Dosage Compensation of the Sex Chromosomes

PubMed Central

Disteche, Christine M.

2013-01-01

Differentiated sex chromosomes evolved because of suppressed recombination once sex became genetically controlled. In XX/XY and ZZ/ZW systems, the heterogametic sex became partially aneuploid after degeneration of the Y or W. Often, aneuploidy causes abnormal levels of gene expression throughout the entire genome. Dosage compensation mechanisms evolved to restore balanced expression of the genome. These mechanisms include upregulation of the heterogametic chromosome as well as repression in the homogametic sex. Remarkably, strategies for dosage compensation differ between species. In organisms where more is known about molecular mechanisms of dosage compensation, specific protein complexes containing noncoding RNAs are targeted to the X chromosome. In addition, the dosage-regulated chromosome often occupies a specific nuclear compartment. Some genes escape dosage compensation, potentially resulting in sex-specific differences in gene expression. This review focuses on dosage compensation in mammals, with comparisons to fruit flies, nematodes, and birds. PMID:22974302

Antiparasitic efficacy of ivermectin in naturally parasitized sheep.

PubMed

Yazwinski, T A; Greenway, T; Presson, B L; Pote, L M; Featherstone, H; Williams, M

1983-11-01

Sixteen sheep harboring naturally acquired parasitisms were allocated to 1 of 2 treatment groups: (i) sheep given ivermectin in an oral solution at the dosage rate of 200 micrograms/kg of body weight, and (ii) those given the vehicle at a dosage rate of 0.25 ml/kg. All animals were necropsied at 2 weeks after treatment. Parasites and percentages of parasitic reductions, as demonstrated in this trial, were: Dictyocaulus filaria (99.4%), Oestrus ovis first stage instars (100%), Trichuris ovis (98.9%), Strongyloides papillosus (99.8%), Nematodirus spathiger (100%), arrested 4th stage Nematodirus spp (96.2%), Trichostrongylus colubriformis (100%), T axei (100%), Oster tagia circumcincta (100%), Haemonchus contortus (100%), and arrested Haemonchus spp 4th stage larvae (99.9%). The sheep showed no adverse effects due to ivermectin or vehicle administration.

Precise metabolic engineering of carotenoid biosynthesis in Escherichia coli towards a low-cost biosensor.

PubMed

Watstein, Daniel M; McNerney, Monica P; Styczynski, Mark P

2015-09-01

Micronutrient deficiencies, including zinc deficiency, are responsible for hundreds of thousands of deaths annually. A key obstacle to allocating scarce treatment resources is the ability to measure population blood micronutrient status inexpensively and quickly enough to identify those who most need treatment. This paper develops a metabolically engineered strain of Escherichia coli to produce different colored pigments (violacein, lycopene, and β-carotene) in response to different extracellular zinc levels, for eventual use in an inexpensive blood zinc diagnostic test. However, obtaining discrete color states in the carotenoid pathway required precise engineering of metabolism to prevent reaction at low zinc concentrations but allow complete reaction at higher concentrations, and all under the constraints of natural regulator limitations. Hence, the metabolic engineering challenge was not to improve titer, but to enable precise control of pathway state. A combination of gene dosage, post-transcriptional, and post-translational regulation was necessary to allow visible color change over physiologically relevant ranges representing a small fraction of the regulator's dynamic response range, with further tuning possible by modulation of precursor availability. As metabolic engineering expands its applications and develops more complex systems, tight control of system components will likely become increasingly necessary, and the approach presented here can be generalized to other natural sensing systems for precise control of pathway state. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

48 CFR 9904.413 - Adjustment and allocation of pension cost.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Adjustment and allocation of pension cost. 9904.413 Section 9904.413 Federal Acquisition Regulations System COST ACCOUNTING... AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.413 Adjustment and allocation of pension...

Fish oil supplemental dose needed to reach 1g% DHA+EPA in mature milk.

PubMed

Stoutjesdijk, E; Schaafsma, A; Dijck-Brouwer, D A J; Muskiet, F A J

2018-01-01

Erythrocyte (RBC) DHA+EPA is considered optimal at 8g%. Mothers with lifetime high fish intakes exhibiting this status produce milk with about 1g% DHA+EPA. We established DHA+EPA supplemental dosages needed to augment RBC DHA+EPA to 8g% and milk DHA+EPA to 1g%. Pregnant women were randomly allocated to DHA+EPA dosages of: 225+90 (n=9), 450+180 (n=9), 675+270 (n=11) and 900+360 (n=7) mg/day. Samples were collected at 20 and 36 gestational weeks and 4 weeks postpartum. Linear regression revealed needed dosages rounded at 750mg/day to reach 8g% RBC DHA+EPA and 1000mg/day for 1g% milk DHA+EPA. RBC DHA+EPA increment depended on baseline values. There was no effect on milk AA, but milk EPA/AA ratio increased. Women with an RBC DHA+EPA status of 5.5g% need 750 and 1000mg DHA+EPA/day to reach 8g% RBC DHA+EPA at the pregnancy end and 1g% mature milk DHA+EPA, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

48 CFR 9904.403 - Allocation of home office expenses to segments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Allocation of home office expenses to segments. 9904.403 Section 9904.403 Federal Acquisition Regulations System COST ACCOUNTING... AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403 Allocation of home office expenses to...

[Oral controlled release dosage forms].

PubMed

Mehuys, Els; Vervaet, Chris

2010-06-01

Several technologies to control drug release from oral dosage forms have been developed. Drug release can be regulated in several ways: sustained release, whereby the drug is released slowly over a prolonged period of time, postponed release, whereby drug release is delayed until passage from the stomach into the intestine (via enteric coating), and targeted release, whereby the drug is targeted to a specific location of the gastrointestinal tract. This article reviews the various oral controlled release dosage forms on the market.

Speaking truth to power: the effect of candid feedback on how individuals with power allocate resources.

PubMed

Oc, Burak; Bashshur, Michael R; Moore, Celia

2015-03-01

Subordinates are often seen as impotent, able to react to but not affect how powerholders treat them. Instead, we conceptualize subordinate feedback as an important trigger of powerholders' behavioral self-regulation and explore subordinates' reciprocal influence on how powerholders allocate resources to them over time. In 2 experiments using a multiparty, multiround dictator game paradigm, we found that when subordinates provided candid feedback about whether they found prior allocations to be fair or unfair, powerholders regulated how self-interested their allocations were over time. However, when subordinates provided compliant feedback about powerholders' prior allocation decisions (offered consistently positive feedback, regardless of the powerholders' prior allocation), those powerholders made increasingly self-interested allocations over time. In addition, we showed that guilt partially mediates this relationship: powerholders feel more guilty after receiving negative feedback about an allocation, subsequently leading to a less self-interested allocation, whereas they feel less guilty after receiving positive feedback about an allocation, subsequently taking more for themselves. Our findings integrate the literature on upward feedback with theory about moral self-regulation to support the idea that subordinates are an important source of influence over those who hold power over them. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

The Role of Xist in X-Chromosome Dosage Compensation.

PubMed

Sahakyan, Anna; Yang, Yihao; Plath, Kathrin

2018-06-14

In each somatic cell of a female mammal one X chromosome is transcriptionally silenced via X-chromosome inactivation (XCI), initiating early in development. Although XCI events are conserved in mouse and human postimplantation development, regulation of X-chromosome dosage in preimplantation development occurs differently. In preimplantation development, mouse embryos undergo imprinted form of XCI, yet humans lack imprinted XCI and instead regulate gene expression of both X chromosomes by dampening transcription. The long non-coding RNA Xist/XIST is expressed in mouse and human preimplantation and postimplantation development to orchestrate XCI, but its role in dampening is unclear. In this review, we discuss recent advances in our understanding of the role of Xist in X chromosome dosage compensation in mouse and human. Copyright © 2018 Elsevier Ltd. All rights reserved.

Convergent origination of a Drosophila-like dosage compensation mechanism in a reptile lineage

PubMed Central

Marin, Ray; Cortez, Diego; Lamanna, Francesco; Pradeepa, Madapura M.; Leushkin, Evgeny; Julien, Philippe; Liechti, Angélica; Halbert, Jean; Brüning, Thoomke; Mössinger, Katharina; Trefzer, Timo; Conrad, Christian; Kerver, Halie N.; Wade, Juli; Tschopp, Patrick; Kaessmann, Henrik

2017-01-01

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (Anolis carolinensis), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that Anolis sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage. The age of this system approximately coincides with the ages of the avian and two mammalian sex chromosomes systems. To compensate for the almost complete Y Chromosome degeneration, X-linked genes have become twofold up-regulated, restoring ancestral expression levels. The highly efficient dosage compensation mechanism of Anolis represents the only vertebrate case identified so far to fully support Ohno's original dosage compensation hypothesis. Further analyses reveal that X up-regulation occurs only in males and is mediated by a male-specific chromatin machinery that leads to global hyperacetylation of histone H4 at lysine 16 specifically on the X Chromosome. The green anole dosage compensation mechanism is highly reminiscent of that of the fruit fly, Drosophila melanogaster. Altogether, our work unveils the convergent emergence of a Drosophila-like dosage compensation mechanism in an ancient reptilian sex chromosome system and highlights that the evolutionary pressures imposed by sex chromosome dosage reductions in different amniotes were resolved in fundamentally different ways. PMID:29133310

Convergent origination of a Drosophila-like dosage compensation mechanism in a reptile lineage.

PubMed

Marin, Ray; Cortez, Diego; Lamanna, Francesco; Pradeepa, Madapura M; Leushkin, Evgeny; Julien, Philippe; Liechti, Angélica; Halbert, Jean; Brüning, Thoomke; Mössinger, Katharina; Trefzer, Timo; Conrad, Christian; Kerver, Halie N; Wade, Juli; Tschopp, Patrick; Kaessmann, Henrik

2017-12-01

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard ( Anolis carolinensis ), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that Anolis sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage. The age of this system approximately coincides with the ages of the avian and two mammalian sex chromosomes systems. To compensate for the almost complete Y Chromosome degeneration, X-linked genes have become twofold up-regulated, restoring ancestral expression levels. The highly efficient dosage compensation mechanism of Anolis represents the only vertebrate case identified so far to fully support Ohno's original dosage compensation hypothesis. Further analyses reveal that X up-regulation occurs only in males and is mediated by a male-specific chromatin machinery that leads to global hyperacetylation of histone H4 at lysine 16 specifically on the X Chromosome. The green anole dosage compensation mechanism is highly reminiscent of that of the fruit fly, Drosophila melanogaster Altogether, our work unveils the convergent emergence of a Drosophila -like dosage compensation mechanism in an ancient reptilian sex chromosome system and highlights that the evolutionary pressures imposed by sex chromosome dosage reductions in different amniotes were resolved in fundamentally different ways. © 2017 Marin et al.; Published by Cold Spring Harbor Laboratory Press.

48 CFR 8.705-3 - Allocation process.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Allocation process. 8.705-3 Section 8.705-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition From Nonprofit Agencies Employing People Who...

76 FR 38554 - Oral Dosage Form New Animal Drugs; Amprolium

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by Cross...

77 FR 4226 - Oral Dosage Form New Animal Drugs; Gentamicin Sulfate

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Gentamicin Sulfate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA...

75 FR 76259 - Oral Dosage Form New Animal Drugs; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by...

75 FR 54492 - Oral Dosage Form New Animal Drugs; Tiamulin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tiamulin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Novartis Animal...

A system for dosage-based functional genomics in poplar

Treesearch

Isabelle M. Henry; Matthew S. Zinkgraf; Andrew T. Groover; Luca Comai

2015-01-01

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by...

Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate.

PubMed

Dawes, H E; Berlin, D S; Lapidus, D M; Nusbaum, C; Davis, T L; Meyer, B J

1999-06-11

In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome dosage compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate dosage compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the dosage compensation complex, suggesting that SDC-2 targets dosage compensation machinery to X chromosomes.

Plasma disposition, milk excretion and parasitological efficacy of mebendazole in donkeys naturally infected by Cyathostominae.

PubMed

Gokbulut, Cengiz; Aksit, Dilek; Santoro, Mario; Roncoroni, Cristina; Mariani, Ugo; Buono, Francesco; Rufrano, Domenico; Fagiolo, Antonio; Veneziano, Vincenzo

2016-02-15

Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body weight (MBZ 1) and at the double horse dosage 20 mg/kg body weight (MBZ 2). Blood and milk samples were collected at various times between 1h and 120 h post treatment and analyzed by high performance liquid chromatography with photodiode array detector. Individual FECs (Faecal Egg Counts) were performed on each animal before the treatment (day-3) and weekly from day 7 until day 56 post treatment using a modified McMaster technique. The plasma concentrations and systemic exposure of MBZ in donkeys were relatively lower compared with the other methylcarbamate benzimidazoles. Dose-dependent plasma dispositions of MBZ were observed at the increased dosage (10 mg/kg vs 20 mg/kg) in donkeys. MBZ was not detected in any milk samples at a dosage of 10 mg/kg. However, the parent drug reached 0.01 μg/ml peak milk concentration at 10.66 h and AUCmilk/AUCplasma value was 0.18 ± 0.02 at a dosage of 20 mg/kg bodyweight. This study indicated that per os administration of MBZ has a minimal disposition rate into the milk and may be used in lactating donkeys with zero milk-withdrawal period. The results of FECRT for both MBZ dosages were efficient (>95% efficacy) until day 28. This trial demonstrates that MBZ oral paste at horse dosage (10 mg/kg B.W.) was effective and safety for the treatment of Cyathostominae in donkeys. Therefore, similar dosage regimens of MBZ could be used for horses and donkeys. Copyright © 2015 Elsevier B.V. All rights reserved.

29 CFR 4044.10 - Manner of allocation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Manner of allocation. 4044.10 Section 4044.10 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN TERMINATIONS ALLOCATION OF ASSETS IN SINGLE-EMPLOYER PLANS Allocation of Assets Allocation of Assets to Benefit Categories § 4044.10 Manner of allocation. (a) General. The...

29 CFR 4044.10 - Manner of allocation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 false Manner of allocation. 4044.10 Section 4044.10 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN TERMINATIONS ALLOCATION OF ASSETS IN SINGLE-EMPLOYER PLANS Allocation of Assets Allocation of Assets to Benefit Categories § 4044.10 Manner of allocation. (a) General. The...

29 CFR 4044.10 - Manner of allocation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Manner of allocation. 4044.10 Section 4044.10 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN TERMINATIONS ALLOCATION OF ASSETS IN SINGLE-EMPLOYER PLANS Allocation of Assets Allocation of Assets to Benefit Categories § 4044.10 Manner of allocation. Link to an...

29 CFR 4044.10 - Manner of allocation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false Manner of allocation. 4044.10 Section 4044.10 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN TERMINATIONS ALLOCATION OF ASSETS IN SINGLE-EMPLOYER PLANS Allocation of Assets Allocation of Assets to Benefit Categories § 4044.10 Manner of allocation. (a) General. The...

48 CFR 31.201-4 - Determining allocability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Determining allocability. 31.201-4 Section 31.201-4 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... for the contract; (b) Benefits both the contract and other work, and can be distributed to them in...

Supply chain carbon footprinting and responsibility allocation under emission regulations.

PubMed

Chen, Jin-Xiao; Chen, Jian

2017-03-01

Reduction of greenhouse gas emissions has become an enormous challenge for any single enterprise and its supply chain because of the increasing concern on global warming. This paper investigates carbon footprinting and responsibility allocation for supply chains involved in joint production. Our study is conducted from the perspective of a social planner who aims to achieve social value optimization. The carbon footprinting model is based on operational activities rather than on firms because joint production blurs the organizational boundaries of footprints. A general model is proposed for responsibility allocation among firms who seek to maximize individual profits. This study looks into ways for the decentralized supply chain to achieve centralized optimality of social value under two emission regulations. Given a balanced allocation for the entire supply chain, we examine the necessity of over-allocation to certain firms under specific situations and find opportunities for the firms to avoid over-allocation. The comparison of the two regulations reveals that setting an emission standard per unit of product will motivate firms to follow the standard and improve their emission efficiencies. Hence, a more efficient and promising policy is needed in contrast to existing regulations on total production. Copyright © 2016 Elsevier Ltd. All rights reserved.

76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... INFORMATION: Bayer HealthCare LLC, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201, filed a...

75 FR 13225 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Flunixin AGENCY: Food and... amending the animal drug regulations to reflect approval of an original abbreviated new animal drug... copy of BANAMINE-S, sponsored by Schering-Plough Animal Health Corp. under NADA 101-479. The ANADA is...

76 FR 40229 - Oral Dosage Form New Animal Drugs; Change of Sponsor

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Change of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug application (NADA) from Virbac AH...

77 FR 4226 - Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application.... 801-808. List of Subjects in 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug...

75 FR 54018 - Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

A System for Dosage-Based Functional Genomics in Poplar

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

Henry, Isabelle M.; Zinkgraf, Matthew S.; Groover, Andrew T.

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-basedmore » functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ~55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis.« less

A System for Dosage-Based Functional Genomics in Poplar

DOE PAGES

Henry, Isabelle M.; Zinkgraf, Matthew S.; Groover, Andrew T.; ...

2015-08-28

Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-basedmore » functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ~55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis.« less

Efficacy of three formulations of diflubenzuron, an insect growth regulator, against Culex quinquefasciatus Say, the vector of Bancroftian filariasis in India

PubMed Central

Sadanandane, C.; Doss, P. S. Boopathi; Jambulingam, P.

2012-01-01

Background & objectives: Insect growth regulators (IGRs) offer alternatives to conventional chemical larvicides that pose problem of resistance and environmental safety. However, only a limited number of IGRs have been approved for use in mosquito control. In the present study, two new formulations of the IGR diflubenzuron, 2 per cent granular (GR) and 2 per cent tablet (DT) were tested for its efficacy against Culex quinquefasciatus, in comparison to its 25 per cent wettable powder (WP) formulation. Methods: The WP, GR and DT formulations were tested in cesspits, street drains and abandoned wells each at four dosages, 25, 50, 75 and 100 g ai/ha. Additionally, the DT formulation was tested at a higher dosage of 1 tablet/m2 (equal to 400 g ai/ha). Results: The WP and GR formulations yielded >80 per cent inhibition of adult emergence (IE) for 7-10 days in cesspits, 4-7 days in street drains and 7-21 days in abandoned wells at all dosages tested. The DT formulation was effective only at higher dosage 100 g ai/ha and or 1 tablet/m2 for 7-15 days at all habitats. Interpretation & conclusions: The trial showed that the dosage 25 g ai/ha of 25 per cent WP could be the field dosage for cesspits and wells, and 50 g ai/ha for drains, to be applied at weekly intervals. The dosages 25, 50 and 100 g ai/ha of 2 per cent GR could be the field dosages for application in cesspits at weekly intervals, in abandoned wells every three weeks and in drains at weekly intervals, respectively. Diflubenzuron 25 per cent WP and 2 per cent GR could be used for larval control of Cx. quinquefasciatus under integrated vector management programme. PMID:23287125

Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

PubMed

Meiklejohn, Colin D; Landeen, Emily L; Cook, Jodi M; Kingan, Sarah B; Presgraves, Daven C

2011-08-01

The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI)--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

29 CFR 4211.4 - Contributions for purposes of the numerator and denominator of the allocation fractions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of the allocation fractions. 4211.4 Section 4211.4 Labor Regulations Relating to Labor (Continued... denominator of the allocation fractions. Each of the allocation fractions used in the presumptive, modified... five-year period. (a) The numerator of the allocation fraction, with respect to a withdrawing employer...

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate.

PubMed

Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-09-27

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes.

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate

PubMed Central

Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-01-01

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes. PMID:27557515

7 CFR 319.40-4 - Application for a permit to import regulated articles; issuance and withdrawal of permits.

Code of Federal Regulations, 2013 CFR

2013-01-01

... and dosage of any chemicals employed in treatments; (5) A description of any processing, treatment, or... where any processing or treatment will be performed and the names and dosage of any chemicals employed... article identified in the application, APHIS shall review the application by applying the plant pest risk...

7 CFR 319.40-4 - Application for a permit to import regulated articles; issuance and withdrawal of permits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... and dosage of any chemicals employed in treatments; (5) A description of any processing, treatment, or... where any processing or treatment will be performed and the names and dosage of any chemicals employed... article identified in the application, APHIS shall review the application by applying the plant pest risk...

Molecular and Cellular Mechanisms for Trapping and Activating Emotional Memories

PubMed Central

Cai, Denise J.; Sano, Yoshitake; Lee, Yong-Seok; Zhou, Yu; Bekal, Pallavi; Deisseroth, Karl; Silva, Alcino J.

2016-01-01

Recent findings suggest that memory allocation to specific neurons (i.e., neuronal allocation) in the amygdala is not random, but rather the transcription factor cAMP-response element binding protein (CREB) modulates this process, perhaps by regulating the transcription of channels that control neuronal excitability. Here, optogenetic studies in the mouse lateral amygdala (LA) were used to demonstrate that CREB and neuronal excitability regulate which neurons encode an emotional memory. To test the role of CREB in memory allocation, we overexpressed CREB in the lateral amygdala to recruit the encoding of an auditory-fear conditioning (AFC) memory to a subset of neurons. Then, post-training activation of these neurons with Channelrhodopsin-2 was sufficient to trigger recall of the memory for AFC, suggesting that CREB regulates memory allocation. To test the role of neuronal excitability in memory allocation, we used a step function opsin (SFO) to transiently increase neuronal excitability in a subset of LA neurons during AFC. Post-training activation of these neurons with Volvox Channelrhodopsin-1 was able to trigger recall of that memory. Importantly, our studies show that activation of the SFO did not affect AFC by either increasing anxiety or by strengthening the unconditioned stimulus. Our findings strongly support the hypothesis that CREB regulates memory allocation by modulating neuronal excitability. PMID:27579481

The micromechanics model analysis of the viscosity regulation of ultra-high strength concrete with low viscosity

NASA Astrophysics Data System (ADS)

Zhu, M.; Wang, F. G.; Wang, F. Z.; Liu, Y. P.

2017-02-01

The plastic viscosity of mortar and concrete with different binder content, sand ratio, water-binder ratio, microbead dosage and different class and dosage of fly ash were tested and calculated according tomicromechanics model proposed by A. Ghanbari and B.L. Karihaloo, The correlations between these parameters and fresh concrete workability were also investigated, which showed i. high consistence with the objective reality. When binder content, microbead dosage, fly ash dosage or the water-binder ratio was increased or sand ratio was reduced, the fresh concrete viscosity would decrease correspondingly. However their effects were not that same. The relationships between T50 a, V-funnel and inverted slump time with fresh concrete viscosity were established, respectively.

47 CFR 64.903 - Cost allocation manuals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Cost allocation manuals. 64.903 Section 64.903... RULES RELATING TO COMMON CARRIERS Allocation of Costs § 64.903 Cost allocation manuals. (a) Each incumbent local exchange carrier having annual revenues from regulated telecommunications operations that...

Dosage Compensation in Mammals

PubMed Central

Brockdorff, Neil; Turner, Bryan M.

2015-01-01

Many organisms show major chromosomal differences between sexes. In mammals, females have two copies of a large, gene-rich chromosome, the X, whereas males have one X and a small, gene-poor Y. The imbalance in expression of several hundred genes is lethal if not dealt with by dosage compensation. The male–female difference is addressed by silencing of genes on one female X early in development. However, both males and females now have only one active X chromosome. This is compensated by twofold up-regulation of genes on the active X. This complex system continues to provide important insights into mechanisms of epigenetic regulation. PMID:25731764

48 CFR 3018.109 - Priorities and allocations.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... 3018.109 Section 3018.109 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) CONTRACT METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS... as authorized by the Defense Priorities and Allocation System (DPAS). (See (HSAR) 48 CFR 3011.602.) ...

48 CFR 3018.109 - Priorities and allocations.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... 3018.109 Section 3018.109 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) CONTRACT METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS... as authorized by the Defense Priorities and Allocation System (DPAS). (See (HSAR) 48 CFR 3011.602.) ...

48 CFR 3018.109 - Priorities and allocations.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... 3018.109 Section 3018.109 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) CONTRACT METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS... as authorized by the Defense Priorities and Allocation System (DPAS). (See (HSAR) 48 CFR 3011.602.) ...

Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.

PubMed

Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

2017-03-01

During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches.

Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling

PubMed Central

Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

2017-01-01

During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches. PMID:28248965

Examining Dosage Effects on Prevention Outcomes: Results from a Multi-Modal Longitudinal Preventive Intervention for Young Disruptive Boys

ERIC Educational Resources Information Center

Charlebois, Pierre; Brendgen, Mara; Vitaro, Frank; Normandeau, Sylvie; Boudreau, Jean-Francois

2004-01-01

The present study examined (a) the predictive effect of disruptive boys' attendance to a prevention program (i.e., dosage) on post-intervention academic achievement and behavior and (b) the potential moderating effects of child and family characteristics in this context. The 3-year intervention program included reading, self-regulation, and social…

Current Subcounty Allocation Practices: Volume I of the Title I, ESEA, Subcounty Allocation Study.

ERIC Educational Resources Information Center

Paller, Alan T.; Gutmann, Babette

In this report, subcounty allocation of Title I of the Elementary and Secondary Education Act (ESEA) funds is described in terms of direct allocation, use of the statutory formula emphasizing census data, United States Office of Education (USOE) regulations, participating states, geographic and administrative overlaps, hold harmless adjustments…

Sexual Dimorphism of Body Size Is Controlled by Dosage of the X-Chromosomal Gene Myc and by the Sex-Determining Gene tra in Drosophila.

PubMed

Mathews, Kristina Wehr; Cavegn, Margrith; Zwicky, Monica

2017-03-01

Drosophila females are larger than males. In this article, we describe how X -chromosome dosage drives sexual dimorphism of body size through two means: first, through unbalanced expression of a key X -linked growth-regulating gene, and second, through female-specific activation of the sex-determination pathway. X -chromosome dosage determines phenotypic sex by regulating the genes of the sex-determining pathway. In the presence of two sets of X -chromosome signal elements (XSEs), Sex-lethal ( Sxl ) is activated in female ( XX ) but not male ( XY ) animals. Sxl activates transformer ( tra ), a gene that encodes a splicing factor essential for female-specific development. It has previously been shown that null mutations in the tra gene result in only a partial reduction of body size of XX animals, which shows that other factors must contribute to size determination. We tested whether X dosage directly affects animal size by analyzing males with duplications of X -chromosomal segments. Upon tiling across the X chromosome, we found four duplications that increase male size by >9%. Within these, we identified several genes that promote growth as a result of duplication. Only one of these, Myc , was found not to be dosage compensated. Together, our results indicate that both Myc dosage and tra expression play crucial roles in determining sex-specific size in Drosophila larvae and adult tissue. Since Myc also acts as an XSE that contributes to tra activation in early development, a double dose of Myc in females serves at least twice in development to promote sexual size dimorphism. Copyright © 2017 by the Genetics Society of America.

48 CFR 1631.203-70 - Allocation techniques.

Code of Federal Regulations, 2011 CFR

2011-10-01

... among cost centers at the initial entry into the cost accounting system shall be made in compliance with... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Allocation techniques. 1631.203-70 Section 1631.203-70 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT...

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

PubMed

Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

2013-04-01

To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

TEOSINTE BRANCHED1 Regulates Inflorescence Architecture and Development in Bread Wheat (Triticum aestivum)[OPEN

PubMed Central

Greenwood, Julian R.; Bencivenga, Stefano; Cockram, James; Cavanagh, Colin; Swain, Steve M.

2018-01-01

The flowers of major cereals are arranged on reproductive branches known as spikelets, which group together to form an inflorescence. Diversity for inflorescence architecture has been exploited during domestication to increase crop yields, and genetic variation for this trait has potential to further boost grain production. Multiple genes that regulate inflorescence architecture have been identified by studying alleles that modify gene activity or dosage; however, little is known in wheat. Here, we show TEOSINTE BRANCHED1 (TB1) regulates inflorescence architecture in bread wheat (Triticum aestivum) by investigating lines that display a form of inflorescence branching known as “paired spikelets.” We show that TB1 interacts with FLOWERING LOCUS T1 and that increased dosage of TB1 alters inflorescence architecture and growth rate in a process that includes reduced expression of meristem identity genes, with allelic diversity for TB1 found to associate genetically with paired spikelet development in modern cultivars. We propose TB1 coordinates formation of axillary spikelets during the vegetative to floral transition and that alleles known to modify dosage or function of TB1 could help increase wheat yields. PMID:29444813

TEOSINTE BRANCHED1 Regulates Inflorescence Architecture and Development in Bread Wheat (Triticum aestivum).

PubMed

Dixon, Laura E; Greenwood, Julian R; Bencivenga, Stefano; Zhang, Peng; Cockram, James; Mellers, Gregory; Ramm, Kerrie; Cavanagh, Colin; Swain, Steve M; Boden, Scott A

2018-03-01

The flowers of major cereals are arranged on reproductive branches known as spikelets, which group together to form an inflorescence. Diversity for inflorescence architecture has been exploited during domestication to increase crop yields, and genetic variation for this trait has potential to further boost grain production. Multiple genes that regulate inflorescence architecture have been identified by studying alleles that modify gene activity or dosage; however, little is known in wheat. Here, we show TEOSINTE BRANCHED1 ( TB1 ) regulates inflorescence architecture in bread wheat ( Triticum aestivum ) by investigating lines that display a form of inflorescence branching known as "paired spikelets." We show that TB1 interacts with FLOWERING LOCUS T1 and that increased dosage of TB1 alters inflorescence architecture and growth rate in a process that includes reduced expression of meristem identity genes, with allelic diversity for TB1 found to associate genetically with paired spikelet development in modern cultivars. We propose TB1 coordinates formation of axillary spikelets during the vegetative to floral transition and that alleles known to modify dosage or function of TB1 could help increase wheat yields. © 2018 American Society of Plant Biologists. All rights reserved.

34 CFR 200.78 - Allocation of funds to school attendance areas and schools.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Allocation of funds to school attendance areas and schools. 200.78 Section 200.78 Education Regulations of the Offices of the Department of Education OFFICE... for the Within-District Allocation of Lea Program Funds § 200.78 Allocation of funds to school...

Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs

PubMed Central

Sharifpoor, Sara; van Dyk, Dewald; Costanzo, Michael; Baryshnikova, Anastasia; Friesen, Helena; Douglas, Alison C.; Youn, Ji-Young; VanderSluis, Benjamin; Myers, Chad L.; Papp, Balázs; Boone, Charles; Andrews, Brenda J.

2012-01-01

A combinatorial genetic perturbation strategy was applied to interrogate the yeast kinome on a genome-wide scale. We assessed the global effects of gene overexpression or gene deletion to map an integrated genetic interaction network of synthetic dosage lethal (SDL) and loss-of-function genetic interactions (GIs) for 92 kinases, producing a meta-network of 8700 GIs enriched for pathways known to be regulated by cognate kinases. Kinases most sensitive to dosage perturbations had constitutive cell cycle or cell polarity functions under standard growth conditions. Condition-specific screens confirmed that the spectrum of kinase dosage interactions can be expanded substantially in activating conditions. An integrated network composed of systematic SDL, negative and positive loss-of-function GIs, and literature-curated kinase–substrate interactions revealed kinase-dependent regulatory motifs predictive of novel gene-specific phenotypes. Our study provides a valuable resource to unravel novel functional relationships and pathways regulated by kinases and outlines a general strategy for deciphering mutant phenotypes from large-scale GI networks. PMID:22282571

5 CFR 319.202 - Allocation of positions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Allocation of positions. 319.202 Section 319.202 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment...

[Consumption of alcoholic beverages: cultural revolution is necessary].

PubMed

Testino, Gianni

2015-11-01

Significant investment in advertising has been made to promote the consumption of alcoholic beverages, but only 0.5% of the GDP is allocated for preventing alcohol use. Although available evidence clearly demonstrates a causal relationship between ethanol and cancer, the perception of risk in the general population remains extremely low. This is partly due to the fact that alcohol consumption is considered as a "normal" habit in our society, mostly as a consequence of the lack of appropriate information. It should also be emphasized the lack of a common language within the healthcare community, in that too often alcohol is identified as a food or a preservative. The fourth edition of the RDA represents a true cultural revolution as it identifies alcohol consumption as a risk, regardless of the amount consumed. Recommended dosages are defined as low-risk dosages. It would be appropriate to correctly apply the Law 125/2001, which provides for inclusion of alcoholism in university education programs.

45 CFR 400.13 - Cost allocation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Grants to States for Refugee Resettlement Award of Grants to States § 400.13 Cost allocation. (a) A State must allocate...

28 CFR 100.14 - Directly allocable costs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Directly allocable costs. 100.14 Section 100.14 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) COST RECOVERY REGULATIONS, COMMUNICATIONS ASSISTANCE FOR LAW ENFORCEMENT ACT OF 1994 § 100.14 Directly allocable costs. (a) A cost is...

28 CFR 100.14 - Directly allocable costs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Directly allocable costs. 100.14 Section 100.14 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) COST RECOVERY REGULATIONS, COMMUNICATIONS ASSISTANCE FOR LAW ENFORCEMENT ACT OF 1994 § 100.14 Directly allocable costs. (a) A cost is...

47 CFR 76.924 - Allocation to service cost categories.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Allocation to service cost categories. 76.924 Section 76.924 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.924 Allocation to service cost...

48 CFR 1631.203-70 - Allocation techniques.

Code of Federal Regulations, 2010 CFR

2010-10-01

... shall consistently apply the methods and techniques established to classify direct and indirect costs... meant to be exhaustive, but rather are examples of allocation methods that may be acceptable under... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Allocation techniques. 1631...

Self-Regulated Reading in Adulthood

PubMed Central

Stine-Morrow, Elizabeth A. L.; Soederberg Miller, Lisa M.; Gagne, Danielle D.; Hertzog, Christopher

2008-01-01

Younger and older adults read a series of passages of three different genres for an immediate assessment of text memory (measured by recall and true-false questions). Word-by-word reading times were measured and decomposed into components reflecting resource allocation to particular linguistic processes using regression. Allocation to word and textbase processes showed some consistency across the three text types and was predictive of memory performance. Older adults allocated more time to word and textbase processes than the young did, but showed enhanced contextual facilitation. Structural equation modeling showed that greater resource allocation to word processes was required among readers with relatively low working memory spans and poorer verbal ability, and that greater resource allocation to textbase processes was engendered by higher verbal ability. Results are discussed in terms of a model of self-regulated language processing suggesting that older readers may compensate for processing deficiencies through greater reliance on discourse context and on increases in resource allocation that are enabled through growth in crystallized ability. PMID:18361662

Efficacy of two low-dose oral tylosin regimens in controlling the relapse of diarrhea in dogs with tylosin-responsive diarrhea: a prospective, single-blinded, two-arm parallel, clinical field trial

PubMed Central

2014-01-01

Background Despite its wide acceptance as a treatment for canine chronic enteropathies, the macrolide antibiotic tylosin lacks official oral dosage recommendations. Not even textbooks share consensus about the dose; daily recommendations vary from 25 to 80 mg/kg and dosing intervals from one to three times daily. The objective of this prospective, single-blinded, two-arm parallel, clinical field trial was to determine whether doses of 5 mg/kg or 15 mg/kg tylosin administered orally once daily for seven days would have a similar effect on fecal consistency in diarrhea relapses to that of a 25 mg/kg dose of tylosin administered once daily for seven days, a dosage that has proved effective in controlling canine tylosin-responsive diarrhea (TRD). A further objective was to compare the efficacy of the 5 mg/kg and 15 mg/kg tylosin dosages. Fifteen client-owned dogs diagnosed with TRD that had responded to a dose of 25 mg/kg tylosin once daily for seven days were enrolled in the study. After a relapse of diarrhea the dogs were allocated into two groups receiving tylosin orally in doses of either 5 mg/kg or 15 mg/kg once daily for seven days. The owners were blinded to the dosage. The elimination of diarrhea was the main criterion in assessing treatment success. The mean fecal consistency score of the last three treatment days for all dosages, including 25 mg/kg, as evaluated by the owners according to a standardized fecal scoring system, served as the primary outcome measures. Results All eight dogs responded to the 5 mg/kg dose, and six of seven dogs responded to the 15 mg/kg dose. The mean fecal consistency scores at the 25 mg/kg tylosin dosage were no significantly different from scores at the 5 mg/kg or 15 mg/kg tylosin dosages (P = 0.672, P = 0.345). Conclusions Interestingly, 14/15 (93%) of the dogs responding to a dose of 25 mg/kg tylosin once daily for seven days also responded to the lower dosages at diarrhea relapse. The data indicate that a suitable dose of tylosin for treating diarrhea relapse in canine TRD could be as low as 5 mg/kg once daily for seven days. PMID:25096196

77 FR 54482 - Allocation of Costs Under the Simplified Methods

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... Allocation of Costs Under the Simplified Methods AGENCY: Internal Revenue Service (IRS), Treasury. ACTION... certain costs to the property and that allocate costs under the simplified production method or the simplified resale method. The proposed regulations provide rules for the treatment of negative additional...

45 CFR 205.150 - Cost allocation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 2 2014-10-01 2012-10-01 true Cost allocation. 205.150 Section 205.150 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS... Social Security Act must provide that the State agency will have an approved cost allocation plan on file...

34 CFR 675.42 - Allocation and reallocation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Allocation and reallocation. 675.42 Section 675.42 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL WORK-STUDY PROGRAMS Work-Colleges Program § 675.42 Allocation and...

45 CFR 304.15 - Cost allocation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... FEDERAL FINANCIAL PARTICIPATION § 304.15 Cost allocation. A State agency in support of its claims under title IV-D of the Social Security Act must have an approved cost allocation plan on file with the...

Biomass Allocation of Stoloniferous and Rhizomatous Plant in Response to Resource Availability: A Phylogenetic Meta-Analysis

PubMed Central

Xie, Xiu-Fang; Hu, Yu-Kun; Pan, Xu; Liu, Feng-Hong; Song, Yao-Bin; Dong, Ming

2016-01-01

Resource allocation to different functions is central in life-history theory. Plasticity of functional traits allows clonal plants to regulate their resource allocation to meet changing environments. In this study, biomass allocation traits of clonal plants were categorized into absolute biomass for vegetative growth vs. for reproduction, and their relative ratios based on a data set including 115 species and derived from 139 published literatures. We examined general pattern of biomass allocation of clonal plants in response to availabilities of resource (e.g., light, nutrients, and water) using phylogenetic meta-analysis. We also tested whether the pattern differed among clonal organ types (stolon vs. rhizome). Overall, we found that stoloniferous plants were more sensitive to light intensity than rhizomatous plants, preferentially allocating biomass to vegetative growth, aboveground part and clonal reproduction under shaded conditions. Under nutrient- and water-poor condition, rhizomatous plants were constrained more by ontogeny than by resource availability, preferentially allocating biomass to belowground part. Biomass allocation between belowground and aboveground part of clonal plants generally supported the optimal allocation theory. No general pattern of trade-off was found between growth and reproduction, and neither between sexual and clonal reproduction. Using phylogenetic meta-analysis can avoid possible confounding effects of phylogeny on the results. Our results shown the optimal allocation theory explained a general trend, which the clonal plants are able to plastically regulate their biomass allocation, to cope with changing resource availability, at least in stoloniferous and rhizomatous plants. PMID:27200071

75 FR 62023 - Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

...] Transmission Planning and Cost Allocation by Transmission Owning and Operating Public Utilities September 29... (75 FR 37884) proposing to amend the transmission planning and cost allocation requirements... transmission needs driven by public policy requirements established by state or federal laws or regulations...

45 CFR 304.15 - Cost allocation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 2 2014-10-01 2012-10-01 true Cost allocation. 304.15 Section 304.15 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... title IV-D of the Social Security Act must have an approved cost allocation plan on file with the...

45 CFR 304.15 - Cost allocation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 2 2011-10-01 2011-10-01 false Cost allocation. 304.15 Section 304.15 Public Welfare Regulations Relating to Public Welfare OFFICE OF CHILD SUPPORT ENFORCEMENT (CHILD SUPPORT... title IV-D of the Social Security Act must have an approved cost allocation plan on file with the...

78 FR 12294 - Proposed Information Collection; Comment Request; Defense Priorities and Allocations System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

... Request; Defense Priorities and Allocations System AGENCY: Bureau of Industry and Security, Commerce...: Direct all written comments to Jennifer Jessup, Departmental Paperwork Clearance Officer, Department of... Priorities and Allocations System regulation (15 CFR part 700) must retain the records for at least 3 years...

75 FR 12173 - Proposed Information Collection; Comment Request; Defense Priorities and Allocations System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... Allocations System regulation (15 CFR part 700) must retain the records for at least 3 years. II. Method of... Request; Defense Priorities and Allocations System AGENCY: Bureau of Industry and Security, Commerce...: Direct all written comments to Diana Hynek, Departmental Paperwork Clearance Officer, Department of...

Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial.

PubMed

Aslih, Nardin; Ellenbogen, Adrian; Shavit, Tal; Michaeli, Medeia; Yakobi, Devora; Shalom-Paz, Einat

2017-08-01

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.

Pinelliae Rhizoma Praeparatum Involved in the Regulation of Bile Acids Metabolism in Hepatic Injury.

PubMed

Guo, Shun; Zhang, Song; Liu, Linna; Yang, Peng; Dang, Xueliang; Wei, Huamei; Hu, Na; Shi, Lei; Zhang, Yan

2018-06-01

Pinelliae Rhizoma Praeparatum (PRP) as traditional Chinese medicine had been used for hepatic diseases in combinative forms. However, the effect of PRP was not clear when used alone. So to explore the hepatoprotective/hepatotoxin of PRP is necessary. The activities of PRP were investigated in acetaminophen-induced hepatic injury mice. Liver function markers, hepatic oxidative stress markers were evaluated. Bile acids metabolic transports and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected. As a drug for the treatment of liver diseases, PRP slightly restored the parameters towards normal in model mice only in low dosage, and also had no antioxidant activity and regulate Nrf2. Cholestasis was significantly elevated in model mice when pretreatment with routine or high dosage of PRP, but had no effect on normal mice. Bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) in model mice were markedly increased when pretreatment with low dose PRP, but significantly decreased when pretreatment in routine or high dosage. Mrp3 was significantly induced in model mice after pretreatment of PRP. But the adjustment effect to bile acids transporters by PRP was not significant in normal mice. These results reveal that PRP has the different effects on bile acids transporter in hepatic injury mice, and therefore, the dosage of PRP need to be paid attention to when it is used in clinical hepatic injury.

Analysis and Research on the Optimal Allocation of Regional Water Resources

NASA Astrophysics Data System (ADS)

rui-chao, Xi; yu-jie, Gu

2018-06-01

Starting from the basic concept of optimal allocation of water resources, taking the allocation of water resources in Tianjin as an example, the present situation of water resources in Tianjin is analyzed, and the multi-objective optimal allocation model of water resources is used to optimize the allocation of water resources. We use LINGO to solve the model, get the optimal allocation plan that meets the economic and social benefits, and put forward relevant policies and regulations, so as to provide theoretical which is basis for alleviating and solving the problem of water shortage.

Comparison of methods of predicting community response to impulsive and nonimpulsive noise

NASA Technical Reports Server (NTRS)

Fidell, Sanford; Pearsons, Karl S.

1994-01-01

Several scientific, regulatory, and policy-coordinating bodies have developed methods for predicting community response to sonic booms. The best known of these is the dosage-response relationship of Working Group 84 of the National Academy of Science's Committee on Hearing, Bioacoustics and Biomechanics. This dosage-response relationship between C-weighted DayNight Average Sound Level and the prevalence of annoyance with high energy impulsive sounds was derived from limited amounts of information about community response to regular, prolonged, and expected exposure to artillery and sonic booms. U.S. Army Regulation 201 adapts this approach to predictions of the acceptability of impulsive noise exposure in communities. This regulation infers equivalent degrees of effect with respect to a well known dosage-response relationship for general (nonimpulsive) transportation noise. Differences in prevalence of annoyance predicted by various relationships lead to different predictions of the compatibility of land uses with sonic boom exposure. An examination of these differences makes apparent several unresolved issues in current practice for predicting and interpreting the prevalence of annoyance due to sonic boom exposure.

Global Dosage Compensation Is Ubiquitous in Lepidoptera, but Counteracted by the Masculinization of the Z Chromosome

PubMed Central

Huylmans, Ann Kathrin; Macon, Ariana; Vicoso, Beatriz

2017-01-01

Abstract While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera. PMID:28957502

SHORT HYPOCOTYL 1 encodes a SMARCA3-like chromatin remodeling factor regulating elongation

USDA-ARS?s Scientific Manuscript database

Understanding the mechanisms and control of hypocotyl elongation is important for greenhouse vegetable crop production. In this study, we identified SHORT HYPOCOTYL1 (SH1) in cucumber which regulates low-dosage ultraviolet B (LDUVB)-dependent hypocotyl elongation by recruiting the cucumber UVR8 sign...

The response of belowground carbon allocation in forests to global change

Treesearch

Christian P. Giardina; Mark Coleman; Dan Binkley; Jessica Hancock; John S. King; Erik Lilleskov; Wendy M. Loya; Kurt S. Pregitzer; Michael G. Ryan; Carl Trettin

2005-01-01

Belowground carbon allocation (BCA) in forests regulates soil organic matter formation and influences biotic and abiotic properties of soil such as bulk density, cation exchange capacity, and water holding capacity. On a global scale, the total quantity of carbon allocated belowground by terrestrial plants is enormous, exceeding by an order of magnitude the quantity of...

75 FR 32122 - Revisions to Defense Priorities and Allocations System Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

...This proposed rule would reorganize and clarify existing standards and procedures by which the Bureau of Industry and Security (BIS) may require that certain contracts or orders that promote the national defense be given priority over other contracts or orders. This rule also sets new standards and procedures by which BIS may allocate materials, services and facilities to promote the national defense. BIS is publishing this rule to comply with a requirement of the Defense Production Act Reauthorization of 2009 to publish regulations providing standards and procedures for prioritization of contracts and orders and for allocation of materials, services and facilities to promote the national defense.

Large Dosage of Chishao in Formulae for Cholestatic Hepatitis: A Systematic Review and Meta-Analysis

PubMed Central

Ma, Xiao; Wang, Ji; He, Xuan; Zhao, Yanling; Wang, Jiabo; Zhang, Ping; Zhu, Yun; Zhong, Lin; Zheng, Quanfu; Xiao, Xiaohe

2014-01-01

Objective. To evaluate the efficacy and safety of large dosage of Chishao in formulae for treatment of cholestatic hepatitis. Methods. The major databases (PubMed, Embase, Cochrane Library, Chinese Biomedical Database Wanfang, VIP medicine information system, and China National Knowledge Infrastructure) were searched until January 2014. Randomized controlled trials (RCTs) of large dosage of Chishao in formulae that reported on publications in treatment of cholestatic hepatitis with total efficacy rate, together with the biochemical indices including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), were extracted by two reviewers. The Cochrane tool was used for the assessment of risk of bias included trials. Data were analyzed with RevMan 5.2.7 software. Results. 11 RCTs involving 1275 subjects with cholestatic hepatitis were included. Compared with essential therapy, large dosage of Chishao in formulae demonstrated more efficiently with down regulation of serum ALT, AST, TBIL, DBIL. Meanwhile, there were no obvious adverse events. Conclusion. As a promising novel treatment approach, widely using large dosage of Chishao in formulae may enhance the curative efficacy for cholestatic hepatitis. Considering being accepted by more and more practitioners, further rigorously designed clinical studies are required. PMID:24987427

Towards an understanding of the molecular regulation of carbon allocation in diatoms: the interaction of energy and carbon allocation.

PubMed

Wagner, Heiko; Jakob, Torsten; Fanesi, Andrea; Wilhelm, Christian

2017-09-05

In microalgae, the photosynthesis-driven CO 2 assimilation delivers cell building blocks that are used in different biosynthetic pathways. Little is known about how the cell regulates the subsequent carbon allocation to, for example, cell growth or for storage. However, knowledge about these regulatory mechanisms is of high biotechnological and ecological importance. In diatoms, the situation becomes even more complex because, as a consequence of their secondary endosymbiotic origin, the compartmentation of the pathways for the primary metabolic routes is different from green algae. Therefore, the mechanisms to manipulate the carbon allocation pattern cannot be adopted from the green lineage. This review describes the general pathways of cellular energy distribution from light absorption towards the final allocation of carbon into macromolecules and summarizes the current knowledge of diatom-specific allocation patterns. We further describe the (limited) knowledge of regulatory mechanisms of carbon partitioning between lipids, carbohydrates and proteins in diatoms. We present solutions to overcome the problems that hinder the identification of regulatory elements of carbon metabolism.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'. © 2017 The Author(s).

Increased dosage of DYRK1A and DSCR1 delays neuronal differentiation in neocortical progenitor cells

PubMed Central

Kurabayashi, Nobuhiro; Sanada, Kamon

2013-01-01

Down's syndrome (DS), a major genetic cause of mental retardation, arises from triplication of genes on human chromosome 21. Here we show that DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) and DSCR1 (DS critical region 1), two genes lying within human chromosome 21 and encoding for a serine/threonine kinase and calcineurin regulator, respectively, are expressed in neural progenitors in the mouse developing neocortex. Increasing the dosage of both proteins in neural progenitors leads to a delay in neuronal differentiation, resulting ultimately in alteration of their laminar fate. This defect is mediated by the cooperative actions of DYRK1A and DSCR1 in suppressing the activity of the transcription factor NFATc. In Ts1Cje mice, a DS mouse model, dysregulation of NFATc in conjunction with increased levels of DYRK1A and DSCR1 was observed. Furthermore, counteracting the dysregulated pathway ameliorates the delayed neuronal differentiation observed in Ts1Cje mice. In sum, our findings suggest that dosage of DYRK1A and DSCR1 is critical for proper neurogenesis through NFATc and provide a potential mechanism to explain the neurodevelopmental defects in DS. PMID:24352425

Volcanic ash dosage calculator: A proof-of-concept tool to support aviation stakeholders during ash events

NASA Astrophysics Data System (ADS)

Dacre, H.; Prata, A.; Shine, K. P.; Irvine, E.

2017-12-01

The volcanic ash clouds produced by Icelandic volcano Eyjafjallajökull in April/May 2010 resulted in `no fly zones' which paralysed European aircraft activity and cost the airline industry an estimated £1.1 billion. In response to the crisis, the Civil Aviation Authority (CAA), in collaboration with Rolls Royce, produced the `safe-to-fly' chart. As ash concentrations are the primary output of dispersion model forecasts, the chart was designed to illustrate how engine damage progresses as a function of ash concentration. Concentration thresholds were subsequently derived based on previous ash encounters. Research scientists and aircraft manufactures have since recognised the importance of volcanic ash dosages; the accumulated concentration over time. Dosages are an improvement to concentrations as they can be used to identify pernicious situations where ash concentrations are acceptably low but the exposure time is long enough to cause damage to aircraft engines. Here we present a proof-of-concept volcanic ash dosage calculator; an innovative, web-based research tool, developed in close collaboration with operators and regulators, which utilises interactive data visualisation to communicate the uncertainty inherent in dispersion model simulations and subsequent dosage calculations. To calculate dosages, we use NAME (Numerical Atmospheric-dispersion Modelling Environment) to simulate several Icelandic eruption scenarios, which result in tephra dispersal across the North Atlantic, UK and Europe. Ash encounters are simulated based on flight-optimal routes derived from aircraft routing software. Key outputs of the calculator include: the along-flight dosage, exposure time and peak concentration. The design of the tool allows users to explore the key areas of uncertainty in the dosage calculation and to visualise how this changes as the planned flight path is varied. We expect that this research will result in better informed decisions from key stakeholders during volcanic ash events through a deeper understanding of the associated uncertainties in dosage calculations.

Oral Medicines for Children in the European Paediatric Investigation Plans

PubMed Central

van Riet – Nales, Diana A.; Römkens, Erwin G. A. W.; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F. A. M.; Egberts, Toine C. G.; Rademaker, Carin M. A.

2014-01-01

Introduction Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. Methods All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. Results A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. Conclusion The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound. PMID:24897509

Oral medicines for children in the European paediatric investigation plans.

PubMed

van Riet-Nales, Diana A; Römkens, Erwin G A W; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F A M; Egberts, Toine C G; Rademaker, Carin M A

2014-01-01

Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound.

76 FR 78703 - American Century Strategic Asset Allocations, Inc., et al.;

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

.... Summary of Application: Applicants request an order to permit open-end management investment companies... Century Strategic Asset Allocations, Inc. (``ACSAA''), American Century Investment Management, Inc... Management, Office of Investment Company Regulation). SUPPLEMENTARY INFORMATION: The following is a summary...

On the dynamics of implicit emotion regulation: counter-regulation after remembering events of high but not of low emotional intensity.

PubMed

Schwager, Susanne; Rothermund, Klaus

2014-01-01

Valence biases in attention allocation were assessed after remembering positive or negative personal events that were either still emotionally hot or to which the person had already adapted psychologically. Differences regarding the current state of psychological adjustment were manipulated experimentally by instructing participants to recall distant vs. recent events (Experiment 1) or affectively hot events vs. events to which the person had accommodated already (Experiment 2). Valence biases in affective processing were measured with a valence search task. Processes of emotional counter-regulation (i.e., attention allocation to stimuli of opposite valence to the emotional event) were elicited by remembering affectively hot events, whereas congruency effects (i.e., attention allocation to stimuli of the same valence as the emotional event) were obtained for events for which a final appraisal had already been established. The results of our study help to resolve conflicting findings from the literature regarding congruent vs. incongruent effects of remembering emotional events on affective processing. We discuss implications of our findings for the conception of emotions and for the dynamics of emotion regulation processes.

7 CFR 1775.37 - Allocation of funds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Allocation of funds. 1775.37 Section 1775.37 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) TECHNICAL ASSISTANCE GRANTS Technical Assistance and Training Grants § 1775.37...

45 CFR 205.150 - Cost allocation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 2 2012-10-01 2012-10-01 false Cost allocation. 205.150 Section 205.150 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION-PUBLIC...

45 CFR 205.150 - Cost allocation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 2 2011-10-01 2011-10-01 false Cost allocation. 205.150 Section 205.150 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION-PUBLIC...

45 CFR 205.150 - Cost allocation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Cost allocation. 205.150 Section 205.150 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION-PUBLIC...

45 CFR 205.150 - Cost allocation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 2 2013-10-01 2012-10-01 true Cost allocation. 205.150 Section 205.150 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION-PUBLIC...

Safety and economic considerations of argatroban use in critically ill patients: a retrospective analysis.

PubMed

Kim, Se-Chan; Tran, Nicole; Schewe, Jens-Christian; Boehm, Olaf; Wittmann, Maria; Graeff, Ingo; Hoeft, Andreas; Baumgarten, Georg

2015-02-07

Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS <30), respectively. For calculations, patients (n = 19) without previous history of HIT were compared to patients (n = 23) with a history of HIT before initiation of argatroban. The mean initial argatroban dosage was below 0.4 mcg/kg/min regardless of SAPS score. Maintenance dosage had to be increased in patients with SAPS <30 to 0.54 ± 0.248 mcg/kg/min (p >0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. Argatroban can be used at doses < 0.4 mcg/kg/min without an increase in transfusion requirements and at a reduced overall treatment cost compared to heparin.

47 CFR 2.100 - International regulations in force.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false International regulations in force. 2.100 Section 2.100 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO....100 International regulations in force. The ITU Radio Regulations, edition of 2004, have been...

24 CFR 576.3 - Allocation of funding.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false Allocation of funding. 576.3 Section 576.3 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

24 CFR 791.403 - Allocation of housing assistance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Allocation of housing assistance. 791.403 Section 791.403 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF THE SECRETARY, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HOUSING...

24 CFR 576.3 - Allocation of funding.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Allocation of funding. 576.3 Section 576.3 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

34 CFR 300.807 - Allocations to States.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Allocations to States. 300.807 Section 300.807 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF...

Dosage and duration effects of nitrogen additions on ectomycorrhizal sporocarp production and functioning: an example from two N-limited boreal forests.

PubMed

Hasselquist, Niles J; Högberg, Peter

2014-08-01

Although it is well known that nitrogen (N) additions strongly affect ectomycorrhizal (EM) fungal community composition, less is known about how different N application rates and duration of N additions affect the functional role EM fungi play in the forest N cycle.We measured EM sporocarp abundance and species richness as well as determined the δ (15)N in EM sporocarps and tree foliage in two Pinus sylvestris forests characterized by short- and long-term N addition histories and multiple N addition treatments. After 20 and 39 years of N additions, two of the long-term N addition treatments were terminated, thereby providing a unique opportunity to examine the temporal recovery of EM sporocarps after cessation of high N loading.In general, increasing N availability significantly reduced EM sporocarp production, species richness, and the amount of N retained in EM sporocarps. However, these general responses were strongly dependent on the application rate and duration of N additions. The annual addition of 20 kg·N·ha(-1) for the past 6 years resulted in a slight increase in the production and retention of N in EM sporocarps, whereas the addition of 100 kg·N·ha(-1)·yr(-1) during the same period nearly eliminated EM sporocarps. In contrast, long-term additions of N at rates of ca. 35 or 70 kg·N·ha(-1)·yr(-1) for the past 40 years did not eliminate tree carbon allocation to EM sporocarps, although there was a decrease in the abundance and a shift in the dominant EM sporocarp taxa. Despite no immediate recovery, EM sporocarp abundance and species richness approached those of the control 20 years after terminating N additions in the most heavily fertilized treatment, suggesting a recovery of carbon allocation to EM sporocarps after cessation of high N loading.Our results provide evidence for a tight coupling between tree carbon allocation to and N retention in EM sporocarps and moreover highlight the potential use of δ (15)N in EM sporocarps as a relative index of EM fungal sink strength for N. However, nitrogen additions at high dosage rates or over long time periods appear to disrupt this feedback, which could have important ramifications on carbon and nitrogen dynamics in these forested ecosystems.

Increased Arf/p53 activity in stem cells, aging and cancer.

PubMed

Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander

2017-04-01

Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators

PubMed Central

Bellott, Daniel W.; Skaletsky, Helen; Cho, Ting-Jan; Brown, Laura; Locke, Devin; Chen, Nancy; Galkina, Svetlana; Pyntikova, Tatyana; Koutseva, Natalia; Graves, Tina; Kremitzki, Colin; Warren, Wesley C.; Clark, Andrew G.; Gaginskaya, Elena; Wilson, Richard K.; Page, David C.

2017-01-01

After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males ZZ, but in mammals females are XX and males XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly-expressed regulators of key cellular processes. We propose that, like the human Y chromosome, the chicken W chromosome is essential for embryonic viability of the heterogametic sex. Unlike other sequenced sex chromosomes, the chicken W did not acquire and amplify genes specifically expressed in reproductive tissues. We speculate that the pressures that drive the acquisition of reproduction related genes on sex chromosomes may be specific to the male germ line. PMID:28135246

Subantibiotic dose of azithromycin attenuates alveolar bone destruction and improves trabecular microarchitectures in a rat model of experimental periodontitis: A study using micro-computed tomography.

PubMed

Park, Hye-Shin; Lee, Yong Sun; Choi, Eun-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2017-06-01

Azithromycin, a macrolide antibiotic, has anti-inflammatory and immunomodulatory activities apart from its antibacterial properties. In this study, we examined the efficacy of subantibiotic dose of azithromycin on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT) imaging and bone parameter analysis. Male Sprague-Dawley rats were allocated to the following four groups: non-ligation (NL) group; ligation-only (L) group; ligation-plus-subantibiotic dose azithromycin (SA) group; and 4) ligation-plus-antibiotic dose azithromycin (AA) group. The rats from Groups L, SA and AA were subjected to periodontitis by placing a ligature around lower right first molar. Immediately after ligation, the rats in SA and AA groups received daily intraperitoneal injections of azithromycin at a dosage of 3.5 or 10mg/kg body weight, respectively. The ligatures were maintained for 2weeks at which time the rats had their mandibles hemisected for micro-CT analysis. Subantibiotic dose of azithromycin strongly suppressed reductions in alveolar bone height and bone volume fraction caused by experimental periodontitis. When subantibiotic dosage of azithromycin was administered to rats, ligature-induced alterations in microarchitectural parameters of trabecular bone were significantly reversed. Rats treated with subantibiotic dose of azithromycin presented no significant difference compared to rats with antibiotic dosage in all parameters. While further studies are necessary, subantibiotic dose of azithromycin could be utilized as a host modulator for the treatment of periodontitis. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for the treatment of acute postpartum metritis in dairy cows.

PubMed

Chenault, John R; McAllister, Joseph F; Chester, S Theodore; Dame, Kenneth J; Kausche, Fabian M; Robb, Edward J

2004-05-15

To evaluate the efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for treatment of acute postpartum metritis (APM) in dairy cows. Multilocation, randomized block, field trial. 406 cows in the first 14 days postpartum. Cows with rectal temperatures > or = 39.5 degrees C (103.1 degrees F) without clinical signs of respiratory or gastrointestinal tract disease and with a fetid vaginal discharge were allocated randomly in blocks of 3 to 3 treatment groups: sterile saline (0.9% NaCl) solution administered at a dosage of 2 mL/45.4 kg (2 mL/100 lb), SC or IM, once daily for 5 days (control); or ceftiofur hydrochloride administered at a dosage of 1.1 or 2.2 mg of ceftiofur equivalents (CE)/kg (0.5 or 1 mg/lb, respectively), SC or IM, once daily for 5 days. Cows were evaluated on days 6, 10, and 14, and clinical cure or failure to cure was determined. Clinical cure was defined as no additional antimicrobial treatment administered, rectal temperature < 39.5 degrees C, and absence of a fetid vaginal discharge. On day 14, clinical cure rates were 77%, 65%, and 62% for the 2.2 mg of CE/kg, 1.1 mg of CE/kg, and control groups, respectively. No significant differences were detected in clinical cure rates between control and treatment groups on day 10 or 6. Ceftiofur hydrochloride administered at a dosage of 2.2 mg of CE/kg, SC or IM, once daily for 5 days was efficacious for treatment of APM in dairy cows.

24 CFR 570.709 - Allocation of loan guarantee assistance.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Allocation of loan guarantee assistance. 570.709 Section 570.709 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF...

24 CFR 576.5 - Allocation of grant amounts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Allocation of grant amounts. 576.5 Section 576.5 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

24 CFR 570.709 - Allocation of loan guarantee assistance.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Allocation of loan guarantee assistance. 570.709 Section 570.709 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF...

24 CFR 570.709 - Allocation of loan guarantee assistance.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false Allocation of loan guarantee assistance. 570.709 Section 570.709 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF...

24 CFR 570.709 - Allocation of loan guarantee assistance.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Allocation of loan guarantee assistance. 570.709 Section 570.709 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF...

24 CFR 570.709 - Allocation of loan guarantee assistance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Allocation of loan guarantee assistance. 570.709 Section 570.709 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF...

24 CFR 576.5 - Allocation of grant amounts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Allocation of grant amounts. 576.5 Section 576.5 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

24 CFR 576.3 - Allocation of funding.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Allocation of funding. 576.3 Section 576.3 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN...

7 CFR 1484.22 - How are Cooperator program funds allocated?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false How are Cooperator program funds allocated? 1484.22 Section 1484.22 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS PROGRAMS TO HELP DEVELOP FOREIGN...

7 CFR 1484.22 - How are Cooperator program funds allocated?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false How are Cooperator program funds allocated? 1484.22 Section 1484.22 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS PROGRAMS TO HELP DEVELOP FOREIGN...

15 CFR 923.110 - Allocation formula.

Code of Federal Regulations, 2010 CFR

2010-01-01

... MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Allocation of Section 306 Program Administration... Coastal Zone Act Reauthorization Amendments of 1990, 1 to 1 for any fiscal year. (2) For programs approved after enactment of the Coastal Zone Act Reauthorization Amendments of 1990, 4 to 1 for the first fiscal...

15 CFR 923.110 - Allocation formula.

Code of Federal Regulations, 2011 CFR

2011-01-01

... MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Allocation of Section 306 Program Administration... Coastal Zone Act Reauthorization Amendments of 1990, 1 to 1 for any fiscal year. (2) For programs approved after enactment of the Coastal Zone Act Reauthorization Amendments of 1990, 4 to 1 for the first fiscal...

15 CFR 303.14 - Allocation factors, duty refund calculations and miscellaneous provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Allocation factors, duty refund calculations and miscellaneous provisions. 303.14 Section 303.14 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF...

34 CFR 300.807 - Allocations to States.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Allocations to States. 300.807 Section 300.807 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH...

24 CFR 570.4 - Allocation of funds.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Allocation of funds. 570.4 Section 570.4 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN...

75 FR 15487 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... comments concerning an existing final notice of proposed rulemaking, REG-208299-90, Allocation and Sourcing... and Sourcing of Income and Deductions Among Taxpayers Engaged in a Global Dealing Operation. OMB... the allocation among controlled taxpayers and sourcing of income, deductions, gains and losses from a...

7 CFR 1940.552 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS (CONTINUED) GENERAL Methodology and Formulas for Allocation of Loan and Grant Program Funds § 1940..., funds will be controlled by the National Office. (b) Basic formula criteria, data source and weight. Basic formulas are used to calculate a basic state factor as a part of the methodology for allocating...

7 CFR 1940.552 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATIONS (CONTINUED) GENERAL Methodology and Formulas for Allocation of Loan and Grant Program Funds § 1940..., funds will be controlled by the National Office. (b) Basic formula criteria, data source and weight. Basic formulas are used to calculate a basic state factor as a part of the methodology for allocating...

7 CFR 1940.552 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REGULATIONS (CONTINUED) GENERAL Methodology and Formulas for Allocation of Loan and Grant Program Funds § 1940..., funds will be controlled by the National Office. (b) Basic formula criteria, data source and weight. Basic formulas are used to calculate a basic state factor as a part of the methodology for allocating...

7 CFR 1940.552 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS (CONTINUED) GENERAL Methodology and Formulas for Allocation of Loan and Grant Program Funds § 1940..., funds will be controlled by the National Office. (b) Basic formula criteria, data source and weight. Basic formulas are used to calculate a basic state factor as a part of the methodology for allocating...

48 CFR 9904.403 - Allocation of home office expenses to segments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... expenses to segments. 9904.403 Section 9904.403 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403 Allocation of home office expenses to...

48 CFR 952.211-70 - Priorities and allocations for energy programs (solicitations):

Code of Federal Regulations, 2013 CFR

2013-10-01

... for energy programs (solicitations): 952.211-70 Section 952.211-70 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-70 Priorities and allocations for energy programs (solicitations): As...

48 CFR 952.211-70 - Priorities and allocations for energy programs (solicitations):

Code of Federal Regulations, 2010 CFR

2010-10-01

... for energy programs (solicitations): 952.211-70 Section 952.211-70 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-70 Priorities and allocations for energy programs (solicitations): As...

48 CFR 952.211-70 - Priorities and allocations for energy programs (solicitations):

Code of Federal Regulations, 2011 CFR

2011-10-01

... for energy programs (solicitations): 952.211-70 Section 952.211-70 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-70 Priorities and allocations for energy programs (solicitations): As...

48 CFR 952.211-70 - Priorities and allocations for energy programs (solicitations):

Code of Federal Regulations, 2012 CFR

2012-10-01

... for energy programs (solicitations): 952.211-70 Section 952.211-70 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-70 Priorities and allocations for energy programs (solicitations): As...

75 FR 33384 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... 8228; TD 8410), Allocation and Apportionment of Interest Expense and Certain Other Expenses (Sec. Sec... to be assured of consideration. ADDRESSES: Direct all written comments to Gerald J. Shields, Internal...: Allocation and Apportionment of Interest Expense and Certain Other Expenses. OMB Number: 1545-1072...

15 CFR 303.6 - Allocation and reallocation of exemptions among producers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Allocation and reallocation of exemptions among producers. 303.6 Section 303.6 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS...

24 CFR 570.4 - Allocation of funds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Allocation of funds. 570.4 Section 570.4 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN...

24 CFR 1003.101 - Area ONAP allocation of funds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Area ONAP allocation of funds. 1003.101 Section 1003.101 Housing and Urban Development Regulations Relating to Housing and Urban... URBAN DEVELOPMENT COMMUNITY DEVELOPMENT BLOCK GRANTS FOR INDIAN TRIBES AND ALASKA NATIVE VILLAGES...

Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.

PubMed

Xie, Ying; Koch, Mia Lee; Zhang, Xin; Hamblen, Melanie J; Godinho, Frank J; Fujiwara, Yuko; Xie, Huafeng; Klusmann, Jan-Henning; Orkin, Stuart H; Li, Zhe

2017-07-01

ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg kd ) in which Erg expression can be conditionally restored by Cre recombinase. Erg kd/kd animals die at E10.5-E11.5 due to defects in endothelial and hematopoietic cells, but can be completely rescued by Tie2-Cre-mediated restoration of Erg in these cells. In Erg kd/+ mice, ∼40% reduction in Erg dosage perturbs both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin - Sca-1 + c-Kit + (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we find that Erg-restored HSPCs outcompete Erg kd/+ HSPCs for contribution to adult hematopoiesis in vivo. This defect is in part due to increased apoptosis of HSPCs with reduced Erg dosage, a phenotype that becomes more drastic during 5-FU-induced stress hematopoiesis. Expression analysis reveals that reduced Erg expression leads to changes in expression of a subset of ERG target genes involved in regulating survival of HSPCs, including increased expression of a pro-apoptotic regulator Bcl2l11 (Bim) and reduced expression of Jun. Collectively, our data demonstrate that ERG controls survival of HSPCs, a property that may be used by leukemic cells. Stem Cells 2017;35:1773-1785. © 2017 AlphaMed Press.

The effects of chronic radiation of gamma ray on protein expression and oxidative stress in Brachypodium distachyon.

PubMed

Kim, Dae Yeon; Hong, Min Jeong; Park, Cheong-Sool; Seo, Yong Weon

2015-05-01

To compare the effects of gamma-irradiation on biochemical responses and growth, six-week-old Brachypodium plants were chronically exposed to gamma-irradiation for 30 days at various dosages. Growth surveys of Brachypodium plants in response to different dosages of gamma-irradiation were conducted to compare physiological changes between irradiated and non-irradiated plants. Photosynthetic pigments, soluble sugar content, activities of antioxidant enzymes, and malonaldehyde (MDA) induced by reactive oxygen species (ROS) production were also measured. Gamma-irradiation had a negative influence on the average plant height, leaf length, leaf width, and fresh weight. Photosynthetic pigment levels decreased with increasing dosages of gamma-irradiation, while soluble sugar content slightly increased. Gamma-irradiation responsive proteins were detected and identified by two-dimensional gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). The proteins had a role in photosynthetic carbon fixation, anabolic pathway glycolysis, mitochondrial ATP production, and oxidative stress response regulation. MDA levels and activities of antioxidant enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD) increased with the increase in gamma-irradiation dosage level. This study provides some basic information regarding responses to gamma-irradiation, and provides valuable physiological and biological data on the effects of different gamma-irradiation dosages on Triticeae species.

Issues impacting therapeutic outcomes in pediatric patients: an overview.

PubMed

Kalra, Atin; Goindi, Shishu

2014-01-01

The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionals for long and often lack of child specific dosage forms and the associated events that follow with it have been considered to be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over the years to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), Pediatric Research Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceutical industry towards development of child friendly dosage forms. Initiatives taken in past by organisations like World Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of child friendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV) and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersible platforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage forms for children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimental effects of additional factors such as parents understanding of label instructions and complexities involved in executing pediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parents and healthcare providers to work for better treatment outcomes in children.

Application of Physiological Self-Regulation and Adaptive Task Allocation Techniques for Controlling Operator Hazardous States of Awareness

NASA Technical Reports Server (NTRS)

Prinzel, Lawrence J., III; Pope, Alan T.; Freeman, Frederick G.

2001-01-01

Prinzel, Hadley, Freeman, and Mikulka found that adaptive task allocation significantly enhanced performance only when used at the endpoints of the task workload continuum (i.e., very low or high workload), but that the technique degraded performance if invoked during other levels of task demand. These researchers suggested that other techniques should be used in conjunction with adaptive automation to help minimize the onset of hazardous states of awareness (HSA) and keep the operator 'in-the-loop.' The paper reports on such a technique that uses psychophysiological self-regulation to modulate the level of task engagement. Eighteen participants were assigned to three groups (self-regulation, false feedback, and control) and performed a compensatory tracking task that was cycled between three levels of task difficulty on the basis of the electroencephalogram (EEG) record. Those participants who had received self-regulation training performed significantly better and reported lower NASA-TLX scores than participants in the false feedback and control groups. Furthermore, the false feedback and control groups had significantly more task allocations resulting in return-to-manual performance decrements and higher EEG difference scores. Theoretical and practical implications of these results for adaptive automation are discussed.

15 CFR 700.4 - Priorities and allocations in a national emergency.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., including domestic emergency preparedness requirements, of approved programs. (b) The special rules... national emergency. 700.4 Section 700.4 Commerce and Foreign Trade Regulations Relating to Commerce and... allocations in a national emergency. (a) In the event of a national emergency, special rules may be...

77 FR 2240 - Allocation and Apportionment of Interest Expense

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... allocation and apportionment of interest expense using the fair market value asset method. The temporary... law by the legislation commonly referred to as the Education Jobs and Medicaid Assistance Act (EJMAA... using the fair market value method. The text of those regulations also serves as the text of these...

34 CFR 370.30 - How does the Secretary allocate funds?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false How does the Secretary allocate funds? 370.30 Section 370.30 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION CLIENT ASSISTANCE PROGRAM How Does...

Understanding the New A-21 Allocation and Documentation Standard.

ERIC Educational Resources Information Center

Sellers, William

1994-01-01

New federal regulations concerning direct cost accounting for college and university research projects are explained. It is concluded that the new standard allows institutions to reduce the signatures required on cost transfers and use reasonable cost allocation methods to simplify distribution of direct costs when research is supported by…

78 FR 56603 - Allocation of Assets in Single-Employer Plans; Benefits Payable in Terminated Single-Employer...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... PENSION BENEFIT GUARANTY CORPORATION 29 CFR Parts 4022 and 4044 Allocation of Assets in Single... Paying Benefits AGENCY: Pension Benefit Guaranty Corporation. ACTION: Final rule. SUMMARY: This final rule amends the Pension Benefit Guaranty Corporation's regulations on Benefits Payable in Terminated...

76 FR 34847 - Allocation of Assets in Single-Employer Plans; Benefits Payable in Terminated Single-Employer...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... PENSION BENEFIT GUARANTY CORPORATION 29 CFR Parts 4022 and 4044 Allocation of Assets in Single... Paying Benefits AGENCY: Pension Benefit Guaranty Corporation. ACTION: Final rule. SUMMARY: This final rule amends the Pension Benefit Guaranty Corporation's regulations on Benefits Payable in Terminated...

48 CFR 952.211-71 - Priorities and allocations for energy programs (contracts).

Code of Federal Regulations, 2010 CFR

2010-10-01

... for energy programs (contracts). 952.211-71 Section 952.211-71 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-71 Priorities and allocations for energy programs (contracts). As prescribed in 911.604(b...

48 CFR 952.211-71 - Priorities and allocations for energy programs (contracts).

Code of Federal Regulations, 2013 CFR

2013-10-01

... for energy programs (contracts). 952.211-71 Section 952.211-71 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-71 Priorities and allocations for energy programs (contracts). As prescribed in 911.604(b...

48 CFR 952.211-71 - Priorities and allocations for energy programs (contracts).

Code of Federal Regulations, 2012 CFR

2012-10-01

... for energy programs (contracts). 952.211-71 Section 952.211-71 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-71 Priorities and allocations for energy programs (contracts). As prescribed in 911.604(b...

48 CFR 952.211-71 - Priorities and allocations for energy programs (contracts).

Code of Federal Regulations, 2011 CFR

2011-10-01

... for energy programs (contracts). 952.211-71 Section 952.211-71 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.211-71 Priorities and allocations for energy programs (contracts). As prescribed in 911.604(b...

78 FR 16916 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... allocation and apportionment of deduction for state income. DATES: Written comments should be received on or before May 20, 2013 to be assured of consideration. ADDRESSES: Direct all written comments to Yvette... INFORMATION: Title: Allocation and Apportionment of Deduction for State Income Taxes. OMB Number: 1545-1224...

15 CFR 700.30 - Priorities and allocations in a national emergency.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Priorities and allocations in a national emergency. 700.30 Section 700.30 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY...

77 FR 19154 - Allocation and Apportionment of Interest Expense; Hearing Cancellation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... Allocation and Apportionment of Interest Expense; Hearing Cancellation AGENCY: Internal Revenue Service (IRS... apportionment of interest expense. DATES: The public hearing, originally scheduled for April 3, 2012 at 10 a.m... cross-reference to temporary regulations and a notice of public hearing instructed those interested in...

Guidelines for spaceborne microwave remote sensors

NASA Technical Reports Server (NTRS)

Litman, V.; Nicholas, J.

1982-01-01

A handbook was developed to provide information and support to the spaceborne remote sensing and frequency management communities: to guide sensor developers in the choice of frequencies; to advise regulators on sensor technology needs and sharing potential; to present sharing analysis models and, through example, methods for determining sensor sharing feasibility; to introduce developers to the regulatory process; to create awareness of proper assignment procedures; to present sensor allocations; and to provide guidelines on the use and limitations of allocated bands. Controlling physical factors and user requirements and the regulatory environment are discussed. Sensor frequency allocation achievable performance and usefulness are reviewed. Procedures for national and international registration, the use of non-allocated bands and steps for obtaining new frequency allocations, and procedures for reporting interference are also discussed.

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats.

PubMed

Peng, Qiuxian; Zhang, Qin; Xiao, Wei; Shao, Meng; Fan, Qin; Zhang, Hongwei; Zou, Yukai; Li, Xin; Xu, Wenxue; Mo, Zhixian; Cai, Hongbing

2014-07-18

Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver. Copyright © 2014. Published by Elsevier Inc.

15 CFR 700.92 - Applicability of this regulation and official actions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Miscellaneous Provisions § 700.92...

78 FR 45614 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for Regulation Project AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... GST Deemed Allocations. OMB Number: 1545-1892. Regulation Project Number: REG-153841-02 (TD 9208...

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats

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

Peng, Qiuxian; Department of Biology, Hong Kong Baptist University, Kowloon Tong; Zhang, Qin

Highlights: • AESM is able to prevent the elevation of ALT and AST, and to decreased LDL-C level. • AESM demonstrates the effects of down-regulating blood fat level and protecting liver. • AESM consistent with the efficacy of simvastatin in NAFLD. - Abstract: Objectives: Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Methods: Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertnmore » group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. Results: High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Conclusions: Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver.« less

26 CFR 26.2632-1 - Allocation of GST exemption.

Code of Federal Regulations, 2011 CFR

2011-04-01

... AND GIFT TAXES GENERATION-SKIPPING TRANSFER TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1986 § 26.2632... United States Gift (and Generation-Skipping Transfer) Tax Return (Form 709) the transfer and the extent... generation-skipping potential, the initial allocation under paragraph (b)(4)(ii)(A)(1)(i) of this section is...

26 CFR 26.2632-1 - Allocation of GST exemption.

Code of Federal Regulations, 2014 CFR

2014-04-01

... AND GIFT TAXES GENERATION-SKIPPING TRANSFER TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1986 § 26.2632... United States Gift (and Generation-Skipping Transfer) Tax Return (Form 709) the transfer and the extent... generation-skipping potential, the initial allocation under paragraph (b)(4)(ii)(A)(1)(i) of this section is...

26 CFR 26.2632-1 - Allocation of GST exemption.

Code of Federal Regulations, 2013 CFR

2013-04-01

... AND GIFT TAXES GENERATION-SKIPPING TRANSFER TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1986 § 26.2632... United States Gift (and Generation-Skipping Transfer) Tax Return (Form 709) the transfer and the extent... generation-skipping potential, the initial allocation under paragraph (b)(4)(ii)(A)(1)(i) of this section is...

26 CFR 26.2632-1 - Allocation of GST exemption.

Code of Federal Regulations, 2012 CFR

2012-04-01

... AND GIFT TAXES GENERATION-SKIPPING TRANSFER TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1986 § 26.2632... United States Gift (and Generation-Skipping Transfer) Tax Return (Form 709) the transfer and the extent... generation-skipping potential, the initial allocation under paragraph (b)(4)(ii)(A)(1)(i) of this section is...

34 CFR 200.75 - Special procedures for allocating concentration grant funds in small States.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Special procedures for allocating concentration grant funds in small States. 200.75 Section 200.75 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE...

15 CFR 303.5 - Application for annual allocations of duty-exemptions and duty-refunds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Application for annual allocations of duty-exemptions and duty-refunds. 303.5 Section 303.5 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE...

47 CFR 74.5 - Cross reference to rules in other parts.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Regulations: (a) Part 1, “Practice and procedure”. (1) Subpart A, “General Rules of Practice and Procedure... Allocations and Radio Treaty Matters, General Rules and Regulations”, including subparts A, “Terminology”; B, “Allocation, Assignments and Use of Radio Frequencies”; C, “Emissions”; D, “Call Signs and Other Forms of...

47 CFR 74.5 - Cross reference to rules in other parts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Regulations: (a) Part 1, “Practice and procedure”. (1) Subpart A, “General Rules of Practice and Procedure... Allocations and Radio Treaty Matters, General Rules and Regulations”, including subparts A, “Terminology”; B, “Allocation, Assignments and Use of Radio Frequencies”; C, “Emissions”; D, “Call Signs and Other Forms of...

47 CFR 74.5 - Cross reference to rules in other parts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Regulations: (a) Part 1, “Practice and procedure”. (1) Subpart A, “General Rules of Practice and Procedure... Allocations and Radio Treaty Matters, General Rules and Regulations”, including subparts A, “Terminology”; B, “Allocation, Assignments and Use of Radio Frequencies”; C, “Emissions”; D, “Call Signs and Other Forms of...

The Impact of a Flexible Assessment System on Students' Motivation, Performance and Attitude

ERIC Educational Resources Information Center

Pacharn, Parunchana; Bay, Darlene; Felton, Sandra

2013-01-01

We examine a flexible assessment system that allows students to determine the weights allocated to each course component and to re-allocate the weights in response to achieved scores. The flexibility is intended to encourage students' participation in the learning process, thereby promoting self-regulated learning skills. We compare this…

34 CFR 200.70 - Allocation of funds to LEAs in general.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Allocation of funds to LEAs in general. 200.70 Section 200.70 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED...

26 CFR 26.2642-6 - Qualified severance.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of GST tax exemption allocated to the trust) divided by $100,000 (the value of the property... value of $200,000. On a timely filed Form 706, T's executor allocates all of T's remaining GST tax... TAXES GENERATION-SKIPPING TRANSFER TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1986 § 26.2642-6...

34 CFR 657.20 - How does the Secretary evaluate an institutional application for an allocation of fellowships?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false How does the Secretary evaluate an institutional application for an allocation of fellowships? 657.20 Section 657.20 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION...

Do tanning salons adhere to new legal regulations? Results of a simulated client trial in Germany.

PubMed

Möllers, Tobias; Pischke, Claudia R; Zeeb, Hajo

2016-03-01

In August 2009 and January 2012, two regulations were passed in Germany to limit UV exposure in the general population. These regulations state that no minors are allowed to use tanning devices. Personnel of tanning salons is mandated to offer counseling regarding individual skin type, to create a dosage plan with the customer and to provide a list describing harmful effects of UV radiation. Furthermore, a poster of warning criteria has to be visible and readable at all times inside the tanning salon. It is unclear whether these regulations are followed by employees of tanning salons in Germany, and we are not aware of any studies examining the implementation of the regulations at individual salons. We performed a simulated client study visiting 20 tanning salons in the city-state of Bremen in the year 2014, using a short checklist of criteria derived from the legal requirements, to evaluate whether legal requirements were followed or not. We found that only 20 % of the tanning salons communicated adverse health effects of UV radiation in visible posters and other materials and that only 60 % of the salons offered the required determination of the skin type to customers. In addition, only 60 % of the salons offered to complete the required dosage plan with their customers. To conclude, our results suggest that the new regulations are insufficiently implemented in Bremen. Additional control mechanisms appear necessary to ensure that consumers are protected from possible carcinogenic effects of excessive UV radiation.

The Market as an Institution for Zoning the Ocean

NASA Astrophysics Data System (ADS)

Clinton, J. E.; Hoagland, P.

2008-12-01

In recent years, spatial conflicts among ocean users have increased significantly, particularly in the coastal ocean. Ocean zoning has been proposed as a promising solution to these conflicts. Strikingly, most ocean zoning proponents focus on a centralized approach, involving government oversight, planning, and spatial allocations. We hypothesize that a market may be more efficient for allocating ocean space, because it tends to put ocean space in the hands of the highest valued uses, and it does not require public decision-makers to compile and analyze large amounts of information. Importantly, where external costs arise, a market in ocean space may need government oversight or regulation. We develop four case studies demonstrating that private allocations of ocean space are taking place already. This evidence suggests that a regulated market in ocean space may perform well as an allocative institution. We find that the proper functioning of a market in ocean space depends positively upon the strength of legal property rights and supportive public policies and negatively upon the number of users and the size of transaction costs.

The regulation of health care providers' payments when horizontal and vertical differentiation matter.

PubMed

Bardey, David; Canta, Chiara; Lozachmeur, Jean-Marie

2012-09-01

This paper analyzes the regulation of payment schemes for health care providers competing in both quality and product differentiation of their services. The regulator uses two instruments: a prospective payment per patient and a cost reimbursement rate. When the regulator can only use a prospective payment, the optimal price involves a trade-off between the level of quality provision and the level of horizontal differentiation. If this pure prospective payment leads to underprovision of quality and overdifferentiation, a mixed reimbursement scheme allows the regulator to improve the allocation efficiency. This is true for a relatively low level of patients' transportation costs. We also show that if the regulator cannot commit to the level of the cost reimbursement rate, the resulting allocation can dominate the one with full commitment. This occurs when the transportation cost is low or high enough, and the full commitment solution either implies full or zero cost reimbursement. Copyright © 2012 Elsevier B.V. All rights reserved.

Research on power source structure optimization for East China Power Grid

NASA Astrophysics Data System (ADS)

Xu, Lingjun; Sang, Da; Zhang, Jianping; Tang, Chunyi; Xu, Da

2017-05-01

The structure of east china power grid is not reasonable for the coal power takes a much higher proportion than hydropower, at present the coal power takes charge of most peak load regulation, and the pressure of peak load regulation cannot be ignored. The nuclear power, wind power, photovoltaic, other clean energy and hydropower, coal power and wind power from outside will be actively developed in future, which increases the pressure of peak load regulation. According to development of economic and social, Load status and load prediction, status quo and planning of power source and the characteristics of power source, the peak load regulation balance is carried out and put forward a reasonable plan of power source allocation. The ultimate aim is to optimize the power source structure and to provide reference for power source allocation in east china.

Tandem repeats of the 5' non-transcribed spacer of Tetrahymena rDNA function as high copy number autonomous replicons in the macronucleus but do not prevent rRNA gene dosage regulation.

PubMed Central

Pan, W J; Blackburn, E H

1995-01-01

The rRNA genes in the somatic macronucleus of Tetrahymena thermophila are normally on 21 kb linear palindromic molecules (rDNA). We examined the effect on rRNA gene dosage of transforming T.thermophila macronuclei with plasmid constructs containing a pair of tandemly repeated rDNA replication origin regions unlinked to the rRNA gene. A significant proportion of the plasmid sequences were maintained as high copy circular molecules, eventually consisting solely of tandem arrays of origin regions. As reported previously for cells transformed by a construct in which the same tandem rDNA origins were linked to the rRNA gene [Yu, G.-L. and Blackburn, E. H. (1990) Mol. Cell. Biol., 10, 2070-2080], origin sequences recombined to form linear molecules bearing several tandem repeats of the origin region, as well as rRNA genes. The total number of rDNA origin sequences eventually exceeded rRNA gene copies by approximately 20- to 40-fold and the number of circular replicons carrying only rDNA origin sequences exceeded rRNA gene copies by 2- to 3-fold. However, the rRNA gene dosage was unchanged. Hence, simply monitoring the total number of rDNA origin regions is not sufficient to regulate rRNA gene copy number. Images PMID:7784211

Spatially resolved metabolic analysis reveals a central role for transcriptional control in carbon allocation to wood.

PubMed

Roach, Melissa; Arrivault, Stéphanie; Mahboubi, Amir; Krohn, Nicole; Sulpice, Ronan; Stitt, Mark; Niittylä, Totte

2017-06-15

The contribution of transcriptional and post-transcriptional regulation to modifying carbon allocation to developing wood of trees is not well defined. To clarify the role of transcriptional regulation, the enzyme activity patterns of eight central primary metabolism enzymes across phloem, cambium, and developing wood of aspen (Populus tremula L.) were compared with transcript levels obtained by RNA sequencing of sequential stem sections from the same trees. Enzymes were selected on the basis of their importance in sugar metabolism and in linking primary metabolism to lignin biosynthesis. Existing enzyme assays were adapted to allow measurements from ~1 mm3 sections of dissected stem tissue. These experiments provided high spatial resolution of enzyme activity changes across different stages of wood development, and identified the gene transcripts probably responsible for these changes. In most cases, there was a clear positive relationship between transcripts and enzyme activity. During secondary cell wall formation, the increases in transcript levels and enzyme activities also matched with increased levels of glucose, fructose, hexose phosphates, and UDP-glucose, emphasizing an important role for transcriptional regulation in carbon allocation to developing aspen wood. These observations corroborate the efforts to increase carbon allocation to wood by engineering gene regulatory networks. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

A Sex Chromosome piRNA Promotes Robust Dosage Compensation and Sex Determination in C. elegans.

PubMed

Tang, Wen; Seth, Meetu; Tu, Shikui; Shen, En-Zhi; Li, Qian; Shirayama, Masaki; Weng, Zhiping; Mello, Craig C

2018-03-26

In metazoans, Piwi-related Argonaute proteins engage piRNAs (Piwi-interacting small RNAs) to defend the genome against invasive nucleic acids, such as transposable elements. Yet many organisms-including worms and humans-express thousands of piRNAs that do not target transposons, suggesting that piRNA function extends beyond genome defense. Here, we show that the X chromosome-derived piRNA 21ux-1 downregulates XOL-1 (XO Lethal), a master regulator of X chromosome dosage compensation and sex determination in Caenorhabditis elegans. Mutations in 21ux-1 and several Piwi-pathway components sensitize hermaphrodites to dosage compensation and sex determination defects. We show that the piRNA pathway also targets xol-1 in C. briggsae, a nematode species related to C. elegans. Our findings reveal physiologically important piRNA-mRNA interactions, raising the possibility that piRNAs function broadly to ensure robust gene expression and germline development. Copyright © 2018. Published by Elsevier Inc.

Co-administration of cholera toxin and apple polyphenol extract as a novel and safe mucosal adjuvant strategy.

PubMed

Yoshino, Naoto; Fujihashi, Kohtaro; Hagiwara, Yukari; Kanno, Hiroyuki; Takahashi, Kiyomi; Kobayashi, Ryoki; Inaba, Noriyuki; Noda, Masatoshi; Sato, Shigehiro

2009-07-30

Although native cholera toxin (CT) is an extremely effective adjuvant, its toxicity prevents its use in humans. We report here that apple polyphenol extract (APE), obtained from unripe apples, reduces CT-induced morphological changes and cAMP accumulation. Based upon this finding, we have attempted to design a novel, effective and safe mucosal vaccine by using CT with several dosages of APE as nasal adjuvants. Mice nasally immunized with OVA plus CT and an optimal dosage of APE showed significantly reduced levels of inflammatory responses as well as total and OVA-specific IgE antibodies when compared with mice given without APE. However, levels of both mucosal and systemic OVA-specific antibody responses were maintained. Further, APE significantly down-regulated accumulation of CT in the olfactory nerves and epithelium. In summary, an optimal dosage of APE would take full advantage of mucosal adjuvanticity of native CT without any toxicity for application in humans.

Cooperation between a hierarchical set of recruitment sites targets the X chromosome for dosage compensation

PubMed Central

Albritton, Sarah Elizabeth; Kranz, Anna-Lena; Winterkorn, Lara Heermans; Street, Lena Annika; Ercan, Sevinc

2017-01-01

In many organisms, it remains unclear how X chromosomes are specified for dosage compensation, since DNA sequence motifs shown to be important for dosage compensation complex (DCC) recruitment are themselves not X-specific. Here, we addressed this problem in C. elegans. We found that the DCC recruiter, SDC-2, is required to maintain open chromatin at a small number of primary DCC recruitment sites, whose sequence and genomic context are X-specific. Along the X, primary recruitment sites are interspersed with secondary sites, whose function is X-dependent. A secondary site can ectopically recruit the DCC when additional recruitment sites are inserted either in tandem or at a distance (>30 kb). Deletion of a recruitment site on the X results in reduced DCC binding across several megabases surrounded by topologically associating domain (TAD) boundaries. Our work elucidates that hierarchy and long-distance cooperativity between gene-regulatory elements target a single chromosome for regulation. DOI: http://dx.doi.org/10.7554/eLife.23645.001 PMID:28562241

76 FR 18869 - Allocation of Assets in Single-Employer Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-06

... PENSION BENEFIT GUARANTY CORPORATION 29 CFR Part 4044 Allocation of Assets in Single-Employer Plans CFR Correction In Title 29 of the Code of Federal Regulations, Part 1927 to End, revised as of July 1, 2010, on page 1007, in the table in Appendix B, in the entry for July 1994, the fourth column...

34 CFR 200.72 - Procedures for adjusting allocations determined by the Secretary to account for eligible LEAs not...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Procedures for adjusting allocations determined by the Secretary to account for eligible LEAs not on the Census list. 200.72 Section 200.72 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION...

34 CFR 200.72 - Procedures for adjusting allocations determined by the Secretary to account for eligible LEAs not...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Procedures for adjusting allocations determined by the Secretary to account for eligible LEAs not on the Census list. 200.72 Section 200.72 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION...

34 CFR 403.116 - How does a State allocate funds under the Postsecondary and Adult Vocational Education Programs?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false How does a State allocate funds under the Postsecondary and Adult Vocational Education Programs? 403.116 Section 403.116 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF...

Regulation of the X Chromosome in the Germline and Soma of Drosophila melanogaster Males.

PubMed

Argyridou, Eliza; Parsch, John

2018-05-04

During the evolution of heteromorphic sex chromosomes, the sex-specific Y chromosome degenerates, while the X chromosome evolves new mechanisms of regulation. Using bioinformatic and experimental approaches, we investigate the expression of the X chromosome in Drosophila melanogaster . We observe nearly complete X chromosome dosage compensation in male somatic tissues, but not in testis. The X chromosome contains disproportionately fewer genes with high expression in testis than the autosomes, even after accounting for the lack of dosage compensation, which suggests that another mechanism suppresses their expression in the male germline. This is consistent with studies of reporter genes and transposed genes, which find that the same gene has higher expression when autosomal than when X-linked. Using a new reporter gene that is expressed in both testis and somatic tissues, we find that the suppression of X-linked gene expression is limited to genes with high expression in testis and that the extent of the suppression is positively correlated with expression level.

Evaluation the anaerobic hydrolysis acidification stage of kitchen waste by pH regulation.

PubMed

Wang, Yaya; Zang, Bing; Li, Guoxue; Liu, Yu

2016-07-01

This study analyzed the composition and characteristic of kitchen waste (KW) from closed cleaning station of Chaoyang District, Beijing. It was featured by high vegetables and peels contents. This study investigated effect of pH regulation and uncontrolled pH (CK) on the lab-scale anaerobic hydrolysis acidification stage of KW. The optimal adjusting mode by NaOH (including dosage and frequency) was evaluated according to indexes of pH, VFAs, NH4(+)-N, TS, VS, TS/VS, TS and VS removal rate. The treatment 4 as first two days adjusting per 16h and then one time per day at pH 7 was chosen as the optimal mode with high VFAs content(47.31g/L), TS and VS removal rate (42.95% and 54.01%, respectively), low adjusting frequency, fewer dosage and practical operability. Thus, adjusting mode of treatment 4 could be considered using in anaerobic hydrolysis acidification stage on engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Postoperative pain management by intravenous patient-controlled analgesia in patients undergoing upper abdominal gastrointestinal surgery].

PubMed

Kajiyama, Seiji; Niihata, Tomoko; Sugimoto, Yuki; Kawamoto, Masashi

2012-10-01

We conducted a retrospective study to evaluate the effectiveness of intravenous patient-controlled analgesia (IVPCA) in the early postoperative period after upper abdominal gastrointestinal surgery. We also evaluated the postoperative effects of intraoperative analgesic dosage in patients after this surgery. A total of 59 adult patients classified as ASA 1-3 were allocated to one of two groups: Group A, 23 patients who requested IVPCA more than 50 times, and Group B, 36 patients with fewer than 50 requests. IVPCA was induced using morphine 1 mg x ml(-1) without a base dose. The bolus dose was 1 ml and the lock-out time was 5 min. There was no significant difference between the two groups in the total intraoperative remifentanil dosage/body weight/surgical duration, predicted effect-site concentration of fentanyl during extubation, and utilization of flurbiprofen. The doses of morphine were significantly higher, and the visual analogue scale scores for pain at rest and during movement tended to be lower in group A than in group B. The results of this study suggest that the effects of intraoperative analgesics may not be significant. Patients who had received the above mentioned anesthetic regimen intraoperatively also required full postoperative analgesia as well.

Increased Maternal Genome Dosage Bypasses the Requirement of the FIS Polycomb Repressive Complex 2 in Arabidopsis Seed Development

PubMed Central

Kradolfer, David; Hennig, Lars; Köhler, Claudia

2013-01-01

Seed development in flowering plants is initiated after a double fertilization event with two sperm cells fertilizing two female gametes, the egg cell and the central cell, leading to the formation of embryo and endosperm, respectively. In most species the endosperm is a polyploid tissue inheriting two maternal genomes and one paternal genome. As a consequence of this particular genomic configuration the endosperm is a dosage sensitive tissue, and changes in the ratio of maternal to paternal contributions strongly impact on endosperm development. The FERTILIZATION INDEPENDENT SEED (FIS) Polycomb Repressive Complex 2 (PRC2) is essential for endosperm development; however, the underlying forces that led to the evolution of the FIS-PRC2 remained unknown. Here, we show that the functional requirement of the FIS-PRC2 can be bypassed by increasing the ratio of maternal to paternal genomes in the endosperm, suggesting that the main functional requirement of the FIS-PRC2 is to balance parental genome contributions and to reduce genetic conflict. We furthermore reveal that the AGAMOUS LIKE (AGL) gene AGL62 acts as a dosage-sensitive seed size regulator and that reduced expression of AGL62 might be responsible for reduced size of seeds with increased maternal genome dosage. PMID:23326241

Curcumin Stimulates Proliferation of Spinal Cord Neural Progenitor Cells via a Mitogen-Activated Protein Kinase Signaling Pathway

PubMed Central

Son, Sihoon; Cho, Dae-Chul; Kim, Hye-Jeong; Sung, Joo-Kyung; Bae, Jae-Sung

2014-01-01

Objective The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs. Methods We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun NH2-terminal kinases (JNKs) and β-actin as the control group. Results Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, 1 µM) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and 1 µM, p<0.05). Conclusion Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations. PMID:25289117

7 CFR 305.8 - Sulfuryl fluoride treatment schedules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Sulfuryl fluoride treatment schedules. 305.8 Section 305.8 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH... fluoride treatment schedules. Treatment schedule Pressure Temperature ( °F) Dosage rate(lb/1000 cubic feet...

The Organ Allocation Controversy: How Did We Arrive Here?

PubMed Central

Van Meter, Clifford H.

1999-01-01

The Department of Health and Human Services (HHS) recently issued a final regulation governing the Organ Procurement and Transplantation Network (OPTN) that directs the allocation of organs to the sickest patients first without regard to a host of medical, geographic, and social factors that members of the transplant community view as an essential part of a sound organ allocation policy. Current organ allocation mechanisms are based on policies that reflect a broad consensus of medical experts and provide equal consideration for both the needs of the sickest patients and the efficient use of organs. This system also reduces potential waste of organs by minimizing cold ischemic time, increases access to transplantation for patients in local communities, provides positive incentives for local citizens and medical professionals to support organ donation initiatives, and decreases the cost of organ transplantation. Representatives of the American Society of Transplant Surgeons have testified before Congress that “giving priority to the sickest patients first over broad geographic areas would be wasteful and dangerous, resulting in fewer patients transplanted, increased death rates, increased retransplantation due to poor organ function, and increased overall cost of transplantation.” In response, Congress enacted a 1-year moratorium on the implementation of the HHS rule and provided for a study of the current organ allocation policy and HHS regulation by The Institute of Medicine. PMID:21845113

Regulating nutrient allocation in plants

DOEpatents

Udvardi, Michael; Yang, Jiading; Worley, Eric

2014-12-09

The invention provides coding and promoter sequences for a VS-1 and AP-2 gene, which affects the developmental process of senescence in plants. Vectors, transgenic plants, seeds, and host cells comprising heterologous VS-1 and AP-2 genes are also provided. Additionally provided are methods of altering nutrient allocation and composition in a plant using the VS-1 and AP-2 genes.

Health Resources Priority and Allocations System (HRPAS). Interim final rule.

PubMed

2015-07-17

This interim final rule establishes standards and procedures by which the U.S. Department of Health and Human Services (HHS) may require that certain contracts or orders that promote the national defense be given priority over other contracts or orders. This rule also sets new standards and procedures by which HHS may allocate materials, services, and facilities to promote the national defense. This rule will implement HHS's administration of priorities and allocations actions, and establish the Health Resources Priorities and Allocation System (HRPAS). The HRPAS will cover health resources pursuant to the authority under Section 101(c) of the Defense Production Act as delegated to HHS by Executive Order 13603. Priorities authorities (and other authorities delegated to the Secretary in E.O. 13603, but not covered by this regulation) may be re-delegated by the Secretary. The Secretary retains the authority for allocations.

75 FR 38699 - Implantation or Injectable Dosage Form New Animal Drugs; Propofol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

...The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a new animal drug application (NADA) filed by Fort Dodge Animal Health, Division of Wyeth. The NADA provides for veterinary prescription use of propofol as an anesthetic in dogs and cats.

Biochemical and Functional Analysis of Drosophila-Sciara Chimeric Sex-Lethal Proteins

PubMed Central

Ruiz, María Fernanda; Sarno, Francesca; Zorrilla, Silvia; Rivas, Germán; Sánchez, Lucas

2013-01-01

Background The Drosophila SXL protein controls sex determination and dosage compensation. It is a sex-specific factor controlling splicing of its own Sxl pre-mRNA (auto-regulation), tra pre-mRNA (sex determination) and msl-2 pre-mRNA plus translation of msl-2 mRNA (dosage compensation). Outside the drosophilids, the same SXL protein has been found in both sexes so that, in the non-drosophilids, SXL does not appear to play the key discriminating role in sex determination and dosage compensation that it plays in Drosophila. Comparison of SXL proteins revealed that its spatial organisation is conserved, with the RNA-binding domains being highly conserved, whereas the N- and C-terminal domains showing significant variation. This manuscript focuses on the evolution of the SXL protein itself and not on regulation of its expression. Methodology Drosophila-Sciara chimeric SXL proteins were produced. Sciara SXL represents the non-sex-specific function of ancient SXL in the non-drosophilids from which presumably Drosophila SXL evolved. Two questions were addressed. Did the Drosophila SXL protein have affected their functions when their N- and C-terminal domains were replaced by the corresponding ones of Sciara? Did the Sciara SXL protein acquire Drosophila sex-specific functions when the Drosophila N- and C-terminal domains replaced those of Sciara? The chimeric SXL proteins were analysed in vitro to study their binding affinity and cooperative properties, and in vivo to analyse their effect on sex determination and dosage compensation by producing Drosophila flies that were transgenic for the chimeric SXL proteins. Conclusions The sex-specific properties of extant Drosophila SXL protein depend on its global structure rather than on a specific domain. This implies that the modifications, mainly in the N- and C-terminal domains, that occurred in the SXL protein during its evolution within the drosophilid lineage represent co-evolutionary changes that determine the appropriate folding of SXL to carry out its sex-specific functions. PMID:23762307

Condensin-driven remodelling of X chromosome topology during dosage compensation

NASA Astrophysics Data System (ADS)

Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

2015-07-01

The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using CRISPR/Cas9 greatly diminished the boundary. Thus, the DCC imposes a distinct higher-order structure onto X chromosomes while regulating gene expression chromosome-wide.

Condensin-Driven Remodeling of X-Chromosome Topology during Dosage Compensation

PubMed Central

Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

2015-01-01

The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure1,2. Here we perform genome-wide chromosome conformation capture analysis, FISH, and RNA-seq to obtain comprehensive 3D maps of the Caenorhabditis elegans genome and to dissect X-chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half3–7. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes5,6. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian Topologically Associating Domains (TADs)8,9. TADs on X have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using CRISPR/Cas9 greatly diminished the boundary. Thus, the DCC imposes a distinct higher-order structure onto X while regulating gene expression chromosome wide. PMID:26030525

48 CFR 3011.602 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 3011.602 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... contractors to acquire products, materials, and services under the Defense Priorities and Allocations System (DPAS) regulations (15 CFR part 700): (1) The U.S. Coast Guard in support of certified national defense...

48 CFR 3011.602 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 3011.602 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... contractors to acquire products, materials, and services under the Defense Priorities and Allocations System (DPAS) regulations (15 CFR part 700): (1) The U.S. Coast Guard in support of certified national defense...

48 CFR 3011.602 - General.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 3011.602 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... contractors to acquire products, materials, and services under the Defense Priorities and Allocations System (DPAS) regulations (15 CFR part 700): (1) The U.S. Coast Guard in support of certified national defense...

48 CFR 3011.602 - General.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 3011.602 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... contractors to acquire products, materials, and services under the Defense Priorities and Allocations System (DPAS) regulations (15 CFR part 700): (1) The U.S. Coast Guard in support of certified national defense...

48 CFR 3011.602 - General.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 3011.602 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... contractors to acquire products, materials, and services under the Defense Priorities and Allocations System (DPAS) regulations (15 CFR part 700): (1) The U.S. Coast Guard in support of certified national defense...

48 CFR 11.602 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

....602 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING... Production Act of 1950 (50 U.S.C. App. 2061, et seq.), the President is authorized to require preferential... programs. (b) The President delegated the priorities and allocations authorities of the Defense Production...

48 CFR 11.602 - General.

Code of Federal Regulations, 2013 CFR

2013-10-01

....602 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING... Production Act of 1950 (50 U.S.C. App. 2061, et seq.), the President is authorized to require preferential... programs. (b) The President delegated the priorities and allocations authorities of the Defense Production...

48 CFR 11.602 - General.

Code of Federal Regulations, 2014 CFR

2014-10-01

....602 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING... Production Act of 1950 (50 U.S.C. App. 2061, et seq.), the President is authorized to require preferential... programs. (b) The President delegated the priorities and allocations authorities of the Defense Production...

48 CFR 11.602 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

....602 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING... Production Act of 1950 (50 U.S.C. App. 2061, et seq.), the President is authorized to require preferential... programs. (b) The President delegated the priorities and allocations authorities of the Defense Production...

48 CFR 11.602 - General.

Code of Federal Regulations, 2012 CFR

2012-10-01

....602 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING... Production Act of 1950 (50 U.S.C. App. 2061, et seq.), the President is authorized to require preferential... programs. (b) The President delegated the priorities and allocations authorities of the Defense Production...

Work-family conflict and self-discrepant time allocation at work.

PubMed

Dahm, Patricia C; Glomb, Theresa M; Manchester, Colleen Flaherty; Leroy, Sophie

2015-05-01

We examine the relationships between work-to-family conflict, time allocation across work activities, and the outcomes of work satisfaction, well-being, and salary in the context of self-regulation and self-discrepancy theories. We posit work-to-family conflict is associated with self-discrepant time allocation such that employees with higher levels of work-to-family conflict are likely to allocate less time than preferred to work activities that require greater self-regulatory resources (e.g., tasks that are complex, or those with longer term goals that delay rewards and closure) and allocate more time than preferred to activities that demand fewer self-regulatory resources or are replenishing (e.g., those that provide closure or are prosocial). We suggest this self-discrepant time allocation (actual vs. preferred time allocation) is one mechanism by which work-to-family conflict leads to negative employee consequences (Allen, Herst, Bruck, & Sutton, 2000; Mesmer-Magnus & Viswesvaran, 2005). Using polynomial regression and response surface methodology, we find that discrepancies between actual and preferred time allocations to work activities negatively relate to work satisfaction, psychological well-being, and physical well-being. Self-discrepant time allocation mediates the relationship between work-to-family conflict and work satisfaction and well-being, while actual time allocation (rather than the discrepancy) mediates the relationship between work-to-family conflict and salary. We find that women are more likely than men to report self-discrepant time allocations as work-to-family conflict increases. (c) 2015 APA, all rights reserved.

Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

PubMed Central

Qi, Wei; Zhao, Ting; Yang, Wen-Wen; Wang, Guang-Hou; Yu, Hua; Zhao, Hai-Xiao; Yang, Chen; Sun, Li-Xin

2011-01-01

The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUC0−t, AUC0−∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosage of 50.0 mg/kg. PMID:29403709

Psycho-social stress, insomnia and temazepam: a sleep laboratory evaluation in a "general practice" sample.

PubMed

Beary, M D; Lacey, J H; Crutchfield, M B; Bhat, A V

1984-01-01

Taking a population of women most of whom were about to seek medication from their general practitioner for stress-induced insomnia, this sleep laboratory study examined--both electro -physiologically and psychologically--the immediate impact of temazepam, at normal prescribed dosage, on sleep. The study was double-blind, controlled with random allocation. Temazepam 20 mg, prepared as a liquid in a soft gelatin capsule, reduced sleep latency and prolonged total sleep time. A reduction in stage shifts to Stages I and II and a reduction in time spent in Stages 0 + I suggest more restful sleep. The sleep "architecture" (including REM/NREM cycling, total SWS and REM time) was relatively undisturbed. Temazepam would seem to be effective as a first-line hypnotic for short-term use in stressed patients.

48 CFR 911.604 - Solicitation provision and contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Solicitation provision and contract clause. 911.604 Section 911.604 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.604 Solicitation...

48 CFR 911.604 - Solicitation provision and contract clause.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Solicitation provision and contract clause. 911.604 Section 911.604 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.604 Solicitation...

48 CFR 911.600 - Scope of subpart.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Scope of subpart. 911.600 Section 911.600 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.600 Scope of subpart. This subpart...

48 CFR 911.600 - Scope of subpart.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Scope of subpart. 911.600 Section 911.600 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.600 Scope of subpart. This subpart...

48 CFR 911.604 - Solicitation provision and contract clause.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Solicitation provision and contract clause. 911.604 Section 911.604 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.604 Solicitation...

48 CFR 911.600 - Scope of subpart.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Scope of subpart. 911.600 Section 911.600 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.600 Scope of subpart. This subpart...

48 CFR 911.600 - Scope of subpart.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Scope of subpart. 911.600 Section 911.600 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.600 Scope of subpart. This subpart...

48 CFR 911.604 - Solicitation provision and contract clause.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Solicitation provision and contract clause. 911.604 Section 911.604 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.604 Solicitation...

48 CFR 911.604 - Solicitation provision and contract clause.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Solicitation provision and contract clause. 911.604 Section 911.604 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.604 Solicitation...

48 CFR 911.600 - Scope of subpart.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Scope of subpart. 911.600 Section 911.600 Federal Acquisition Regulations System DEPARTMENT OF ENERGY COMPETITION ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 911.600 Scope of subpart. This subpart...

Structure and function of histone acetyltransferase MOF

PubMed Central

Chen, Qiao Yi; Costa, Max; Sun, Hong

2016-01-01

MOF was first identified in Drosophila melanogaster as an important component of the dosage compensation complex. As a member of MYST family of histone acetyltransferase, MOF specifically deposits the acetyl groups to histone H4 lysine 16. Throughout evolution, MOF and its mammalian ortholog have retained highly conserved substrate specificity and similar enzymatic activities. MOF plays important roles in dosage compensation, ESC self-renewal, DNA damage and repair, cell survival, and gene expression regulation. Dysregulation of MOF has been implicated in tumor formation and progression of many types of human cancers. This review will discuss the structure and activity of mammalian hMOF as well as its function in H4K16 acetylation, DNA damage response, stem cell pluripotency, and carcinogenesis. PMID:28503659

FDA Expands List of "Do Not Compound" Drug Products.

PubMed

2017-03-01

EDITOR'S ABSTRACT On October 3, 2016, the U.S. Food and Drug Administration published in the Federal Register an expanded list of drug products that are not to be used in compounding extemporaneous dosage forms. This list contains numerous analgesic or anti-inflammatory agents and other chemicals sometimes used to manage pain and related symptoms. Because pharmacies are licensed by the states and other jurisdictions (districts, territories) as opposed to the federal government, regulation of extemporaneous compounding is inconsistent across the nation and minimal to nonexistent is some jurisdictions. Clinicians are urged to assure that pharmacies they and their patients use adhere to this list and compound only dosage forms for which there is good evidence of both safety and efficacy.

Structure and function of histone acetyltransferase MOF.

PubMed

Chen, Qiao Yi; Costa, Max; Sun, Hong

2015-01-01

MOF was first identified in Drosophila melanogaster as an important component of the dosage compensation complex. As a member of MYST family of histone acetyltransferase, MOF specifically deposits the acetyl groups to histone H4 lysine 16. Throughout evolution, MOF and its mammalian ortholog have retained highly conserved substrate specificity and similar enzymatic activities. MOF plays important roles in dosage compensation, ESC self-renewal, DNA damage and repair, cell survival, and gene expression regulation. Dysregulation of MOF has been implicated in tumor formation and progression of many types of human cancers. This review will discuss the structure and activity of mammalian hMOF as well as its function in H4K16 acetylation, DNA damage response, stem cell pluripotency, and carcinogenesis.

A mutually exclusive stem–loop arrangement in roX2 RNA is essential for X-chromosome regulation in Drosophila

PubMed Central

Ilik, Ibrahim Avsar; Maticzka, Daniel; Georgiev, Plamen; Gutierrez, Noel Marie; Backofen, Rolf; Akhtar, Asifa

2017-01-01

The X chromosome provides an ideal model system to study the contribution of RNA–protein interactions in epigenetic regulation. In male flies, roX long noncoding RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X-chromosomal regulation. However, how these interactions provide the mechanics of spreading remains unknown. By using the uvCLAP (UV cross-linking and affinity purification) methodology, which provides unprecedented information about RNA secondary structures in vivo, we identified the minimal functional unit of roX2 RNA. By using wild-type and various MLE mutant derivatives, including a catalytically inactive MLE derivative, MLEGET, we show that the minimal roX RNA contains two mutually exclusive stem–loops that exist in a peculiar structural arrangement: When one stem–loop is unwound by MLE, an alternate structure can form, likely trapping MLE in this perpetually structured region. We show that this functional unit is necessary for dosage compensation, as mutations that disrupt this formation lead to male lethality. Thus, we propose that roX2 lncRNA contains an MLE-dependent affinity switch to enable reversible interactions of the MSL complex to allow dosage compensation of the X chromosome. PMID:29066499

GENOME-ENABLED DISCOVERY OF CARBON SEQUESTRATION GENES IN POPLAR

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

DAVIS J M

2007-10-11

Plants utilize carbon by partitioning the reduced carbon obtained through photosynthesis into different compartments and into different chemistries within a cell and subsequently allocating such carbon to sink tissues throughout the plant. Since the phytohormones auxin and cytokinin are known to influence sink strength in tissues such as roots (Skoog & Miller 1957, Nordstrom et al. 2004), we hypothesized that altering the expression of genes that regulate auxin-mediated (e.g., AUX/IAA or ARF transcription factors) or cytokinin-mediated (e.g., RR transcription factors) control of root growth and development would impact carbon allocation and partitioning belowground (Fig. 1 - Renewal Proposal). Specifically, themore » ARF, AUX/IAA and RR transcription factor gene families mediate the effects of the growth regulators auxin and cytokinin on cell expansion, cell division and differentiation into root primordia. Invertases (IVR), whose transcript abundance is enhanced by both auxin and cytokinin, are critical components of carbon movement and therefore of carbon allocation. Thus, we initiated comparative genomic studies to identify the AUX/IAA, ARF, RR and IVR gene families in the Populus genome that could impact carbon allocation and partitioning. Bioinformatics searches using Arabidopsis gene sequences as queries identified regions with high degrees of sequence similarities in the Populus genome. These Populus sequences formed the basis of our transgenic experiments. Transgenic modification of gene expression involving members of these gene families was hypothesized to have profound effects on carbon allocation and partitioning.« less

Experimental evidence of a risk-sensitive reproductive allocation in a long-lived mammal.

PubMed

Bårdsen, Bard-Jørgen; Fauchald, Per; Tveraa, Torkild; Langeland, Knut; Yoccoz, Nigel Gilles; Ims, Rolf Anker

2008-03-01

When reproduction competes with the amount of resources available for survival during an unpredictable nonbreeding season, individuals should adopt a risk-sensitive regulation of their reproductive allocation. We tested this hypothesis on female reindeer (Rangifer tarandus), which face a trade-off between reproduction and acquisition of body reserves during spring and summer, with autumn body mass functioning as insurance against stochastic winter climatic severity. The study was conducted in a population consisting of two herds: one that received supplementary winter feeding for four years while the other utilized natural pastures. The females receiving additional forage allocated more to their calves. Experimental translocation of females between the herds was conducted to simulate two contrasting rapid alterations of winter conditions. When females receiving supplementary feeding were moved to natural pastures, they promptly reduced their reproductive allocation the following summer. However, when winter conditions were improved, females were reluctant to increase their reproductive allocation. This asymmetric response to improved vs. reduced winter conditions is consistent with a risk-averse adjustment in reproductive allocation. The ability of individuals to track their environment and the concordant risk-sensitive adjustment of reproductive allocation may render subarctic reindeer more resilient to climate change than previously supposed.

Reduction of serum TARC levels in atopic dermatitis by topical anti-inflammatory treatments.

PubMed

Yasukochi, Yumi; Nakahara, Takeshi; Abe, Takeru; Kido-Nakahara, Makiko; Kohda, Futoshi; Takeuchi, Satoshi; Hagihara, Akihito; Furue, Masutaka

2014-09-01

Serum thymus and activation-regulated chemokine (TARC) levels are associated with the disease activity of patients with atopic dermatitis (AD) and sensitively reflect short-term changes in skin conditions. The main treatment for AD is topical agent application. This study investigated the relationship between serum TARC levels and the dosage of topical agents, including corticosteroids and/or tacrolimus, in patients with AD. The serum TARC levels of 56 AD patients and the amounts of topical agents prescribed to them were investigated retrospectively. The weekly reduction in serum TARC levels and weekly dosage of topical agents among AD patients were compared and their associations were evaluated. The dosage of topical agents was closely related to serum TARC levels. One gram of strong rank steroid or the equivalent amount of steroid/tacrolimus is required to reduce serum TARC levels by 9.94 pg/mL weekly in moderate to severe AD patients. Higher initial TARC levels require more topical agent, which results in a more rapid decrease in TARC levels. The serum TARC levels and eosinophil numbers in peripheral blood are significantly correlated. Serum TARC level improvement and topical agent dosage are strongly correlated. TARC and eosinophil numbers are significantly correlated, but the wider range of TARC levels seems to be clinically more useful for monitoring AD severity. The serum TARC level is a very sensitive biomarker for monitoring the severity and treatment response in AD.

48 CFR 511.600 - Scope of subpart.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Scope of subpart. 511.600 Section 511.600 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 511.600 Scope of subpart. Pursuant to...

48 CFR 511.600 - Scope of subpart.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Scope of subpart. 511.600 Section 511.600 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Priorities and Allocations 511.600 Scope of subpart. Pursuant to...

Dosage-Sensitive Function of RETINOBLASTOMA RELATED and Convergent Epigenetic Control Are Required during the Arabidopsis Life Cycle

PubMed Central

Johnston, Amal J.; Kirioukhova, Olga; Barrell, Philippa J.; Rutten, Twan; Moore, James M.; Baskar, Ramamurthy; Grossniklaus, Ueli; Gruissem, Wilhelm

2010-01-01

The plant life cycle alternates between two distinct multi-cellular generations, the reduced gametophytes and the dominant sporophyte. Little is known about how generation-specific cell fate, differentiation, and development are controlled by the core regulators of the cell cycle. In Arabidopsis, RETINOBLASTOMA RELATED (RBR), an evolutionarily ancient cell cycle regulator, controls cell proliferation, differentiation, and regulation of a subset of Polycomb Repressive Complex 2 (PRC2) genes and METHYLTRANSFERASE 1 (MET1) in the male and female gametophytes, as well as cell fate establishment in the male gametophyte. Here we demonstrate that RBR is also essential for cell fate determination in the female gametophyte, as revealed by loss of cell-specific marker expression in all the gametophytic cells that lack RBR. Maintenance of genome integrity also requires RBR, because diploid plants heterozygous for rbr (rbr/RBR) produce an abnormal portion of triploid offspring, likely due to gametic genome duplication. While the sporophyte of the diploid mutant plants phenocopied wild type due to the haplosufficiency of RBR, genetic analysis of tetraploid plants triplex for rbr (rbr/rbr/rbr/RBR) revealed that RBR has a dosage-dependent pleiotropic effect on sporophytic development, trichome differentiation, and regulation of PRC2 subunit genes CURLY LEAF (CLF) and VERNALIZATION 2 (VRN2), and MET1 in leaves. There were, however, no obvious cell cycle and cell proliferation defects in these plant tissues, suggesting that a single functional RBR copy in tetraploids is capable of maintaining normal cell division but is not sufficient for distinct differentiation and developmental processes. Conversely, in leaves of mutants in sporophytic PRC2 subunits, trichome differentiation was also affected and expression of RBR and MET1 was reduced, providing evidence for a RBR-PRC2-MET1 regulatory feedback loop involved in sporophyte development. Together, dosage-sensitive RBR function and its genetic interaction with PRC2 genes and MET1 must have been recruited during plant evolution to control distinct generation-specific cell fate, differentiation, and development. PMID:20585548

15 CFR 700.74 - Violations, penalties, and remedies.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Violations, penalties, and remedies. 700.74 Section 700.74 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade... REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Compliance § 700.74 Violations, penalties, and remedies...

Health tourism and the UK: some new developments.

PubMed

McHale, Jean

Pre-empting the implementation of the EU draft Patient's Rights directive, the UK Government has issued regulations governing the reimbursement of costs of treatment to patients seeking treatment overseas. This article explores the new regulations and how they may impact on NHS resource allocation in the future.

Epigenetic modification and inheritance in sexual reversal of fish.

PubMed

Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei; Zhang, Yong; Wang, Jun; Zhang, Guojie

2014-04-01

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

Uterine Development and Fertility Are Dependent on Gene Dosage of the Nuclear Receptor Coregulator REA

PubMed Central

Park, Sunghee; Yoon, Sangyeon; Zhao, Yuechao; Park, Seong-Eun; Liao, Lan; Xu, Jianming; Lydon, John P.; DeMayo, Francesco J.; O'Malley, Bert W.; Bagchi, Milan K.

2012-01-01

Although the effectiveness of nuclear hormone-receptor complexes is known to depend on coregulator partner proteins, relatively little is known about the roles of coregulators in uterine development and early stages of pregnancy and implantation. Because conventional genetic deletion of the coregulator, repressor of estrogen receptor activity (REA), was embryonic lethal, we here study REA conditional knockout mice generated by cre-loxP recombination, in which REA function was abrogated only in progesterone receptor-expressing tissues, to define the roles of REA in postembryonic stages and in a tissue-specific manner. We find that REA has gene dose-dependent activity impacting uterine development and fertility. Conditional homozygous mutant (REAd/d) mice developed to adulthood and showed normal ovarian function, but females were infertile with severely compromised uterine development and function characterized by cell cycle arrest, apoptosis, and altered adenogenesis (endometrial gland morphogenesis), resulting in failure of implantation and decidualization. By contrast, mice heterozygous for REA (REAf/d) had a very different phenotype, with estradiol treatment resulting in hyperstimulated, large uteri showing increased proliferation of luminal epithelial cells, and enhanced fluid imbibition associated with altered regulation of aquaporins. These REAf/d female mice showed a subfertility phenotype with reduced numbers and sizes of litters. These findings highlight that uterine development and regulation of estrogen receptor activities show a bimodal dependence on the gene dosage of REA. Optimal uterine development and functional activities require the normal gene dosage of REA, with partial or complete deletion resulting in hyperresponsiveness or underresponsiveness to hormone and subfertility or infertility, respectively. PMID:22585830

Comparison and evaluation of gene therapy and epigenetic approaches for wound healing.

PubMed

Cutroneo, K R; Chiu, J F

2000-01-01

During the past decade considerable evidence has mounted concerning the importance of growth factors in the wound healing process both for cell replication and for stimulating reparative cells to synthesize and secrete extracellular matrix components. During normal wound healing the growth factor concentration has to be maintained at a certain level. If the growth factor concentration is too low, normal healing fails to occur. Whereas if the growth factor concentration is too high due to either over-expression of the growth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between the beneficial therapeutic effect and toxic effects with increasing gene dosage, an agent may be necessary to give in combination with gene therapy to regulate the over-expression of growth factor. In addition to genetic approaches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound healing. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a particular collagen gene. This exogenous oligodeoxynucleotide will compete with the cis element in the collagen gene for the trans-acting factor which regulates promoter activity. These epigenetic approaches afford the opportunity to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approaches for regulating the wound healing process, either normal or aberrant wound healing, have certain advantages and disadvantages which are discussed in the present article.

41 CFR 109-26.501-50 - Authority and allocations for the acquisition of passenger motor vehicles.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Contracts and Property Management Federal Property Management Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 26-PROCUREMENT SOURCES AND PROGRAM 26.5-GSA... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Authority and...

Symbiotic regulation of plant growth, development and reproduction

Treesearch

Russell J. Rodriguez; D. Carl Freeman; E. Durant McArthur; Yong Ok Kim; Regina S. Redman

2009-01-01

The growth and development of rice (Oryzae sativa) seedlings was shown to be regulated epigenetically by a fungal endophyte. In contrast to un-inoculated (nonsymbiotic) plants, endophyte colonized (symbiotic) plants preferentially allocated resources into root growth until root hairs were well established. During that time symbiotic roots expanded at...

Semester-Long Inquiry-Based Molecular Biology Laboratory: Transcriptional Regulation in Yeast

ERIC Educational Resources Information Center

Oelkers, Peter M.

2017-01-01

A single semester molecular biology laboratory has been developed in which students design and execute a project examining transcriptional regulation in "Saccharomyces cerevisiae." Three weeks of planning are allocated to developing a hypothesis through literature searches and use of bioinformatics. Common experimental plans address a…

75 FR 41405 - Energy Priorities and Allocations System Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... Production Act Reauthorization of 2009 (Pub. L. 111-67) to publish regulations providing standards and... maximize domestic energy supplies pursuant to its authority under Section 101(c) of the Defense Production... for the production or delivery of industrial resources are required to be given priority over other...

43 CFR 3270.10 - What types of geothermal operations are governed by these utilization regulations?

Code of Federal Regulations, 2011 CFR

2011-10-01

... of geothermal resources. This includes: (1) Electrical generation facilities; (2) Direct use facilities; (3) Related utilization facility operations; (4) Actual and allocated well field production and injection; and (5) Related well field operations. (b) The utilization regulations in subparts 3270 through...

76 FR 31017 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... information collection requirements related to New Markets Tax Credits. DATES: Written comments should be... . SUPPLEMENTARY INFORMATION: Title: New Markets Tax Credits. OMB Number: 1545-1765. Regulation Project Number: REG... a new markets tax credit allocation may claim a 5- percent tax credit with respect to the qualified...

Cureton's Basic Principles of Physical Fitness Work (Rules for Conducting Exercise).

ERIC Educational Resources Information Center

President's Council on Physical Fitness and Sports, Washington, DC.

This document is an annotated list of 20 rules for conducting exercise. Among the rules described are the warm-up rule, the rule for regulation of exercise dosage, recuperation rule, posture rule, glandular fitness rule, maximum respiration rule, and maximum circulation rule. The time of workout and procedures for taking cool baths are…

75 FR 63085 - Certain Other Dosage Form New Animal Drugs; Progesterone Intravaginal Inserts

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

... synchronization of estrus in lactating dairy cows. DATES: This rule is effective October 14, 2010. FOR FURTHER... cows. The NADA is approved as of July 22, 2010, and the regulations are amended in 21 CFR 529.1940 to.... * * * * * (d) * * * (2) Cows. This product is approved with the concurrent use of dinoprost solution when used...

The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the PRINC (Plavix Response in Coronary Intervention) trial.

PubMed

Gladding, Patrick; Webster, Mark; Zeng, Irene; Farrell, Helen; Stewart, Jim; Ruygrok, Peter; Ormiston, John; El-Jack, Seif; Armstrong, Guy; Kay, Patrick; Scott, Douglas; Gunes, Arzu; Dahl, Marja-Liisa

2008-12-01

This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil. Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day. A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week. Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01). In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).

Urine and plasma metabolomics study on potential hepatoxic biomarkers identification in rats induced by Gynura segetum.

PubMed

Qiu, Shoubei; Zhang, Haixia; Fei, Qianqian; Zhu, Fenxia; Wang, Jing; Jia, Xiaobin; Chen, Bin

2018-04-24

Gynura segetum (GS) is an herbal medicine containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal obstruction syndrome (HSOS). To discover potential biomarkers and metabolic mechanisms involved in the hepatotoxicity induced by GS. SD rats were randomly divided into 4 groups including Saline, the decoction of GS high, medium and low dosage at dosages of 3.75g • kg -1 , 7.5g • kg -1 and 15g • kg -1 . A metabolomics approach using Ultraperformance Liquid Chromatography -Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) was developed to perform the plasma and urinary metabolic profiling analysis, and identified differential metabolites by comparing the saline control group and decoction of GS groups. The herbal was presented dosage-dependent led to ingravescence of hepatotoxicity after the rats were consecutively given with the decoction of GS at varied dosages. A total of 18 differential metabolites of decoction of GS-induced hepatotoxicity were identified, while 10 of them including arginine, proline, glutamate, creatine, valine, linoleic acid, arachidonic acid, sphinganine, phytosphingosine, and citric acid could be discovered in urine and plasma, and primarily involved in Amino acid metabolism, Lipids metabolism and Energy metabolism. The results suggested that the differential metabolites of arginine, creatine, valine, glutamine and citric acid were verified as potential markers of GS-induced hepatotoxicity via the regulation of multiple metabolic pathways primarily involving in Amino acids metabolism and Energy metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.

PubMed

Srisawasdi, Pornpen; Vanwong, Natchaya; Hongkaew, Yaowaluck; Puangpetch, Apichaya; Vanavanan, Somlak; Intachak, Boontarika; Ngamsamut, Nattawat; Limsila, Penkhae; Sukasem, Chonlaphat; Kroll, Martin H

2017-08-01

To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein. The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses. Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Changes in cytokinins are sufficient to alter developmental patterns of defense metabolites in Nicotiana attenuata

PubMed Central

Brütting, Christoph; Schäfer, Martin; Vanková, Radomira; Gase, Klaus; Baldwin, Ian T.; Meldau, Stefan

2016-01-01

Plant defense metabolites are well-known to be regulated developmentally. The OD theory posits that a tissue’s fitness values and probability of attack should determine defense metabolite allocations. Young leaves are expected to provide a larger fitness-value to the plant and therefore their defense allocations should be higher when compared to older leaves. The mechanisms which coordinate development with defense remain unknown and frequently confound tests of the OD theory predictions. Here we demonstrate that cytokinins modulate ontogeny-dependent defenses in Nicotiana attenuata. We found that leaf cytokinin levels highly correlate with inducible defense expressions with high levels in young and low levels in older leaves. We genetically manipulated the developmental patterns of two different cytokinin classes by using senescence- and chemically-inducible expression of cytokinin biosynthesis genes. Genetically modifying the levels of different cytokinins in leaves was sufficient to alter ontogenic patterns of defense metabolites. We conclude that the developmental regulation of growth hormones that include cytokinins plays central roles in connecting development with defense and therefore in establishing optimal patterns of defense allocation in plants. PMID:27557345

Something's got to give: the effects of dual-goal difficulty, goal progress, and expectancies on resource allocation.

PubMed

Schmidt, Aaron M; Dolis, Chad M

2009-05-01

The current study developed and tested a model of the interplay among goal difficulty, goal progress, and expectancy over time in influencing resource allocation toward competing demands. The results provided broad support for the theoretical model. As predicted, dual-goal expectancy-the perceived likelihood of meeting both goals in competition-played a central role, moderating the relationship between relative goal progress and resource allocation. Dual-goal difficulty was also found to exert an important influence on multiple-goal self-regulation. Although it did not influence total productivity across both tasks combined, it did combine with other model components to influence the relative emphasis of one task over another. These results suggest that the cumulative demands placed by multiple difficult goals may exceed individuals' perceived capabilities and may lead to partial or total abandonment of 1 goal to ensure attainment of the other. The model helps shed light on some of the conflicting theoretical propositions and empirical results obtained in prior work. Implications for theory and research regarding multiple-goal self-regulation are discussed. (c) 2009 APA, all rights reserved.

Vehicle dynamics control of four in-wheel motor drive electric vehicle using gain scheduling based on tyre cornering stiffness estimation

NASA Astrophysics Data System (ADS)

Xiong, Lu; Yu, Zhuoping; Wang, Yang; Yang, Chen; Meng, Yufeng

2012-06-01

This paper focuses on the vehicle dynamic control system for a four in-wheel motor drive electric vehicle, aiming at improving vehicle stability under critical driving conditions. The vehicle dynamics controller is composed of three modules, i.e. motion following control, control allocation and vehicle state estimation. Considering the strong nonlinearity of the tyres under critical driving conditions, the yaw motion of the vehicle is regulated by gain scheduling control based on the linear quadratic regulator theory. The feed-forward and feedback gains of the controller are updated in real-time by online estimation of the tyre cornering stiffness, so as to ensure the control robustness against environmental disturbances as well as parameter uncertainty. The control allocation module allocates the calculated generalised force requirements to each in-wheel motor based on quadratic programming theory while taking the tyre longitudinal/lateral force coupling characteristic into consideration. Simulations under a variety of driving conditions are carried out to verify the control algorithm. Simulation results indicate that the proposed vehicle stability controller can effectively stabilise the vehicle motion under critical driving conditions.

New insight into sludge reduction induced by different substrate allocation strategy between oxygen and nitrate/nitrite as terminal electron acceptor.

PubMed

Yan, Peng; Guo, Jin-Song; Xu, Yu-Feng; Chen, You-Peng; Wang, Jing; Liu, Zhi-Ping; Fang, Fang

2018-06-01

Sludge reduction based on regulating substrate allocation between catabolism and anabolism as a strategy is proposed to reduce energy and chemicals consumption during wastewater treatment. The results indicated that a sludge reduction of 14.8% and excellent nutrient removal were simultaneously achieved in the low dissolved oxygen (LDO) activated sludge system with a hydraulic retention time of 24 h at 25 °C. Denitrifiers comprised nearly 1/4 of all microorganisms in the system. These denitrifiers converted NO x - to N 2 obtaining a lower biomass yield. The oxidoreductase activity proteins in the LDO sample was more than twice that of the normal DO sample, indicating that catabolism was stimulated by NO x - when replacing O 2 as electron acceptor. Less substrate was used for cell synthesis in the LDO system. Stable sludge reduction without extra energy and chemicals inputs was achieved by regulating the substrate allocation by inducing the bacteria to utilize NO x - instead of O 2 . Copyright © 2018 Elsevier Ltd. All rights reserved.

15 CFR 700.14 - Preferential scheduling.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.14 Preferential scheduling. (a) A...

Fixed allocation patterns, rather than plasticity, benefit recruitment and recovery from drought in seedlings of a desert shrub

PubMed Central

Zhang, Yao; Li, Yan; Xie, Jiang-Bo

2016-01-01

The response of plants to drought is controlled by the interaction between physiological regulation and morphological adjustment. Although recent studies have highlighted the long-term morphological acclimatization of plants to drought, there is still debate on how plant biomass allocation patterns respond to drought. In this study, we performed a greenhouse experiment with first-year seedlings of a desert shrub in control, drought and re-water treatments, to examine their physiological and morphological traits during drought and subsequent recovery. We found that (i) biomass was preferentially allocated to roots along a fixed allometric trajectory throughout the first year of development, irrespective of the variation in water availability; and (ii) this fixed biomass allocation pattern benefited the post-drought recovery. These results suggest that, in a stressful environment, natural selection has favoured a fixed biomass allocation pattern rather than plastic responses to environmental variation. The fixed ‘preferential allocation to root’ biomass suggests that roots may play a critical role in determining the fate of this desert shrub during prolonged drought. As the major organ for resource acquisition and storage, how the root system functions during drought requires further investigation. PMID:27073036

Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development.

PubMed

Cerqueira, Débora M; Bodnar, Andrew J; Phua, Yu Leng; Freer, Rachel; Hemker, Shelby L; Walensky, Loren D; Hukriede, Neil A; Ho, Jacqueline

2017-08-01

Low nephron endowment at birth has been associated with an increased risk for developing hypertension and chronic kidney disease. We demonstrated in an earlier study that conditional deletion of the microRNA (miRNA)-processing enzyme Dicer from nephron progenitors results in premature depletion of the progenitors and increased expression of the proapoptotic protein Bim (also known as Bcl-2L11). In this study, we generated a compound mouse model with conditional deletion of both Dicer and Bim , to determine the biologic significance of increased Bim expression in Dicer -deficient nephron progenitors. The loss of Bim partially restored the number of nephron progenitors and improved nephron formation. The number of progenitors undergoing apoptosis was significantly reduced in kidneys with loss of a single allele, or both alleles, of Bim compared to mutant kidneys. Furthermore, 2 miRNAs expressed in nephron progenitors ( miR-17 and miR-106b) regulated Bim levels in vitro and in vivo Together, these data suggest that miRNA-mediated regulation of Bim controls nephron progenitor survival during nephrogenesis, as one potential means of regulating nephron endowment.-Cerqueira, D. M., Bodnar, A. J., Phua, Y. L., Freer, R., Hemker, S. L., Walensky, L. D., Hukriede, N. A., Ho, J. Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development. © FASEB.

Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis.

PubMed

Tremante, Elisa; Santarelli, Lory; Lo Monaco, Elisa; Sampaoli, Camilla; Ingegnere, Tiziano; Guerrieri, Roberto; Tomasetti, Marco; Giacomini, Patrizio

2015-10-13

Alpha-tocopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations. Similar effects were observed herein in melanoma cells, although αTOS behaved as an antagonist. Interestingly, suboptimal cell death-inducing concentrations (1.5 μM αTOS/20 μM AA/0.2 μM VK3) effectively up-regulated activating Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of the NKG2D receptor), and/or the ligands of at least one of the natural cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1, ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression. Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with the corresponding activating receptors. These results provide the first evidence for concerted induction of cell death by cell-autonomous and extrinsic (immune) mechanisms. Alarming the immune system much below the cell damage threshold may have evolved as a sensitive readout of neoplastic transformation and oxidative stress. Cocktails of vitamin analogues at slightly supra-physiological dosages may find application as mild complements of melanoma treatment, and in chemoprevention.

Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis

PubMed Central

Tremante, Elisa; Santarelli, Lory; Monaco, Elisa Lo; Sampaoli, Camilla; Ingegnere, Tiziano; Guerrieri, Roberto

2015-01-01

Alpha-tochopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations. Similar effects were observed herein in melanoma cells, although αTOS behaved as an antagonist. Interestingly, suboptimal cell death-inducing concentrations (1.5 μM αTOS/20 μM AA/0.2 μM VK3) effectively up-regulated activating Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of the NKG2D receptor), and/or the ligands of at least one of the natural cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1, ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression. Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with the corresponding activating receptors. These results provide the first evidence for concerted induction of cell death by cell-autonomous and extrinsic (immune) mechanisms. Alarming the immune system much below the cell damage threshold may have evolved as a sensitive readout of neoplastic transformation and oxidative stress. Cocktails of vitamin analogues at slightly supra-physiological dosages may find application as mild complements of melanoma treatment, and in chemoprevention. PMID:26427039

Out of Lust or Jealousy: The Effects of Mate-Related Motives on Study-Time Allocation to Faces Varying in Attractiveness.

PubMed

Li, Weijian; Zhang, Yuchi; Li, Fengying; Li, Xinyu; Li, Ping; Jia, Xiaoyu; Chen, Haide; Ji, Haojie

2015-01-01

Although a growing number of empirical studies have revealed that activating mate-related motives might exert a specific set of consequences for human cognition and behaviors, such as attention and memory, little is known about whether mate-related motives affect self-regulated learning. The present study examined the effects of mate-related motives (mate-search and mate-guarding) on study-time allocation to faces varying in attractiveness. In two experiments, participants in mate-related priming conditions (Experiment 1: mate-search; Experiment 2: mate-guarding) or control conditions studied 20 female faces (10 highly attractive, 10 less attractive) during a self-paced study task, and then were given a yes/no face recognition task. The finding of Experiment 1 showed that activating a mate-search motive led the male participants to allocate more time to highly attractive female faces (i.e., perceived potential mates) than to less attractive ones. In Experiment 2, female participants in the mate-guarding priming condition spent more time studying highly attractive female faces (i.e., perceived potential rivals) than less attractive ones, compared to participants in the control condition. These findings illustrate the highly specific consequences of mate-related motives on study-time allocation, and highlight the value of exploring human cognition and motivation within evolutionary and self-regulated learning frameworks.

Out of Lust or Jealousy: The Effects of Mate-Related Motives on Study-Time Allocation to Faces Varying in Attractiveness

PubMed Central

Li, Fengying; Li, Xinyu; Li, Ping; Jia, Xiaoyu; Chen, Haide; Ji, Haojie

2015-01-01

Although a growing number of empirical studies have revealed that activating mate-related motives might exert a specific set of consequences for human cognition and behaviors, such as attention and memory, little is known about whether mate-related motives affect self-regulated learning. The present study examined the effects of mate-related motives (mate-search and mate-guarding) on study-time allocation to faces varying in attractiveness. In two experiments, participants in mate-related priming conditions (Experiment 1: mate-search; Experiment 2: mate-guarding) or control conditions studied 20 female faces (10 highly attractive, 10 less attractive) during a self-paced study task, and then were given a yes/no face recognition task. The finding of Experiment 1 showed that activating a mate-search motive led the male participants to allocate more time to highly attractive female faces (i.e., perceived potential mates) than to less attractive ones. In Experiment 2, female participants in the mate-guarding priming condition spent more time studying highly attractive female faces (i.e., perceived potential rivals) than less attractive ones, compared to participants in the control condition. These findings illustrate the highly specific consequences of mate-related motives on study-time allocation, and highlight the value of exploring human cognition and motivation within evolutionary and self-regulated learning frameworks. PMID:26121131

CREB regulates memory allocation in the insular cortex

PubMed Central

Sano, Yoshitake; Shobe, Justin L.; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J.; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J.

2016-01-01

Summary The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory [1, 2]. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cAMP response element binding protein (CREB) are more likely to be recruited into encoding and storing fear memory [3–6]. To determine whether specific mechanisms also regulate memory allocation in other brain regions, and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (CS) with the experience of malaise (such as that induced by LiCl; US). The insular cortex is required for CTA memory formation and retrieval [7–12]. CTA learning activates a subpopulation of neurons in this structure [13–15], and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation [16, 17]. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc Fluorescence In Situ Hybridization (FISH) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory. PMID:25454591

Anchoring of Heterochromatin to the Nuclear Lamina Reinforces Dosage Compensation-Mediated Gene Repression.

PubMed

Snyder, Martha J; Lau, Alyssa C; Brouhard, Elizabeth A; Davis, Michael B; Jiang, Jianhao; Sifuentes, Margarita H; Csankovszki, Györgyi

2016-09-01

Higher order chromosome structure and nuclear architecture can have profound effects on gene regulation. We analyzed how compartmentalizing the genome by tethering heterochromatic regions to the nuclear lamina affects dosage compensation in the nematode C. elegans. In this organism, the dosage compensation complex (DCC) binds both X chromosomes of hermaphrodites to repress transcription two-fold, thus balancing gene expression between XX hermaphrodites and XO males. X chromosome structure is disrupted by mutations in DCC subunits. Using X chromosome paint fluorescence microscopy, we found that X chromosome structure and subnuclear localization are also disrupted when the mechanisms that anchor heterochromatin to the nuclear lamina are defective. Strikingly, the heterochromatic left end of the X chromosome is less affected than the gene-rich middle region, which lacks heterochromatic anchors. These changes in X chromosome structure and subnuclear localization are accompanied by small, but significant levels of derepression of X-linked genes as measured by RNA-seq, without any observable defects in DCC localization and DCC-mediated changes in histone modifications. We propose a model in which heterochromatic tethers on the left arm of the X cooperate with the DCC to compact and peripherally relocate the X chromosomes, contributing to gene repression.

Anchoring of Heterochromatin to the Nuclear Lamina Reinforces Dosage Compensation-Mediated Gene Repression

PubMed Central

Brouhard, Elizabeth A.; Jiang, Jianhao; Sifuentes, Margarita H.

2016-01-01

Higher order chromosome structure and nuclear architecture can have profound effects on gene regulation. We analyzed how compartmentalizing the genome by tethering heterochromatic regions to the nuclear lamina affects dosage compensation in the nematode C. elegans. In this organism, the dosage compensation complex (DCC) binds both X chromosomes of hermaphrodites to repress transcription two-fold, thus balancing gene expression between XX hermaphrodites and XO males. X chromosome structure is disrupted by mutations in DCC subunits. Using X chromosome paint fluorescence microscopy, we found that X chromosome structure and subnuclear localization are also disrupted when the mechanisms that anchor heterochromatin to the nuclear lamina are defective. Strikingly, the heterochromatic left end of the X chromosome is less affected than the gene-rich middle region, which lacks heterochromatic anchors. These changes in X chromosome structure and subnuclear localization are accompanied by small, but significant levels of derepression of X-linked genes as measured by RNA-seq, without any observable defects in DCC localization and DCC-mediated changes in histone modifications. We propose a model in which heterochromatic tethers on the left arm of the X cooperate with the DCC to compact and peripherally relocate the X chromosomes, contributing to gene repression. PMID:27690361

Regulation of X-chromosome dosage compensation in human: mechanisms and model systems.

PubMed

Sahakyan, Anna; Plath, Kathrin; Rougeulle, Claire

2017-11-05

The human blastocyst forms 5 days after one of the smallest human cells (the sperm) fertilizes one of the largest human cells (the egg). Depending on the sex-chromosome contribution from the sperm, the resulting embryo will either be female, with two X chromosomes (XX), or male, with an X and a Y chromosome (XY). In early development, one of the major differences between XX female and XY male embryos is the conserved process of X-chromosome inactivation (XCI), which compensates gene expression of the two female X chromosomes to match the dosage of the single X chromosome of males. Most of our understanding of the pre-XCI state and XCI establishment is based on mouse studies, but recent evidence from human pre-implantation embryo research suggests that many of the molecular steps defined in the mouse are not conserved in human. Here, we will discuss recent advances in understanding the control of X-chromosome dosage compensation in early human embryonic development and compare it to that of the mouse.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'. © 2017 The Author(s).

48 CFR 9905.502 - Cost accounting standard-consistency in allocating costs incurred for the same purpose by...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Cost accounting standard... 9905.502 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST...

41 CFR 102-74.300 - How must space available for employee parking be allocated among occupant agencies?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 74-FACILITY MANAGEMENT Facility Management Parking Facilities § 102-74... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false How must space available...

Circadian Modulation of Short-Term Memory in "Drosophila"

ERIC Educational Resources Information Center

Lyons, Lisa C.; Roman, Gregg

2009-01-01

Endogenous biological clocks are widespread regulators of behavior and physiology, allowing for a more efficient allocation of efforts and resources over the course of a day. The extent that different processes are regulated by circadian oscillators, however, is not fully understood. We investigated the role of the circadian clock on short-term…

48 CFR 9904.402 - Cost accounting standard-consistency in allocating costs incurred for the same purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402 Cost... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Cost accounting standard...

77 FR 6492 - Fisheries of the Exclusive Economic Zone Off Alaska; Community Development Quota Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-08

... CDQ allocation process, the transfer of groundfish CDQ and halibut prohibited species quota, and the.... 679.2, Removing all regulations in Sec. 679.30 (except paragraph (e)(1) related to quota transfers... PSQ catch limits. However, it will amend regulations to allow the transfer of halibut PSQ either...

Oversight on National Direct Student Loan Program Regulations. Hearing Before the Subcommittee on Postsecondary Education of the Committee on Education and Labor. House of Representatives, Ninety-Seventh Congress, Second Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

Hearings on the Department of Education's final regulation governing the National Direct Student Loan (NDSL) Program are presented. The final regulation makes three changes: calculation of the federal capital contribution, which is the amount of new federal dollars allocated to institutions each year; the eligibility of institutions to receive…

Toward a mechanistic modeling of nitrogen limitation on vegetation dynamics.

PubMed

Xu, Chonggang; Fisher, Rosie; Wullschleger, Stan D; Wilson, Cathy J; Cai, Michael; McDowell, Nate G

2012-01-01

Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO(2) concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO(2) concentration, temperature, and radiation when evaluated against published data of V(c,max) (maximum carboxylation rate) and J(max) (maximum electron transport rate). A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO(2) concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions and the vegetation feedbacks to climate in Earth system models.

Toward a Mechanistic Modeling of Nitrogen Limitation on Vegetation Dynamics

PubMed Central

Xu, Chonggang; Fisher, Rosie; Wullschleger, Stan D.; Wilson, Cathy J.; Cai, Michael; McDowell, Nate G.

2012-01-01

Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO2 concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO2 concentration, temperature, and radiation when evaluated against published data of Vc,max (maximum carboxylation rate) and Jmax (maximum electron transport rate). A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO2 concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions and the vegetation feedbacks to climate in Earth system models. PMID:22649564

50 CFR 679.30 - General CDQ regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... visual representation of the qualified applicant's entire organizational structure, including all... narrative description of how the CDQ group intends to harvest and process its CDQ allocations, including a...

Regulating unfolded protein response activator HAC1p for production of thermostable raw-starch hydrolyzing α-amylase in Pichia pastoris.

PubMed

Huang, Mengmeng; Gao, Yanyun; Zhou, Xiangshan; Zhang, Yuanxing; Cai, Menghao

2017-03-01

Unfolded protein response (UPR) usually happens when expressing heterologous proteins in high level, which may help cells to facilitate protein processing. Here, we evaluated the effects of the UPR activator HAC1p on a raw-starch hydrolyzing α-amylase (Gs4j-amyA), so as to improve heterologous production of the enzyme in Pichia pastoris. The gene (amyA) encoding Gs4j-amyA was first codon-optimized and expressed in P. pastoris under the control of the AOX1 promoter. A high gene dosage (12 copies) of amyA facilitated amylase expression which produced an enzyme activity of 305 U/ml. A spliced HAC1 encoding an UPR activator HAC1p was then co-expressed and the dosage effects of HAC1 on amylase expression was investigated. Six copies of HAC1 driven by AOX1 promoter produced a high amylase activity of 2200 U/ml, further increasing by 621%. However, excessive gene dosages driven by the same promoter led to a titration effect of its transcription factors and decreased the amount of amyA transcripts. Thus, constitutive expression of HAC1 by GAP promotor was further involved and Gs4j-amyA activity reached 3700 U/ml finally, which was further increased by 68.2%. Moreover, Gs4j-amyA was glycosylated in P. pastoris which generated higher enzyme activity than that in E. coli. Generally, regulating HAC1p expression by different strategies enhanced amylase production by 11.1 folds, indicating a reference for expression of other proteins in P. pastoris.

The phenotype of mes-2, mes-3, mes-4 and mes-6, maternal-effect genes required for survival of the germline in Caenorhabditis elegans, is sensitive to chromosome dosage.

PubMed Central

Garvin, C; Holdeman, R; Strome, S

1998-01-01

Mutations in mes-2, mes-3, mes-4, and mes-6 result in maternal-effect sterility: hermaphrodite offspring of mes/mes mothers are sterile because of underproliferation and death of the germ cells, as well as an absence of gametes. Mutant germ cells do not undergo programmed cell death, but instead undergo a necrotic-type death, and their general poor health apparently prevents surviving germ cells from forming gametes. Male offspring of mes mothers display a significantly less severe germline phenotype than their hermaphrodite siblings, and males are often fertile. This differential response of hermaphrodite and male offspring to the absence of mes+ product is a result of their different X chromosome compositions; regardless of their sexual phenotype, XX worms display a more severe germline phenotype than XO worms, and XXX worms display the most severe phenotype. The sensitivity of the mutant phenotype to chromosome dosage, along with the similarity of two MES proteins to chromatin-associated regulators of gene expression in Drosophila, suggest that the essential role of the mes genes is in control of gene expression in the germline. An additional, nonessential role of the mes genes in the soma is suggested by the surprising finding that mutations in the mes genes, like mutations in dosage compensation genes, feminize animals whose male sexual identity is somewhat ambiguous. We hypothesize that the mes genes encode maternally supplied regulators of chromatin structure and gene expression in the germline and perhaps in somatic cells of the early embryo, and that at least some of their targets are on the X chromosomes. PMID:9475730

X chromosome regulation: diverse patterns in development, tissues and disease

PubMed Central

Deng, Xinxian; Berletch, Joel B.; Nguyen, Di K.; Disteche, Christine M.

2014-01-01

Genes on the mammalian X chromosome are present in one copy in males and two copies in females. The complex mechanisms that regulate the X chromosome lead to evolutionary and physiological variability in gene expression between species, the sexes, individuals, developmental stages, tissues and cell types. In early development, delayed and incomplete X chromosome inactivation (XCI) in some species causes variability in gene expression. Additional diversity stems from escape from XCI and from mosaicism or XCI skewing in females. This causes sex-specific differences that manifest as differential gene expression and associated phenotypes. Furthermore, the complexity and diversity of X dosage regulation affect the severity of diseases caused by X-linked mutations. PMID:24733023

Plants in a crowded stand regulate their height growth so as to maintain similar heights to neighbours even when they have potential advantages in height growth.

PubMed

Nagashima, Hisae; Hikosaka, Kouki

2011-07-01

Although being tall is advantageous in light competition, plant height growth is often similar among dominant plants in crowded stands (height convergence). Previous theoretical studies have suggested that plants should not overtop neighbours because greater allocation to supporting tissues is necessary in taller plants, which in turn lowers leaf mass fraction and thus carbon gain. However, this model assumes that a competitor has the same potential of height growth as their neighbours, which does not necessarily account for the fact that height convergence occurs even among individuals with various biomass. Stands of individually potted plants of Chenopodium album were established, where target plants were lifted to overtop neighbours or lowered to be overtopped. Lifted plants were expected to keep overtopping because they intercept more light without increased allocation to stems, or to regulate their height to similar levels of neighbours, saving biomass allocation to the supporting organ. Lowered plants were expected to be suppressed due to the low light availability or to increase height growth so as to have similar height to the neighbours. Lifted plants reduced height growth in spite of the fact that they received higher irradiance than others. Lowered plants, on the other hand, increased the rate of stem elongation despite the reduced irradiance. Consequently, lifted and lowered plants converged to the same height. In contrast to the expectation, lifted plants did not increase allocation to leaf mass despite the decreased stem length. Rather, they allocated more biomass to roots, which might contribute to improvement of mechanical stability or water status. It is suggested that decreased leaf mass fraction is not the sole cost of overtopping neighbours. Wind blowing, which may enhance transpiration and drag force, might constrain growth of overtopping plants. The results show that plants in crowded stands regulate their height growth to maintain similar height to neighbours even when they have potential advantages in height growth. This might contribute to avoidance of stresses caused by wind blowing.

The Male-Specific Lethal-One (Msl-1) Gene of Drosophila Melanogaster Encodes a Novel Protein That Associates with the X Chromosome in Males

PubMed Central

Palmer, M. J.; Mergner, V. A.; Richman, R.; Manning, J. E.; Kuroda, M. I.; Lucchesi, J. C.

1993-01-01

male-specific lethal-one (msl-1) is one of four genes that are required for dosage compensation in Drosophila males. To determine the molecular basis of msl-1 regulation of dosage compensation, we have cloned the gene and characterized its products. The predicted msl-1 protein (MSL-1) has no significant similarity to proteins in the current data bases but contains an acidic N terminus characteristic of proteins involved in transcription and chromatin modeling. We present evidence that the msl-1 protein is associated with hundreds of sites along the length of the X chromosome in male, but not in female, nuclei. Our findings support the hypothesis that msl-1 plays a direct role in increasing the level of X-linked gene transcription in male nuclei. PMID:8325488

Regimes for the ocean, outer space, and weather

NASA Technical Reports Server (NTRS)

Brown, S.; Cornell, N. W.; Fabian, L. L.; Weiss, E. B.

1977-01-01

The allocation of resources among users of the oceans, outer space and the weather is discussed. Attention is given to the international management of maritime navigation, the control of fisheries, offshore oil and gas exploitation, mineral exploitation in the deep seabed (especially the mining of manganese nodules), and the regulation of oceanographic studies. The management of outer space is considered, with special reference to remote sensing by satellites, television broadcasting, the technical requirements of maritime satellites, and problems associated with satellite frequency and orbit allocation. Rainmaking and typhoon modification, as well as the distribution of weather modification capabilities in the world, are also mentioned. The United Nations, international agencies and tribunals, and multi- or bilateral agreements are some of the implements suggested for use in the regulation of the oceans, outer space and the weather.

Allocation of authority in European health policy.

PubMed

Adolph, Christopher; Greer, Scott L; Massard da Fonseca, Elize

2012-11-01

Although many study the effects of different allocations of health policy authority, few ask why countries assign responsibility over different policies as they do. We test two broad theories: fiscal federalism, which predicts rational governments will concentrate information-intensive operations at lower levels, and redistributive and regulatory functions at higher levels; and "politicized federalism", which suggests a combination of systematic and historically idiosyncratic political variables interfere with efficient allocation of authority. Drawing on the WHO Health in Transition country profiles, we present new data on the allocation of responsibility for key health care policy tasks (implementation, provision, finance, regulation, and framework legislation) and policy areas (primary, secondary and tertiary care, public health and pharmaceuticals) in the 27 EU member states and Switzerland. We use a Bayesian multinomial mixed logit model to analyze how different countries arrive at different allocations of authority over each task and area of health policy, and find the allocation of powers broadly follows fiscal federalism. Responsibility for pharmaceuticals, framework legislation, and most finance lodges at the highest levels of government, acute and primary care in the regions, and provision at the local and regional levels. Where allocation does not follow fiscal federalism, it appears to reflect ethnic divisions, the population of states and regions, the presence of mountainous terrain, and the timing of region creation. Copyright © 2012 Elsevier Ltd. All rights reserved.

A randomized controlled trial comparing periodic mask CPAP with physiotherapy after abdominal surgery.

PubMed

Denehy, L; Carroll, S; Ntoumenopoulos, G; Jenkins, S

2001-01-01

Physiotherapists use a variety of techniques aimed at improving lung volumes and secretion clearance in patients after surgery. Periodic continuous positive airway pressure (PCPAP) is used to treat patients following elective upper abdominal surgery. However, the optimal method of application has not been identified, more specifically, the dosage of application of PCPAP. The present randomized controlled trial compared the effects of two dosages of PCPAP application and 'traditional' physiotherapy upon functional residual capacity (FRC), vital capacity (VC), oxyhaemoglobin saturation (SpO2), incidence of post-operative pulmonary complications and length of stay with a control group receiving 'traditional' physiotherapy only. Fifty-seven subjects were randomly allocated to one of three groups. All groups received 'traditional' physiotherapy twice daily for a minimum of three post-operative days. In addition, two groups received PCPAP for 15 or 30 minutes, four times per day, for three days. Fifty subjects (39 male; 11 female) completed the study. There were no significant differences in any variables between the three groups. The overall incidence of post-operative pulmonary complications was 22% in the control group, 11% and 6% in the PCPAP 15-minute and PCPAP 30-minute groups, respectively. Length of hospital stay was not significantly different between the groups but for subjects who developed post-operative pulmonary complications, the length of stay was significantly greater (Z = -2.32; p = 0.021). The addition of PCPAP to a traditional physiotherapy post-operative treatment regimen after upper abdominal surgery did not significantly affect physiological or clinical outcomes.

40 CFR 78.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... disapproval of the transfer of allowances for the replacement of thermal energy; (iii) The approval or... and Renewal Energy Reserve; (iii) The decision on the allocation of allowances under regulations...

40 CFR 78.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... disapproval of the transfer of allowances for the replacement of thermal energy; (iii) The approval or... and Renewal Energy Reserve; (iii) The decision on the allocation of allowances under regulations...

40 CFR 78.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... disapproval of the transfer of allowances for the replacement of thermal energy; (iii) The approval or... and Renewal Energy Reserve; (iii) The decision on the allocation of allowances under regulations...

76 FR 33615 - Energy Priorities and Allocations System Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

... 44 U.S.C. 1510. #0; #0;The Code of Federal Regulations is sold by the Superintendent of Documents. #0... domestic energy supplies pursuant to its authority under Section 101(c) of the Defense Production Act (50 U... order to promote the national defense pursuant to its DPA authorities other than section 101(c). The...

Design of a regulated system of compensation for living kidney donors.

PubMed

Matas, Arthur J

2008-01-01

The pros and cons of a regulated system of financial incentives for living donors are being actively debated. To date, a detailed proposal on how such a system could work has not been developed. Herein, the specifics of a potential model, using the infrastructure already in place for deceased donor evaluation and allocation, are outlined.

Forest control and regulation ... a comparison of traditional methods and alternatives

Treesearch

LeRoy C. Hennes; Michael J. Irving; Daniel I. Navon

1971-01-01

Two traditional techniques of forest control and regulation-formulas and area-volume check-are compared to linear programing, as used in a new computerized planning system called Timber Resource Allocation Method ( Timber RAM). Inventory data from a National Forest in California illustrate how each technique is used. The traditional methods are simpler to apply and...

77 FR 57544 - Native American Housing Assistance and Self-Determination Reauthorization Act of 1996: Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-18

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT 24 CFR Part 1000 [Docket No. FR-5650-N-02] Native...) program. The regulations governing the IHBG formula allocation are codified in subpart D of part 1000 of... negotiated rulemaking required by Section 106 of NAHASDA and program regulations found at 24 CFR 1000.306...

48 CFR 1631.203-71 - Business unit General and Administrative (G&A) expenses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Business unit General and Administrative (G&A) expenses. G&A expenses shall be allocated to final cost... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Business unit General and Administrative (G&A) expenses. 1631.203-71 Section 1631.203-71 Federal Acquisition Regulations System OFFICE OF...

The QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions

USDA-ARS?s Scientific Manuscript database

The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua Quine Starch, At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates...

15 CFR 700.17 - Use of rated orders.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.17 Use of rated orders. (a) A person...

20 CFR 658.602 - ETA national office responsibility.

Code of Federal Regulations, 2013 CFR

2013-04-01

... regulations and programs; (d) Have report validation surveys conducted in support of resource allocations; (e..., the National MSFW Monitor Advocate shall include both a quantitative and qualitative analysis of his...

20 CFR 658.602 - ETA national office responsibility.

Code of Federal Regulations, 2012 CFR

2012-04-01

... regulations and programs; (d) Have report validation surveys conducted in support of resource allocations; (e..., the National MSFW Monitor Advocate shall include both a quantitative and qualitative analysis of his...

20 CFR 658.602 - ETA national office responsibility.

Code of Federal Regulations, 2010 CFR

2010-04-01

... regulations and programs; (d) Have report validation surveys conducted in support of resource allocations; (e..., the National MSFW Monitor Advocate shall include both a quantitative and qualitative analysis of his...

20 CFR 658.602 - ETA national office responsibility.

Code of Federal Regulations, 2011 CFR

2011-04-01

... regulations and programs; (d) Have report validation surveys conducted in support of resource allocations; (e..., the National MSFW Monitor Advocate shall include both a quantitative and qualitative analysis of his...

20 CFR 658.602 - ETA national office responsibility.

Code of Federal Regulations, 2014 CFR

2014-04-01

... regulations and programs; (d) Have report validation surveys conducted in support of resource allocations; (e..., the National MSFW Monitor Advocate shall include both a quantitative and qualitative analysis of his...

Linking state regulation, brain laterality, and self-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in adults.

PubMed

Mohamed, Saleh M H; Börger, Norbert A; Geuze, Reint H; van der Meere, Jaap J

2016-10-01

Many clinical studies have shown that performance of subjects with attention-deficit/hyperactivity disorder (ADHD) is impaired when stimuli are presented at a slow rate compared to a medium or fast rate. According to the cognitive-energetic model, this finding may reflect difficulty in allocating sufficient effort to regulate the motor activation state. Other studies have shown that the left hemisphere is relatively responsible for keeping humans motivated, allocating sufficient effort to complete their tasks. This leads to a prediction that poor effort allocation might be associated with an affected left-hemisphere functioning in ADHD. So far, this prediction has not been directly tested, which is the aim of the present study. Seventy-seven adults with various scores on the Conners' Adult ADHD Rating Scale performed a lateralized lexical decision task in three conditions with stimuli presented in a fast, a medium, and a slow rate. The left-hemisphere functioning was measured in terms of visual field advantage (better performance for the right than for the left visual field). All subjects showed an increased right visual field advantage for word processing in the slow presentation rate of stimuli compared to the fast and the medium rate. Higher ADHD scores were related to a reduced right visual field advantage in the slow rate only. The present findings suggest that ADHD symptomatology is associated with less involvement of the left hemisphere when extra effort allocation is needed to optimize the low motor activation state.

Changes in cytokinins are sufficient to alter developmental patterns of defense metabolites in Nicotiana attenuata.

PubMed

Brütting, Christoph; Schäfer, Martin; Vanková, Radomíra; Gase, Klaus; Baldwin, Ian T; Meldau, Stefan

2017-01-01

Plant defense metabolites are well known to be regulated developmentally. The optimal defense (OD) theory posits that a tssue's fitness values and probability of attack should determine defense metabolite allocations. Young leaves are expected to provide a larger fitness value to the plant, and therefore their defense allocations should be higher when compared with older leaves. The mechanisms that coordinate development with defense remain unknown and frequently confound tests of the OD theory predictions. Here we demonstrate that cytokinins (CKs) modulate ontogeny-dependent defenses in Nicotiana attenuata. We found that leaf CK levels highly correlate with inducible defense expressions with high levels in young and low levels in older leaves. We genetically manipulated the developmental patterns of two different CK classes by using senescence- and chemically inducible expression of CK biosynthesis genes. Genetically modifying the levels of different CKs in leaves was sufficient to alter ontogenic patterns of defense metabolites. We conclude that the developmental regulation of growth hormones that include CKs plays central roles in connecting development with defense and therefore in establishing optimal patterns of defense allocation in plants. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Veterans with post-traumatic stress disorder exhibit altered emotional processing and attentional control during an emotional Stroop task.

PubMed

Khanna, M M; Badura-Brack, A S; McDermott, T J; Embury, C M; Wiesman, A I; Shepherd, A; Ryan, T J; Heinrichs-Graham, E; Wilson, T W

2017-08-01

Post-traumatic stress disorder (PTSD) is often associated with attention allocation and emotional regulation difficulties, but the brain dynamics underlying these deficits are unknown. The emotional Stroop task (EST) is an ideal means to monitor these difficulties, because participants are asked to attend to non-emotional aspects of the stimuli. In this study, we used magnetoencephalography (MEG) and the EST to monitor attention allocation and emotional regulation during the processing of emotionally charged stimuli in combat veterans with and without PTSD. A total of 31 veterans with PTSD and 20 without PTSD performed the EST during MEG. Three categories of stimuli were used, including combat-related, generally threatening and neutral words. MEG data were imaged in the time-frequency domain and the network dynamics were probed for differences in processing threatening and non-threatening words. Behaviorally, veterans with PTSD were significantly slower in responding to combat-related relative to neutral and generally threatening words. Veterans without PTSD exhibited no significant differences in responding to the three different word types. Neurophysiologically, we found a significant three-way interaction between group, word type and time period across multiple brain regions. Follow-up testing indicated stronger theta-frequency (4-8 Hz) responses in the right ventral prefrontal (0.4-0.8 s) and superior temporal cortices (0.6-0.8 s) of veterans without PTSD compared with those with PTSD during the processing of combat-related words. Our data indicated that veterans with PTSD exhibited deficits in attention allocation and emotional regulation when processing trauma cues, while those without PTSD were able to regulate emotion by directing attention away from threat.

26 CFR 1.148-6A - General allocation and accounting rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable to Certain Bonds Sold Prior to... (3) There is an independent verification (e.g., from an independent certified public accountant) that...

15 CFR 700.20 - Use of priority ratings.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities for Energy Programs § 700.20 Use of... maintenance of energy facilities. ...

15 CFR 700.16 - Changes or cancellations of priority ratings and rated orders.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700...

Ising game: Nonequilibrium steady states of resource-allocation systems

NASA Astrophysics Data System (ADS)

Xin, C.; Yang, G.; Huang, J. P.

2017-04-01

Resource-allocation systems are ubiquitous in the human society. But how external fields affect the state of such systems remains poorly explored due to the lack of a suitable model. Because the behavior of spins pursuing energy minimization required by physical laws is similar to that of humans chasing payoff maximization studied in game theory, here we combine the Ising model with the market-directed resource-allocation game, yielding an Ising game. Based on the Ising game, we show theoretical, simulative and experimental evidences for a formula, which offers a clear expression of nonequilibrium steady states (NESSs). Interestingly, the formula also reveals a convertible relationship between the external field (exogenous factor) and resource ratio (endogenous factor), and a class of saturation as the external field exceeds certain limits. This work suggests that the Ising game could be a suitable model for studying external-field effects on resource-allocation systems, and it could provide guidance both for seeking more relations between NESSs and equilibrium states and for regulating human systems by choosing NESSs appropriately.

A global resource allocation strategy governs growth transition kinetics of Escherichia coli

PubMed Central

Erickson, David W; Schink, Severin J.; Patsalo, Vadim; Williamson, James R.; Gerland, Ulrich; Hwa, Terence

2018-01-01

A grand challenge of systems biology is to predict the kinetic responses of living systems to perturbations starting from the underlying molecular interactions. Changes in the nutrient environment have long been used to study regulation and adaptation phenomena in microorganisms1–3 and they remain a topic of active investigation4–11. Although much is known about the molecular interactions that govern the regulation of key metabolic processes in response to applied perturbations12–17, they are insufficiently quantified for predictive bottom-up modelling. Here we develop a top-down approach, expanding the recently established coarse-grained proteome allocation models15,18–20 from steady-state growth into the kinetic regime. Using only qualitative knowledge of the underlying regulatory processes and imposing the condition of flux balance, we derive a quantitative model of bacterial growth transitions that is independent of inaccessible kinetic parameters. The resulting flux-controlled regulation model accurately predicts the time course of gene expression and biomass accumulation in response to carbon upshifts and downshifts (for example, diauxic shifts) without adjustable parameters. As predicted by the model and validated by quantitative proteomics, cells exhibit suboptimal recovery kinetics in response to nutrient shifts owing to a rigid strategy of protein synthesis allocation, which is not directed towards alleviating specific metabolic bottlenecks. Our approach does not rely on kinetic parameters, and therefore points to a theoretical framework for describing a broad range of such kinetic processes without detailed knowledge of the underlying biochemical reactions. PMID:29072300

34 CFR 299.2 - What general administrative regulations apply to ESEA programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... programs (as defined in 34 CFR 75.1(b)), and programs under title XI of ESEA. (b) 34 CFR part 80 also..., ensure that costs are allocable to a particular cost objective. (Authority: 20 U.S.C. 1221e-3(a)(1)) ... 34 Education 1 2014-07-01 2014-07-01 false What general administrative regulations apply to ESEA...

Time to Learn, Time to Develop? Change Processes in Three Schools with Weak National Time Regulation

ERIC Educational Resources Information Center

Nyroos, Mikaela

2007-01-01

This article analyses change of time use and time allocation in three schools participating in a Swedish five-year national experiment in which State regulation of teaching time was weakened. Participating schools could freely decide how to use and distribute teaching time. The experiment was launched at a late stage in a 25-year decentralisation…

Lignin Modification Leads to Increased Nodule Numbers in Alfalfa1[C][W][OPEN

PubMed Central

Gallego-Giraldo, Lina; Bhattarai, Kishor; Pislariu, Catalina I.; Nakashima, Jin; Jikumaru, Yusuke; Kamiya, Yuji; Udvardi, Michael K.; Monteros, Maria J.; Dixon, Richard A.

2014-01-01

Reduction of lignin levels in the forage legume alfalfa (Medicago sativa) by down-regulation of the monolignol biosynthetic enzyme hydroxycinnamoyl coenzyme A:shikimate hydroxycinnamoyl transferase (HCT) results in strongly increased digestibility and processing ability of lignocellulose. However, these modifications are often also associated with dwarfing and other changes in plant growth. Given the importance of nitrogen fixation for legume growth, we evaluated the impact of constitutively targeted lignin modification on the belowground organs (roots and nodules) of alfalfa plants. HCT down-regulated alfalfa plants exhibit a striking reduction in root growth accompanied by an unexpected increase in nodule numbers when grown in the greenhouse or in the field. This phenotype is associated with increased levels of gibberellins and certain flavonoid compounds in roots. Although HCT down-regulation reduced biomass yields in both the greenhouse and field experiments, the impact on the allocation of nitrogen to shoots or roots was minimal. It is unlikely, therefore, that the altered growth phenotype of reduced-lignin alfalfa is a direct result of changes in nodulation or nitrogen fixation efficiency. Furthermore, HCT down-regulation has no measurable effect on carbon allocation to roots in either greenhouse or 3-year field trials. PMID:24406794

Novel Effect of Berberine on Thermoregulation in Mice Model Induced by Hot and Cold Environmental Stimulation

PubMed Central

Lei, Fan; Kheir, Michael M.; Wang, Xin-Pei; Chai, Yu-Shuang; Yuan, Zhi-Yi; Lu, Xi; Xing, Dong-Ming; Du, Feng; Du, Li-Jun

2013-01-01

The purpose of this study was to assess the effects of berberine (BBR) on thermoregulation in mice exposed to hot (40°C) and cold (4°C) environmental conditions. Four groups of mice were assembled with three different dosages of BBR (0.2, 0.4, and 0.8 mg/kg) and normal saline (control). In room temperature, our largest dosage of BBR (0.8 mg/kg) can reduce rectal temperatures (Tc) of normal mice. In hot conditions, BBR can antagonize the increasing core body temperature and inhibit the expression of HSP70 and TNFα in mice; conversely, in cold conditions, BBR can antagonize the decreasing core body temperature and enhance the expression of TRPM8. This study demonstrates the dual ability of BBR in maintaining thermal balance, which is of great relevance to the regulation of HSP70, TNFα and TRPM8. PMID:23335996

Characterisation of medical-waste sterilisation-plant wastewater and a preliminary study of coagulation-flocculation treatment options.

PubMed

Ozkan, O; Mihçiokur, H; Azgin, S T; Ozdemir, O

2010-01-01

Wastewater from a medical-waste sterilisation plant (MWSP) contains unique pollutants and requires on-site treatment to prevent contamination of the municipal sewage system and receiving water bodies. Therefore, to meet the prescribed discharge standards and comply with the legal regulations, pre-treatment must be applied to MWSP wastewater. In this study, the capabilities of coagulation-flocculation processes were investigated for MWSP wastewater treatment. Processes using ferric chloride, ferrous sulfate and aluminium sulfate as coagulants were characterised. During the coagulation experiments, seven different coagulant dosages and four different pH values were evaluated to determine the optimum coagulant dosage and pH value. The highest removal efficiency of chemical oxygen demand (COD) was obtained using 300 mg/L of ferric chloride at pH 10. A COD removal of about 60% as well as considerable reductions in the amounts of suspended solids, nitrogen and phosphorus were realised.

Adaptive control of bivalirudin in the cardiac intensive care unit.

PubMed

Zhao, Qi; Edrich, Thomas; Paschalidis, Ioannis Ch

2015-02-01

Bivalirudin is a direct thrombin inhibitor used in the cardiac intensive care unit when heparin is contraindicated due to heparin-induced thrombocytopenia. Since it is not a commonly used drug, clinical experience with its dosing is sparse. In earlier work [1], we developed a dynamic system model that accurately predicts the effect of bivalirudin given dosage over time and patient physiological characteristics. This paper develops adaptive dosage controllers that regulate its effect to desired levels. To that end, and in the case that bivalirudin model parameters are available, we develop a Model Reference Control law. In the case that model parameters are unknown, an indirect Model Reference Adaptive Control scheme is applied to estimate model parameters first and then adapt the controller. Alternatively, direct Model Reference Adaptive Control is applied to adapt the controller directly without estimating model parameters first. Our algorithms are validated using actual patient data from a large hospital in the Boston area.

Weakener of White (Wow), a Gene That Modifies the Expression of the White Eye Color Locus and That Suppresses Position Effect Variegation in Drosophila Melanogaster

PubMed Central

Birchler, J. A.; Bhadra, U.; Rabinow, L.; Linsk, R.; Nguyen-Huynh, A. T.

1994-01-01

A locus is described in Drosophila melanogaster that modifies the expression of the white eye color gene. This trans-acting modifier reduces the expression of the white gene in the eye, but elevates the expression in other adult tissues. Because of the eye phenotype in which the expression of white is lessened but not eliminated, the newly described locus is called the Weakener of white (Wow). Northern analysis reveals that Wow can exert an inverse or direct modifying effect depending upon the developmental stage. Two related genes, brown and scarlet, that are coordinately expressed with white, are also affected by Wow. In addition, Wow modulates the steady state RNA level of the retrotransposon, copia. When tested with a white promoter-Alcohol dehydrogenase reporter, Wow confers the modifying effect to the reporter, suggesting a requirement of the white regulatory sequences for mediating the response. In addition to being a dosage sensitive regulator of white, brown, scarlet and copia, Wow acts as a suppressor of position effect variegation. There are many dosage sensitive suppressors of position effect variegation and many dosage-sensitive modifiers of gene expression. The Wow mutations provide evidence for an overlap between the two types of modifiers. PMID:7982560

Regulation characteristics of oxide generation and formaldehyde removal by using volume DBD reactor

NASA Astrophysics Data System (ADS)

Bingyan, CHEN; Xiangxiang, GAO; Ke, CHEN; Changyu, LIU; Qinshu, LI; Wei, SU; Yongfeng, JIANG; Xiang, HE; Changping, ZHU; Juntao, FEI

2018-02-01

Discharge plasmas in air can be accompanied by ultraviolet (UV) radiation and electron impact, which can produce large numbers of reactive species such as hydroxyl radical (OH·), oxygen radical (O·), ozone (O3), and nitrogen oxides (NO x ), etc. The composition and dosage of reactive species usually play an important role in the case of volatile organic compounds (VOCs) treatment with the discharge plasmas. In this paper, we propose a volume discharge setup used to purify formaldehyde in air, which is configured by a plate-to-plate dielectric barrier discharge (DBD) channel and excited by an AC high voltage source. The results show that the relative spectral-intensity from DBD cell without formaldehyde is stronger than the case with formaldehyde. The energy efficiency ratios (EERs) of both oxides yield and formaldehyde removal can be regulated by the gas flow velocity in DBD channel, and the most desirable processing effect is the gas flow velocity within the range from 2.50 to 3.33 m s-1. Moreover, the EERs of both the generated dosages of oxides (O3 and NO2) and the amount of removed formaldehyde can also be regulated by both of the applied voltage and power density loaded on the DBD cell. Additionally, the EERs of both oxides generation and formaldehyde removal present as a function of normal distribution with increasing the applied power density, and the peak of the function is appeared in the range from 273.5 to 400.0 W l-1. This work clearly demonstrates the regulation characteristic of both the formaldehyde removal and oxides yield by using volume DBD, and it is helpful in the applications of VOCs removal by using discharge plasma.

On p53 revival using system oriented drug dosage design.

PubMed

Haseeb, Muhammad; Azam, Shumaila; Bhatti, A I; Azam, Rizwan; Ullah, Mukhtar; Fazal, Sahar

2017-02-21

We propose a new paradigm in the drug design for the revival of the p53 pathway in cancer cells. It is shown that the current strategy of using small molecule based Mdm2 inhibitors is not enough to adequately revive p53 in cancerous cells, especially when it comes to the extracting pulsating behavior of p53. This fact has come to notice when a novel method for the drug dosage design is introduced using system oriented concepts. As a test case, small molecule drug Mdm2 repressor Nutlin 3a is considered. The proposed method determines the dose of Nutlin to revive p53 pathway functionality. For this purpose, PBK dynamics of Nutlin have also been integrated with p53 pathway model. The p53 pathway is the focus of researchers for the last thirty years for its pivotal role as a frontline cancer suppressant protein due to its effect on cell cycle checkpoints and cell apoptosis in response to a DNA strand break. That is the reason for finding p53 being absent in more than 50% of tumor cancers. Various drugs have been proposed to revive p53 in cancer cells. Small molecule based drugs are at the foremost and are the subject of advanced clinical trials. The dosage design of these drugs is an important issue. We use control systems concepts to develop the drug dosage so that the cancer cells can be treated in appropriate time. We investigate by using a computational model how p53 protein responds to drug Nutlin 3a, an agent that interferes with the MDM2-mediated p53 regulation. The proposed integrated model describes in some detail the regulation network of p53 including the negative feedback loop mediated by MDM2 and the positive feedback loop mediated by Mdm2 mRNA as well as the reversible represses of MDM2 caused by Nutlin. The reported PBK dynamics of Nutlin 3a are also incorporated to see the full effect. It has been reported that p53 response to stresses in two ways. Either it has a sustained (constant) p53 response, or there are oscillations in p53 concentration. The claimed dosage strategy achieves the p53 response in the first case. However, for the induction of oscillations, it is shown through bifurcation analysis that to achieve oscillating behavior of p53 inhibition of Mdm2 is not enough, rather antirepression of the p53-Mdm2 complex is also needed which leads to the need of a new drug design paradigm. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of dietary slow-release urea on growth performance, organ development and serum biochemical parameters of mutton sheep.

PubMed

Ji, S K; Zhang, F; Sun, Y K; Deng, K D; Wang, B; Tu, Y; Zhang, N F; Jiang, C G; Wang, S Q; Diao, Q Y

2017-10-01

Eighty Dorper × thin-tailed Han cross-bred non-castrated male lambs [mean body weight (BW), 25.87 ± 1.06 kg] were randomly allocated to one of five different concentrations of slow-release urea (urea phosphate, UP). The feed consisted of an equal amount of concentrate diet and roughage; the concentrate feed was formulated to be isoenergetic and isonitrogenic and contained 0%, 1%, 2%, 4% and 8% UP (UP0.0, UP1.0, UP2.0, UP4.0 and UP8.0, respectively) as a replacement for soya bean meal. Feed intake, BW, average daily gain (ADG), feed utilisation efficiency (FUE), absolute and relative organ weights and biochemical and histopathological parameters were measured. Feed intake, BW, ADG and FUE significantly decreased in the group receiving UP8.0 (p < 0.05), but no difference was found among the other groups (p > 0.05). Quadratic equations were developed between the UP dosage in the concentrate feed and ADG or FUE (r 2  = 0.973 for ADG and r 2  = 0.761 for FUE) to determine the appropriate dosage of UP given the desire to maximise either ADG or FUE, the appropriate dosage (feed concentration) was calculated as 2.01% UP to achieve the greatest ADG or 2.13% UP to achieve the best FUE. The relative weight of the liver (% BW) in the UP2.0 groups was significantly greater than that of UP0.0 (p < 0.05), and the relative weight of the intestine in the UP8.0 was significantly greater than that of UP0.0 (p < 0.05); the relative weight of the carcass, heart, spleen, lung, kidney, rumen, reticulum, omasum and abomasum did not differ among treatments (p > 0.05). The UP8.0 treatment significantly increased serum phosphorus levels (p < 0.05) and decreased the levels of alkaline phosphatase, glucose and calcium (Ca) compared with the lower UP dosage (p < 0.05). No histopathological differences were found in either hepatic tissues or renal tissues among treatments. Dietary UP as a replacement for soya bean in concentrate feeds for mutton sheep should not exceed 4%, as higher dosing may cause malnutrition and mineral disorders. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Vigabatrin pediatric dosing information for refractory complex partial seizures: results from a population dose-response analysis.

PubMed

Nielsen, Jace C; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G; Wesche, David L

2014-12-01

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

77 FR 76380 - Partner's Distributive Share

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

...'s Distributive Share AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final regulations... partnership's allocations are substantial. However, this commenter also explained that many partnerships are... partnership. This commenter further explained that, provided the partnership's assumptions are reasonable...

48 CFR 511.603 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... symbol from the DoD Master Urgency List and may only do so when GSA is acting as the procuring agent for... follow all the provisions of the Defense Priorities and Allocations System regulation (15 CFR part 700...

15 CFR Appendix I to Part 700 - Form BIS-999-Request for Special Priorities Assistance

Code of Federal Regulations, 2010 CFR

2010-01-01

... and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Pt. 700, App. I Appendix I...

48 CFR 2527.7001 - General.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 2527.7001 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7001 General. National Science Foundation policies, procedures, and clauses governing allocation of rights to inventions made...

48 CFR 2527.7001 - General.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 2527.7001 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7001 General. National Science Foundation policies, procedures, and clauses governing allocation of rights to inventions made...

48 CFR 2527.7001 - General.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 2527.7001 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7001 General. National Science Foundation policies, procedures, and clauses governing allocation of rights to inventions made...

48 CFR 2527.7001 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 2527.7001 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7001 General. National Science Foundation policies, procedures, and clauses governing allocation of rights to inventions made...

48 CFR 2527.7001 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 2527.7001 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7001 General. National Science Foundation policies, procedures, and clauses governing allocation of rights to inventions made...

The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity

PubMed Central

Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H.; Allen, Andrew S.; Goldstein, David B.

2015-01-01

Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene’s proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS), termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene’s regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1) genes that are known to cause disease through haploinsufficiency, 2) genes curated as dosage sensitive in ClinGen’s Genome Dosage Map, 3) genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4) genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding importance, ncCADD and ncGWAVA, and find both scores are significantly predictive of human dosage sensitive genes and appear to carry information beyond conservation, as assessed by ncGERP. These results highlight that the intolerance of noncoding sequence stretches in the human genome can provide a critical complementary tool to other genome annotation approaches to help identify the parts of the human genome increasingly likely to harbor mutations that influence risk of disease. PMID:26332131

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

PubMed

Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

2016-05-24

Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

Gene dosage imbalance during DNA replication controls bacterial cell-fate decision

NASA Astrophysics Data System (ADS)

Igoshin, Oleg

Genes encoding proteins in a common regulatory network are frequently located close to one another on the chromosome to facilitate co-regulation or couple gene expression to growth rate. Contrasting with these observations, here we demonstrate a functional role for the arrangement of Bacillus subtilis sporulation network genes on opposite sides of the chromosome. We show that the arrangement of two sporulation network genes, one located close to the origin, the other close to the terminus leads to a transient gene dosage imbalance during chromosome replication. This imbalance is detected by the sporulation network to produce cell-cycle coordinated pulses of the sporulation master regulator Spo0A~P. This pulsed response allows cells to decide between sporulation and continued vegetative growth during each cell-cycle spent in starvation. Furthermore, changes in DNA replication and cell-cycle parameters with decreased growth rate in starvation conditions enable cells to indirectly detect starvation without the need for evaluating specific metabolites. The simplicity of the uncovered coordination mechanism and starvation sensing suggests that it may be widely applicable in a variety of gene regulatory and stress-response settings. This work is supported by National Science Foundation Grants MCB-1244135, EAGER-1450867, MCB-1244423, NIH NIGMS Grant R01 GM088428 and HHMI International Student Fellowship.

Disinfection of an advanced primary effluent using peracetic acid or ultraviolet radiation for its reuse in public services.

PubMed

Julio, Flores R; Hilario, Terres-Peña; Mabel, Vaca M; Raymundo, López C; Arturo, Lizardi-Ramos; Ma Neftalí, Rojas-Valencia

2015-03-01

The disinfection of a continuous flow of an effluent from an advanced primary treatment (coagulation-flocculation-sedimentation) with or without posterior filtration, using either peracetic acid (PAA) or ultraviolet (UV) radiation was studied. We aimed to obtain bacteriological quality to comply with the microbiological standard established in the Mexican regulations for treated wastewater reuse (NOM-003-SEMARNAT-1997), i.e., less than 240 MPN (most probable number) FC/100 mL. The concentrations of PAA were 10, 15, and 20 mg/L, with contact times of 10, and 15 min. Fecal coliforms (FC) inactivation ranged from 0.93 up to 6.4 log units, and in all cases it reached the limits set by the mentioned regulation. Water quality influenced the PAA disinfection effectiveness. An efficiency of 91% was achieved for the unfiltered effluent, as compared to 99% when wastewater was filtered. UV radiation was applied to wastewater flows of 21, 30 and 39 L/min, with dosages from 1 to 6 mJ/cm². This treatment did not achieve the bacteriological quality required for treated wastewater reuse, since the best inactivation of FC was 1.62 log units, for a flow of 21 L/min of filtered wastewater and a UV dosage of 5.6 mJ/cm².

XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators.

PubMed

Luz, John Gately; Hassig, Christian A; Pickle, Catherine; Godzik, Adam; Meyer, Barbara J; Wilson, Ian A

2003-04-15

In Caenorhabditis elegans, an X chromosome-counting mechanism specifies sexual fate. Specific genes termed X-signal elements, which are present on the X chromosome, act in a concerted dose-dependent fashion to regulate levels of the developmental switch gene xol-1. In turn, xol-1 levels determine sexual fate and the activation state of the dosage compensation mechanism. The crystal structure of the XOL-1 protein at 1.55 A resolution unexpectedly reveals that xol-1 encodes a GHMP kinase family member, despite sequence identity of 10% or less. Because GHMP kinases, thus far, have only been characterized as small molecule kinases involved in metabolic pathways, for example, amino acid and cholesterol synthesis, XOL-1 is the first member that controls nonmetabolic processes. Biochemical investigations demonstrated that XOL-1 does not bind ATP under standard conditions, suggesting that XOL-1 acts by a mechanism distinct from that of other GHMP kinases. In addition, we have cloned a XOL-1 ortholog from Caenorhabditis briggsae, a related nematode that diverged from C. elegans approximately 50-100 million years ago. These findings demonstrate an unanticipated role for GHMP kinase family members as mediators of sexual differentiation and dosage compensation and, possibly, other aspects of differentiation and development.

Interferon-targeted therapy in systemic lupus erythematosus: Is this an alternative to targeting B and T cells?

PubMed

Kalunian, K C

2016-09-01

Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti-interferon-α monoclonal antibody, was studied in patients who had discontinued immunosuppressants. This study failed to show efficacy as assessed by both two outcome assessments; however, in low interferon signature patients, response was higher and corticosteroid usage was less in rontalizumab-treated patients. Sifalimumab, another anti-interferon-α monoclonal antibody, was studied in patients who remained on standard of care therapy. This study showed significantly better efficacy in patients treated with two sifalimumab dosages; significant differences were seen in the high interferon signature group. In a similar design and in a similar population as the sifalimumab study, anifrolumab, a monoclonal antibody that binds to a type I interferon receptor, was studied in patients who remained on standard of care therapy. In this study, one dosage group demonstrated efficacy and statistically significant effects were achieved in both tested dosage groups with secondary end points. Oral corticosteroid reduction to ≤7.5 mg daily was achieved in one of the tested dosage groups and organ-specific outcomes were significantly improved in that same group. For all studies, no significant differences in serious adverse effects were seen; although, herpes zoster infections were increased in sifalimumab- and anifrolumab-treated patients and influenza rates were increased in anifrolumab-treated patients. Anifrolumab is currently in pivotal phase III studies. Data appear to support the concept that targeting type I interferon in SLE patients associates with clinical efficacy and safety. Further data are forthcoming from ongoing phase III clinical trials of anifrolumab. Other drug development efforts should be considered that target plasmacytoid dendritic cells and toll like receptors given the effects these components have on interferon production. © The Author(s) 2016.

Toward an Application Guide for Safety Integrity Level Allocation in Railway Systems.

PubMed

Ouedraogo, Kiswendsida Abel; Beugin, Julie; El-Koursi, El-Miloudi; Clarhaut, Joffrey; Renaux, Dominique; Lisiecki, Frederic

2018-02-02

The work in the article presents the development of an application guide based on feedback and comments stemming from various railway actors on their practices of SIL allocation to railway safety-related functions. The initial generic methodology for SIL allocation has been updated to be applied to railway rolling stock safety-related functions in order to solve the SIL concept application issues. Various actors dealing with railway SIL allocation problems are the intended target of the methodology; its principles will be summarized in this article with a focus on modifications and precisions made in order to establish a practical guide for railway safety authorities. The methodology is based on the flowchart formalism used in CSM (common safety method) European regulation. It starts with the use of quantitative safety requirements, particularly tolerable hazard rates (THR). THR apportioning rules are applied. On the one hand, the rules are related to classical logical combinations of safety-related functions preventing hazard occurrence. On the other hand, to take into account technical conditions (last safety weak link, functional dependencies, technological complexity, etc.), specific rules implicitly used in existing practices are defined for readjusting some THR values. SIL allocation process based on apportioned and validated THR values is finally illustrated through the example of "emergency brake" subsystems. Some specific SIL allocation rules are also defined and illustrated. © 2018 Society for Risk Analysis.

26 CFR 1.1502-94A - Coordination with section 382 and the regulations thereunder when a corporation becomes a member...

Code of Federal Regulations, 2011 CFR

2011-04-01

...(d)(1). The testing period for L commences on May 1, Year 4. C's purchase of all the P stock causes... (CONTINUED) Regulations Applying Section 382 with Respect to Testing Dates (and Corporations Joining Or... allocation of income and loss). (2) Adjustment to value. The value of the new loss member is adjusted to the...

Development of near zero-order release dosage forms using three-dimensional printing (3-DP) technology.

PubMed

Wang, Chen-Chao; Tejwani Motwani, Monica R; Roach, Willie J; Kay, Jennifer L; Yoo, Jaedeok; Surprenant, Henry L; Monkhouse, Donald C; Pryor, Timothy J

2006-03-01

Three near zero-order controlled-release pseudoephedrine hydrochloride (PEH) formulations demonstrating proportional release rates were developed using 3-Dimensional Printing (3-DP) technology. Mixtures of Kollidon SR and hydroxypropylmethyl cellulose (HPMC) were used as drug carriers. The release rates were adjusted by varying the Kollidon SR-HPMC ratio while keeping fabrication parameters constant. The dosage forms were composed of an immediate release core and a release rate regulating shell, fabricated with an aqueous PEH and an ethanolic triethyl citrate (TEC) binder, respectively. The dosage form design called for the drug to be released via diffusional pathways formed by HPMC in the shell matrix. The release rate was shown to increase correspondingly with the fraction of HPMC contained in the polymer blend. The designed formulations resulted in dosage forms that were insensitive to changes in pH of the dissolution medium, paddle stirring rate, and the presence/absence of a sinker. The near zero-order release properties were unchanged regardless of the dissolution test being performed on either single cubes or on a group of eight cubes encased within a gelatin capsule shell. The chemical and dissolution properties of the three formulations remained unchanged following 1 month's exposure to 25 degrees C/60% RH or 40 degrees C/75% RH environment under open container condition. The in vivo performance of the three formulations was evaluated using a single-dose, randomized, open-label, four-way crossover clinical study composed of 10 fasted healthy volunteers. The pharmacokinetic parameters were analyzed using a noncompartmental model. Qualitative rank order linear correlations between in vivo absorption profiles and in vitro dissolution parameters (with slope and intercept close to unity and origin, respectively) were obtained for all three formulations, indicating good support for a Level A in vivo/in vitro correlation.

The Caenorhabditis elegans RDE-10/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification.

PubMed

Zhang, Chi; Montgomery, Taiowa A; Fischer, Sylvia E J; Garcia, Susana M D A; Riedel, Christian G; Fahlgren, Noah; Sullivan, Christopher M; Carrington, James C; Ruvkun, Gary

2012-05-22

In nematodes, plants, and fungi, RNAi is remarkably potent and persistent due to the amplification of initial silencing signals by RNA-dependent RNA polymerases (RdRPs). In Caenorhabditis elegans (C. elegans), the interaction between the RNA-induced silencing complex (RISC) loaded with primary small interfering RNAs (siRNAs) and the target messenger RNA (mRNA) leads to the recruitment of RdRPs and synthesis of secondary siRNAs using the target mRNA as the template. The mechanism and genetic requirements for secondary siRNA accumulation are not well understood. From a forward genetic screen for C. elegans genes required for RNAi, we identified rde-10, and through proteomic analysis of RDE-10-interacting proteins, we identified a protein complex containing the new RNAi factor RDE-11, the known RNAi factors RSD-2 and ERGO-1, and other candidate RNAi factors. The RNAi defective genes rde-10 and rde-11 encode a novel protein and a RING-type zinc finger domain protein, respectively. Mutations in rde-10 and rde-11 genes cause dosage-sensitive RNAi deficiencies: these mutants are resistant to low dosage but sensitive to high dosage of double-stranded RNAs. We assessed the roles of rde-10, rde-11, and other dosage-sensitive RNAi-defective genes rsd-2, rsd-6, and haf-6 in both exogenous and endogenous small RNA pathways using high-throughput sequencing and qRT-PCR. These genes are required for the accumulation of secondary siRNAs in both exogenous and endogenous RNAi pathways. The RDE-10/RDE-11 complex is essential for the amplification of RNAi in C. elegans by promoting secondary siRNA accumulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage has impaired glucose tolerance independent of body weight.

PubMed

Jelinek, David; Castillo, Joseph J; Garver, William S

2013-09-15

The human Niemann-Pick C1 (NPC1) gene has been found to be associated with extreme (early-onset and morbid-adult) obesity and type 2 diabetes independent of body weight. We previously performed growth studies using BALB/cJ Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mice and determined that decreased Npc1 gene dosage interacts with a high-fat diet to promote weight gain and adiposity. The present study was performed using both BALB/cJ and C57BL/6J Npc1+/+ and Npc1+/- mice to determine if decreased Npc1 gene dosage predisposes to metabolic features associated with type 2 diabetes. The results indicated that C57BL/6J Npc1+/- mice, but not BALB/cJ Npc1+/- mice, have impaired glucose tolerance when fed a low-fat diet and independent of body weight. The results also suggest that an accumulation of liver free fatty acids and hepatic lipotoxicity marked by an elevation in the amount of plasma alanine aminotransferase (ALT) may be responsible for hepatic insulin resistance and impaired glucose tolerance. Finally, the peroxisome-proliferator activated receptor α (PPARα) and sterol regulatory element-binding protein-1 (SREBP-1) pathways known to have a central role in regulating free fatty acid metabolism were downregulated in the livers, but not in the adipose or muscle, of C57BL/6J Npc1+/- mice compared to C57BL/6J Npc1+/+ mice. Therefore, decreased Npc1 gene dosage among two different mouse strains interacts with undefined modifying genes to manifest disparate yet often related metabolic diseases. Published by Elsevier B.V.

Quantitative assessment of hTERT mRNA expression in dysplastic nodules of HBV-related hepatocarcinogenesis.

PubMed

Oh, Bong-Kyeong; Kim, Young-Joo; Park, Young Nyun; Choi, Jinsub; Kim, Kyung Sik; Park, Chanil

2006-04-01

Telomerase reverse transcriptase (hTERT) is the rate-limiting determinant of telomerase, which is critical for carcinogenesis. Dysplastic nodules (DNs) appear to be preneoplastic lesions of hepatocellular carcinomas (HCCs). In this study, in order to characterize DNs, hTERT mRNA, hTERT gene dosage, and mRNA for c-myc, a transcriptional activator of hTERT were studied in human multi-step hepatocarcinogenesis. Fifty four hepatic nodules including 5 large regenerative nodules, 14 low-grade DNs, 7 high-grade DNs, 11 DNs with HCC foci and 17 HCCs, 23 livers with chronic hepatitis/cirrhosis, and 6 normal livers were examined. Transcript levels were measured by real-time quantitative RT-PCR and gene dosages by real-time PCR and Southern blotting. The hTERT mRNA levels increased with the progression of hepatocarcinogenesis, and a significant induction in the transition between low- and high-grade DNs was seen. Most high-grade DNs strongly expressed hTERT mRNA at levels similar to those of HCCs. Twenty-one percent of low-grade DNs had high levels of hTERT mRNA, up to those of high-grade DNs and there was no difference in the pathological features between low-grade DNs with and without increased hTERT mRNA levels. No correlation was found between hTERT mRNA levels, hTERT gene dosage, and c-myc mRNA levels. These results suggest that the induction of hTERT mRNA is an important early event and that its measurement by real-time quantitative RT-PCR is a useful tool to detect premalignant/malignant tendencies in hepatic nodules. However, hTERT gene dosage and c-myc expression are not the main mechanisms regulating hTERT expression in hepatocarcinogenesis.

The Caenorhabditis elegans RDE-10/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification

PubMed Central

Zhang, Chi; Montgomery, Taiowa A.; Fischer, Sylvia E. J.; Garcia, Susana M. D. A.; Riedel, Christian G.; Fahlgren, Noah; Sullivan, Christopher M.; Carrington, James C.; Ruvkun, Gary

2012-01-01

SUMMARY Background In nematodes, plants and fungi, RNAi is remarkably potent and persistent due to the amplification of initial silencing signals by RNA-dependent RNA polymerases (RdRPs). In Caenorhabditis elegans (C. elegans), the interaction between the RNA-induced silencing complex (RISC) loaded with primary siRNAs and the target mRNA leads to the recruitment of RdRPs and synthesis of secondary siRNAs using the target mRNA as the template. The mechanism and genetic requirements for secondary siRNA accumulation are not well understood. Results From a forward genetic screen for C. elegans genes required for RNAi, we identified rde-10 and through proteomic analysis of RDE-10-interacting proteins, we identified a protein complex containing the new RNAi factor RDE-11, the known RNAi factors RSD-2 and ERGO-1, as well as other candidate RNAi factors. The RNAi defective genes rde-10 and rde-11 encode a novel protein and a RING-type zinc finger domain protein, respectively. Mutations in rde-10 and rde-11 genes cause dosage-sensitive RNAi deficiencies: these mutants are resistant to low dosage, but sensitive to high dosage of double-stranded RNAs (dsRNAs). We assessed the roles of rde-10, rde-11, and other dosage-sensitive RNAi-defective genes rsd-2, rsd-6 and haf-6 in both exogenous and endogenous small RNA pathways using high-throughput sequencing and qRT-PCR. These genes are required for the accumulation of secondary siRNAs in both exogenous and endogenous RNAi pathways. Conclusions The RDE-10/RDE-11 complex is essential for the amplification of RNAi in C. elegans by promoting secondary siRNA accumulation. PMID:22542102

Tissue-Specific Effects of Reduced β-catenin Expression on Adenomatous Polyposis Coli Mutation-Instigated Tumorigenesis in Mouse Colon and Ovarian Epithelium

PubMed Central

Feng, Ying; Sakamoto, Naoya; Wu, Rong; Liu, Jie-yu; Wiese, Alexandra; Green, Maranne E.; Green, Megan; Akyol, Aytekin; Roy, Badal C.; Zhai, Yali; Cho, Kathleen R.; Fearon, Eric R.

2015-01-01

Adenomatous polyposis coli (APC) inactivating mutations are present in most human colorectal cancers and some other cancers. The APC protein regulates the β-catenin protein pool that functions as a co-activator of T cell factor (TCF)-regulated transcription in Wnt pathway signaling. We studied effects of reduced dosage of the Ctnnb1 gene encoding β-catenin in Apc-mutation-induced colon and ovarian mouse tumorigenesis and cell culture models. Concurrent somatic inactivation of one Ctnnb1 allele, dramatically inhibited Apc mutation-induced colon polyposis and greatly extended Apc-mutant mouse survival. Ctnnb1 hemizygous dose markedly inhibited increases in β-catenin levels in the cytoplasm and nucleus following Apc inactivation in colon epithelium, with attenuated expression of key β-catenin/TCF-regulated target genes, including those encoding the EphB2/B3 receptors, the stem cell marker Lgr5, and Myc, leading to maintenance of crypt compartmentalization and restriction of stem and proliferating cells to the crypt base. A critical threshold for β-catenin levels in TCF-regulated transcription was uncovered for Apc mutation-induced effects in colon epithelium, along with evidence of a feed-forward role for β-catenin in Ctnnb1 gene expression and CTNNB1 transcription. The active β-catenin protein pool was highly sensitive to CTNNB1 transcript levels in colon cancer cells. In mouse ovarian endometrioid adenocarcinomas (OEAs) arising from Apc- and Pten-inactivation, while Ctnnb1 hemizygous dose affected β-catenin levels and some β-catenin/TCF target genes, Myc induction was retained and OEAs arose in a fashion akin to that seen with intact Ctnnb1 gene dose. Our findings indicate Ctnnb1 gene dose exerts tissue-specific differences in Apc mutation-instigated tumorigenesis. Differential expression of selected β-catenin/TCF-regulated genes, such as Myc, likely underlies context-dependent effects of Ctnnb1 gene dosage in tumorigenesis. PMID:26528816

The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats.

PubMed

Gokbulut, C; Karademir, U; Boyacioglu, M; McKellar, Q A

2008-10-01

The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.

Organ Transplantation in the Face of Donor Shortage - Ethical Implications with a Focus on Liver Allocation

PubMed Central

Lauerer, Michael; Kaiser, Katharina; Nagel, Eckhard

2016-01-01

Background Transplantation medicine is associated with several ethical issues related to the lack of organs. Major questions concern the regulations for giving permission for organ removal, informing the public about organ donation, setting of organ allocation priorities, waiting list access, and strategies to counteract scarcity. Methods This contribution is based on analyses of legal regulations, guidelines of self-regulatory bodies, administrative data, and literature from medical, normative, and empiric disciplines. It addresses the above-mentioned issues descriptively with a focus on Germany and liver transplantation. Results The basic principle of beneficence justifies a shift from voluntariness towards an obligation to document one's decision regarding organ donation. Organ allocation is obviously tangent to fundamental values and concepts of justice. At that, there is no consistent agreement on whether to prioritize the sickest patient or to maximize the overall health benefit. Restrictions relating to waiting list access are the subject of controversies. The reasons for denial of access are largely related to high demands on the prospect of success. Strategies to counteract organ scarcity partly conflict with the respect for autonomy, non-maleficence, beneficence, or justice. Conclusion We propose to focus on recent most promising strategies to counteract scarcity in the short-term: demanding a documented decision on organ donation and an orientation towards the Spanish model of organization. Concepts for waiting list access should constantly be reviewed considering all medical evidence and must not be based on moralism. Moreover, we suggest to consider public preferences for organ allocation and strengthen the confidence in transplantation medicine. PMID:27722165

Organ Transplantation in the Face of Donor Shortage - Ethical Implications with a Focus on Liver Allocation.

PubMed

Lauerer, Michael; Kaiser, Katharina; Nagel, Eckhard

2016-08-01

Transplantation medicine is associated with several ethical issues related to the lack of organs. Major questions concern the regulations for giving permission for organ removal, informing the public about organ donation, setting of organ allocation priorities, waiting list access, and strategies to counteract scarcity. This contribution is based on analyses of legal regulations, guidelines of self-regulatory bodies, administrative data, and literature from medical, normative, and empiric disciplines. It addresses the above-mentioned issues descriptively with a focus on Germany and liver transplantation. The basic principle of beneficence justifies a shift from voluntariness towards an obligation to document one's decision regarding organ donation. Organ allocation is obviously tangent to fundamental values and concepts of justice. At that, there is no consistent agreement on whether to prioritize the sickest patient or to maximize the overall health benefit. Restrictions relating to waiting list access are the subject of controversies. The reasons for denial of access are largely related to high demands on the prospect of success. Strategies to counteract organ scarcity partly conflict with the respect for autonomy, non-maleficence, beneficence, or justice. We propose to focus on recent most promising strategies to counteract scarcity in the short-term: demanding a documented decision on organ donation and an orientation towards the Spanish model of organization. Concepts for waiting list access should constantly be reviewed considering all medical evidence and must not be based on moralism. Moreover, we suggest to consider public preferences for organ allocation and strengthen the confidence in transplantation medicine.

[Requirements for the successful implementation of unity of care: study of a computer-assisted dispensation of pharmaceuticals].

PubMed

Lezin, B; Thouin, A; Besnehard, J; Lobbedez, T; Ollivier, C; Ryckelynck, J P

1999-08-01

Even though computerized workstations bring undisputed benefits in nursing units, introducing them is still hard when most of the staff members have to share the workstation. We took advantage of the implementation of the drug prescription software SAUPHIX in a nephrology department to better define the encountered difficulties. The workstation described in this paper is shared by physicians who enter their prescriptions (proprietary names, doses, routes of administration), nurses who use dosage schedules for drug administration, and the chemist who has authority to control prescription orders. Six months after the implementation of the workstation, physicians and nurses had to fill out an anonymous questionnaire aimed at assessing each function of the software. Prescriptions proved to be more accurate and legible, while management of drugs was more precise. However, interns complained that entering data was time consuming. Furthermore, they raised objections to control of prescription orders. Nurses criticized dosage schedules, the primary reason being that they had to change their practice. The convenience of notebooks was questioned by both physicians and nurses who would have preferred a greater number of desktop computers at their disposition. The implementation of a computerized workstation requires information, diplomacy and negotiations to obtain real implication of the staff. Tasks and schedules must be specified for everybody. The system has to be carefully customized, according to the requirement of the unit. Computers must be properly chosen and allocated in sufficient number. Finally, appropriate preparation, staff training and follow-up of the computerized system are essential.

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication*

PubMed Central

Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

2016-01-01

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under nonoptimal culture conditions but also provide valuable insights into intriguing biological principles, including the balance of proteome resource allocation and the role of gene duplication in evolutionary history. PMID:26560065

Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication.

PubMed

Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

2016-01-01

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under nonoptimal culture conditions but also provide valuable insights into intriguing biological principles, including the balance of proteome resource allocation and the role of gene duplication in evolutionary history. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

PubMed Central

Díaz, Paula; Powell, Theresa L.; Jansson, Thomas

2014-01-01

ABSTRACT The placenta mediates maternal-fetal exchange and has historically been regarded as a passive conduit for nutrients. However, emerging evidence suggests that the placenta actively responds to nutritional and metabolic signals from the mother and the fetus. We propose that the placenta integrates a multitude of maternal and fetal nutritional cues with information from intrinsic nutrient-sensing signaling pathways to match fetal demand with maternal supply by regulating maternal physiology, placental growth, and nutrient transport. This process, which we have called placental nutrient sensing, ensures optimal allocation of resources between the mother and the fetus to maximize the chances for propagation of parental genes without jeopardizing maternal health. We suggest that these mechanisms have evolved because of the evolutionary pressures of maternal undernutrition, which result in decreased placental growth and down-regulation of nutrient transporters, thereby limiting fetal growth to ensure maternal survival. These regulatory loops may also function in response to maternal overnutrition, leading to increased placental growth and nutrient transport in cases of maternal obesity or gestational diabetes. Thus, placental nutrient sensing modulates maternal-fetal resource allocation to increase the likelihood of reproductive success. This model implies that the placenta plays a critical role in mediating fetal programming and determining lifelong health. PMID:25122064

The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation.

PubMed

Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

2017-01-01

Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5-4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

PubMed Central

Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

2017-01-01

Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep. PMID:29213231

Resource allocation to reproduction in animals.

PubMed

Kooijman, Sebastiaan A L M; Lika, Konstadia

2014-11-01

The standard Dynamic Energy Budget (DEB) model assumes that a fraction κ of mobilised reserve is allocated to somatic maintenance plus growth, while the rest is allocated to maturity maintenance plus maturation (in embryos and juveniles) or reproduction (in adults). All DEB parameters have been estimated for 276 animal species from most large phyla and all chordate classes. The goodness of fit is generally excellent. We compared the estimated values of κ with those that would maximise reproduction in fully grown adults with abundant food. Only 13% of these species show a reproduction rate close to the maximum possible (assuming that κ can be controlled), another 4% have κ lower than the optimal value, and 83% have κ higher than the optimal value. Strong empirical support hence exists for the conclusion that reproduction is generally not maximised. We also compared the parameters of the wild chicken with those of races selected for meat and egg production and found that the latter indeed maximise reproduction in terms of κ, while surface-specific assimilation was not affected by selection. We suggest that small values of κ relate to the down-regulation of maximum body size, and large values to the down-regulation of reproduction. We briefly discuss the ecological context for these findings. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

Sugar Allocation to Metabolic Pathways is Tightly Regulated and Affects the Virulence of Streptococcus mutans

PubMed Central

Kawada-Matsuo, Miki; Oogai, Yuichi; Komatsuzawa, Hitoshi

2016-01-01

Bacteria take up and metabolize sugar as a carbohydrate source for survival. Most bacteria can utilize many sugars, including glucose, sucrose, and galactose, as well as amino sugars, such as glucosamine and N-acetylglucosamine. After entering the cytoplasm, the sugars are mainly allocated to the glycolysis pathway (energy production) and to various bacterial component biosynthesis pathways, including the cell wall, nucleic acids and amino acids. Sugars are also utilized to produce several virulence factors, such as capsule and lipoteichoic acid. Glutamine-fructose-6-phosphate aminotransferase (GlmS) and glucosamine-6-phosphate deaminase (NagB) have crucial roles in sugar distribution to the glycolysis pathway and to cell wall biosynthesis. In Streptococcus mutans, a cariogenic pathogen, the expression levels of glmS and nagB are coordinately regulated in response to the presence or absence of amino sugars. In addition, the disruption of this regulation affects the virulence of S. mutans. The expression of nagB and glmS is regulated by NagR in S. mutans, but the precise mechanism underlying glmS regulation is not clear. In Staphylococcus aureus and Bacillus subtilis, the mRNA of glmS has ribozyme activity and undergoes self-degradation at the mRNA level. However, there is no ribozyme activity region on glmS mRNA in S. mutans. In this review article, we summarize the sugar distribution, particularly the coordinated regulation of GlmS and NagB expression, and its relationship with the virulence of S. mutans. PMID:28036052

[The academic characteristics of acupuncture and moxibustion of professor ZHANG Yongshu:a famous acupuncturist in Southern Fujian].

PubMed

Xu, Weiwei; Meng, Xianjun; Zhu, Anning; Wang, Yu; Luo, Wuyougumo; Kuang, Zifang

2017-01-12

Professor ZHANG Yongshu , who studied from professor LIU Zhangjie , is a famous acupuncturist in Quanzhou of Southern Fujian. The publications authored by professor ZHANG Yongshu were collected in this study to summarize his academic characteristics of acupuncture and moxibustion. The result indicated he highly valued the regulation of yang qi , and established the theory of "developing yang to nourish yin ", which proposes to develop yang qi to achieve the effect of culturing yin ; he summarized eight methods to regulate the governor vessel and conception vessel, which can condition the body's yin and yang ; he paid attention to moxibustion therapy and its dosage, and made the best of direct moxibustion. In addition, he focused on meridian theory with effective application of meridian syndrome differentiation; in clinical treatment, he regulated the hand- yangming meridian to treat diseases by nourishing yang , generating yin and regulating fu .

29 CFR 1625.8 - Bona fide seniority systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN... equitable allocation of available employment opportunities and prerogatives among younger and older workers... systems which segregate, classify, or otherwise discriminate against individuals on the basis of race...

29 CFR 1625.8 - Bona fide seniority systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN... equitable allocation of available employment opportunities and prerogatives among younger and older workers... systems which segregate, classify, or otherwise discriminate against individuals on the basis of race...

29 CFR 1625.8 - Bona fide seniority systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN... equitable allocation of available employment opportunities and prerogatives among younger and older workers... systems which segregate, classify, or otherwise discriminate against individuals on the basis of race...

29 CFR 1625.8 - Bona fide seniority systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN... equitable allocation of available employment opportunities and prerogatives among younger and older workers... systems which segregate, classify, or otherwise discriminate against individuals on the basis of race...

29 CFR 1625.8 - Bona fide seniority systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AGE DISCRIMINATION IN... equitable allocation of available employment opportunities and prerogatives among younger and older workers... systems which segregate, classify, or otherwise discriminate against individuals on the basis of race...

48 CFR 9904.406-60 - Illustrations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 9904.406-60 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.406-60 Illustrations. (a) A contractor allocates general management...

76 FR 32407 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... acquisition'') when an appropriate election is made. Section 1060 provides rules for the allocation of... reflected in the burden of Form 8594. The burden for the collection of information in Sec. 1.338- 2T(e)(4...

Cytokine Regulation Immunoglobulin Isotype Production

DTIC Science & Technology

1994-11-08

been shown to involve the activation of a newly di scovered subgroup of tyro sine kinases known as the Janus kinases (26 1 -270). Upon binding of IFN-r...indiCated reagents at dosages indiCated in Figure 1 . Culture supernatants were then harvested for determination of Ig isotype concentrations by ELISA ...Ig - immunoglobulin Iy2b - intronic gamma 2b regIOn IL - interleukin IP3 - inositol triphosphate XXlll JAK - Janus kinase LA P latency

Provision of menstrual regulation with medication among pharmacies in three municipal districts of Bangladesh: a situation analysis.

PubMed

Huda, Fauzia Akhter; Mahmood, Hassan Rushekh; Alam, Anadil; Ahmmed, Faisal; Karim, Farzana; Sarker, Bidhan Krishna; Al Haque, Nafis; Ahmed, Anisuddin

2018-02-01

The objective was to assess the provision of the combination of mifepristone-misoprostol for menstrual regulation (MR) in randomly selected urban pharmacies in Bangladesh. We conducted a cross-sectional survey among 553 pharmacy workers followed by 548 mystery client visits to the same pharmacies in 3 municipal districts during July 2014-December 2015. The survey found that 99% of pharmacy workers visited had knowledge of MR procedures but only two-thirds (67%) could state the legal time limit correctly; they mentioned misoprostol (86%) over mifepristone-misoprostol combination (78%) as a procedure of MR with medication (MRM); 36% reported knowing the recommended dosage of mifepristone-misoprostol combination; 70% reported providing information on effectiveness of the medicines; 50% reported recommending at least one follow-up visit to them; 63% reported explaining possible complications of using the medications; and 47% reported offering any post-MR contraception to their clients. In contrast, mystery client visits found that the mifepristone-misoprostol combination (69%) was suggested over misoprostol (51%) by the pharmacy workers; 54% provided the recommended dosage of mifepristone-misoprostol combination; 42% provided information on its effectiveness; 12% recommended at least one follow-up visit; 11% counseled on possible complications; and only 5% offered post-MR contraceptives to the mystery clients. We found knowledge gaps regarding recommended dosage for MRM and inconsistent practice in informing women on effectiveness, follow-up visits, possible complications and provision of post-MR contraceptives among the pharmacy workers, particularly during the mystery client visits. Pharmacy workers in Bangladesh need to be trained on legal time limits for MR services provision, on providing accurate information on disbursed medicine, and on proper referral mechanisms. A strong monitoring and regulatory system for pharmacy provision of MRM in pharmacies should be established. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Improving the Academic Achievement of the Disadvantaged; Migrant Education Program. Final Rule. Federal Register, Department of Education, 34 CFR Part 200

ERIC Educational Resources Information Center

National Archives and Records Administration, 2008

2008-01-01

The Secretary amends the regulations governing the Migrant Education Program (MEP) administered under Part C of Title I of the Elementary and Secondary Education Act of 1965, as amended (ESEA). These final regulations adjust the base amounts of the MEP Basic State Formula grant allocations for fiscal year (FY) 2006 and subsequent years (as well…

Dynamic equilibrium strategy for drought emergency temporary water transfer and allocation management

NASA Astrophysics Data System (ADS)

Xu, Jiuping; Ma, Ning; Lv, Chengwei

2016-08-01

Efficient water transfer and allocation are critical for disaster mitigation in drought emergencies. This is especially important when the different interests of the multiple decision makers and the fluctuating water resource supply and demand simultaneously cause space and time conflicts. To achieve more effective and efficient water transfers and allocations, this paper proposes a novel optimization method with an integrated bi-level structure and a dynamic strategy, in which the bi-level structure works to deal with space dimension conflicts in drought emergencies, and the dynamic strategy is used to deal with time dimension conflicts. Combining these two optimization methods, however, makes calculation complex, so an integrated interactive fuzzy program and a PSO-POA are combined to develop a hybrid-heuristic algorithm. The successful application of the proposed model in a real world case region demonstrates its practicality and efficiency. Dynamic cooperation between multiple reservoirs under the coordination of a global regulator reflects the model's efficiency and effectiveness in drought emergency water transfer and allocation, especially in a fluctuating environment. On this basis, some corresponding management recommendations are proposed to improve practical operations.

Energetic cost of communication.

PubMed

Stoddard, Philip K; Salazar, Vielka L

2011-01-15

Communication signals may be energetically expensive or inexpensive to produce, depending on the function of the signal and the competitive nature of the communication system. Males of sexually selected species may produce high-energy advertisement signals, both to enhance detectability and to signal their size and body condition. Accordingly, the proportion of the energy budget allocated to signal production ranges from almost nothing for many signals to somewhere in excess of 50% for acoustic signals in short-lived sexually selected species. Recent data from gymnotiform electric fish reveal mechanisms that regulate energy allocated to sexual advertisement signals through dynamical remodeling of the excitable membranes in the electric organ. Further, males of the short-lived sexually selected species, Brachyhypopomus gauderio, trade off among different metabolic compartments, allocating energy to signal production while reducing energy used in other metabolic functions. Female B. gauderio, by contrast, do not trade off energy between signaling and other functions. To fuel energetically expensive signal production, we expect a continuum of strategies to be adopted by animals of different life history strategies. Future studies should explore the relation between life history and energy allocation trade-offs.

Energetic cost of communication

PubMed Central

Stoddard, Philip K.; Salazar, Vielka L.

2011-01-01

Communication signals may be energetically expensive or inexpensive to produce, depending on the function of the signal and the competitive nature of the communication system. Males of sexually selected species may produce high-energy advertisement signals, both to enhance detectability and to signal their size and body condition. Accordingly, the proportion of the energy budget allocated to signal production ranges from almost nothing for many signals to somewhere in excess of 50% for acoustic signals in short-lived sexually selected species. Recent data from gymnotiform electric fish reveal mechanisms that regulate energy allocated to sexual advertisement signals through dynamical remodeling of the excitable membranes in the electric organ. Further, males of the short-lived sexually selected species, Brachyhypopomus gauderio, trade off among different metabolic compartments, allocating energy to signal production while reducing energy used in other metabolic functions. Female B. gauderio, by contrast, do not trade off energy between signaling and other functions. To fuel energetically expensive signal production, we expect a continuum of strategies to be adopted by animals of different life history strategies. Future studies should explore the relation between life history and energy allocation trade-offs. PMID:21177941

Indications, usage, and dosage of the transfer factor.

PubMed

Berrón-Pérez, Renato; Chávez-Sánchez, Raúl; Estrada-García, Iris; Espinosa-Padilla, Sara; Cortez-Gómez, Rudyard; Serrano-Miranda, Ernestina; Ondarza-Aguilera, Rodolfo; Pérez-Tapia, Mayra; Pineda Olvera, Benjamín; Jiménez-Martínez, María del Carmen; Portugués, Abraham; Rodríguez, Azucena; Cano, Laura; Pacheco, Pedro Urcino; Barrientos, Javier; Chacón, Rommel; Serafín, Jeannet; Mendez, Patricia; Monges, Abelardo; Cervantes, Edgar; Estrada-Parra, Sergio

2007-01-01

The transfer factor (TF) was described in 1955 by S. Lawrence. In 1992 Kirkpatrick characterized the specific TF at molecular level. The TF is constituted by a group of numerous molecules, of low molecular weight, from 1.0 to 6.0 kDa. The 5 kDa fraction corresponds to the TF specific to antigens. There are a number of publications about the clinical indications of the TF for diverse diseases, in particular those where the cellular immune response is compromised or in those where there is a deficient regulation of the immune response. In this article we present our clinical and basic experiences, especially regarding the indications, usage and dosage of the TF. Our group demonstrated that the TF increases the expression of IFN-gamma and RANTES, while decreases the expression of osteopontine. Using animal models we have worked with M. tuberculosis, and with a model of glioma with good therapeutic results. In the clinical setting we have worked with herpes zoster, herpes simplex type I, herpetic keratitis, atopic dermatitis, osteosarcoma, tuberculosis, asthma, post-herpetic neuritis, anergic coccidioidomycosis, leishmaniasis, toxoplasmosis, mucocutaneous candidiasis, pediatric infections produced by diverse pathogen germs, sinusitis, pharyngitis, and otits media. All of these diseases were studied through protocols which main goals were to study the therapeutic effects of the TF, and to establish in a systematic way diverse dosage schema and time for treatment to guide the prescription of the TF.

Genome-wide haploinsufficiency screen reveals a novel role for γ-TuSC in spindle organization and genome stability

PubMed Central

Choy, John S.; O'Toole, Eileen; Schuster, Breanna M.; Crisp, Matthew J.; Karpova, Tatiana S.; McNally, James G.; Winey, Mark; Gardner, Melissa K.; Basrai, Munira A.

2013-01-01

How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved γ-tubulin small complex (γ-TuSC), which nucleates microtubule assembly. We found that hemizygous γ-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that γ-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles. PMID:23825022

Genome-wide haploinsufficiency screen reveals a novel role for γ-TuSC in spindle organization and genome stability.

PubMed

Choy, John S; O'Toole, Eileen; Schuster, Breanna M; Crisp, Matthew J; Karpova, Tatiana S; McNally, James G; Winey, Mark; Gardner, Melissa K; Basrai, Munira A

2013-09-01

How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved γ-tubulin small complex (γ-TuSC), which nucleates microtubule assembly. We found that hemizygous γ-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that γ-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles.

[Formulation and special investigations of innovative intraoral solid dosage forms.

PubMed

Kristo, K; kATONA, B; Piukovics, P; Olah, I; Sipos, B; Sipos, S E; Sovany, T; Hodi, K; Ifi Regdon, G

During our work, we summarized the types of solid dosage forms which were in the focus of attention in the last years because of their innovative pharmaceutical technology solution and simple use. The biopharmaceutics of solid dosage forms for intraoral use and the advantages of the use of these dosages forms were presented in general. However, these dosage forms cannot always be prepared with conventional pharmaceutical processes, therefore the special pharmaceutical solutions which can be applied for their preparation were presented. In addition to testing the European Pharmacopoeia dosage forms, the special tests which can be applied for the characterization of innovative solid dosage forms were highlighted.

30 CFR 250.1201 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR... measurement. The measured volumes are used in the allocation process. Liquid hydrocarbons (free liquids... at which custody transfer takes place (not necessarily a royalty meter). Seal—a device or approved...

47 CFR 2.801 - Radiofrequency device defined.

Code of Federal Regulations, 2011 CFR

2011-10-01

....801 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.801 Radiofrequency device..., but are not limited to: (a) The various types of radio communication transmitting devices described...

50 CFR 660.409 - Inseason actions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... resource, any adjudicated Indian fishing rights, and the ocean allocation scheme in the fishery management..., the following: (i) Modification of quotas and/or fishing seasons. (ii) Modification of the species... retention regulations. (iii) Modification of recreational bag limits and recreational fishing days per...

50 CFR 660.409 - Inseason actions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... resource, any adjudicated Indian fishing rights, and the ocean allocation scheme in the fishery management..., the following: (i) Modification of quotas and/or fishing seasons. (ii) Modification of the species... retention regulations. (iii) Modification of recreational bag limits and recreational fishing days per...

5 CFR 319.203 - Establishment of positions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Establishment of positions. 319.203 Section 319.203 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment...

5 CFR 451.303 - Restrictions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS AWARDS Presidential Rank Awards... (SL) and Scientific-Professional (ST) positions; and (2) The number of senior career employees awarded... appointees to OPM-allocated Senior-Level (SL) and Scientific-Professional (ST) positions. (c) Frequency of...

29 CFR 1952.104 - Final approval determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Assistant Secretary determined that, in operation, Oregon's occupational safety and health program (with the... accordance with 29 CFR part 1953; to allocate sufficient safety and health enforcement staff to meet the...

Dosage Parameters in Pediatric Outcome Studies Reported in 9 Peer-Reviewed Occupational Therapy Journals from 2008 to 2014: A Content Analysis

PubMed Central

Gee, Bryan M.; Lloyd, Kimberly; Devine, Nancy; Tyrrell, Erin; Evans, Trisha; Hill, Rebekah; Dineen, Stacee; Magalogo, Kristin

2016-01-01

Occupational therapists determine the dosage when establishing the plan of care for their pediatric clients. A content analysis was conducted using 123 pediatric occupational therapy outcomes studies from 9 scholarly international occupational therapy journals. The parameters of dosage were calculated using descriptive statistics in order to obtain a representation of dosage available within the current collage of pediatric occupational therapy outcomes studies. The results revealed that most studies reported portions of dosage parameters within the published studies. The average findings for the subcomponents related to dosage were session length (minutes) M = 58.7, duration of plan of care (weeks) M = 12.1, session frequency (per week) M = 3.4, and total hours of therapy (hours) M = 18.1. This first attempt at describing and calculating dosage related to pediatric occupational therapy practice indicates that evidence is lacking within the published literature to adequately guide OT dosage decisions. Further research related to dosage in pediatric occupational therapy practice is needed. PMID:26949547

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

A global trait-based approach to estimate leaf nitrogen functional allocation from observations

DOE PAGES

Ghimire, Bardan; Riley, William J.; Koven, Charles D.; ...

2017-03-28

Nitrogen is one of the most important nutrients for plant growth and a major constituent of proteins that regulate photosynthetic and respiratory processes. However, a comprehensive global analysis of nitrogen allocation in leaves for major processes with respect to different plant functional types is currently lacking. This study integrated observations from global databases with photosynthesis and respiration models to determine plant-functional-type-specific allocation patterns of leaf nitrogen for photosynthesis (Rubisco, electron transport, light absorption) and respiration (growth and maintenance), and by difference from observed total leaf nitrogen, an unexplained “residual” nitrogen pool. Based on our analysis, crops partition the largest fractionmore » of nitrogen to photosynthesis (57%) and respiration (5%) followed by herbaceous plants (44% and 4%). Tropical broadleaf evergreen trees partition the least to photosynthesis (25%) and respiration (2%) followed by needle-leaved evergreen trees (28% and 3%). In trees (especially needle-leaved evergreen and tropical broadleaf evergreen trees) a large fraction (70% and 73% respectively) of nitrogen was not explained by photosynthetic or respiratory functions. Compared to crops and herbaceous plants, this large residual pool is hypothesized to emerge from larger investments in cell wall proteins, lipids, amino acids, nucleic acid, CO2 fixation proteins (other than Rubisco), secondary compounds, and other proteins. Our estimates are different from previous studies due to differences in methodology and assumptions used in deriving nitrogen allocation estimates. Unlike previous studies, we integrate and infer nitrogen allocation estimates across multiple plant functional types, and report substantial differences in nitrogen allocation across different plant functional types. Furthermore, the resulting pattern of nitrogen allocation provides insights on mechanisms that operate at a cellular scale within leaves, and can be integrated with ecosystem models to derive emergent properties of ecosystem productivity at local, regional, and global scales.« less

A global trait-based approach to estimate leaf nitrogen functional allocation from observations

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

Ghimire, Bardan; Riley, William J.; Koven, Charles D.

Nitrogen is one of the most important nutrients for plant growth and a major constituent of proteins that regulate photosynthetic and respiratory processes. However, a comprehensive global analysis of nitrogen allocation in leaves for major processes with respect to different plant functional types is currently lacking. This study integrated observations from global databases with photosynthesis and respiration models to determine plant-functional-type-specific allocation patterns of leaf nitrogen for photosynthesis (Rubisco, electron transport, light absorption) and respiration (growth and maintenance), and by difference from observed total leaf nitrogen, an unexplained “residual” nitrogen pool. Based on our analysis, crops partition the largest fractionmore » of nitrogen to photosynthesis (57%) and respiration (5%) followed by herbaceous plants (44% and 4%). Tropical broadleaf evergreen trees partition the least to photosynthesis (25%) and respiration (2%) followed by needle-leaved evergreen trees (28% and 3%). In trees (especially needle-leaved evergreen and tropical broadleaf evergreen trees) a large fraction (70% and 73% respectively) of nitrogen was not explained by photosynthetic or respiratory functions. Compared to crops and herbaceous plants, this large residual pool is hypothesized to emerge from larger investments in cell wall proteins, lipids, amino acids, nucleic acid, CO2 fixation proteins (other than Rubisco), secondary compounds, and other proteins. Our estimates are different from previous studies due to differences in methodology and assumptions used in deriving nitrogen allocation estimates. Unlike previous studies, we integrate and infer nitrogen allocation estimates across multiple plant functional types, and report substantial differences in nitrogen allocation across different plant functional types. Furthermore, the resulting pattern of nitrogen allocation provides insights on mechanisms that operate at a cellular scale within leaves, and can be integrated with ecosystem models to derive emergent properties of ecosystem productivity at local, regional, and global scales.« less

Ecotoxicological effects of buprofezin on fecundity, growth, development, and predation of the wolf spider Pirata piratoides (Schenkel).

PubMed

Deng, Lingling; Xu, Muqi; Cao, Hong; Dai, Jiayin

2008-11-01

The toxicological effects of buprofezin, an insect growth regulator, on the fecundity, development, and pest control potential of the wolf spider Pirata piratoides (Schenkel) (Araneae: Lycosidae) were investigated in the laboratory. It was shown that buprofezin had low toxicity to P. piratoides and that the median lethal dosage (LD(50)) 48 h and 10% lethal dosage (LD(10)) after topical application for female spiders were 653 and 316 mg buprofezin/mg fresh weight of spider, respectively. Buprofezin significantly reduced the percent hatching of spiders' eggs but had only a slight effect on egg production. No negative effects on the development and growth were observed. However, spider predation rates were strongly affected: Insecticide-treated females predated on fewer prey than the controls, and their predation rate did not recover even 5 days after insecticide application. This indicated that their pest control potential might be influenced by buprofezin, and the use of buprofezin in biological control of insects is discussed.

A critical evaluation of Internet marketing of products that contain ephedra.

PubMed

Ashar, Bimal H; Miller, Redonda G; Getz, Kelly J; Pichard, Carmen P

2003-08-01

To evaluate information contained within Internet sites that advertise and market dietary supplements containing ephedra. We conducted an Internet search to identify Web sites advertising weight-loss supplements that contained ephedra. Between July 7 and July 18, 2002, 4 search engines were used by entering the term herbal weight loss. Outcome measures included disclosure of potential adverse effects of or contraindications to ephedra-containing supplements, disclosure of ephedra alkaloid dosage, and presence of misleading or incorrect information. Thirty-two products and advertisements were identified and systematically evaluated for deviance from truth-in-advertising standards. Of the 32 Web sites analyzed, 13 (41%) failed to disclose potential adverse effects or contraindications to supplement use. Seventeen (53%) did not reveal the dosage of ephedra alkaloids that was recommended. More importantly, 11 sites (34%) contained incorrect or misleading statements, some of which could directly result in serious harm to consumers. If dietary supplements containing ephedra are to continue to be marketed freely, substantial reform in advertising regulation and enforcement is warranted.

Double-blind cross-over investigation of the effectiveness and safety of two doses of indoprofen compared with an ASA preparation and placebo in patients suffering from osteoarthritis.

PubMed

Valtonen, E; Bergamini, N; Groppi, W; Mandelli, V

1981-01-01

Eighty patients suffering from osteoarthritis of the large joints were admitted to the study and randomly allocated to a 4-treatment sequence, according to a multiple replication of a 4 x 4 Latin square design, with proper balancing of treatments, of periods and of the residual effects of drugs. Each treatment (indoprofen 300 or 600 mg/day, ASA 1500 + diazepam 6 mg/day, and matching placebo) was administered for 7 days. Examinations were carried out on admission, after a 3-4 day wash-out period, and then repeated at the end of each treatment period. Treatment with active drugs was significantly better than placebo in relieving overall pain, and in patient's and investigator's opinion on effectiveness. Treatment with indoprofen, at both dosages, was preferred more frequently than others. The incidence of adverse events during each period did not seem to depend either on the treatment being given during that period or on the previous one.

Toward Higher QA: From Parametric Release of Sterile Parenteral Products to PAT for Other Pharmaceutical Dosage Forms.

PubMed

Hock, Sia Chong; Constance, Neo Xue Rui; Wah, Chan Lai

2012-01-01

Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most ideal approach for determining the pharmaceutical quality of the finished dosage form. In the case of terminally sterilized parenteral products, the limitations of conventional batch testing have been successfully addressed with the application of parametric release (the release of a product based on control of process parameters instead of batch sterility testing at the end of the manufacturing process). Consequently, there has been an increasing interest in applying parametric release to other pharmaceutical dosage forms, beyond terminally sterilized parenteral products. For parametric release to be possible, manufacturers must be capable of designing quality into the product, monitoring the manufacturing processes, and controlling the quality of intermediates and finished products in real-time. Process analytical technology (PAT) has been thought to be capable of contributing to these prerequisites. It is believed that the appropriate use of PAT tools can eventually lead to the possibility of real-time release of other pharmaceutical dosage forms, by-passing the need for end-product batch testing. Hence, this literature review attempts to present the basic principles of PAT, introduce the various PAT tools that are currently available, present their recent applications to pharmaceutical processing, and explain the potential benefits that PAT can bring to conventional ways of processing and quality assurance of pharmaceutical products. Last but not least, current regulations governing the use of PAT and the manufacturing challenges associated with PAT implementation are also discussed. Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most ideal approach. In the case of terminally sterilized parenteral products, these limitations have been successfully addressed with the application of parametric release (the release of a product based on control of process parameters instead of batch sterility testing at the end of the manufacturing process). Consequently, there has been an increasing interest in applying parametric release to other pharmaceutical dosage forms. With the advancement of process analytical technology (PAT), it is possible to monitor the manufacturing processes closely. This will eventually enable quality control of the intermediates and finished products, and thus their release in real-time. Hence, this literature review attempts to present the basic principles of PAT, introduce the various PAT tools that are currently available, present their recent applications to pharmaceutical processing, and explain the potential benefits that PAT can bring to conventional ways of processing and quality assurance of pharmaceutical products. It will also discuss the current regulations governing the use of PAT and the manufacturing challenges associated with the implementation of PAT.

Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements.

PubMed

Zhang, Tingting; Stilwell, Jackie L; Gerion, Daniele; Ding, Lianghao; Elboudwarej, Omeed; Cooke, Patrick A; Gray, Joe W; Alivisatos, A Paul; Chen, Fanqing Frank

2006-04-01

Quantum dots (Qdots) are now used extensively for labeling in biomedical research, and this use is predicted to grow because of their many advantages over alternative labeling methods. Uncoated Qdots made of core/shell CdSe/ZnS are toxic to cells because of the release of Cd2+ ions into the cellular environment. This problem has been partially overcome by coating Qdots with polymers, poly(ethylene glycol) (PEG), or other inert molecules. The most promising coating to date, for reducing toxicity, appears to be PEG. When PEG-coated silanized Qdots (PEG-silane-Qdots) are used to treat cells, toxicity is not observed, even at dosages above 10-20 nM, a concentration inducing death when cells are treated with polymer or mercaptoacid coated Qdots. Because of the importance of Qdots in current and future biomedical and clinical applications, we believe it is essential to more completely understand and verify this negative global response from cells treated with PEG-silane-Qdots. Consequently, we examined the molecular and cellular response of cells treated with two different dosages of PEG-silane-Qdots. Human fibroblasts were exposed to 8 and 80 nM of these Qdots, and both phenotypic as well as whole genome expression measurements were made. PEG-silane-Qdots did not induce any statistically significant cell cycle changes and minimal apoptosis/necrosis in lung fibroblasts (IMR-90) as measured by high content image analysis, regardless of the treatment dosage. A slight increase in apoptosis/necrosis was observed in treated human skin fibroblasts (HSF-42) at both the low and the high dosages. We performed genome-wide expression array analysis of HSF-42 exposed to doses 8 and 80 nM to link the global cell response to a molecular and genetic phenotype. We used a gene array containing approximately 22,000 total probe sets, containing 18,400 probe sets from known genes. Only approximately 50 genes (approximately 0.2% of all the genes tested) exhibited a statistically significant change in expression level of greater than 2-fold. Genes activated in treated cells included those involved in carbohydrate binding, intracellular vesicle formation, and cellular response to stress. Conversely, PEG-silane-Qdots induce a down-regulation of genes involved in controlling the M-phase progression of mitosis, spindle formation, and cytokinesis. Promoter analysis of these results reveals that expression changes may be attributed to the down-regulation of FOXM and BHLB2 transcription factors. Remarkably, PEG-silane-Qdots, unlike carbon nanotubes, do not activate genes indicative of a strong immune and inflammatory response or heavy-metal-related toxicity. The experimental evidence shows that CdSe/ZnS Qdots, if appropriately protected, induce negligible toxicity to the model cell system studied here, even when exposed to high dosages. This study indicates that PEG-coated silanized Qdots pose minimal impact to cells and are a very promising alternative to uncoated Qdots.

Essays on optimal capacity and optimal regulation of interconnection infrastructures

NASA Astrophysics Data System (ADS)

Boffa, Federico

The integration between geographically differentiated markets or between vertically related industries generate effects on welfare that depend on the structure of the underlying markets. My thesis investigates the impact of geographical interconnection on welfare, and illustrates welfare-enhancing modes of regulation of vertically integrated industries and of geographically integrated markets. The first chapter analyzes the effects of interconnection between two formerly fully-separated markets under the assumptions that producers in the two markets are capacity-constrained, and tacitly collude whenever it is rational for them to do so. I find that there exists a set of assumptions under which interconnection brings about greater collusion, hence it reduces overall welfare. The second chapter analyzes the optimal interconnection capacity allocation mechanism for a benevolent electricity regulator when generation is not competitive. The regulator's intervention should not only ensure that interconnection capacity is efficiently allocated to the most efficient firms, but it should also induce a higher welfare in the upstream generation market. In a two-node setting, with one firm per node, I show that the regulatory intervention becomes more effective as the cost asymmetries between the two firms become more pronounced. The third chapter illustrates a regulation mechanism for vertically related industries. Ownership shares of the upstream industry (that displays economies of scale) are allocated to the downstream (competitive) firms in proportion to their shares in the final goods market. I show that the mechanism combines the benefits of vertical integration with those of vertical separation. The advantages of vertical integration consist in avoiding double marginalization, and in internalizing the reduction in average cost resulting from the upstream increase in output; on the other hand, vertical separation allows to preserve the competitiveness of the downstream sector. I also show that this mechanism improves in efficiency with respect to the Demsetz auction, and, finally, that it displays desirable properties as far as collusion and quality levels are concerned. The fourth chapter empirically estimates the benefit of removing the most crucial transmission bottleneck in the Italian electricity market, by building additional transmission capacity. Benefits are found to be relevant.

Constraint-induced movement therapy (CIMT) for young children with cerebral palsy: effects of therapeutic dosage.

PubMed

DeLuca, Stephanie C; Case-Smith, Jane; Stevenson, Richard; Ramey, Sharon Landesman

2012-01-01

To compare effects of 2 dosage levels of constraint-induced movement therapy (CIMT) for children with hemiplegic cerebral palsy (CP). We hypothesized that high-dosage CIMT would produce larger benefits than moderate-dosage. Three sites enrolled a total of 18 children (6 children per site from 3-6 years) with unilateral CP. Children were randomly assigned to CIMT for 21 days for either 6 hours/day (high-dosage=126 hours) or 3 hours/day (moderate-dosage=63 hours); both groups wore a long-arm cast. Evaluators (blind to dosage) assessed children 1-week prior, then 1-week and 1-month after treatment with the Assisting Hand Assessment (AHA), The Quality of Upper Extremity Skills Test (QUEST) Dissociated Movement and Grasp sections, the Shriners Hospital Upper Extremity Evaluation (SHUEE), and the Pediatric Motor Activity Log (PMAL). All children responded well to casting and received the full intended dosage. Both groups showed statistically significant gains on the AHA, QUEST, SHUEE, and PMAL. Effect sizes ranged from 0.36-0.79. Overall, both groups showed comparable improvements at 1-week and 1-month post-treatment. Pediatric CIMT at both moderate and high dosages produced positive effects across multiple reliable, valid outcome measures. The findings refuted the hypothesis of differential dosage benefits. Future research should address long-term effects, enroll larger and more diverse samples, and assess lower dosages to ascertain a minimal-efficacy threshold.

Comprehensive review on additives of topical dosage forms for drug delivery.

PubMed

Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-12-01

Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

47 CFR 2.301 - Station identification requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 2.301 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Call Signs and Other Forms of Identifying Radio... the enforcement of the Communications Act of 1934, as amended, and the Commission's rules. [34 FR 5104...

15 CFR 700.18 - Limitations on placing rated orders.

Code of Federal Regulations, 2012 CFR

2012-01-01

... transportation (Department of Transportation); (v) Water resources (Department of Defense/U.S. Army Corps of... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.18 Limitations on placing...

15 CFR 700.18 - Limitations on placing rated orders.

Code of Federal Regulations, 2014 CFR

2014-01-01

... transportation (Department of Transportation); (v) Water resources (Department of Defense/U.S. Army Corps of... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.18 Limitations on placing...

15 CFR 700.18 - Limitations on placing rated orders.

Code of Federal Regulations, 2013 CFR

2013-01-01

... transportation (Department of Transportation); (v) Water resources (Department of Defense/U.S. Army Corps of... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.18 Limitations on placing...

45 CFR 95.509 - Cost allocation plan amendments and certifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... 95.509 Section 95.509 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION-GRANT PROGRAMS (PUBLIC ASSISTANCE, MEDICAL ASSISTANCE AND STATE CHILDREN'S HEALTH... plan become outdated because of organizational changes, changes in Federal law or regulations, or...

45 CFR 95.509 - Cost allocation plan amendments and certifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... 95.509 Section 95.509 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION-GRANT PROGRAMS (PUBLIC ASSISTANCE, MEDICAL ASSISTANCE AND STATE CHILDREN'S HEALTH... plan become outdated because of organizational changes, changes in Federal law or regulations, or...

48 CFR 5452.249 - Allocation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 5452.249 Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE... Fuel Supply Center is authorized to use the following clause in domestic and overseas petroleum... Defense that the Defense Fuel Supply Center be provided contract volumes exceeding the pro rata amount of...

48 CFR 5452.249 - Allocation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Section 5452.249 Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE... Fuel Supply Center is authorized to use the following clause in domestic and overseas petroleum... Defense that the Defense Fuel Supply Center be provided contract volumes exceeding the pro rata amount of...

48 CFR 5452.249 - Allocation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Section 5452.249 Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE... Fuel Supply Center is authorized to use the following clause in domestic and overseas petroleum... Defense that the Defense Fuel Supply Center be provided contract volumes exceeding the pro rata amount of...

48 CFR 5452.249 - Allocation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Section 5452.249 Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE... Fuel Supply Center is authorized to use the following clause in domestic and overseas petroleum... Defense that the Defense Fuel Supply Center be provided contract volumes exceeding the pro rata amount of...

48 CFR 5452.249 - Allocation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Section 5452.249 Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE... Fuel Supply Center is authorized to use the following clause in domestic and overseas petroleum... Defense that the Defense Fuel Supply Center be provided contract volumes exceeding the pro rata amount of...

7 CFR 982.30 - Establishment and membership.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... is hereby established a Hazelnut Marketing Board consisting of 10 members, each of whom shall have an... the same eligibility qualifications. The 10 member positions shall be allocated as follows: (b) Four...

7 CFR 662.4 - Regional Equity implementation procedure.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 662.4 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES... through a merit-based, natural resource focused allocation process as determined by the Chief. (b... priorities; (B) Historic trends in program interest; and (C) State priority natural resource concerns. (ii...

15 CFR 700.10 - Delegation of authority.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.10 Delegation of authority. (a) The... respect to industrial resources have been delegated to the Secretary of Commerce under Executive Order...

15 CFR 700.93 - Communications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Communications. 700.93 Section 700.93 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF... PRIORITIES AND ALLOCATIONS SYSTEM Miscellaneous Provisions § 700.93 Communications. All communications...

48 CFR 9905.505-50 - Techniques for application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... this cost accounting principle does not require that allocation of unallowable costs to final cost.... 9905.505-50 Section 9905.505-50 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.505-50 Techniques for...

15 CFR 700.93 - Communications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Communications. 700.93 Section 700.93 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF... PRIORITIES AND ALLOCATIONS SYSTEM Miscellaneous Provisions § 700.93 Communications. All communications...

ROOT BIOMASS ALLOCATION IN THE WORLD'S UPLAND FORESTS

EPA Science Inventory

Because the world's forests play a major role in regulating nutrient and carbon cycles, there is much interest in estimating their biomass. Estimates of aboveground biomass based on well-established methods are relatively abundant; estimates of root biomass based on standard meth...

5 CFR 319.201 - Coverage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Coverage. 319.201 Section 319.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment § 319.201 Coverage. This section...

5 CFR 319.201 - Coverage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Coverage. 319.201 Section 319.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment § 319.201 Coverage. This section...

5 CFR 319.201 - Coverage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Coverage. 319.201 Section 319.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment § 319.201 Coverage. This section...

5 CFR 319.201 - Coverage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Coverage. 319.201 Section 319.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment § 319.201 Coverage. This section...

5 CFR 319.201 - Coverage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Coverage. 319.201 Section 319.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Position Allocations and Establishment § 319.201 Coverage. This section...

Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain

PubMed Central

Ratnu, Vikram S.; Emami, Michael R.; Bredy, Timothy W.

2016-01-01

There are inherent biological differences between males and females that contribute to sex differences in brain function and to many sex-specific illnesses and disorders. Traditionally, it has been thought that such differences are largely due to hormonal regulation; however, there are also genetic and epigenetic effects caused by the inheritance and unequal dosage of genes located on the X- and Y-chromosomes. Here we discuss the evidence in favor of a genetic and epigenetic basis for sexually dimorphic behavior, as a consequence of underlying differences in the regulation of genes that drive brain function. A better understanding of sex-specific molecular processes in the brain will provide further insight for the development of novel therapeutic approaches for the treatment of neuropsychiatric disorders characterized by gender/sex differences. PMID:27870402

Queen pheromone regulates egg production in a termite.

PubMed

Yamamoto, Yuuka; Matsuura, Kenji

2011-10-23

In social insects, resource allocation is a key factor that influences colony survival and growth. Optimal allocation to queens and brood is essential for maximum colony productivity, requiring colony members to have information on the total reproductive power in colonies. However, the mechanisms regulating egg production relative to the current labour force for brood care remain poorly known. Recently, a volatile chemical was identified as a termite queen pheromone that inhibits the differentiation of new neotenic reproductives (secondary reproductives developed from nymphs or workers) in Reticulitermes speratus. The same volatile chemical is also emitted by eggs. This queen pheromone would therefore be expected to act as an honest message of the reproductive power about queens. In this study, we examined how the queen pheromone influences the reproductive rate of queens in R. speratus. We compared the number of eggs produced by each queen between groups with and without exposure to artificial queen pheromone. Exposure to the pheromone resulted in a significant decrease in egg production in both single-queen and multiple-queen groups. This is the first report supporting the role of queen pheromones as a signal regulating colony-level egg production, using synthetically derived compounds in a termite.

Queen pheromone regulates egg production in a termite

PubMed Central

Yamamoto, Yuuka; Matsuura, Kenji

2011-01-01

In social insects, resource allocation is a key factor that influences colony survival and growth. Optimal allocation to queens and brood is essential for maximum colony productivity, requiring colony members to have information on the total reproductive power in colonies. However, the mechanisms regulating egg production relative to the current labour force for brood care remain poorly known. Recently, a volatile chemical was identified as a termite queen pheromone that inhibits the differentiation of new neotenic reproductives (secondary reproductives developed from nymphs or workers) in Reticulitermes speratus. The same volatile chemical is also emitted by eggs. This queen pheromone would therefore be expected to act as an honest message of the reproductive power about queens. In this study, we examined how the queen pheromone influences the reproductive rate of queens in R. speratus. We compared the number of eggs produced by each queen between groups with and without exposure to artificial queen pheromone. Exposure to the pheromone resulted in a significant decrease in egg production in both single-queen and multiple-queen groups. This is the first report supporting the role of queen pheromones as a signal regulating colony-level egg production, using synthetically derived compounds in a termite. PMID:21543395

Dosage optimization in positron emission tomography: state-of-the-art methods and future prospects

PubMed Central

Karakatsanis, Nicolas A; Fokou, Eleni; Tsoumpas, Charalampos

2015-01-01

Positron emission tomography (PET) is widely used nowadays for tumor staging and therapy response in the clinic. However, average PET radiation exposure has increased due to higher PET utilization. This study aims to review state-of-the-art PET tracer dosage optimization methods after accounting for the effects of human body attenuation and scan protocol parameters on the counting rate. In particular, the relationship between the noise equivalent count rate (NECR) and the dosage (NECR-dosage curve) for a range of clinical PET systems and body attenuation sizes will be systematically studied to prospectively estimate the minimum dosage required for sufficiently high NECR. The optimization criterion can be determined either as a function of the peak of the NECR-dosage curve or as a fixed NECR score when NECR uniformity across a patient population is important. In addition, the systematic NECR assessments within a controllable environment of realistic simulations and phantom experiments can lead to a NECR-dosage response model, capable of predicting the optimal dosage for every individual PET scan. Unlike conventional guidelines suggesting considerably large dosage levels for obese patients, NECR-based optimization recommends: i) moderate dosage to achieve 90% of peak NECR for obese patients, ii) considerable dosage reduction for slimmer patients such that uniform NECR is attained across the patient population, and iii) prolongation of scans for PET/MR protocols, where longer PET acquisitions are affordable due to lengthy MR sequences, with motion compensation becoming important then. Finally, the need for continuous adaptation of dosage optimization to emerging technologies will be discussed. PMID:26550543

First-graders' allocation of attentional resources in an emotional Stroop task: The role of heart period variability and classroom climate.

PubMed

Scrimin, Sara; Moscardino, Ughetta; Mason, Lucia

2018-06-11

Children's ability to remain focused on a task despite the presence of emotionally salient distractors in the environment is crucial for successful learning and academic performance. This study investigated first-graders' allocation of attentional resources in the presence of distracting emotional, school-related social interaction stimuli. Moreover, we examined whether such attentional processes were influenced by students' self-regulation, as indexed by heart period variability, observed classroom climate, or their interaction. Seventy-two-first graders took part in the study. To assess allocation of attentional resources, students' reaction times on an emotional Stroop task were registered by recording response times to colour frames placed around pictures of distracting emotional, school-related social interaction stimuli (i.e., emotional interference index). Moreover, heart period variability was measured by recording children's electrocardiogram at rest during an individual session, whereas classroom climate was observed during class activities by a trained researcher. Images representing negative social interactions required greater attentional resources than images depicting positive ones. Heart period variability and classroom climate were each significantly and independently associated with the emotional interference index. A significant interaction also emerged, indicating that among children experiencing a negative classroom climate, those who had a higher basal heart period variability (higher self-regulation) were less distracted by negative emotional material and remained more focused on a task compared to those with lower heart period variability (lower self-regulation). Negative interactions require greater attentional resources than positive scenes. Moreover, with a negative classroom climate, higher basal heart period variability is a protective factor. Implications for theory and practice are discussed. © 2018 The British Psychological Society.

QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions

PubMed Central

Li, Ling; Zheng, Wenguang; Zhu, Yanbing; Ye, Huaxun; Tang, Buyun; Arendsee, Zebulun W.; Jones, Dallas; Li, Ruoran; Ortiz, Diego; Zhao, Xuefeng; Du, Chuanlong; Nettleton, Dan; Scott, M. Paul; Salas-Fernandez, Maria G.; Yin, Yanhai; Wurtele, Eve Syrkin

2015-01-01

The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background and original protein content of the cultivar. Furthermore, transgenic QQS expression increases the protein content of maize, a C4 species (a species that uses 4-carbon photosynthesis), and rice, a protein-poor agronomic crop, both highly divergent from Arabidopsis. We determine that QQS protein binds to the transcriptional regulator AtNF-YC4 (Arabidopsis nuclear factor Y, subunit C4). Overexpression of AtNF-YC4 in Arabidopsis mimics the QQS-overexpression phenotype, increasing protein and decreasing starch levels. NF-YC, a component of the NF-Y complex, is conserved across eukaryotes. The NF-YC4 homologs of soybean, rice, and maize also bind to QQS, which provides an explanation of how QQS can act in species where it does not occur endogenously. These findings are, to our knowledge, the first insight into the mechanism of action of QQS in modulating carbon and nitrogen allocation across species. They have major implications for the emergence and function of orphan genes, and identify a nontransgenic strategy for modulating protein levels in crop species, a trait of great agronomic significance. PMID:26554020

QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions.

PubMed

Li, Ling; Zheng, Wenguang; Zhu, Yanbing; Ye, Huaxun; Tang, Buyun; Arendsee, Zebulun W; Jones, Dallas; Li, Ruoran; Ortiz, Diego; Zhao, Xuefeng; Du, Chuanlong; Nettleton, Dan; Scott, M Paul; Salas-Fernandez, Maria G; Yin, Yanhai; Wurtele, Eve Syrkin

2015-11-24

The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background and original protein content of the cultivar. Furthermore, transgenic QQS expression increases the protein content of maize, a C4 species (a species that uses 4-carbon photosynthesis), and rice, a protein-poor agronomic crop, both highly divergent from Arabidopsis. We determine that QQS protein binds to the transcriptional regulator AtNF-YC4 (Arabidopsis nuclear factor Y, subunit C4). Overexpression of AtNF-YC4 in Arabidopsis mimics the QQS-overexpression phenotype, increasing protein and decreasing starch levels. NF-YC, a component of the NF-Y complex, is conserved across eukaryotes. The NF-YC4 homologs of soybean, rice, and maize also bind to QQS, which provides an explanation of how QQS can act in species where it does not occur endogenously. These findings are, to our knowledge, the first insight into the mechanism of action of QQS in modulating carbon and nitrogen allocation across species. They have major implications for the emergence and function of orphan genes, and identify a nontransgenic strategy for modulating protein levels in crop species, a trait of great agronomic significance.

The effect of dosages of microbial consortia formulation and synthetic fertilizer on the growth and yield of field-grown chili

NASA Astrophysics Data System (ADS)

Istifadah, N.; Sapta, D.; Krestini, H.; Natalie, B.; Suryatmana, P.; Nurbaity, A.; Hidersah, R.

2018-03-01

Chili (Capsicum annuum, L) is one of important horticultural crop in Indonesia. Formulation of microbial consortia containing Bacillus subtilis, Pseudomonas sp., Azotobacter chroococcum and Trichoderma harzianum has been developed. This study evaluated the effects of dosage of the microbial formulation combined with NPK fertilizer on growth and yield of chili plants in the field experiment. The experiment was arranged in completely randomized design of factorial, in which the first factor was dosage of formulation (0, 2.5, 5.0, 7.5, 10 g per plant) and the second factor was NPK fertilizer dosage (0, 25, 50 and 75% of the standard dosage). The treatments were replicated three times. For application, the formulation was mixed with chicken manure 1:10 (w/v). The results showed that application of microbial formulation solely improved the chili growth. There was interaction between dosages of the microbial formulation and NPK fertilizer in improving plant height, nitrogen availability and the chili yield, while there was no interaction between those dosages in improving the root length. Combination between microbial formulation at the dosage of 5.0-7.5 g per plant combined with NPK fertilizer with the dosage 50 or 75% of the standard dosage support relatively better growth and the chili yield.

The fate of recently fixed carbon after drought release: towards unravelling C storage regulation in Tilia platyphyllos and Pinus sylvestris.

PubMed

Galiano, Lucía; Timofeeva, Galina; Saurer, Matthias; Siegwolf, Rolf; Martínez-Vilalta, Jordi; Hommel, Robert; Gessler, Arthur

2017-09-01

Carbon reserves are important for maintaining tree function during and after stress. Increasing tree mortality driven by drought globally has renewed the interest in how plants regulate allocation of recently fixed C to reserve formation. Three-year-old seedlings of two species (Tilia platyphyllos and Pinus sylvestris) were exposed to two intensities of experimental drought during ~10 weeks, and 13 C pulse labelling was subsequently applied with rewetting. Tracking the 13 C label across different organs and C compounds (soluble sugars, starch, myo-inositol, lipids and cellulose), together with the monitoring of gas exchange and C mass balances over time, allowed for the identification of variations in C allocation priorities and tree C balances that are associated with drought effects and subsequent drought release. The results demonstrate that soluble sugars accumulated in P. sylvestris under drought conditions independently of growth trends; thus, non-structural carbohydrates (NSC) formation cannot be simply considered a passive overflow process in this species. Once drought ceased, C allocation to storage was still prioritized at the expense of growth, which suggested the presence of 'drought memory effects', possibly to ensure future growth and survival. On the contrary, NSC and growth dynamics in T. platyphyllos were consistent with a passive (overflow) view of NSC formation. © 2017 John Wiley & Sons Ltd.

10 CFR 216.8 - Communications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 3 2011-01-01 2011-01-01 false Communications. 216.8 Section 216.8 Energy DEPARTMENT OF ENERGY OIL MATERIALS ALLOCATION AND PRIORITY PERFORMANCE UNDER CONTRACTS OR ORDERS TO MAXIMIZE DOMESTIC ENERGY SUPPLIES § 216.8 Communications. All written communications concerning these regulations shall be...

15 CFR 700.2 - Introduction.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Introduction. 700.2 Section 700.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF... PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.2 Introduction. (a) Certain national defense and energy...

78 FR 22512 - Proposed Information Collection; Comment Request; Special Priorities Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... from defense contractors and suppliers on Form BIS-999, Request for Special Priorities Assistance, is required for the enforcement and administration of special priorities assistance under the Defense Production Act, the Selective Service Act and the Defense Priorities and Allocation System regulation...

7 CFR 932.25 - Establishment and membership.

Code of Federal Regulations, 2010 CFR

2010-01-01

... representation of the producer members shall be two from District 1, four from District 2, and two from District 3. Allocation of the handler members shall be four members to represent cooperative marketing... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing...

15 CFR 2011.104 - Waiver.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Waiver. 2011.104 Section 2011.104 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE ALLOCATION OF TARIFF-RATE QUOTA ON IMPORTED SUGARS, SYRUPS AND MOLASSES Certificate...

15 CFR 2011.101 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false General. 2011.101 Section 2011.101 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE ALLOCATION OF TARIFF-RATE QUOTA ON IMPORTED SUGARS, SYRUPS AND MOLASSES Certificate...

15 CFR 2011.201 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false General. 2011.201 Section 2011.201 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE ALLOCATION OF TARIFF-RATE QUOTA ON IMPORTED SUGARS, SYRUPS AND MOLASSES Specialty...

15 CFR 2011.104 - Waiver.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Waiver. 2011.104 Section 2011.104 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE ALLOCATION OF TARIFF-RATE QUOTA ON IMPORTED SUGARS, SYRUPS AND MOLASSES Certificate...

15 CFR 2011.101 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false General. 2011.101 Section 2011.101 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE ALLOCATION OF TARIFF-RATE QUOTA ON IMPORTED SUGARS, SYRUPS AND MOLASSES Certificate...

50 CFR 679.80 - Initial allocation of rockfish QS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Act of 2004 (Public Law 108-199). Additional regulations that implement specific portions of the...) Duration. The Rockfish Program authorized under this part expires on December 31, 2011. (3) Seasons. The... social security number, permanent business mailing address, business telephone number, and business fax...

10 CFR 217.93 - Communications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false Communications. 217.93 Section 217.93 Energy DEPARTMENT OF ENERGY OIL ENERGY PRIORITIES AND ALLOCATIONS SYSTEM Miscellaneous Provisions § 217.93 Communications. All communications concerning this part, including requests for copies of the regulation and explanatory information...

10 CFR 216.8 - Communications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false Communications. 216.8 Section 216.8 Energy DEPARTMENT OF ENERGY OIL MATERIALS ALLOCATION AND PRIORITY PERFORMANCE UNDER CONTRACTS OR ORDERS TO MAXIMIZE DOMESTIC ENERGY SUPPLIES § 216.8 Communications. All written communications concerning these regulations shall be...

39 CFR 775.6 - Categorical exclusions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... that involve no commitment of resources other than manpower and funding allocations. (3) Award of... personal services. (4) Research activities and studies and routine data collection when such actions are... replacement or any lead based paint abatement actions regulated under the provisions of the Toxic Substances...

39 CFR 775.6 - Categorical exclusions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... that involve no commitment of resources other than manpower and funding allocations. (3) Award of... personal services. (4) Research activities and studies and routine data collection when such actions are... replacement or any lead based paint abatement actions regulated under the provisions of the Toxic Substances...

39 CFR 775.6 - Categorical exclusions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... that involve no commitment of resources other than manpower and funding allocations. (3) Award of... personal services. (4) Research activities and studies and routine data collection when such actions are... replacement or any lead based paint abatement actions regulated under the provisions of the Toxic Substances...

39 CFR 775.6 - Categorical exclusions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... that involve no commitment of resources other than manpower and funding allocations. (3) Award of... personal services. (4) Research activities and studies and routine data collection when such actions are... replacement or any lead based paint abatement actions regulated under the provisions of the Toxic Substances...

47 CFR 2.815 - External radio frequency power amplifiers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false External radio frequency power amplifiers. 2.815 Section 2.815 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.815...

47 CFR 2.815 - External radio frequency power amplifiers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false External radio frequency power amplifiers. 2.815 Section 2.815 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.815...

Into the 80s: Our Schools and Their Purposes.

ERIC Educational Resources Information Center

South Australia Education Dept., Adelaide.

Complementing existing regulations, this policy statement for South Australian schools presents educational goals and priorities for the decade and general implications for classroom, curriculum, and resource allocation. Background discussion covers factors influencing recent developments in South Australian education, a summary of the role of…

7 CFR 235.6 - Use of funds.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS STATE ADMINISTRATIVE EXPENSE FUNDS § 235.6 Use of funds. (a) Funds allocated... of Management and Budget Circular A-87. (c) In addition to State Administrative Expense funds made...

7 CFR 235.6 - Use of funds.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS STATE ADMINISTRATIVE EXPENSE FUNDS § 235.6 Use of funds. (a) Funds allocated... of Management and Budget Circular A-87. (c) In addition to State Administrative Expense funds made...

7 CFR 235.6 - Use of funds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS STATE ADMINISTRATIVE EXPENSE FUNDS § 235.6 Use of funds. (a) Funds allocated... of Management and Budget Circular A-87. (c) In addition to State Administrative Expense funds made...

7 CFR 235.6 - Use of funds.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS STATE ADMINISTRATIVE EXPENSE FUNDS § 235.6 Use of funds. (a) Funds allocated... of Management and Budget Circular A-87. (c) In addition to State Administrative Expense funds made...

7 CFR 235.6 - Use of funds.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS STATE ADMINISTRATIVE EXPENSE FUNDS § 235.6 Use of funds. (a) Funds allocated... of Management and Budget Circular A-87. (c) In addition to State Administrative Expense funds made...

Impact of physical maltreatment on the regulation of negative affect and aggression.

PubMed

Shackman, Jessica E; Pollak, Seth D

2014-11-01

Physically maltreated children are at risk for developing externalizing behavioral problems characterized by reactive aggression. The current experiment tested the relationships between individual differences in a neural index of social information processing, histories of child maltreatment, child negative affect, and aggressive behavior. Fifty boys (17 maltreated) performed an emotion recognition task while the P3b component of the event-related potential was recorded to index attention allocation to angry faces. Children then participated in a peer-directed aggression task. Negative affect was measured by recording facial electromyography, and aggression was indexed by the feedback that children provided to a putative peer. Physically maltreated children exhibited greater negative affect and more aggressive behavior, compared to nonmaltreated children, and this relationship was mediated by children's allocation of attention to angry faces. These data suggest that physical maltreatment leads to inappropriate regulation of both negative affect and aggression, which likely place maltreated children at increased risk for the development and maintenance of externalizing behavior disorders.

Investment choice and perceived mating intentions regulated by external resource cues and internal fluctuation in blood glucose levels

PubMed Central

Rao, Li-Lin; Wang, Xiao-Tian; Li, Shu

2015-01-01

We examined resource allocation priorities in the framework of an updated Maslow hierarchy of fundamental human needs. In Experiment 1, the participants in the food abundance priming condition viewing photos of high-calorie food allocated more money to savings than to spending. However, the participants preferred spending to savings under the condition of mating availability priming with romantic photographs. In Experiment 2, before and after drinking either water or a sugary beverage, fasting participants rated photos of a conversation between a man and a woman. Water drinking lowered the rating scores of mating intentions as well as blood glucose (BG) levels. The sugary drink buffered this decline in sexual perceptivity. Overall, the change in BG levels was positively associated with changes in the ratings of mating intentions but was not associated with other likelihood ratings. These results suggest that both external cues of food and mating resources and internal BG fluctuation regulate the cognitive priority of physiological needs vs. mate acquisition and retention. PMID:25610412

A fair share for the orphans: ethical guidelines for a fair distribution of resources within the bounds of the 10-year-old European Orphan Drug Regulation.

PubMed

Pinxten, Wim; Denier, Yvonne; Dooms, Marc; Cassiman, Jean-Jacques; Dierickx, Kris

2012-03-01

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and leave unanswered the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases.

Investment choice and perceived mating intentions regulated by external resource cues and internal fluctuation in blood glucose levels.

PubMed

Rao, Li-Lin; Wang, Xiao-Tian; Li, Shu

2014-01-01

We examined resource allocation priorities in the framework of an updated Maslow hierarchy of fundamental human needs. In Experiment 1, the participants in the food abundance priming condition viewing photos of high-calorie food allocated more money to savings than to spending. However, the participants preferred spending to savings under the condition of mating availability priming with romantic photographs. In Experiment 2, before and after drinking either water or a sugary beverage, fasting participants rated photos of a conversation between a man and a woman. Water drinking lowered the rating scores of mating intentions as well as blood glucose (BG) levels. The sugary drink buffered this decline in sexual perceptivity. Overall, the change in BG levels was positively associated with changes in the ratings of mating intentions but was not associated with other likelihood ratings. These results suggest that both external cues of food and mating resources and internal BG fluctuation regulate the cognitive priority of physiological needs vs. mate acquisition and retention.

Impact of physical maltreatment on the regulation of negative affect and aggression

PubMed Central

SHACKMAN, JESSICA E.; POLLAK, SETH D.

2015-01-01

Physically maltreated children are at risk for developing externalizing behavioral problems characterized by reactive aggression. The current experiment tested the relationships between individual differences in a neural index of social information processing, histories of child maltreatment, child negative affect, and aggressive behavior. Fifty boys (17 maltreated) performed an emotion recognition task while the P3b component of the event-related potential was recorded to index attention allocation to angry faces. Children then participated in a peer-directed aggression task. Negative affect was measured by recording facial electromyography, and aggression was indexed by the feedback that children provided to a putative peer. Physically maltreated children exhibited greater negative affect and more aggressive behavior, compared to nonmaltreated children, and this relationship was mediated by children’s allocation of attention to angry faces. These data suggest that physical maltreatment leads to inappropriate regulation of both negative affect and aggression, which likely place maltreated children at increased risk for the development and maintenance of externalizing behavior disorders. PMID:24914736

Histone modifications in the male germ line of Drosophila.

PubMed

Hennig, Wolfgang; Weyrich, Alexandra

2013-02-22

In the male germ line of Drosophila chromatin remains decondensed and highly transcribed during meiotic prophase until it is rapidly compacted. A large proportion of the cell cycle-regulated histone H3.1 is replaced by H3.3, a histone variant encoded outside the histone repeat cluster and not subject to cell cycle controlled expression. We investigated histone modification patterns in testes of D. melanogaster and D. hydei. In somatic cells of the testis envelope and in germ cells these modification patterns differ from those typically seen in eu- and heterochromatin of other somatic cells. During the meiotic prophase some modifications expected in active chromatin are not found or are found at low level. The absence of H4K16ac suggests that dosage compensation does not take place. Certain histone modifications correspond to either the cell cycle-regulated histone H3.1 or to the testis-specific variant H3.3. In spermatogonia we found H3K9 methylation in cytoplasmic histones, most likely corresponding to the H3.3 histone variant. Most histone modifications persist throughout the meiotic divisions. The majority of modifications persist until the early spermatid nuclei, and only a minority further persist until the final chromatin compaction stages before individualization of the spermatozoa. Histone modification patterns in the male germ line differ from expected patterns. They are consistent with an absence of dosage compensation of the X chromosome during the male meiotic prophase. The cell cycle-regulated histone variant H3.1 and H3.3, expressed throughout the cell cycle, also vary in their modification patterns. Postmeiotically, we observed a highly complex pattern of the histone modifications until late spermatid nuclear elongation stages. This may be in part due to postmeiotic transcription and in part to differential histone replacement during chromatin condensation.

Treatment with Myf5-morpholino results in somite patterning and brain formation defects in zebrafish.

PubMed

Chen, Yau-Hung; Tsai, Huai-Jen

2002-10-01

Myf-5 is a stage-dependent transcription factor associated with somitogenesis. To study its biological functions in zebrafish, we injected the Myf5-morpholinos ZMF-MO (antisense nucleotides 28 to 52) and ZMF-OTHER (antisense nucleotides 3 to 27) into zebrafish embryos to establish a myf-5 gene knockdown. No phenotypic abnormalities were observed following injection with 0.2 ng of ZMF-MO, but defects were displayed in 2 of 118 (1.7%) surviving embryos injected with 1 ng ZMF-MO. Morphological defects became more severe with increased dosages: 105 of 270 (38.9%) surviving embryos injected with 4.5 ng of ZMF-MO displayed such abnormalities as the absence of eyes or brains in addition to the following low-dosage defects in 24 hpf embryos: longitudinal yolk sacs, incomplete epiboly coverage, abnormal and suspended tail buds, diffused somite boundaries, and head shrinkage. Similar results were observed in the 4.5 ng ZMF-OTHER injection group. However, when fish were co-injected with 4.5 ng ZMF-MO and 4.5 ng myf-5 mRNA, abnormality rates decreased from 49.6% to 5.5%. Our results show that the brain krox20 gene was down-regulated at rhombomere 3; the pax2.1 gene was completely down-regulated; myoD was expressed normally; myogenin was substantially down-regulated in whole somites; and desmin was partly inhibited in newly forming somites. Our conclusion is that zebrafish Myf-5 may play important roles in brain formation and in the convergence and extension of shield epiblasts and tail buds during early embryogenesis, in addition to its well-understood role as a muscle regulatory factor in somites.

Perk Gene Dosage Regulates Glucose Homeostasis by Modulating Pancreatic β-Cell Functions

PubMed Central

Wang, Rong; Munoz, Elyse E.; Zhu, Siying; McGrath, Barbara C.; Cavener, Douglas R.

2014-01-01

Background Insulin synthesis and cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in either aspect leads to development of diabetes. PERK (EIF2AK3) loss of function mutations in humans and mice exhibit permanent neonatal diabetes that is characterized by insufficient β-cell mass and reduced proinsulin trafficking and insulin secretion. Unexpectedly, we found that Perk heterozygous mice displayed lower blood glucose levels. Methodology Longitudinal studies were conducted to assess serum glucose and insulin, intracellular insulin synthesis and storage, insulin secretion, and β-cell proliferation in Perk heterozygous mice. In addition, modulation of Perk dosage specifically in β-cells showed that the glucose homeostasis phenotype of Perk heterozygous mice is determined by reduced expression of PERK in the β-cells. Principal Findings We found that Perk heterozygous mice first exhibited enhanced insulin synthesis and secretion during neonatal and juvenile development followed by enhanced β-cell proliferation and a substantial increase in β-cell mass at the adult stage. These differences are not likely to entail the well-known function of PERK to regulate the ER stress response in cultured cells as several markers for ER stress were not differentially expressed in Perk heterozygous mice. Conclusions In addition to the essential functions of PERK in β-cells as revealed by severely diabetic phenotype in humans and mice completely deficient for PERK, reducing Perk gene expression by half showed that intermediate levels of PERK have a profound impact on β-cell functions and glucose homeostasis. These results suggest that an optimal level of PERK expression is necessary to balance several parameters of β-cell function and growth in order to achieve normoglycemia. PMID:24915520

Dynamic Control of Chromosome Topology and Gene Expression by a Chromatin Modification.

PubMed

Bian, Qian; Anderson, Erika C; Brejc, Katjuša; Meyer, Barbara J

2018-02-22

The function of chromatin modification in establishing higher-order chromosome structure during gene regulation has been elusive. We dissected the machinery and mechanism underlying the enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during Caenorhabditis elegans dosage compensation and discovered a key role for H4K20me1 in regulating X-chromosome topology and chromosome-wide gene expression. Structural and functional analysis of the dosage compensation complex (DCC) subunit DPY-21 revealed a novel Jumonji C demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Inactivation of demethylase activity in vivo by genome editing eliminated H4K20me1 enrichment on X chromosomes of somatic cells, increased X-linked gene expression, reduced X-chromosome compaction, and disrupted X-chromosome conformation by diminishing the formation of topologically associated domains. H4K20me1 is also enriched on the inactive X of female mice, making our studies directly relevant to mammalian development. Unexpectedly, DPY-21 also associates specifically with autosomes of nematode germ cells in a DCC-independent manner to enrich H4K20me1 and trigger chromosome compaction. Thus, DPY-21 is an adaptable chromatin regulator. Its H4K20me2 demethylase activity can be harnessed during development for distinct biological functions by targeting it to diverse genomic locations through different mechanisms. In both somatic cells and germ cells, H4K20me1 enrichment modulates three-dimensional chromosome architecture, demonstrating the direct link between chromatin modification and higher-order chromosome structure. © 2017 Bian et al.; Published by Cold Spring Harbor Laboratory Press.

An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming

PubMed Central

Radford, Elizabeth J.; Isganaitis, Elvira; Jimenez-Chillaron, Josep; Schroeder, Joshua; Molla, Michael; Andrews, Simon; Didier, Nathalie; Charalambous, Marika; McEwen, Kirsten; Marazzi, Giovanna; Sassoon, David; Patti, Mary-Elizabeth; Ferguson-Smith, Anne C.

2012-01-01

Environmental factors during early life are critical for the later metabolic health of the individual and of future progeny. In our obesogenic environment, it is of great socioeconomic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. Furthermore, it has also been suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypic heritability following early life insults. Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. We therefore analyse the role of imprinted genes in multiple tissues in two affected generations of an established murine model of the developmental origins of health and disease using microarrays and quantitative RT–PCR. We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. Nor do we find any evidence that the epigenetic reprogramming of ICRs in the germline is susceptible to nutritional restriction. However, we propose that those imprinted genes that are affected may play important roles in the foetal response to undernutrition and potentially its long-term sequelae. We suggest that recently described instances of dosage regulation by relaxation of imprinting are rare and likely to be highly regulated. PMID:22511876

Activity of closantel in the prevention of Gasterophilus and Strongylus vulgaris larval infections in equine foals and yearlings.

PubMed

Guerrero, J; Newcomb, K; Seibert, B P; Michael, B F

1985-01-01

Two controlled tests were conducted in equine foals and yearlings to determine the optimal oral dosage and the duration of activity of closantel for the prevention of Gasterophilus spp larval infections. Additional data were collected on the activity of closantel against Strongylus vulgaris larval infections. In experiment 1, 12 foals and 12 yearlings were equally allocated to 4 experimental groups, and were given oral treatments with closantel at dosages of 0 (nontreated controls), 2, 5, or 8 mg/kg of body weight every 2 months during bot season. The foals and yearlings were allowed to graze on open pasture throughout the experiment to provide a natural source for bot and helminth infections. All animals were euthanatized and necropsied 6 weeks after the final treatment. Closantel was highly effective (98.6% to 100%) at all doses in preventing Gasterophilus spp larval infections in the foals, but only the 8 mg/kg dose had significant (P less than 0.05) activity (99.7%) in the yearlings. This dose also significantly reduced the numbers of 4th-stage and immature adult S vulgaris (86.0%) in the mesenteric arteries as compared with nontreated controls. In experiment 2, 9 foals and 9 yearlings received a single oral treatment of 8 mg of closantel/kg of body weight; 3 foals and 3 yearlings were kept as nontreated controls. Groups of 6 treated (3 foals, 3 yearlings) and 2 control (1 foal, 1 yearling) animals were euthanatized and necropsied 1, 2, and 3 months after treatment. Closantel remained effective for 2 months in preventing infections of G intestinalis larvae in these foals and yearlings. Clinical signs of toxicosis were not observed in the treated animals of either study.

Evaluation of orally administered robenacoxib versus ketoprofen for treatment of acute pain and inflammation associated with musculoskeletal disorders in cats.

PubMed

Giraudel, Jerome M; Gruet, Philippe; Alexander, Debbie G; Seewald, Wolfgang; King, Jonathan N

2010-07-01

To evaluate the efficacy and tolerability of oral administration of robenacoxib for treatment of acute pain and inflammation associated with musculoskeletal disorders in cats. 155 cats requiring relief of signs of pain and inflammation associated with acute musculoskeletal disorders. The study was a multicenter, prospective, randomized, masked, noninferiority field trial. Cats were allocated randomly to 1 of 3 treatment groups: group 1 (1.0 to 2.4 mg of robenacoxib/kg, q 24 h), group 2 (1.0 to 2.4 mg of robenacoxib/kg, q 12 h [daily dosage, 2.0 to 4.8 mg/kg]), and group 3 (ketoprofen [mean dosage, 1 mg/kg, q 24 h]). All cats were administered tablets PO for 5 or 6 days. The primary efficacy endpoint was the investigator global assessment score, which was the sum of scores of signs of pain, inflammation, and mobility assessed in a masked manner by veterinary investigators at baseline, day 2, and day 4 or 5. Cat owners monitored in a nonmasked manner secondary responses by observation of cats' activity, behavior, appetite, and interactions. Safety was assessed by monitoring adverse events, clinical signs, and hematologic and plasma biochemical variables (before and after treatment). No significant differences were detected among the 3 treatment groups for any primary or secondary efficacy endpoints or for tolerability variables. Robenacoxib tablets administered once daily were significantly more palatable than ketoprofen tablets. Robenacoxib tablets administered once daily had noninferior efficacy and tolerability, and superior palatability, compared with the active control drug, ketoprofen, for the treatment of signs of acute pain and inflammation associated with musculoskeletal disorders in cats.

A randomised clinical trial on the efficacy of oxytetracycline dose through water medication of nursery pigs on diarrhoea, faecal shedding of Lawsonia intracellularis and average daily weight gain.

PubMed

Larsen, Inge; Hjulsager, Charlotte Kristiane; Holm, Anders; Olsen, John Elmerdahl; Nielsen, Søren Saxmose; Nielsen, Jens Peter

2016-01-01

Oral treatment with antimicrobials is widely used in pig production for the control of gastrointestinal infections. Lawsonia intracellularis (LI) causes enteritis in pigs older than six weeks of age and is commonly treated with antimicrobials. The objective of this study was to evaluate the efficacy of three oral dosage regimens (5, 10 and 20mg/kg body weight) of oxytetracycline (OTC) in drinking water over a five-day period on diarrhoea, faecal shedding of LI and average daily weight gain (ADG). A randomised clinical trial was carried out in four Danish pig herds. In total, 539 animals from 37 batches of nursery pigs were included in the study. The dosage regimens were randomly allocated to each batch and initiated at presence of assumed LI-related diarrhoea. In general, all OTC doses used for the treatment of LI infection resulted in reduced diarrhoea and LI shedding after treatment. Treatment with a low dose of 5mg/kg OTC per kg body weight, however, tended to cause more watery faeces and resulted in higher odds of pigs shedding LI above detection level when compared to medium and high doses (with odds ratios of 5.5 and 8.4, respectively). No association was found between the dose of OTC and the ADG. In conclusion, a dose of 5mg OTC per kg body weight was adequate for reducing the high-level LI shedding associated with enteropathy, but a dose of 10mg OTC per kg body weight was necessary to obtain a maximum reduction in LI shedding. Copyright © 2015 Elsevier B.V. All rights reserved.

Light Remodels Lipid Biosynthesis in Nannochloropsis gaditana by Modulating Carbon Partitioning between Organelles1[OPEN

PubMed Central

Vitulo, Nicola; Diretto, Gianfranco; Block, Maryse; Jouhet, Juliette; Meneghesso, Andrea; Valle, Giorgio; Giuliano, Giovanni; Maréchal, Eric

2016-01-01

The seawater microalga Nannochloropsis gaditana is capable of accumulating a large fraction of reduced carbon as lipids. To clarify the molecular bases of this metabolic feature, we investigated light-driven lipid biosynthesis in Nannochloropsis gaditana cultures combining the analysis of photosynthetic functionality with transcriptomic, lipidomic and metabolomic approaches. Light-dependent alterations are observed in amino acid, isoprenoid, nucleic acid, and vitamin biosynthesis, suggesting a deep remodeling in the microalgal metabolism triggered by photoadaptation. In particular, high light intensity is shown to affect lipid biosynthesis, inducing the accumulation of diacylglyceryl-N,N,N-trimethylhomo-Ser and triacylglycerols, together with the up-regulation of genes involved in their biosynthesis. Chloroplast polar lipids are instead decreased. This situation correlates with the induction of genes coding for a putative cytosolic fatty acid synthase of type 1 (FAS1) and polyketide synthase (PKS) and the down-regulation of the chloroplast fatty acid synthase of type 2 (FAS2). Lipid accumulation is accompanied by the regulation of triose phosphate/inorganic phosphate transport across the chloroplast membranes, tuning the carbon metabolic allocation between cell compartments, favoring the cytoplasm, mitochondrion, and endoplasmic reticulum at the expense of the chloroplast. These results highlight the high flexibility of lipid biosynthesis in N. gaditana and lay the foundations for a hypothetical mechanism of regulation of primary carbon partitioning by controlling metabolite allocation at the subcellular level. PMID:27325666

Study on the technology of dual-tube layered injection in ASP flooding

NASA Astrophysics Data System (ADS)

Yang, Ye; Zhang, Yongping; Xu, Dekui; Cai, Meng; Yang, Zhigang; Wang, Hailong; Song, Xingliang

2017-10-01

For the single-tube layered injection technology cannot solve the problem of interlayer pressure difference is greater than 2MPa injection wells, through the development of dual-tube packer, dual-tube injection allocator, downhole plug, the ground pressure regulator and molecular weight regulator. Dual-tube layered injection technology is formed. According to the data of ASP flooding injection wells in the field, the whole well is divided into high permeability and low permeability oil reservoir. Two separate injection channels can be formed by using dual-tube packer and dual-tube injection allocator. Through the use of the ground pressure regulator, the problem of the high permeability layer and low permeability layer of the injection pressure difference is solved. Through the use of the ground molecular weight regulator, the problem that the same molecular weight ASP solution is not suitable for high and low permeability is solved. By replacing the downhole plug, the grouping transformation of some oil layer can be achieved. The experiment and field application of 3 wells results show that: the flow control range is 20m3/d-70m3/d; the max. Throttling differential pressure is 3.5MPa; the viscosity loss rate of solution is less than 5%; and the molecular weight adjusting range is 20%-50%. The utilization degree of oil layer is obviously increased through the use of the dual-tube layered injection technology.

Mechanical Performance Test of Rubber-Powder Modified Concrete

NASA Astrophysics Data System (ADS)

Zhang, Yan Cong; Gao, Ling Ling

2018-06-01

A number of rubber cement concrete specimens that rubber powder dosage different were obtained using same cement, water and fine aggregates, by adjusting the dosage of rubber powder. Then it was used to research the influence of rubber powder dosage on performance of cement concrete by measuring its liquidity, strength and toughness. The results show that: when water-cement ratio was equal and rubber powder replacing the same volume sand, the fluidity of cement concrete almost linear increased with rubber powder dosage increasing. With dosage of rubber powder increasing, compressive strength and flexural strength reduced, but toughness linear growth trend when dosage of rubber powder less 30%.

The coming changes in tax-exempt health care finance.

PubMed

Carlile, L L; Serchuk, B M

1995-01-01

On December 30, 1994, the Internal Revenue Service (IRS) published proposed regulations (Proposed Regulations) that if enacted would significantly change the climate and rules of federal income tax law controlling the issuance and maintenance of tax-exempt bonds for governmental and 501(c)(3) health care borrowers. This article (1) summarizes the aspects of the Proposed Regulations dealing with private activity tests, management contracts, allocation and accounting rules, change in use of financed facilities, and antiabuse rules, and (2) summarizes the possible interrelationship of the IRS's audit program for tax-exempt bonds and the Proposed Regulations. The article reviews features of the Proposed Regulations that will affect either the costs or administrative burdens of managing the federal tax compliance of future tax-exempt health care borrowings.

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

48 CFR 352.231-70 - Precontract costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... entitled to reimbursement for allowable, allocable, and reasonable costs incurred during the period of... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Precontract costs. 352.231... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 352.231-70 Precontract costs. As...

15 CFR 303.7 - Issuance of licenses and shipment permits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS WATCHES....5 the Director shall issue a non-transferable license (Form ITA-333) to each producer. The Director shall also issue a replacement license if a producer's allocation is reduced pursuant to § 303.6. (2...

15 CFR 303.7 - Issuance of licenses and shipment permits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS WATCHES....5 the Director shall issue a non-transferable license (Form ITA-333) to each producer. The Director shall also issue a replacement license if a producer's allocation is reduced pursuant to § 303.6. (2...

48 CFR 1631.203-72 - Home office expense.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Home office expense. 1631... PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1631.203-72 Home office expense. A carrier's practices for allocating home office expenses to the segments of the carrier will be acceptable...

48 CFR 1631.203-72 - Home office expense.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Home office expense. 1631... PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1631.203-72 Home office expense. A carrier's practices for allocating home office expenses to the segments of the carrier will be acceptable...

48 CFR 1631.203-72 - Home office expense.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Home office expense. 1631... PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1631.203-72 Home office expense. A carrier's practices for allocating home office expenses to the segments of the carrier will be acceptable...

48 CFR 1631.203-72 - Home office expense.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Home office expense. 1631... PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1631.203-72 Home office expense. A carrier's practices for allocating home office expenses to the segments of the carrier will be acceptable...

48 CFR 1631.203-72 - Home office expense.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Home office expense. 1631... PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 1631.203-72 Home office expense. A carrier's practices for allocating home office expenses to the segments of the carrier will be acceptable...

Political Issues in Gifted Education

ERIC Educational Resources Information Center

Gallagher, James J.

2015-01-01

In this article, James J. Gallagher proposes that understanding the political issues and the debate surrounding the education of gifted students is based on the recognition that education policy (including rules, regulations, financial allocations, etc.) reflects social policy. Hence, society prioritizes needs so that the most important of these…

75 FR 43799 - Employee Contribution Elections and Contribution Allocations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... or deferred arrangements established for private-sector employees under section 401(k) of the... tribal governments and the private sector have been assessed. This regulation will not compel the..., or by the private sector. Therefore, a statement under Sec. 1532 is not required. Submission to...

47 CFR 2.813 - Transmitters operated in the Instructional Television Fixed Service.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Transmitters operated in the Instructional Television Fixed Service. 2.813 Section 2.813 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency...

47 CFR 2.813 - Transmitters operated in the Instructional Television Fixed Service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Transmitters operated in the Instructional Television Fixed Service. 2.813 Section 2.813 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency...

47 CFR 2.807 - Statutory exceptions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS AND RADIO TREATY MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.807 Statutory exceptions. As provided by Section 302(c) of the Communications Act of 1934, as amended, § 2.803 shall not be applicable to: (a...

15 CFR 700.7 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Compliance. 700.7 Section 700.7 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF... PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.7 Compliance. (a) Compliance with the provisions of this...

15 CFR 700.7 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Compliance. 700.7 Section 700.7 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF... PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.7 Compliance. (a) Compliance with the provisions of this...

Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury.

PubMed

Li, Haixia; Wang, Jingtao; Wang, Pengqian; Zhang, Yingying; Liu, Jun; Yu, Yanan; Li, Bing; Wang, Zhong

2018-01-01

Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed genes obtained in microarrays of mice belonging to four groups (Sham, Vehicle, JA, and 2·JA), aiming to elucidate differences in JA and 2·JA's dose-dependent pharmacological mechanism from a system's perspective. The top 10 enriched pathways in the 2·JA condition were mainly involved in neuroprotection (70% of the pathways), apoptosis and survival (40%), and anti-inflammation (20%), while JA induced pathways were mainly involved in apoptosis and survival (60%), anti-inflammation (20%), and lipid metabolism (20%). Regarding shared pathways and processes, 3, 1, and 3 pathways overlapped between the Vehicle and JA, Vehicle and 2·JA, and JA and 2·JA conditions, respectively; for the top ten overlapped processes these numbers were 3, 0, and 4, respectively. The common pathways and processes in the 2·JA condition included differentially expressed genes significantly different from those in JA. Seven representative pathways were only activated by 2·JA, such as Gamma-Secretase regulation of neuronal cell development. Process network comparison indicated that significant nodes, such as alpha-MSH , ACTH , PKR1 , and WNT , were involved in the pharmacological mechanism of 2·JA. Function distribution was different between JA and 2·JA groups, indicating a dosage additive mechanism in cerebral ischemia treatment. Such systemic approach based on whole-genome multiple pathways and networks may provide an effective and alternative approach to identify alterations underlining dosage-dependent therapeutic benefits of pharmacological compounds on complex disease processes.

Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster

PubMed Central

Schunter, Sarah; Villa, Raffaella; Flynn, Victoria; Heidelberger, Jan B.; Classen, Anne-Kathrin; Beli, Petra; Becker, Peter B.

2017-01-01

The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the ‘Non-Specific-Lethal’ (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF’s overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies. PMID:28510597

Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

PubMed

Schunter, Sarah; Villa, Raffaella; Flynn, Victoria; Heidelberger, Jan B; Classen, Anne-Kathrin; Beli, Petra; Becker, Peter B

2017-01-01

The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

[Differences of bi-directional regulative effects between acu-moxibustion and Chinese materia medica interventions].

PubMed

Cao, Xin; Yu, Zhi; Xu, Bin

2012-10-01

Bi-directional regulation is referred to a balancing effect of both acu-moxibustion and Chinese materia medica interventions when the human body is experiencing a hyperactivity or hypoactivity due to abnormal intrinsic or external factors. In the present paper, the authors analyze their identical and different characteristics from: 1) definition; 2) characters of regulative effects of acu-moxibustion therapy: A) differentiation of meridian and zangfu-organs being the basis of treatment, B) four factors (acupoint-location, body's functional state, acupoint-formula and needle-manipulation techniques) dependant, C) entirety regulation, and D) centrotaxis modulation; 3) characters of Chinese materia medica intervention: including a) correspondence between the drug property and the syndrome being the basis of the regulative effect, b) multi-factors [components (antagonist and agonist), combination, dosages and processing quality of Chinese materia medica, and functional state of the human body] dependant, c) entirety regulation, and d) both centrotaxis and deviation adjustment. In one word, the bi-directional regulation effect is one of the basic characteristics of both acu-moxibustion and Chinese materia medica in clinical practice, but their basis and modes for inducing effects are different.

Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

PubMed

Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

2011-01-01

The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of <3% and estimate the remaining medication volume with an accuracy of >98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The Development of Teaching Efficacy for Drug-Dosage Calculation Instruction: A Nursing Faculty Perspective

ERIC Educational Resources Information Center

Vitale, Gail A.

2011-01-01

The purpose of this study was to examine how nursing efficacy for drug-dosage calculation instruction is determined. Medication administration is a critical function of nurses in healthcare settings. An essential component of safe medication administration is accurate drug-dosage calculation, but instruction in drug-dosage calculation methods…

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...