Jorge Lima - Academia.edu (original) (raw)

Papers by Jorge Lima

Frontiers in Optics 2007/Laser Science XXIII/Organic Materials and Devices for Displays and Energy Conversion, 2007

The Multi-Conjugate Adaptive Optics Demonstrator (MAD) built by ESO with the contribution of two ... more The Multi-Conjugate Adaptive Optics Demonstrator (MAD) built by ESO with the contribution of two external consortia is a powerful test bench for proving the feasibility of Multi-Conjugate (MCAO) and Ground Layer Adaptive Optics (GLAO) techniques both in the laboratory and on the sky. MAD is based on a two deformable mirrors correction system and on two multi-reference wavefront sensors (Star Oriented and Layer Oriented) capable to observe simultaneously some pre-selected configurations of Natural Guide Stars. MAD corrects up to 2 arcmin field of view in K band. After a long laboratory test phase, it has been installed at the VLT and it successfully performed on-sky demonstration runs on several astronomical targets for evaluating the correction performance under different atmospheric turbulence conditions. In this paper we present the results obtained on the sky in Star Oriented mode for MCAO and GLAO configurations and we correlate them with different atmospheric turbulence parameters. Finally we compare some of the on-sky results with numerical simulations including real turbulence profile measured at the moment of the observations.

Storage and Retrieval for Image and Video Databases, 2004

The CAMCAO instrument is a high resolution near infrared (NIR) camera conceived to operate togeth... more The CAMCAO instrument is a high resolution near infrared (NIR) camera conceived to operate together with the new ESO Multi-conjugate Adaptive optics Demonstrator (MAD) with the goal of evaluating the feasibility of Multi-Conjugate Adaptive Optics techniques (MCAO) on the sky. It is a high-resolution wide field of view (FoV) camera that is optimized to use the extended correction of the atmospheric turbulence provided by MCAO. While the first purpose of this camera is the sky observation, in the MAD setup, to validate the MCAO technology, in a second phase, the CAMCAO camera is planned to attach directly to the VLT for scientific astrophysical studies. The camera is based on the 2k×2k HAWAII2 infrared detector controlled by an ESO external IRACE system and includes standard IR band filters mounted on a positional filter wheel. The CAMCAO design requires that the optical components and the IR detector should be kept at low temperatures in order to avoid emitting radiation and lower detector noise in the region analysis. The cryogenic system includes a lN 2 tank and a specially developed pulse tube cryo-cooler. Field and pupil cold stops are implemented to reduce the infrared background and the stray-light. The CAMCAO optics provide diffraction limited performance down to J Band, but the detector sampling fulfills the Nyquist criterion for the K band (2.2 mm).

Nature, Jan 25, 2011

Atmospheric aerosols exert an important influence on climate through their effects on stratiform ... more Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.

Ground-based and Airborne Instrumentation for Astronomy III, 2010

The main scientific drivers for ESPRESSO are the search and characterisation of rocky exoplanets ... more The main scientific drivers for ESPRESSO are the search and characterisation of rocky exoplanets in the habitable zone of quiet, nearby G to M dwarf stars and the analysis of the variability of fundamental physical constants. As an ultrastable highresolution spectrograph however, ESPRESSO will allow new frontiers to be explored in most domains of astrophys ics. The project passed its final design review in May 2013 and has entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and is planned to begin operations by the end of that year.

Ground-based and Airborne Instrumentation for Astronomy, 2006

This paper presents the integration and first results for the CAMCAO NIR camera. The camera was b... more This paper presents the integration and first results for the CAMCAO NIR camera. The camera was built for the ESO Multi-conjugate Adaptive optics Demonstrator, where it is presently operating, to evaluate the feasibility of this Adaptive Optics technique. On a second phase it will work directly at the Nasmyth focus of the VLT. CAMCAO is a high resolution, wide field of view NIR camera, that is using the 2k×2k HgCdTe HAWAII-2 infrared detector from Rockwell Scientific, controlled by the ESO IRACE system. The camera operates in the near infrared region between 1.0 µm and 2.5 µm wavelength using an eight position filter wheel with J, H, K', K-continuum and Brγ filters. Both the integration experience and the results obtained in the mechanical, vacuum, cryogenics and optical tests are presented, including all relevant parameters in the ESO specifications. The requirement of mechanical stiffness together with light weight was achieved yielding a total weight of less than 90 Kg. The camera fulfills both cryogenic and vacuum stability requirements. The temperature within the detector is maintained at 80 K by an accurate control loop, ensuring m K stability, after cooling down the detector at a rate kept below 0.5 K/min. The optical performance tests were made using a Fizeau interferometer both for the individual optical components and complete setup. The infrared optical validation measurements were performed by re-imaging a point source in the camera focal plane and measuring the PSF with the detector. The computed Strehl ratio reached 95% in the central region of the FoV, with values larger than 90% in a area covering 88% of the focal plane.

Nature, 2011

Nature Communications, 2013

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechani... more Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

American Journal of Pathology, 2002

In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) a... more In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the mtDNA in 79 benign and malignant tumors (43 Hürthle and 36 non-Hürthle cell neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was evaluated by semiquantitative polymerase chain reaction. Somatic point mutations and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations, mostly transitions, in 34 tumors and 253 sequence variants in 59 patients. Follicular and papillary carcinomas carried a significantly higher prevalence of nonsilent point mutations of complex I genes than adenomas. We also detected a significantly higher prevalence of complex I and complex IV sequence variants in the normal parenchyma adjacent to the malignant tumors. Every Hürthle cell tumor displayed a relatively high percentage (up to 16%) of mtDNA CD independently of the lesion's histotype. The percentage of deleted mtDNA molecules was significantly higher in tumors with D-loop mutations than in mtDNA stable tumors. Sequence variants of the ATPase 6 gene, one of the complex V genes thought to play a role in mtDNA maintenance and integrity in yeast, were significantly more prevalent in patients with Hürthle cell tumors than in patients with non-Hürthle cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of complex I and complex IV genes seem to be involved in thyroid tumorigenesis. Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of mtDNA CD, the hallmark of Hürthle cell tumors.

Cancer Letters, 2005

Our findings both support and extend those of Nikiforova et al. [M.N. Nikiforova, R. Ciampi, G. S... more Our findings both support and extend those of Nikiforova et al. [M.N. Nikiforova, R. Ciampi, G. Salvatore, M. Santoro, M. Gandhi, J.A. Knauf, et al., Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas, Cancer Lett. 209 (2004) 1–6]: BRAF mutations are rare in childhood PTC, both in an irradiation setting and in sporadic tumors.

C cell hyperplasia is associated with medullary carcinoma of the thyroid in the inherited MEN2 sy... more C cell hyperplasia is associated with medullary carcinoma of the thyroid in the inherited MEN2 syndromes, in which the great majority of cases have been shown to be due to a mutation in the RET oncogene. We report a study of a family with C cell hyperplasia and hypercalcitoninemia in which no cases of medullary carcinoma have yet occurred and which lacked an identifiable causative RET mutation. Four of the family members showed hypercalcitoninemia, and marked C cell hyperplasia was present in each of the three in whom thyroidectomy has been performed. We investigated the possible involvement of the SDHD gene, because somatic and germline mutations in this gene have been found in a variety of tumors of neural crest-derived tissue. A germline mutation in exon 2 of the SDHD gene (c149 A-G, His 50 Arg) was found in six members of the family; all the four available members with hypercalcitoninemia possessed the mutation. One of the five available members without hypercalcitoninemia, an 18-yr-old female, also showed the mutation. We conclude that we have identified a new syndrome, characterized by familial non-RET C cell hyperplasia. Our studies suggest that a mutation in SDHD may be causative. These observations have implications for apparently incidental cases of hypercalcitoninemia or C cell hyperplasia. (J Clin Endocrinol Metab 88: 4932-4937,

The BRAF gene has been shown to be a major target for mutations in papillary thyroid carcinoma (P... more The BRAF gene has been shown to be a major target for mutations in papillary thyroid carcinoma (PTC) (36 -69%), which forms almost all of the over 2000 cases of thyroid carcinoma that have occurred in Chernobyl. BRAF is activated by point mutation, and were it to occur at a high frequency in Chernobyl-related tumors, it would challenge the dominant role of double-strand breaks in radiation-induced PTC. In a previous study, we detected the BRAF V600E mutation in 46% (23 of 50) of sporadic adult PTC. Using the same methodology, we have analyzed 34 post-Chernobyl PTC and detected RET/PTC rearrangements in 14 (41%) and BRAF mutations (V600E) in four (12%). These two alterations did not coexist in any PTCs. The mean age at exposure of patients with PTC showing BRAF mutation was higher than that of patients with tumors without BRAF mutation irrespective of their RET status. We have also analyzed 17 sporadic cases of childhood PTC and found that only one (6%) harbored the BRAF V600E mutation. We conclude that the frequency of BRAF mutations is significantly lower (P ‫؍‬ 0.0008) in post-Chernobyl PTC than in adult sporadic PTC, whereas no significant difference was found between post-Chernobyl and sporadic childhood PTCs. (J Clin Endocrinol Metab 89: 4267-4271, 2004) Abbreviations: FA, Follicular adenoma; PTC, papillary thyroid carcinoma; SSCP, single strand conformation polymorphism. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community.

Biochimica et biophysica acta, 2011

In order to investigate the cell death-inducing effects of rotenone, a plant extract commonly use... more In order to investigate the cell death-inducing effects of rotenone, a plant extract commonly used as a mitochondrial complex I inhibitor, we studied cancer cell lines with different genetic backgrounds. Rotenone inhibits cell growth through the induction of cell death and cell cycle arrest, associated with the development of mitotic catastrophe. The cell death inducer staurosporine potentiates the inhibition of cell growth by rotenone in a dose-dependent synergistic manner. The tumor suppressor p53 is involved in rotenone-induced cell death, since the drug treatment results in increased expression, phosphorylation and nuclear localization of the protein.

Advances in Anatomic Pathology, 2008

GRIM-19, a gene associated with retinoid interferoninduced mortality, was originally identified a... more GRIM-19, a gene associated with retinoid interferoninduced mortality, was originally identified as a critical regulatory protein for interferon-b and retinoic acid-induced cell death. It was also demonstrated that GRIM-19 is involved in mitochondrial metabolism, as an integrant component of complex I of the mitochondrial respiratory chain. GRIM-19 appears, therefore, as a dual function protein involved in cell death and mitochondrial metabolism. GRIM-19 knock out leads to Complex I assembly disruption and embryonic lethality in mice, showing that it is a crucial component of the mitochondrial respiratory chain essential for early embryonic development. Recently, mutations in GRIM-19 were described in Hu¨rthle cell (mitochondrion-rich) tumors of the thyroid and down-regulation or loss of its expression were found in renal cell carcinomas, suggesting a role for GRIM-19 in tumorigenesis. As GRIM-19 binds and inhibits the signal transducer and activator of transcription-3 (STAT3), which has been shown to be activated in several human tumors it is tempting to advance that GRIM-19 may function as a tumor suppressor gene in tumors in which STAT3 plays a major role.

Virchows Archiv, 2009

The authors review the role played by mutations in mitochondrial DNA and in nuclear genes encodin... more The authors review the role played by mutations in mitochondrial DNA and in nuclear genes encoding mitochondrial proteins in cancer development, with an emphasis on the alterations of the oxidative phosphorylation system and glycolysis.

Virchows Archiv, 2009

Endocrinology and Metabolism Clinics of North America, 2008

The close genotype-phenotype relationship that characterizes thyroid oncology stimulated the auth... more The close genotype-phenotype relationship that characterizes thyroid oncology stimulated the authors to address this article by using a mixed, genetic and phenotypic approach. As such, this article addresses the following aspects of intragenic mutations in thyroid cancer: thyroid stimulating hormone receptor and guanine-nucleotide-binding proteins of the stimulatory family mutations in hyperfunctioning tumors; mutations in RAS and other genes and aneuploidy; PAX8-PPARgamma rearrangements; BRAF mutations; mutations in oxidative phosphorylation and Krebs cycle genes in Hürthle cell tumors; mutations in succinate dehydrogenase genes in medullary carcinoma and C-cell hyperplasia; and mutations in TP53 and other genes in poorly differentiated and anaplastic carcinomas.

Mitochondrion, 2005

Despite the numerous studies describing a high frequency of mitochondrial DNA (mtDNA) somatic mut... more Despite the numerous studies describing a high frequency of mitochondrial DNA (mtDNA) somatic mutations in many types of human primary tumors the mechanisms that generate such mutations and the role of mtDNA mutations in tumor development remain unclear. We present the results obtained in the study of mtDNA displacement-loop (D-Loop) region in a series of 66 thyroid tumors, and respective adjacent parenchyma, including benign (adenomas, n=30) and malignant tumors (follicular carcinomas, n=17 and papillary carcinomas, n=19). Three repetitive regions were analyzed [two mononucleotide repetitive (D310 and D568) and one dinucleotide repetitive (D514)]. Thirty-two (48.5%) of the 66 tumors [15/30 (50.0%) adenomas, 8/17 (47.1%) follicular carcinomas and 9/19 (47.4%) papillary carcinomas] harbored somatic insertions in D-Loop repetitive regions. Twenty (30.3%) of the 66 tumors [12/30 (40%) adenomas, 3/17 (17.6%) follicular carcinomas and 5/19 (26.3%) papillary carcinomas] harbored somatic insertions at the D310 mononucleotide repeat. Three (4.6%) of the 66 tumors [1/30 (3.3%) adenomas and 2/17 (11.8%) follicular carcinomas] harbored somatic insertions at the D568 mononucleotide repeat. Fifteen (22.7%) of the 66 tumors [3/30 (10.0%) adenomas, 5/17 (29.4%) follicular carcinomas and 7/19 (36.8%) papillary carcinomas] harbored somatic insertions at the D514 dinucleotide repeat. Five (7.6%) of the 66 tumors [1/30 (3.3%) adenomas, 1/17 (5.9%) follicular carcinomas and 2/19 (10.5%) papillary carcinomas] harbored somatic insertions in more than one region, and in one of them (a carcinoma) alterations were detected in the three regions. We conclude that mutations in the mtDNA D-Loop region are frequent in benign and malignant thyroid tumors and cannot be considered a marker of malignancy. Our study shows, furthermore, two repetitive regions (D310 and D514) that appear to be susceptible to mutation in thyroid tumors.

Oncogene, 2003

Rearrangement of RET proto-oncogene is the major event in the etiopathogenesis of papillary thyro... more Rearrangement of RET proto-oncogene is the major event in the etiopathogenesis of papillary thyroid carcinoma (PTC). We report a high prevalence of BRAF V599E mutation in sporadic PTC and in PTC-derived cell lines. The BRAF V599E mutation was detected in 23 of 50 PTC (46%) and in three of four PTC-derived cell lines. The prevalence of the BRAF V599E mutation in PTC is the highest reported to date in human carcinomas, being only exceeded by melanoma. PTC with RET/PTC rearrangement as well as the TPC-1 cell line (the only one harboring RET/PTC rearrangement) did not show the BRAF V599E mutation. BRAF V599E mutation was not detected in any of 23 nodular goiters, 51 follicular adenomas and 18 follicular carcinomas. A distinct mutation in BRAF (codon K600E) was detected in a follicular adenoma. Activating mutations in RAS genes were detected in 15% of FA, 33% of FTC and 7% of PTC. BRAF V599E mutation did not coexist with alterations in any of the RAS genes in any of the tumors. These results suggest that BRAF V599E mutation is frequent in the etiopathogenesis of PTC. The BRAF V599E mutation appears to be an alternative event to RET/PTC rearrangement rather than to RAS mutations, which are rare in PTC. BRAF V599E may represent an alternative pathway to oncogenic MAPK activation in PTCs without RET/PTC activation.

Virchows Archiv, 2005

A high prevalence of the BRAFV600E somatic mutation was recently reported in several series of pa... more A high prevalence of the BRAFV600E somatic mutation was recently reported in several series of papillary thyroid carcinomas (PTC). This mutation appears to be particularly prevalent in PTC with a predominantly papillary architecture. Another BRAF mutation (K601E) was detected in a follicular adenoma and in some cases of the follicular variant of PTC. The few studies on record provided controversial data on the relationship between the occurrence of BRAF mutations and clinicopathologic parameters such as gender, age and tumour staging. In an attempt to clarify such controversies we decided to enlarge our previous series to 315 tumours or tumour-like lesions diagnosed in 280 patients, including a thorough analysis of several clinicopathologic features. The BRAFV600E mutation was exclusively detected in PTC with a papillary or mixed follicular/papillary architecture both of the conventional type (46%) and of other histotypes, such as microcarcinoma (43%), Warthin-like PTC (75%) and oncocytic variant of PTC (55%). The BRAFK601E mutation was detected in four of the 54 cases of the follicular variant of PTC (7%). The mean age of patients with conventional PTC harbouring BRAFV600E (46.7 years) was significantly higher (PBRAFV600E (29.5 years). The BRAF (BRAFV600E) mutated PTC did not exhibit signs of higher aggressiveness (size, vascular invasion, extra-thyroid extension and nodal metastasis) and were in fact less often multicentric than PTC without the mutation.

Genes, Chromosomes and Cancer, 2003

Frontiers in Optics 2007/Laser Science XXIII/Organic Materials and Devices for Displays and Energy Conversion, 2007

Storage and Retrieval for Image and Video Databases, 2004

Nature, Jan 25, 2011

Ground-based and Airborne Instrumentation for Astronomy III, 2010

Ground-based and Airborne Instrumentation for Astronomy, 2006

Nature, 2011

Nature Communications, 2013

American Journal of Pathology, 2002

Cancer Letters, 2005

Biochimica et biophysica acta, 2011

Advances in Anatomic Pathology, 2008

Virchows Archiv, 2009

Endocrinology and Metabolism Clinics of North America, 2008

Mitochondrion, 2005

Oncogene, 2003

Virchows Archiv, 2005

Genes, Chromosomes and Cancer, 2003