Primordial nucleosynthesis

With the advent of the new extragalactic deuterium observations, Big Bang nucleosynthesis (BBN) is on the verge of undergoing a transformation. In the past, the emphasis has been on demonstrating the concordance of the BBN model with the abundances of the light isotopes extrapolated back to their primordial values by using stellar and galactic evolution theories. As a direct measure of primordial deuterium is converged upon, the nature of the field will shift to using the much more precise primordial D/H to constrain the more flexible stellar and galactic evolution models (although the question of potential systematic error in 4He abundance determinations remains open). The remarkable success of the theory to date in establishing the concordance has led to the very robust conclusion of BBN regarding the baryon density. This robustness remains even through major model variations such as an assumed first-order quark-hadron phase transition. The BBN constraints on the cosmological baryon density are reviewed and demonstrate that the bulk of the baryons are dark and also that the bulk of the matter in the universe is nonbaryonic. Comparison of baryonic density arguments from Lyman-α clouds, x-ray gas in clusters, and the microwave anisotropy are made.

Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited blinding diseases caused by mutations in multiple genes including RDS. RDS encodes rds/peripherin (rds), a 36-kDa glycoprotein in the rims of rod and cone outer-segment (OS) discs. Rom1 is related to rds with similar membrane topology and the identical distribution in OS. In contrast to RDS, no mutations in ROM1 alone have been associated with retinal disease. However, an unusual digenic form of RP has been described. Affected individuals in several families were doubly heterozygous for a mutation in RDS causing a leucine 185 to proline substitution in rds (L185P) and a null mutation in ROM1. Neither mutation alone caused clinical abnormalities. Here, we generated transgenic/knockout mice that duplicate the amino acid substitutions and predicted levels of rds and rom1 in patients with RDS-mediated digenic and dominant RP. Photoreceptor degeneration in the mouse model of digenic RP was faster than in the wild-type and monogenic controls by histological, electroretinographic, and biochemical analysis. We observed a positive correlation between the rate of photoreceptor loss and the extent of OS disorganization in mice of several genotypes. Photoreceptor degeneration in RDS-mediated RP appears to be caused by a simple deficiency of rds and rom1. The critical threshold for the combined abundance of rds and rom1 is ≈60% of wild type. Below this value, the extent of OS disorganization results in clinically significant photoreceptor degeneration.

ATPase activity of Escherichia coli Rep helicase crosslinked to single-stranded DNA: implications for ATP driven helicase translocation.

To examine the coupling of ATP hydrolysis to helicase translocation along DNA, we have purified and characterized complexes of the Escherichia coli Rep protein, a dimeric DNA helicase, covalently crosslinked to a single-stranded hexadecameric oligodeoxynucleotide (S). Crosslinked Rep monomers (PS) as well as singly ligated (P2S) and doubly ligated (P2S2) Rep dimers were characterized. The equilibrium and kinetic constants for Rep dimerization as well as the steady-state ATPase activities of both PS and P2S crosslinked complexes were identical to the values determined for un-crosslinked Rep complexes formed with dT16. Therefore, ATP hydrolysis by both PS and P2S complexes are not coupled to DNA dissociation. This also rules out a strictly unidirectional sliding mechanism for ATP-driven translocation along single-stranded DNA by either PS or the P2S dimer. However, ATP hydrolysis by the doubly ligated P2S2 Rep dimer is coupled to single-stranded DNA dissociation from one subunit of the dimer, although loosely (low efficiency). These results suggest that ATP hydrolysis can drive translocation of the dimeric Rep helicase along DNA by a "rolling" mechanism where the two DNA binding sites of the dimer alternately bind and release DNA. Such a mechanism is biologically important when one subunit binds duplex DNA, followed by subsequent unwinding.

A joint hazard and time scaling model to compare survival curves.

To provide a more general method for comparing survival experience, we propose a model that independently scales both hazard and time dimensions. To test the curve shape similarity of two time-dependent hazards, h1(t) and h2(t), we apply the proposed hazard relationship, h12(tKt)/ h1(t) = Kh, to h1. This relationship doubly scales h1 by the constant hazard and time scale factors, Kh and Kt, producing a transformed hazard, h12, with the same underlying curve shape as h1. We optimize the match of h12 to h2 by adjusting Kh and Kt. The corresponding survival relationship S12(tKt) = [S1(t)]KtKh transforms S1 into a new curve S12 of the same underlying shape that can be matched to the original S2. We apply this model to the curves for regional and local breast cancer contained in the National Cancer Institute's End Results Registry (1950-1973). Scaling the original regional curves, h1 and S1 with Kt = 1.769 and Kh = 0.263 produces transformed curves h12 and S12 that display congruence with the respective local curves, h2 and S2. This similarity of curve shapes suggests the application of the more complete curve shapes for regional disease as templates to predict the long-term survival pattern for local disease. By extension, this similarity raises the possibility of scaling early data for clinical trial curves according to templates of registry or previous trial curves, projecting long-term outcomes and reducing costs. The proposed model includes as special cases the widely used proportional hazards (Kt = 1) and accelerated life (KtKh = 1) models.

Targeted disruption of the Rad51 gene leads to lethality in embryonic mice.

The mouse Rad51 gene is a mammalian homologue of the Escherichia coli recA and yeast RAD51 genes, both of which are involved in homologous recombination and DNA repair. To elucidate the physiological role of RAD51 protein, the gene was targeted in embryonic stem (ES) cells. Mice heterozygous for the Rad51 null mutation were intercrossed and their offspring were genotyped. There were no homozygous (Rad51-/-) pups among 148 neonates examined but a few Rad51-/- embryos were identified when examined during the early stages of embryonic development. Doubly knocked-out ES cells were not detected under conditions of selective growth. These results are interpreted to mean that RAD51 protein plays an essential role in the proliferation of cell. The homozygous Rad51 null mutation can be categorized in cell-autonomous defects. Pre-implantational lethal mutations that disrupt basic molecular functions will thus interfere with cell viability.

The presence of codon-anticodon pairs in the acceptor stem of tRNAs.

A total of 1268 available (excluding mitochondrial) tRNA sequences was used to reconstruct the common consensus image of their acceptor domains. Its structure appeared as a 11-bp-long double-stranded palindrome with complementary triplets in the center, each flanked by the 3'-ACCD and NGGU-5' motifs on each strand (D, base determinator). The palindrome readily extends up to the modern tRNA-like cloverleaf passing through an intermediate hairpin having in the center the single-stranded triplet, in supplement to its double-stranded precursor. The latter might represent an original anticodon-codon pair mapped at 1-2-3 positions of the present-day tRNA acceptors. This conclusion is supported by the striking correlation: in pairs of consensus tRNAs with complementary anticodons, their bases at the 2nd position of the acceptor stem were also complementary. Accordingly, inverse complementarity was also evident at the 71st position of the acceptor stem. With a single exception (tRNA(Phe)-tRNA(Glu) pair), the parallelism is especially impressive for the pairs of tRNAs recognized by aminoacyl-tRNA synthetases (aaRS) from the opposite classes. The above complementarity still doubly presented at the key central position of real single-stranded anticodons and their hypothetical double-stranded precursors is consistent with our previous data pointing to the double-strand use of ancient RNAs in the origin of the main actors in translation- tRNAs with complementary anticodons and the two classes of aaRS.

The putative actin-binding role of hydrophobic residues Trp546 and Phe547 in chicken gizzard heavy meromyosin.

In the course of myosin-catalyzed ATP hydrolysis, certain amino acid residues in myosin interact with counterparts in actin to produce the relational changes that underlie muscle contraction; some of these interactions are ionic, but the stronger interactions are hydrophobic. In an effort to identify myosin residues participating in hydrophobic interactions, myosin (from smooth muscle) fragments with mutations at suspected sites were engineered and compared with wild-type fragments. It was found that the ATPase of doubly mutated (Trp546Ser and Phe547His) fragments was minimally activated by actin and did not decorate actin well to form the regular arrowhead pattern characteristic of myosin binding to actin filaments. Thus, we suggest that Trp546 and Phe547 are important participants in the hydrophobic actin-myosin interaction.

Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E.

To develop a murine model system to test the role of monocyte-derived macrophage in atherosclerosis, the osteopetrotic (op) mutation in the macrophage colony-stimulating factor gene was bred onto the apolipoprotein E (apoE)-deficient background. The doubly mutant (op/apoE-deficient) mice fed a low-fat chow diet had significantly smaller proximal aortic lesions at an earlier stage of progression than their apoE-deficient control littermates. These lesions in the doubly mutant mice were composed of macrophage foam cells. The op/apoE-deficient mice also had decreased body weights, decreased blood monocyte differentials, and increased mean cholesterol levels of approximately 1300 mg/dl. Statistical analysis determined that atherosclerosis lesion area was significantly affected by the op genotype and gender. The confounding variables of body weight, plasma cholesterol, and monocyte differential, which were all affected by op genotype, had no significant additional effect on lesion area once they were adjusted for the effects of op genotype and gender. Unexpectedly, there was a significant inverse correlation between plasma cholesterol and lesion area, implying that each may be the result of a common effect of macrophage colony-stimulating factor levels. The data support the hypothesis that macrophage colony-stimulating factor and its effects on macrophage development and function play a key role in atherogenesis.

The Role of Hope in Rehabilitation and Long-term Outcomes among patients with Comorbid Spinal Cord and Traumatic Brain Injuries.

Spinal cord injury (SCI) and traumatic brain injury (TBI) are two potentially devastating conditions alone; when they co-occur in an individual they can be doubly so. The role of hope in rehabilitating oneself and recovering emotionally is examined in this paper. More specifically, Snyder's Model of Hope (1991) is examined as a tool that can aid in the rehabilitative process and help treatment providers, their patients, and the families of patients keep hope alive during a time of physical and emotional upheaval. This paper further examines the roles of hope in a rehabilitation program at Craig Hospital, a private, non-profit hospital dedicated exclusively to the rehabilitation of SCIs and TBIs and designated as a TBI and SCI Model Systems Center.

L'évolution des voix/voies de femmes dans leurs écrits sur l'Église aux XVIIe et XVIIIe siècles

Feminist movements have allowed many female authors to become decisive and influential figures in literary history by studying their experiences, voices and forms of resistance. This thesis, however, focuses specifically on religious women, those seeking divine comfort outside the confines of institutional laws, or those who, out of protest, are caught in the middle. Founded on historical and feminist perspectives, this study examines the heterodox resistance of six French women living within or outside of Church boundaries during the 17th and 18th centuries: two eras that are particularly significant for women’s progress and modernity. This work strives to demonstrate how these women, doubly subjected to Church discourse and that of society, managed to live out their vocation (female and Christian) and make social, cultural and religious statements that contributed to changing the place of women in society. It aims to grasp the similarities and differences between the actions and ideas of women belonging to both the religious and secular spheres. Regardless of the century, the space and their background, women resist to masculine, patriarchal, ecclesial, political and social mediation and institutions. In locating examples of how they oppose the practices, rules and constraints that are imposed upon them, as well as of their exclusion from the socio-political space, this thesis also seeks to identify epistemological changes that mark the transition from the 17th to the 18th century. This thesis firstly outlines the necessary feminist theory upon which the project is based before identifying the evolution of women’s positions within the socio-ideological and political framework in which they lived. The questions of confession and spiritual direction are of particular interest since they serve as prime examples of masculine mediation and its issues and consequences – most notably the control of the female body and mind. The illustration of bodily metamorphoses bear testament to ideological changes, cultural awareness and female subjectivity, just as the scriptural inscriptions of unorthodox ideas and writing. The female body, both object and subject of the quest for individual and collective liberties, attests, in this way, to the movement towards Enlightenment values of freedom and justice.

Caractérisation bioinformatique des nouvelles protéines mitochondriales chez les moules d’eau douce (Bivalvia : Unionoida)

Malgré que le contenu des génomes mitochondriaux animaux soit dit bien conservé, des nouveaux gènes mitochondriaux ont été identifiés chez plusieurs espèces, surtout des invertébrés. Par exemple, les bivalves exhibant la double transmission uniparentale de leurs génomes mitochondriaux possèdent des nouveaux gènes spécifiques au sexe (M-ORF dans l’ADN de type M, F-ORF dans l’ADN de type F) qui ont été caractérisés in silico chez trois espèces de l’ordre Mytiloida, une espèce de Veneroida et une espèce de Unionoida par une précédente étude. Même si les séquences varient beaucoup entre ces trois ordres, cette étude à montré que des hélices transmembranaires ainsi que des peptides signaux sont conservés pour toutes les séquences. L’étude a aussi montré que les nouveaux gènes pourraient avoir des rôles dans la signalisation cellulaire, le cycle cellulaire et la réponse immunitaire et qu’ils pourraient être le résultat de l’endogénisation de l’ADN viral. Le projet présenté ici a pour but de mieux caractériser ces nouveaux gènes et leur origine potentielle, en plus d’étudier le H-ORF particulier aux hermaphrodites, en ciblant les espèces des unionidés. Les résultats montrent que les hélices transmembranaires et peptides signaux sont conservés chez les unionidés, les protéines semblent être associées à la membrane et être capables de lier des acides nucléiques et protéines, et les fonctions potentielles sont conservées. Les M-ORFs semblent avoir un rôle dans le transport et des processus cellulaires tels que la signalisation, le cycle cellulaire et la division, et l’organisation du cytosquelette. Les F-ORFs semblent être impliqués dans le trafic et transport cellulaire et la réponse immunitaire. Finalement, les H-ORFs semblent être des glycoprotéines structurales avec des rôles dans la signalisation, le transport et la transcription. Les résultats de ce projet pourraient supporter une origine virale ou mitochondriale pour ces gènes.

Effects of fiscal consolidations in Latin America

We use new data on cyclically adjusted primary balances for Latin America and the Caribbean to estimate e ects of scal consolidations on GDP and some of its components. Identi cation is conducted through a doubly-robust estimation procedure that controls for non-randomness in the "treatment assignment" by inverse probability weighting and impulse responses are generated by local projections. Results suggest output contraction by more than one percent on impact, with economy starting to recover from the second year on. Composition e ects indicate that revenue-based adjustments are way more contractionary than expenditure-based ones. Disentangling efects between demand components, we nd consumption being in general less responsive to consolidations than investment, although nonlinearities associated to initial levels of debt and taxation might play an important role.

Caractérisation bioinformatique des nouvelles protéines mitochondriales chez les moules d’eau douce (Bivalvia : Unionoida).

Malgré que le contenu des génomes mitochondriaux animaux soit dit bien conservé, des nouveaux gènes mitochondriaux ont été identifiés chez plusieurs espèces, surtout des invertébrés. Par exemple, les bivalves exhibant la double transmission uniparentale de leurs génomes mitochondriaux possèdent des nouveaux gènes spécifiques au sexe (M-ORF dans l’ADN de type M, F-ORF dans l’ADN de type F) qui ont été caractérisés in silico chez trois espèces de l’ordre Mytiloida, une espèce de Veneroida et une espèce de Unionoida par une précédente étude. Même si les séquences varient beaucoup entre ces trois ordres, cette étude à montré que des hélices transmembranaires ainsi que des peptides signaux sont conservés pour toutes les séquences. L’étude a aussi montré que les nouveaux gènes pourraient avoir des rôles dans la signalisation cellulaire, le cycle cellulaire et la réponse immunitaire et qu’ils pourraient être le résultat de l’endogénisation de l’ADN viral. Le projet présenté ici a pour but de mieux caractériser ces nouveaux gènes et leur origine potentielle, en plus d’étudier le H-ORF particulier aux hermaphrodites, en ciblant les espèces des unionidés. Les résultats montrent que les hélices transmembranaires et peptides signaux sont conservés chez les unionidés, les protéines semblent être associées à la membrane et être capables de lier des acides nucléiques et protéines, et les fonctions potentielles sont conservées. Les M-ORFs semblent avoir un rôle dans le transport et des processus cellulaires tels que la signalisation, le cycle cellulaire et la division, et l’organisation du cytosquelette. Les F-ORFs semblent être impliqués dans le trafic et transport cellulaire et la réponse immunitaire. Finalement, les H-ORFs semblent être des glycoprotéines structurales avec des rôles dans la signalisation, le transport et la transcription. Les résultats de ce projet pourraient supporter une origine virale ou mitochondriale pour ces gènes.

Illustrations of political economy.

v. 1. Life in the wilds. The hill and the valley. Brooke and Brooke farm.--v. 2. Demerara. Ella of Garveloch. Weal and woe in Garveloch.--v. 3. A Manchester strike. Cousin Marshall. Ireland.--v. 4. Homes abroad. For each and for all. French wines and politics.--v. 5. The charmed sea. Berkeley the banker. In two parts.--v. 6. Messrs. Vanderput and Snoek. The loom and the lugger. In two parts.--v. 7. Sowers not reapers. Cinnamon and pearls. A tale of the Tyne.--v. 8. Briery Creek. The three ages.--v. 9. The Farrers of Budge-row. The moral of many fables.--v. 10-11 Illustrations of taxation.

Quantum interference effects in a cavity QED system

We consider the effect of quantum interference on population distribution and photon statistics of a cavity field interacting with dressed states of a strongly driven three-level atom. We analyse three coupling configurations of the cavity field to the driven atom, with the cavity frequency tuned to the outer Rabi sideband, the inner Rabi sideband and the central frequency of the 'singly dressed' three-level atom. The quantum doubly dressed states for each configuration are identified and the population distribution and photon statistics are interpreted in terms of transitions among these dressed states and their populations. We find that the population distribution depends strongly on quantum interference and the cavity damping. For the cavity field tuned to the outer or inner Rabi sidebands the cavity damping induces transitions between the dressed states which are forbidden for the ordinary spontaneous emission. Moreover, we find that in the case of the cavity field coupled to the inner Rabi sideband the population distribution is almost Poissonian with a large average number of photons that can be controlled by quantum interference. This system can be considered as a one-atom dressed-state laser with controlled intensity.