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Search Results: 1 - 10 of 2084 matches for " Gerald Salen "
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The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension
Jianliang Chen, Ashok Batta, Shuqin Zheng, Wayne R Fitzgibbon, Michael E Ullian, Hongwei Yu, Patrick Tso, Gerald Salen, Shailendra B Patel
BMC Genetics , 2005, DOI: 10.1186/1471-2156-6-40
Abstract: To investigate whether the missense change in Abcg5 is responsible for the sitosterolemia we performed a segregation analysis in 103 F2 rats from a SHR × SD cross. Additionally, we measured tail-cuff blood pressure and measured intestinal lipid transport to identify possible mechanisms whereby this mutation causes sitosterolemia.Segregation analysis showed that the inheritance of the Gly583Cys mutation Abcg5 segregated with elevated plant sterols and this pattern was recessive, proving that this genetic change is responsible for the sitosterolemia in these rat strains. Tail-cuff monitoring of blood pressure in conscious animals showed no significant differences between wild-type, heterozygous and homozygous mutant F2 rats, suggesting that this alteration may not be a significant determinant of hypertension in these rats on a chow diet.This study shows that the previously identified Gly583Cys change in Abcg5 in three hypertension-susceptible rats is responsible for the sitosterolemia, but may not be a major determinant of blood pressure in these rats.Sitosterolemia is an autosomal recessive disease, characterized by significantly increased plasma levels of plant sterols (such as sitosterol, campesterol), and is associated with premature atherosclerotic disease [1]. This disease has been mapped to a single locus, STSL, on human chromosome 2p21 [2,3]. Mutations in both alleles of one of two genes, ABCG5 or ABCG8, that comprise this locus, are now known to cause this disease [4-6]. No phytosterolemic patient with a single mutant ABCG5 allele and a mutant ABCG8 allele has been reported, suggesting these genes are not only linked physically, but their protein products may act as obligate heterodimers. ABCG5 and ABCG8 encode for sterolin-1 and sterolin-2 respectively. These genes are expressed in the liver, gall bladder and intestine and are implicated in determining biliary sterol excretion and selectivity of sterol absorption at the apical surfaces of the enterocytes [7-
New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids
Michel de Lorgeril, Patricia Salen
BMC Medicine , 2012, DOI: 10.1186/1741-7015-10-50
Abstract: Cardiovascular disease (CVD) is a leading cause of death in most countries. Reducing saturated fatty acid (SFA) intakes is still at the heart of dietary recommendations to reduce CVD, mainly because of its effect on blood cholesterol [1]. This view has recently been challenged. First, a review of epidemiological studies failed to conclude that SFAs are associated with an increased risk of CVD [2]. Second, the validity of meta-analyses of clinical trials showing that CVD can be prevented by replacing SFAs with polyunsaturated fatty acids (PUFAs) has been questioned [3,4] because they omitted relevant trials with unfavorable outcomes (selection bias) and included others that were poorly designed (no randomization) [5,6]. Third, it has been claimed that the effect of diet on a single biomarker (such as plasma cholesterol) is insufficient evidence to assess CVD risk [7]. Fourth, the hypothetical protective effect of omega-6 PUFAs has been said to be considerably exaggerated [8,9], because of the failure to draw a line between the trials that selectively increased omega-6 PUFAs and those that substantially increased omega-3 PUFAs - known to reduce CVD risk [10,11] - together with omega-6 PUFAs to replace SFAs [3,4]. Finally, clinical and epidemiological studies exploring the dietary fat issue failed to provide a clear biological understanding of the effect of the various dietary fats on the risk of CVD.There is one exception: the Mediterranean diet [12], which is a complex interplay between the different series of dietary lipids, including conjugated or non-conjugated (animal or industrial) trans fatty acids, short-, medium- and long-chain SFAs, various series - at least the omega-7 and omega-9 - of monounsaturated fatty acids, and the various series of PUFAs, including omega-3 and omega-6 [12,13]. All these lipids and their interactions should be taken into account when analyzing the effect of dietary fat on CVD complications and mortality. Besides the Mediterranean die
The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats
Hongwei Yu, Bhaswati Pandit, Eric Klett, Mi-Hye Lee, Kangmo Lu, Khalil Helou, Ikuo Ikeda, Nami Egashira, Masao Sato, Richard Klein, Ashok Batta, Gerald Salen, Shailendra B Patel
BMC Cardiovascular Disorders , 2003, DOI: 10.1186/1471-2261-3-4
Abstract: To investigate whether mutations in Abcg5 or Abcg8 exist in SHR, SHRSP, WKY and GH rats, we initiated a systematic search for the genetic variation in coding and non-coding region of Abcg5 and Abcg8 genes in these strains. We isolated the rat cDNAs for these genes and characterized the genomic structure and tissue expression patterns, using standard molecular biology techniques and FISH for chromosomal assignments.Both rat Abcg5 and Abcg8 genes map to chromosome band 6q12. These genes span ~40 kb and contain 13 exons and 12 introns each, in a pattern identical to that of the STSL loci in mouse and man. Both Abcg5 and Abcg8 were expressed only in liver and intestine. Analyses of DNA from SHR, SHRSP, GH, WKY, Wistar, Wistar King A (WKA) and Brown Norway (BN) rat strains revealed a homozygous G to T substitution at nucleotide 1754, resulting in the coding change Gly583Cys in sterolin-1 only in rats that are both sitosterolemic and hypertensive (SHR, SHRSP and WKY).The rat STSL locus maps to chromosome 6q12. A non-synonymous mutation in Abcg5, Gly583Cys, results in sitosterolemia in rat strains that are also hypertensive (WKY, SHR and SHRSP). Those rat strains that are hypertensive, but not sitosterolemic (e.g. GH rat) do not have mutations in Abcg5 or Abcg8. This mutation allows for expression and apparent apical targeting of Abcg5 protein in the intestine. These rat strains may therefore allow us to study the pathophysiological mechanisms involved in the human disease of sitosterolemia.The human disorder of sitosterolemia, also known as phytosterolemia (MIM 210250), is an autosomal recessive disorder characterized by the marked elevation of plasma phytosterols e.g. β-sitosterol, campesterol and stigmasterol [1,2]. Hypercholesterolemia primarily during childhood, accelerated atherosclerosis in some adult patients leading to premature death, as well a hemolytic anaemia, arthralgias and tendon and tuberous xanthoma formations are other clinical features. Studies have sho
Rupture sismique des fondations par perte de capacité portante: Le cas des semelles circulaires
Charisis Chatzigogos,Alain Pecker,J. Salen?on
Physics , 2008,
Abstract: Within the context of earthquake-resistant design of shallow foundations, the present study is concerned with the determination of the seismic bearing capacity of a circular footing resting on the surface of a heterogene-ous purely cohesive semi-infinite soil layer. In the first part of the paper, a database, containing case histories of civil engineering structures that sustained a foundation seismic bearing capacity failure, is briefly pre-sented, aiming at a better understanding of the studied phenomenon and offering a number of case studies useful for validation of theoretical computations. In the second part of the paper, the aforementioned problem is addressed using the kinematic approach of the Yield Design theory, thus establishing optimal upper bounds for the ultimate seismic loads supported by the soil-footing system. The results lead to the establishment of some very simple guidelines that extend the existing formulae for the seismic bearing capacity contained in the European norms (proposed for strip footings on homogeneous soils) to the case of circular footings and to that of heterogeneous cohesive soils.
A Macro-Element for Dynamic Soil-Structure Interaction Analyses of Shallow Foundations
Charisis Chatzigogos,Alain Pecker,Jean Salen?on
Physics , 2008,
Abstract: The scope of the paper is to present some aspects of the development of a "macro-element" for dynamic soil-structure interaction analyses of shallow foundations. Initially the concept of "macro-element" is introduced and is illustrated with the aid of a very simple example originating from structural engineering. Then the link is made with the modeling of the dynamic response of shallow foundations and the objectives and structure of such a tool are described with reference to the specific configuration of a circular footing resting on the surface of a heterogeneous purely cohesive soil. The principal features of the "macro-element" are then presented; the soil-structure interaction domain is reduced to a point that coincides with the center of the footing and all the (material and geometric) non-linearities are lumped at this point. A discussion on the most appropriate way to treat these non-linearities is undertaken based on experience gained with earlier works. It is suggested that the non-linearities be incorporated in the model within a unified formalism making use of the theory of multi-mechanism plasticity. Initial results concerning the definition of the ultimate surface for such a plasticity model, corresponding to the seismic bearing capacity of the foundation, are finally presented.
Macroelement modeling of shallow foundations
Charisis Chatzigogos,Alain Pecker,J. Salen?on
Physics , 2008,
Abstract: The paper presents a new macroelement model for shallow foundations. The model is defined through a non-linear constitutive law written in terms of some generalized force and displacement parameters. The linear part of this constitutive law comes from the dynamic impedances of the foundation. The non-linear part comprises two mechanisms. One is due to the irreversible elastoplastic soil behavior: it is described with a bounding surface hypoplastic model, adapted for the description of the cyclic soil response. An original feature of the formulation is that the bounding surface is considered independently of the surface of ultimate loads of the system. The second mechanism is the detachment that can take place at the soil-footing interface (foundation uplift). It is totally reversible and non-dissipative and can thus be described by a phenomenological non-linear elastic model. The macroelement is qualitatively validated by application to soil-structure interaction analyses of simple real structures.
Attosecond-Scale Probing of the Electron Motion in the H-Atom Groundstate  [PDF]
Gerald Rosen
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.312230
Abstract: Based on recent advances in attosecond strong-field spectroscopy and the current feasibility for trapping individual groundstate H-atoms from a neon-gas matrix, an experiment to probe the groundstate motion of the electron in the H-atom is proposed here.
A Mathematical Proof: Focus during Weekdays Should Be on Supply for the Sabbath a Support for Workable Competition  [PDF]
Gerald Aranoff
Modern Economy (ME) , 2012, DOI: 10.4236/me.2012.38116
Abstract: This paper proves mathematically in a defined model with restrictive assumptions that consumers are better off when they have more food for the Sabbath at the expense of having less food for the other six days of the week! Like the manna that fell from heaven for forty years in the desert—an omer to a person, Sunday through Friday with double portions on Friday—we assume that consumers buy standardized semi-perishable food baskets, one basket per person per day, Sunday through Friday with extra baskets for the Sabbath. We analyze benefits to consumers according to two alternative pricing schemes, whereby consumer expenditures and weekly food consumed are the same. We prove that consumers are better off according to the pricing scheme that allows for more food for the Sabbath day. This agrees with business cycle theories that urge social focus on increasing and prolonging cyclical peaks. This supports John M. Clark’s workable competition thesis and will surprise supporters of SR marginal-cost pricing.
A Model Illustrating Consumer Inconstancy: Demand and Supply Sides  [PDF]
Gerald Aranoff
Modern Economy (ME) , 2013, DOI: 10.4236/me.2013.412088
Abstract:

John M. Clark in his classic 1923 Economics of Overhead Costs asks if anyone knows what it costs to supply demand irregularity. He also asks if consumers need demand irregularity, consciously or unconsciously. We provide a model for a plausible theoretical basis to begin to answer each question. The models permit mathematical proofs and graphic demonstrations of the costs to society of supplying for demand irregularity and of the willingness to pay on the part of consumers for demand irregularity. JEL (D24).

 

A Model of Manufacturers and Buyers of Cars over the Business Cycle Illustrating Competitive Manufacturing  [PDF]
Gerald Aranoff
Theoretical Economics Letters (TEL) , 2014, DOI: 10.4236/tel.2014.47070
Abstract:

We illustrate competitive manufacturing with an original theoretical model of manufacturers and buyers of cars over a business cycle that have peak and off-peak demand periods. There are two types of plants manufacturing cars, plantK and plantL, each having linear total costs with absolute capacity limits. PlantK operates with low VC and high FC by being capital intensive. PlantK is output-rates rigid since it produces throughout the business cycle and always at capacity. PlantL operates with low FC and high VC by relying on outsourcing major components and parts. PlantL is output-rates flexible since it produces only in the peak-demand periods. We show results under SRMC pricing. Then we examine an alternate arrangement which

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