jo ca | Drexel University (original) (raw)
Papers by jo ca
Biochemical Pharmacology, 2001
The effects of clozapine on the activities of nicotinic acetylcholine receptors (nAChRs) and volt... more The effects of clozapine on the activities of nicotinic acetylcholine receptors (nAChRs) and voltage-sensitive calcium channels (VSCCs) were investigated and compared with those of chlorpromazine (CPZ) in bovine adrenal chromaffin cells. [3H]Norepinephrine ([3H]NE) secretion induced by activation of nAChRs was inhibited by clozapine and CPZ with half-maximal inhibitory concentrations (ic50) of 10.4 ± 1.1 and 3.9 ± 0.2 μM, respectively.
Cyclops is a new architecture for high performance parallel computers being developed at the IBM ... more Cyclops is a new architecture for high performance parallel computers being developed at the IBM T. J. Watson Research Center. The basic cell of this architecture is a single-chip SMP system with multiple threads of execution, embedded memory, and integrated communications hardware. Massive intra-chip parallelism is used to tolerate memory and functional unit latencies. Large systems with thousands of chips can be built by replicating this basic cell in a regular pattern. In this paper we describe the Cyclops architecture and evaluate two of its new hardware features: memory hierarchy with flexible cache organization and fast barrier hardware. Our experiments with the STREAM benchmark show that a particular design can achieve a sustainable memory bandwidth of 40 GB/s, equal to the peak hardware bandwidth and similar to the performance of a 128-processor SGI Origin 3800. For small vectors, we have observed in-cache bandwidth above 80 GB/s. We also show that the fast barrier hardware can improve the performance of the Splash-2 FFT kernel by up to 10%. Our results demonstrate that the Cyclops approach of integrating a large number of simple processing elements and multiple memory banks in the same chip is an effective alternative for designing high performance systems.
Tumor Biology, 1992
In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovaria... more In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovarian cancer [121 with active disease, 108 in complete remission (CR)], and in 20 patients with other malignancies. Abnormal levels of CA 125 were found in 90% of patients with active ovarian cancer, in 1.8% of those in CR and in 38% of cases with other malignancies. Abnormal CA 19.9 serum levels were found in 36, 9 and 48% of these groups, respectively. Serum levels of both tumor markers were related to tumor stage and histological type. The highest levels of CA 125 were found in serous adenocarcinoma and the lowest in the mucinous type (p < 0.0001). In contrast, significantly higher CA 19.9 values were found in mucinous carcinoma than in other histologies (p < 0.0001). CA 125 and CA 19.9 were useful for monitoring disease activity in 88.3 and 32%, respectively, while one or other tumor marker was useful in 92% of patients. At the time of the second-look operation, abnormal CA 125 serum levels were found in 32% (6/19) of patients with active disease and in none of those with CR (0/38). CA 125 sensitivity was 83% (5/6) in those patients with residual tumor > 2 cm and in 8% (1/13) in those with tumor < 2 cm. CA 19.9 values were abnormally high in 16% of cases with persistent disease and in 11% of CR patients. In conclusion, our results confirm that CA 125 is a useful marker in ovarian carcinoma. CA 19.9 improves the results obtained with CA 125 alone only in mucinous adenocarcinomas.
Lancet Oncology, 2009
Background A population-based cohort of children aged 1-18 years with acute lymphoblastic leukaem... more Background A population-based cohort of children aged 1-18 years with acute lymphoblastic leukaemia (ALL) was treated with a dexamethasone-based protocol (Dutch Childhood Oncology Group [DCOG] ALL-9). We aimed to confi rm the results of the most eff ective DCOG ALL protocol for non-high-risk (NHR) patients to date (ALL-6), compare results with ALL-7 and ALL-8, and study prognostic factors in a non-randomised setting.
Biochimica Et Biophysica Acta-molecular Cell Research, 2009
Extracellular agonists increase the cytosolic free Ca 2+ concentration ([Ca 2+ ] c ) by Ca 2+ inf... more Extracellular agonists increase the cytosolic free Ca 2+ concentration ([Ca 2+ ] c ) by Ca 2+ influx and by stimulating Ca 2+ release from intracellular stores, mainly the endoplasmic reticulum and to a lesser extent also later compartments of the secretory pathway, particularly the Golgi. The Golgi takes up Ca 2+ via Sarco/Endoplasmic Reticulum Ca 2+ ATPases (SERCAs) and the Secretory-Pathway Ca 2+ ATPases (SPCAs). The endogenous expression of SERCAs and SPCAs neutrophils was demonstrated by Western blotting and immunocytochemistry. Up till now, all cytosolic Ca 2+ transients due to intracellular Ca 2+ release have been found to originate from SERCA-dependent stores. We found that human neutrophils also present Ca 2+ release from a SERCA-independent store. Changes in [Ca 2+ ] c of neutrophils were investigated during chemokinesis induced by chemotactic factors in Ca 2+ -free solution with and without the SERCA-specific inhibitor thapsigargin. Using N-formyl-methionyl-leucyl-phenylalanine or interleukin-8 as agonists, Ca 2+ release from intracellular stores was observed in respectively about 40% and 20% of the neutrophils pre-treated with Ca 2+free solution and thapsigargin. In the latter condition, 20-30% of the cells preserved migratory behaviour. These results indicate that both SERCA-dependent and SERCA-independent (presumably SPCA-dependent) intracellular Ca 2+ stores contribute to Ca 2+ signaling during chemokinesis of human neutrophil granulocytes.
Febs Letters, 1996
NSCP, a sarcoplasmic Ca2+/Mg2+-binding protein which have specific properties, different from the... more NSCP, a sarcoplasmic Ca2+/Mg2+-binding protein which have specific properties, different from the intact molefrom Nereis diversicolor, shows an ailosteric change during Ca 2~ cule [5]. binding and a high positive cooperativity for Mg 2+ binding. Here
Journal of Early Intervention, 1994
![Research paper thumbnail of Epigallocatechin-3-gallate increases intracellular [Ca 2+ ] in U87 cells mainly by influx of extracellular Ca 2+ and partly by release of intracellular stores](https://attachments.academia-assets.com/49455280/thumbnails/1.jpg)
](Naunyn-schmiedebergs Archives of Pharmacology, 2004
Green tea has been receiving considerable attention as a possible preventive agent against cancer... more Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 µM) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 µM) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 µM) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 µM) and flufenamic acid (100 µM), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 µM) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.
The temperature of the deep ocean plays a vital role in the Earth's climate system. Paleo-reconst... more The temperature of the deep ocean plays a vital role in the Earth's climate system. Paleo-reconstructions of deep-sea temperatures are generally dependent on Mg/Ca ratios measured from the carbonate tests of fossilized benthic foraminifera. Current Mg/Ca-temperature calibrations are based on empirical relationships which have been developed under present day environmental and chemical ocean conditions. However, the incorporation of Mg (DMg) into foraminiferal calcite is not solely dependent on temperature, but is also influenced by seawater chemistry. The Mg/Ca ratio of seawater in particular, plays a crucial role in determining the degree of incorporation of Mg in test carbonate. Due to its long oceanic residence time Mg concentrations remain relatively constant over time scales of a few hundred thousand years, yet can vary significantly over longer geological time scales. Therefore the accurate reconstruction of past temperatures using foraminiferal Mg/Ca ratios hinges on our understanding of Mg/Ca seawater changes over geological time. Here we present an independent approach to reconstructing paleo-seawater Mg/Ca using the temperature dependent offset in DMg incorporation between porcelaneous (high Mg) and hyaline (low Mg) foraminifera. Porcelaneous foraminifera produce smooth opaque tests made of needle shaped high Mg calcite, while hyaline foraminifera build perforate tests made of radial low Mg calcite. As DMg values are species specific, using foraminifera from the same time interval and environment (i.e. the same sample) eliminates the effect of temperature and seawater chemistry on DMg. Subsequently, combining a newly constructed Mg/Ca-temperature calibration for porcelaneous Pyrgo spp.(one of the few porcelaneous taxe present in the deep sea) with an existing calibration of hyaline Cibicides spp. allows us to mathematically solve for changes in Mg/Ca seawater through time using the species specific offset in DMg. Our results correspond well to changes in Mg/Ca of seawater as derived from geochemical models. Applying the newly reconstructed Mg/Casw curve to the published fossil record indicates that current Mg/Ca based temperature reconstructions prior to the mid Pleistocene, are significantly underestimating absolute temperature and therefore overestimating the growth of ice sheets via δ18Oc-Mg/Ca combined δ18Ow reconstructions.
British Journal of Cancer, 1993
Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemoth... more Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemotherapy was studied in 60 ovarian cancer patients and compared to known prognostic factors.
Biochemical Pharmacology, 2001
The effects of clozapine on the activities of nicotinic acetylcholine receptors (nAChRs) and volt... more The effects of clozapine on the activities of nicotinic acetylcholine receptors (nAChRs) and voltage-sensitive calcium channels (VSCCs) were investigated and compared with those of chlorpromazine (CPZ) in bovine adrenal chromaffin cells. [3H]Norepinephrine ([3H]NE) secretion induced by activation of nAChRs was inhibited by clozapine and CPZ with half-maximal inhibitory concentrations (ic50) of 10.4 ± 1.1 and 3.9 ± 0.2 μM, respectively.
Cyclops is a new architecture for high performance parallel computers being developed at the IBM ... more Cyclops is a new architecture for high performance parallel computers being developed at the IBM T. J. Watson Research Center. The basic cell of this architecture is a single-chip SMP system with multiple threads of execution, embedded memory, and integrated communications hardware. Massive intra-chip parallelism is used to tolerate memory and functional unit latencies. Large systems with thousands of chips can be built by replicating this basic cell in a regular pattern. In this paper we describe the Cyclops architecture and evaluate two of its new hardware features: memory hierarchy with flexible cache organization and fast barrier hardware. Our experiments with the STREAM benchmark show that a particular design can achieve a sustainable memory bandwidth of 40 GB/s, equal to the peak hardware bandwidth and similar to the performance of a 128-processor SGI Origin 3800. For small vectors, we have observed in-cache bandwidth above 80 GB/s. We also show that the fast barrier hardware can improve the performance of the Splash-2 FFT kernel by up to 10%. Our results demonstrate that the Cyclops approach of integrating a large number of simple processing elements and multiple memory banks in the same chip is an effective alternative for designing high performance systems.
Tumor Biology, 1992
In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovaria... more In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovarian cancer [121 with active disease, 108 in complete remission (CR)], and in 20 patients with other malignancies. Abnormal levels of CA 125 were found in 90% of patients with active ovarian cancer, in 1.8% of those in CR and in 38% of cases with other malignancies. Abnormal CA 19.9 serum levels were found in 36, 9 and 48% of these groups, respectively. Serum levels of both tumor markers were related to tumor stage and histological type. The highest levels of CA 125 were found in serous adenocarcinoma and the lowest in the mucinous type (p < 0.0001). In contrast, significantly higher CA 19.9 values were found in mucinous carcinoma than in other histologies (p < 0.0001). CA 125 and CA 19.9 were useful for monitoring disease activity in 88.3 and 32%, respectively, while one or other tumor marker was useful in 92% of patients. At the time of the second-look operation, abnormal CA 125 serum levels were found in 32% (6/19) of patients with active disease and in none of those with CR (0/38). CA 125 sensitivity was 83% (5/6) in those patients with residual tumor > 2 cm and in 8% (1/13) in those with tumor < 2 cm. CA 19.9 values were abnormally high in 16% of cases with persistent disease and in 11% of CR patients. In conclusion, our results confirm that CA 125 is a useful marker in ovarian carcinoma. CA 19.9 improves the results obtained with CA 125 alone only in mucinous adenocarcinomas.
Lancet Oncology, 2009
Background A population-based cohort of children aged 1-18 years with acute lymphoblastic leukaem... more Background A population-based cohort of children aged 1-18 years with acute lymphoblastic leukaemia (ALL) was treated with a dexamethasone-based protocol (Dutch Childhood Oncology Group [DCOG] ALL-9). We aimed to confi rm the results of the most eff ective DCOG ALL protocol for non-high-risk (NHR) patients to date (ALL-6), compare results with ALL-7 and ALL-8, and study prognostic factors in a non-randomised setting.
Biochimica Et Biophysica Acta-molecular Cell Research, 2009
Extracellular agonists increase the cytosolic free Ca 2+ concentration ([Ca 2+ ] c ) by Ca 2+ inf... more Extracellular agonists increase the cytosolic free Ca 2+ concentration ([Ca 2+ ] c ) by Ca 2+ influx and by stimulating Ca 2+ release from intracellular stores, mainly the endoplasmic reticulum and to a lesser extent also later compartments of the secretory pathway, particularly the Golgi. The Golgi takes up Ca 2+ via Sarco/Endoplasmic Reticulum Ca 2+ ATPases (SERCAs) and the Secretory-Pathway Ca 2+ ATPases (SPCAs). The endogenous expression of SERCAs and SPCAs neutrophils was demonstrated by Western blotting and immunocytochemistry. Up till now, all cytosolic Ca 2+ transients due to intracellular Ca 2+ release have been found to originate from SERCA-dependent stores. We found that human neutrophils also present Ca 2+ release from a SERCA-independent store. Changes in [Ca 2+ ] c of neutrophils were investigated during chemokinesis induced by chemotactic factors in Ca 2+ -free solution with and without the SERCA-specific inhibitor thapsigargin. Using N-formyl-methionyl-leucyl-phenylalanine or interleukin-8 as agonists, Ca 2+ release from intracellular stores was observed in respectively about 40% and 20% of the neutrophils pre-treated with Ca 2+free solution and thapsigargin. In the latter condition, 20-30% of the cells preserved migratory behaviour. These results indicate that both SERCA-dependent and SERCA-independent (presumably SPCA-dependent) intracellular Ca 2+ stores contribute to Ca 2+ signaling during chemokinesis of human neutrophil granulocytes.
Febs Letters, 1996
NSCP, a sarcoplasmic Ca2+/Mg2+-binding protein which have specific properties, different from the... more NSCP, a sarcoplasmic Ca2+/Mg2+-binding protein which have specific properties, different from the intact molefrom Nereis diversicolor, shows an ailosteric change during Ca 2~ cule [5]. binding and a high positive cooperativity for Mg 2+ binding. Here
Journal of Early Intervention, 1994
Naunyn-schmiedebergs Archives of Pharmacology, 2004
Green tea has been receiving considerable attention as a possible preventive agent against cancer... more Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 µM) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 µM) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 µM) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 µM) and flufenamic acid (100 µM), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 µM) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.
The temperature of the deep ocean plays a vital role in the Earth's climate system. Paleo-reconst... more The temperature of the deep ocean plays a vital role in the Earth's climate system. Paleo-reconstructions of deep-sea temperatures are generally dependent on Mg/Ca ratios measured from the carbonate tests of fossilized benthic foraminifera. Current Mg/Ca-temperature calibrations are based on empirical relationships which have been developed under present day environmental and chemical ocean conditions. However, the incorporation of Mg (DMg) into foraminiferal calcite is not solely dependent on temperature, but is also influenced by seawater chemistry. The Mg/Ca ratio of seawater in particular, plays a crucial role in determining the degree of incorporation of Mg in test carbonate. Due to its long oceanic residence time Mg concentrations remain relatively constant over time scales of a few hundred thousand years, yet can vary significantly over longer geological time scales. Therefore the accurate reconstruction of past temperatures using foraminiferal Mg/Ca ratios hinges on our understanding of Mg/Ca seawater changes over geological time. Here we present an independent approach to reconstructing paleo-seawater Mg/Ca using the temperature dependent offset in DMg incorporation between porcelaneous (high Mg) and hyaline (low Mg) foraminifera. Porcelaneous foraminifera produce smooth opaque tests made of needle shaped high Mg calcite, while hyaline foraminifera build perforate tests made of radial low Mg calcite. As DMg values are species specific, using foraminifera from the same time interval and environment (i.e. the same sample) eliminates the effect of temperature and seawater chemistry on DMg. Subsequently, combining a newly constructed Mg/Ca-temperature calibration for porcelaneous Pyrgo spp.(one of the few porcelaneous taxe present in the deep sea) with an existing calibration of hyaline Cibicides spp. allows us to mathematically solve for changes in Mg/Ca seawater through time using the species specific offset in DMg. Our results correspond well to changes in Mg/Ca of seawater as derived from geochemical models. Applying the newly reconstructed Mg/Casw curve to the published fossil record indicates that current Mg/Ca based temperature reconstructions prior to the mid Pleistocene, are significantly underestimating absolute temperature and therefore overestimating the growth of ice sheets via δ18Oc-Mg/Ca combined δ18Ow reconstructions.
British Journal of Cancer, 1993
Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemoth... more Serum CA 125 regression after cytoreductive surgery and during the first three courses of chemotherapy was studied in 60 ovarian cancer patients and compared to known prognostic factors.