3,388 research outputs found
The value of cell-free circulating tumour DNA profiling in advanced non-small cell lung cancer (NSCLC) management
Liquid biopsy (LB) has boosted a remarkable change in the management of cancer patients by contributing to tumour genomic profiling. Plasma circulating cell-free tumour DNA (ctDNA) is the most widely searched tumour-related element for clinical application. Specifically, for patients with lung cancer, LB has revealed valuable to detect the diversity of targetable genomic alterations and to detect and monitor the emergence of resistance mechanisms. Furthermore, its non-invasive nature helps to overcome the difficulty in obtaining tissue samples, offering a comprehensive view about tumour diversity. However, the use of the LB to support diagnostic and therapeutic decisions still needs further clarification. In this sense, this review aims to provide a critical view of the clinical importance of plasma ctDNA analysis, the most widely applied LB, and its limitations while anticipating concepts that will intersect the present and future of LB in non-small cell lung cancer patients
On O(1) contributions to the free energy in Bethe Ansatz systems: the exact g-function
We investigate the sub-leading contributions to the free energy of Bethe
Ansatz solvable (continuum) models with different boundary conditions. We show
that the Thermodynamic Bethe Ansatz approach is capable of providing the O(1)
pieces if both the density of states in rapidity space and the quadratic
fluctuations around the saddle point solution to the TBA are properly taken
into account. In relativistic boundary QFT the O(1) contributions are directly
related to the exact g-function. In this paper we provide an all-orders proof
of the previous results of P. Dorey et al. on the g-function in both massive
and massless models. In addition, we derive a new result for the g-function
which applies to massless theories with arbitrary diagonal scattering in the
bulk.Comment: 28 pages, 2 figures, v2: minor corrections, v3: minor corrections and
references adde
Economic History and History of Economics: Complementary Approaches to Portuguese Economic Development
This chapter focuses on how the problems of economic development were addressed by the Portuguese historiography of the late nineteenth and twentieth centuries. The ensuing discussion benefits from the simultaneous consideration of two historiographical domains that complement each other: economic history and the history of economics. On the one hand, there are the authors and texts of economic history that seek to describe the facts and circumstances related to the functioning and dynamics of economic reality, for a given period or succession of periods, in order to establish evolutionary trends. On the other hand, there are the authors and texts of the history of economics that seek to adopt analytical forms (principles and laws) and doctrinal and programmatic frameworks (visions and ideologies) aimed at providing explanatory meaning to the observed economic changes, phenomena and regularities. A true understanding of the important issues pertaining to Portuguese economic development is to be found, however, in the intersection of these distinct but complementary historiographical perspectives.info:eu-repo/semantics/publishedVersio
Comparison between perfusion and balloon techniques for performing anorectal manometry in children with intestinal constipation
A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis
Inborn errors of the IL-17-mediated signaling have been associated with chronic mucocutaneous candidiasis (CMC). We describe a patient with CMC, atopic dermatitis, enamel dysplasia, and recurrent parotitis harboring a novel compound heterozygous mutation of TRAF3IP2, leading to autosomal recessive ACT1 deficiency and deficient IL-17 signaling.info:eu-repo/semantics/publishedVersio
The Mechanical Behavior of a 25Cr Super Duplex Stainless Steel at Elevated Temperature
Peer reviewedPostprin
Mutational mechanism for DAB1 (ATTTC) n insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution
Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n . Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT-rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process.We are grateful to the families and individuals who participated in this work. We
thank Patricia Ribeiro for technical assistance. This study was financed by Fundo
Europeu de Desenvolvimento Regional (FEDER), through the COMPETE 2020
Operational Pro- gram for Competitiveness and Internationalization (POCI) of Portugal
2020, and by the Fundacão para a Ciência e a Tecnologia (FCT) and Ministério
da Ciência, Tecnologia e Ensino Superior (Portugal), in the framework of the project
POCI-01-0145-FEDER-029255; (PTDC/MED-GEN/29255/2017) to I.S. J.R.L. and
C.L.O. were sup- ported by scholarships from PEst-C/SAU/LA0002/2013. S.M. is
funded by the project IF/00930/2013/ CP1184/CT0002 from FCT. This work was
also funded by the Porto Neurosciences and Neurologic Disease Research Initiative
at the Instituto de Investigação e Inovação em Saúde (Norte-01-0145-FEDER-
000008), supported by Norte Portugal Regional Operational Programme (NORTE
2020), under the PORTU- GAL 2020 Partnership Agreement with FEDER
Silicon-based spin and charge quantum computation
Silicon-based quantum-computer architectures have attracted attention because
of their promise for scalability and their potential for synergetically
utilizing the available resources associated with the existing Si technology
infrastructure. Electronic and nuclear spins of shallow donors (e.g.
phosphorus) in Si are ideal candidates for qubits in such proposals due to the
relatively long spin coherence times. For these spin qubits, donor electron
charge manipulation by external gates is a key ingredient for control and
read-out of single-qubit operations, while shallow donor exchange gates are
frequently invoked to perform two-qubit operations. More recently, charge
qubits based on tunnel coupling in P substitutional molecular ions in Si
have also been proposed. We discuss the feasibility of the building blocks
involved in shallow donor quantum computation in silicon, taking into account
the peculiarities of silicon electronic structure, in particular the six
degenerate states at the conduction band edge. We show that quantum
interference among these states does not significantly affect operations
involving a single donor, but leads to fast oscillations in electron exchange
coupling and on tunnel-coupling strength when the donor pair relative position
is changed on a lattice-parameter scale. These studies illustrate the
considerable potential as well as the tremendous challenges posed by donor spin
and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy
of Science
Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch
Cellular transformations which involve a significant phenotypical change of
the cell's state use bistable biochemical switches as underlying decision
systems. In this work, we aim at linking cellular decisions taking place on a
time scale of years to decades with the biochemical dynamics in signal
transduction and gene regulation, occuring on a time scale of minutes to hours.
We show that a stochastic bistable switch forms a viable biochemical mechanism
to implement decision processes on long time scales. As a case study, the
mechanism is applied to model the initiation of follicle growth in mammalian
ovaries, where the physiological time scale of follicle pool depletion is on
the order of the organism's lifespan. We construct a simple mathematical model
for this process based on experimental evidence for the involved genetic
mechanisms. Despite the underlying stochasticity, the proposed mechanism turns
out to yield reliable behavior in large populations of cells subject to the
considered decision process. Our model explains how the physiological time
constant may emerge from the intrinsic stochasticity of the underlying gene
regulatory network. Apart from ovarian follicles, the proposed mechanism may
also be of relevance for other physiological systems where cells take binary
decisions over a long time scale.Comment: 14 pages, 4 figure
The Role of Liquid Biopsy in Early Diagnosis of Lung Cancer
Liquid biopsy is an emerging technology with a potential role in the screening and early detection of lung cancer. Several liquid biopsy-derived biomarkers have been identified and are currently under ongoing investigation. In this article, we review the available data on the use of circulating biomarkers for the early detection of lung cancer, focusing on the circulating tumor cells, circulating cell-free DNA, circulating micro-RNAs, tumor-derived exosomes, and tumor-educated platelets, providing an overview of future potential applicability in the clinical practice. While several biomarkers have shown exciting results, diagnostic performance and clinical applicability is still limited. The combination of different biomarkers, as well as their combination with other diagnostic tools show great promise, although further research is still required to define and validate the role of liquid biopsies in clinical practice.This work is financed by the ERDF—European Regional Development Fund through the Operational Programme for Competitiveness and Internationalization—COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT—Fundação para a Ciência e a Tecnologia within project POCI-01-0145-FEDER-030263.
Authors thank Abílio Cunha and Francisco Correia for the illustration work. NC-M acknowledges the Portuguese Foundation for Science and Technology under Horizon 2020 Program (PTDC/PSI-GER/28076/2017)
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