Teniasis/Cisticercosis (T/C) es un binomio que refiere a dos enfermedades diferentes ocasionadas ... more Teniasis/Cisticercosis (T/C) es un binomio que refiere a dos enfermedades diferentes ocasionadas por Tenia solium: Teniasis, debida al establecimiento del estadío adulto en el ser humano y Cisticercosis, por el estadio larvario, en el cerdo o humano. La Cisticercosis es ...
Http Dx Doi Org 10 1080 13504851 2013 848015, Oct 16, 2013
ABSTRACT This article analyses the selectivity and market timing abilities of international Socia... more ABSTRACT This article analyses the selectivity and market timing abilities of international Socially Responsible Investment (SRI) funds, from eight European markets, in comparison to conventional funds with similar characteristics. The results show that differences in market timing abilities of international SRI funds and their conventional peers are not statistically significant. However, SRI funds investing in European equities are significantly worse stock pickers than conventional funds, whereas for funds investing globally, selectivity abilities are similar among both fund groups. Hence, our results suggest that a broader investment universe might increase SRI fund managers’ stock picking abilities and, consequently, improve SRI fund performance.
ABSTRACT This paper investigates how past performance, as measured by alternative risk-adjusted m... more ABSTRACT This paper investigates how past performance, as measured by alternative risk-adjusted measures is informative of future performance. Performance results based on the Sharpe Ratio and several downside risk-adjusted performance measures (the Sortino ratio, excess return on Cornish-Fisher VaR, excess return on VaR, and excess return on Expected Shortfall) are compared. VaR and Expected Shortfall are computed using Filtered Historical Simulation (FHS), a hybrid methodology that combines the use of volatility models with bootstrapping techniques and is robust to the stylized facts of time series data on financial asset returns. Recent empirical evidence is somewhat controversial. Some studies suggest that the use of different risk-adjusted performance measures (traditional vs downside risk-adjusted) does not seem to matter for investment fund decisions (Eling & Schuhmacher, 2007; Eling, 2008) while others suggest that it matters at least for some of the measures (Ornelas et al. 2010; Zakamouline, 2010). In most of the cases, the observed level of statistical association between the Sharpe Ratio and the downside risk-adjusted measures of performance is not as low as would be expected. However, even if in empirical research statistical tests are not able to capture significant differences between rankings based on different measures, the economic significance of these differences may be relevant for investors and fund managers. In fact, it is of interest to assess to what extent the ex ante use of each of these measures can lead to better ex post performance results, regardless of the correlation between performance rankings and measures.Our sample includes portfolios of Large Cap US funds over the period 1999 to 2010. In each month, portfolios of funds are created based on the rankings of the funds resulting from the different risk-adjusted performance measures. A estimation window of five years is used. The cumulative return of the top performing funds is then compared with the bottom performing funds.
microRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation... more microRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation of messenger RNA targets, these noncoding RNAs can regulate the expression of more than half of all protein-coding genes in mammalian genomes. Aberrant miRNA expression is well characterized in cancer progression and has prognostic implications for cancer in general. Over the past several years, accumulating evidence has demonstrated that genomic alterations in miRNA genes are correlated with all aspects of cancer biology. In this review, we describe the effects of miRNA deregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells as well as in cancer diagnosis and therapy in humans.
Http Dx Doi Org 10 1080 13518470802697378, Dec 1, 2010
... Cortez, Paxson, and Armada 199913. Cortez, MC, Paxson, D. and Armada, MR 1999. Persistence in... more ... Cortez, Paxson, and Armada 199913. Cortez, MC, Paxson, D. and Armada, MR 1999. Persistence in Portuguese mutual fund performance. European Journal of Finance , 5: 342–65. [Taylor & Francis Online] View all references). ...
In this paper we investigate if past performance can be used to predict future performance in the... more In this paper we investigate if past performance can be used to predict future performance in the European bond fund market. Both unconditional and conditional measures of performance are considered. To our knowledge, this is the first study, which directly analyses the impact of conditioning information in assessing the persistence phenomenon in relation to bond funds.
CiteSeerX - Document Details (Isaac Councill, Lee Giles): * Ph.D. Student, Associate Professor an... more CiteSeerX - Document Details (Isaac Councill, Lee Giles): * Ph.D. Student, Associate Professor and Full Professor of Finance, respectively, at the.
Synovial sarcomas are high-grade malignant mesenchymal tumors that account for 10% of all softtis... more Synovial sarcomas are high-grade malignant mesenchymal tumors that account for 10% of all softtissue sarcomas. Almost 95% of these tumors are characterized by a nonrandom chromosomal abnormality, t(X;18)(p11.2;q11.2), that is observed in both biphasic and monophasic variants. In this article, we present the case of a 57-year-old woman diagnosed with high-grade biphasic synovial sarcoma in which conventional cytogenetic analysis revealed the constant presence of a unique t(18;22)(q12;q13), in addition to trisomy 8. The rearrangement was confirmed by fluorescence in situ hybridization. The use of the whole chromosome painting probes WCPX did not detect any rearrangements involving chromosome X, although reverse-transcriptase polymerase chain reaction (PCR) analysis demonstrated the conspicuous presence of a SYT/SXX1 fusion gene. Spectral karyotyping (SKY) was also performed and revealed an insertion of material from chromosome 18 into one of the X chromosomes at position Xp11.2. Thus, the karyotype was subsequently interpreted as 47,X,der(X)ins(X;18) (p11.2;q11.2q11.2),der(18)del(18)(q11.2q11.2)t(18;22)(q12;q13),der(22)t(18;22). Real-time PCR analysis of BCL2 expression in the tumor sample showed a 433-fold increase. This rare finding exemplifies that thorough molecularecytogenetic analyses are required to elucidate complex and/or cryptic tumor-specific translocations. Ó
MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; lo... more MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC), among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3' untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.
Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non-small cell l... more Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non-small cell lung cancer (NSCLC), the regulation of PDL1 expression is poorly understood. Here, we show that PDL1 is regulated by p53 via miR-34. p53 wild-type and p53-deficient cell lines (p53(-/-) and p53(+/+) HCT116, p53-inducible H1299, and p53-knockdown H460) were used to determine if p53 regulates PDL1 via miR-34. PDL1 and miR-34a expression were analyzed in samples from patients with NSCLC and mutated p53 vs wild-type p53 tumors from The Cancer Genome Atlas for Lung Adenocarcinoma (TCGA LUAD). We confirmed that PDL1 is a direct target of miR-34 with western blotting and luciferase assays and used a p53(R172HΔ)g/+K-ras(LA1/+) syngeneic mouse model (n = 12) to deliver miR-34a-loaded liposomes (MRX34) plus radiotherapy (XRT) and assessed PDL1 expression and tumor-infiltrating lymphocytes (TILs). A two-sided t test was applied to compare the mean between different treatments. We found that p53 regu...
This paper examines the performance of Portuguese equity funds investing in the domestic and in t... more This paper examines the performance of Portuguese equity funds investing in the domestic and in the European Union market, using several unconditional and conditional multi-factor models. In terms of overall performance, we find that National funds are neutral performers, while European Union funds under-perform the market significantly. These results do not seem to be a consequence of management fees. Overall, our findings are supportive of the robustness of conditional multi-factor models. In fact, Portuguese equity funds seem to be relatively more exposed to small-caps and more value-oriented. Also, they present strong evidence of time-varying betas and, in the case of the European Union funds, of time-varying alphas too. Finally, in terms of market timing, our tests suggest that mutual fund managers in our sample do not exhibit any market timing abilities. Nevertheless, we find some evidence of time-varying conditional market timing abilities but only at the individual fund level.
Radiation therapy controls local disease but also prompts the release of tumor-associated antigen... more Radiation therapy controls local disease but also prompts the release of tumor-associated antigens and stress-related danger signals that primes T cells to promote tumor regression at unirradiated sites known as the abscopal effect. This may be enhanced by blocking inhibitory immune signals that modulate immune activity through a variety of mechanisms. Indeed, abscopal responses have occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody and radiation. Other approaches involve expanding and reinfusing T or NK cells or engineered T cells to express receptors that target specific tumor peptides. These approaches may be useful for immunocompromised patients receiving radiation. Preclinical and clinical studies are testing both immune checkpoint-based strategies and adoptive immunotherapies with radiation.
The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC... more The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC) are poorly characterized. We performed an integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemo-refractory LUAC and identified three robust subsets of KRAS-mutant LUAC dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP) and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further reveal biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules and improved relapse-free survival. Differences in drug sensitivity patt...
Teniasis/Cisticercosis (T/C) es un binomio que refiere a dos enfermedades diferentes ocasionadas ... more Teniasis/Cisticercosis (T/C) es un binomio que refiere a dos enfermedades diferentes ocasionadas por Tenia solium: Teniasis, debida al establecimiento del estadío adulto en el ser humano y Cisticercosis, por el estadio larvario, en el cerdo o humano. La Cisticercosis es ...
Http Dx Doi Org 10 1080 13504851 2013 848015, Oct 16, 2013
ABSTRACT This article analyses the selectivity and market timing abilities of international Socia... more ABSTRACT This article analyses the selectivity and market timing abilities of international Socially Responsible Investment (SRI) funds, from eight European markets, in comparison to conventional funds with similar characteristics. The results show that differences in market timing abilities of international SRI funds and their conventional peers are not statistically significant. However, SRI funds investing in European equities are significantly worse stock pickers than conventional funds, whereas for funds investing globally, selectivity abilities are similar among both fund groups. Hence, our results suggest that a broader investment universe might increase SRI fund managers’ stock picking abilities and, consequently, improve SRI fund performance.
ABSTRACT This paper investigates how past performance, as measured by alternative risk-adjusted m... more ABSTRACT This paper investigates how past performance, as measured by alternative risk-adjusted measures is informative of future performance. Performance results based on the Sharpe Ratio and several downside risk-adjusted performance measures (the Sortino ratio, excess return on Cornish-Fisher VaR, excess return on VaR, and excess return on Expected Shortfall) are compared. VaR and Expected Shortfall are computed using Filtered Historical Simulation (FHS), a hybrid methodology that combines the use of volatility models with bootstrapping techniques and is robust to the stylized facts of time series data on financial asset returns. Recent empirical evidence is somewhat controversial. Some studies suggest that the use of different risk-adjusted performance measures (traditional vs downside risk-adjusted) does not seem to matter for investment fund decisions (Eling & Schuhmacher, 2007; Eling, 2008) while others suggest that it matters at least for some of the measures (Ornelas et al. 2010; Zakamouline, 2010). In most of the cases, the observed level of statistical association between the Sharpe Ratio and the downside risk-adjusted measures of performance is not as low as would be expected. However, even if in empirical research statistical tests are not able to capture significant differences between rankings based on different measures, the economic significance of these differences may be relevant for investors and fund managers. In fact, it is of interest to assess to what extent the ex ante use of each of these measures can lead to better ex post performance results, regardless of the correlation between performance rankings and measures.Our sample includes portfolios of Large Cap US funds over the period 1999 to 2010. In each month, portfolios of funds are created based on the rankings of the funds resulting from the different risk-adjusted performance measures. A estimation window of five years is used. The cumulative return of the top performing funds is then compared with the bottom performing funds.
microRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation... more microRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation of messenger RNA targets, these noncoding RNAs can regulate the expression of more than half of all protein-coding genes in mammalian genomes. Aberrant miRNA expression is well characterized in cancer progression and has prognostic implications for cancer in general. Over the past several years, accumulating evidence has demonstrated that genomic alterations in miRNA genes are correlated with all aspects of cancer biology. In this review, we describe the effects of miRNA deregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells as well as in cancer diagnosis and therapy in humans.
Http Dx Doi Org 10 1080 13518470802697378, Dec 1, 2010
... Cortez, Paxson, and Armada 199913. Cortez, MC, Paxson, D. and Armada, MR 1999. Persistence in... more ... Cortez, Paxson, and Armada 199913. Cortez, MC, Paxson, D. and Armada, MR 1999. Persistence in Portuguese mutual fund performance. European Journal of Finance , 5: 342–65. [Taylor & Francis Online] View all references). ...
In this paper we investigate if past performance can be used to predict future performance in the... more In this paper we investigate if past performance can be used to predict future performance in the European bond fund market. Both unconditional and conditional measures of performance are considered. To our knowledge, this is the first study, which directly analyses the impact of conditioning information in assessing the persistence phenomenon in relation to bond funds.
CiteSeerX - Document Details (Isaac Councill, Lee Giles): * Ph.D. Student, Associate Professor an... more CiteSeerX - Document Details (Isaac Councill, Lee Giles): * Ph.D. Student, Associate Professor and Full Professor of Finance, respectively, at the.
Synovial sarcomas are high-grade malignant mesenchymal tumors that account for 10% of all softtis... more Synovial sarcomas are high-grade malignant mesenchymal tumors that account for 10% of all softtissue sarcomas. Almost 95% of these tumors are characterized by a nonrandom chromosomal abnormality, t(X;18)(p11.2;q11.2), that is observed in both biphasic and monophasic variants. In this article, we present the case of a 57-year-old woman diagnosed with high-grade biphasic synovial sarcoma in which conventional cytogenetic analysis revealed the constant presence of a unique t(18;22)(q12;q13), in addition to trisomy 8. The rearrangement was confirmed by fluorescence in situ hybridization. The use of the whole chromosome painting probes WCPX did not detect any rearrangements involving chromosome X, although reverse-transcriptase polymerase chain reaction (PCR) analysis demonstrated the conspicuous presence of a SYT/SXX1 fusion gene. Spectral karyotyping (SKY) was also performed and revealed an insertion of material from chromosome 18 into one of the X chromosomes at position Xp11.2. Thus, the karyotype was subsequently interpreted as 47,X,der(X)ins(X;18) (p11.2;q11.2q11.2),der(18)del(18)(q11.2q11.2)t(18;22)(q12;q13),der(22)t(18;22). Real-time PCR analysis of BCL2 expression in the tumor sample showed a 433-fold increase. This rare finding exemplifies that thorough molecularecytogenetic analyses are required to elucidate complex and/or cryptic tumor-specific translocations. Ó
MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; lo... more MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC), among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3' untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.
Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non-small cell l... more Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non-small cell lung cancer (NSCLC), the regulation of PDL1 expression is poorly understood. Here, we show that PDL1 is regulated by p53 via miR-34. p53 wild-type and p53-deficient cell lines (p53(-/-) and p53(+/+) HCT116, p53-inducible H1299, and p53-knockdown H460) were used to determine if p53 regulates PDL1 via miR-34. PDL1 and miR-34a expression were analyzed in samples from patients with NSCLC and mutated p53 vs wild-type p53 tumors from The Cancer Genome Atlas for Lung Adenocarcinoma (TCGA LUAD). We confirmed that PDL1 is a direct target of miR-34 with western blotting and luciferase assays and used a p53(R172HΔ)g/+K-ras(LA1/+) syngeneic mouse model (n = 12) to deliver miR-34a-loaded liposomes (MRX34) plus radiotherapy (XRT) and assessed PDL1 expression and tumor-infiltrating lymphocytes (TILs). A two-sided t test was applied to compare the mean between different treatments. We found that p53 regu...
This paper examines the performance of Portuguese equity funds investing in the domestic and in t... more This paper examines the performance of Portuguese equity funds investing in the domestic and in the European Union market, using several unconditional and conditional multi-factor models. In terms of overall performance, we find that National funds are neutral performers, while European Union funds under-perform the market significantly. These results do not seem to be a consequence of management fees. Overall, our findings are supportive of the robustness of conditional multi-factor models. In fact, Portuguese equity funds seem to be relatively more exposed to small-caps and more value-oriented. Also, they present strong evidence of time-varying betas and, in the case of the European Union funds, of time-varying alphas too. Finally, in terms of market timing, our tests suggest that mutual fund managers in our sample do not exhibit any market timing abilities. Nevertheless, we find some evidence of time-varying conditional market timing abilities but only at the individual fund level.
Radiation therapy controls local disease but also prompts the release of tumor-associated antigen... more Radiation therapy controls local disease but also prompts the release of tumor-associated antigens and stress-related danger signals that primes T cells to promote tumor regression at unirradiated sites known as the abscopal effect. This may be enhanced by blocking inhibitory immune signals that modulate immune activity through a variety of mechanisms. Indeed, abscopal responses have occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody and radiation. Other approaches involve expanding and reinfusing T or NK cells or engineered T cells to express receptors that target specific tumor peptides. These approaches may be useful for immunocompromised patients receiving radiation. Preclinical and clinical studies are testing both immune checkpoint-based strategies and adoptive immunotherapies with radiation.
The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC... more The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC) are poorly characterized. We performed an integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemo-refractory LUAC and identified three robust subsets of KRAS-mutant LUAC dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP) and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further reveal biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules and improved relapse-free survival. Differences in drug sensitivity patt...
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