Essays in Household and Demographic Economics

This dissertation consists of three empirical studies that are believed to provide new contributions to the literature exploring the determinants of children/adolescents achievement test scores (Chapter 2), adolescent health risk behaviors (Chapter 3), and children time use patterns (Chapter 4). The second and third studies look at the separate roles of fathers and of mothers in influencing outcomes, wherein parental time is the resource input of interest quantitatively measured and directly derived from time diaries. The last chapter looks at the time allocation of children and how it varies according to child and household characteristics.

Simulazione di front-end GPS per la verifica di algoritmi di navigazione per satelliti LEO

Descrizione di un software di simulazione, realizzato attraverso la programmazione in Labview, che estrapola i dati immagazzinati nei file RINEX di navigazione e di osservazione della missione GRACE e li invia con le stesse modalità con cui lo farebbe il ricevitore OEM615 della NovAtel. L'obiettivo è creare un software che permetta di testare, nell'ambito della missione ESEO dell'ESA, il ricevitore GPS che farà parte del payoload della stessa missione, costituita da un micro-satellite che orbiterà in orbita bassa LEO, e che sarà composto da un ricevitore OEM615, da un'antenna GPS e da un processore di navigazione.

Sintesi e caratterizzazione di sistemi catalitici a base di pd-cu e loro utilizzo nella reazione di idrodeclorurazione di molecole clorofluorurate

Questo lavoro di tesi ha avuto come obiettivo quello di individuare e studiare diverse strategie di sintesi per la preparazione di catalizzatori a base di Pd-Cu supportati su materiali mesoporosi a basi di SiO2. Queste strategie sono state mirate a migliorare: -Distribuzione della fase metallica attiva e la sua accessibilità; -Formazione della fase mista Pd-Cu; -Dimensione delle specie metalliche sulla superficie; -Differenti caratteristiche morfologiche del supporto. I diversi catalizzatori preparati sono stati poi testati sulla reazione di idrodeclorurazione del 1,2-dicloro-1,1,2-trifluoro-2-(triflurometossi)etano (AM), svolta in fase gas con idrogeno a pressione atmosferica, con lo scopo di ottenere il composto insaturo corrispondente 1,1,2-trifluoro-2-(trifluorometossi)etene (MVE). Attualmente, il processo industriale per la produzione di MVE, è condotto con l’utilizzo di quantità stechiometriche di Zn in dimetilformammide; questo processo a causa delle quantità stechiometriche di ZnCl2 prodotto e dell'elevato consumo di solvente tossico risulta assai dispendioso dal punto di vista economico ed ambientale. La tipologia di materiali microporosi, già investigata, può limitare l'efficienza verso substrati ingombranti, è quindi interessante investigare catalizzatori con dimensione dei pori mesoporosi a base di silice; in particolare sono stati analizzati MCM-41 e silice amorfa GRACE® DAVICAT - 1401. In particolare, durante il lavoro di tesi sono stati sviluppati i seguenti argomenti: 1.Studio degli effetti della metodologia di sintesi e del contenuto metallico sui parametri chimico-fisici e catalitici dei sistemi a base di Pd-Cu supportati su MCM-41 e GRACE® DAVICAT - 1401; 2.Ottimizzazione del processo di sintesi dei supporti di MCM-41, ponendo attenzione alle quantità dei reagenti utilizzati, alla metodologia di eliminazione del templante e al tempo di trattamento idrotermale; 3.Ottimizzazione del processo di sintesi dei sistemi catalitici a base di Pd-Cu, al fine di ottenere una fase attiva costituita da particelle con dimensioni ridotte composte da una fase mista Pd-Cu.

Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model

BACKGROUND: Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects. We investigated the mechanisms of this heterogeneity in a mouse model with heterozygous targeted disruption of Scn5a (Scn5a(+/-) mice) and compared our results to those obtained in patients with loss-of-function mutations in SCN5A. METHODOLOGY/PRINCIPAL FINDINGS: Based on ECG, 10-week-old Scn5a(+/-) mice were divided into 2 subgroups, one displaying severe ventricular conduction defects (QRS interval>18 ms) and one a mild phenotype (QRS< or = 18 ms; QRS in wild-type littermates: 10-18 ms). Phenotypic difference persisted with aging. At 10 weeks, the Na+ channel blocker ajmaline prolonged QRS interval similarly in both groups of Scn5a(+/-) mice. In contrast, in old mice (>53 weeks), ajmaline effect was larger in the severely affected subgroup. These data matched the clinical observations on patients with SCN5A loss-of-function mutations with either severe or mild conduction defects. Ventricular tachycardia developed in 5/10 old severely affected Scn5a(+/-) mice but not in mildly affected ones. Correspondingly, symptomatic SCN5A-mutated Brugada patients had more severe conduction defects than asymptomatic patients. Old severely affected Scn5a(+/-) mice but not mildly affected ones showed extensive cardiac fibrosis. Mildly affected Scn5a(+/-) mice had similar Na(v)1.5 mRNA but higher Na(v)1.5 protein expression, and moderately larger I(Na) current than severely affected Scn5a(+/-) mice. As a consequence, action potential upstroke velocity was more decreased in severely affected Scn5a(+/-) mice than in mildly affected ones. CONCLUSIONS: Scn5a(+/-) mice show similar phenotypic heterogeneity as SCN5A-mutated patients. In Scn5a(+/-) mice, phenotype severity correlates with wild-type Na(v)1.5 protein expression.

Properdin in childhood and its association with wheezing and atopy

Properdin, a serum glycoprotein, is an important component of innate immunity, the only known positive regulator of complement, acting as an initiation point for alternative pathway activation. As an X-linked protein, we hypothesized that properdin may play a modulatory role in the pathogenesis of viral wheeze in children, which tends to be more common and more severe in boys. We aimed to determine properdin levels in a community-based paediatric sample, and to assess whether levels of properdin were associated with childhood wheeze phenotypes and atopy. We studied 137 school-children aged 8-12 yrs, a nested sample from a cohort study. Properdin was measured by a commercial enzyme-linked immunoabsorbant assay. We assessed wheeze by questionnaire, validated it by a nurse-led interview and performed skin prick tests and a methacholine challenge in all children. Forty children (29%) reported current wheeze. Serum properdin levels ranged between 18 and 40 microg/ml. Properdin was not associated with age, gender, atopy, bronchial responsiveness, current wheeze (neither the viral wheeze nor multiple-trigger wheeze phenotype) or severity of wheeze, but was slightly lower in south Asian (median 21.8 microg/ml) compared with white children (23.3 microg/ml; p = 0.006). Our data make it unlikely that properdin deficiency is common in healthy children or that levels of properdin are a major risk factor for wheeze or atopy.

Problem of Tragedy and Tragic Consciousness in Russia at the turn of the 19th Century

This project intertwines philosophical and historico-literary themes, taking as its starting point the concept of tragic consciousness inherent in the epoch of classicism. The research work makes use of ontological categories in order to describe the underlying principles of the image of the world which was created in philosophical and scientific theories of the 17th century as well as in contemporary drama. Using these categories brought Mr. Vilk to the conclusion that the classical picture of the world implied a certain dualism; not the Manichaean division between light and darkness but the discrimination between nature and absolute being, i.e. God. Mr. Vilk begins with an examination of the philosophical essence of French classical theatre of the XVII and XVIII centuries. The history of French classical tragedy can be divided into three periods: from the mid 17th to early 19th centuries when it triumphed all over France and exerted a powerful influence over almost all European countries; followed by the period of its rejection by the Romantics, who declared classicism to be "artificial and rational"; and finally our own century which has taken a more moderate line. Nevertheless, French classical tragedy has never fully recovered its status. Instead, it is ancient tragedy and the works of Shakespeare that are regarded to be the most adequate embodiment of the tragic. Consequently they still provoke a great number of new interpretations ranging from specialised literary criticism to more philosophical rumination. An important feature of classical tragedy is a system of rules and unities which reveals a hidden ontological structure of the world. The ontological picture of the dramatic world can be described in categories worked out by medieval philosophy - being, essence and existence. The first category is to be understood as a tendency toward permanency and stability (within eternity) connected with this or that fragment of dramatic reality. The second implies a certain set of permanent elements that make up the reality. And the third - existence - should be understood as "an act of being", as a realisation of permanently renewed processes of life. All of these categories can be found in every artistic reality but the accents put on one or another and their interrelations create different ontological perspectives. Mr. Vilk plots the movement of thought, expressed in both philosophical and scientific discourses, away from Aristotle's essential forms, and towards a prioritising of existence, and shows how new forms of literature and drama structured the world according to these evolving requirements. At the same time the world created in classical tragedy fully preserves another ontological paradigm - being - as a fundamental permanence. As far as the tragic hero's motivations are concerned this paradigm is revealed in the dedication of his whole self to some cause, and his oath of fidelity, attitudes which shape his behaviour. It may be the idea of the State, or personal honour, or something borrowed from the emotional sphere, passionate love. Mr. Vilk views the conflicting ambivalence of existence and being, duty as responsibility and duty as fidelity, as underlying the main conflict of classical tragedy of the 17th century. Having plotted the movement of the being/existence duality through its manifestations in 17th century tragedy, Mr. Vilk moves to the 18th century, when tragedy took a philosophical turn. A dualistic view of the world became supplanted by the Enlightenment idea of a natural law, rooted in nature. The main point of tragedy now was to reveal that such conflicts as might take place had an anti-rational nature, that they arose as the result of a kind of superstition caused by social reasons. These themes Mr. Vilk now pursues through Russian dramatists of the 18th and early 19th centuries. He begins with Sumarakov, whose philosophical thought has a religious bias. According to Sumarakov, the dualism of the divineness and naturalness of man is on the one hand an eternal paradox, and on the other, a moral challenge for humans to try to unite the two opposites. His early tragedies are not concerned with social evils or the triumph of natural feelings and human reason, but rather the tragic disharmony in the nature of man and the world. Mr Vilk turns next to the work of Kniazhnin. He is particularly keen to rescue his reputation from the judgements of critics who accuse him of being imitative, and in order to do so, analyses in detail the tragedy "Dido", in which Kniazhnin makes an attempt to revive the image of great heroes and city-founders. Aeneas represents the idea of the "being" of Troy, his destiny is the re-establishment of the city (the future Rome). The moral aspect behind this idea is faithfulness, he devotes himself to Gods. Dido is also the creator of a city, endowed with "natural powers" and abilities, but her creation is lacking internal stability grounded in "being". The unity of the two motives is only achieved through Dido's sacrifice of herself and her city to Aeneus. Mr Vilk's next subject is Kheraskov, whose peculiarity lies in the influence of free-mason mysticism on his work. This section deals with one of the most important philosophical assumptions contained in contemporary free-mason literature of the time - the idea of the trinitarian hierarchy inherent in man and the world: body - soul - spirit, and nature - law - grace. Finally, Mr. Vilk assess the work of Ozerov, the last major Russian tragedian. The tragedies which earned him fame, "Oedipus in Athens", "Fingal" and "Dmitri Donskoi", present a compromise between the Enlightenment's emphasis on harmony and ontological tragic conflict. But it is in "Polixene" that a real meeting of the Russian tradition with the age-old history of the genre takes place. The male and female characters of "Polixene" distinctly express the elements of "being" and "existence". Each of the participants of the conflict possesses some dominant characteristic personifying a certain indispensable part of the moral world, a certain "virtue". But their independent efforts are unable to overcome the ontological gap separating them. The end of the tragedy - Polixene's sacrificial self-immolation - paradoxically combines the glorification of each party involved in the conflict, and their condemnation. The final part of Mr. Vilk's research deals with the influence of "Polixene" upon subsequent dramatic art. In this respect Katenin's "Andromacha", inspired by "Polixene", is important to mention. In "Andromacha" a decisive divergence from the principles of the philosophical tragedy of Russian classicism and the ontology of classicism occurs: a new character appears as an independent personality, directed by his private interest. It was Katenin who was to become the intermediary between Pushkin and classical tragedy.

Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

Novel sst2-selective somatostatin agonists. Three-dimensional consensus structure by NMR

The 3D NMR structures of six octapeptide agonist analogues of somatostatin (SRIF) in the free form are described. These analogues, with the basic sequence H-DPhe/Phe2-c[Cys3-Xxx7-DTrp8-Lys9-Thr10-Cys14]-Thr-NH2 (the numbering refers to the position in native SRIF), with Xxx7 being Ala/Aph, exhibit potent and highly selective binding to human SRIF type 2 (sst2) receptors. The backbone of these sst2-selective analogues have the usual type-II' beta-turn reported in the literature for sst2/3/5-subtype-selective analogues. Correlating the biological results and NMR studies led to the identification of the side chains of DPhe2, DTrp8, and Lys9 as the necessary components of the sst2 pharmacophore. This is the first study to show that the aromatic ring at position 7 (Phe7) is not critical for sst2 binding and that it plays an important role in sst3 and sst5 binding. This pharmacophore is, therefore, different from that proposed by others for sst2/3/5 analogues.

Mechanisms of unexpected death and autopsy findings in Leigh syndrome (subacute necrotising encephalomyelopathy)

A 21-year-old previously-well woman who was undergoing medical investigations for problems with balance and suspected multiple sclerosis, developed a headache and breathing difficulties, and died suddenly and unexpected at home. The autopsy was unremarkable except for pulmonary and cerebral oedema. However, subsequent microscopy of the brain revealed characteristic features of Leigh syndrome with multifocal areas of astrogliosis, capillary proliferation, and parenchymal vacuolation. While Leigh syndrome is more commonly diagnosed in infancy, manifestations may occur throughout early life into adulthood. Sudden and unexpected death is a rare presentation that may be associated with cerebral necrosis and oedema. An awareness of the variable manifestations of Leigh syndrome is necessary in forensic practice as not all cases will present in a typical manner and sudden death may occur before a diagnosis has been established. The heritable nature of this condition makes accuracy of diagnosis essential.

Expression of CD95 on mature leukocytes of MRL/lpr mice after transplantation of genetically modified bone marrow stem cells

Bone marrow transplantation (BMT) is commonly used for the treatment of severe haematological and immunological diseases. For instance, the autoimmune lymphoproliferative syndrome (ALPS) caused by a complete expression defect of CD95 (Fas, APO-1) can be cured by allogeneic BMT. However, since this therapy may not generate satisfactory results when only partially compatible donors are available, we were interested in the development of a potential alternative treatment by using lentiviral gene transfer of a normal copy of CD95 cDNA in hematopoietic stem cells. Here, we show that this approach applied to MRL/lpr mice results in the expression of functional CD95 receptors on the surface of lymphocytes, monocytes, and granulocytes. This suggests that correction of CD95 deficiency can be achieved by gene therapy.

Three-dimensional consensus structure of sst2-selective somatostatin (SRIF) antagonists by NMR

The three-dimensional NMR structures of seven octapeptide analogs of somatostatin (SRIF), based on octreotide, with the basic sequence H-Cpa/Phe2-c[DCys3-Xxx7-DTrp/DAph(Cbm)8-Lys9-Thr10-Cys14]-Yyy-NH2 (the numbering refers to the position in native SRIF), with Xxx7 being Aph(Cbm)/Tyr/Agl(NMe,benzoyl) and Yyy being Nal/DTyr/Thr, are presented here. Most of these analogs exhibit potent and highly selective binding to sst2 receptors, and all of the analogs are antagonists inhibiting receptor signaling. Based on their consensus 3D structure, the pharmacophore of the sst2-selective antagonist has been defined. The pharmacophore involves the side chains of Cpa2, DTrp/DAph(Cbm)8, and Lys9, with the backbone for most of the sst2-selective antagonists comprised a Type-II' beta-turn. Hence, the sst2-selective antagonist pharmacophore is very similar to the sst2-selective agonist pharmacophore previously described.

Ring size of somatostatin analogues (ODT-8) modulates receptor selectivity and binding affinity

The synthesis, biological testing, and NMR studies of several analogues of H-c[Cys (3)-Phe (6)-Phe (7)-DTrp (8)-Lys (9)-Thr (10)-Phe (11)-Cys (14)]-OH (ODT-8, a pan-somatostatin analogue, 1) have been performed to assess the effect of changing the stereochemistry and the number of atoms in the disulfide bridge on binding affinity. Cysteine at positions 3 and/or 14 (somatostatin numbering) were/was substituted with d-cysteine, norcysteine, D-norcysteine, homocysteine, and/or D-homocysteine. The 3D structure analysis of selected partially selective, bioactive analogues (3, 18, 19, and 21) was carried out in dimethylsulfoxide. Interestingly and not unexpectedly, the 3D structures of these analogues comprised the pharmacophore for which the analogues had the highest binding affinities (i.e., sst 4 in all cases).

Ring size in octreotide amide modulates differently agonist versus antagonist binding affinity and selectivity

H-DPhe (2)-c[Cys (3)-Phe (7)-DTrp (8)-Lys (9)-Thr (10)-Cys (14)]-Thr (15)-NH2 (1) (a somatostatin agonist, SRIF numbering) and H-Cpa (2)-c[DCys (3)-Tyr (7)-DTrp (8)-Lys (9)-Thr (10)-Cys (14)]-Nal (15)-NH2 (4) (a somatostatin antagonist) are based on the structure of octreotide that binds to three somatostatin receptor subtypes (sst 2/3/5) with significant binding affinity. Analogues of 1 and 4 were synthesized with norcysteine (Ncy), homocysteine (Hcy), or D-homocysteine (DHcy) at positions 3 and/or 14. Introducing Ncy at positions 3 and 14 constrained the backbone flexibility, resulting in loss of binding affinity at all sst s. The introduction of Hcy at positions 3 and 14 improved selectivity for sst 2 as a result of significant loss of binding affinity at the other sst s. Substitution by DHcy at position 3 in the antagonist scaffold (5), on the other hand, resulted in a significant loss of binding affinity at sst 2 and sst 3 as compared to the different affinities of the parent compound (4). The 3D NMR structures of the analogues in dimethylsulfoxide are consistent with the observed binding affinities.

THE INFLUENCE OF DIET COMPOSITION, PLANT DEFENSIVE CHEMICALS, AND WINTER SEVERITY ON THE NUTRITIONAL CONDITION OF A FREERANGING, GENERALIST HERBIVORE

Herbivory requires animals to manage intake of toxic phytochemicals. Detoxification and excretion of these chemicals prevents toxicity, but is energetically expensive. I investigated the relationship between investment in detoxification and nutritional condition for moose on Isle Royale National Park (Alces alces) during winter, using urinary indices from urine samples collected in snow. The ratio of urinary urea nitrogen:creatinine is an indicator of nutritional condition, and the ratio of glucuronic acid:creatinine is an indicator of investment in detoxification. Nutritional condition declined with greater investment in detoxification. An alternative means of managing defensive chemical intake is to diversify the diet. Microhistological analysis of fecal pellets determined diet composition. Diet diversity was weakly associated with improved nutritional condition. However, the strongest predictors of nutritional condition were winter severity and proportion of balsam fir in the diet (a dominant food for moose in this ecosystem).