In Pursuit of Human Dignity

The discussion of human dignity raises such complex issues, and the issues that current scholarship now considers central to its understanding are so daunting, that we are in danger of not being able to see the forest for the trees. This Introduction forms the first chapter of a book of essays (Christopher McCrudden (ed.), UNDERSTANDING HUMAN DIGNITY,
Proceedings of the British Academy/Oxford University Press, in press) by a multi-disciplinary group of historians, legal academics, judges, political scientists, theologians, and philosophers, arising from a Conference held in Rhodes House, Oxford In June 2012. The Introduction aims to provide a guide, a map, through the thicket of current dignity scholarship. It situates the subsequent chapters of the book within an overview of the terrain that currently constitutes debates about the use of dignity in these fields. I have not attempted to put forward my own
comprehensive account of dignity. Mostly based on the rich conversations that took place at the Conference, I have sought, rather, to probe the potential strengths and weaknesses of all of the principal positions identified, at least in some contexts taking on the role of a Devil’s Advocate.

The Extra-territorial Obligations of European States regarding Human Rights in the Context of Terrorism

This chapter focuses on the growing tendency of international human rights law to require states to protect the rights of non-nationals who are in the state unlawfully and of nationals and non-nationals who are outside the state, especially when any of these people are involved in terrorist or counter-terrorist activity. It reviews these additional obligations within a European context, focusing on EU law and the law of the European Convention on Human Rights and drawing on the case law of UK courts. Part 1 considers when a European state must grant asylum to alleged terrorists on the basis that otherwise they would suffer human rights abuses in the state from which they are fleeing. Part 2 examines whether, outside of asylum claims, a European state must not deport or extradite an alleged terrorist because he or she might suffer an abuse of human rights in the receiving state. Part 3 looks at whether a European state whose security forces are engaged in counter-terrorism activities abroad is obliged to protect the human rights of the individuals serving in those forces and/or the human rights of the alleged terrorists they are confronting. While welcoming the extension of state responsibility, the chapter notes that it is occurring in a way which introduces three aspects of relativity into the protection of human rights. First, European law protects only some human rights extra-territorially. Second, it protects those rights only when there is ‘a real risk’ of their being violated. Third, sometimes it protects those rights only when there is a real risk of their being violated ‘flagrantly’.

Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.

Salud y crecimiento económico: un modelo de generaciones traslapadas, expectativa de vida endógena y capital humano

Este trabajo desarrolla un modelo de generaciones traslapadas con expectativa de vida endógena y capital humano. Recoge parte de la evidencia empírica acerca de la transición demográfica explicada por Notestein en 1945, donde variaciones en la longevidad de los individuos afectan positivamente el crecimiento económico de un país. El modelo establece que la falta de incentivos para invertir en salud estanca a una economía en una trampa de pobreza y muestra que incrementos en la productividad en el sector de producción de capital humano, al igual que cambios tecnológicos sesgados al uso intensivo del mismo, incrementan el producto de estado estacionario y pueden sacar a una economía de una trampa de pobreza.

Human capital and growth under political uncertainty

In this paper we show how political uncertainty may impede economic growth by reducing public investment in the formation of human capital, and how this negative effect of political uncertainty can be offset by a government contract. We present a model of growth with accumulation of human capital and government investment in education. We show that in a country with an unstable political system the government is reluctant to invest in human capital. Low government spending on education negatively affects productivity and slows growth. Furthermore, a politically unstable economy may be trapped in a stagnant equilibrium. We also demonstrate the role of a government retirement contract. Public investment in education and economic growth are higher when the future retirement compensation of the government depends on the future national income, in comparison with investment under zero or fixed retirement compensation.

Human versus animal: contrasting decomposition dynamics of mammalian analogues in experimental taphonomy

Taphonomic studies regularly employ animal analogues for human decomposition due to ethical restrictions relating to the use of human tissue. However, the validity of using animal analogues in soil decomposition studies is still questioned. This study compared the decomposition of skeletal muscle tissues (SMTs) from human (Homo sapiens), pork (Sus scrofa), beef (Bos taurus), and lamb (Ovis aries) interred in soil microcosms. Fixed interval samples were collected from the SMT for microbial activity and mass tissue loss determination; samples were also taken from the underlying soil for pH, electrical conductivity, and nutrient (potassium, phosphate, ammonium, and nitrate) analysis. The overall patterns of nutrient fluxes and chemical changes in nonhuman SMT and the underlying soil followed that of human SMT. Ovine tissue was the most similar to human tissue in many of the measured parameters. Although no single analogue was a precise predictor of human decomposition in soil, all models offered close approximations in decomposition dynamics.

On the evolution of TFP in Latin America

Due to several policy distortions, including import-substitution industrialization, widespread government intervention and both domestic and international competitive barriers, there has been a general presumption that Latin America has been much less productive than the leading economies in the last decades. In this paper we show, however, that until the late seventies Latin American countries had high productivity levels relative to the United States. It is only after the late seventies that we observe a fast decrease of relative TFP in Latin America. We also show that the inclusion of human capital in the production function makes a crucial diference in the TFP calculations for Latin America.

Career concerns: a human capital perspective

We introduce human capital accumulation, in the form of learning by doing, in a life cycle model of career concerns and analyze how human capital acquisition a ects implicit incentives for performance. We show that standard results from the career concerns literature can be reversed in the presence of human capital accumulation. Namely, implicit incentives need not decrease over time and may decrease with the degree of uncertainty about an individual's talent. Furthermore, increasing the pre-cision of output measurement can weaken rather than strengthen implicit incentives. Overall, our results contribute to shed new light on the ability of markets to discipline moral hazard in the absence of explicit contracts linking pay to performance.

On the evolution of TFP in Latin America

Due to several policy distortions, including import-substitution industrialization, widespread government intervention and both domestic and international competitive barriers, there has been a general presumption that Latin America has been much less productive than the leading economies in the last decades. In this paper we show, however, that until the late seventies Latin American countries had high productivity levels relative to the United States. It is only after the late seventies that we observe a fast decrease of relative TFP in Latin America. We also show that the inclusion of human capital in the production function makes a crucial difference in the TFP calculations for Latin America.

Habitat suitability of Anopheles vector species and association with human malaria in the Atlantic Forest in south-eastern brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors. © 2005 Elsevier Inc. All rights reserved.

Globalizing talent and human capital: implications for developing countries

Includes bibliography

Latin America’s emergence in global services A new driver of structural change in the region?

Includes bibliography.