilation”. The reader is referred to Special Report 10 for more complete information on location, rock type, dating method, and literature references for each age entry. A listing of dates in Special Report lo which require correction or deletion is included S table 2. Corrected and additional entries are listed in table 3. The listings in tables 2 and 3 follow the format of Special Report 10. Table 4 is a glossary of abbreviations used for quadrangle name, rock type, mineral dated, and type of dating method used.

Radiometric age map of southcentral Alaska

USGS Publications Warehouse

Wilson, Frederic H.; Turner, D.L.

1975-01-01

This map includes published, thesis, and open-file radiometric data available to us as of June, 1975. Some dates are not plotted because of inadequate location data in the original references.The map is divided into five sections, based on 1:1,000,000 scale enlargements of the National Atlas maps of Alaska. Within each section (e.g., southeastern Alaska), radiometric dates are plotted and keyed to 1:250,000 scale quadrangles. Accompanying each map section is table 1, listing map numbers and the sample identification numbers used in DGGS Special Report 10: Radiometric Dates from Alaska-A 1975 Compilation”. The reader is referred to Special Report 10 for more complete information on location, rock type, dating method, and literature references for each age entry. A listing of dates in Special Report lo which require correction or deletion is included S table 2. Corrected and additional entries are listed in table 3. The listings in tables 2 and 3 follow the format of Special Report 10. Table 4 is a glossary of abbreviations used for quadrangle name, rock type, mineral dated, and type of dating method used.

Radiometric age map of southwest Alaska

USGS Publications Warehouse

Wilson, Frederic H.; Turner, D.L.

1975-01-01

This map includes published, thesis, and open-file radiometric data available to us as of June, 1975. Some dates are not plotted because of inadequate location data in the original references.The map is divided into five sections, based on 1:1,000,000 scale enlargements of the National Atlas maps of Alaska. Within each section (e.g., southeastern Alaska), radiometric dates are plotted and keyed to 1:250,000 scale quadrangles. Accompanying each map section is table 1, listing map numbers and the sample identification numbers used in DGGS Special Report 10: Radiometric Dates from Alaska-A 1975 Compilation”. The reader is referred to Special Report 10 for more complete information on location, rock type, dating method, and literature references for each age entry. A listing of dates in Special Report lo which require correction or deletion is included S table 2. Corrected and additional entries are listed in table 3. The listings in tables 2 and 3 follow the format of Special Report 10. Table 4 is a glossary of abbreviations used for quadrangle name, rock type, mineral dated, and type of dating method used.

Radiometric age map of southeast Alaska

USGS Publications Warehouse

Wilson, Frederic H.; Turner, D.L.

1975-01-01

This map includes published, thesis, and open-file radiometric data available to us as of June, 1975. Some dates are not plotted because of inadequate location data in the original references.The map is divided into five sections, based on 1:1,000,000 scale enlargements of the National Atlas maps of Alaska. Within each section (e.g., southeastern Alaska), radiometric dates are plotted and keyed to 1:250,000 scale quadrangles. Accompanying each map section is table 1, listing map numbers and the sample identification numbers used in DGGS Special Report 10: Radiometric Dates from Alaska-A 1975 Compilation”. The reader is referred to Special Report 10 for more complete information on location, rock type, dating method, and literature references for each age entry. A listing of dates in Special Report lo which require correction or deletion is included S table 2. Corrected and additional entries are listed in table 3. The listings in tables 2 and 3 follow the format of Special Report 10. Table 4 is a glossary of abbreviations used for quadrangle name, rock type, mineral dated, and type of dating method used.

Radiometric age map of northern Alaska

USGS Publications Warehouse

Wilson, Frederic H.; Turner, D.L.

1975-01-01

This map includes published, thesis, and open-file radiometric data available to us as of June, 1975. Some dates are not plotted because of inadequate location data in the original references.The map is divided into five sections, based on 1:1,000,000 scale enlargements of the National Atlas maps of Alaska. Within each section (e.g., southeastern Alaska), radiometric dates are plotted and keyed to 1:250,000 scale quadrangles. Accompanying each map section is table 1, listing map numbers and the sample identification numbers used in DGGS Special Report 10: Radiometric Dates from Alaska-A 1975 Compilation”. The reader is referred to Special Report 10 for more complete information on location, rock type, dating method, and literature references for each age entry. A listing of dates in Special Report lo which require correction or deletion is included S table 2. Corrected and additional entries are listed in table 3. The listings in tables 2 and 3 follow the format of Special Report 10. Table 4 is a glossary of abbreviations used for quadrangle name, rock type, mineral dated, and type of dating method used.

Annotated Bibliography for Preadolescents from Divorced Families and Their Parents and Teachers.

ERIC Educational Resources Information Center

Woodman, Larry

Addressing the effects of rapidly escalating divorce rates on children, this 86-item annotated bibliography looks at using bibliotherapy individually, in designated groups, or for whole classes as a means of providing support and growth for preadolescents. Topics and specific problems addressed by the entries in the annotated bibliography include:…

The Design Process of Physical Security as Applied to a U.S. Border Port of Entry

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

Wagner, G.G.

1999-02-22

This paper details the application of a standard physical security system design process to a US Border Port of Entry (PoE) for vehicle entry/exit. The physical security design methodology is described as well as the physical security similarities to facilities currently at a US Border PoE for vehicles. The physical security design process description includes the various elements that make up the methodologies well as the considerations that must be taken into account when dealing with system integration of those elements. The distinctions between preventing unlawful entry/exit of illegal contraband and personnel are described. The potential to enhance the functionsmore » of drug/contraband detection in the Pre-Primary Inspection area through the application of emerging technologies are also addressed.« less

Managed Entry Agreements for Pharmaceuticals in the Context of Adaptive Pathways in Europe

PubMed Central

Bouvy, Jacoline C.; Sapede, Claudine; Garner, Sarah

2018-01-01

As per the EMA definition, adaptive pathways is a scientific concept for the development of medicines which seeks to facilitate patient access to promising medicines addressing high unmet need through a prospectively planned approach in a sustainable way. This review reports the findings of activities undertaken by the ADAPT-SMART consortium to identify enablers and explore the suitability of managed entry agreements for adaptive pathways products in Europe. We found that during 2006–2016 outcomes-based managed entry agreements were not commonly used for products with a conditional marketing authorization or authorized under exceptional circumstances. The barriers and enablers to develop workable managed entry agreements models for adaptive pathways products were discussed through interviews and a multi-stakeholder workshop with a number of recommendations made in this paper. PMID:29636692

Medical student satisfaction, coping and burnout in direct-entry versus graduate-entry programmes.

PubMed

DeWitt, Dawn; Canny, Benedict J; Nitzberg, Michael; Choudri, Jennifer; Porter, Sarah

2016-06-01

There is ongoing debate regarding the optimal length of medical training, with concern about the cost of prolonged training. Two simultaneous tracks currently exist in Australia: direct entry from high school and graduate entry for students with a bachelor degree. Medical schools are switching to graduate entry based on maturity, academic preparedness and career-choice surety. We tested the assumption that graduate entry is better by exploring student preferences, coping, burnout, empathy and alcohol use. From a potential pool of 2188 participants, enrolled at five Australian medical schools, a convenience sample of 688 (31%) first and second year students completed a survey in the middle of the academic year. Participants answered questions about demographics, satisfaction and coping and completed three validated instruments. Over 90% of students preferred their own entry-type, though more graduate-entry students were satisfied with their programme (82.4% versus 65.3%, p < 0.001). There was no difference between graduate-entry and direct-entry students in self-reported coping or in the proportion of students meeting criteria for burnout (50.7% versus 51.2%). Direct-entry students rated significantly higher for empathy (concern, p = 0.022; personal distress, p = 0.031). Graduate-entry students reported significantly more alcohol use and hazardous drinking (30.0% versus 22.8%; p = 0.017). Our multi-institution data confirm that students are generally satisfied with their choice of entry pathway and do not confirm significant psychosocial benefits of graduate entry. Overall, our data suggest that direct-entry students cope with the workload and psychosocial challenges of medical school, in the first 2 years, as well as graduate-entry students. Burnout and alcohol use should be addressed in both pathways. Despite studies showing similar academic outcomes, and higher total costs, more programmes in Australia are becoming graduate entry. Further research on non-cognitive issues and outcomes is needed so that universities, government funders and the medical profession can decide whether graduate entry, direct entry, or a mix, is ideal. © 2016 John Wiley & Sons Ltd.

Potent D-peptide inhibitors of HIV-1 entry

PubMed Central

Welch, Brett D.; VanDemark, Andrew P.; Heroux, Annie; Hill, Christopher P.; Kay, Michael S.

2007-01-01

During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC50 = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS. PMID:17942675

Mesh-Based Entry Vehicle and Explosive Debris Re-Contact Probability Modeling

NASA Technical Reports Server (NTRS)

McPherson, Mark A.; Mendeck, Gavin F.

2011-01-01

The risk to a crewed vehicle arising from potential re-contact with fragments from an explosive breakup of any jettisoned spacecraft segments during entry has long sought to be quantified. However, great difficulty lies in efficiently capturing the potential locations of each fragment and their collective threat to the vehicle. The method presented in this paper addresses this problem by using a stochastic approach that discretizes simulated debris pieces into volumetric cells, and then assesses strike probabilities accordingly. Combining spatial debris density and relative velocity between the debris and the entry vehicle, the strike probability can be calculated from the integral of the debris flux inside each cell over time. Using this technique it is possible to assess the risk to an entry vehicle along an entire trajectory as it separates from the jettisoned segment. By decoupling the fragment trajectories from that of the entry vehicle, multiple potential separation maneuvers can then be evaluated rapidly to provide an assessment of the best strategy to mitigate the re-contact risk.

Alirocumab, a Therapeutic Human Antibody to PCSK9, Does Not Affect CD81 Levels or Hepatitis C Virus Entry and Replication into Hepatocytes.

PubMed

Ramanathan, Aarti; Gusarova, Viktoria; Stahl, Neil; Gurnett-Bander, Anne; Kyratsous, Christos A

2016-01-01

Proprotein convertase subtilisin/kexin type 9 (PSCK9) is secreted mainly from the liver and binds to the low-density lipoprotein receptor (LDLR), reducing LDLR availability and thus resulting in an increase in LDL-cholesterol. While the LDLR has been implicated in the cell entry process of the hepatitis C virus (HCV), overexpression of an artificial non-secreted, cell membrane-bound form of PCSK9 has also been shown to reduce surface expression of CD81, a major component of the HCV entry complex, leading to concerns that pharmacological inhibition of PCSK9 may increase susceptibility to HCV infection by increasing either CD81 or LDLR availability. Here, we evaluated effects of PCSK9 and PCSK9 blockade on CD81 levels and HCV entry with a physiologically relevant model using native secreted PCSK9 and a monoclonal antibody to PCSK9, alirocumab. Flow cytometry and Western blotting of human hepatocyte Huh-7 cells showed that, although LDLR levels were reduced when cells were exposed to increasing PCSK9 concentrations, there was no correlation between total or surface CD81 levels and the presence and amount of soluble PCSK9. Moreover, inhibiting PCSK9 with the monoclonal antibody alirocumab did not affect expression levels of CD81. In an in vitro model of HCV entry, addition of soluble PCSK9 or treatment with alirocumab had no effect on the ability of either lentiviral particles bearing the HCV glycoproteins or JFH-1 based cell culture virus to enter hepatocytes. Consistent with these in vitro findings, no differences were observed in hepatic CD81 levels using in vivo mouse models, including Pcsk9-/- mice compared with wild-type controls and hyperlipidemic mice homozygous for human Pcsk9 and heterozygous for Ldlr deletion, treated with either alirocumab or isotype control antibody. These results suggest that inhibition of PCSK9 with alirocumab has no effect on CD81 and does not result in increased susceptibility to HCV entry.

The intermingled history of occupational therapy and anatomical education: A retrospective exploration.

PubMed

Carroll, Melissa A; Lawson, Katherine

2014-01-01

Few research articles have addressed the anatomical needs of entry-level occupational therapy students. Given this paucity of empirical evidence, there is a lack of knowledge regarding anatomical education in occupational therapy. This article will primarily serve as a retrospective look at the inclusion of anatomical education in the occupational therapy curriculum. Focusing on the historical inclusion is the first step to address the gap in existing knowledge. Examining the history of anatomy in occupational therapy provides an educational context for curricular developments and helps current anatomical educators understand the evolution of occupational therapy as a profession. Exploring the educational history also offers anatomy educators an identity, as significant contributors, in the training and preparedness of entry-level professionals while focusing on the ideals of occupational therapy. However, there is a critical need for empirical evidence of best teaching practices in occupational therapy and anatomical education. This manuscript provides a foundation and a starting point for further investigation into the anatomical competencies for entry-level occupational therapists. © 2014 American Association of Anatomists.

Evaluation of manhole inserts as structural barriers to mosquito entry into belowground stormwater systems using a simulated treatment device.

PubMed

Harbison, Justin E; Metzger, Marco E; Allen, Vaikko; Hu, Renjie

2009-09-01

Belowground proprietary stormwater treatment devices can produce mosquitoes, including vectors of West Nile virus. Elimination of vertical entry points such as pick holes in manhole covers may reduce the number of mosquitoes entering and reproducing in these structures. Plastic manhole dish inserts were evaluated as structural barriers against mosquito entry through pick holes in a simulated stormwater treatment device. Inserts were 100% effective at preventing mosquito entry through covers when no other openings existed. In devices configured with an open lateral conveyance pipe, the addition of an insert under the cover reduced mosquito oviposition significantly. Subsequent trials to further elucidate mosquito entry through manhole covers found a significant positive correlation between increasing number of pick holes and mosquito oviposition. Results of the study suggest the potential for manhole dish inserts to decrease the number of mosquitoes entering belowground structures. The different available stormwater treatment systems and site-specific installations may, however, provide a much greater variety of possible alternate entry points for mosquitoes than was addressed in the current study. Further work is needed in field installations to quantify the significance of pick holes to mosquito entry and determine under what conditions, if any, manhole dish inserts would be most effective and appropriate.

School as the Entry Point: Assessing Adherence to the Basic Tenets of the Wraparound Approach

ERIC Educational Resources Information Center

Epstein, Michael H.; Nordness, Philip D.; Gallagher, Ken; Nelson, J. Ron; Lewis, Linda; Schrepf, Sheryl

2005-01-01

In an effort to address the problem behaviors of children and youth, professionals have advocated for the implementation of three-tiered prevention programs: primary, secondary, and tertiary. The wraparound approach has been advanced as an appropriate tertiary program that can be used to address the complex behaviors and needs of students and…

Characterization of hemizygous deletions in Citrus using array-Comparative Genomic Hybridization and microsynteny comparisons with the poplar genome

PubMed Central

Ríos, Gabino; Naranjo, Miguel A; Iglesias, Domingo J; Ruiz-Rivero, Omar; Geraud, Marion; Usach, Antonio; Talón, Manuel

2008-01-01

Background Many fruit-tree species, including relevant Citrus spp varieties exhibit a reproductive biology that impairs breeding and strongly constrains genetic improvements. In citrus, juvenility increases the generation time while sexual sterility, inbreeding depression and self-incompatibility prevent the production of homozygous cultivars. Genomic technology may provide citrus researchers with a new set of tools to address these various restrictions. In this work, we report a valuable genomics-based protocol for the structural analysis of deletion mutations on an heterozygous background. Results Two independent fast neutron mutants of self-incompatible clementine (Citrus clementina Hort. Ex Tan. cv. Clemenules) were the subject of the study. Both mutants, named 39B3 and 39E7, were expected to carry DNA deletions in hemizygous dosage. Array-based Comparative Genomic Hybridization (array-CGH) using a Citrus cDNA microarray allowed the identification of underrepresented genes in these two mutants. Subsequent comparison of citrus deleted genes with annotated plant genomes, especially poplar, made possible to predict the presence of a large deletion in 39B3 of about 700 kb and at least two deletions of approximately 100 and 500 kb in 39E7. The deletion in 39B3 was further characterized by PCR on available Citrus BACs, which helped us to build a partial physical map of the deletion. Among the deleted genes, ClpC-like gene coding for a putative subunit of a multifunctional chloroplastic protease involved in the regulation of chlorophyll b synthesis was directly related to the mutated phenotype since the mutant showed a reduced chlorophyll a/b ratio in green tissues. Conclusion In this work, we report the use of array-CGH for the successful identification of genes included in a hemizygous deletion induced by fast neutron irradiation on Citrus clementina. The study of gene content and order into the 39B3 deletion also led to the unexpected conclusion that microsynteny and local gene colinearity in this species were higher with Populus trichocarpa than with the phylogenetically closer Arabidopsis thaliana. This work corroborates the potential of Citrus genomic resources to assist mutagenesis-based approaches for functional genetics, structural studies and comparative genomics, and hence to facilitate citrus variety improvement. PMID:18691431

Command generator tracker based direct model reference adaptive tracking guidance for Mars atmospheric entry

NASA Astrophysics Data System (ADS)

Li, Shuang; Peng, Yuming

2012-01-01

In order to accurately deliver an entry vehicle through the Martian atmosphere to the prescribed parachute deployment point, active Mars entry guidance is essential. This paper addresses the issue of Mars atmospheric entry guidance using the command generator tracker (CGT) based direct model reference adaptive control to reduce the adverse effect of the bounded uncertainties on atmospheric density and aerodynamic coefficients. Firstly, the nominal drag acceleration profile meeting a variety of constraints is planned off-line in the longitudinal plane as the reference model to track. Then, the CGT based direct model reference adaptive controller and the feed-forward compensator are designed to robustly track the aforementioned reference drag acceleration profile and to effectively reduce the downrange error. Afterwards, the heading alignment logic is adopted in the lateral plane to reduce the crossrange error. Finally, the validity of the guidance algorithm proposed in this paper is confirmed by Monte Carlo simulation analysis.

Therapist adherence to a motivational-interviewing intervention improves treatment entry for substance-misusing adolescents with low problem perception.

PubMed

Smith, Douglas C; Hall, James A; Jang, Mijin; Arndt, Stephan

2009-01-01

This study evaluated whether adherence to the Strengths-Oriented Referral for Teens (SORT) model, a motivational interviewing (MI)-consistent intervention addressing ambivalence about attending treatment, positively predicted adolescents' initial-session attendance. Therapist adherence was rated in 54 audiotaped SORT sessions by coders who were blind to treatment-entry status. Higher adherence scores reflected greater use of MI and solution focused language, discussion of client strengths, and dialogue with families on treatment need and options. Therapist adherence during adolescent segments interacted with adolescent problem perception. Predicted probabilities of attending initial sessions increased for low-problem-perception adolescents at increasingly higher therapist adherence. Although replication studies are needed, the SORT model of providing MI-consistent debriefing following initial assessments appears to be a promising approach for increasing treatment entry. Initial support for the treatment-matching hypothesis was found for substance-misusing adolescents contemplating treatment entry.

Shuttle Performance: Lessons Learned, Part 2

NASA Technical Reports Server (NTRS)

Arrington, J. P. (Compiler); Jones, J. J. (Compiler)

1983-01-01

Several areas of Space Shuttle technology were addressed including aerothermal environment, thermal protection, measurement and analysis, Shuttle carrier aerodynamics, entry analysis of the STS-3, and an overview of each section.

Uterine Deletion of Gp130 or Stat3 Shows Implantation Failure with Increased Estrogenic Responses

PubMed Central

Sun, Xiaofei; Bartos, Amanda; Whitsett, Jeffrey A.

2013-01-01

Leukemia inhibitory factor (LIF), a downstream target of estrogen, is essential for implantation in mice. LIF function is thought to be mediated by its binding to LIF receptor (LIFR) and recruitment of coreceptor GP130 (glycoprotein 130), and this receptor complex then activates signal transducer and activator of transcription (STAT)1/3. However, the importance of LIFR and GP130 acting via STAT3 in implantation remains uncertain, because constitutive inactivation of Lifr, Gp130, or Stat3 shows embryonic lethality in mice. To address this issue, we generated mice with conditional deletion of uterine Gp130 or Stat3 and show that both GP130 and STAT3 are critical for uterine receptivity and implantation. Implantation failure in these deleted mice is associated with higher uterine estrogenic responses prior to the time of implantation. These heightened estrogenic responses are not due to changes in ovarian hormone levels or expression of their nuclear receptors. In the deleted mice, estrogen-responsive gene, Lactoferrin (Ltf), and Mucin 1 protein, were up-regulated in the uterus. In addition, progesterone-responsive genes, Hoxa10 and Indian hedgehog (Ihh), were markedly down-regulated in STAT3-inactivated uteri. These changes in uteri of deleted mice were reflected by the failure of differentiation of the luminal epithelium, which is essential for blastocyst attachment. PMID:23885093

A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans.

PubMed

Khanna, Amit; Kumar, Jitendra; Vargas, Misha A; Barrett, LaKisha; Katewa, Subhash; Li, Patrick; McCloskey, Tom; Sharma, Amit; Naudé, Nicole; Nelson, Christopher; Brem, Rachel; Killilea, David W; Mooney, Sean D; Gill, Matthew; Kapahi, Pankaj

2016-12-13

Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C. elegans, remain poorly characterized. To systematically identify bacterial components that influence dauer formation and aging in C. elegans, we utilized the individual gene deletion mutants in E. coli (K12). We identified 56 diverse E. coli deletion mutants that enhance dauer formation in an insulin-like receptor mutant (daf-2) background. We describe the mechanism of action of a bacterial mutant cyaA, that is defective in the production of cyclic AMP, which extends lifespan and enhances dauer formation through the modulation of TGF-β (daf-7) signaling in C. elegans. Our results demonstrate the importance of bacterial components in influencing developmental decisions and lifespan in C. elegans. Furthermore, we demonstrate that C. elegans is a useful model to study bacterial-host interactions.

Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

PubMed

Qian, Chen; Wong, Carol Wing Yan; Wu, Zhongluan; He, Qiuming; Xia, Huimin; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen; Lui, Vincent Chi Hang

2017-01-01

Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures. To address the temporal requirement of Pdgfra in embryonic development. We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies. Current study showed that (i) conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5) resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii) the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives. Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a) the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b) if mutations / sequence variations of these regulatory elements cause these anomalies.

Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis

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

Corridoni, D.; Rodriguez-Palacios, A.; Di Stefano, G.

Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn’s disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well asmore » acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation.« less

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer

PubMed Central

Allen, John C.; Kim, Go Woon; Lee, Jae Cheol; Yatabe, Yasushi; Soda, Manabu; Mano, Hiroyuki; Soo, Ross A.; Chin, Tan-Min; Ebi, Hiromichi; Yano, Seiji; Matsuo, Keitaro; Niu, Xiaomin; Lu, Shun; Isobe, Kazutoshi; Lee, Jih-Hsiang; Yang, James C.; Zhao, Mingchuan; Zhou, Caicun; Lee, June-Koo; Lee, Se-Hoon; Lee, Ji Yun; Ahn, Myung-Ju; Tan, Tira J.; Tan, Daniel S.; Tan, Eng-Huat; Ong, S. Tiong; Lim, Wan-Teck

2017-01-01

Background A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. Results In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06–2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251–2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603–4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063–1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. Materials and Methods 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. Conclusions In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised. PMID:28467813

A Loss-of-Function Mutation in the PAS Kinase Rim15p Is Related to Defective Quiescence Entry and High Fermentation Rates of Saccharomyces cerevisiae Sake Yeast Strains

PubMed Central

Watanabe, Daisuke; Araki, Yuya; Zhou, Yan; Maeya, Naoki; Akao, Takeshi

2012-01-01

Sake yeast cells have defective entry into the quiescent state, allowing them to sustain high fermentation rates. To reveal the underlying mechanism, we investigated the PAS kinase Rim15p, which orchestrates initiation of the quiescence program in Saccharomyces cerevisiae. We found that Rim15p is truncated at the carboxyl terminus in modern sake yeast strains as a result of a frameshift mutation. Introduction of this mutation or deletion of the full-length RIM15 gene in a laboratory strain led to a defective stress response, decreased synthesis of the storage carbohydrates trehalose and glycogen, and impaired G1 arrest, which together closely resemble the characteristic phenotypes of sake yeast. Notably, expression of a functional RIM15 gene in a modern sake strain suppressed all of these phenotypes, demonstrating that dysfunction of Rim15p prevents sake yeast cells from entering quiescence. Moreover, loss of Rim15p or its downstream targets Igo1p and Igo2p remarkably improved the fermentation rate in a laboratory strain. This finding verified that Rim15p-mediated entry into quiescence plays pivotal roles in the inhibition of ethanol fermentation. Taken together, our results suggest that the loss-of-function mutation in the RIM15 gene may be the key genetic determinant of the increased ethanol production rates in modern sake yeast strains. PMID:22447585

A loss-of-function mutation in the PAS kinase Rim15p is related to defective quiescence entry and high fermentation rates of Saccharomyces cerevisiae sake yeast strains.

PubMed

Watanabe, Daisuke; Araki, Yuya; Zhou, Yan; Maeya, Naoki; Akao, Takeshi; Shimoi, Hitoshi

2012-06-01

Sake yeast cells have defective entry into the quiescent state, allowing them to sustain high fermentation rates. To reveal the underlying mechanism, we investigated the PAS kinase Rim15p, which orchestrates initiation of the quiescence program in Saccharomyces cerevisiae. We found that Rim15p is truncated at the carboxyl terminus in modern sake yeast strains as a result of a frameshift mutation. Introduction of this mutation or deletion of the full-length RIM15 gene in a laboratory strain led to a defective stress response, decreased synthesis of the storage carbohydrates trehalose and glycogen, and impaired G(1) arrest, which together closely resemble the characteristic phenotypes of sake yeast. Notably, expression of a functional RIM15 gene in a modern sake strain suppressed all of these phenotypes, demonstrating that dysfunction of Rim15p prevents sake yeast cells from entering quiescence. Moreover, loss of Rim15p or its downstream targets Igo1p and Igo2p remarkably improved the fermentation rate in a laboratory strain. This finding verified that Rim15p-mediated entry into quiescence plays pivotal roles in the inhibition of ethanol fermentation. Taken together, our results suggest that the loss-of-function mutation in the RIM15 gene may be the key genetic determinant of the increased ethanol production rates in modern sake yeast strains.

9 CFR 93.905 - Declaration and other documents for live fish, fertilized eggs, and gametes.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Animal Species General Provisions for Svc-Regulated Fish Species § 93.905 Declaration and other documents... entry, the name and address of the importer, the name and address of the broker, the origin of the live fish, fertilized eggs, or gametes, the number, species, and the purpose of the importation, the name of...

9 CFR 93.905 - Declaration and other documents for live fish, fertilized eggs, and gametes.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Animal Species General Provisions for Svc-Regulated Fish Species § 93.905 Declaration and other documents... entry, the name and address of the importer, the name and address of the broker, the origin of the live fish, fertilized eggs, or gametes, the number, species, and the purpose of the importation, the name of...

9 CFR 93.905 - Declaration and other documents for live fish, fertilized eggs, and gametes.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Animal Species General Provisions for Svc-Regulated Fish Species § 93.905 Declaration and other documents... entry, the name and address of the importer, the name and address of the broker, the origin of the live fish, fertilized eggs, or gametes, the number, species, and the purpose of the importation, the name of...

Library Resources for the Blind and Physically Handicapped: A Directory with FY 1998 Statistics on Readership, Circulation, Budget, Staff, and Collections.

ERIC Educational Resources Information Center

Library of Congress, Washington, DC. National Library Service for the Blind and Physically Handicapped.

This directory lists National Library Service for the Blind and Physically Handicapped libraries and machine-lending agencies alphabetically by state. Each entry includes address, phone and fax numbers, e-mail address, World Wide Web site, area served, librarian name, hours, book collection, special collections, assistive devices, special…

19 CFR 111.30 - Notification of change of business address, organization, name, or location of business records...

Code of Federal Regulations, 2014 CFR

2014-04-01

... Notification of change of business address, organization, name, or location of business records; status report... part of the organization, or entry into bankruptcy protection). (c) Change in name. A broker who changes his name, or who proposes to operate under a trade or fictitious name in one or more States within...

19 CFR 111.30 - Notification of change of business address, organization, name, or location of business records...

Code of Federal Regulations, 2013 CFR

2013-04-01

... Notification of change of business address, organization, name, or location of business records; status report... part of the organization, or entry into bankruptcy protection). (c) Change in name. A broker who changes his name, or who proposes to operate under a trade or fictitious name in one or more States within...

19 CFR 111.30 - Notification of change of business address, organization, name, or location of business records...

Code of Federal Regulations, 2011 CFR

2011-04-01

... Notification of change of business address, organization, name, or location of business records; status report... part of the organization, or entry into bankruptcy protection). (c) Change in name. A broker who changes his name, or who proposes to operate under a trade or fictitious name in one or more States within...

19 CFR 111.30 - Notification of change of business address, organization, name, or location of business records...

Code of Federal Regulations, 2012 CFR

2012-04-01

... Notification of change of business address, organization, name, or location of business records; status report... part of the organization, or entry into bankruptcy protection). (c) Change in name. A broker who changes his name, or who proposes to operate under a trade or fictitious name in one or more States within...

12 CFR 391.14 - Enforcement of orders.

Code of Federal Regulations, 2012 CFR

2012-01-01

... credit commitment, of the borrower's overall financial condition and resources, the financial... deleted; d. An explanation of how the customer may obtain a credit report free of charge; and e... to the FTC, and should provide the FTC's Web site address and toll-free telephone number that...

76 FR 70427 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... General Counsel, Manpower and Health Affairs) is deleting systems of records notice from its existing... which result in a contrary determination. ADDRESSES: You may submit comments, identified by docket... Position Applications by the Office of the Assistant General Counsel (Manpower and Health Affairs), it has...

75 FR 14142 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-24

... result in a contrary determination. ADDRESSES: You may submit comments, identified by docket number and... Archive/Management Information System, Defense Manpower Data Center, DoD Center, Monterey Bay, 400 Gigling..., Defense Manpower Data Center, 400 Gigling Road, Seaside, CA 93955-6771.'' Notification procedure: Delete...

76 FR 10009 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-23

... received which result in a contrary determination. ADDRESSES: You may submit comments, identified by docket... Joint Manpower Automation System Files, (February 22, 1993, 58 FR 10557). Reason: The Joint Staff... responsible for maintaining data on training completion. Deletion: JS003SMB Manpower, Personnel and Security...

Radio/FADS/IMU integrated navigation for Mars entry

NASA Astrophysics Data System (ADS)

Jiang, Xiuqiang; Li, Shuang; Huang, Xiangyu

2018-03-01

Supposing future orbiting and landing collaborative exploration mission as the potential project background, this paper addresses the issue of Mars entry integrated navigation using radio beacon, flush air data sensing system (FADS), and inertial measurement unit (IMU). The range and Doppler information sensed from an orbiting radio beacon, the dynamic pressure and heating data sensed from flush air data sensing system, and acceleration and attitude angular rate outputs from an inertial measurement unit are integrated in an unscented Kalman filter to perform state estimation and suppress the system and measurement noise. Computer simulations show that the proposed integrated navigation scheme can enhance the navigation accuracy, which enables precise entry guidance for the given Mars orbiting and landing collaborative exploration mission.

Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors.

PubMed

Riddick, Nadeene E; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M; Plishka, Ronald J; Buckler-White, Alicia; Brenchley, Jason M; Hirsch, Vanessa M

2015-12-09

African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4(+) T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4(+) T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4(+) T cells, the preferred target cells of SIV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors

PubMed Central

Riddick, Nadeene E.; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M.; Plishka, Ronald J.; Buckler-White, Alicia; Brenchley, Jason M.

2015-01-01

ABSTRACT African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4+ T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4+ T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. IMPORTANCE African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4+ T cells, the preferred target cells of SIV. PMID:26656714

8 CFR 235.12 - Global Entry program.

Code of Federal Regulations, 2013 CFR

2013-01-01

... from the applicant (e.g., a set of ten fingerprints and/or digital photograph) to conduct background... letter should address any facts or conduct listed in the notification from CBP as contributing to the...

8 CFR 235.12 - Global Entry program.

Code of Federal Regulations, 2014 CFR

2014-01-01

... from the applicant (e.g., a set of ten fingerprints and/or digital photograph) to conduct background... letter should address any facts or conduct listed in the notification from CBP as contributing to the...

Stakeholder identification of advanced technology opportunities at international ports of entry

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

Parker, S.K.; Icerman, L.

As part of the Advanced Technologies for International and Intermodal Ports of Entry (ATIPE) Project, a diverse group of stakeholders was engaged to help identify problems experienced at inland international border crossings, particularly those at the US-Mexican border. The fundamental issue at international ports of entry is reducing transit time through the required documentation and inspection processes. Examples of other issues or problems, typically manifested as time delays at border crossings, repeatedly mentioned by stakeholders include: (1) lack of document standardization; (2) failure to standardize inspection processes; (3) inadequate information and communications systems; (4) manual fee and tariff collection; (5)more » inconsistency of processes and procedures; and (6) suboptimal cooperation among governmental agencies. Most of these issues can be addressed to some extent by the development of advanced technologies with the objective of allowing ports of entry to become more efficient while being more effective. Three categories of technologies were unambiguously of high priority to port of entry stakeholders: (1) automated documentation; (2) systems integration; and (3) vehicle and cargo tracking. Together, these technologies represent many of the technical components necessary for pre-clearance of freight approaching international ports of entry. Integration of vehicle and cargo tracking systems with port of entry information and communications systems, as well as existing industry legacy systems, should further enable border crossings to be accomplished consistently with optimal processing times.« less

75 FR 34405 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... future actions under Superfund. This partial deletion pertains to the surface media (soil, surface water... in contamination of structures, soil, surface water, and groundwater. As a result of this... Superfund Site located upgradient (south) of RMA (1990). OU 03: On-Post--Addresses soil and groundwater...

76 FR 13994 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... received which result in a contrary determination. ADDRESSES: You may submit comments, identified by dock... of Defense. Deletion: K700.03 Manpower and Personnel System (MAPS) (February 22, 1993, 58 FR 10562). Reason: Manpower and Personnel System (MAPS) has been replaced with Open Source Corporate Management...

MicroRNA-21 accelerates hepatocyte proliferation in vitro via PI3K/Akt signaling by targeting PTEN

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

Yan-nan, Bai; Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou 350001, Fujian Province; Zhao-yan, Yu

2014-01-17

Highlights: •miRNAs-expression patterns of primary hepatocytes under proliferative status. •miR-21 expression level peaked at 12 h after stimulated by EGF. •miR-21 drive rapid S phase entry of primary hepatocytes. •PI3K/Akt signaling was modulated via targeting PTEN by miR-21. -- Abstract: MicroRNAs (miRNAs) are involved in controlling hepatocyte proliferation during liver regeneration. In this study, we established the miRNAs-expression patterns of primary hepatocytes in vitro under stimulation of epidermal growth factor (EGF), and found that microRNA-21 (miR-21) was appreciably up-regulated and peaked at 12 h. In addition, we further presented evidences indicating that miR-21 promotes primary hepatocyte proliferation through in vitromore » transfecting with miR-21 mimics or inhibitor. We further demonstrated that phosphatidylinositol 3′-OH kinase (PI3K)/Akt signaling was altered accordingly, it is, by targeting phosphatase and tensin homologue deleted on chromosome 10, PI3K/Akt signaling is activated by miR-21 to accelerate hepatocyte rapid S-phase entry and proliferation in vitro.« less

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

PubMed Central

Delio, Maria; Guo, Tingwei; McDonald-McGinn, Donna M.; Zackai, Elaine; Herman, Sean; Kaminetzky, Mark; Higgins, Anne Marie; Coleman, Karlene; Chow, Carolyn; Jarlbrzkowski, Maria; Bearden, Carrie E.; Bailey, Alice; Vangkilde, Anders; Olsen, Line; Olesen, Charlotte; Skovby, Flemming; Werge, Thomas M.; Templin, Ludivine; Busa, Tiffany; Philip, Nicole; Swillen, Ann; Vermeesch, Joris R.; Devriendt, Koen; Schneider, Maude; Dahoun, Sophie; Eliez, Stephan; Schoch, Kelly; Hooper, Stephen R.; Shashi, Vandana; Samanich, Joy; Marion, Robert; van Amelsvoort, Therese; Boot, Erik; Klaassen, Petra; Duijff, Sasja N.; Vorstman, Jacob; Yuen, Tracy; Silversides, Candice; Chow, Eva; Bassett, Anne; Frisch, Amos; Weizman, Abraham; Gothelf, Doron; Niarchou, Maria; van den Bree, Marianne; Owen, Michael J.; Suñer, Damian Heine; Andreo, Jordi Rosell; Armando, Marco; Vicari, Stefano; Digilio, Maria Cristina; Auton, Adam; Kates, Wendy R.; Wang, Tao; Shprintzen, Robert J.; Emanuel, Beverly S.; Morrow, Bernice E.

2013-01-01

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6–1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin. PMID:23453669

Differences in behavioural phenotype between parental deletion and maternal uniparental disomy in Prader-Willi syndrome: an ERP study.

PubMed

Stauder, Johannes E A; Boer, Harm; Gerits, Rolf H A; Tummers, Anke; Whittington, Joyce; Curfs, Leopold M G

2005-06-01

Paternal deletion and maternal uniparental disomy are the principal genetic subtypes associated with Prader-Willi syndrome (PWS). Recent clinical findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho-physiological setup. Behaviour and event-related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT-AX) in adults with paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal controls (n=11). The dependent behavioural variables of the CPT-AX task were reaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality-specific inhibition and late general inhibition, respectively. The disomy group had fewer correct scores and increased reaction times as compared to the CPT-AX task than the control and deletion group. Both PWS subgroups differed significantly from the control group for the N200 amplitude. Only the control group showed the typical task modulation for the N200 amplitude. The amplitude of the P300 component was considerably smaller in the uniparental disomy group than in the deletion and control groups. The ERP results suggest that early modality specific inhibition is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a common impairment in early visual inhibition processing, uniparental disomy and parental deletion genetic PWS subtypes clearly differ in their behavioural and brain activation phenotypes. The present study is the first experimental demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11-q13g in PWS result in different behavioural phenotype.

Multi‐layered inhibition of Streptomyces development: BldO is a dedicated repressor of whiB

PubMed Central

Chandra, Govind; Findlay, Kim C.; Buttner, Mark J.

2017-01-01

Summary BldD‐(c‐di‐GMP) sits on top of the regulatory network that controls differentiation in Streptomyces, repressing a large regulon of developmental genes when the bacteria are growing vegetatively. In this way, BldD functions as an inhibitor that blocks the initiation of sporulation. Here, we report the identification and characterisation of BldO, an additional developmental repressor that acts to sustain vegetative growth and prevent entry into sporulation. However, unlike the pleiotropic regulator BldD, we show that BldO functions as the dedicated repressor of a single key target gene, whiB, and that deletion of bldO or constitutive expression of whiB is sufficient to induce precocious hypersporulation. PMID:28271577

Comparing the demands of destination entry using Google Glass and the Samsung Galaxy S4 during simulated driving.

PubMed

Beckers, Niek; Schreiner, Sam; Bertrand, Pierre; Mehler, Bruce; Reimer, Bryan

2017-01-01

The relative impact of using a Google Glass based voice interface to enter a destination address compared to voice and touch-entry methods using a handheld Samsung Galaxy S4 smartphone was assessed in a driving simulator. Voice entry (Google Glass and Samsung) had lower subjective workload ratings, lower standard deviation of lateral lane position, shorter task durations, faster remote Detection Response Task (DRT) reaction times, lower DRT miss rates, and resulted in less time glancing off-road than the primary visual-manual interaction with the Samsung Touch interface. Comparing voice entry methods, using Google Glass took less time, while glance metrics and reaction time to DRT events responded to were similar. In contrast, DRT miss rate was higher for Google Glass, suggesting that drivers may be under increased distraction levels but for a shorter period of time; whether one or the other equates to an overall safer driving experience is an open question. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sample Returns Missions in the Coming Decade

NASA Technical Reports Server (NTRS)

Desai, Prasun N.; Mitcheltree, Robert A.; Cheatwood, F. McNeil

2000-01-01

In the coming decade, several missions will attempt to return samples to Earth from varying parts of the solar system. These samples will provide invaluable insight into the conditions present during the early formation of the solar system, and possibly give clues to how life began on Earth. A description of five sample return missions is presented (Stardust, Genesis, Muses-C. Mars Sample Return, and Comet Nucleus Sample Return). An overview of each sample return mission is given, concentrating particularly on the technical challenges posed during the Earth entry, descent, and landing phase of the missions. Each mission faces unique challenges in the design of an Earth entry capsule. The design of the entry capsule must address the aerodynamic, heating, deceleration, landing, and recovery requirements for the safe return of samples to Earth.

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

PubMed

Sun, Daqiang; Ching, Christopher R K; Lin, Amy; Forsyth, Jennifer K; Kushan, Leila; Vajdi, Ariana; Jalbrzikowski, Maria; Hansen, Laura; Villalon-Reina, Julio E; Qu, Xiaoping; Jonas, Rachel K; van Amelsvoort, Therese; Bakker, Geor; Kates, Wendy R; Antshel, Kevin M; Fremont, Wanda; Campbell, Linda E; McCabe, Kathryn L; Daly, Eileen; Gudbrandsen, Maria; Murphy, Clodagh M; Murphy, Declan; Craig, Michael; Vorstman, Jacob; Fiksinski, Ania; Koops, Sanne; Ruparel, Kosha; Roalf, David R; Gur, Raquel E; Schmitt, J Eric; Simon, Tony J; Goodrich-Hunsaker, Naomi J; Durdle, Courtney A; Bassett, Anne S; Chow, Eva W C; Butcher, Nancy J; Vila-Rodriguez, Fidel; Doherty, Joanne; Cunningham, Adam; van den Bree, Marianne B M; Linden, David E J; Moss, Hayley; Owen, Michael J; Murphy, Kieran C; McDonald-McGinn, Donna M; Emanuel, Beverly; van Erp, Theo G M; Turner, Jessica A; Thompson, Paul M; Bearden, Carrie E

2018-06-13

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

High-speed rail turnout literature review : final report.

DOT National Transportation Integrated Search

2016-08-01

High-speed rail (HSR) turnout design criteria generally address unbalanced lateral acceleration or cant deficiency (CD), cant deficiency change rate (CDCR), and entry and exit jerk. Various countries have adopted different design values for their HSR...

LARGE BUILDING RADON MANUAL

EPA Science Inventory

The report summarizes information on how bilding systems -- especially the heating, ventilating, and air-conditioning (HVAC) system -- inclurence radon entry into large buildings and can be used to mitigate radon problems. It addresses the fundamentals of large building HVAC syst...

19 CFR 10.1 - Domestic products; requirements on entry.

Code of Federal Regulations, 2010 CFR

2010-04-01

... manufacture or other means. Marks Number Quantity Description Value, in U.S. coin (Date) (Signature) (Address... knowledge of the facts shall furnish a written declaration which may be made on the reverse side of Customs...

31 CFR 353.3 - Converting definitive savings bonds to book-entry bonds in New Treasury Direct.

Code of Federal Regulations, 2012 CFR

2012-07-01

... New Treasury Direct, an online system for holding Treasury securities. The Web address for New... bonds should follow online instructions for conversion. Regulations governing converted bonds are found...

31 CFR 353.3 - Converting definitive savings bonds to book-entry bonds in New Treasury Direct.

Code of Federal Regulations, 2010 CFR

2010-07-01

... New Treasury Direct, an online system for holding Treasury securities. The Web address for New... bonds should follow online instructions for conversion. Regulations governing converted bonds are found...

31 CFR 353.3 - Converting definitive savings bonds to book-entry bonds in New Treasury Direct.

Code of Federal Regulations, 2013 CFR

2013-07-01

... New Treasury Direct, an online system for holding Treasury securities. The Web address for New... bonds should follow online instructions for conversion. Regulations governing converted bonds are found...

The Creative Web.

ERIC Educational Resources Information Center

Yudess, Jo

2003-01-01

This article lists the Web sites of 12 international not-for-profit creativity associations designed to trigger more creative thought and research possibilities. Along with Web addresses, the entries include telephone contact information and a brief description of the organization. (CR)

New developments in Smith-Magenis syndrome (del 17p11.2).

PubMed

Gropman, Andrea L; Elsea, Sarah; Duncan, Wallace C; Smith, Ann C M

2007-04-01

Recent clinical, neuroimaging, sleep, and molecular cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review. Cross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith-Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype. Findings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder.

Horry-Georgetown Technical College Summary Report on Institutional Effectiveness.

ERIC Educational Resources Information Center

Wilson, H. Neyle

This document is the Horry-Georgetown Technical College comprehensive assessment of missions, goals, and objectives. The assessment addressed the mission statement of the college as well as its long-term goals. The mission statement was unchanged. In regards to long-term goals for the college, the college deleted one goal that had already been…

77 FR 52331 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

... on or before September 28, 2012. ADDRESSES: Submit your comments, identified by docket identification... action, identified by docket identification (ID) number EPA-HQ-OPP-2012-0548, is available either... Pyrethrins and Piperonyl Use on Pre-Harvest Tree Butoxide. Nuts, Cereal Grains and Pasture Grasses. 2724-761...

5 CFR 294.106 - Handbook of Publications, Periodicals, and OPM Issuances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... adjudication of cases; (ii) OPM policy statements and interpretations adopted by OPM but not published in the... delete identifying details when it makes available or publishes an opinion, statement of policy... found in OPM's Library in room 5H27 at the address listed in paragraph (b) of this section. (d) As...

45 CFR 5b.7 - Procedures for correction or amendment of records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... making a request to amend or correct his record shall address his request to the responsible Department... informed of the responsible Department official's decision on the request within that 10 day period. (c) If... individual will be informed in writing of the correction, amendment, or deletion and, if accounting was made...

78 FR 45064 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-26

... not take effect. ADDRESSES: Submit your comments, identified by Docket ID no. EPA-HQ- SFUND-1983-0002... the deletion will not take effect. EPA will, as appropriate, prepare a response to comments and... action. Section IV discusses the Cannon Engineering Corp. (CEC) Superfund Site and demonstrates how it...

76 FR 18066 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

...-site) 518 tons of contaminated soil. During the removal, water samples taken from the storm drain... demolition phase took place immediately prior to and in connection with the relocation of soil and sediment... informing the public that the deletion will not take effect. ADDRESSES: Submit your comments, identified by...

75 FR 82581 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-48; Small Entity Compliance Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-30

..., Payrolls and Basic Records to delete the requirement for submission of full social security numbers and... requires contractors and subcontractors to maintain the full social security number and current address of... Wage and Hour Division of the Department of Labor for purposes of an investigation or audit of...

75 FR 21061 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... exchange to a fully automated limit-order matching system. This filing would alter or eliminate references... Article 6, Rule 11 (Continuing Education for Registered Persons), we are deleting the rule text which was..., which addressed cancellation or modification of transactions due to systems malfunctions or disruptions...

PrOtocols for WatERmarking (POWER)

DTIC Science & Technology

2011-03-01

22. Page 57 of 94 Figure 22: Exemplary watermark structure incl. the structure of the embedded ToC The segmented watermarking approach for...somewhere within the cover. The addresses addressSLji belonging to the different access levels Li are stored in a table of contents ( ToC ) entry, along...then embedded into the ToC -segment Stoc. Several assumptions have to be made before describing the actual functions of the presented system

Inhibition of Sphingosine Kinase 1 Ameliorates Angiotensin II-Induced Hypertension and Inhibits Transmembrane Calcium Entry via Store-Operated Calcium Channel

PubMed Central

Wilson, Parker C.; Fitzgibbon, Wayne R.; Garrett, Sara M.; Jaffa, Ayad A.; Luttrell, Louis M.; Brands, Michael W.

2015-01-01

Angiotensin II (AngII) plays a critical role in the regulation of vascular tone and blood pressure mainly via regulation of Ca2+ mobilization. Several reports have implicated sphingosine kinase 1 (SK1)/sphingosine 1-phosphate (S1P) in the mobilization of intracellular Ca2+ through a yet-undefined mechanism. Here we demonstrate that AngII-induces biphasic calcium entry in vascular smooth muscle cells, consisting of an immediate peak due to inositol tris-phosphate-dependent release of intracellular calcium, followed by a sustained transmembrane Ca2+ influx through store-operated calcium channels (SOCs). Inhibition of SK1 attenuates the second phase of transmembrane Ca2+ influx, suggesting a role for SK1 in AngII-dependent activation of SOC. Intracellular S1P triggers SOC-dependent Ca2+ influx independent of S1P receptors, whereas external application of S1P stimulated S1P receptor-dependent Ca2+ influx that is insensitive to inhibitors of SOCs, suggesting that the SK1/S1P axis regulates store-operated calcium entry via intracellular rather than extracellular actions. Genetic deletion of SK1 significantly inhibits both the acute hypertensive response to AngII in anaesthetized SK1 knockout mice and the sustained hypertensive response to continuous infusion of AngII in conscious animals. Collectively these data implicate SK1 as the missing link that connects the angiotensin AT1A receptor to transmembrane Ca2+ influx and identify SOCs as a potential intracellular target for SK1. PMID:25871850

UL74 of Human Cytomegalovirus Contributes to Virus Release by Promoting Secondary Envelopment of Virions▿ †

PubMed Central

Jiang, Xiao Jing; Adler, Barbara; Sampaio, Kerstin Laib; Digel, Margarete; Jahn, Gerhard; Ettischer, Nicole; Stierhof, York-Dieter; Scrivano, Laura; Koszinowski, Ulrich; Mach, Michael; Sinzger, Christian

2008-01-01

The glycoprotein (g) complex gH/gL represents an essential part of the herpesvirus fusion machinery mediating entry of cell-free virions and cell-associated viral spread. In some herpesviruses additional proteins are associated with gH/gL contributing to the cell tropism of the respective virus. Human cytomegalovirus (HCMV) gH/gL forms complexes with either gO (UL74) or proteins of the UL128-131A gene locus. While a contribution of UL128-131A to endothelial cell tropism is known, the role of gO is less clear. We studied the role of gH/gL-associated proteins in HCMV replication in human foreskin fibroblasts (HFF) and human umbilical vein endothelial cells (HUVEC). Deletions of UL74 alone or in combination with mutations of the UL128-131A gene region were introduced into bacterial artificial chromosome vectors derived from the endotheliotropic strain TB40/E. Deletion of UL74 caused a profound defect regarding virus release from infected HFF and HUVEC. Large numbers of capsids accumulated in the cytoplasm of infected HFF but failed to acquire an envelope. Clear cell type differences were observed in the cell-associated spread of the UL74-defective virus. In HFF, focal growth was severely impaired, whereas it was normal in HUVEC. Deletion of UL131A abolished focal growth in endothelial cells. UL74/UL128-131A dual mutants showed severely impaired reconstitution efficiency. Our data suggest that gO plays a critical role in secondary envelopment and release of cell-free virions independent of the cell type but affects cell-associated growth specifically in HFF, whereas UL128-131A contributes to cell-associated spread in HFF and HUVEC. PMID:18184717

Crystal structure of full-length Mycobacterium tuberculosis H37Rv glycogen branching enzyme: insights of N-terminal beta-sandwich in substrate specificity and enzymatic activity.

PubMed

Pal, Kuntal; Kumar, Shiva; Sharma, Shikha; Garg, Saurabh Kumar; Alam, Mohammad Suhail; Xu, H Eric; Agrawal, Pushpa; Swaminathan, Kunchithapadam

2010-07-02

The open reading frame Rv1326c of Mycobacterium tuberculosis (Mtb) H37Rv encodes for an alpha-1,4-glucan branching enzyme (MtbGlgB, EC 2.4.1.18, Uniprot entry Q10625). This enzyme belongs to glycoside hydrolase (GH) family 13 and catalyzes the branching of a linear glucose chain during glycogenesis by cleaving a 1-->4 bond and making a new 1-->6 bond. Here, we show the crystal structure of full-length MtbGlgB (MtbGlgBWT) at 2.33-A resolution. MtbGlgBWT contains four domains: N1 beta-sandwich, N2 beta-sandwich, a central (beta/alpha)(8) domain that houses the catalytic site, and a C-terminal beta-sandwich. We have assayed the amylase activity with amylose and starch as substrates and the glycogen branching activity using amylose as a substrate for MtbGlgBWT and the N1 domain-deleted (the first 108 residues deleted) MtbDelta108GlgB protein. The N1 beta-sandwich, which is formed by the first 105 amino acids and superimposes well with the N2 beta-sandwich, is shown to have an influence in substrate binding in the amylase assay. Also, we have checked and shown that several GH13 family inhibitors are ineffective against MtbGlgBWT and MtbDelta108GlgB. We propose a two-step reaction mechanism, for the amylase activity (1-->4 bond breakage) and isomerization (1-->6 bond formation), which occurs in the same catalytic pocket. The structural and functional properties of MtbGlgB and MtbDelta108GlgB are compared with those of the N-terminal 112-amino acid-deleted Escherichia coli GlgB (ECDelta112GlgB).

Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors.

PubMed

Tantra, M; Guo, L; Kim, J; Zainolabidin, N; Eulenburg, V; Augustine, G J; Chen, A I

2018-02-15

Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebellar cortex. To assess the function of Cdh13 and utilize the manipulation of Cdh13 expression in Golgi cells as an entry point to examine cerebellar-mediated function, we generated mice carrying Cdh13-floxed alleles and conditionally deleted Cdh13 with GlyT2::Cre mice. Loss of Cdh13 results in a decrease in the expression/localization of GAD67 and reduces spontaneous inhibitory postsynaptic current (IPSC) in cerebellar Golgi cells without disrupting spontaneous excitatory postsynaptic current (EPSC). At the behavioral level, loss of Cdh13 in the cerebellum, piriform cortex and endopiriform claustrum have no impact on gross motor coordination or general locomotor behaviors, but leads to deficits in cognitive and social abilities. Mice lacking Cdh13 exhibit reduced cognitive flexibility and loss of preference for contact region concomitant with increased reciprocal social interactions. Together, our findings show that Cdh13 is critical for inhibitory function of Golgi cells, and that GlyT2::Cre-mediated deletion of Cdh13 in non-executive centers of the brain, such as the cerebellum, may contribute to cognitive and social behavioral deficits linked to neurological disorders. © 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

UNIX Software Directory.

ERIC Educational Resources Information Center

Darwin, Ian

1984-01-01

Presented is a comprehensive listing of over 300 UNIX operating system programs from over 100 different sources. Entries are arranged by such categories as accounting applications, database programs, industrial applications, and languages. A cross-references guide of UNIX vendor addresses accompanies the listing. (JN)

31 CFR 360.3 - Converting definitive savings bonds to book-entry bonds in New Treasury Direct.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Treasury Direct, an online system for holding Treasury securities. The Web address for New Treasury Direct... follow online instructions for conversion. Regulations governing converted bonds are found at 31 CFR part...

An Annotated Partial List of Science-Related Computer Bulletin Board Systems.

ERIC Educational Resources Information Center

Journal of Student Research, 1990

1990-01-01

A list of science-related computer bulletin board systems is presented. Entries include geographic area, phone number, and a short explanation of services. Also included are the addresses and phone numbers of selected commercial services. (KR)

Transit Bus Manufacturers' Profiles

DOT National Transportation Integrated Search

1982-03-01

This report is an analytic paper addressing the trend toward entry into the U.S. transit bus market by new foreign manufacturers. The purpose of this study is to provide an explanation, and outline the implications of why so many companies are intere...

Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms

PubMed Central

Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C.; Trump, Lisa; Salipante, Stephen J.; Cheng, Jerry C.; Donadieu, Jean; Glaubach, Taly; Corey, Seth J.; Grimes, H. Leighton; Lutzko, Carolyn; Cancelas, Jose A.

2014-01-01

Hereditary neutropenia is usually caused by heterozygous germline mutations in the ELANE gene encoding neutrophil elastase (NE). How mutations cause disease remains uncertain, but two hypotheses have been proposed. In one, ELANE mutations lead to mislocalization of NE. In the other, ELANE mutations disturb protein folding, inducing an unfolded protein response in the endoplasmic reticulum (ER). In this study, we describe new types of mutations that disrupt the translational start site. At first glance, they should block translation and are incompatible with either the mislocalization or misfolding hypotheses, which require mutant protein for pathogenicity. We find that start-site mutations, instead, force translation from downstream in-frame initiation codons, yielding amino-terminally truncated isoforms lacking ER-localizing (pre) and zymogen-maintaining (pro) sequences, yet retain essential catalytic residues. Patient-derived induced pluripotent stem cells recapitulate hematopoietic and molecular phenotypes. Expression of the amino-terminally deleted isoforms in vitro reduces myeloid cell clonogenic capacity. We define an internal ribosome entry site (IRES) within ELANE and demonstrate that adjacent mutations modulate IRES activity, independently of protein-coding sequence alterations. Some ELANE mutations, therefore, appear to cause neutropenia via the production of amino-terminally deleted NE isoforms rather than by altering the coding sequence of the full-length protein. PMID:24184683

Resistance of herpes simplex virus type 2 to neomycin maps to the N-terminal portion of glycoprotein C.

PubMed Central

Oyan, A M; Dolter, K E; Langeland, N; Goins, W F; Glorioso, J C; Haarr, L; Crumpacker, C S

1993-01-01

Entry of herpes simplex virus (HSV) into cells is believed to be mediated by specific binding of envelope proteins to a cellular receptor. Neomycin specifically blocks this initial step in infection by HSV-1 but not HSV-2. Resistance of HSV-2 to this compound maps to a region of the genome encoding glycoprotein C (gC-2). We have studied the function of gC-2 in the initial interaction of the virus with the host cell, using HSV-2 mutants deleted for gC-2 and gC-2-rescued recombinants. Resistance to neomycin was directly linked to the presence of gC-2 within the viral genome. In addition, deletion of the gC-2 gene caused a marked delay in adsorption to cells relative to the wild-type virus. HSV-1 recombinants containing chimeric gC genes composed of HSV-1 and HSV-2 sequences were used to localize neomycin resistance within the N-terminal 223 amino acids of gC-2. This region of the glycoprotein comprises an important domain responsible for binding of HSV-2 to cell receptors in the presence of neomycin. A gC-2-negative mutant is still infectious, indicating that HSV-2 also has an alternative pathway of adsorption. Images PMID:8386261

Safety concerns for first entry operations of orbiting spacecraft

NASA Technical Reports Server (NTRS)

Wilson, Steven H.; Limero, Thomas F.; James, John T.

1994-01-01

The Space Station Freedom crew will face operational problems unique to the spacecraft environment due to the absence of convection currents and the confined atmosphere within the habitable modules. Airborne contaminants from the materials offgassing or contingency incidents like thermodegradation may accumulate until they reach hazardous concentrations. Flow modeling and experiences from previous space flight missions confirm that caution must be exercised during first-entry operations. A review of the first-entry procedures performed during the Skylab Program will be presented to highlight the necessity for carefully planned operations. Many of the environmental conditions that can be expected on the Space Station are analogous to those which exist in confined storage or work spaces in the industrial setting. Experience with closed-loop environmental operations (e.g., atmospheric control of submarines) have also demonstrated that the buildup of trace contaminant gases could result in conditions that lead to mission termination or loss of crew. Consequently, some first-entry issues for the Station can be addressed by comparing them to familiar techniques developed on Earth. The instruments of the Environmental Health System (EHS) will provide the necessary monitoring capability to protect crew health and safety during the planned first-entry procedures of the MTC phase of the SSF Program. The authors of this paper will describe those procedures and will cite an example of the consequences when proper first-entry procedures are not followed.

Attitudes towards statistics of graduate entry medical students: the role of prior learning experiences

PubMed Central

2014-01-01

Background While statistics is increasingly taught as part of the medical curriculum, it can be an unpopular subject and feedback from students indicates that some find it more difficult than other subjects. Understanding attitudes towards statistics on entry to graduate entry medical programmes is particularly important, given that many students may have been exposed to quantitative courses in their previous degree and hence bring preconceptions of their ability and interest to their medical education programme. The aim of this study therefore is to explore, for the first time, attitudes towards statistics of graduate entry medical students from a variety of backgrounds and focus on understanding the role of prior learning experiences. Methods 121 first year graduate entry medical students completed the Survey of Attitudes toward Statistics instrument together with information on demographics and prior learning experiences. Results Students tended to appreciate the relevance of statistics in their professional life and be prepared to put effort into learning statistics. They had neutral to positive attitudes about their interest in statistics and their intellectual knowledge and skills when applied to it. Their feelings towards statistics were slightly less positive e.g. feelings of insecurity, stress, fear and frustration and they tended to view statistics as difficult. Even though 85% of students had taken a quantitative course in the past, only 24% of students described it as likely that they would take any course in statistics if the choice was theirs. How well students felt they had performed in mathematics in the past was a strong predictor of many of the components of attitudes. Conclusion The teaching of statistics to medical students should start with addressing the association between students’ past experiences in mathematics and their attitudes towards statistics and encouraging students to recognise the difference between the two disciplines. Addressing these issues may reduce students’ anxiety and perception of difficulty at the start of their learning experience and encourage students to engage with statistics in their future careers. PMID:24708762

Attitudes towards statistics of graduate entry medical students: the role of prior learning experiences.

PubMed

Hannigan, Ailish; Hegarty, Avril C; McGrath, Deirdre

2014-04-04

While statistics is increasingly taught as part of the medical curriculum, it can be an unpopular subject and feedback from students indicates that some find it more difficult than other subjects. Understanding attitudes towards statistics on entry to graduate entry medical programmes is particularly important, given that many students may have been exposed to quantitative courses in their previous degree and hence bring preconceptions of their ability and interest to their medical education programme. The aim of this study therefore is to explore, for the first time, attitudes towards statistics of graduate entry medical students from a variety of backgrounds and focus on understanding the role of prior learning experiences. 121 first year graduate entry medical students completed the Survey of Attitudes toward Statistics instrument together with information on demographics and prior learning experiences. Students tended to appreciate the relevance of statistics in their professional life and be prepared to put effort into learning statistics. They had neutral to positive attitudes about their interest in statistics and their intellectual knowledge and skills when applied to it. Their feelings towards statistics were slightly less positive e.g. feelings of insecurity, stress, fear and frustration and they tended to view statistics as difficult. Even though 85% of students had taken a quantitative course in the past, only 24% of students described it as likely that they would take any course in statistics if the choice was theirs. How well students felt they had performed in mathematics in the past was a strong predictor of many of the components of attitudes. The teaching of statistics to medical students should start with addressing the association between students' past experiences in mathematics and their attitudes towards statistics and encouraging students to recognise the difference between the two disciplines. Addressing these issues may reduce students' anxiety and perception of difficulty at the start of their learning experience and encourage students to engage with statistics in their future careers.

Deletion of Tsc2 in Nociceptors Reduces Target Innervation, Ion Channel Expression, and Sensitivity to Heat

PubMed Central

Carlin, Dan; Golden, Judith P.; Monk, Kelly R.

2018-01-01

Abstract The mechanistic target of rapamycin complex 1 (mTORC1) is known to regulate cellular growth pathways, and its genetic activation is sufficient to enhance regenerative axon growth following injury to the central or peripheral nervous systems. However, excess mTORC1 activation may promote innervation defects, and mTORC1 activity mediates injury-induced hypersensitivity, reducing enthusiasm for the pathway as a therapeutic target. While mTORC1 activity is required for full expression of some pain modalities, the effects of pathway activation on nociceptor phenotypes and sensory behaviors are currently unknown. To address this, we genetically activated mTORC1 in mouse peripheral sensory neurons by conditional deletion of its negative regulator Tuberous Sclerosis Complex 2 (Tsc2). Consistent with the well-known role of mTORC1 in regulating cell size, soma size and axon diameter of C-nociceptors were increased in Tsc2-deleted mice. Glabrous skin and spinal cord innervation by C-fiber neurons were also disrupted. Transcriptional profiling of nociceptors enriched by fluorescence-associated cell sorting (FACS) revealed downregulation of multiple classes of ion channels as well as reduced expression of markers for peptidergic nociceptors in Tsc2-deleted mice. In addition to these changes in innervation and gene expression, Tsc2-deleted mice exhibited reduced noxious heat sensitivity and decreased injury-induced cold hypersensitivity, but normal baseline sensitivity to cold and mechanical stimuli. Together, these data show that excess mTORC1 activity in sensory neurons produces changes in gene expression, neuron morphology and sensory behavior. PMID:29766046

School re-entry of the pediatric heart transplant recipient.

PubMed

Weil, Constance M; Rodgers, S; Rubovits, S

2006-12-01

Pediatric cardiac transplant has become increasingly frequent in the last decade and survival rates have improved remarkably. Outcome research on this population suggests that the majority of children have the capacity for healthy adaptation although 25-40% have been shown to have some type of psychiatric difficulties. As school plays a major role in these children's lives, early intervention and close liaison with schools is indicated to reduce psychological morbidity, enhance adaptation within the school environment and enhance overall adjustment. This paper proposes a model for a school re-entry program for this population. The school re-entry program is aimed at children who are undergoing cardiac transplant and will be entering or re-entering the school system. They may range in academic age from preschool to college level and have been attending private or public schools with placements in regular education programs, regular education programs with resource support, special education programs, and alternative school programs. Others may not have been attending school because of the severity of their medical condition and have been receiving in-home tutoring. Each child is offered school re-entry assistance by a multi-disciplinary team composed of members from the Cardiology Transplant Service. The re-entry program includes cognitive and psychosocial assessment, liaison with the child's school pre- and post-transplant, academic planning and provision of academic, emotional, and behavioral support before, during, and immediately after transplant, a school re-entry visit, and an ongoing school consultation. The goal is to address issues necessary for a successful school re-entry including appropriate academic placement and support, psychosocial adjustment, education of school personnel and ongoing health needs of the student. The next step is to formally evaluate the efficacy of this program in successful school re-entry.

Woven Thermal Protection System Based Heat-shield for Extreme Entry Environments Technology (HEEET)

NASA Technical Reports Server (NTRS)

Ellerby, Donald; Venkatapathy, Ethiraj; Stackpoole, Margaret; Chinnapongse, Ronald; Munk, Michelle; Dillman, Robert; Feldman, Jay; Prabhu, Dinesh; Beerman, Adam

2013-01-01

NASA's future robotic missions utilizing an entry system into Venus and the outer planets, namely, Saturn, Uranus, Neptune, result in extremely high entry conditions that exceed the capabilities of state of the art low to mid density ablators such as PICA or Avcoat. Therefore mission planners typically assume the use of a fully dense carbon phenolic heat shield similar to what was flown on Pioneer Venus and Galileo. Carbon phenolic is a robust TPS material however its high density and relatively high thermal conductivity constrain mission planners to steep entries, with high heat fluxes and pressures and short entry durations, in order for CP to be feasible from a mass perspective. The high entry conditions pose challenges for certification in existing ground based test facilities and the longer-term sustainability of CP will continue to pose challenges. In 2012 the Game Changing Development Program (GCDP) in NASA's Space Technology Mission Directorate funded NASA ARC to investigate the feasibility of a Woven Thermal Protection System (WTPS) to meet the needs of NASA's most challenging entry missions. This project was highly successful demonstrating that a Woven TPS solution compares favorably to CP in performance in simulated reentry environments and provides the opportunity to manufacture graded materials that should result in overall reduced mass solutions and enable a much broader set of missions than does CP. Building off the success of the WTPS project GCDP has funded a follow on project to further mature and scale up the WTPS concept for insertion into future NASA robotic missions. The matured WTPS will address the CP concerns associated with ground based test limitations and sustainability. This presentation will briefly discuss results from the WTPS Project and the plans for WTPS maturation into a heat-shield for extreme entry environment.

Woven Thermal Protection System Based Heat-shield for Extreme Entry Environments Technology (HEEET)

NASA Technical Reports Server (NTRS)

Chinnapongse, Ronald; Ellerbe, Donald; Stackpoole, Maragaret; Venkatapathy, Ethiraj; Beerman, Adam; Feldman, Jay; Peterson Keith; Prabhu, Dinesh; Dillman, Robert; Munk, Michelle

2013-01-01

NASA's future robotic missions utilizing an entry system into Venus and the outer planets, namely, Saturn, Uranus, Neptune, result in extremely severe entry conditions that exceed the capabilities of state of the art low to mid density ablators such as PICA or Avcoat. Therefore mission planners typically assume the use of a fully dense carbon phenolic heat shield similar to what was flown on Pioneer Venus and Galileo. Carbon phenolic (CP) is a robust TPS material however its high density and relatively high thermal conductivity constrain mission planners to steep entries, with high heat fluxes and pressures and short entry durations, in order for CP to be feasible from a mass perspective. The high entry conditions pose challenges for certification in existing ground based test facilities and the longer-­-term sustainability of CP will continue to pose challenges. In 2012 the Game Changing Development Program (GCDP) in NASA's Space Technology Mission Directorate funded NASA ARC to investigate the feasibility of a Woven Thermal Protection System (WTPS) to meet the needs of NASA's most challenging entry missions. This project was highly successful demonstrating that a Woven TPS solution compares favorably to CP in performance in simulated reentry environments and provides the opportunity to manufacture graded materials that should result in overall reduced mass solutions and enable a much broader set of missions than does CP. Building off the success of the WTPS project GCDP has funded a follow on project to further mature and scale up the WTPS concept for insertion into future NASA robotic missions. The matured WTPS will address the CP concerns associated with ground based test limitations and sustainability. This presentation will briefly discuss results from the WTPS Project and the plans for WTPS maturation into a heat-­-shield for extreme entry environment.

Improving laboratory data entry quality using Six Sigma.

PubMed

Elbireer, Ali; Le Chasseur, Julie; Jackson, Brooks

2013-01-01

The Uganda Makerere University provides clinical laboratory support to over 70 clients in Uganda. With increased volume, manual data entry errors have steadily increased, prompting laboratory managers to employ the Six Sigma method to evaluate and reduce their problems. The purpose of this paper is to describe how laboratory data entry quality was improved by using Six Sigma. The Six Sigma Quality Improvement (QI) project team followed a sequence of steps, starting with defining project goals, measuring data entry errors to assess current performance, analyzing data and determining data-entry error root causes. Finally the team implemented changes and control measures to address the root causes and to maintain improvements. Establishing the Six Sigma project required considerable resources and maintaining the gains requires additional personnel time and dedicated resources. After initiating the Six Sigma project, there was a 60.5 percent reduction in data entry errors from 423 errors a month (i.e. 4.34 Six Sigma) in the first month, down to an average 166 errors/month (i.e. 4.65 Six Sigma) over 12 months. The team estimated the average cost of identifying and fixing a data entry error to be $16.25 per error. Thus, reducing errors by an average of 257 errors per month over one year has saved the laboratory an estimated $50,115 a year. The Six Sigma QI project provides a replicable framework for Ugandan laboratory staff and other resource-limited organizations to promote quality environment. Laboratory staff can deliver excellent care at a lower cost, by applying QI principles. This innovative QI method of reducing data entry errors in medical laboratories may improve the clinical workflow processes and make cost savings across the health care continuum.

Implementing an ADA Kernel on NEBULA.

DTIC Science & Technology

1983-08-01

physical address(es). No instruction supports directly semaphore operations , or spin-locks, or other entities used in the synchronisation of tasks...these operations It is found that NEBULA supports admirably the control structures oil Ada, but its Memory Mamagement system is not very suitable. Entry... operating system . With the advent of Ada, in theory at least, the whole program can be written in Ada in a manner that is independent of the computer and of

Airline Deregulation: Addressing the Air Service Problems of Some Communities

DOT National Transportation Integrated Search

1997-06-25

Airline deregulation has led to lower airfares and better service for most air : travelers, due largely to increased competition spurred by the entry of new : airlines into the industry and established airlines into new markets. However, : some airpo...

31 CFR 353.3 - Converting definitive savings bonds to book-entry bonds in TreasuryDirect®.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TreasuryDirect®, an online system for holding Treasury securities. The Web address for TreasuryDirect® is... follow online instructions for conversion. Regulations governing converted bonds are found at 31 CFR part...

31 CFR 360.3 - Converting definitive savings bonds to book-entry bonds in New Treasury Direct.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Direct, an online system for holding Treasury securities. The Web address for New Treasury Direct is www.treasurydirect.gov. Bond owners who wish to convert their definitive savings bonds should follow online...

31 CFR 360.3 - Converting definitive savings bonds to book-entry bonds in New Treasury Direct.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Direct, an online system for holding Treasury securities. The Web address for New Treasury Direct is www.treasurydirect.gov. Bond owners who wish to convert their definitive savings bonds should follow online...

Ultralightweight Ballute Technology Advances

NASA Technical Reports Server (NTRS)

Masciarelli, Jim; Miller, Kevin

2005-01-01

Ultralightweight ballutes offer the potential to provide the deceleration for entry and aerocapture missions at a fraction of the mass of traditional methods. A team consisting of Ball Aerospace, ILC Dover, NASA Langley, NASA Johnson, and the Jet Propulsion Laboratory has been addressing the technical issues associated with ultralightweight ballutes for aerocapture at Titan. Significant progress has been made in the areas of ballute materials, aerothermal analysis, trajectory control, and aeroelastic modeling. The status and results of efforts in these areas are presented. The results indicate that an ultralightweight ballute system mass of 8 to 10 percent of the total entry mass is possible.

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

"rsed" is an R package that contains tools for stream editing: manipulating text files by making insertions, replacements, deletions, substitutions, or commenting. It hails from the powerful Unix command, "sed". While the "rsed" package is not nearly as powerful as "see", it is much simpler to use. R programmers often write scripts that may require simple manipulation of text files. "rsed" addresses that need.

Reporting the Use of Multiple Imputation for Missing Data in Higher Education Research

ERIC Educational Resources Information Center

Manly, Catherine A.; Wells, Ryan S.

2015-01-01

Higher education researchers using survey data often face decisions about handling missing data. Multiple imputation (MI) is considered by many statisticians to be the most appropriate technique for addressing missing data in many circumstances. In particular, it has been shown to be preferable to listwise deletion, which has historically been a…

Venus In Situ Explorer Mission design using a mechanically deployed aerodynamic decelerator

NASA Astrophysics Data System (ADS)

Smith, B.; Venkatapathy, E.; Wercinski, P.; Yount, B.; Prabhu, D.; Gage, P.; Glaze, L.; Baker, C.

The Venus In Situ Explorer (VISE) Mission addresses the highest priority science questions within the Venus community outlined in the National Research Council's Decadal Survey. The heritage Venus atmospheric entry system architecture, a 45° sphere-cone rigid aeroshell with a carbon phenolic thermal protection system, may no longer be the preferred entry system architecture compared to other viable alternatives being explored at NASA. A mechanically-deployed aerodynamic decelerator, known as the Adaptive Deployable Entry and Placement Technology (ADEPT), is an entry system alternative that can provide key operational benefits and risk reduction compared to a rigid aeroshell. This paper describes a mission feasibility study performed with the objectives of identifying potential adverse interactions with other mission elements and establishing requirements on decelerator performance. Feasibility is assessed through a launch-to-landing mission design study where the Venus Intrepid Tessera Lander (VITaL), a VISE science payload designed to inform the Decadal Survey results, is repackaged from a rigid aeroshell into the ADEPT decelerator. It is shown that ADEPT reduces the deceleration load on VITaL by an order of magnitude relative to a rigid aeroshell. The more benign entry environment opens up the VISE mission design environment for increased science return, reduced risk, and reduced cost. The ADEPT-VITAL mission concept of operations is presented and details of the entry vehicle structures and mechanisms are given. Finally, entry aerothermal analysis is presented that defines the operational requirements for a revolutionary structural-TPS material employed by ADEPT: three-dimensionally woven carbon cloth. Ongoing work to mitigate key risks identified in this feasibility study is presented.

Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function

PubMed Central

Jackson, Ben; Mileham, Alan J.; Ait-Ali, Tahar; Whitelaw, C. Bruce A.

2017-01-01

Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages. PMID:28231264

An origin-deficient yeast artificial chromosome triggers a cell cycle checkpoint.

PubMed

van Brabant, A J; Buchanan, C D; Charboneau, E; Fangman, W L; Brewer, B J

2001-04-01

Checkpoint controls coordinate entry into mitosis with the completion of DNA replication. Depletion of nucleotide precursors by treatment with the drug hydroxyurea triggers such a checkpoint response. However, it is not clear whether the signal for this hydroxyurea-induced checkpoint pathway is the presence of unreplicated DNA, or rather the persistence of single-stranded or damaged DNA. In a yeast artificial chromosome (YAC) we have engineered an approximately 170 kb region lacking efficient replication origins that allows us to explore the specific effects of unreplicated DNA on cell cycle progression. Replication of this YAC extends the length of S phase and causes cells to engage an S/M checkpoint. In the absence of Rad9 the YAC becomes unstable, undergoing deletions within the origin-free region.

Intelligent Weather Agent

NASA Technical Reports Server (NTRS)

Spirkovska, Liljana (Inventor)

2006-01-01

Method and system for automatically displaying, visually and/or audibly and/or by an audible alarm signal, relevant weather data for an identified aircraft pilot, when each of a selected subset of measured or estimated aviation situation parameters, corresponding to a given aviation situation, has a value lying in a selected range. Each range for a particular pilot may be a default range, may be entered by the pilot and/or may be automatically determined from experience and may be subsequently edited by the pilot to change a range and to add or delete parameters describing a situation for which a display should be provided. The pilot can also verbally activate an audible display or visual display of selected information by verbal entry of a first command or a second command, respectively, that specifies the information required.

An Updated Protocol to Detect Invalid Entries in an Online Survey of Men Who Have Sex with Men (MSM): How Do Valid and Invalid Submissions Compare?

PubMed Central

Konstan, Joseph; Iantaffi, Alex; Wilkerson, J. Michael; Galos, Dylan; Simon Rosser, B. R.

2017-01-01

Researchers use protocols to screen for suspicious survey submissions in online studies. We evaluated how well a de-duplication and cross-validation process detected invalid entries. Data were from the Sexually Explicit Media Study, an Internet-based HIV prevention survey of men who have sex with men. Using our protocol, 146 (11.6 %) of 1254 entries were identified as invalid. Most indicated changes to the screening questionnaire to gain entry (n = 109, 74.7 %), matched other submissions’ payment profiles (n = 56, 41.8 %), or featured an IP address that was recorded previously (n = 43, 29.5 %). We found few demographic or behavioral differences between valid and invalid samples, however. Invalid submissions had lower odds of reporting HIV testing in the past year (OR 0.63), and higher odds of requesting no payment compared to check payments (OR 2.75). Thus, rates of HIV testing would have been underestimated if invalid submissions had not been removed, and payment may not be the only incentive for invalid participation. PMID:25805443

The characteristics of registered nurses whose licenses expire: why they leave nursing and implications for retention and re-entry.

PubMed

Skillman, Susan M; Palazzo, Lorella; Hart, L Gary; Keepnews, David

2010-01-01

Little is known about RNs who drop their licenses and their potential re-entry into the nursing workforce. The results of this study provide insight into reasons nurses leave their careers and the barriers to re-entry, all important indicators of the current professional climate for nursing. While representing only one state, these findings suggest that RNs who allow their licenses to expire do so because they have reached retirement age or, among those who do not cite age as a factor, because many are unable or unwilling to work in the field. Inactive nurses who might otherwise appear to be likely candidates for re-entry into the profession may not be easily encouraged to practice nursing again without significant changes in their personal circumstances or the health care work environment. Effective ways to address current and pending RN workforce shortages include expanding RN education capacity to produce more RNs who can contribute to the workforce across the coming decades, and promote work environments in which RNs want to, and are able to, practice across a long nursing career.

Complications of Laparoscopy in Connection with Entry Techniques

PubMed Central

2017-01-01

Abstract The anatomy of the human being has not changed. However, technical developments in operating materials and methods call for improvements in surgical procedures as well as the management of complications. A fundamental distinction between any operating method and laparoscopy is that, in the latter, the initial entry is usually performed in blind fashion. Blind entry may result in vessel or organ damage, especially in patients who have undergone previous surgery. One of the difficulties associated with the entry is that the damage may not be identified immediately and then necessitate major abdominal repair. Furthermore, the improvement of surgical instruments and techniques enables the surgeon to perform even major operations by the laparoscopic approach. This is associated with renewed learning curves and a high rate of complications due to vascular, bowel, uterine, or bladder damage. The improvement of surgical techniques must be accompanied by advancements in the management of complications. The aim of this review is to address the risks of laparoscopy as well as their correct and professional management. (J GYNECOL SURG 33:81) PMID:28663686

7 CFR 47.4 - Service and proof of service.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the date of the re-mailing by ordinary mail to the same address. (2) Any document or paper, other than... official record of the postal service; (3) An entry on a docket record or a copy placed in a docket filed...

7 CFR 47.4 - Service and proof of service.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the date of the re-mailing by ordinary mail to the same address. (2) Any document or paper, other than... official record of the postal service; (3) An entry on a docket record or a copy placed in a docket filed...

Process Instrumentation. Teacher Edition.

ERIC Educational Resources Information Center

Brown, A. O., III; Fowler, Malcolm

This module provides instructional materials that are designed to help teachers train students in job skills for entry-level jobs as instrumentation technicians. This text addresses the basics of troubleshooting control loops, and the transducers, transmitters, signal conditioners, control valves, and controllers that enable process systems to…

ANALYSIS OF RADON MITIGATION TECHNIQUES USED IN EXISTING U.S. HOUSES

EPA Science Inventory

This paper reviews the full range of techniques that have been installed in existing US houses for the purpose of reducing indoor radon concentrations resulting from soil gas entry. The review addresses the performance, installation and operating costs, applicability, mechanisms,...

Information Technology in Education: The Best of ERIC.

ERIC Educational Resources Information Center

Ely, Donald P.

This publication highlights 48 recent ERIC listings which help to explain the variety of emerging technologies for the delivery of information in educational settings. Specific technologies addressed include cable television, electronic mail, satellite communication, teleconferencing, videodisc, and videotex. Entries were selected for inclusion…

First Things First: Internet Relay Chat Openings.

ERIC Educational Resources Information Center

Rintel, E. Sean; Mulholland, Joan; Pittam, Jeffery

2001-01-01

Argues that Internet Relay Chat (IRC) research needs to systematically address links between interaction structures, technological mediation and the instantiation and development of interpersonal relationships. Finds that openings that occur directly following user's entries into public IRC channels are often ambiguous, can disrupt relationship…

Familial hypercholesterolemia with extensive coronary artery disease and tuberous and tendinous xanthomas: A case report and mutation analysis.

PubMed

Agirbasli, Deniz; Hyatt, Tommy; Agirbasli, Mehmet

2018-04-26

This is a case report of a 38-year-old Syrian refugee male with early-onset extensive atherosclerosis. The physical and laboratory examination were remarkable with severe xanthomas in the upper and lower extremities and with low-density lipoprotein cholesterol (LDL-C) 417 mg/dL, total cholesterol 495 mg/dL, high-density lipoprotein cholesterol 30 mg/dL, and triglycerides 242 mg/dL. LDL-C level responded poorly to the high-dose statin treatment. The genetic analysis indicated that the patient had a large homozygous deletion in LDL receptor gene including the exons 7-14. A 12-kb deletion had occurred between the 2 Alu repetitive sequences that were oriented in opposite directions, one in intron 6 and the other in intron 14. This deletion eliminated exons 7-14, which exactly corresponded to the entire exon sequence coding the epidermal growth factor precursor homology domain. This deletion in LDL receptor was previously reported. This rare case of homozygous familial hypercholesterolemia presenting with multiple large and widely distributed xanthomas implicates the need for novel treatment options in familial hypercholesterolemia patients. The case is a Syrian refugee and emphasizes the urgent need to address orphan disease in refugee populations throughout the world. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy

PubMed Central

Bornert, Olivier; Kühl, Tobias; Bremer, Jeroen; van den Akker, Peter C; Pasmooij, Anna MG; Nyström, Alexander

2016-01-01

Genetically evoked deficiency of collagen VII causes dystrophic epidermolysis bullosa (DEB)—a debilitating disease characterized by chronic skin fragility and progressive fibrosis. Removal of exons carrying frame-disrupting mutations can reinstate protein expression in genetic diseases. The therapeutic potential of this approach is critically dependent on gene, protein, and disease intrinsic factors. Naturally occurring exon skipping in COL7A1, translating collagen VII, suggests that skipping of exons containing disease-causing mutations may be feasible for the treatment of DEB. However, despite a primarily in-frame arrangement of exons in the COL7A1 gene, no general conclusion of the aptitude of exon skipping for DEB can be drawn, since regulation of collagen VII functionality is complex involving folding, intra- and intermolecular interactions. To directly address this, we deleted two conceptually important exons located at both ends of COL7A1, exon 13, containing recurrent mutations, and exon 105, predicted to impact folding. The resulting recombinantly expressed proteins showed conserved functionality in biochemical and in vitro assays. Injected into DEB mice, the proteins promoted skin stability. By demonstrating functionality of internally deleted collagen VII variants, our study provides support of targeted exon deletion or skipping as a potential therapy to treat a large number of individuals with DEB. PMID:27157667

Loss of Either Rac1 or Rac3 GTPase Differentially Affects the Behavior of Mutant Mice and the Development of Functional GABAergic Networks

PubMed Central

Pennucci, Roberta; Talpo, Francesca; Astro, Veronica; Montinaro, Valentina; Morè, Lorenzo; Cursi, Marco; Castoldi, Valerio; Chiaretti, Sara; Bianchi, Veronica; Marenna, Silvia; Cambiaghi, Marco; Tonoli, Diletta; Leocani, Letizia; Biella, Gerardo; D'Adamo, Patrizia; de Curtis, Ivan

2016-01-01

Rac GTPases regulate the development of cortical/hippocampal GABAergic interneurons by affecting the early development and migration of GABAergic precursors. We have addressed the function of Rac1 and Rac3 proteins during the late maturation of hippocampal interneurons. We observed specific phenotypic differences between conditional Rac1 and full Rac3 knockout mice. Rac1 deletion caused greater generalized hyperactivity and cognitive impairment compared with Rac3 deletion. This phenotype matched with a more evident functional impairment of the inhibitory circuits in Rac1 mutants, showing higher excitability and reduced spontaneous inhibitory currents in the CA hippocampal pyramidal neurons. Morphological analysis confirmed a differential modification of the inhibitory circuits: deletion of either Rac caused a similar reduction of parvalbumin-positive inhibitory terminals in the pyramidal layer. Intriguingly, cannabinoid receptor-1-positive terminals were strongly increased only in the CA1 of Rac1-depleted mice. This increase may underlie the stronger electrophysiological defects in this mutant. Accordingly, incubation with an antagonist for cannabinoid receptors partially rescued the reduction of spontaneous inhibitory currents in the pyramidal cells of Rac1 mutants. Our results show that Rac1 and Rac3 have independent roles in the formation of GABAergic circuits, as highlighted by the differential effects of their deletion on the late maturation of specific populations of interneurons. PMID:26582364

Re-refinement from deposited X-ray data can deliver improved models for most PDB entries.

PubMed

Joosten, Robbie P; Womack, Thomas; Vriend, Gert; Bricogne, Gérard

2009-02-01

The deposition of X-ray data along with the customary structural models defining PDB entries makes it possible to apply large-scale re-refinement protocols to these entries, thus giving users the benefit of improvements in X-ray methods that have occurred since the structure was deposited. Automated gradient refinement is an effective method to achieve this goal, but real-space intervention is most often required in order to adequately address problems detected by structure-validation software. In order to improve the existing protocol, automated re-refinement was combined with structure validation and difference-density peak analysis to produce a catalogue of problems in PDB entries that are amenable to automatic correction. It is shown that re-refinement can be effective in producing improvements, which are often associated with the systematic use of the TLS parameterization of B factors, even for relatively new and high-resolution PDB entries, while the accompanying manual or semi-manual map analysis and fitting steps show good prospects for eventual automation. It is proposed that the potential for simultaneous improvements in methods and in re-refinement results be further encouraged by broadening the scope of depositions to include refinement metadata and ultimately primary rather than reduced X-ray data.

75 FR 38770 - Siskiyou, OR Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

.... Written comments should be sent to Paul Galloway, Medford Interagency Office, 3040 Biddle Road, Medford... facilitate entry into the building. FOR FURTHER INFORMATION CONTACT: Paul Galloway, Acting Public Affairs... the opportunity to address the Committee during that session. Dated: June 24, 2010. Scott D. Conroy...

Careers Guide: Opportunities in the Professions, Industry and Commerce.

ERIC Educational Resources Information Center

Central Youth Employment Executive, London (England).

This directory contains basic occupational information about 100 career opportunities in business, industry, and the professions in Great Britain. Entry-level employment qualifications, brief job descriptions, salary ranges, employment projections, and resource addresses are provided for each career. Educational and training requirements are…

Addressing Perceived Skill Deficiencies in Student Affairs Graduate Preparation Programs

ERIC Educational Resources Information Center

Cooper, Jay; Mitchell, Donald, Jr.; Eckerle, Kayle; Martin, Kyle

2016-01-01

This article explores existing literature on perceived skill deficiencies among entry-level student affairs practitioners. Through a review of recent literature, seven perceived skill deficiencies were identified, including budgeting and financial management, strategic planning, research and assessment, legal knowledge and standards, supervision,…

Contract Attorneys Course Deskbook. Volume 1

DTIC Science & Technology

2007-06-21

sources ; exceptions,” deletes “specialty metals ” from the listed items in § 2533a and creates a whole new section to address specialty metals . The...Acquisition Procedures 11 Commercial Item Acquisitions 12 Contract Pricing 13 Bid Protests 14 Competitive Sourcing ii 15...Requirements Part 7: Acquisition Planning Part 8: Required Sources of Supplies and Services Part 9: Contractor Qualifications Part 10: Market

77 FR 68851 - Mr. Brandon D. Neff, [HOME ADDRESS DELETED UNDER 10 CFR 2.390]; Order Prohibiting Involvement in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... the above conditions upon demonstration by Mr. Brandon D. Neff of good cause. V In accordance with 10... 30 days of its publication in the Federal Register. Where good cause is shown, consideration will be..., and include a statement of good cause for the extension. All documents filed in the NRC adjudicatory...

Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops.

PubMed

Kolchinsky, P; Kiprilov, E; Bartley, P; Rubinstein, R; Sodroski, J

2001-04-01

The gp120 envelope glycoprotein of primary human immunodeficiency virus type 1 (HIV-1) promotes virus entry by sequentially binding CD4 and the CCR5 chemokine receptor on the target cell. Previously, we adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for CD4-independent replication were limited to the V2 loop-V1/V2 stem. Here we show that elimination of a single glycosylation site at asparagine 197 in the V1/V2 stem is sufficient for CD4-independent gp120 binding to CCR5 and for HIV-1 entry into CD4-negative cells expressing CCR5. Deletion of the V1/V2 loops also allowed CD4-independent viral entry and gp120 binding to CCR5. The binding of the wild-type ADA gp120 to CCR5 was less dependent upon CD4 at 4 degrees C than at 37 degrees C. In the absence of the V1/V2 loops, neither removal of the N-linked carbohydrate at asparagine 197 nor lowering of the temperature increased the CD4-independent phenotypes. A CCR5-binding conformation of gp120, achieved by CD4 interaction or by modification of temperature, glycosylation, or variable loops, was preferentially recognized by the monoclonal antibody 48d. These results suggest that the CCR5-binding region of gp120 is occluded by the V1/V2 variable loops, the position of which can be modulated by temperature, CD4 binding, or an N-linked glycan in the V1/V2 stem.

Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function.

PubMed

Xing, Juan; Petranka, John G; Davis, Felicity M; Desai, Pooja N; Putney, James W; Bird, Gary S

2014-03-01

Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.

Using water and sanitation as an entry point to fight poverty and respond to HIV/AIDS: The case of Isulabasha Small Medium Enterprise

NASA Astrophysics Data System (ADS)

Manase, G.; Nkuna, Z.; Ngorima, E.

South Africa is faced by a number of challenges that include low water and sanitation coverage in rural and peri-urban areas, high unemployment and increasing inequality between the rich and the poor as indicated by a Gini coefficient of 0.77; the second highest inequality in the world after Brazil. The situation is compounded by high HIV prevalence with South Africa having the largest HIV infection in the world. This case study demonstrates how water and sanitation is used as an entry point to address these major challenges and to empower communities. The project has two main components: the Small Medium Enterprise (SME) that trades in water and sanitation facilities and a community garden that ensures food security and nutrition for people living with HIV/AIDS. Income generated through these activities is ploughed back into the community through construction of sanitation facilities, maintenance of water pipes and paying school fees for orphans. In addition to creating employment, the project has also empowered the community to mobilise and address other challenges such as gender, child abuse and crime. The case study identifies weaknesses with projects designed solely to provide domestic drinking water and sanitation and calls for an integrated approach that uses water and sanitation as an entry point to unlock opportunities and empower the targeted communities.

Sorting cancer karyotypes using double-cut-and-joins, duplications and deletions.

PubMed

Zeira, Ron; Shamir, Ron

2018-05-03

Problems of genome rearrangement are central in both evolution and cancer research. Most genome rearrangement models assume that the genome contains a single copy of each gene and the only changes in the genome are structural, i.e., reordering of segments. In contrast, tumor genomes also undergo numerical changes such as deletions and duplications, and thus the number of copies of genes varies. Dealing with unequal gene content is a very challenging task, addressed by few algorithms to date. More realistic models are needed to help trace genome evolution during tumorigenesis. Here we present a model for the evolution of genomes with multiple gene copies using the operation types double-cut-and-joins, duplications and deletions. The events supported by the model are reversals, translocations, tandem duplications, segmental deletions, and chromosomal amplifications and deletions, covering most types of structural and numerical changes observed in tumor samples. Our goal is to find a series of operations of minimum length that transform one karyotype into the other. We show that the problem is NP-hard and give an integer linear programming formulation that solves the problem exactly under some mild assumptions. We test our method on simulated genomes and on ovarian cancer genomes. Our study advances the state of the art in two ways: It allows a broader set of operations than extant models, thus being more realistic, and it is the first study attempting to reconstruct the full sequence of structural and numerical events during cancer evolution. Code and data are available in https://github.com/Shamir-Lab/Sorting-Cancer-Karyotypes. ronzeira@post.tau.ac.il, rshamir@tau.ac.il. Supplementary data are available at Bioinformatics online.

Graduate entry nurses' initial perspectives on nursing: Content analysis of open-ended survey questions.

PubMed

McKenna, Lisa; Brooks, Ingrid; Vanderheide, Rebecca

2017-02-01

Graduate entry nursing courses offer individuals with prior degrees the opportunity to gain nursing qualifications and facilitate career change. While it is known that accelerated graduate entry courses are increasingly popular, the perceptions of nursing held by such individuals and the influence this has on those seeking to enter the profession are less clearly understood. To explore graduate entry nursing students' perceptions of nursing on entering their pre-registration course. A descriptive design utilising cross-section survey with two open-ended questions: What do you believe the role of the nurse is? What things have influenced that view? were asked. Demographic data were analysed using descriptive frequencies, while the two open-ended questions were analysed using summative content analysis. One university-based postgraduate graduate entry nursing course in Australia PARTICIPANTS: Eight cohorts (n=286) commencing students with prior degrees other than nursing. The course attracts students from diverse backgrounds. Exposure to nursing and nurses, either as a consumer of health care or other health care role, plays a primary role in influencing career change. However, similar to those found with school leavers, there remains much misinformation about nurses' roles for students in these courses. Most identify the role of caring in nursing. For some, media representations are the only information sources. Graduate entry courses offer opportunities to attract new nurses and contribute to addressing workforce shortages. However, there is still a lack of knowledge of nursing roles among students on entry. More work is required by the profession to ensure nursing is accurately and positively represented to the community. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Different phospholipase-C-coupled receptors differentially regulate capacitative and non-capacitative Ca2+ entry in A7r5 cells

PubMed Central

Moneer, Zahid; Pino, Irene; Taylor, Emily J. A.; Broad, Lisa M.; Liu, Yingjie; Tovey, Stephen C.; Staali, Leila; Taylor, Colin W.

2005-01-01

Several receptors, including those for AVP (Arg8-vasopressin) and 5-HT (5-hydroxytryptamine), share an ability to stimulate PLC (phospholipase C) and so production of IP3 (inositol 1,4,5-trisphosphate) and DAG (diacylglycerol) in A7r5 vascular smooth muscle cells. Our previous analysis of the effects of AVP on Ca2+ entry [Moneer, Dyer and Taylor (2003) Biochem. J. 370, 439–448] showed that arachidonic acid released from DAG stimulated NO synthase. NO then stimulated an NCCE (non-capacitative Ca2+ entry) pathway, and, via cGMP and protein kinase G, it inhibited CCE (capacitative Ca2+ entry). This reciprocal regulation ensured that, in the presence of AVP, all Ca2+ entry occurred via NCCE to be followed by a transient activation of CCE only when AVP was removed [Moneer and Taylor (2002) Biochem. J. 362, 13–21]. We confirm that, in the presence of AVP, all Ca2+ entry occurs via NCCE, but 5-HT, despite activating PLC and evoking release of Ca2+ from intracellular stores, stimulates Ca2+ entry only via CCE. We conclude that two PLC-coupled receptors differentially regulate CCE and NCCE. We also address evidence that, in some A7r5 cells lines, AVP fails either to stimulate NCCE or inhibit CCE [Brueggemann, Markun, Barakat, Chen and Byron (2005) Biochem. J. 388, 237–244]. Quantitative PCR analysis suggests that these cells predominantly express TRPC1 (transient receptor potential canonical 1), whereas cells in which AVP reciprocally regulates CCE and NCCE express a greater variety of TRPC subtypes (TRPC1=6>2>3). PMID:15918794

Entry risk into the juvenile justice system: African American, American Indian, Asian American, European American, and Hispanic children and adolescents.

PubMed

Vazsonyi, Alexander T; Chen, Pan

2010-06-01

Findings on disproportionate minority contact remain mixed. Few empirical studies have examined to what extent entry risk into juvenile justice varies across ethnic/racial groups, and to what extent childhood aggressive behaviors foretell later deviance and entry risk. In the current study, we sought to address these shortcomings by implementing a survival analysis on a representative sample of youth followed from age 8 to 18. The sample included N = 2,754 lower to lower-middle SES youth from five different ethnic/racial groups (African American, American Indian, Asian American, European American, and Hispanic youth), part of a large-scale violence prevention effort. Aggressive behaviors were rated by teachers during elementary school, entry risk into juvenile justice was measured by official data, while SES was based on census data. Developmental entry risk into the juvenile justice system peaked at age 14 and subsequently declined. No differences were found across the four racial groups; however, Hispanic youth were at elevated risk (by 73%). Only childhood physical aggressive behavior increased entry risk (by 87%); this was above and beyond a 'simple' maturational liability we found and net any effects by sex, race/ethnicity, and SES. Some evidence suggested disproportionate minority contact, but only for Hispanic youth. Entry risk was invariant by race, but differed for males versus females and for youth from relatively higher socioeconomic status (SES) strata compared to youth from lower ones. Intervention efforts should target physically aggressive children during the elementary school years; however, some of the evidence also suggests that there exists a 'maturational liability' developmentally over time, between the ages of 8 and 18, independent of any of the focal predictors tested.

Flexible thermal protection materials for entry systems

NASA Astrophysics Data System (ADS)

Kourtides, Demetrius A.

1993-02-01

Current programs addressed in aeroassist flight experiment are: (1) evaluation of thermal performance of advanced rigid and flexible insulations and reflective coating; (2) investigation of lighter than baseline materials; (3) investigation of rigid insulations which perform well; (4) study of flexible insulations which require ceramic coating; and (5) study of reflective coating effective at greater than 15 percent. In National Aerospace Plane (NASP), the programs addressed are: (1) high and low temperature insulations; and (2) attachment/standoff methodology critical which affects thermal performance.

Flexible thermal protection materials for entry systems

NASA Technical Reports Server (NTRS)

Kourtides, Demetrius A.

1993-01-01

Current programs addressed in aeroassist flight experiment are: (1) evaluation of thermal performance of advanced rigid and flexible insulations and reflective coating; (2) investigation of lighter than baseline materials; (3) investigation of rigid insulations which perform well; (4) study of flexible insulations which require ceramic coating; and (5) study of reflective coating effective at greater than 15 percent. In National Aerospace Plane (NASP), the programs addressed are: (1) high and low temperature insulations; and (2) attachment/standoff methodology critical which affects thermal performance.

Children's Ideas about Fossils and Foundational Concepts Related to Fossils

ERIC Educational Resources Information Center

Borgerding, Lisa A.; Raven, Sara

2018-01-01

Many standards documents and learning progressions recommend evolution learning in elementary grades. Given young children's interest in dinosaurs and other fossils, fossil investigations can provide a rich entry into evolutionary biology for young learners. Educational psychology literature has addressed children's reasoning about foundational…

Biography. Advisory List of Instructional Media.

ERIC Educational Resources Information Center

North Carolina State Dept. of Public Instruction, Raleigh. Div. of Media Evaluation Service.

The 65 biographies reviewed in this annotated bibliography are suitable for readers in grades pre-kindergarten through 12. Full bibliographic data, appropriate grade level indication, and annotations are supplied for each entry. The names and addresses of the publishers are also provided. Biographies of women, children, authors, actors, historical…

THE EDUCATIONAL MEDIA INDEX.

ERIC Educational Resources Information Center

Educational Media Council, Inc., New York, NY.

THIS 14-VOLUME SERIES INCLUDES TITLES AND DESCRIPTIONS FOR ALL CURRENT AND GENERALLY AVAILABLE EDUCATIONAL MEDIA, EXCLUDING STANDARD PRINT MATERIALS. EACH VOLUME COVERS A SPECIFIC SUBJECT AREA, LISTS TITLES ALPHABETICALLY AND BY SUBJECT, DESCRIBES EACH ENTRY, AND LISTS NAMES AND ADDRESSES OF SOURCES FOR THE MATERIALS. VOLUME 14 IS A CUMULATIVE…

Population Education Accessions List, September-December 1996.

ERIC Educational Resources Information Center

United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

This issue of the Population Education Accessions List is an output from United Nation's Educational Social and Cultural Organization's (UNESCO) computerized bibliographic database. It categorizes entries into three parts. Part I, Population Education, consists of titles that address various aspects of population education arranged by country in…

Idea Notebook.

ERIC Educational Resources Information Center

Ross, Janet; And Others

1986-01-01

Three entries address various outdoor education issues. The first outlines eight steps for promoting professional work. The second suggests ways to adapt 16 games, group initiatives, and ropes course elements to teach environmental concepts. The third explains the use of belay anchors, or cork-screw anchors designed to tether large dogs. (JHZ)

3 CFR 8989 - Proclamation 8989 of May 31, 2013. Lesbian, Gay, Bisexual, and Transgender Pride Month, 2013

Code of Federal Regulations, 2014 CFR

2014-01-01

... identity and repealed “Don't Ask, Don't Tell.” We lifted the HIV entry ban and ensured hospital visitation..., as well as the National HIV/AIDS Strategy, which addresses the disparate impact of the HIV epidemic...

Oxygen-Dependent Globin Coupled Sensor Signaling Modulates Motility and Virulence of the Plant Pathogen Pectobacterium carotovorum.

PubMed

Burns, Justin L; Jariwala, Parth B; Rivera, Shannon; Fontaine, Benjamin M; Briggs, Laura; Weinert, Emily E

2017-08-18

Bacterial pathogens utilize numerous signals to identify the presence of their host and coordinate changes in gene expression that allow for infection. Within plant pathogens, these signals typically include small molecules and/or proteins from their plant hosts and bacterial quorum sensing molecules to ensure sufficient bacterial cell density for successful infection. In addition, bacteria use environmental signals to identify conditions when the host defenses are weakened and potentially to signal entry into an appropriate host/niche for infection. A globin coupled sensor protein (GCS), termed PccGCS, within the soft rot bacterium Pectobacterium carotovorum ssp. carotovorum WPP14 has been identified as an O 2 sensor and demonstrated to alter virulence factor excretion and control motility, with deletion of PccGCS resulting in decreased rotting of a potato host. Using small molecules that modulate bacterial growth and quorum sensing, PccGCS signaling also has been shown to modulate quorum sensing pathways, resulting in the PccGCS deletion strain being more sensitive to plant-derived phenolic acids, which can function as quorum sensing inhibitors, and exhibiting increased N-acylhomoserine lactone (AHL) production. These findings highlight a role for GCS proteins in controlling key O 2 -dependent phenotypes of pathogenic bacteria and suggest that modulating GCS signaling to limit P. carotovorum motility may provide a means to decrease rotting of plant hosts.

Characterization of Bombyx mori nucleopolyhedrovirus orf68 gene that encodes a novel structural protein of budded virus.

PubMed

Iwanaga, Masashi; Kurihara, Masaaki; Kobayashi, Masahiko; Kang, WonKyung

2002-05-25

All lepidopteran baculovirus genomes sequenced to date encode a homolog of the Bombyx mori nucleopolyhedrovirus (BmNPV) orf68 gene, suggesting that it performs an important role in the virus life cycle. In this article we describe the characterization of BmNPV orf68 gene. Northern and Western analyses demonstrated that orf68 gene was expressed as a late gene and encoded a structural protein of budded virus (BV). Immunohistochemical analysis by confocal microscopy showed that ORF68 protein was localized mainly in the nucleus of infected cells. To examine the function of orf68 gene, we constructed orf68 deletion mutant (BmD68) and characterized it in BmN cells and larvae of B. mori. BV production was delayed in BmD68-infected cells. The larval bioassays also demonstrated that deletion of orf68 did not reduce the infectivity, but mutant virus took 70 h longer to kill the host than wild-type BmNPV. In addition, dot-blot analysis showed viral DNA accumulated more slowly in mutant infected cells. Further examination suggested that BmD68 was less efficient in entry and budding from cells, although it seemed to possess normal attachment ability. These results suggest that ORF68 is a BV-associated protein involved in secondary infection from cell-to-cell. (c) 2002 Elsevier Science (USA).

Slack KNa Channels Influence Dorsal Horn Synapses and Nociceptive Behavior.

PubMed

Evely, Katherine M; Pryce, Kerri D; Bausch, Anne E; Lukowski, Robert; Ruth, Peter; Haj-Dahmane, Samir; Bhattacharjee, Arin

2017-01-01

The sodium-activated potassium channel Slack (Kcnt1, Slo2.2) is highly expressed in dorsal root ganglion neurons where it regulates neuronal firing. Several studies have implicated the Slack channel in pain processing, but the precise mechanism or the levels within the sensory pathway where channels are involved remain unclear. Here, we furthered the behavioral characterization of Slack channel knockout mice and for the first time examined the role of Slack channels in the superficial, pain-processing lamina of the dorsal horn. We performed whole-cell recordings from spinal cord slices to examine the intrinsic and synaptic properties of putative inhibitory and excitatory lamina II interneurons. Slack channel deletion altered intrinsic properties and synaptic drive to favor an overall enhanced excitatory tone. We measured the amplitudes and paired pulse ratio of paired excitatory post-synaptic currents at primary afferent synapses evoked by electrical stimulation of the dorsal root entry zone. We found a substantial decrease in the paired pulse ratio at synapses in Slack deleted neurons compared to wildtype, indicating increased presynaptic release from primary afferents. Corroborating these data, plantar test showed Slack knockout mice have an enhanced nociceptive responsiveness to localized thermal stimuli compared to wildtype mice. Our findings suggest that Slack channels regulate synaptic transmission within the spinal cord dorsal horn and by doing so establishes the threshold for thermal nociception.

Computational study of a calcium release-activated calcium channel

NASA Astrophysics Data System (ADS)

Talukdar, Keka; Shantappa, Anil

2016-05-01

The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

How do children with a chronic or long-term illness perceive their school re-entry after a period of homebound instruction?

PubMed

Boonen, H; Petry, K

2012-07-01

A considerable number of children are confronted with a chronic or long-term illness in their lives. For these children, absenteeism is problematic, because education plays a major role in stimulating their cognitive development and in promoting a sense of normalcy and psychosocial well-being. In the literature, a great deal of attention has been paid to school reintegration programmes, which try to counter the barriers that these children may face when they return to school. Another way of surmounting these barriers is through the use of homebound instruction, in which the educational process for the child is continued during the period of absence. Despite the growing awareness of the necessity of education for these children, there is still little empirical research available addressing programmes that facilitate school re-entry. The major goal of this study is to investigate how parents and their children with a chronic or long-term illness perceive school re-entry after a period of homebound instruction, by using a descriptive-explorative, multi-informant research design. Participants were 60 children and their parents who filled in a self-constructed questionnaire. Both parents and children perceived the period of homebound instruction, as well as their school re-entry, predominantly positively. Most of the children stated that they had been able to keep up with their subjects, and that they had good contact with their peers when they returned to school. According to parents, homebound instruction made a positive contribution to the school re-entry of their child. The current study is one of the first to explore the school re-entry of children with a chronic or long-term illness. According to both parents and children, the school re-entry process passed off positively. However, more research is needed with regard to the quality of education and the programmes aimed at facilitating school re-entry. © 2011 Blackwell Publishing Ltd.

Re-refinement from deposited X-ray data can deliver improved models for most PDB entries

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

Joosten, Robbie P.; Womack, Thomas; Vriend, Gert, E-mail: vriend@cmbi.ru.nl

2009-02-01

An evaluation of validation and real-space intervention possibilities for improving existing automated (re-)refinement methods. The deposition of X-ray data along with the customary structural models defining PDB entries makes it possible to apply large-scale re-refinement protocols to these entries, thus giving users the benefit of improvements in X-ray methods that have occurred since the structure was deposited. Automated gradient refinement is an effective method to achieve this goal, but real-space intervention is most often required in order to adequately address problems detected by structure-validation software. In order to improve the existing protocol, automated re-refinement was combined with structure validation andmore » difference-density peak analysis to produce a catalogue of problems in PDB entries that are amenable to automatic correction. It is shown that re-refinement can be effective in producing improvements, which are often associated with the systematic use of the TLS parameterization of B factors, even for relatively new and high-resolution PDB entries, while the accompanying manual or semi-manual map analysis and fitting steps show good prospects for eventual automation. It is proposed that the potential for simultaneous improvements in methods and in re-refinement results be further encouraged by broadening the scope of depositions to include refinement metadata and ultimately primary rather than reduced X-ray data.« less

A questionnaire survey of second year graduate-entry medical students' perception of obstetrics and gynaecology as a future career speciality.

PubMed

Ismail, Sharif I M F; Kevelighan, Euan H

2018-02-12

The aim of this study was to explore the impressions of second year graduate-entry medical students of Obstetrics and Gynaecology, before their attachment in the speciality in the subsequent year, so as to improve its appeal to them and increase their recruitment into it. A total of 74 questionnaires were distributed at the end of the Learning Opportunities in Clinical Setting (LOCS) week in the speciality and 66 (89.19%) completed questionnaires were returned. Over 4% of the respondents were considering the speciality as their career choice and less than half would consider it as a second option. Whilst more than a third perceived some of the demerits of the speciality, more than a third endorsed its merits. This showed the need to explore and address their concerns about training and working in the speciality. Having a health-related primary degree, prior employment and being female were significantly associated with choosing the speciality as a career (p < .001). Barriers for male respondents were flagged, which need to be addressed, and a bias towards Obstetrics was noted, which reflects the narrow focus on the Labour Ward and necessitates a broader exposure to the speciality. Impact statement What is already known on this subject? The perception of third year graduate-entry medical students of Obstetrics and Gynaecology is biased towards Obstetrics, and they have apprehensions about the challenges of training and working in the speciality. What do the results of this study add? The views of second year graduate-entry medical students are consistent with the views of third year graduate-entry medical students, which shows that these views may be formed early. What are the implications of these findings for clinical practice and/or further research? More research is needed to establish and understand the perception of the speciality earlier than second year and explore the value of practical steps that may improve this perception and increase the interest in it and recruitment into its training programmes.

HERA: an atmospheric probe to unveil the depths of Saturn

NASA Astrophysics Data System (ADS)

Mousis, Olivier; Atkinson, David H.; Amato, Michael; Aslam, Shahid; Atreya, Sushil K.; Blanc, Michel; Bolton, Scott J.; Brugger, Bastien; Calcutt, Simon; Cavalié, Thibault; Charnoz, Sébastien; Coustenis, Athena; DELEUIL, Magali; Ferri, Francesca; Fletcher, Leigh N.; Guillot, Tristan; Hartogh, Paul; Holland, Andrew; Hueso, Ricardo; Keller, Christoph; Kessler, Ernst; Lebreton, Jean-Pierre; leese, Mark; Lellouch, Emmanuel; Levacher, Patrick; Marty, Bernard; Morse, Andrew; Nixon, Conor; Reh, Kim R.; Renard, Jean-Baptiste; Sanchez-Lavega, Agustin; Schmider, François-Xavier; Sheridan, Simon; Simon, Amy A.; Snik, Frans; Spilker, Thomas R.; Stam, Daphne M.; Venkatapathy, Ethiraj; Vernazza, Pierre; Waite, J. Hunter; Wurz, Peter

2016-10-01

The Hera Saturn entry probe mission is proposed as an M-class mission led by ESA with a significant collaboration with NASA. It consists of a Saturn atmospheric probe and a Carrier-Relay spacecraft. Hera will perform in situ measurements of the chemical and isotopic compositions as well as the dynamics of Saturn's atmosphere, with the goal of improving our understanding of the origin, formation, and evolution of Saturn, the giant planets and their satellite systems, with extrapolation to extrasolar planets.The primary science objectives will be addressed by an atmospheric entry probe that would descend under parachute and carry out in situ measurements beginning in the stratosphere to help characterize the location and properties of the tropopause, and continue into the troposphere to pressures of at least 10 bars. All of the science objectives, except for the abundance of oxygen, which may be only addressed indirectly via observations of species whose abundances are tied to the abundance of water, can be achieved by reaching 10 bars. As in previous highly successful collaborative efforts between ESA and NASA, the proposed mission has a baseline concept based on a NASA-provided carrier/data relay spacecraft that would deliver the ESA-provided atmospheric probe to the desired atmospheric entry point at Saturn. ESA's proposed contribution should fit well into the M5 Cosmic Vision ESA call cost envelope.A nominal mission configuration would consist of a probe that detaches from the carrier one to several months prior to probe entry. Subsequent to probe release, the carrier trajectory would be deflected to optimize the over-flight phasing of the probe descent location for both probe data relay as well as performing carrier approach and flyby science, and would allow multiple retransmissions of the probe data for redundancy. The Saturn atmospheric entry probe would in many respects resemble the Jupiter Galileo probe. It is anticipated that the probe architecture for this mission would be battery-powered and accommodate a data relay to the carrier for data collection, storage on board the carrier/data relay, for later retransmission to Earth.

Search Complexities for HTN Planning

DTIC Science & Technology

2013-01-01

AUTHORS 7. PERFORMING ORGANIZATION NAMES AND ADDRESSES 15. SUBJECT TERMS b . ABSTRACT 2. REPORT TYPE 17. LIMITATION OF ABSTRACT 15. NUMBER OF...43 3.1 Complexity of plan-existence for propositional delete-free STRIPS and HTN planning with various restrictions ( k ...paper, we are concerned with two HTN decision problems: plan-existence, for whether a problem has any solution, and k -length-plan-existence, for whether a

Television, Dialogue Journals, and Feedback in the EFL Classroom.

ERIC Educational Resources Information Center

Ennis, Mark

1997-01-01

An approach used to teach English as a foreign language (EFL) and American culture that addresses the four language skills (listening, speaking, reading writing) in a complementary, non-contrived way is described. Classroom activities combine television viewing, discussion, writing, and reading journal entries. Students watch small segments of…

Energy Education Resources: Kindergarten through 12th Grade.

ERIC Educational Resources Information Center

Energy Information Administration (DOE), Washington, DC.

This guide is published by the National Energy Information Center (NEIC), a service of the Energy Information Administration (EIA), with the goal of providing students, educators, and other information users a list of generally available free or low-cost energy-related educational materials. Each entry includes the address, telephone number, and…

Foods from an Iowa Farm. A Resource Guide.

ERIC Educational Resources Information Center

Iowa State Dept. of Agriculture and Land Stewardship, Des Moines.

Prepared for elementary and secondary teachers, this guide provides an annotated list of 72 instructional materials for teaching about farming and the products of Iowa farms. Entries, listed under the organization that provides the materials, state type of instructional material, major topics addressed, grades for which materials are appropriate,…

Vignettes of Several Existing Resources for Improving Rural Science, Mathematics, and Technology Education.

ERIC Educational Resources Information Center

Crosby, Greg, Comp.

This directory lists 24 organizations providing educational resource materials on rural science and technology, conservation, and the environment. Each entry contains the address and phone number of the organization, name of a contact person, and brief description of programs, activities, publications, and services available. Resource materials…

Nevada Library Directory and Statistics 1996.

ERIC Educational Resources Information Center

Nevada State Library and Archives, Carson City.

This document, a directory of Nevada libraries, is divided into sections for academic and special libraries, school libraries (public and private), and public libraries. Entries for individual libraries typically list key staff, postal and electronic addresses, phone and fax numbers, and hours of operation. Lists of 1996 Nevada Library Association…

The Tree Worker's Manual.

ERIC Educational Resources Information Center

Smithyman, S. J.

This manual is designed to prepare students for entry-level positions as tree care professionals. Addressed in the individual chapters of the guide are the following topics: the tree service industry; clothing, eqiupment, and tools; tree workers; basic tree anatomy; techniques of pruning; procedures for climbing and working in the tree; aerial…

29 CFR 525.10 - Prevailing wage rates.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... Such data may be obtained by surveying comparable firms in the area that employ primarily nondisabled... services which only provide entry level wage data are not acceptable as sources for prevailing wage... with firm or other source; (2) Name, address, and phone number of firm or other source contacted; (3...

Build It and They Will Come: Addressing the Problem of Declining Entry-Level Skills.

ERIC Educational Resources Information Center

Koontz, Paul

2000-01-01

The growing gap between the skills of the work force and the technical requirements of today's jobs have reemphasized the need to transform the educational system to provide the solid academic and technical skills required by the jobs of today and tomorrow. (Author)

Buying and Selling Words: What Every Good Librarian Should Know about the Dictionary Business.

ERIC Educational Resources Information Center

Kister, Ken

1993-01-01

Discusses features to consider when selecting dictionaries. Topics addressed include the publishing industry; the dictionary market; profits from dictionaries; pricing; competitive marketing tactics, including similar titles, claims to numbers of entries and numbers of definitions, and similar physical appearance; a trademark infringement case;…

75 FR 53020 - Proposed Collection: Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... record for the tax imposed on the entry of taxable fuel into the U.S. and revises definition of ``enterer.... ADDRESSES: Direct all written comments to Gerald Shields, Internal Revenue Service, Room 6129, 1111... the administration of any internal revenue law. Generally, tax returns and tax return information are...

American Indian & Alaska Native Sources of Health Materials.

ERIC Educational Resources Information Center

Office of Minority Health (PHS/DHHS), Washington, DC.

This brief directory lists 28 agencies providing culturally sensitive printed health materials for American Indians and Alaska Natives. Each entry provides the agency's address; telephone number; fax number; and annotated titles available, with price. Many materials are free. There is also a subject index with these categories: adolescent…

Population Education Accessions List. January-April, 1999.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Bangkok (Thailand). Regional Office for Education in Asia and the Pacific.

This document features output from a computerized bibliographic database. The list categorizes entries into three parts. Part I, Population Education, consists of titles that address various aspects of population education arranged by country in the first section and general materials in the second. Part II, Knowledge Base Information, consists of…

Stories of Social Justice from Superintendents of Color: Intersections of Resistance

ERIC Educational Resources Information Center

Rosilez, Anthony John

2011-01-01

Current literature on public school superintendents of color emphasize how these leaders leverage personal characteristics of resiliency, networking, and a commitment to equity to overcome obstacles to entry and retention in the superintendency. However, this literature fails to address with detail the nature of the resistance these administrators…

Innovation with Impact: Industry-Education Partnerships in Massachusetts. Publication #15311.

ERIC Educational Resources Information Center

Freedman, Susan; Aschheim, Barbara

This document describes six industry-education partnerships in Massachusetts selected as exemplary and 14 selected as outstanding. They represent innovative and collaborative ways to address dropout prevention, at-risk and special needs students, adult literacy, basic skill development, and enrichment needs of students. Each entry provides this…

Making Economic Principles Personal: Student Journals and Reflection Papers

ERIC Educational Resources Information Center

Brewer, Stephanie M.; Jozefowicz, James J.

2006-01-01

The authors address two informal writing assignments implemented in introductory economics classes. One assignment involves students writing short reflection papers, and the other assignment involves students writing short journal entries for a designated period of time. Both assignments are designed to help students realize that economics is…

Women in Computer Sciences.

ERIC Educational Resources Information Center

Rose, Clare; Menninger, Sally Ann

The keynote address of a conference that focused on the future of women in science and engineering fields and the opportunities available to them in the computer sciences is presented. Women's education in the sciences and education and entry into the job market in these fields has steadily been increasing. Excellent employment opportunities are…

Insights into Departure Intention: A Qualitative Case Study

ERIC Educational Resources Information Center

Natoli, Riccardo; Jackling, Beverley; Siddique, Salina

2015-01-01

Efforts to address attrition rates at universities have been driven by Tinto's (1975) model of student engagement with its focus on student: (a) pre entry attributes; (b) academic engagement; and (c) social engagement. Using an ethnographic approach, the study involves interviews with business students to explore the links between these aspects…

Semantic and Phonological Ability to Adjust Recoding: A Unique Correlate of Word Reading Skill?

ERIC Educational Resources Information Center

Kearns, Devin M.; Rogers, H. Jane; Koriakin, Taylor; Al Ghanem, Reem

2016-01-01

This study addresses whether reading involves a process termed semantic and phonological ability to adjust recoding (SPAAR). It was hypothesized that SPAAR helps readers link inaccurate pronunciations to lexical entries (e.g., "spynitch" to "spinach"). Psychometric properties of the Mispronunciation Correction Task (MCT), a…

48 CFR 53.104 - Overprinting.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND FORMS FORMS General 53.104 Overprinting. Standard and optional forms (obtained as required by 53.107) may be overprinted with names, addresses, and other uniform entries that are consistent with the purpose of the form and that do not alter the form in any way. Exception approval for overprinting is not...

Analysis of bluetooth and wi-fi technology to measure wait times of personal vehicles at Arizona-Mexico ports of entry.

DOT National Transportation Integrated Search

2015-11-01

Robust travel time data collection is possible using Bluetooth or Wi-Fi technology that : matches anonymous MAC addresses from discoverable electronic devices (e.g., smart phones) : to determine travel time along a roadway segment. Several hundred...

Machine Operator Training Program and Curriculum.

ERIC Educational Resources Information Center

St. Cyr, David; And Others

This curriculum contains materials for use in duplicating the 11-week course for machine operators that was implemented at New Hampshire Vocational-Technical College in Nashua, New Hampshire. Addressed in the course, which is designed to prepare entry-level employees, are the following topics: basic math, blueprint reading, layout tools and…

Curriculum Model for Optometry: Outcomes of the Process.

ERIC Educational Resources Information Center

Berman, Morris S.

1994-01-01

A national conference of colleges of optometry focused on planning for optometric curricular reform and faculty development. Issues addressed included changes needed to meet entry-level professional needs, available resources, changes in optometry practice, and optometry's role in health care reform. Task forces worked together to develop a…

Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells.

PubMed

Ruud, Johan; Wilhelms, Daniel Björk; Nilsson, Anna; Eskilsson, Anna; Tang, Yan-Juan; Ströhle, Peter; Caesar, Robert; Schwaninger, Markus; Wunderlich, Thomas; Bäckhed, Fredrik; Engblom, David; Blomqvist, Anders

2013-05-01

Loss of appetite is a hallmark of inflammatory diseases. The underlying mechanisms remain undefined, but it is known that myeloid differentiation primary response gene 88 (MyD88), an adaptor protein critical for Toll-like and IL-1 receptor family signaling, is involved. Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions. We found that MyD88-knockout mice, which are resistant to bacterial lipopolysaccharide (LPS)-induced anorexia, displayed anorexia when transplanted with wild-type bone marrow cells. Furthermore, mice with a targeted deletion of MyD88 in hematopoietic or myeloid cells were largely protected against LPS-induced anorexia and displayed attenuated weight loss, whereas mice with MyD88 deletion in hepatocytes or in neural cells or the cerebrovascular endothelium developed anorexia and weight loss of similar magnitude as wild-type mice. Furthermore, in a model for cancer-induced anorexia-cachexia, deletion of MyD88 in hematopoietic cells attenuated the anorexia and protected against body weight loss. These findings demonstrate that MyD88-dependent signaling within the brain is not required for eliciting inflammation-induced anorexia. Instead, we identify MyD88 signaling in hematopoietic/myeloid cells as a critical component for acute inflammatory-driven anorexia, as well as for chronic anorexia and weight loss associated with malignant disease.

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry

PubMed Central

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-01-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1CreERT2/+ mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms’ tumor 1 (Wt1) gene expression. We visualized WT1+ mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin+ fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific. PMID:24130328

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry.

PubMed

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-11-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1(CreERT2/+) mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms' tumor 1 (Wt1) gene expression. We visualized WT1(+) mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin(+) fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific.

Entry, Descent, and Landing with Propulsive Deceleration: Supersonic Retropropulsion Wind Tunnel Testing and Shock Phenomena

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan

2014-01-01

The future exploration of the Solar System will require innovations in transportation and the use of entry, descent, and landing (EDL) systems at many planetary landing sites. The cost of space missions has always been prohibitive, and using the natural planetary and planet's moon atmospheres for entry, and descent can reduce the cost, mass, and complexity of these missions. This paper will describe some of the EDL ideas for planetary entry and survey the overall technologies for EDL that may be attractive for future Solar System missions. Future EDL systems may include an inflatable decelerator for the initial atmospheric entry and an additional supersonic retropropulsion (SRP) rocket system for the final soft landing. A three engine retropropulsion configuration with a 2.5 in. diameter sphere-cone aeroshell model was tested in the NASA Glenn Research Center's 1- by 1-ft (1×1) Supersonic Wind Tunnel (SWT). The testing was conducted to identify potential blockage issues in the tunnel, and visualize the rocket flow and shock interactions during supersonic and hypersonic entry conditions. Earlier experimental testing of a 70deg Viking-like (sphere-cone) aeroshell was conducted as a baseline for testing of a SRP system. This baseline testing defined the flow field around the aeroshell and from this comparative baseline data, retropropulsion options will be assessed. Images and analyses from the SWT testing with 300- and 500-psia rocket engine chamber pressures are presented here. In addition, special topics of electromagnetic interference with retropropulsion induced shock waves and retropropulsion for Earth launched booster recovery are also addressed.

Entry, Descent, and Landing with Propulsive Deceleration: Supersonic Retropropulsion Wind Tunnel Testing and Shock Phenomena

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan

2013-01-01

The future exploration of the Solar System will require innovations in transportation and the use of entry, descent, and landing (EDL) systems at many planetary landing sites. The cost of space missions has always been prohibitive, and using the natural planetary and planet's moon atmospheres for entry, and descent can reduce the cost, mass, and complexity of these missions. This paper will describe some of the EDL ideas for planetary entry and survey the overall technologies for EDL that may be attractive for future Solar System missions. Future EDL systems may include an inflatable decelerator for the initial atmospheric entry and an additional supersonic retro-propulsion (SRP) rocket system for the final soft landing. A three engine retro-propulsion configuration with a 2.5 inch diameter sphere-cone aeroshell model was tested in the NASA Glenn 1x1 Supersonic Wind Tunnel (SWT). The testing was conducted to identify potential blockage issues in the tunnel, and visualize the rocket flow and shock interactions during supersonic and hypersonic entry conditions. Earlier experimental testing of a 70 degree Viking-like (sphere-cone) aeroshell was conducted as a baseline for testing of a supersonic retro-propulsion system. This baseline testing defined the flow field around the aeroshell and from this comparative baseline data, retro-propulsion options will be assessed. Images and analyses from the SWT testing with 300- and 500-psia rocket engine chamber pressures are presented here. In addition, special topics of electromagnetic interference with retro-propulsion induced shock waves and retro-propulsion for Earth launched booster recovery are also addressed.

Pathways to the PhD in Nursing: An Analysis of Similarities and Differences.

PubMed

Nehls, Nadine; Barber, Gale; Rice, Elizabeth

2016-01-01

New educational pathways are needed to increase the number of doctor of philosophy (PhD)-prepared nurses. To address this need, an early-entry PhD option designed to engage students in PhD coursework and research during the undergraduate nursing major was developed at the University of Wisconsin-Madison. An evaluation comparing the early-entry option with two more conventional entry points was conducted. Three groups (N = 84) comprised the sample: (a) early-entry students admitted as undergraduates or immediately upon graduation (N = 29), (b) mid-entry students with baccalaureate degrees and at least 1 year of work experience (N = 27), and (c) delayed-entry students with master's degrees and 1 or more years of work experience (N = 28). Qualitative and quantitative data were collected from the 3 groups of students who were admitted from 2002 to 2011. The sources of data were transcriptions of individual interviews and reviews of existing data. Seventy-seven percent of the sample participated in the individual interviews. The database review included all students who matriculated into the PhD program. Common themes among the 3 groups included a need for educational funding, the importance of a faculty mentor, and concern about preparation for the teaching role and the academic work environment. The groups were also comparable in terms of research productivity during doctoral study and postgraduation employment. Differences were found on measures of diversity, program progression, and perceptions of clinical competence. The findings provide needed data for the development and expansion of educational pathways to the PhD in nursing. Copyright © 2016 Elsevier Inc. All rights reserved.

Range Sensor-Based Efficient Obstacle Avoidance through Selective Decision-Making.

PubMed

Shim, Youngbo; Kim, Gon-Woo

2018-03-29

In this paper, we address a collision avoidance method for mobile robots. Many conventional obstacle avoidance methods have been focused solely on avoiding obstacles. However, this can cause instability when passing through a narrow passage, and can also generate zig-zag motions. We define two strategies for obstacle avoidance, known as Entry mode and Bypass mode. Entry mode is a pattern for passing through the gap between obstacles, while Bypass mode is a pattern for making a detour around obstacles safely. With these two modes, we propose an efficient obstacle avoidance method based on the Expanded Guide Circle (EGC) method with selective decision-making. The simulation and experiment results show the validity of the proposed method.

Spatial harmonics and pattern specification in early Drosophila development. Part II. The four colour wheels model.

PubMed

Kauffman, S A; Goodwin, B C

1990-06-07

We review the evidence presented in Part I showing that transcripts and protein products of maternal, gap, pair-rule, and segment polarity genes exhibit increasingly complex, multipeaked longitudinal waveforms in the early Drosophila embryo. The central problem we address in Part II is the use the embryo makes of these wave forms to specify longitudinal pattern. Based on the fact that mutants of many of these genes generate deletions and mirror symmetrical duplications of pattern elements on length scales ranging from about half the egg to within segments, we propose that position is specified by measuring a "phase angle" by use of the ratios of two or more variables. Pictorially, such a phase angle can be thought of as a colour on a colour wheel. Any such model contains a phaseless singularity where all or many phases, or colours, come together. We suppose as well that positional values sufficiently close to the singularity are meaningless, hence a "dead zone". Duplications and deletions are accounted for by deformation of the cycle of morphogen values occurring along the antero-posterior axis. If the cycle of values surrounds the singularity and lies outside the dead zone, pattern is normal. If the curve transects the dead zone, pattern elements are deleted. If the curve lies entirely on one side of the singularity, pattern elements are deleted and others are duplicated with mirror symmetry. The existence of different wavelength transcript patterns in maternal, gap, pair-rule, and segment polarity genes and the roles of those same genes in generating deletions and mirror symmetrical duplications on a variety of length scales lead us to propose that position is measured simultaneously on at least four colour wheels, which cycle different numbers of times along the anterior-posterior axis. These yield progressively finer grained positional information. Normal pattern specification requires a unique angle, outside of the dead zone, from each of the four wheels. Deformations of the cycle of gene product concentrations yield the deletions and mirror symmetric duplications observed in the mutants discussed. The alternative familiar hypothesis that longitudinal position is specified in an "on" "off" combinatorial code does not readily account for the duplication deletion phenomena.

Store-operated Ca2+ entry controls ameloblast cell function and enamel development

PubMed Central

Eckstein, Miriam; Vaeth, Martin; Fornai, Cinzia; Vinu, Manikandan; Bromage, Timothy G.; Nurbaeva, Meerim K.; Sorge, Jessica L.; Coelho, Paulo G.; Idaghdour, Youssef; Feske, Stefan; Lacruz, Rodrigo S.

2017-01-01

Loss-of-function mutations in stromal interaction molecule 1 (STIM1) impair the activation of Ca2+ release–activated Ca2+ (CRAC) channels and store-operated Ca2+ entry (SOCE), resulting in a disease syndrome called CRAC channelopathy that is characterized by severe dental enamel defects. The cause of these enamel defects has remained unclear given a lack of animal models. We generated Stim1/2K14cre mice to delete STIM1 and its homolog STIM2 in enamel cells. These mice showed impaired SOCE in enamel cells. Enamel in Stim1/2K14cre mice was hypomineralized with decreased Ca content, mechanically weak, and thinner. The morphology of SOCE-deficient ameloblasts was altered, showing loss of the typical ruffled border, resulting in mislocalized mitochondria. Global gene expression analysis of SOCE-deficient ameloblasts revealed strong dysregulation of several pathways. ER stress genes associated with the unfolded protein response were increased in Stim1/2-deficient cells, whereas the expression of components of the glutathione system were decreased. Consistent with increased oxidative stress, we found increased ROS production, decreased mitochondrial function, and abnormal mitochondrial morphology in ameloblasts of Stim1/2K14cre mice. Collectively, these data show that loss of SOCE in enamel cells has substantial detrimental effects on gene expression, cell function, and the mineralization of dental enamel. PMID:28352661

The human insulin receptor mRNA contains a functional internal ribosome entry segment

PubMed Central

Spriggs, Keith A.; Cobbold, Laura C.; Ridley, Simon H.; Coldwell, Mark; Bottley, Andrew; Bushell, Martin; Willis, Anne E.; Siddle, Kenneth

2009-01-01

Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capable of independent regulation. Here, we show by using dicistronic luciferase reporter vectors that the 5′-UTR of the mRNA encoding human insulin receptor (hIR) contains a functional IRES. RNAi-mediated knockdown showed that the protein PTB was required for maximum IRES activity. Electrophoretic mobility shift assays confirmed that PTB1, PTB2 and nPTB, but not unr or PTB4, bound to hIR mRNA, and deletion mapping implicated a CCU motif 448 nt upstream of the initiator AUG in PTB binding. The IR-IRES was functional in a number of cell lines, and most active in cells of neuronal origin, as assessed by luciferase reporter assays. The IRES was more active in confluent than sub-confluent cells, but activity did not change during differentiation of 3T3-L1 fibroblasts to adipocytes. IRES activity was stimulated by insulin in sub-confluent cells. The IRES may function to maintain expression of IR protein in tissues such as the brain where mRNA translation by cap-dependent scanning is less effective. PMID:19654240

Laminin-411 Is a Vascular Ligand for MCAM and Facilitates TH17 Cell Entry into the CNS

PubMed Central

Flanagan, Ken; Fitzgerald, Kent; Baker, Jeanne; Regnstrom, Karin; Gardai, Shyra; Bard, Frederique; Mocci, Simonetta; Seto, Pui; You, Monica; Larochelle, Catherine; Prat, Alexandre; Chow, Samuel; Li, Lauri; Vandevert, Chris; Zago, Wagner; Lorenzana, Carlos; Nishioka, Christopher; Hoffman, Jennifer; Botelho, Raquel; Willits, Christopher; Tanaka, Kevin; Johnston, Jennifer; Yednock, Ted

2012-01-01

TH17 cells enter tissues to facilitate pathogenic autoimmune responses, including multiple sclerosis (MS). However, the adhesion molecules involved in the unique migratory capacity of TH17 cells, into both inflamed and uninflamed tissues remain unclear. Herein, we characterize MCAM (CD146) as an adhesion molecule that defines human TH17 cells in the circulation; following in vitro restimulation of human memory T cells, nearly all of the capacity to secrete IL-17 is contained within the population of cells expressing MCAM. Furthermore, we identify the MCAM ligand as laminin 411, an isoform of laminin expressed within the vascular endothelial basement membranes under inflammatory as well as homeotstatic conditions. Purified MCAM-Fc binds to laminin 411 with an affinity of 27 nM, and recognizes vascular basement membranes in mouse and human tissue. MCAM-Fc binding was undetectable in tissue from mice with targeted deletion of laminin 411, indicating that laminin 411 is a major tissue ligand for MCAM. An anti-MCAM monoclonal antibody, selected for inhibition of laminin binding, as well as soluble MCAM-Fc, inhibited T cell adhesion to laminin 411 in vitro. When administered in vivo, the antibody reduced TH17 cell infiltration into the CNS and ameliorated disease in an animal model of MS. Our data suggest that MCAM and laminin 411 interact to facilitate TH17 cell entry into tissues and promote inflammation. PMID:22792325

Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs.

PubMed

Risal, Sanjiv; Adhikari, Deepak; Liu, Kui

2016-01-01

Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

Bibliographic Resources for the Historian of Astronomy

NASA Astrophysics Data System (ADS)

Corbin, B. G.

1999-12-01

Many large library collections now have online bibliographic catalogs on the web. These provide many hidden resources for the historian of astronomy. Special searching techniques will allow the historian to scan bibliographic records of hundreds of entries relating to biographies of astronomers, collected works of astronomers, ancient and medieval astronomy and many other historical subjects. Abstract databases such as the Astrophysics Data System and ARIBIB are also adding much historical bibliographic information. ARIBIB will eventually contain scanned images of the Astronomischer Jahresbericht containing bibliographic entries for all literature of astronomy from 1899 to 1968 and Astronomy and Astrophysics Abstracts from 1969 to present. Commercial services such as UnCover and FirstSearch provide a means of reaching bibliographic entries for journal and book literature in the history of astronomy which were not easily located in the past. A broad overview of these collections and services will be given, and searching techniques for finding ``hidden" bibliographic data will be presented. Web page addresses will be given for all sources covered.

Public university entry in Ghana: Is it equitable?

NASA Astrophysics Data System (ADS)

Yusif, Hadrat; Yussof, Ishak; Osman, Zulkifly

2013-06-01

Public universities in Ghana are highly subsidised by the central government and account for about 80 per cent of university students in the country. Yet issues of fairness in terms of entry into the public university system have so far hardly been addressed. To find out whether participation in public university education is equitable, the authors of this paper carried out a binary logistic regression analysis. Individual data were collected from 1,129 (614 male and 515 female) final year senior high school (SHS) students for the 2009 cohort. The authors measured student, father and mother characteristics likely to influence admission to a public university. The results show that the major predictors of public university entry are students' academic ability, quality of SHS attended and number of siblings. This seems to suggest that there is a significant bias in the selection of students from different socio-economic groups for admission to highly subsidised public universities. The implication is that public financing of university education in Ghana may not be equitable.

Analysis of the obstacles related to treatment entry, adherence and drop-out among alcoholic patients.

PubMed

Fonsi Elbreder, Márcia; Carvalho De Humerez, Dorisdaia; Laranjeira, Ronaldo

2009-01-01

Alcoholism is a complex syndrome involving social, psychological and individual factors in addition to a series of obstacles regarding treatment entry, adherence, and drop-out. These obstacles contribute negatively to both clinical evolution and prognosis of the patients, affecting their quality of life and raising the social costs. This is a bibliographical study in which we address this theme as well as other experiences observed in our daily practice in the Alcohol and Drug Research Unit (UNIAD) based at the Federal University of São Paulo (UNIFESP). The analysis of the obstacles related to treatment entry, attendance, and drop-out among alcoholic patients shows that systemic, social, cultural, and individual factors are all involved, including the structural ones. Women have more obstacles compared to men, and what is thought to be a barrier to one patient may be a factor motivating another patient to search for help. We conclude that several factors at different levels exist that prevent the patient from overcoming these treatment obstacles.

Treatment process in prison therapeutic communities: motivation, participation, and outcome.

PubMed

Melnick, G; De Leon, G; Thomas, G; Kressel, D; Wexler, H K

2001-11-01

Although the largest effects of prison-based therapeutic community (TC) programs are associated with entry into aftercare, only a minority of prisoners volunteer for these aftercare programs. The study addresses the gap in our knowledge concerning these low rates of voluntary entry. A theoretical formulation of the TC process involving the effect of the interaction of clients' motivation and participation in the activities of the TC on entry into aftercare was tested on a sample of 110 volunteers in a prison-based TC for whom there were client and staff ratings of 3-month participation and 12-month follow-up data on relapse and recidivism. Path analyses support a model in which the interaction of motivation and 3-month participation ratings have a direct effect on the selection of aftercare, and aftercare has a direct effect on relapse and recidivism. The use of a combination of enhanced motivation and early program participation as a means of increasing the utilization and effectiveness of aftercare is discussed.

Crystal Structure of Full-length Mycobacterium tuberculosis H37Rv Glycogen Branching Enzyme; Insights of N-Terminal [beta]-Sandwich in Sustrate Specifity and Enzymatic Activity

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

Pal, Kuntal; Kumar, Shiva; Sharma, Shikha

2010-07-13

The open reading frame Rv1326c of Mycobacterium tuberculosis (Mtb) H37Rv encodes for an {alpha}-1,4-glucan branching enzyme (MtbGlgB, EC 2.4.1.18, Uniprot entry Q10625). This enzyme belongs to glycoside hydrolase (GH) family 13 and catalyzes the branching of a linear glucose chain during glycogenesis by cleaving a 1 {yields} 4 bond and making a new 1 {yields} 6 bond. Here, we show the crystal structure of full-length MtbGlgB (MtbGlgBWT) at 2.33-{angstrom} resolution. MtbGlgBWT contains four domains: N1 {beta}-sandwich, N2 {beta}-sandwich, a central ({beta}/{alpha}){sub 8} domain that houses the catalytic site, and a C-terminal {beta}-sandwich. We have assayed the amylase activity with amylosemore » and starch as substrates and the glycogen branching activity using amylose as a substrate for MtbGlgBWT and the N1 domain-deleted (the first 108 residues deleted) Mtb{Delta}108GlgB protein. The N1 {beta}-sandwich, which is formed by the first 105 amino acids and superimposes well with the N2 {beta}-sandwich, is shown to have an influence in substrate binding in the amylase assay. Also, we have checked and shown that several GH13 family inhibitors are ineffective against MtbGlgBWT and Mtb{Delta}108GlgB. We propose a two-step reaction mechanism, for the amylase activity (1 {yields} 4 bond breakage) and isomerization (1 {yields} 6 bond formation), which occurs in the same catalytic pocket. The structural and functional properties of MtbGlgB and Mtb{Delta}108GlgB are compared with those of the N-terminal 112-amino acid-deleted Escherichia coli GlgB (EC{Delta}112GlgB).« less

Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors

PubMed Central

Liu, Jing; Guo, Ming

2016-01-01

Background: Leptin, an adipose-derived hormone, has been implicated in emotional regulation. We have previously shown that systemic administration of leptin produces anxiolytic-like effects and deletion of the leptin receptor, LepRb, in midbrain dopamine neurons leads to an anxiogenic phenotype. This study investigated whether activation or deletion of LepRb in the ventral tegmental area of adult mice is capable of inducing anxiolytic and anxiogenic effects, respectively. Methods: Mice were cannulated in the ventral tegmental area and received bilateral intra-ventral tegmental area infusions of leptin or the JAK2/STAT3 inhibitor AG490. Anxiety-like behaviors were assessed using the elevated plus-maze, light-dark box, and novelty suppressed feeding tests. Deletion of LepRb in the ventral tegmental area was achieved by bilateral injection of AAV-Cre into the ventral tegmental area of adult Leprflox/flox mice. Anxiety-related behaviors were evaluated 3 weeks after viral injection. Results: Intra-ventral tegmental area infusions of leptin reduced anxiety-like behaviors, as indicated by increased percent open-arm time and open-arm entries in the elevated plus-maze test, increased time spent in the light side and decreased latency to enter the light side of the light-dark box, and decreased latency to feed in the novelty suppressed feeding test. Blockade of JAK2/STAT3 signaling in the ventral tegmental area by AG490 attenuated the anxiolytic effect produced by systemic administration of leptin. Leprflox/flox mice injected with AAV-Cre into the ventral tegmental area showed decreased leptin-induced STAT3 phosphorylation and enhanced anxiety-like behaviors in the elevated plus-maze test and the novelty suppressed feeding test. Conclusions: These findings suggest that leptin-LepRb signaling in the ventral tegmental area plays an important role in the regulation of anxiety-related behaviors. PMID:26438799

SOFIA: A Stratospheric Observatory for Infrared Astronomy

NASA Technical Reports Server (NTRS)

Erickson, E. F.; Davidson, J. A.; Thorley, G.; Caroff, L. J.

1991-01-01

SOFIA is described as it was originally (May 1988) for the Space and Earth Sciences Advisory Committee (SESAC). The format and questions were provided by SESAC as a standard for judging the merit of potential U.S. space science projects. This version deletes Section IIF, which addressed development costs of the SOFIA facility. SOFIA's unique astronomical potential is described and it is shown how it complements and supports existing and planned facilities.

Allied Health Occupations I (Health Assistant). Middletown Public Schools Curriculum Standards.

ERIC Educational Resources Information Center

Middletown Public Schools, CT.

This volume outlines the requirements and content of a first-year course in allied health occupations education that is intended to prepare students for entry-level employment in such allied health occupations as nurse's aide and health assistant. Addressed in the individual units of the course are the following topics: health worker…

77 FR 25055 - Addition of Certain Persons to the Entity List

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

... under the countries of Afghanistan, Pakistan and the United Arab Emirates (U.A.E.). The Entity List... Entity List consist of twelve entries in Afghanistan, three in Pakistan, and three in the U.A.E. Two of...; and --Haji Khalil. Shahreno, Kabul, Afghanistan (See alternate address in Pakistan); (4) Heim German...

A Short Course in Family Therapy: Translating Research Into Practice

ERIC Educational Resources Information Center

Williams, Robert

2005-01-01

This article outlines a graduate-level, one-time-only family therapy course that prepares counseling trainees to be competent at entry-level family therapy in the United States. The approach outlined addresses the training concerns of programs that significantly emphasize individual-focused paradigms and that have limited time to train counseling…

Pavement, bridge, and safety cost evaluation tool for overweight truck corridors serving coastal port regions and border ports of entry

DOT National Transportation Integrated Search

2017-08-01

To address the need for a rational but fast method to determine costs and a proposed permit fee, the research team developed the Stage 1 Expedient Analysis Method. The method was used to evaluate potential oversize/overweight (OS/OW) freight corridor...

Agricultural Safety and Health: A Resource Guide. Rural Information Center Publication Series, No. 40. Revised Edition.

ERIC Educational Resources Information Center

Zimmerman, Joy, Comp.

This guide lists resource materials that address agricultural occupational injuries and diseases and their prevention. Many of the entries were derived from the AGRICOLA database produced by the National Agricultural Library and include journal articles, books, government reports, training materials, and audiovisual materials. The first section…

Using Microcomputers Simulations in the Classroom: Examples from Undergraduate and Faculty Computer Literacy Courses.

ERIC Educational Resources Information Center

Hart, Jeffrey A.

1985-01-01

Presents a discussion of how computer simulations are used in two undergraduate social science courses and a faculty computer literacy course on simulations and artificial intelligence. Includes a list of 60 simulations for use on mainframes and microcomputers. Entries include type of hardware required, publisher's address, and cost. Sample…

The Intermingled History of Occupational Therapy and Anatomical Education: A Retrospective Exploration

ERIC Educational Resources Information Center

Carroll, Melissa A.; Lawson, Katherine

2014-01-01

Few research articles have addressed the anatomical needs of entry-level occupational therapy students. Given this paucity of empirical evidence, there is a lack of knowledge regarding anatomical education in occupational therapy. This article will primarily serve as a retrospective look at the inclusion of anatomical education in the occupational…

Energy Education Resources: Kindergarten through 12th Grade. [Revised.

ERIC Educational Resources Information Center

Energy Information Administration (DOE), Washington, DC.

This publication is the result of a study undertaken by the National Energy Information Center (NEIC) to provide its customers with a list of generally free or low-cost energy-related educational materials available for students and educators. Each entry includes the address, telephone number, and description of the organization and the…

Marching to a Different Beat: A Bibliography of Materials about Children at Risk because of Disabilities and/or Abilities.

ERIC Educational Resources Information Center

Buckingham, Betty Jo

This annotated bibliography covers materials about children at risk because of disabilities and/or abilities. The bibliography includes approximately 560 entries. The following categories are addressed: autism; gifted; handicapped--general and multiple; hearing impaired/deaf; learning disabilities; mental illness; mentally handicapped/brain…

Maneuver Analysis and Targeting Strategy for the Stardust Re-Entry Capsule

NASA Technical Reports Server (NTRS)

Helfrich, Clifford E.; Bhat, Ram; Kangas, Julie; Wilson, Roby; Wong, Mau; Potts, Chris; Williams, Ken

2006-01-01

Stardust employed biased maneuvers to limit turns and minimize execution errors. Biased maneuvers also addressed planetary protection and safety issues. Stardust utilized a fixed-direction burn for the final maneuver to match the prevailing attitude so no turns were needed. Performance of the final burn was calibrated in flight.

76 FR 14038 - TWIC/MTSA Policy Advisory Council; Voluntary Use of TWIC Readers

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... and would like to know that they reached the Facility, please enclose a stamped, self-addressed... regulatory requirements for effective (1) identity verification, (2) card validity, and (3) card... access is granted. 33 CFR 101.514. At each entry, the TWIC must be checked for (1) identity verification...

Private Security Contractors: The Other Force

DTIC Science & Technology

2011-03-22

improving PSC oversight. This paper will not address private contractors conducting Police force training , governmental use of PSCs outside of Iraq...theater entry requirements, conduct mandatory training , conduct weapons training and qualification and conduct security verification and criminal...an effective oversight program including contractor deployment tracking, limited contract oversight personnel, and untrained Contract Officer

75 FR 25882 - Notice of Proposed Withdrawal Extension and Opportunity for Public Meeting; Arizona

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... National Forest System land from the mining laws for use as a base camp site for the Smithsonian..., 2010. ADDRESSES: Comments and meeting request should be sent to the Coronado National Forest Office... acres of National Forest System land located in Santa Cruz County, Arizona, from location and entry...

Pennsylvania's Energy Curriculum for the Secondary Grades: Industrial Arts.

ERIC Educational Resources Information Center

Wighaman, Paul F.; Zimmerman, Earl R.

Compiled in this guide are 23 previously published documents for use by secondary school industrial arts teachers who want to incorporate energy studies into their curricula. Over half of the entries describe energy-related projects such as fireplaces, solar water heaters, and solar ovens. Other materials presented address the place of energy in…

Advanced Entry Adult Apprenticeship Training Scheme: A Case Study

ERIC Educational Resources Information Center

Sparks, Alan; Ingram, Hadyn; Phillips, Sunny

2009-01-01

Purpose: The purpose of this paper is to evaluate an innovative way to train adult apprentices for the construction industry. Design/methodology/approach: The paper emphasizes that, in order to address skills shortages for international construction, training methods must be improved. It looks at the example of an adult apprenticeship scheme in…

Barriers to Successful Treatment Completion in Child Sexual Abuse Survivors

ERIC Educational Resources Information Center

McPherson, Paul; Scribano, Philip; Stevens, Jack

2012-01-01

Child sexual abuse (CSA) often requires psychological treatment to address the symptoms of victim trauma. Barriers to entry and completion of counseling services can compromise long-term well-being. An integrated medical and mental health evaluation and treatment model of a child advocacy center (CAC) has the potential to reduce barriers to mental…

Connecticut E.S.E.A. Title III Catalog.

ERIC Educational Resources Information Center

Area Cooperative Educational Services, New Haven, CT. Educational Resources Center.

Title III projects conducted by local education agencies in Connecticut are listed alphabetically by agency and described. Each entry gives project title, amount and term of funding, target population, major objectives, evaluation design, findings to date, and dissemination plan. The agency name and address and the project director for each of the…

Youth, Education and Work. World Yearbook of Education 1995.

ERIC Educational Resources Information Center

Bash, Leslie, Ed.; Green, Andy, Ed.

This book addresses themes related to the transition from childhood to adulthood. Entry into employment and other areas of social life that are symbolic of maturity and the attainment of full citizenship differs from society to society and is contingent upon appropriate political and economic factors. The volume draws upon a diversity of…

Mechanisms of Masked Priming: Testing the Entry Opening Model

ERIC Educational Resources Information Center

Wu, Hongmei

2012-01-01

Since it was introduced in Forster and Davis (1984), masked priming has been widely adopted in the psycholinguistic research on visual word recognition, but there has been little consensus on its actual mechanisms, i.e. how it occurs and how it should be interpreted. This dissertation addresses two different interpretations of masked priming, one…

From Crayons to Perfume: Getting beyond Contrived Collegiality

ERIC Educational Resources Information Center

Beatty, Brenda

2011-01-01

Based on reflections from over a decade of research, scholarship, and programmatic applications, this article provides evidence of impact from the work of Professor Andy Hargreaves with a specific focus on his concept of contrived collegiality. Explorations into matters of emotion provided an entry point through which the author has addressed the…

What Predicts Health Students' Self-Reported Preparedness to Work in Indigenous Health Settings?

ERIC Educational Resources Information Center

Bullen, Jonathan; Roberts, Lynne; Hoffman, Julie

2017-01-01

Australian undergraduate programs are implementing curriculum aimed at better preparing graduates to work in culturally diverse settings, but there remains uncertainty over the role of extant student attitudes towards Indigenous Australians. To begin to address this, we obtained baseline data on student attitudes upon entry to tertiary education.…

University Reaches Out--Programs Bring Education to Communities.

ERIC Educational Resources Information Center

Grant, Agnes

Brandon University's teacher education programs address the need to train Native people to teach in Indian schools. A mature entry policy allows students to enter the university without a high school diploma, provided they are at least 21 years old. Several programs lead to four-year Bachelor of Education degrees. Through the Program for Educating…

Preparing Occupational Therapy Students to Address Mental Health Promotion, Prevention, and Intervention in School-Based Practice

ERIC Educational Resources Information Center

Blackwell, Cindy DeRuiter; Bilics, Andrea

2018-01-01

Directors of entry-level occupational therapy (OT) programs were surveyed regarding how their programs prepare students to become mental health practitioners in schools. Analysis of quantitative data included descriptive statistics to examine participants' ratings of their program's ability to prepare students for mental health practice. We found…

School Counselors: Key Stakeholders Helping Underserved Students to Be Career Ready

ERIC Educational Resources Information Center

Paolini, Allison C.

2015-01-01

This paper addresses the role that school counselors play in assisting underserved students to be prepared for post-secondary enrollment and/or career entry upon high school graduation. Counselors' responsibilities are outlined, including assisting students in identifying their strengths and inner resources, in order to achieve their goals.…

77 FR 48986 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

..., and data collection was conducted for six months based upon an emergency information collection... minimize duplicate data entry and to maximize the flexibility of users. In addition, to help adjust to the new data system, weekly calls are held with issuers to address any other questions which may emerge...

ALA Fingertip Guide to National Health-Information Resources. 1995-1996 Reference Desk Edition.

ERIC Educational Resources Information Center

Kovacs, Beatrice

In response to a growing need for personal health and fitness information, this guide provides the telephone numbers and addresses of organizations serving public information interests. Features include: alphabetical entries for 404 organizations from AIDS Clinical Trials Information Service, Air Ambulance America to Visiting Nurse Association of…

NABTE Review: A Journal of the National Association for Business Teacher Education, 2002.

ERIC Educational Resources Information Center

Moore, Wayne, Ed.

2002-01-01

This issue reports research that addresses the needs and future of business education, work-based initiatives, business educators' use of the Web, and technology skills for entry-level workers. "Editorial Comment: Scholarship of the 21st Century" (Moore) provides an overview of the issue. "Quality Business Teacher Education:…

Inquiry as an Entry Point to Equity in the Classroom

ERIC Educational Resources Information Center

Tang, Gail; El Turkey, Houssein; Cilli-Turner, Emily; Savic, Milos; Karakok, Gulden; Plaxco, David

2017-01-01

Although many policy documents include equity as part of mathematics education standards and principles, researchers continue to explore means by which equity might be supported in classrooms and at the institutional level. Teaching practices that include opportunities for students to engage in active learning have been proposed to address equity.…

75 FR 10253 - Environmental Impact Statements and Regulations; Availability of EPA Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... concerns about storage, transportation and disposal of hazardous waste and radioactive wastes. EPA... wastes will need to be addressed as the project progresses. Rating EC2. EIS No. 20090378, ERP No. D-COE.... EIS No. 20100008, ERP No. D-GSA-F65079-00, International Falls Land Port of Entry Improvements Study...

A Term Project in Visual Basic: The Downhill Snowboard Shop

ERIC Educational Resources Information Center

Simkin, Mark G.

2007-01-01

Most commercial programming applications are considerably more complex than the end-of-chapter exercises found in programming textbooks. This case addresses this problem by requiring the students in entry-level Visual Basic programming classes to create an application that helps users order ski equipment from a retailer. For convenience, the forms…

Improving data collection, documentation, and workflow in a dementia screening study.

PubMed

Read, Kevin B; LaPolla, Fred Willie Zametkin; Tolea, Magdalena I; Galvin, James E; Surkis, Alisa

2017-04-01

A clinical study team performing three multicultural dementia screening studies identified the need to improve data management practices and facilitate data sharing. A collaboration was initiated with librarians as part of the National Library of Medicine (NLM) informationist supplement program. The librarians identified areas for improvement in the studies' data collection, entry, and processing workflows. The librarians' role in this project was to meet needs expressed by the study team around improving data collection and processing workflows to increase study efficiency and ensure data quality. The librarians addressed the data collection, entry, and processing weaknesses through standardizing and renaming variables, creating an electronic data capture system using REDCap, and developing well-documented, reproducible data processing workflows. NLM informationist supplements provide librarians with valuable experience in collaborating with study teams to address their data needs. For this project, the librarians gained skills in project management, REDCap, and understanding of the challenges and specifics of a clinical research study. However, the time and effort required to provide targeted and intensive support for one study team was not scalable to the library's broader user community.

Construction and characterization of poliovirus subgenomic replicons.

PubMed

Kaplan, G; Racaniello, V R

1988-05-01

Poliovirus RNAs containing in-frame deletions within the capsid-coding region were produced by in vitro transcription of altered poliovirus type 1 cDNA by using bacteriophage T7 RNA polymerase. Three RNAs were transcribed that contained deletions of 2,317 nucleotides (bases 747 to 3064), 1,781 nucleotides (bases 1,175 to 2,956), and 1,295 nucleotides (bases 1,175 to 2,470). All three subgenomic RNAs replicated after transfection into HeLa cells, demonstrating that sequences encoding the capsid polypeptides are not essential for viral RNA replication in vivo. Viral RNA containing the largest deletion (R1) replicated approximately three times better than full-length RNA produced in vitro. Northern blot (RNA blot) hybridization analysis of total cellular RNA from HeLa cells at different times after transfection with R1 demonstrated the presence of increasing amounts of the expected 5.1-kilobase subgenomic RNA. Analysis by immunoprecipitation of viral proteins induced after transfection of R1 RNA into HeLa cells revealed the presence of proteins 2Apro, 2C, and 3Dpol and its precursors, suggesting that the polyprotein cleavages are similar to those occurring in virus-infected cells. Replication of P2/Lansing virion RNA was inhibited by cotransfection with the R1 replicon, as demonstrated by hybridization analysis with a serotype-specific oligonucleotide probe. A higher level of inhibition of RNA replication was observed when P2/Lansing RNA was cotransfected into HeLa cells with truncated R1 transcripts (R1-PvuII) that were missing 395 3' nucleotides and a poly(A) tail. These internally and terminally deleted RNAs inhibited the replication of subgenomic replicons R1, R2, and R3 and caused a reduction in plaque size when cotransfected with P1/Mahoney or P2/Lansing viral RNA, suggesting that individual cells had received both RNAs. No inhibition of plaque size was observed when replicon RNAs were used that were missing 1,384 or 1,839 3' nucleotides or contained plasmid-derived sequences downstream of the 3' poly(A). The trans-acting inhibitory effect of R1-PvuII on the replication of poliovirus P2/Lansing RNA did not involve entry of RNA into cells and appeared to reduce viral translation and RNA synthesis late in the infection cycle.

Optometrists Association Australia Universal (entry-level) and Therapeutic Competency Standards for Optometry 2008.

PubMed

Kiely, Patricia M

2009-07-01

Competency standards for entry-level to the profession of optometry in Australia were first developed in 1993, revised in 1997 and expanded in 2000 to include therapeutic competency standards. The entry-level standards cover the competencies required by a person entering the profession without therapeutic endorsement of their registration. The therapeutic competency standards address the additional competencies required for therapeutic endorsement of registration. This paper presents a revised version of the universal (entry-level) and therapeutic competency standards for the profession of optometry in Australia in 2008. Expert members of the profession and representatives from schools of optometry, registration boards in Australia, state divisions of Optometrists Association Australia and the New Zealand Association of Optometrists were consulted in the process of updating the standards. Three new elements of competency have been added to the standards. Twenty-three new performance criteria with associated indicators have been added. Some performance criteria from the earlier document have been combined. Substantial alterations were made to the presentation of indicators throughout the document. The updated entry-level (universal) and therapeutic competency standards were adopted on behalf of the profession by the National Council of Optometrists Association Australia in November 2008. Competency standards are used by Australian and New Zealand registration authorities for the purposes of registration and therapeutic endorsement of registration via the Optometry Council of Australia and New Zealand accreditation and assessment processes. They have also been used as the basis of the World Council of Optometry Global Competency-Based Model.

Predictors of functional status at service entry and discharge among young people with first episode psychosis.

PubMed

Cotton, S M; Lambert, M; Schimmelmann, B G; Filia, K; Rayner, V; Hides, L; Foley, D L; Ratheesh, A; Watson, A; Rodger, P; McGorry, P D; Conus, P

2017-05-01

Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

The Androgen Receptor Gene Mutations Database.

PubMed

Gottlieb, B; Lehvaslaiho, H; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

1998-01-01

The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 272 to 309 in the past year. We have expanded the database: (i) by giving each entry an accession number; (ii) by adding information on the length of polymorphic polyglutamine (polyGln) and polyglycine (polyGly) tracts in exon 1; (iii) by adding information on large gene deletions; (iv) by providing a direct link with a completely searchable database (courtesy EMBL-European Bioinformatics Institute). The addition of the exon 1 polymorphisms is discussed in light of their possible relevance as markers for predisposition to prostate or breast cancer. The database is also available on the internet (http://www.mcgill. ca/androgendb/ ), from EMBL-European Bioinformatics Institute (ftp. ebi.ac.uk/pub/databases/androgen ), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca).

The Androgen Receptor Gene Mutations Database.

PubMed Central

Gottlieb, B; Lehvaslaiho, H; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

1998-01-01

The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 272 to 309 in the past year. We have expanded the database: (i) by giving each entry an accession number; (ii) by adding information on the length of polymorphic polyglutamine (polyGln) and polyglycine (polyGly) tracts in exon 1; (iii) by adding information on large gene deletions; (iv) by providing a direct link with a completely searchable database (courtesy EMBL-European Bioinformatics Institute). The addition of the exon 1 polymorphisms is discussed in light of their possible relevance as markers for predisposition to prostate or breast cancer. The database is also available on the internet (http://www.mcgill. ca/androgendb/ ), from EMBL-European Bioinformatics Institute (ftp. ebi.ac.uk/pub/databases/androgen ), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca). PMID:9399843

A phenol-enriched cuticle is ancestral to lignin evolution in land plants.

PubMed

Renault, Hugues; Alber, Annette; Horst, Nelly A; Basilio Lopes, Alexandra; Fich, Eric A; Kriegshauser, Lucie; Wiedemann, Gertrud; Ullmann, Pascaline; Herrgott, Laurence; Erhardt, Mathieu; Pineau, Emmanuelle; Ehlting, Jürgen; Schmitt, Martine; Rose, Jocelyn K C; Reski, Ralf; Werck-Reichhart, Danièle

2017-03-08

Lignin, one of the most abundant biopolymers on Earth, derives from the plant phenolic metabolism. It appeared upon terrestrialization and is thought critical for plant colonization of land. Early diverging land plants do not form lignin, but already have elements of its biosynthetic machinery. Here we delete in a moss the P450 oxygenase that defines the entry point in angiosperm lignin metabolism, and find that its pre-lignin pathway is essential for development. This pathway does not involve biochemical regulation via shikimate coupling, but instead is coupled with ascorbate catabolism, and controls the synthesis of the moss cuticle, which prevents desiccation and organ fusion. These cuticles share common features with lignin, cutin and suberin, and may represent the extant representative of a common ancestor. Our results demonstrate a critical role for the ancestral phenolic metabolism in moss erect growth and cuticle permeability, consistent with importance in plant adaptation to terrestrial conditions.

A phenol-enriched cuticle is ancestral to lignin evolution in land plants

PubMed Central

Renault, Hugues; Alber, Annette; Horst, Nelly A.; Basilio Lopes, Alexandra; Fich, Eric A.; Kriegshauser, Lucie; Wiedemann, Gertrud; Ullmann, Pascaline; Herrgott, Laurence; Erhardt, Mathieu; Pineau, Emmanuelle; Ehlting, Jürgen; Schmitt, Martine; Rose, Jocelyn K. C.; Reski, Ralf; Werck-Reichhart, Danièle

2017-01-01

Lignin, one of the most abundant biopolymers on Earth, derives from the plant phenolic metabolism. It appeared upon terrestrialization and is thought critical for plant colonization of land. Early diverging land plants do not form lignin, but already have elements of its biosynthetic machinery. Here we delete in a moss the P450 oxygenase that defines the entry point in angiosperm lignin metabolism, and find that its pre-lignin pathway is essential for development. This pathway does not involve biochemical regulation via shikimate coupling, but instead is coupled with ascorbate catabolism, and controls the synthesis of the moss cuticle, which prevents desiccation and organ fusion. These cuticles share common features with lignin, cutin and suberin, and may represent the extant representative of a common ancestor. Our results demonstrate a critical role for the ancestral phenolic metabolism in moss erect growth and cuticle permeability, consistent with importance in plant adaptation to terrestrial conditions. PMID:28270693

Ground-state transcriptional requirements for skin-derived precursors.

PubMed

Suflita, Michael T; Pfaltzgraff, Elise R; Mundell, Nathan A; Pevny, Larysa H; Labosky, Patricia A

2013-06-15

Skin-derived precursors (SKPs) are an attractive stem cell model for cell-based therapies. SKPs can be readily generated from embryonic and adult mice and adult humans, exhibit a high degree of multipotency, and have the potential to serve as a patient autologous stem cell. The advancement of these cells toward therapeutic use depends on the ability to control precisely the self-renewal and differentiation of SKPs. Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs. Deletion of Foxd3 completely abolishes the sphere-forming potential of these cells. In the absence of Sox2, SKP spheres can be formed, but with reduced size and frequency. Our results provide entry points into the gene regulatory networks dictating SKP behavior, and pave the way for future studies on a therapeutically relevant stem cell.

Ground-State Transcriptional Requirements for Skin-Derived Precursors

PubMed Central

Suflita, Michael T.; Pfaltzgraff, Elise R.; Mundell, Nathan A.; Pevny, Larysa H.

2013-01-01

Skin-derived precursors (SKPs) are an attractive stem cell model for cell-based therapies. SKPs can be readily generated from embryonic and adult mice and adult humans, exhibit a high degree of multipotency, and have the potential to serve as a patient autologous stem cell. The advancement of these cells toward therapeutic use depends on the ability to control precisely the self-renewal and differentiation of SKPs. Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs. Deletion of Foxd3 completely abolishes the sphere-forming potential of these cells. In the absence of Sox2, SKP spheres can be formed, but with reduced size and frequency. Our results provide entry points into the gene regulatory networks dictating SKP behavior, and pave the way for future studies on a therapeutically relevant stem cell. PMID:23316968

The role of syncytins in human reproduction and reproductive organ cancers.

PubMed

Soygur, Bikem; Sati, Leyla

2016-11-01

Human life begins with sperm and oocyte fusion. After fertilization, various fusion events occur during human embryogenesis and morphogenesis. For example, the fusion of trophoblastic cells constitutes a key process for normal placental development. Fusion in the placenta is facilitated by syncytin 1 and syncytin 2. These syncytins arose from retroviral sequences that entered the primate genome 25 million and more than 40 million years ago respectively. About 8% of the human genome consists of similar human endogenous retroviral (HERVs) sequences. Many are inactive because of mutations or deletions. However, the role of the few that remain transcriptionally active has not been fully elucidated. Syncytin proteins maintain cell-cell fusogenic activity based on ENV: gene-mediated viral cell entry. In this review, we summarize how syncytins and their receptors are involved in fusion events during human reproduction. The significance of syncytins in tumorigenesis is also discussed. © 2016 Society for Reproduction and Fertility.

T cell-specific deletion of the inositol phosphatase SHIP reveals its role in regulating Th1/Th2 and cytotoxic responses

PubMed Central

Tarasenko, Tatyana; Kole, Hemanta K.; Chi, Anthony W.; Mentink-Kane, Margaret M.; Wynn, Thomas A.; Bolland, Silvia

2007-01-01

The 5′-phosphoinositol phosphatase SHIP negatively regulates signaling pathways triggered by antigen, cytokine and Fc receptors in both lymphocytes and myeloid cells. Mice with germ-line (null) deletion of SHIP develop a myeloproliferative-like syndrome that causes early lethality. Lymphocyte anomalies have been observed in SHIP-null mice, but it is unclear whether they are due to an intrinsic requirement of SHIP in these cells or a consequence of the severe myeloid pathology. To precisely address the function of SHIP in T cells, we have generated mice with T cell-specific deletion of SHIP. In the absence of SHIP, we found no differences in thymic selection or in the activation state and numbers of regulatory T cells in the periphery. In contrast, SHIP-deficient T cells do not skew efficiently to Th2 in vitro. Mice with T cell-specific deletion of SHIP show poor antibody responses on Alum/NP-CGG immunization and diminished Th2 cytokine production when challenged with Schistosoma mansoni eggs. The failure to skew to Th2 responses may be the consequence of increased basal levels of the Th1-associated transcriptional factor T-bet, resulting from enhanced sensitivity to cytokine-mediated T-bet induction. SHIP-deficient CD8+ cells show enhanced cytotoxic responses, consistent with elevated T-bet levels in these cells. Overall our experiments indicate that in T cells SHIP negatively regulates cytokine-mediated activation in a way that allows effective Th2 responses and limits T cell cytotoxicity. PMID:17585010

Field Monitoring of Avian Influenza Viruses: Whole-Genome Sequencing and Tracking of Neuraminidase Evolution Using 454 Pyrosequencing

PubMed Central

Croville, Guillaume; Soubies, Sébastien Mathieu; Barbieri, Johanna; Klopp, Christophe; Mariette, Jérôme; Bouchez, Olivier; Camus-Bouclainville, Christelle

2012-01-01

Adaptation of avian influenza viruses (AIVs) from waterfowl to domestic poultry with a deletion in the neuraminidase (NA) stalk has already been reported. The way the virus undergoes this evolution, however, is thus far unclear. We address this question using pyrosequencing of duck and turkey low-pathogenicity AIVs. Ducks and turkeys were sampled at the very beginning of an H6N1 outbreak, and turkeys were swabbed again 8 days later. NA stalk deletions were evidenced in turkeys by Sanger sequencing. To further investigate viral evolution, 454 pyrosequencing was performed: for each set of samples, up to 41,500 reads of ca. 400 bp were generated and aligned. Genetic polymorphisms between duck and turkey viruses were tracked on the whole genome. NA deletion was detected in less than 2% of reads in duck feces but in 100% of reads in turkey tracheal specimens collected at the same time. Further variations in length were observed in NA from turkeys 8 days later. Similarly, minority mutants emerged on the hemagglutinin (HA) gene, with substitutions mostly in the receptor binding site on the globular head. These critical changes suggest a strong evolutionary pressure in turkeys. The increasing performances of next-generation sequencing technologies should enable us to monitor the genomic diversity of avian influenza viruses and early emergence of potentially pathogenic variants within bird flocks. The present study, based on 454 pyrosequencing, suggests that NA deletion, an example of AIV adaptation from waterfowl to domestic poultry, occurs by selection rather than de novo emergence of viral mutants. PMID:22718944

Psychiatric symptoms and antiretroviral nonadherence in US youth with perinatal HIV: a longitudinal study.

PubMed

Kacanek, Deborah; Angelidou, Konstantia; Williams, Paige L; Chernoff, Miriam; Gadow, Kenneth D; Nachman, Sharon

2015-06-19

The relationship of specific psychiatric conditions to adherence has not been examined in longitudinal studies of youth with perinatal HIV infection (PHIV). We examined associations between psychiatric conditions and antiretroviral nonadherence over 2 years. Longitudinal study in 294 PHIV youth, 6-17 years old, in the United States and Puerto Rico. We annually assessed three nonadherence outcomes: missed above 5% of doses in the past 3 days, missed a dose within the past month, and unsuppressed viral load (>400 copies/ml). We fit multivariable logistic models for nonadherence using Generalized Estimating Equations, and evaluated associations of psychiatric conditions (attention deficit hyperactivity disorder, disruptive behavior, depression, anxiety) at entry with incident nonadherence using multivariable logistic regression. Nonadherence prevalence at study entry was 14% (3-day recall), 32% (past month nonadherence), and 38% (unsuppressed viral load), remaining similar over time. At entry, 38% met symptom cut-off criteria for at least one psychiatric condition. Greater odds of 3-day recall nonadherence were observed at week 96 for those with depression [adjusted odds ratio (aOR) 4.14, 95% confidence interval (CI) 1.11-15.42] or disruptive behavior (aOR 3.36, 95% CI 1.02-11.10], but not at entry. Those with vs. without attention deficit hyperactivity disorder had elevated odds of unsuppressed viral load at weeks 48 (aOR 2.46, 95% CI 1.27-4.78) and 96 (aOR 2.35, 95% CI 1.01-5.45), but not at entry. Among 232 youth adherent at entry, 16% reported incident 3-day recall nonadherence. Disruptive behavior conditions at entry were associated with incident 3-day recall nonadherence (aOR 3.01, 95% CI 1.24-7.31). In PHIV youth, comprehensive adherence interventions that address psychiatric conditions throughout the transition to adult care are needed.

The role of digital data entry in participatory environmental monitoring.

PubMed

Brammer, Jeremy R; Brunet, Nicolas D; Burton, A Cole; Cuerrier, Alain; Danielsen, Finn; Dewan, Kanwaljeet; Herrmann, Thora Martina; Jackson, Micha V; Kennett, Rod; Larocque, Guillaume; Mulrennan, Monica; Pratihast, Arun Kumar; Saint-Arnaud, Marie; Scott, Colin; Humphries, Murray M

2016-12-01

Many argue that monitoring conducted exclusively by scientists is insufficient to address ongoing environmental challenges. One solution entails the use of mobile digital devices in participatory monitoring (PM) programs. But how digital data entry affects programs with varying levels of stakeholder participation, from nonscientists collecting field data to nonscientists administering every step of a monitoring program, remains unclear. We reviewed the successes, in terms of management interventions and sustainability, of 107 monitoring programs described in the literature (hereafter programs) and compared these with case studies from our PM experiences in Australia, Canada, Ethiopia, Ghana, Greenland, and Vietnam (hereafter cases). Our literature review showed that participatory programs were less likely to use digital devices, and 2 of our 3 more participatory cases were also slow to adopt digital data entry. Programs that were participatory and used digital devices were more likely to report management actions, which was consistent with cases in Ethiopia, Greenland, and Australia. Programs engaging volunteers were more frequently reported as ongoing, but those involving digital data entry were less often sustained when data collectors were volunteers. For the Vietnamese and Canadian cases, sustainability was undermined by a mismatch in stakeholder objectives. In the Ghanaian case, complex field protocols diminished monitoring sustainability. Innovative technologies attract interest, but the foundation of effective participatory adaptive monitoring depends more on collaboratively defined questions, objectives, conceptual models, and monitoring approaches. When this foundation is built through effective partnerships, digital data entry can enable the collection of more data of higher quality. Without this foundation, or when implemented ineffectively or unnecessarily, digital data entry can be an additional expense that distracts from core monitoring objectives and undermines project sustainability. The appropriate role of digital data entry in PM likely depends more on the context in which it is used and less on the technology itself. © 2016 Society for Conservation Biology.

Optometry Australia Entry-level Competency Standards for Optometry 2014.

PubMed

Kiely, Patricia M; Slater, Jared

2015-01-01

Competency standards for entry-level to the profession of optometry in Australia were first developed in 1993, revised in 1997 and 2000, and again in 2008, when therapeutic competency standards were introduced but differentiated from the entry-level competencies. Therapeutic competencies were an additional requirement for the purpose of endorsing optometric registration to allow prescription of medicines for conditions of the eye. Recent changes to educational and registration requirements mean that therapeutic competencies are now required at entry-level. To address this and to ensure the standards reflect current best practice, a full revision of the standards was undertaken. A steering committee oversaw the review of the standards, which involved a literature review, workshops with optometrists and broad consultation with stakeholders, including the Optometry Board of Australia, individual optometrists and employers of optometrists, to identify changes needed. Representatives of the profession from Australia and New Zealand and from academia in Australia were involved. A modified document based on the feedback received was circulated to the State Divisions and the National Board of the then Optometrists Association Australia. The updated standards reflect the state of entry to the optometric profession in 2014; competencies for prescribing of scheduled medicines are included, new material has been added, other areas have been modified. The updated entry-level competency standards were adopted on behalf of the profession by the National Board of the then Optometrists Association Australia in March 2014. Competency standards have been updated so that they continue to be current and useful for the profession, individual optometrists and Australian and New Zealand registration authorities for the purposes of accreditation of optometric programs and assessment of overseas-trained optometrists. This paper details the revision process and presents the 2014 version of competency standards for entry-level to the profession of optometry in Australia. © 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometry Australia.

A Survey of the Rapidly Emerging Field of Nanotechnology: Potential Applications for Scientific Instruments and Technologies for Atmospheric Entry Probes

NASA Technical Reports Server (NTRS)

Meyyappan, M.; Arnold, J. O.

2005-01-01

The field of Nanotechnology is well funded worldwide and innovations applicable to Solar System Exploration are emerging much more rapidly than thought possible just a few years ago. This presentation will survey recent innovations from nanotechnololgy with a focus on novel applications to atmospheric entry science and probe technology, in a fashion similar to that presented by Arnold and Venkatapathy at the previous workshop forum at Lisbon Portugal, October 6-9, 2003. Nanotechnology is a rapidly emerging field that builds systems, devices and materials from the bottom up, atom by atom, and in so doing provides them with novel and remarkable macro-scale performance. This technology has the potential to revolutionize space exploration by reducing mass and simultaneously increasing capability. Thermal, Radiation, Impact Protective Shields: Atmospheric probes and humans on long duration deep space missions involved in Solar System Exploration must safely endure 3 significant hazards: (i) atmospheric entry; (ii) radiation; and (iii) micrometeorite or debris impact. Nanostructured materials could be developed to address all three hazards with a single protective shield, which would involve much less mass than a traditional approach. The concept can be ready in time for incorporation into NASA s Crew Exploration Vehicle, and possible entry probes to fly on the Jupiter Icy Moons

Parachute Swivel Mechanism for planetary entry

NASA Technical Reports Server (NTRS)

Birner, R.; Kaese, J.; Koller, F.; Muehlner, E.; Luhmann, H.-J.

1993-01-01

A parachute swivel mechanism (PSM) for planetary entry missions such as a Mars probe (MARSNET) or return of cometary material samples (ROSETTA mission) has been developed. The purpose of the PSM is to decouple the spin of the probe from the parachute, with low friction torque, during both the deployment and descent phases. Critical requirements are high shock loads, low friction, low temperatures, and several years of storage in the deep space environment (during the cruise phase of the probe, prior to operation). The design uses a main thrust ball bearing to cope with the load requirement and a smaller thrust ball bearing for guiding of the shaft. Except for use on the Viking and Galileo swivels, it appears that this type of bearing has very rarely been employed in space mechanisms, so that little is known of its friction behavior with dry lubrication. A slip ring assembly allows the transfer of electrical power for post-reefing of the parachute. A test program has been conducted covering the environmental conditions of Mars entry and Earth reentry. This paper describes requirement constraints, model missions of planetary entries, a bearing trade-off, analyses performed, design details, the lubrication system, and test results (friction torque versus load/spin rate). In addition, the design of the test rig is addressed.

The entry-level physical therapist: a case for COMFORT communication training.

PubMed

Goldsmith, Joy; Wittenberg-Lyles, Elaine; Frisby, Brandi N; Platt, Christine Small

2015-01-01

Entry-level physical therapists provide clinical care for patients with functional mobility limitations. Their care spans the continuum of settings, disease processes, and diagnoses. Although effective communication skills are required to conduct physical therapy work, there is limited instruction provided in physical therapy education and students receive little exposure to seriously or chronically ill patients. The goal of this study was to assess the effects of communication training for the entry-level physical therapist facing palliative and end-of-life communication with patients/families. A pre-post survey design and narrative writing were used to assess the effect of the COMFORT communication training curriculum provided to doctorally trained, graduating physical therapists. The study demonstrated decreased student apprehension about communicating with dying patients and their families, and a comparison of mean scores reflecting the students' communication knowledge, confidence, and behaviors increased in a positive direction. As students became more willing to communicate, they were also more adept at integrating task and relational messages, as well as assimilating emotional support messages for patients and families. This study shows promise for the feasibility and utilization of the COMFORT curriculum for entry-level physical therapists. Further research should address the integration of COMFORT earlier into physical therapy education, as well as assess evidence of COMFORT communication skills in the clinical context.

The importance of integumentary knowledge and skill in physical therapist entry-level education: are they prepared for practice?

PubMed

Gibbs, Karen A; Furney, Steven R

2013-01-01

Physical therapist practice is grounded in patient management principles encompassing all body systems and focuses on prevention, education, and functional outcomes. As such, management of the integumentary system crosses all practice settings, emphasizing the importance that basic integumentary content be adequately addressed during entry-level education. The purpose of this qualitative study was to compare the self-reported integumentary knowledge and skill of recent graduates to profession-determined expectations for education. Participants were 7 licensed physical therapists experienced in wound management. Semi-structured interview data were recorded, transcribed, and coded. A matrix compiling professional expectations for integumentary education was utilized to identify topics as absent, covered only briefly, or covered only during clinical rotations. Compression, vascular screening, infection, factors impacting healing, modalities, dressings, wound measurements, topicals, and sutures/staples were among the most commonly reported areas of deficiency. While integumentary care makes up a small percentage of physical therapy practice, it is a significant part of a comprehensively educated therapist. This study found participants did not perceive themselves to have received the minimum entry-level integumentary knowledge and skill deemed necessary by the profession. Study results are supported by current literature and demonstrate the need for integumentary curriculum review in entry-level programs.

Molecular Determinants of Sporulation in Ashbya gossypii

PubMed Central

Wasserstrom, Lisa; Lengeler, Klaus B.; Walther, Andrea; Wendland, Jürgen

2013-01-01

Regulation of development and entry into sporulation is critical for fungi to ensure survival of unfavorable environmental conditions. Here we present an analysis of gene sets regulating sporulation in the homothallic ascomycete Ashbya gossypii. Deletion of components of the conserved pheromone/starvation MAP kinase cascades, e.g., STE11 and STE7, results in increased sporulation. In kar3 mutants sporulation is severely reduced, while deletion of KAR4 as well as of homologs of central Saccharomyces cerevisiae regulators of sporulation, IME1, IME2, IME4, and NDT80, abolishes sporulation in A. gossypii. Comparison of RNAseq transcript profiles of sporulation-deficient mutants identified a set of 67 down-regulated genes, most of which were up-regulated in the oversporulating ste12 mutant. One of these differentially expressed genes is an endoglucanase encoded by ENG2. We found that Eng2p promotes hyphal fragmentation as part of the developmental program of sporulation, which generates single-celled sporangia. Sporulation-deficient strains are arrested in their development but form sporangia. Supply of new nutrients enabled sporangia to return to hyphal growth, indicating that these cells are not locked in meiosis. Double-strand break (DSB) formation by Spo11 is apparently not required for sporulation; however, the absence of DMC1, which repairs DSBs in S. cerevisiae, results in very poor sporulation in A. gossypii. We present a comprehensive analysis of the gene repertoire governing sporulation in A. gossypii and suggest an altered regulation of IME1 expression compared to S. cerevisiae. PMID:23833180

Molecular determinants of sporulation in Ashbya gossypii.

PubMed

Wasserstrom, Lisa; Lengeler, Klaus B; Walther, Andrea; Wendland, Jürgen

2013-09-01

Regulation of development and entry into sporulation is critical for fungi to ensure survival of unfavorable environmental conditions. Here we present an analysis of gene sets regulating sporulation in the homothallic ascomycete Ashbya gossypii. Deletion of components of the conserved pheromone/starvation MAP kinase cascades, e.g., STE11 and STE7, results in increased sporulation. In kar3 mutants sporulation is severely reduced, while deletion of KAR4 as well as of homologs of central Saccharomyces cerevisiae regulators of sporulation, IME1, IME2, IME4, and NDT80, abolishes sporulation in A. gossypii. Comparison of RNAseq transcript profiles of sporulation-deficient mutants identified a set of 67 down-regulated genes, most of which were up-regulated in the oversporulating ste12 mutant. One of these differentially expressed genes is an endoglucanase encoded by ENG2. We found that Eng2p promotes hyphal fragmentation as part of the developmental program of sporulation, which generates single-celled sporangia. Sporulation-deficient strains are arrested in their development but form sporangia. Supply of new nutrients enabled sporangia to return to hyphal growth, indicating that these cells are not locked in meiosis. Double-strand break (DSB) formation by Spo11 is apparently not required for sporulation; however, the absence of DMC1, which repairs DSBs in S. cerevisiae, results in very poor sporulation in A. gossypii. We present a comprehensive analysis of the gene repertoire governing sporulation in A. gossypii and suggest an altered regulation of IME1 expression compared to S. cerevisiae.

Oxidative stress induced in E. coli by the human antimicrobial peptide LL-37

PubMed Central

2017-01-01

Antimicrobial peptides (AMPs) are thought to kill bacterial cells by permeabilizing their membranes. However, some antimicrobial peptides inhibit E. coli growth more efficiently in aerobic than in anaerobic conditions. In the attack of the human cathelicidin LL-37 on E. coli, real-time, single-cell fluorescence imaging reveals the timing of membrane permeabilization and the onset of oxidative stress. For cells growing aerobically, a CellROX Green assay indicates that LL-37 induces rapid formation of oxidative species after entry into the periplasm, but before permeabilization of the cytoplasmic membrane (CM). A cytoplasmic Amplex Red assay signals a subsequent burst of oxidative species, most likely hydrogen peroxide, shortly after permeabilization of the CM. These signals are much stronger in the presence of oxygen, a functional electron transport chain, and a large proton motive force (PMF). They are much weaker in cells growing anaerobically, by either fermentation or anaerobic respiration. In aerobic growth, the oxidative signals are attenuated in a cytochrome oxidase–bd deletion mutant, but not in a –bo3 deletion mutant, suggesting a specific effect of LL-37 on the electron transport chain. The AMPs melittin and LL-37 induce strong oxidative signals and exhibit O2-sensitive MICs, while the AMPs indolicidin and cecropin A do not. These results suggest that AMP activity in different tissues may be tuned according to the local oxygen level. This may be significant for control of opportunistic pathogens while enabling growth of commensal bacteria. PMID:28665988

Interactions and Nuclear Import of the N and P Proteins of Sonchus Yellow Net Virus, a Plant Nucleorhabdovirus

PubMed Central

Goodin, Michael M.; Austin, Jennifer; Tobias, Renée; Fujita, Miki; Morales, Christina; Jackson, Andrew O.

2001-01-01

We have characterized the interaction and nuclear localization of the nucleocapsid (N) protein and phosphoprotein (P) of sonchus yellow net nucleorhabdovirus. Expression studies with plant and yeast cells revealed that both N and P are capable of independent nuclear import. Site-specific mutagenesis and deletion analyses demonstrated that N contains a carboxy-terminal bipartite nuclear localization signal (NLS) located between amino acids 465 and 481 and that P contains a karyophillic region between amino acids 40 and 124. The N NLS was fully capable of functioning outside of the context of the N protein and was able to direct the nuclear import of a synthetic protein fusion consisting of green fluorescent protein fused to glutathione S-transferase (GST). Expression and mapping studies suggested that the karyophillic domain in P is located within the N-binding domain. Coexpression of N and P drastically affected their localization patterns relative to those of individually expressed proteins and resulted in a shift of both proteins to a subnuclear region. Yeast two-hybrid and GST pulldown experiments verified the N-P and P-P interactions, and deletion analyses have identified the N and P interacting domains. N NLS mutants were not transported to the nucleus by import-competent P, presumably because N binding masks the P NLS. Taken together, our results support a model for independent entry of N and P into the nucleus followed by associations that mediate subnuclear localization. PMID:11533202

Quantitative impact of thymic selection on Foxp3+ and Foxp3- subsets of self-peptide/MHC class II-specific CD4+ T cells.

PubMed

Moon, James J; Dash, Pradyot; Oguin, Thomas H; McClaren, Jennifer L; Chu, H Hamlet; Thomas, Paul G; Jenkins, Marc K

2011-08-30

It is currently thought that T cells with specificity for self-peptide/MHC (pMHC) ligands are deleted during thymic development, thereby preventing autoimmunity. In the case of CD4(+) T cells, what is unclear is the extent to which self-peptide/MHC class II (pMHCII)-specific T cells are deleted or become Foxp3(+) regulatory T cells. We addressed this issue by characterizing a natural polyclonal pMHCII-specific CD4(+) T-cell population in mice that either lacked or expressed the relevant antigen in a ubiquitous pattern. Mice expressing the antigen contained one-third the number of pMHCII-specific T cells as mice lacking the antigen, and the remaining cells exhibited low TCR avidity. In mice lacking the antigen, the pMHCII-specific T-cell population was dominated by phenotypically naive Foxp3(-) cells, but also contained a subset of Foxp3(+) regulatory cells. Both Foxp3(-) and Foxp3(+) pMHCII-specific T-cell numbers were reduced in mice expressing the antigen, but the Foxp3(+) subset was more resistant to changes in number and TCR repertoire. Therefore, thymic selection of self-pMHCII-specific CD4(+) T cells results in incomplete deletion within the normal polyclonal repertoire, especially among regulatory T cells.

Analysis of apolipoprotein A5, C3 and plasma triglyceride concentrations in genetically engineered mice

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

Baroukh, Nadine; Bauge, Eric; Akiyama, Jennifer

2004-03-11

To address the relationship between the apolipoprotein A5 and C3 genes, we generated independent lines of mice that either over-expressed or completely lacked both genes. We report both lines display normal triglyceride concentrations compared to over-expression or deletion of either gene alone. Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

STS-121: Discovery Entry Flight Director Post Landing Press Conference

NASA Technical Reports Server (NTRS)

2006-01-01

Steve Stitch, STS-121 Entry Flight Director, and Wayne Hale, Space Shuttle Program is shown in this post landing press conference. Steve Stitch begins with discussing the following topics: 1) Weather at Kennedy Space Center; 2) Gap filler protrusion; 3) De-orbit burn; 4) Space Shuttle Landing; 5) Global Position Satellite System (GPSS) performance; and 6) Post-landing rain showers. Wayne Hale discusses external tank observations at launch and the goals that were obtained by this flight, which are to deliver 4000 pounds of scientific equipment, increase the crew members to three on the International Space Station (ISS), and repair the ISS. Questions from the press on lessons learned from the Auxiliary Power Unit (APU) leak, and flight readiness reviews are addressed.

The strategic marketing reaction of conventional nonprofit hospitals to the market entry of alternative care provider organizations.

PubMed

Schul, P L; Remington, S J; Planchon, J M

1994-01-01

A study was conducted examining the competitive reaction of incumbent firms to the market entry of new form competition in the health care services industry. Specifically, the study addressed the relative impact of both objective and perceptual characteristics of the threat potential posed by the entrance of alternative care facilities (ACF's) into markets previously dominated by nonprofit hospital organizations. The results showed that incumbent hospitals tend to rely most extensively on limited, low-risk market differentiation when responding to the threat posed by ACF entrants. Objective characteristics reflective of the structural complexity of the threat were found to be less important in influencing incumbent reaction than were administrators' perceptions of new entrant threat.

Future exploration of Venus (post-Pioneer Venus 1978)

NASA Technical Reports Server (NTRS)

Colin, L.; Evans, L. C.; Greeley, R.; Quaide, W. L.; Schaupp, R. W.; Seiff, A.; Young, R. E.

1976-01-01

A comprehensive study was performed to determine the major scientific unknowns about the planet Venus to be expected in the post-Pioneer Venus 1978 time frame. Based on those results the desirability of future orbiters, atmospheric entry probes, balloons, and landers as vehicles to address the remaining scientific questions were studied. The recommended mission scenario includes a high resolution surface mapping radar orbiter mission for the 1981 launch opportunity, a multiple-lander mission for 1985 and either an atmospheric entry probe or balloon mission in 1988. All the proposed missions can be performed using proposed space shuttle upper stage boosters. Significant amounts of long-lead time supporting research and technology developments are required to be initiated in the near future to permit the recommended launch dates.

Examination of the Entry to Burn and Burn Control for the ITER 15 MA Baseline and Other Scenarios

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

Kesse, Charles E.; Kim, S-H.; Koechl, F.

2014-09-01

The entry to burn and flattop burn control in ITER will be a critical need from the first DT experiments. Simulations are used to address time-dependent behavior under a range of possible conditions that include injected power level, impurity content (W, Ar, Be), density evolution, H-mode regimes, controlled parameter (Wth, Pnet, Pfusion), and actuator (Paux, fueling, fAr), with a range of transport models. A number of physics issues at the L-H transition require better understanding to project to ITER, however, simulations indicate viable control with sufficient auxiliary power (up to 73 MW), while lower powers become marginal (as low asmore » 43 MW).« less

The Development and Implementation of a School-to-Work Apprenticeship Model at a Technical Career Center.

ERIC Educational Resources Information Center

Kraft, James A.

A business and education partnership model addressed a shortage of local, qualified, entry-level, technically skilled workers through a school-to-work apprenticeship program at the North Montco Technical Career Center in Lansdale, Pennsylvania. The research-based solution plan of the Pennsylvania Youth Apprenticeship Program (PYAP) included three…

Don't Pit Tenure against Contingent Faculty Rights

ERIC Educational Resources Information Center

Street, Steve

2008-01-01

By August, Steven D. Levitt's March 3, 2007, entry on his "Freakonomics" blog, titled "Let's Just Get Rid of Tenure (Including Mine)," had sparked sixty-eight responses, ranging from applause to scrutiny of his facts. Only one response, however, addressed the concept of tenure as it affects the 68 percent of faculty nationwide without it: the…

Association of Small Computer Users in Education (ASCUE) Summer Conference. Proceedings (27th, North Myrtle Beach, South Carolina, June 12-16, 1994).

ERIC Educational Resources Information Center

Huston, Rick, Ed.; Armel, Donald, Ed.

Topics addressed by 40 papers from a conference on microcomputers include: developing a campus wide computer ethics policy; integrating new technologies into professional education; campus computer networks; computer assisted instruction; client/server architecture; competencies for entry-level computing positions; auditing and professional…

Assessment and Education of Deaf-Blind Children. Proceedings of the Special Study Institute (Los Angeles, CA, March 17-19, 1978).

ERIC Educational Resources Information Center

Southwestern Region Deaf-Blind Center, Sacramento, CA.

The document contains nine conference papers which address several approaches to assessment of deaf blind children. Entries include the following titles and authors: "Parent-Teacher Relationships and the Deaf-Blind Child" (M. Schleifer); "Congenital Rubella--The Teenage Years" (P. Ziring); "Psychological Assessment" (guidelines for assessing the…

75 FR 18871 - Notification of the Imposition of Conditions of Entry for Certain Vessel Arriving to the United...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-13

... become effective April 27, 2010. ADDRESSES: This notice will be available for inspection and copying at the Docket Management Facility at the U.S. Department of Transportation, Room W12-140 on the Ground... the United States on vessels arriving from ports that are not maintaining effective anti- terrorism...

Flexible Learning Options: The Experiences and Perceptions of Regional Youth

ERIC Educational Resources Information Center

Msapenda, Vanessa; Hudson, Cate

2013-01-01

Over the past few decades a variety of alternative or re-entry educational programs have been developed in Australia as an approach to address early school leaving and promote engagement with learning. In South Australia, one of the largest initiatives has been the implementation of Flexible Learning Programs (FLPs) as part of the State…

Indiana Developmental School Counseling Idea Book.

ERIC Educational Resources Information Center

Indiana State Dept. of Education, Indianapolis.

This book is intended to present guidance curriculum activities which address students' needs in the areas of learning to live, learning to learn, and learning to work. The activities are divided into four developmental levels: K-5, grades 6-8, grades 9-12, and K-12. At the bottom of each entry the name of the contributing school counselor, school…

Validated Competency Task Lists for General Merchandise Retailing, Food Service Management, and Business and Personal Services Marketing.

ERIC Educational Resources Information Center

Faught, Suzanne G.

This publication contains competency task lists that address principal entry-level and career-sustaining jobs in the occupational categories of general merchandise retailing, food service management, and business and personal services marketing. Section I, Development of the Competency Task Lists, provides details on how the competencies were…

32 CFR 326.14 - Disclosure of records to person other than subject.

Code of Federal Regulations, 2010 CFR

2010-07-01

... disclosures required by the Freedom of Information Act, an accounting will be kept of all disclosures of.... Accounting entries will record the date, kind of information, purpose of each disclosure, and the name and address of the person or agency to whom the disclosure is made. Accounting records will be maintained for...

Effecting Successful Community Re-Entry: Systems of Care Community Based Mental Health Services

ERIC Educational Resources Information Center

Estes, Rebecca I.; Fette, Claudette; Scaffa, Marjorie E.

2005-01-01

The need for system reform for child and adolescent mental health services, long recognized as a vital issue, continues to challenge mental health professionals. While past legislation has not adequately addressed the issues, the 2003 President's New Freedom Commission may begin to reorient mental health systems toward recovery. Supported by this…

78 FR 53269 - Approval and Promulgation of Implementation Plans; Arkansas; Interstate Transport of Fine...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

...] Approval and Promulgation of Implementation Plans; Arkansas; Interstate Transport of Fine Particulate... technical supplement submitted on March 20, 2013, to address interstate transport for the 1997 and 2006 PM 2... SIP'' is amended by adding an entry at the end for ``Interstate transport for the 1997 and 2006 PM 2.5...

Directory of Academic Institutions and Organizations Offering Drug, Alcohol, and Employee Assistance Program Educational Resources.

ERIC Educational Resources Information Center

National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

This directory lists academic institutions, State offices of alcohol and drug abuse, and national organizations which offer drug, alcohol, and employee assistance program (EAP) educational resources. A matrix format is used. Entries include name, address, telephone number, and contact person. A dot appears directly under column headings which are…

Instructional Strategies Used to Improve Students' Comfort and Skill in Addressing the Occupational Therapy Process

ERIC Educational Resources Information Center

Knecht-Sabres, Lisa Jean; Egan, Brad E.; Wallingford, Minetta S.; Kovic, Mark

2015-01-01

The purpose of this study was to investigate the effectiveness of an intentional blending of instructional strategies in an occupational therapy (OT) entry-level master's course. The OT Adult Practice course uses case-based instructional strategies, clinical skills labs, and standardized patient experiences in a dovetailed approach across three…

Overview of the National Health Educator Competencies Update Project, 1998-2004

ERIC Educational Resources Information Center

Gilmore, Gary David; Olsen, Larry K.; Taub, Alyson; Connell, David

2005-01-01

The National Health Educator Competencies Update Project (CUP), conducted during 1998-2004, addressed what health educators currently do in practice, the degree to which the role definition of the entry-level health educator is still up-to-date, and the validation of advanced-level competencies. A 19-page questionnaire was sent to a representative…

78 FR 46903 - Control Date for Qualifying Landings History and to Limit Speculative Entry into the Illex Squid...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

.... Dated: July 30, 2013. Alan D. Risenhoover, Director, Office of Sustainable Fisheries, performing the... Council considers if and how access to the Illex squid fishery should be controlled. DATES: August 2, 2013... before September 3, 2013. ADDRESSES: You may submit comments on this document, identified by NOAA-NMFS...

The Transition to Kindergarten for Typically Developing Children: A Survey of School Psychologists' Involvement

ERIC Educational Resources Information Center

McIntyre, Laura Lee; Eckert, Tanya L.; Arbolino, Lauren A.; DiGennaro Reed, Florence D.; Fiese, Barbara H.

2014-01-01

Research suggests that a large percentage of kindergarten children do not successfully transition to school (Rimm-Kaufman et al. 2000). As a result, a number of school transition initiatives have been developed by educators and policy makers to address the difficulties young children may experience upon kindergarten entry. Despite this attention,…

Methods and Strategies: Teaching about Animals

ERIC Educational Resources Information Center

Palmeri, Amy

2007-01-01

When asking about animals, it is hard to find a person who doesn't recall a beloved pet or share that they've always loved dolphins, snakes, or ladybugs. A study of animals in an early childhood classroom, then, would seem an easy entry into science explorations with children. The article includes reflections on teaching to address the gaps…

International Conference on Environmental Education (Vigyan Bhavan, New Delhi, India, December 16-20, 1981). Abstracts.

ERIC Educational Resources Information Center

Bhat, J. L., Ed.; Bandhu, Desh, Ed.

Abstracts of papers presented at the International Conference on Environmental Education are included in this document. Although title, author(s), and abstract are provided for each of the 124 entries, a table of contents and author/subject index are not included. Topics and issues addressed focus on various aspects of environmental education…

Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus

PubMed Central

Okubo, Yu; Wakata, Aika; Suzuki, Takuma; Shibata, Tomoko; Ikeda, Hitomi; Yamaguchi, Miki; Cohen, Justus B.; Glorioso, Joseph C.; Tagaya, Mitsuo; Hamada, Hirofumi; Tahara, Hideaki

2016-01-01

ABSTRACT Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains. To address this question, we took advantage of mutant viruses whose viral entry into cells relies on the uniquely specific interaction of an engineered gD with epidermal growth factor receptor (EGFR). We introduced selected syncytial mutations into gB and/or gK of the EGFR-retargeted HSV and found that these mutations, especially when combined, enabled formation of extensive syncytia by human cancer cell lines that express the target receptor; these syncytia were substantially larger than the plaques formed by the parental retargeted HSV strain. We assessed the EGFR dependence of entry and spread separately by using direct entry and infectious center assays, respectively, and we found that the syncytial mutations did not override the receptor specificity of the retargeted viruses at either stage. We discuss the implications of these results for the development of more effective targeted oncolytic HSV vectors. IMPORTANCE Herpes simplex virus (HSV) is investigated not only as a human pathogen but also as a promising agent for oncolytic virotherapy. We previously showed that both the initial entry and subsequent lateral spread of HSV can be retargeted to cells expressing tumor-associated antigens by single-chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD-retargeted HSVs to determine whether viral tropism remained dependent on the interaction of gD with the target receptor. Entry and spread profiles of the recombinant viruses indicated that gD retargeting does not abolish the hyperfusogenic activity of syncytial mutations and that these mutations do not eliminate the dependence of HSV entry and spread on a specific gD-receptor interaction. These observations suggest that syncytial mutations may be valuable for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors. PMID:27707922

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

PubMed Central

Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G.; Zhang, Nianshu

2016-01-01

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding ‘signaling’ proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast. PMID:27923067

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases.

PubMed

Cao, Lu; Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G; Zhang, Nianshu

2016-12-01

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast.

Remote Monitoring Systems for Chronic Patients on Home Hemodialysis: Field Test of a Copresence-Enhanced Design

PubMed Central

Liu, Na; Jung, Younhyun; Arisy, Adani; Nicdao, Mary Ann; Mikaheal, Mary; Baldacchino, Tanya; Khadra, Mohamed; Sud, Kamal

2017-01-01

Background Patients undertaking long-term and chronic home hemodialysis (HHD) are subject to feelings of isolation and anxiety due to the absence of physical contact with their health care professionals and lack of feedback in regards to their dialysis treatments. Therefore, it is important for these patients to feel the “presence” of the health care professionals remotely while on hemodialysis at home for better compliance with the dialysis regime and to feel connected with health care professionals. Objective This study presents an HHD system design for hemodialysis patients with features to enhance patient’s perceived “copresence” with their health care professionals. Various mechanisms to enhance this perception were designed and implemented, including digital logbooks, emotion sharing, and feedback tools. The mechanism in our HHD system aims to address the limitations associated with existing self-monitoring tools for HHD patients. Methods A field trial involving 3 nurses and 74 patients was conducted to test the pilot implementation of the copresence design in our HHD system. Mixed method research was conducted to evaluate the system, including surveys, interviews, and analysis of system data. Results Patients created 2757 entries of dialysis cases during the period of study. Altogether there were 492 entries submitted with “Very Happy” as the emotional status, 2167 entries with a “Happy” status, 56 entries with a “Neutral” status, 18 entries with an “Unhappy” status, and 24 entries with a “Very unhappy” status. Patients felt assured to share their emotions with health care professionals. Health care professionals were able to prioritize the review of the entries based on the emotional status and also felt assured to see patients’ change in mood. There were 989 entries sent with short notes. Entries with negative emotions had a higher percentage of supplementary notes entered compared to the entries with positive and neutral emotions. The qualitative data further showed that the HHD system was able to improve patients’ feelings of being connected with their health care professionals and thus enhance their self-care on HHD. The health care professionals felt better assured with patients’ status with the use of the system and reported improved productivity and satisfaction with the copresence enhancement mechanism. The survey on the system usability indicated a high level of satisfaction among patients and nurses. Conclusions The copresence enhancement design complements the conventional use of a digitized HHD logbook and will further benefit the design of future telehealth systems. PMID:28851680

Evidence of superficial knowledge regarding antibiotics and their use: Results of two cross-sectional surveys in an urban informal settlement in Kenya

PubMed Central

Omulo, Sylvia; Thumbi, Samuel M.; Lockwood, Svetlana; Verani, Jennifer R.; Bigogo, Godfrey; Masyongo, Geoffrey

2017-01-01

We assessed knowledge and practices related to antibiotic use in Kibera, an urban informal settlement in Kenya. Surveys was employed at the beginning (entry) and again at the end (exit) of a 5-month longitudinal study of AMR. Two-hundred households were interviewed at entry, of which 149 were also interviewed at exit. The majority (>65%) of respondents in both surveys could name at least one antibiotic, with amoxicillin and cotrimoxazole jointly accounting for 85% and 77% of antibiotics mentioned during entry and exit, respectively. More than 80% of respondents felt antibiotics should not be shared or discontinued following the alleviation of symptoms. Nevertheless, 66% and 74% of respondents considered antibiotics effective for treating colds and flu in the entry and exit surveys, respectively. There was a high (87%, entry; 70% exit) level of reported antibiotic use (past 12 months) mainly for colds/flu, coughs and fever, with >80% of respondents obtaining antibiotics from health facilities and pharmacies. Less than half of respondents remembered getting information on the correct use of antibiotics, although 100% of those who did reported improved attitudes towards antibiotic use. Clinicians and community pharmacists were highly trusted information sources. Paired household responses (n = 149) generally showed improved knowledge and attitudes by the exit survey although practices were largely unchanged. Weak agreement (κ = -0.003 to 0.22) between survey responses suggest both that unintended learning had not occurred, and that participant responses were not based on established knowledge or behaviors. Targeted public education regarding antibiotics is needed to address this gap. PMID:28968447

Evidence of superficial knowledge regarding antibiotics and their use: Results of two cross-sectional surveys in an urban informal settlement in Kenya.

PubMed

Omulo, Sylvia; Thumbi, Samuel M; Lockwood, Svetlana; Verani, Jennifer R; Bigogo, Godfrey; Masyongo, Geoffrey; Call, Douglas R

2017-01-01

We assessed knowledge and practices related to antibiotic use in Kibera, an urban informal settlement in Kenya. Surveys was employed at the beginning (entry) and again at the end (exit) of a 5-month longitudinal study of AMR. Two-hundred households were interviewed at entry, of which 149 were also interviewed at exit. The majority (>65%) of respondents in both surveys could name at least one antibiotic, with amoxicillin and cotrimoxazole jointly accounting for 85% and 77% of antibiotics mentioned during entry and exit, respectively. More than 80% of respondents felt antibiotics should not be shared or discontinued following the alleviation of symptoms. Nevertheless, 66% and 74% of respondents considered antibiotics effective for treating colds and flu in the entry and exit surveys, respectively. There was a high (87%, entry; 70% exit) level of reported antibiotic use (past 12 months) mainly for colds/flu, coughs and fever, with >80% of respondents obtaining antibiotics from health facilities and pharmacies. Less than half of respondents remembered getting information on the correct use of antibiotics, although 100% of those who did reported improved attitudes towards antibiotic use. Clinicians and community pharmacists were highly trusted information sources. Paired household responses (n = 149) generally showed improved knowledge and attitudes by the exit survey although practices were largely unchanged. Weak agreement (κ = -0.003 to 0.22) between survey responses suggest both that unintended learning had not occurred, and that participant responses were not based on established knowledge or behaviors. Targeted public education regarding antibiotics is needed to address this gap.

Cognitive analysis of physicians' medication ordering activity.

PubMed

Pelayo, Sylvia; Leroy, Nicolas; Guerlinger, Sandra; Degoulet, Patrice; Meaux, Jean-Jacques; Beuscart-Zéphir, Marie-Catherine

2005-01-01

Computerized Physician Order Entry (CPOE) addresses critical functions in healthcare systems. As the name clearly indicates, these systems focus on order entry. With regard to medication orders, such systems generally force physicians to enter exhaustively documented orders. But a cognitive analysis of the physician's medication ordering task shows that order entry is the last (and least) important step of the entire cognitive therapeutic decision making task. We performed a comparative analysis of these complex cognitive tasks in two working environments, computer-based and paper-based. The results showed that information gathering, selection and interpretation are critical cognitive functions to support the therapeutic decision making. Thus the most important requirement from the physician's perspective would be an efficient display of relevant information provided first in the form of a summarized view of the patient's current treatment, followed by in a more detailed focused display of those items pertinent to the current situation. The CPOE system examined obviously failed to provide the physicians this critical summarized view. Following these results, consistent with users' complaints, the Company decided to engage in a significant re-engineering process of their application.

Is graduate entry education a solution to increasing numbers of men in nursing?

PubMed

McKenna, Lisa; Vanderheide, Rebecca; Brooks, Ingrid

2016-03-01

Males have traditionally constituted a very small proportion of the nursing workforce in many countries, including Australia. Together with a need to address the gender imbalance, nursing workforce shortages require strategies for recruiting new nurses, including males. This study examined characteristics of males entering one accelerated graduate entry masters pre-registration nursing program in Victoria, Australia. A quantitative survey gathered a variety of demographic data and factors relating to participants' decisions to undertake nursing. Data were analysed using descriptive statistics including frequencies and distributions. Forty-three male nursing students from four cohorts of the Master of Nursing Practice (MNP) course from 2009 to 2011 completed the survey. The proportion of males (30%) was considerably greater than traditional nursing courses and the profession generally. Participants demonstrated wide distributions in age ranges, professional backgrounds and previous years in the workforce. Graduate entry appears attractive to males of varying ages, personal and professional backgrounds. More research is needed to examine this phenomenon on a larger scale. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Preventing lethal violence in schools: the case for entry-based weapons screening.

PubMed

Mawson, Anthony R; Lapsley, Peter M; Hoffman, Allan M; Guignard, John C

2002-04-01

Violence-related behavior in schools has declined in recent years, but the perception of risk remains high. Disturbingly high percentages of students and teachers report staying home out of fear, and many students bring weapons to school for protection. Current proposals for preventing school violence include punishing the violence-prone, expulsion for weapon carriers, and creating a culture of nonviolence through various behavioral methods like conflict resolution. None of these proposals address the issue of lethal violence and hence personal safety. The risk of lethal violence in schools (related mainly to firearms) could be substantially reduced by creating an effective barrier between firearms and people. This could be achieved by using entry-based weapons detection systems similar to those now used in airports and courts. Decreasing the risk and fear of violence by converting schools into weapons-free zones would also be expected to increase attendance and improve scholastic performance. Randomized, controlled studies should be undertaken to evaluate the efficacy and cost-effectiveness of entry-based weapons detection systems for achieving these outcomes.

A Stiffness Switch in Human Immunodeficiency Virus

PubMed Central

Kol, Nitzan; Shi, Yu; Tsvitov, Marianna; Barlam, David; Shneck, Roni Z.; Kay, Michael S.; Rousso, Itay

2007-01-01

After budding from the cell, human immunodeficiency virus (HIV) and other retrovirus particles undergo a maturation process that is required for their infectivity. During maturation, HIV particles undergo a significant internal morphological reorganization, changing from a roughly spherically symmetric immature particle with a thick protein shell to a mature particle with a thin protein shell and conical core. However, the physical principles underlying viral particle production, maturation, and entry into cells remain poorly understood. Here, using nanoindentation experiments conducted by an atomic force microscope (AFM), we report the mechanical measurements of HIV particles. We find that immature particles are more than 14-fold stiffer than mature particles and that this large difference is primarily mediated by the HIV envelope cytoplasmic tail domain. Finite element simulation shows that for immature virions the average Young's modulus drops more than eightfold when the cytoplasmic tail domain is deleted (930 vs. 115 MPa). We also find a striking correlation between the softening of viruses during maturation and their ability to enter cells, providing the first evidence, to our knowledge, for a prominent role for virus mechanical properties in the infection process. These results show that HIV regulates its mechanical properties at different stages of its life cycle (i.e., stiff during viral budding versus soft during entry) and that this regulation may be important for efficient infectivity. Our report of this maturation-induced “stiffness switch” in HIV establishes the groundwork for mechanistic studies of how retroviral particles can regulate their mechanical properties to affect biological function. PMID:17158573

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function.

PubMed

Concepcion, Axel R; Vaeth, Martin; Wagner, Larry E; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S; Cuk, Mario; Yule, David I; Feske, Stefan

2016-11-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.

The dicistronic RNA from the mouse LINE-1 retrotransposon contains an internal ribosome entry site upstream of each ORF: implications for retrotransposition

PubMed Central

2006-01-01

Most eukaryotic mRNAs are monocistronic and translated by cap-dependent initiation. LINE-1 RNA is exceptional because it is naturally dicistronic, encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Here, we show that sequences upstream of ORF1 and ORF2 in mouse L1 function as internal ribosome entry sites (IRESes). Deletion analysis of the ORF1 IRES indicates that RNA structure is critical for its function. Conversely, the ORF2 IRES localizes to 53 nt near the 3′ end of ORF1, and appears to depend upon sequence rather than structure. The 40 nt intergenic region (IGR) is not essential for ORF2 IRES function or retrotransposition. Because of strong cis-preference for both proteins during L1 retrotransposition, correct stoichiometry of the two proteins can only be achieved post-transcriptionally. Although the precise stoichiometry is unknown, the retrotransposition intermediate likely contains hundreds of ORF1ps for every ORF2p, together with one L1 RNA. IRES-mediated translation initiation is a well-established mechanism of message-specific regulation, hence, unique mechanisms for the recognition and control of these two IRESes in the L1 RNA could explain differences in translational efficiency of ORF1 and ORF2. In addition, translational regulation may provide an additional layer of control on L1 retrotransposition efficiency, thereby protecting the integrity of the genome. PMID:16464823

Implementation of a Web-Based Organ Donation Educational Intervention: Development and Use of a Refined Process Evaluation Model

PubMed Central

Harker, Laura; Bamps, Yvan; Flemming, Shauna St. Clair; Perryman, Jennie P; Thompson, Nancy J; Patzer, Rachel E; Williams, Nancy S DeSousa; Arriola, Kimberly R Jacob

2017-01-01

Background The lack of available organs is often considered to be the single greatest problem in transplantation today. Internet use is at an all-time high, creating an opportunity to increase public commitment to organ donation through the broad reach of Web-based behavioral interventions. Implementing Internet interventions, however, presents challenges including preventing fraudulent respondents and ensuring intervention uptake. Although Web-based organ donation interventions have increased in recent years, process evaluation models appropriate for Web-based interventions are lacking. Objective The aim of this study was to describe a refined process evaluation model adapted for Web-based settings and used to assess the implementation of a Web-based intervention aimed to increase organ donation among African Americans. Methods We used a randomized pretest-posttest control design to assess the effectiveness of the intervention website that addressed barriers to organ donation through corresponding videos. Eligible participants were African American adult residents of Georgia who were not registered on the state donor registry. Drawing from previously developed process evaluation constructs, we adapted reach (the extent to which individuals were found eligible, and participated in the study), recruitment (online recruitment mechanism), dose received (intervention uptake), and context (how the Web-based setting influenced study implementation) for Internet settings and used the adapted model to assess the implementation of our Web-based intervention. Results With regard to reach, 1415 individuals completed the eligibility screener; 948 (67.00%) were determined eligible, of whom 918 (96.8%) completed the study. After eliminating duplicate entries (n=17), those who did not initiate the posttest (n=21) and those with an invalid ZIP code (n=108), 772 valid entries remained. Per the Internet protocol (IP) address analysis, only 23 of the 772 valid entries (3.0%) were within Georgia, and only 17 of those were considered unique entries and could be considered for analyses. With respect to recruitment, 517 of the 772 valid entries (67.0%) of participants were recruited from a Web recruiter. Regarding dose received, no videos from the intervention website were watched in their entirety, and the average viewing duration was 17 seconds over the minimum. With respect to context, context analysis provided us with valuable insights into factors in the Internet environment that may have affected study implementation. Although only active for a brief period of time, the Craigslist website advertisement may have contributed the largest volume of fraudulent responses. Conclusions We determined fraud and low uptake to be serious threats to this study and further confirmed the importance of conducting a process evaluation to identify such threats. We suggest checking participants’ IP addresses before study initiation, selecting software that allows for automatic duplicate protection, and tightening minimum requirements for intervention uptake. Further research is needed to understand how process evaluation models can be used to monitor implementation of Web-based studies. PMID:29191799

Identification of YfiH and the Catalase CatA As Polyphenol Oxidases of Aeromonas media and CatA as a Regulator of Pigmentation by Its Peroxyl Radical Scavenging Capacity

PubMed Central

Chai, Baozhong; Qiao, Yunqian; Wang, He; Zhang, Xiaoming; Wang, Jiao; Wang, Choushi; Zhou, Ping; Chen, Xiangdong

2017-01-01

Pyomelanin is the major constituent of pigment in melanogenic Aeromonas strains of bacteria. However, eumelanin, synthesized from tyrosine via L-DOPA and polyphenol oxidases (PPOs), may also be present in this genus since L-DOPA is frequently detected in culture fluids of several species. To address this question, we used a deletion mutant of Aeromonas media strain WS, in which pyomelanin synthesis is completely blocked under normal culture conditions. When tyrosine was supplied to the medium, we observed residual melanin accumulation, which we interpret as evidence for existence of the DOPA-melanin pathway. We traced enzymatic activity in this bacterium using native-polyacrylamide gel electrophoresis. Two PPOs: YfiH, a laccase-like protein, and CatA, a catalase, were identified. However, neither protein was critical for the residual pigmentation in pyomelanin-deficient mutant. We speculate that eumelanin synthesis may require other unknown enzymes. Deletion of yfiH did not affect pigmentation in A. media strain WS, while deletion of the CatA-encoding gene katE resulted in a reduction of melanin accumulation, but it started 9 h earlier than in the wild-type. Since catalases regulate reactive oxygen species levels during melanogenesis, we speculated that CatA affects pigmentation through its peroxyl radical scavenging capacity. Consistent with this, expression of the catalases Hpi or Hpii from Escherichia coli in the katE deletion strain of A. media strain WS restored pigmentation to the wild-type level. Hpi and Hpii also exhibited PPO activity, suggesting that catalase may represent a new class of PPOs. PMID:29051758

Enhanced oxygen consumption in Herbaspirillum seropedicae fnr mutants leads to increased NifA mediated transcriptional activation.

PubMed

Batista, Marcelo Bueno; Wassem, Roseli; Pedrosa, Fábio de Oliveira; de Souza, Emanuel Maltempi; Dixon, Ray; Monteiro, Rose Adele

2015-05-07

Orthologous proteins of the Crp/Fnr family have been previously implicated in controlling expression and/or activity of the NifA transcriptional activator in some diazotrophs. This study aimed to address the role of three Fnr-like proteins from H. seropedicae SmR1 in controlling NifA activity and consequent NifA-mediated transcription activation. The activity of NifA-dependent transcriptional fusions (nifA::lacZ and nifB::lacZ) was analysed in a series of H. seropedicae fnr deletion mutant backgrounds. We found that combined deletions in both the fnr1 and fnr3 genes lead to higher expression of both the nifA and nifB genes and also an increased level of nifH transcripts. Expression profiles of nifB under different oxygen concentrations, together with oxygen consumption measurements suggest that the triple fnr mutant has higher respiratory activity when compared to the wild type, which we believe to be responsible for greater stability of the oxygen sensitive NifA protein. This conclusion was further substantiated by measuring the levels of NifA protein and its activity in fnr deletion strains in comparison with the wild-type. Fnr proteins are indirectly involved in controlling the activity of NifA in H. seropedicae, probably as a consequence of their influence on respiratory activity in relation to oxygen availability. Additionally we can suggest that there is some redundancy in the physiological function of the three Fnr paralogs in this organism, since altered respiration and effects on NifA activity are only observed in deletion strains lacking both fnr1 and fnr3.

Representations of Linguistic and Ethnocultural Diversity in Poland's Education Policy, National School Curricula and Textbooks

ERIC Educational Resources Information Center

Kowalski, Ewa

2008-01-01

With its recent entry into the European Union (EU) and the adoption of multiethnic democracy as a national policy, a key challenge for Poland is to transform its education policy and practice in ways that are consistent with multicultural and pluralist values. This paper examines Poland's efforts to address these issues by exploring changes in the…

Can Genetics and Genomics Nursing Competencies Be Successfully Taught in a Prenursing Microbiology Course?

ERIC Educational Resources Information Center

Shuster, Michele

2011-01-01

In recognition of the entry into the era of personalized medicine, a new set of genetics and genomics competencies for nurses was introduced in 2006. Since then, there have been a number of reports about the critical importance of these competencies for nursing practices and about the challenges of addressing these competencies in the preservice…

Modeling Developmental Language Difficulties from School Entry into Adulthood: Literacy, Mental Health, and Employment Outcomes

ERIC Educational Resources Information Center

Law, James; Rush, Robert; Schoon, Ingrid; Parsons, Samantha

2009-01-01

Purpose: Understanding the long-term outcomes of developmental language difficulties is key to knowing what significance to attach to them. To date, most prognostic studies have tended to be clinical rather than population-based, which necessarily affects the interpretation. This study sought to address this issue using data from a U.K. birth…

Preschool Center Quality and School Readiness: Quality Main Effects and Variation by Demographic and Child Characteristics

ERIC Educational Resources Information Center

Dang, Tran T.; Farkas, George; Burchinal, Margaret R.; Duncan, Greg J.; Vandell, Deborah L.; Li, Weilin; Ruzek, Erik A.; Howes, Carollee

2011-01-01

The aim of this paper is to address two research questions related to the policy goal of having all children ready to learn at kindergarten entry. First, to what extent are children's cognitive and achievement skills higher when they experience higher quality preschools? Second, are the effects of preschool center quality on these school readiness…

78 FR 6849 - Agency Information Collection (eBenefits Portal) Activity under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... for a single sign-on credential that will ultimately be shared by other VA and DoD portals. The e...: Comments must be submitted on or before March 4, 2013. ADDRESSES: Submit written comments on the collection..., a joint project between the VA and DoD, is intended to serve as a single point of entry for benefits...

76 FR 62149 - Proposed Collection; Comment Request; Renewal With Changes to a Currently Approved Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... , again with a caption, in the body of the text, ``Attention: PRA Comments--MSB Registration--Form 107... box to indicate a foreign country, adds a box to indicate the type of taxpayer identification number... entry expansion, TIN and TIN type as in part II. E-mail address and Web site info is added and removes...

Supporting New Special Education Teachers: How Online Resources and Web 2.0 Technologies Can Help

ERIC Educational Resources Information Center

Billingsley, Bonnie; Israel, Maya; Smith, Sean

2011-01-01

New special education teachers (SETs) face some typical challenges as well as ones that are specific to their particular work settings. Providing support that addresses teachers' unique needs is important for increasing their effectiveness, helping them make a smooth entry into teaching, and reducing their stress and turnover. Nearly 20 years ago,…

Environmental Field Trips - Some Places to Visit in Maryland, Virginia and the District of Columbia.

ERIC Educational Resources Information Center

Meetre, Jeff

This publication lists 40 places in the metropolitan Washington, D.C. area that could be visited on an environmental field trip. The sites are placed into five categories: (1) Air Monitoring; (2) Ecology and Nature Study; (3) Solid Waste Management; (4) Wastewater Treatment; and (5) Water Supply. Each entry includes name, address, and phone number…

Publicaciones Periodicas de Educacion de America Latina y el Caribe (Educational Publications of Latin America and the Caribbean).

ERIC Educational Resources Information Center

Oficina Regional de Educacion de la Unesco para America Latina y el Caribe, Santiago (Chile).

The periodicals listed in this bibliography are those published in Latin America and the Caribbean that deal exclusively with educational themes. Information for each entry, when available, includes the title, subtitle, name and address of publisher, frequency of publication, year the publication began and/or terminated, any previous title, and…

Drawing Parallels in Search of Educational Equity: A Multicultural Education Delegation to China Looks Outside to See Within

ERIC Educational Resources Information Center

Carjuzaa, Jioanna; Fenimore-Smith, J. Kay; Fuller, Ethlyn Davis; Howe, William A.; Kugler, Eileen; London, Arcenia P.; Ruiz, Ivette; Shin, Barbara

2008-01-01

In 2004, a professional delegation of multicultural educators visited the People's Republic of China to explore how diversity issues are addressed and how students are prepared for entry into the international workforce. The delegation, sponsored by the People to People Ambassador Programs, observed numerous parallels to the American system of…

78 FR 28794 - Control Date for Qualifying Landings History and To Limit Speculative Entry Into the Longfin...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... should be controlled. DATES: May 16, 2013, shall be known as the ``control date'' for the longfin squid... laws. Written comments must be received on or before 5 p.m., local time June 17, 2013. ADDRESSES: You may submit comments on this document, identified by NOAA-NMFS-2013-0076 by any of the following...

77 FR 53901 - Notification of the Imposition of Conditions of Entry for Certain Vessels Arriving to the United...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-04

... Principe, Syria, Timor-Leste, Venezuela, and Yemen. This current list is also available in the policy... Hodeidah. DATES: The policy announced in this notice will become effective September 18, 2012. ADDRESSES... telephone number is 202-366-9329. This policy is also available at www.homeport.uscg.mil under the Maritime...

Education: Guide to European Organizations and Programmes. A Guide to European Organizations Involved in Education, including Individual Programmes and Projects.

ERIC Educational Resources Information Center

Hayes, Heledd

This report presents a guide to European organizations involved in education, including individual programs and projects. Entries are brief as they are intended as simple outlines of the organizations or programs, but full addresses and telephone numbers are provided. Divided into four categories, the organizations listed are as follows: (1)…

Improving data collection, documentation, and workflow in a dementia screening study

PubMed Central

Read, Kevin B.; LaPolla, Fred Willie Zametkin; Tolea, Magdalena I.; Galvin, James E.; Surkis, Alisa

2017-01-01

Background A clinical study team performing three multicultural dementia screening studies identified the need to improve data management practices and facilitate data sharing. A collaboration was initiated with librarians as part of the National Library of Medicine (NLM) informationist supplement program. The librarians identified areas for improvement in the studies’ data collection, entry, and processing workflows. Case Presentation The librarians’ role in this project was to meet needs expressed by the study team around improving data collection and processing workflows to increase study efficiency and ensure data quality. The librarians addressed the data collection, entry, and processing weaknesses through standardizing and renaming variables, creating an electronic data capture system using REDCap, and developing well-documented, reproducible data processing workflows. Conclusions NLM informationist supplements provide librarians with valuable experience in collaborating with study teams to address their data needs. For this project, the librarians gained skills in project management, REDCap, and understanding of the challenges and specifics of a clinical research study. However, the time and effort required to provide targeted and intensive support for one study team was not scalable to the library’s broader user community. PMID:28377680

Entry mechanisms of herpes simplex virus 1 into murine epidermis: involvement of nectin-1 and herpesvirus entry mediator as cellular receptors.

PubMed

Petermann, Philipp; Thier, Katharina; Rahn, Elena; Rixon, Frazer J; Bloch, Wilhelm; Özcelik, Semra; Krummenacher, Claude; Barron, Martin J; Dixon, Michael J; Scheu, Stefanie; Pfeffer, Klaus; Knebel-Mörsdorf, Dagmar

2015-01-01

Skin keratinocytes represent a primary entry site for herpes simplex virus 1 (HSV-1) in vivo. The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) act as efficient receptors for both serotypes of HSV and are sufficient for disease development mediated by HSV-2 in mice. How HSV-1 enters skin and whether both nectin-1 and HVEM are involved are not known. We addressed the impact of nectin-1 during entry of HSV-1 into murine epidermis and investigated the putative contribution of HVEM. Using ex vivo infection of murine epidermis, we showed that HSV-1 entered the basal keratinocytes of the epidermis very efficiently. In nectin-1-deficient epidermis, entry was strongly reduced. Almost no entry was observed, however, in nectin-1-deficient keratinocytes grown in culture. This observation correlated with the presence of HVEM on the keratinocyte surface in epidermis and with the lack of HVEM expression in nectin-1-deficient primary keratinocytes. Our results suggest that nectin-1 is the primary receptor in epidermis, while HVEM has a more limited role. For primary murine keratinocytes, on which nectin-1 acts as a single receptor, electron microscopy suggested that HSV-1 can enter both by direct fusion with the plasma membrane and via endocytic vesicles. Thus, we concluded that nectin-1 directs internalization into keratinocytes via alternative pathways. In summary, HSV-1 entry into epidermis was shown to strongly depend on the presence of nectin-1, but the restricted presence of HVEM can potentially replace nectin-1 as a receptor, illustrating the flexibility employed by HSV-1 to efficiently invade tissue in vivo. Herpes simplex virus (HSV) can cause a range of diseases in humans, from uncomplicated mucocutaneous lesions to life-threatening infections. The skin is one target tissue of HSV, and the question of how the virus overcomes the protective skin barrier and penetrates into the tissue to reach its receptors is still open. Previous studies analyzing entry into cells grown in vitro revealed nectin-1 and HVEM as HSV receptors. To explore the contributions of nectin-1 and HVEM to entry into a natural target tissue, we established an ex vivo infection model. Using nectin-1- or HVEM-deficient mice, we demonstrated the distinct involvement of nectin-1 and HVEM for HSV-1 entry into epidermis and characterized the internalization pathways. Such advances in understanding the involvement of receptors in tissue are essential preconditions for unraveling HSV invasion of skin, which in turn will allow the development of antiviral reagents. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Efficient genome engineering of a virulent Klebsiella bacteriophage using CRISPR-Cas9.

PubMed

Shen, Juntao; Zhou, Jinjie; Chen, Guo-Qiang; Xiu, Zhi-Long

2018-06-13

Klebsiella pneumoniae is one of the most common nosocomial opportunistic pathogens usually with multiple drug-resistance. Phage therapy, a potential new therapeutics to replace or supplement antibiotics, has attracted much attention. However, very few Klebsiella phages have been well-characterized as the lack of efficient genome editing tools. Here, Cas9 from Streptococcus pyogenes and a single guide RNA (sgRNA) were used to modify a virulent Klebsiella bacteriophage phiKpS2. We firstly evaluated the distribution of sgRNA activity in phages and proved that it's largely inconsistent with the predicted activity from current models trained on eukaryotic cell datasets. A simple CRISPR-based phage genome editing procedure was developed based on the discovery that homologous arms as short as 30-60 bp was sufficient to introduce point mutation, gene deletion and swap. We also demonstrated that weak sgRNAs could be used for precise phage genome editing but failed to select random recombinants, possibly because inefficient cleavage can be tolerated through continuous repair by homologous recombination with the uncut genomes. Small frameshift deletion was proved to be an efficient way to evaluate the essentiality of phage genes. By using the above strategies, a putative promoter and nine genes of phiKpS2 were successfully deleted. Interestingly, the holin gene can be deleted with little effect on phiKpS2 infection, but the reason is not yet clear. This study established an efficient, time-saving, and cost-effective procedure for phage genome editing, which is expected to significantly promote the development of bacteriophage therapy. IMPORTANCE In the present study, we have addressed an efficient, time-saving and cost-effective CRISPR-based phage genome editing of Klebsiella phage, which has the potential to significantly expand our knowledge of phage-host interactions and to promote the applications of phage therapy. The distribution of sgRNA activity was first evaluated in phages. Short homologous arms were proved enough to introduce point mutation, small frameshift deletion, gene deletion and swap into phages, and weak sgRNAs were proved useful for precise phage genome editing but failed to select random recombinants, which all make the CRISPR-based phage genome editing easier to use. Copyright © 2018 American Society for Microbiology.

Base Flow Investigation of the Apollo AS-202 Command Module. Chapter 6

NASA Technical Reports Server (NTRS)

Walpot, Louis M. G.; Wright, Michael J.; Noeding, Peter; Schrijer, Ferry

2011-01-01

In recent years, both Europe and the US are developing hypersonic research and operational vehicles. These include (re)entry capsules (both ballistic and lifting) and lifting bodies such as ExoMars, EXPERT, ARV, CEV and IXV. The research programs are meant to enable technology and engineering capabilities to support during the next decade the development of affordable (possibly reusable) space transportation systems as well as hypersonic weapons systems for time critical targets. These programs have a broad range of goals, ranging from the qualification of thermal protection systems, the assessment of RCS performances, the development of GNC algorithms, to the full demonstration of the performance and operability of the integrated vehicles. Since the aerothermodynamic characteristics influence nearly all elements of the vehicle design, the accurate prediction of the aerothermal environment is a prerequisite for the design of efficient hypersonic systems. Significant uncertainties in the prediction of the hypersonic aerodynamic and the aerothermal loads can lead to conservative margins in the design of the vehicle including its Outer Mould Line (OML), thermal protection system, structure, and required control system robustness. The current level of aerothermal prediction uncertainties results therefore in reduced vehicle performances (e.g., sub-optimal payload to mass ratio, increased operational constraints). On the other hand, present computational capabilities enable the simulation of three dimensional flow fields with complex thermo-chemical models over complete trajectories and ease the validation of these tools by, e.g., reconstruction of detailed wind tunnel tests performed under identified and controlled conditions (flow properties and vehicle attitude in particular). These controlled conditions are typically difficult to achieve when performing in flight measurements which in turn results in large associated measurement uncertainties. Similar problems arise when attempting to rebuild measurements performed in "hot" ground facilities, where the difficulty level is increased by the addition of the free-flow characterization itself. The implementation of ever more sophisticated thermochemical models is no obvious cure to the aforementioned problems since their effect is often overwhelmed by the large measurement uncertainties incurred in both flight and ground high enthalpy facilities. Concurrent to the previous considerations, a major contributor to the overall vehicle mass of re-entry vehicles is the afterbody thermal protection system. This is due to the large acreage (equal or bigger than that of the forebody) to be protected. The present predictive capabilities for base flows are comparatively lower than those for windward flowfields and offer therefore a substantial potential for improving the design of future re-entry vehicles. To that end, it is essential to address the accuracy of high fidelity CFD tools exercised in the US and EU, which motivates a thorough investigation of the present status of hypersonic flight afterbody heating. This paper addresses the predictive capabilities of after body flow fields of re-entry vehicles investigated in the frame of the NATO/RTO - RTG-043 Task Group and is structured as follows: First, the verification of base flow topologies on the basis of available wind-tunnel results performed under controlled supersonic conditions (i.e., cold flows devoid of reactive effects) is performed. Such tests address the detailed characterization of the base flow with particular emphasis on separation/reattachment and their relation to Mach number effects. The tests have been performed on an Apollo-like re-entry capsule configuration. Second, the tools validated in the frame of the previous effort are exercised and appraised against flight-test data collected during the Apollo AS-202 re-entry.

Public Risk Assessment Program

NASA Technical Reports Server (NTRS)

Mendeck, Gavin

2010-01-01

The Public Entry Risk Assessment (PERA) program addresses risk to the public from shuttle or other spacecraft re-entry trajectories. Managing public risk to acceptable levels is a major component of safe spacecraft operation. PERA is given scenario inputs of vehicle trajectory, probability of failure along that trajectory, the resulting debris characteristics, and field size and distribution, and returns risk metrics that quantify the individual and collective risk posed by that scenario. Due to the large volume of data required to perform such a risk analysis, PERA was designed to streamline the analysis process by using innovative mathematical analysis of the risk assessment equations. Real-time analysis in the event of a shuttle contingency operation, such as damage to the Orbiter, is possible because PERA allows for a change to the probability of failure models, therefore providing a much quicker estimation of public risk. PERA also provides the ability to generate movie files showing how the entry risk changes as the entry develops. PERA was designed to streamline the computation of the enormous amounts of data needed for this type of risk assessment by using an average distribution of debris on the ground, rather than pinpointing the impact point of every piece of debris. This has reduced the amount of computational time significantly without reducing the accuracy of the results. PERA was written in MATLAB; a compiled version can run from a DOS or UNIX prompt.

Magnetohydrodynamic Power Generation in the Laboratory Simulated Martian Entry Plasma

NASA Technical Reports Server (NTRS)

Vuskovic, L.; Popovic, S.; Drake, J.; Moses, R. W.

2005-01-01

This paper addresses the magnetohydrodynamic (MHD) conversion of the energy released during the planetary entry phase of an interplanetary vehicle trajectory. The effect of MHD conversion is multi-fold. It reduces and redirects heat transferred to the vehicle, and regenerates the dissipated energy in reusable and transportable form. A vehicle on an interplanetary mission carries about 10,000 kWh of kinetic energy per ton of its mass. This energy is dissipated into heat during the planetary atmospheric entry phase. For instance, the kinetic energy of Mars Pathfinder was about 4220 kWh. Based on the loss in velocity, Mars Pathfinder lost about 92.5% of that energy during the plasma-sustaining entry phase that is approximately 3900 kWh. An ideal MHD generator, distributed over the probe surface of Mars Pathfinder could convert more than 2000 kWh of this energy loss into electrical energy, which correspond to more than 50% of the kinetic energy loss. That means that the heat transferred to the probe surface can be reduced by at least 50% if the converted energy is adequately stored, or re-radiated, or directly used. Therefore, MHD conversion could act not only as the power generating, but also as the cooling process. In this paper we describe results of preliminary experiments with light and microwave emitters powered by model magnetohydrodynamic generators and discuss method for direct use of converted energy.

Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis

PubMed Central

Jackson, Abigail; Kasah, Sahrunizam; Mansour, Suzanne L.; Morrow, Bernice; Basson, M. Albert

2015-01-01

Background The T-box transcription factor Tbx1, is essential for the normal development of multiple organ systems in the embryo. One of the most striking phenotypes in Tbx1−/− embryos is the failure of the caudal pharyngeal pouches to evaginate from the foregut endoderm. Despite considerable interest in the role of Tbx1 in development, the mechanisms whereby Tbx1 controls caudal pouch formation have remained elusive. In particular, the question as to how Tbx1 expression in the pharyngeal endoderm regulates pharyngeal pouch morphogenesis in the mouse embryo is not known. Results To address this question, we produced mouse embryos in which Tbx1 was specifically deleted from the pharyngeal endoderm and as expected, embryos failed to form caudal pharyngeal pouches. To determine the molecular mechanism, we examined expression of Fgf3 and Fgf8 ligands and downstream effectors. Although Fgf8 expression is greatly reduced in Tbx1-deficient endoderm, FGF signaling levels are unaffected. Furthermore, pouch morphogenesis is only partially perturbed by the loss of both Fgf3 and Fgf8 from the endoderm, indicating that neither are required for pouch formation. Conclusions Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified. PMID:24812002

Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis

PubMed Central

Xuan, Shouhong; Borok, Matthew J.; Decker, Kimberly J.; Battle, Michele A.; Duncan, Stephen A.; Hale, Michael A.; Macdonald, Raymond J.; Sussel, Lori

2012-01-01

Pancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 and Gata6 are expressed in several endoderm-derived tissues, including the pancreas. To analyze the functions of GATA4 and/or GATA6 during mouse pancreatic development, we generated pancreas-specific deletions of Gata4 and Gata6. Surprisingly, loss of either Gata4 or Gata6 in the pancreas resulted in only mild pancreatic defects, which resolved postnatally. However, simultaneous deletion of both Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis, and a subsequent failure to induce the differentiation of progenitor cells expressing carboxypeptidase A1 (CPA1) and neurogenin 3 (NEUROG3). These studies address the conserved and nonconserved mechanisms underlying GATA4 and GATA6 function during pancreas development and provide a new mouse model to characterize the underlying developmental defects associated with pancreatic agenesis. PMID:23006325

Interaction of hemoglobin Grey Lynn (Vientiane) with a non-deletional α(+)-thalassemia in an adult Thai proband.

PubMed

Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

2014-01-01

Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a substitution of Phe for Leu at position 91 of α1-globin chain, originally described in individual of unknown ethnic background. This article addresses the interaction of Hb Grey Lynn with a non-deletional α(+)-thalassemia found in Thailand, a hitherto un-described condition. The proband was adult Thai woman referred for investigation of mild anemia with Hb 90 g/L. Hb analyses using low pressure liquid chromatography raised a suspicion of abnormal Hb presence, which was failed to demonstrate by cellulose acetate electrophoresis and capillary electrophoresis. DNA sequencing identified a CTT (Leu) to TTT (Phe) mutation at codon 91 corresponding to the Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1) on α1-globin gene and a C deletion between codons 36 and 37 on α2-globin gene causing α(+)-thalassemia. As compared to those observed in a compound heterozygote for Hb Grey Lynn / α(0)-thalassemia reported previously, higher MCV (81.7 fL) and MCH (26.3 pg) values with a lower level of Hb Grey Lynn (19.7%) were observed in the proband. The normochromic normocytic anemia observed could be due to the interaction of Hb Grey Lynn with α(+)-thalassemia. The two mutations could be identified using PCR-RFLP and allele-specific PCR assays developed.

Incidental findings on array comparative genomic hybridization: detection of carrier females of dystrophinopathy without any family history.

PubMed

Nguyen, K; Putoux, A; Busa, T; Cordier, M P; Sigaudy, S; Till, M; Chabrol, B; Michel-Calemard, L; Bernard, R; Julia, S; Malzac, P; Labalme, A; Missirian, C; Edery, P; Popovici, C; Philip, N; Sanlaville, D

2015-05-01

Array comparative genomic hybridization (aCGH) has progressively replaced conventional karyotype in the diagnostic strategy of intellectual disability (ID) and congenital malformations. This technique increases not only the diagnostic rate but also the possibility of finding unexpected variants unrelated to the indication of referral, namely incidental findings. The incidental finding of copy number variants (CNVs) located in X-linked genes in girls addresses the crucial question of genetic counseling in the family. We report here five cases of CNVs involving the dystrophin gene detected by aCGH in girls referred for developmental delay, without any family history of dystrophinopathy. The rearrangements included three in-frame deletions; one maternally and two paternally inherited, and two frameshift duplications: one de novo and one from undetermined inheritance. In two cases, the deletion identified in a girl was transmitted by the asymptomatic father. In the case of the maternally inherited deletion, prenatal diagnosis of dystrophinopathy was proposed for an ongoing pregnancy, whereas the cause of developmental delay in the index case remained unknown. Through these cases, we discussed the challenges of genetic counseling in the family, regarding the predictive issues for male individuals at risk for a muscular dystrophy without precise knowledge of the clinical consequences of some CNVs in the DMD gene. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Deletion of Ku80 causes early aging independent of chronic inflammation and Rag-1-induced DSBs.

PubMed

Holcomb, Valerie B; Vogel, Hannes; Hasty, Paul

2007-01-01

Animal models of premature aging are often defective for DNA repair. Ku80-mutant mice are disabled for nonhomologous end joining; a pathway that repairs both spontaneous DNA double-strand breaks (DSBs) and induced DNA DSBs generated by the action of a complex composed of Rag-1 and Rag-2 (Rag). Rag is essential for inducing DSBs important for assembling V(D)J segments of antigen receptor genes that are required for lymphocyte development. Thus, deletion of either Rag-1 or Ku80 causes severe combined immunodeficiency (scid) leading to chronic inflammation. In addition, Rag-1 induces breaks at non-B DNA structures. Previously we reported Ku80-mutant mice undergo premature aging, yet we do not know the root cause of this phenotype. Early aging may be caused by either defective repair of spontaneous DNA damage, defective repair of Rag-1-induced breaks or chronic inflammation caused by scid. To address this issue, we analyzed aging in control and Ku80-mutant mice deleted for Rag-1 such that both cohorts are scid and suffer from chronic inflammation. We make two observations: (1) chronic inflammation does not cause premature aging in these mice and (2) Ku80-mutant mice exhibit early aging independent of Rag-1. Therefore, this study supports defective repair of spontaneous DNA damage as the root cause of early aging in Ku80-mutant mice.

Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models

PubMed Central

Nguyen, Liem H.; Robinton, Daisy A.; Seligson, Marc; Wu, Linwei; Li, Lin; Rakheja, Dinesh; Comerford, Sarah; Ramezani, Saleh; Sun, Xiankai; Parikh, Monisha; Yang, Erin; Powers, John T.; Shinoda, Gen; Shah, Samar; Hammer, Robert; Daley, George Q.; Zhu, Hao

2014-01-01

SUMMARY Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Thus, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. PMID:25117712