Douglas Leal - Academia.edu (original) (raw)
Papers by Douglas Leal
Plant Molecular Biology, 1993
A cDNA library was made from poly(A)+ RNA isolated from developing Douglas fir (Pseudotsuga menzi... more A cDNA library was made from poly(A)+ RNA isolated from developing Douglas fir (Pseudotsuga menziesii) embryo and megagametophytic tissue, and the cDNA clones were identified by immunoscreening with polyclonal antiserum against the crystalloid storage protein complex of Douglas fir. The nucleotide sequence of the longest cDNA insert (DF1) was analysed. The amino acid sequence derived from the DNA sequence verified its identity as a legumin-like storage protein (pseudotsugin) and confirmed that the protein is synthesized as a precursor similar to the 11–12S storage globulins. The transcripts corresponding to cDNA insert DF1 were abundant in the early-to mid-stages of embryogenesis in the diploid embryonic axes as well as in the haploid megagametophytic tissue. The deduced amino acid sequence of pseudotsugin consists of a 29 amino acid N-terminal signal peptide preceding the acidic polypeptide region (286 amino acids) and the subsequent basic polypeptide region (212 amino acids). The site for post-transcriptional cleavage of the precursor polypeptide to make the A and B polypeptides is localized between asparagine −315 and glycine −316 and is highly conserved between angiosperms and gymnosperms. The deduced amino acid sequence for the DF1 cDNA clone reveals that pseudotsugin is rich in arginine, glutamic acid and serine and is low in cysteine, methionine and lysine. Comparison of the deduced amino acid sequence of Douglas fir pseudotsugin shows between 29–38.5% identity with angiosperm species, 63% identity with interior spruce, and 60% identity with eastern white pine.
Obstetrics and Gynecology, 2001
... However, you may be able to access this article under your organization's agreement with... more ... However, you may be able to access this article under your organization's agreement with Elsevier. Victoria E. Carr-Brendel PhD, Dennis R. Stewart PhD, Douglas C. Harrington , JG Garza Leal MD and Thierry Vancaillie MD. Adiana, Inc, Redwood City, CA, USA. ...
Lasers in Medical Science, 2011
In the last years, phototherapy has becoming a promising tool to improve skeletal muscle recovery... more In the last years, phototherapy has becoming a promising tool to improve skeletal muscle recovery after exercise, however, it was not compared with other modalities commonly used with this aim. In the present study we compared the short-term effects of cold water immersion therapy (CWIT) and light emitting diode therapy (LEDT) with placebo LEDT on biochemical markers related to skeletal muscle recovery after high-intensity exercise. A randomized double-blind placebo-controlled crossover trial was performed with six male young futsal athletes. They were treated with CWIT (5°C of temperature [SD ±1°]), active LEDT (69 LEDs with wavelengths 660/850 nm, 10/30 mW of output power, 30 s of irradiation time per point, and 41.7 J of total energy irradiated per point, total of ten points irradiated) or an identical placebo LEDT 5 min after each of three Wingate cycle tests. Pre-exercise, post-exercise, and post-treatment measurements were taken of blood lactate levels, creatine kinase (CK) activity, and C-reactive protein (CRP) levels. There were no significant differences in the work performed during the three Wingate tests (p > 0.05). All biochemical parameters increased from baseline values (p < 0.05) after the three exercise tests, but only active LEDT decreased blood lactate levels (p = 0.0065) and CK activity (p = 0.0044) significantly after treatment. There were no significant differences in CRP values after treatments. We concluded that treating the leg muscles with LEDT 5 min after the Wingate cycle test seemed to inhibit the expected post-exercise increase in blood lactate levels and CK activity. This suggests that LEDT has better potential than 5 min of CWIT for improving short-term post-exercise recovery.
Journal of Applied Physiology, 2010
Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eu... more Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-kappaB (NF-kappaB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 microg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (DeltaP1) and viscoelastic (DeltaP2) pressures, static elastance (E(st)), and viscoelastic component of elastance (DeltaE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-alpha was determined by ELISA. Lung tissue expression of NF-kappaB was determined by EMSA. DeltaP1, DeltaP2, E(st), and DeltaE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-alpha levels and NF-kappaB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.
The redistributed chip packaging is an embedded chip technology that eliminates the need for wire... more The redistributed chip packaging is an embedded chip technology that eliminates the need for wirebonds and flip chip bumps. This technology enables smaller packages at a lower cost, while providing improved mechanical, electrical and thermal performance. The process involves producing panels placing the chip active face down along with an embedded ground plane (EGP) and screen printing encapsulant to embed the die. Subsequently alternate layers of dielectric and Cu metallization are built up and the packages are sawn into individual units. The use of wafer fabrication tools enables finer lines and spaces in the build-up layers. This paper will discuss process conditions during the panelization and the integration of the base function of an i.275 GSM/EDGE mobile phone into a single module measuring a maximum of 1 square inch. The design of the EGP and the role of simulations to achieve a robust, reliable package will also be discussed. The outputs included moisture sensitivity level (MSL) 3 testing, air-to-air thermal cycling (- 40C/125C) and unbiased highly accelerated stress testing (HAST). Testing of RCP packages will also be discussed.
Journal of Medicinal Chemistry, 2005
The heptapeptide 1, NAc-Gly-Val-DIle-Thr-Arg-Ile-ArgNHEt, a structurally modified fragment derive... more The heptapeptide 1, NAc-Gly-Val-DIle-Thr-Arg-Ile-ArgNHEt, a structurally modified fragment derived from the second type-1 repeat of thrombospondin-1 (TSP-1), is known to possess antiangiogenic activity. However, therapeutic utility could not be demonstrated because this peptide has a very short half-life in rodents. To optimize the PD/PK profile of 1, we initiated a systematic SAR study. The initial structural modifications were performed at positions 5 and 7 of peptide 1 and at the N- and C-termini. Out of several hundred peptides synthesized, the nonapeptide 5 (ABT-526) emerged as a promising lead. ABT-526 inhibited VEGF-induced HMVEC cell migration and tube formation in the nanomolar range and increased apoptosis of HUAEC cells. ABT-526 showed acceptable PK in rodents, dog, and monkey. ABT-526, when incorporated in an angiogenic pellet implanted in the rat cornea at 10 microM, reduced neovascularization by 92%. Substitution of DalloIle in place of DIle in ABT-526 provided nonapeptide 6 (ABT-510), which was 30-fold less active than ABT-526 in the EC migration but 20-fold more active in the tube formation assay. In comparison to ABT-526, ABT-510 has increased water solubility and slower clearance in dog and monkey. Radiolabeled ABT-510 demonstrated saturable binding to HMVEC cells at 0.02-20 nM concentrations and was displaceable by TSP-1. ABT-510 and ABT-526 were shown to significantly increase apoptosis of HUAEC cells. ABT-510 was effective in blocking neovascularization in the mouse Matrigel plug model and inhibited tumor growth in the mouse Lewis lung carcinoma model. Previous studies had shown that ABT-510 was effective in inhibiting the outgrowth of murine melanoma metastases in syngeneic mice and in blocking the growth of human bladder carcinoma implanted in nude mice. It had been also shown that ABT-510 could regress tumor lesions in pet dogs or cause unexpected stabilization of the disease in advanced canine cancer. ABT-526 and ABT-510 are the first compounds in the class of potent inhibitors of angiogenesis that mimic the antiangiogenic function of TSP-1. ABT-510 is currently in phase II clinical studies.
Materials Science Forum, 2005
It is well known that colloidal powder particles (between 1 mm and 0.001 mm) tend to agglomerate ... more It is well known that colloidal powder particles (between 1 mm and 0.001 mm) tend to agglomerate due to electrostatic forces. Then assuring an optimal dispersion condition is essential for good particle-size analysis results, since aggregates or weak agglomerates can be measured as single particles. In this paper the particle size distribution of an alumina powder A1000SG (ALCOA) was measured using distinct dispersion procedures. Distilled water was used as dispersant liquid in the pure state and with additives (citric acid and Duramax D-3005). Dispersion by supersonic vibration was also investigated, but only the application time was varied. Particle size analysis was accomplished by laser scattering technique and the dispersion condition was evaluated through zeta potential. The results showed that the Duramax's electrosteric impediment is more efficient than citric acid's electrostatic force, thereby providing better dispersion. Although useful, the supersonic vibration was not good enough to assure an optimal dispersion, at least for the material tested here.
O trabalho teve por objetivo comparar os interpoladores: inverso do quadrado da distância, krigag... more O trabalho teve por objetivo comparar os interpoladores: inverso do quadrado da distância, krigagem ordinária e spline usando observações de precipitação pluvial média anual, de modo a dar suporte para a análise do comportamento espacial da chuva e do planejamento urbano, especialmente no que se refere à ocorrência de eventos extremos. Escolheu-se como recorte o Distrito Federal, mais especificamente a Bacia do Paranoá, por tratar-se da área que abrange a maior parte do perímetro urbano. Com base em dados fornecidos pela Companhia de Água e Esgoto de Brasília, bem como na Normal Climatológica elaborada pelo Instituto Nacional de Meteorologia, foi analisado o período de 1990 a 2008, em 13 estações tendo por parâmetro a data de dez de abril. Os resultados mostraram que a diferença entre os valores observados e estimados pelo spline foi menor do que para outros métodos, indicando ser esse o interpolador a ser usado na distribuição espacial da precipitação pluvial para os dados em estudo.Por fim, tenciona-se ampliar a discussão acerca da definição e dos parâmetros de avaliação de evento extremo, propondo-se uma apreciação que envolva uma quantidade maior de variáveis relativas aos aspectos do planejamento urbano.
Plant Molecular Biology, 1993
A cDNA library was made from poly(A)+ RNA isolated from developing Douglas fir (Pseudotsuga menzi... more A cDNA library was made from poly(A)+ RNA isolated from developing Douglas fir (Pseudotsuga menziesii) embryo and megagametophytic tissue, and the cDNA clones were identified by immunoscreening with polyclonal antiserum against the crystalloid storage protein complex of Douglas fir. The nucleotide sequence of the longest cDNA insert (DF1) was analysed. The amino acid sequence derived from the DNA sequence verified its identity as a legumin-like storage protein (pseudotsugin) and confirmed that the protein is synthesized as a precursor similar to the 11–12S storage globulins. The transcripts corresponding to cDNA insert DF1 were abundant in the early-to mid-stages of embryogenesis in the diploid embryonic axes as well as in the haploid megagametophytic tissue. The deduced amino acid sequence of pseudotsugin consists of a 29 amino acid N-terminal signal peptide preceding the acidic polypeptide region (286 amino acids) and the subsequent basic polypeptide region (212 amino acids). The site for post-transcriptional cleavage of the precursor polypeptide to make the A and B polypeptides is localized between asparagine −315 and glycine −316 and is highly conserved between angiosperms and gymnosperms. The deduced amino acid sequence for the DF1 cDNA clone reveals that pseudotsugin is rich in arginine, glutamic acid and serine and is low in cysteine, methionine and lysine. Comparison of the deduced amino acid sequence of Douglas fir pseudotsugin shows between 29–38.5% identity with angiosperm species, 63% identity with interior spruce, and 60% identity with eastern white pine.
Obstetrics and Gynecology, 2001
... However, you may be able to access this article under your organization's agreement with... more ... However, you may be able to access this article under your organization's agreement with Elsevier. Victoria E. Carr-Brendel PhD, Dennis R. Stewart PhD, Douglas C. Harrington , JG Garza Leal MD and Thierry Vancaillie MD. Adiana, Inc, Redwood City, CA, USA. ...
Lasers in Medical Science, 2011
In the last years, phototherapy has becoming a promising tool to improve skeletal muscle recovery... more In the last years, phototherapy has becoming a promising tool to improve skeletal muscle recovery after exercise, however, it was not compared with other modalities commonly used with this aim. In the present study we compared the short-term effects of cold water immersion therapy (CWIT) and light emitting diode therapy (LEDT) with placebo LEDT on biochemical markers related to skeletal muscle recovery after high-intensity exercise. A randomized double-blind placebo-controlled crossover trial was performed with six male young futsal athletes. They were treated with CWIT (5°C of temperature [SD ±1°]), active LEDT (69 LEDs with wavelengths 660/850 nm, 10/30 mW of output power, 30 s of irradiation time per point, and 41.7 J of total energy irradiated per point, total of ten points irradiated) or an identical placebo LEDT 5 min after each of three Wingate cycle tests. Pre-exercise, post-exercise, and post-treatment measurements were taken of blood lactate levels, creatine kinase (CK) activity, and C-reactive protein (CRP) levels. There were no significant differences in the work performed during the three Wingate tests (p > 0.05). All biochemical parameters increased from baseline values (p < 0.05) after the three exercise tests, but only active LEDT decreased blood lactate levels (p = 0.0065) and CK activity (p = 0.0044) significantly after treatment. There were no significant differences in CRP values after treatments. We concluded that treating the leg muscles with LEDT 5 min after the Wingate cycle test seemed to inhibit the expected post-exercise increase in blood lactate levels and CK activity. This suggests that LEDT has better potential than 5 min of CWIT for improving short-term post-exercise recovery.
Journal of Applied Physiology, 2010
Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eu... more Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-kappaB (NF-kappaB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 microg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (DeltaP1) and viscoelastic (DeltaP2) pressures, static elastance (E(st)), and viscoelastic component of elastance (DeltaE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-alpha was determined by ELISA. Lung tissue expression of NF-kappaB was determined by EMSA. DeltaP1, DeltaP2, E(st), and DeltaE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-alpha levels and NF-kappaB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.
The redistributed chip packaging is an embedded chip technology that eliminates the need for wire... more The redistributed chip packaging is an embedded chip technology that eliminates the need for wirebonds and flip chip bumps. This technology enables smaller packages at a lower cost, while providing improved mechanical, electrical and thermal performance. The process involves producing panels placing the chip active face down along with an embedded ground plane (EGP) and screen printing encapsulant to embed the die. Subsequently alternate layers of dielectric and Cu metallization are built up and the packages are sawn into individual units. The use of wafer fabrication tools enables finer lines and spaces in the build-up layers. This paper will discuss process conditions during the panelization and the integration of the base function of an i.275 GSM/EDGE mobile phone into a single module measuring a maximum of 1 square inch. The design of the EGP and the role of simulations to achieve a robust, reliable package will also be discussed. The outputs included moisture sensitivity level (MSL) 3 testing, air-to-air thermal cycling (- 40C/125C) and unbiased highly accelerated stress testing (HAST). Testing of RCP packages will also be discussed.
Journal of Medicinal Chemistry, 2005
The heptapeptide 1, NAc-Gly-Val-DIle-Thr-Arg-Ile-ArgNHEt, a structurally modified fragment derive... more The heptapeptide 1, NAc-Gly-Val-DIle-Thr-Arg-Ile-ArgNHEt, a structurally modified fragment derived from the second type-1 repeat of thrombospondin-1 (TSP-1), is known to possess antiangiogenic activity. However, therapeutic utility could not be demonstrated because this peptide has a very short half-life in rodents. To optimize the PD/PK profile of 1, we initiated a systematic SAR study. The initial structural modifications were performed at positions 5 and 7 of peptide 1 and at the N- and C-termini. Out of several hundred peptides synthesized, the nonapeptide 5 (ABT-526) emerged as a promising lead. ABT-526 inhibited VEGF-induced HMVEC cell migration and tube formation in the nanomolar range and increased apoptosis of HUAEC cells. ABT-526 showed acceptable PK in rodents, dog, and monkey. ABT-526, when incorporated in an angiogenic pellet implanted in the rat cornea at 10 microM, reduced neovascularization by 92%. Substitution of DalloIle in place of DIle in ABT-526 provided nonapeptide 6 (ABT-510), which was 30-fold less active than ABT-526 in the EC migration but 20-fold more active in the tube formation assay. In comparison to ABT-526, ABT-510 has increased water solubility and slower clearance in dog and monkey. Radiolabeled ABT-510 demonstrated saturable binding to HMVEC cells at 0.02-20 nM concentrations and was displaceable by TSP-1. ABT-510 and ABT-526 were shown to significantly increase apoptosis of HUAEC cells. ABT-510 was effective in blocking neovascularization in the mouse Matrigel plug model and inhibited tumor growth in the mouse Lewis lung carcinoma model. Previous studies had shown that ABT-510 was effective in inhibiting the outgrowth of murine melanoma metastases in syngeneic mice and in blocking the growth of human bladder carcinoma implanted in nude mice. It had been also shown that ABT-510 could regress tumor lesions in pet dogs or cause unexpected stabilization of the disease in advanced canine cancer. ABT-526 and ABT-510 are the first compounds in the class of potent inhibitors of angiogenesis that mimic the antiangiogenic function of TSP-1. ABT-510 is currently in phase II clinical studies.
Materials Science Forum, 2005
It is well known that colloidal powder particles (between 1 mm and 0.001 mm) tend to agglomerate ... more It is well known that colloidal powder particles (between 1 mm and 0.001 mm) tend to agglomerate due to electrostatic forces. Then assuring an optimal dispersion condition is essential for good particle-size analysis results, since aggregates or weak agglomerates can be measured as single particles. In this paper the particle size distribution of an alumina powder A1000SG (ALCOA) was measured using distinct dispersion procedures. Distilled water was used as dispersant liquid in the pure state and with additives (citric acid and Duramax D-3005). Dispersion by supersonic vibration was also investigated, but only the application time was varied. Particle size analysis was accomplished by laser scattering technique and the dispersion condition was evaluated through zeta potential. The results showed that the Duramax's electrosteric impediment is more efficient than citric acid's electrostatic force, thereby providing better dispersion. Although useful, the supersonic vibration was not good enough to assure an optimal dispersion, at least for the material tested here.
O trabalho teve por objetivo comparar os interpoladores: inverso do quadrado da distância, krigag... more O trabalho teve por objetivo comparar os interpoladores: inverso do quadrado da distância, krigagem ordinária e spline usando observações de precipitação pluvial média anual, de modo a dar suporte para a análise do comportamento espacial da chuva e do planejamento urbano, especialmente no que se refere à ocorrência de eventos extremos. Escolheu-se como recorte o Distrito Federal, mais especificamente a Bacia do Paranoá, por tratar-se da área que abrange a maior parte do perímetro urbano. Com base em dados fornecidos pela Companhia de Água e Esgoto de Brasília, bem como na Normal Climatológica elaborada pelo Instituto Nacional de Meteorologia, foi analisado o período de 1990 a 2008, em 13 estações tendo por parâmetro a data de dez de abril. Os resultados mostraram que a diferença entre os valores observados e estimados pelo spline foi menor do que para outros métodos, indicando ser esse o interpolador a ser usado na distribuição espacial da precipitação pluvial para os dados em estudo.Por fim, tenciona-se ampliar a discussão acerca da definição e dos parâmetros de avaliação de evento extremo, propondo-se uma apreciação que envolva uma quantidade maior de variáveis relativas aos aspectos do planejamento urbano.