String Breaking in Quenched QCD

We present preliminary quenched results on a new operator for the investigation of string-breaking within SU(2)-colour QCD. The ground-state of a spatially-separated static-light meson-antimeson pair is a combination of a state with two distinct mesons, expected to dominate for large separations, and a state where the light-quarks have annihilated, which contributes for short distances. The crossover between these two regimes provides a measure of the string-breaking scale length.Comment: LATTICE98(confine), 3 pages, 4 figure

Rights in mind: Thinking differently about dementia and disability

The aim of this paper is to argue for the utility of a relational model of disability, as a way of conceptualizing dementia. We explore whether dementia should be considered as a disability, and whether people with dementia might consider themselves as disabled people. We review examples of, and issues raised by, the political activism of people with dementia. We consider how language constructs dementia negatively. We discuss how the environment influences the experience of dementia. In conclusion, we show that a relational model of dementia lays the basis for a human rights approach to the condition, based on collaborative partnerships between people with dementia and people from other disability communities

Eye tracking – The overlooked method to measure cognition in neurodegeneration?

Eye tracking (ET) studies are becoming increasingly popular due to rapid methodological and technological advances as well as the development of cost efficient and portable eye trackers. Although historically ET has been mostly employed in psychophysics or developmental cognition studies, there is also promising scope to use ET for movement disorders and measuring cognitive processes in neurodegeneration. Particularly, ET can be a powerful tool for cognitive and neuropsychological assessments of patients with pathologies affecting motor and verbal abilities, as tasks can be adapted without requiring motor (except eye movements) or verbal responses. In this review, we will examine the existing evidence of ET methods in neurodegenerative conditions and its potential clinical impact for cognitive assessment. We highlight that current evidence for ET is mostly focused on diagnostics of cognitive impairments in neurodegenerative disorders, where it is debatable whether it has any more sensitivity or specificity than existing cognitive assessments. By contrast, there is currently a lack of ET studies in more advanced disease stages, when patients’ motor and verbal functions can be significantly affected, and standard cognitive assessments are challenging or often not possible. We conclude that ET is a promising method not only for cognitive diagnostics but more importantly, for potential cognitive disease tracking in progressive neurodegenerative conditions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

EUI-YouGov survey on solidarity in Europe

2 data files; 1 codebookThe EUI-YouGov survey on Solidarity in Europe (2020) is a dataset containing the answers to a survey of a representative sample of more than 20,000 adults from 13 European countries and the UK. The survey has been implemented by YouGov in collaboration with the EUI. The over 70 questions cover a number of topics focused on: the concept of solidarity among EU states and beyond; response to different crises through various instruments, including the recent Covid-19 outbreak; satisfaction and trust towards governments, the EU and international actors; strength of national and European identities; value of democracy; importance and salience of various issues and threats; intention in a EU-membership referendum and other EU-related indicators including differentiated integration; world politics; left-right self-placement; gender, religion and age group; vote record in past national elections

Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery

Choline kinase α (ChoKα) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles in regulation of cell proliferation, oncogenic transformation, and human carcinogenesis. Since several inhibitors of ChoKα display antiproliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoKα as an oncogenic target and explore the activity of novel small molecule inhibitors of ChoKα. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoKα. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth, and induction of apoptosis at low micromolar concentrations. The druglike lead series presented here is optimizable for improvements in cellular potency, drug target residence time, and pharmacokinetic parameters. These inhibitors may be utilized not only to further validate ChoKα as antioncogenic target but also as novel chemical matter that may lead to antitumor agents that specifically interfere with cancer cell metabolism

Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-Based Drug Discovery

Choline kinase α (ChoKα) is an enzyme involved in the synthesis of phospholipids and thereby plays key roles in regulation of cell proliferation, oncogenic transformation, and human carcinogenesis. Since several inhibitors of ChoKα display antiproliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoKα as an oncogenic target and explore the activity of novel small molecule inhibitors of ChoKα. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoKα. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth, and induction of apoptosis at low micromolar concentrations. The druglike lead series presented here is optimizable for improvements in cellular potency, drug target residence time, and pharmacokinetic parameters. These inhibitors may be utilized not only to further validate ChoKα as antioncogenic target but also as novel chemical matter that may lead to antitumor agents that specifically interfere with cancer cell metabolism

Winckelmann, Lessing e Herder: estéticas do efeito? Winckelmann, Lessing and Herder: aesthetics of the effect?

Este artigo investiga, sob a perspectiva de uma estética do efeito, as origens da assim chamada "estética da época de Goethe", segundo a obra de Lessing, Winckelmann e Herder. Pretende-se mostrar que há nestes autores tanto uma influência do parâmetro do efeito, suscitado pela obra de arte no espectador, quanto o apontamento para uma instância, por assim dizer crítica, idealista e especulativa de apreciação do fenômeno artístico.<br>We analyse in this article, from the point of view of an aesthetics of the effect, the sources of the so called "aesthetics of Goethe's time", according to the works of Lessing, Winckelmann and Herder. Our aim is to show that there are in those authors both an influence of the parameter of the effect, elicited by the work of art on the spectactor, and the pointing to a dimension, so to speak critical, idealistic and speculative of appreciation of the artistic phenomenon