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ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC sympto

Research on Ru anti-cancer drugs is on the rise with many complexes in clinical trials. Inductively coupled plasma-mass spectrometry (ICP-MS) has been the standard technique for bioanalytical studies on Ru and Pt complexes in biological media. Tedious ICP-MS methods rely on detecting and quantifying the element while lacking important structural information of the original complexes. Despite being equally sensitive, more accessible, and highly selective to the target species, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not been validated for the analysis of Ru drugs. Using USFDA guidelines, we report here the optimization and validation of a facile LC-MS/MS method for the detection and quantification of three Ru(II) polypyridyl complexes in cells, plasma, and urine matrices. Importantly, a fast (10 min), single-step procedure was efficient for both extraction and sample purification, and analytes were rapidly eluted over a 3 min simple isocratic run. Specific parent ions were differentially fragmented by tandem MS, thus forming a unique and rational ligand dissociation chemistry that exhibits high selectivity to the target species with no measurable interferences or matrix effects. The developed LC-MS/MS method was advantageous vis-à-vis the prototypical ICP-MS based techniques both in vitro and in vivo, paving the way for its utilization in elaborate cellular uptake, pharmacokinetics, and pharmacodynamics studies.

Photoactivated chemotherapy (PACT) is an emerging strategy for targeted cancer therapy. Strained Ru complexes with pseudo-octahedral geometry may undergo photo-induced ligand dissociation, forming aquated photoproducts that are significantly more cytotoxic compared to the precursor complex. The complexes investigated were the strained complex [Ru(bpy)2BC]Cl2 (where bpy = 2,2′-bipyridine and BC = bathocuproine) and its unstrained control [Ru(bpy)2phen]Cl2 (where phen = 1,10-phenanthroline). The uptake of [Ru(bpy)2BC]Cl2, assessed by ICP/MS, started immediately post-incubation and plateaued after 24 h. Active transport was found as the main mode of intracellular transport. Cell viability assays on A375 cells indicated a mean phototoxicity index of 340-fold, and the effect was shown to be primarily mediated by the aquated photoproducts rather than the dissociating ligands. A significant increase in ROS production and DNA damage was also observed. Flow cytometry confirmed the induction of early apoptosis at 48 h that proceeds to late apoptosis/necrosis by 72 h post-treatment. Western blot analysis of pro- and anti-apoptotic proteins revealed that apoptosis was mediated through an interplay between the intrinsic and extrinsic pathways, as well as autophagy and via inhibition of the MAPK and PI3K pathways. In conclusion, this study demonstrates that [Ru(bpy)2BC]Cl2 is a multi-mechanistic PACT drug which exhibits promising anticancer potential.

The photoactivatable Ru (II) complex 1 [Ru(bipy)2(dpphen)]Cl2 (where bipy = 2,2′-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) has been shown to possess promising anticancer activity against triple negative adenocarcinoma MDA-MB-231 cells. The present study aims to elucidate the plausible mechanism of action of the photoactivatable complex 1 against MDA-MB-231 cells. Upon photoactivation, complex 1 exhibited time-dependent cytotoxic activity with a phototoxicity index (P Index) of >100 after 72 h. A significant increase in cell rounding and detachment, loss of membrane integrity, ROS accumulation and DNA damage was observed. Flow cytometry and a fluorescent apoptosis/necrosis assay showed an induction of cell apoptosis. Western blot analysis revealed the induction of intrinsic and extrinsic pathways and inhibition of the MAPK and PI3K pathways. The photoproduct of complex 1 showed similar effects on key apoptotic protein expression confirming that it is behind the observed cell death. In conclusion, the present study revealed that complex 1 is a potent multi-mechanistic photoactivatable chemotherapeutic drug that may serve as a potential lead molecule for targeted cancer chemotherapy.

Visible light has long been recognized as a treatment for many diseases and an essential component of photo-induced chemotherapy. While previous data proved its inherent cytotoxicity, this study is the first to explore the use of a commercially available, high-intensity white LED light (24.5 mW.cm−2) as a treatment for skin tumors. After a 9-h exposure in vitro, the viability of Human Malignant Melanoma cells (A375) decreased by around 70%. Western blot analysis suggested an apoptotic cell death confirmed by the upregulation of Bax, cleaved PARP/caspase-3/8, cytochrome c, and t-bid. Additionally, cellular ROS accumulation and DNA damage were induced upon irradiation with blue light. When tested on a DMBA/TPA skin carcinogenesis model, a 90-min exposure to white light thrice weekly resulted in a significant decrease in tumor volumes/incidence compared to control and cisplatin groups, and restored normal morphological features, as confirmed by histopathology. Toxicological evaluation of ight-treated animals indicated a 100% survival rate, no skin irritation, no signs of discomfort or changes in body weight/behavior, and no toxicities to vital organs. Although these results must be confirmed by further studies, this research showed that short-exposure by commercially available high-intensity white LED light irradiation may be a promising approach for the treatment of superficial malignancies.

The purpose of this study is to analyse the perceptions of Comrades Marathon runners concerning the application of virtual reality technologies as a strategic response to the effects of COVID-19 in South Africa. Furthermore, the study also assesses the runners’ challenges and readiness to participate in virtualised marathons post-COVID-19 pandemic. Data were collected from Comrades Marathon runners using online interviews. However, the study results showed mixed perceptions concerning virtual reality application to an outdoor sporting event like the Comrades Marathon in South Africa. Regardless of these perceptions, managers of sporting events are encouraged to make significant investments for the strategic development of virtual sports in the wake of the second wave of the COVID-19 pandemic.

The purpose of this study is to analyse the perceptions of Comrades Marathon runners concerning the application of virtual reality technologies as a strategic response to the effects of COVID-19 in South Africa. Furthermore, the study also assesses the runners’ challenges and readiness to participate in virtualised marathons post-COVID-19 pandemic. Data were collected from Comrades Marathon runners using online interviews. However, the study results showed mixed perceptions concerning virtual reality application to an outdoor sporting event like the Comrades Marathon in South Africa. Regardless of these perceptions, managers of sporting events are encouraged to make significant investments for the strategic development of virtual sports in the wake of the second wave of the COVID-19 pandemic.

PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse

PURPOSE The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5x upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5x upper limit of normal as an additional adverse prognostic factor.

PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse

PURPOSE The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5x upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5x upper limit of normal as an additional adverse prognostic factor.

PURPOSEClinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.PATIENTS AND METHODSData from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.RESULTSMedian time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.CONCLUSIONOutcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).

PURPOSEClinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.PATIENTS AND METHODSData from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.RESULTSMedian time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.CONCLUSIONOutcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).

In 2016, the World Health Organization classification system of testicular tumors included the new entity prepubertal-type teratoma based on its morphological and molecular profile, and the realization that these tumors may occur in postpubertal men. For treatment and prognostic purposes, it is important to distinguish prepubertal-type teratoma from the usual postpubertal-type teratoma, because the former is benign unlike the latter. The distinction may be challenging. In this study, we investigated clinical, morphological, and molecular criteria for distinguishing prepubertal-type teratoma from postpubertal-type teratoma in a prospective series of pure testicular teratomas. All cases of pure teratoma in postpubertal men assessed at Barts Health NHS Trust or in consultation since the introduction of routine investigation of chromosome 12p status in 2010 were reviewed. Morphological features suggestive of prepubertal-type teratoma were observed in 14 out of 35 cases. All underwent molecular testing and none displayed 12p amplification. Mean tumor size was 16 mm (range 7-28 mm). None had associated germ cell neoplasia in situ or significant atrophy. Four incorporated a well-differentiated neuroendocrine tumor, 1-2 mm in size. Of the ten patients with follow-up information, none have recurred or metastasized. Twenty-one of the 35 cases were diagnosed as postpubertal-type teratoma, mean tumor size 40 mm (range 6-90 mm). One case underwent molecular testing: a tumor of pure skeletal muscle differentiation and possessed 12p amplification. Three cases presented with clinical metastases. Eight cases contained immature areas, ten cases had associated germ cell neoplasia in situ, and 17 cases had severe atrophy of the parenchyma. One case with neither germ cell neoplasia in situ nor atrophy showed necrosis. We conclude that both morphological and molecular features are of help in differentiating prepubertal-type teratoma from postpubertal-type teratoma. In nearly all postp

PURPOSE Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment. PATIENTS AND METHODS Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses. RESULTS Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes. CONCLUSION Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).

The current study investigates [Ru(bipy)2(dpphen)]Cl2 [where bipy = 2,2′‐bipyridine and dpphen = 2,9‐diphenyl‐1,10‐phenanthroline] (complex 1) for photoactivatable chemotherapy (PACT) application on five cancer cell lines. [Ru(bipy)2(phen)]Cl2 [where phen = 1,10‐phenanthroline] (complex 2) was included as an unstrained control. Upon excitation with visible light, complex 2 proved to be photostable while complex 1 underwent a quantitative dissociation of the bipy ligand and formation of a RuII polypyridyl aqua complex in water. Complex 1 demonstrated only marginal activity in the dark; its cytotoxicity increased significantly upon photoactivation with a high phototoxicity index (PI = [IC50 dark]/[IC50 light]) ranging from 39.2‐fold in A549 to over 100‐fold in MDA‐MB‐231. Complex 2, on the other hand, did not show much difference in anticancer activity between dark and light conditions. Importantly, the IC50 of the photoproduct of complex 1 was several folds lower than that of cisplatin in all tested cell lines. Furthermore, the dissociating ligand (bipy) was biologically inert in almost all cell lines investigated confirming that phototoxicity was mediated primarily by the Ru aqua complex that is released upon irradiation. In conclusion, the Ru‐centered complex 1 could represent a potential photoactivatable chemotherapeutic drug that increases selectivity to tumors and offers alternative treatment in the light of increasing cisplatin resistance.

Damage to podocytes is a key event in glomerulopathies. While energy dense food can contribute to kidney damage, the role of the orixegenic hormone “ghrelin” in podocyte biology is still unknown. In the present study, we investigated the effect of ghrelin on podocyte survival as well as the signalling pathways mediating ghrelin effect in immortalized cultured rat podocytes. RT‐PCR analysis revealed that GHS‐R1 is expressed in rat podocytes. Western blot analysis showed that ghrelin upregulated COX‐2 protein expression in a time and dose‐dependent manner. Additionally, ghrelin activated P38 MAPK, AKT, and ERK1/2 pathways and also induced P38 MAPK phosphorylation in high glucose conditions. Ghrelin induced ROS release and dose dependently reduced podocyte survival. Ghrelin mediated podocyte cell death was partially reversed by pharmacologically inhibiting P38 MAPK or phospholipase C (PLC). Furthermore, PLC inhibitor (U73122) inhibited ghrelin induced P38 MAPK activation. While PI3K inhibitor (LY294002) was without effect on cell survival or P38 MAPK activation, it inhibited ghrelin induced ERK1/2 phosphorylation. Finally, ghrelin induced TAU phosphorylation was reversed by pharmacologic inhibitors of either P38 MAPK or PKA. In conclusion, ghrelin activated harmful molecular pathways in podocytes that can be damaging to the glomerular filtration barrier

The use of ruthenium complexes as chemotherapeutic agents has been recently explored as one of the alternatives to conventional treatments. In the present study, two Ru(II) polypyridyl complexes were synthesized and characterized: a strained [Ru(bipy)2(BC)]Cl2 (complex 1) where [bipy = 2,2′-bipyridine and BC = bathocuproine] along with the unstrained control [Ru(bipy)2(phen)]Cl2 (complex 2) where [phen = 1,10-phenanthroline]. The photophysical and photochemical analyses proved that unlike the photostable complex 2, complex 1 ejected both bipy and BC ligands at a ratio of 3[thin space (1/6-em)]:[thin space (1/6-em)]1 respectively. Results showed that the activity of complex 1 was significantly enhanced upon photoactivation. The response was however particularly significant in B16-F10 melanoma cells where phototoxicity index (PI = IC50 dark/IC50 light) was >900. When compared to cisplatin, the photoproducts were more potent against all tested cell lines, implying that the complex acquired significant chemotherapeutic potential upon irradiation. Cellular uptake of complex 1 and the free BC ligand were found to be significantly facilitated as evidenced by 400–600 fold increase in concentration of the compounds inside the cells relative to the extracellular culture medium. Complex 2 exhibited 35 times lower cellular concentration relative to complex 1. Flow cytometry and plasmid DNA gel electrophoresis measurements showed that complex 1 interacts with DNA inducing apoptosis in the dark and either late-apoptosis or necrosis upon irradiation. These findings corroborate the importance of lipophilic ligands such as BC to enhance uptake and subsequently improve the photochemotherapy potential of Ru(II) polypyridyl complexes.

The current study investigates [Ru(bipy)2(dpphen)]Cl2 [where bipy = 2,2′‐bipyridine and dpphen = 2,9‐diphenyl‐1,10‐phenanthroline] (complex 1) for photoactivatable chemotherapy (PACT) application on five cancer cell lines. [Ru(bipy)2(phen)]Cl2 [where phen = 1,10‐phenanthroline] (complex 2) was included as an unstrained control. Upon excitation with visible light, complex 2 proved to be photostable while complex 1 underwent a quantitative dissociation of the bipy ligand and formation of a RuII polypyridyl aqua complex in water. Complex 1 demonstrated only marginal activity in the dark; its cytotoxicity increased significantly upon photoactivation with a high phototoxicity index (PI = [IC50 dark]/[IC50 light]) ranging from 39.2‐fold in A549 to over 100‐fold in MDA‐MB‐231. Complex 2, on the other hand, did not show much difference in anticancer activity between dark and light conditions. Importantly, the IC50 of the photoproduct of complex 1 was several folds lower than that of cisplatin in all tested cell lines. Furthermore, the dissociating ligand (bipy) was biologically inert in almost all cell lines investigated confirming that phototoxicity was mediated primarily by the Ru aqua complex that is released upon irradiation. In conclusion, the Ru‐centered complex 1 could represent a potential photoactivatable chemotherapeutic drug that increases selectivity to tumors and offers alternative treatment in the light of increasing cisplatin resistance.

The use of ruthenium complexes as chemotherapeutic agents has been recently explored as one of the alternatives to conventional treatments. In the present study, two Ru(II) polypyridyl complexes were synthesized and characterized: a strained [Ru(bipy)2(BC)]Cl2 (complex 1) where [bipy = 2,2′-bipyridine and BC = bathocuproine] along with the unstrained control [Ru(bipy)2(phen)]Cl2 (complex 2) where [phen = 1,10-phenanthroline]. The photophysical and photochemical analyses proved that unlike the photostable complex 2, complex 1 ejected both bipy and BC ligands at a ratio of 3[thin space (1/6-em)]:[thin space (1/6-em)]1 respectively. Results showed that the activity of complex 1 was significantly enhanced upon photoactivation. The response was however particularly significant in B16-F10 melanoma cells where phototoxicity index (PI = IC50 dark/IC50 light) was >900. When compared to cisplatin, the photoproducts were more potent against all tested cell lines, implying that the complex acquired significant chemotherapeutic potential upon irradiation. Cellular uptake of complex 1 and the free BC ligand were found to be significantly facilitated as evidenced by 400–600 fold increase in concentration of the compounds inside the cells relative to the extracellular culture medium. Complex 2 exhibited 35 times lower cellular concentration relative to complex 1. Flow cytometry and plasmid DNA gel electrophoresis measurements showed that complex 1 interacts with DNA inducing apoptosis in the dark and either late-apoptosis or necrosis upon irradiation. These findings corroborate the importance of lipophilic ligands such as BC to enhance uptake and subsequently improve the photochemotherapy potential of Ru(II) polypyridyl complexes.

Background: Germ cell tumor patients with intermediate prognosis (IPGCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification represent a heterogeneous group with different clinical features. This analysis was performed to investigate the prognostic impact of different tumor marker levels prior to first line chemotherapy within IPGCT. Methods: For this study an international registry for IPGCT was established. Eligibility criteria were intermediate prognosis according to IGCCCG criteria, nonseminomatous histology, male sex, and age ≥ 16 years. Uni- and multivariate analysis were conducted to identify characteristics associated with survival outcomes. Receiver-Operating-Characteristic curve analysis was applied to find cut-off parameters. Five-year overall survival (OS) rate was the primary and 5-year progression-free survival rate the secondary endpoint. Results: This database included 634 IPGCT with a median follow-up of 9.0 years (interquartile range: 14.35). Patients received first line treatment with platinum based chemotherapy, associated with a 5-year OS rate of 87%. The stratification of patients according to AFP levels revealed a correlation between AFP levels and outcome, associated with 5-year OS rates of 88% for AFP levels <1,000 IU/ml (n = 303), 89% for 1,000 to 2,000 IU/ml (n = 82), 87% for >2,000 to 6,000 IU/ml (n = 121), and 82% for >6,000 IU/ml (n = 57) prior first course of chemotherapy, respectively (P= 0.013). LDH levels prior fist course of chemotherapy also correlated with outcome associated with 5-year OS rates of 92% for <2 UNL (n = 271), 89% for ≥2 to 3 UNL (n = 85), 78% for >3 to 4 UNL (n = 34), and 77% for >4 UNL (n = 79), respectively (P= 0.03). Different HCG levels prior chemotherapy were not associated with outcome. In multivariable analysis AFP levels >6,000 IU/ml (P= 0.023; hazard ratio HR 2.263) or >1,982 IU/ml (P= 0.031; HR 1.722), and LDH levels >3 UNL (P< 0.001

Background: Germ cell tumor patients with intermediate prognosis (IPGCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification represent a heterogeneous group with different clinical features. This analysis was performed to investigate the prognostic impact of different tumor marker levels prior to first line chemotherapy within IPGCT. Methods: For this study an international registry for IPGCT was established. Eligibility criteria were intermediate prognosis according to IGCCCG criteria, nonseminomatous histology, male sex, and age ≥ 16 years. Uni- and multivariate analysis were conducted to identify characteristics associated with survival outcomes. Receiver-Operating-Characteristic curve analysis was applied to find cut-off parameters. Five-year overall survival (OS) rate was the primary and 5-year progression-free survival rate the secondary endpoint. Results: This database included 634 IPGCT with a median follow-up of 9.0 years (interquartile range: 14.35). Patients received first line treatment with platinum based chemotherapy, associated with a 5-year OS rate of 87%. The stratification of patients according to AFP levels revealed a correlation between AFP levels and outcome, associated with 5-year OS rates of 88% for AFP levels <1,000 IU/ml (n = 303), 89% for 1,000 to 2,000 IU/ml (n = 82), 87% for >2,000 to 6,000 IU/ml (n = 121), and 82% for >6,000 IU/ml (n = 57) prior first course of chemotherapy, respectively (P= 0.013). LDH levels prior fist course of chemotherapy also correlated with outcome associated with 5-year OS rates of 92% for <2 UNL (n = 271), 89% for ≥2 to 3 UNL (n = 85), 78% for >3 to 4 UNL (n = 34), and 77% for >4 UNL (n = 79), respectively (P= 0.03). Different HCG levels prior chemotherapy were not associated with outcome. In multivariable analysis AFP levels >6,000 IU/ml (P= 0.023; hazard ratio HR 2.263) or >1,982 IU/ml (P= 0.031; HR 1.722), and LDH levels >3 UNL (P< 0.001

The current study investigates [Ru(bipy)2(dpphen)]Cl2 [where bipy = 2,2′‐bipyridine and dpphen = 2,9‐diphenyl‐1,10‐phenanthroline] (complex 1) for photoactivatable chemotherapy (PACT) application on five cancer cell lines. [Ru(bipy)2(phen)]Cl2 [where phen = 1,10‐phenanthroline] (complex 2) was included as an unstrained control. Upon excitation with visible light, complex 2 proved to be photostable while complex 1 underwent a quantitative dissociation of the bipy ligand and formation of a RuII polypyridyl aqua complex in water. Complex 1 demonstrated only marginal activity in the dark; its cytotoxicity increased significantly upon photoactivation with a high phototoxicity index (PI = [IC50 dark]/[IC50 light]) ranging from 39.2‐fold in A549 to over 100‐fold in MDA‐MB‐231. Complex 2, on the other hand, did not show much difference in anticancer activity between dark and light conditions. Importantly, the IC50 of the photoproduct of complex 1 was several folds lower than that of cisplatin in all tested cell lines. Furthermore, the dissociating ligand (bipy) was biologically inert in almost all cell lines investigated confirming that phototoxicity was mediated primarily by the Ru aqua complex that is released upon irradiation. In conclusion, the Ru‐centered complex 1 could represent a potential photoactivatable chemotherapeutic drug that increases selectivity to tumors and offers alternative treatment in the light of increasing cisplatin resistance.

The feasibility study on Chlorella sp. lipid extraction using an electrolysis treatment (ET) as pre-treatment was investigated. Stainless steel was used as the anode and cathode material. The ET method was conducted in a batch or continuous system with or without air aeration and recycling flow. The total lipid in Chlorella sp. AWET and AWET were not analysed due to small sample volume. Approximately same amount of lipids were attained from Chlorella sp. BWOET (7.97 ± 0.43% glipid/gdry wt) and BWET (7.95 ± 0.37% glipid/gdry wt) if treated at 5 V/cm and aerated at 16.7 µm3 /s for 1800s. Whereas, if Chlorella sp. was treated at 13 V/cm and aerated at 16.7 µm3 /s for 1800 s, the total lipid obtained in Chlorella sp. CWOET (8.18 ± 0.49% glipid/gdry wt) was 1.13-fold higher than CWET (7.22 ± 0.47% glipid/gdry wt). Meanwhile under semi-continuous system, similar pattern of result was achieved in Chlorella sp. DWOET (8.58 ± 0.49% glipid/gdry wt) with 1.11-fold higher than DWET (7.72 ± 0.54% glipid/gdry wt), if treated at 14 V/cm and recycled at 2.3 µm3 /s for 3000s. This corresponded to lipid oxidation that might have occurred during the ET method. The fatty acid methyl ester (FAME) composition of Chlorella sp. DWOET and DWET contained predominantly methyl linolenate (C18:3) and methyl palmitate (C16:0). The concentrations of methyl palmitate attained in Chlorella sp. DWOET and DWET were 0.049 ± 0.005 g/m3 and 0.045 ± 0.005 g/m3 , respectively.

The feasibility study on Chlorella sp. lipid extraction using an electrolysis treatment (ET) as pre-treatment was investigated. Stainless steel was used as the anode and cathode material. The ET method was conducted in a batch or continuous system with or without air aeration and recycling flow. The total lipid in Chlorella sp. AWET and AWET were not analysed due to small sample volume. Approximately same amount of lipids were attained from Chlorella sp. BWOET (7.97 ± 0.43% glipid/gdry wt) and BWET (7.95 ± 0.37% glipid/gdry wt) if treated at 5 V/cm and aerated at 16.7 µm3 /s for 1800s. Whereas, if Chlorella sp. was treated at 13 V/cm and aerated at 16.7 µm3 /s for 1800 s, the total lipid obtained in Chlorella sp. CWOET (8.18 ± 0.49% glipid/gdry wt) was 1.13-fold higher than CWET (7.22 ± 0.47% glipid/gdry wt). Meanwhile under semi-continuous system, similar pattern of result was achieved in Chlorella sp. DWOET (8.58 ± 0.49% glipid/gdry wt) with 1.11-fold higher than DWET (7.72 ± 0.54% glipid/gdry wt), if treated at 14 V/cm and recycled at 2.3 µm3 /s for 3000s. This corresponded to lipid oxidation that might have occurred during the ET method. The fatty acid methyl ester (FAME) composition of Chlorella sp. DWOET and DWET contained predominantly methyl linolenate (C18:3) and methyl palmitate (C16:0). The concentrations of methyl palmitate attained in Chlorella sp. DWOET and DWET were 0.049 ± 0.005 g/m3 and 0.045 ± 0.005 g/m3 , respectively.

The feasibility study on Chlorella sp. lipid extraction using an electrolysis treatment (ET) as pre-treatment was investigated. Stainless steel was used as the anode and cathode material. The ET method was conducted in a batch or continuous system with or without air aeration and recycling flow. The total lipid in Chlorella sp. AWET and AWET were not analysed due to small sample volume. Approximately same amount of lipids were attained from Chlorella sp. BWOET (7.97 ± 0.43% glipid/gdry wt) and BWET (7.95 ± 0.37% glipid/gdry wt) if treated at 5 V/cm and aerated at 16.7 µm3 /s for 1800s. Whereas, if Chlorella sp. was treated at 13 V/cm and aerated at 16.7 µm3 /s for 1800 s, the total lipid obtained in Chlorella sp. CWOET (8.18 ± 0.49% glipid/gdry wt) was 1.13-fold higher than CWET (7.22 ± 0.47% glipid/gdry wt). Meanwhile under semi-continuous system, similar pattern of result was achieved in Chlorella sp. DWOET (8.58 ± 0.49% glipid/gdry wt) with 1.11-fold higher than DWET (7.72 ± 0.54% glipid/gdry wt), if treated at 14 V/cm and recycled at 2.3 µm3 /s for 3000s. This corresponded to lipid oxidation that might have occurred during the ET method. The fatty acid methyl ester (FAME) composition of Chlorella sp. DWOET and DWET contained predominantly methyl linolenate (C18:3) and methyl palmitate (C16:0). The concentrations of methyl palmitate attained in Chlorella sp. DWOET and DWET were 0.049 ± 0.005 g/m3 and 0.045 ± 0.005 g/m3 , respectively.

The feasibility study on Chlorella sp. lipid extraction using an electrolysis treatment (ET) as pre-treatment was investigated. Stainless steel was used as the anode and cathode material. The ET method was conducted in a batch or continuous system with or without air aeration and recycling flow. The total lipid in Chlorella sp. AWET and AWET were not analysed due to small sample volume. Approximately same amount of lipids were attained from Chlorella sp. BWOET (7.97 ± 0.43% glipid/gdry wt) and BWET (7.95 ± 0.37% glipid/gdry wt) if treated at 5 V/cm and aerated at 16.7 µm3 /s for 1800s. Whereas, if Chlorella sp. was treated at 13 V/cm and aerated at 16.7 µm3 /s for 1800 s, the total lipid obtained in Chlorella sp. CWOET (8.18 ± 0.49% glipid/gdry wt) was 1.13-fold higher than CWET (7.22 ± 0.47% glipid/gdry wt). Meanwhile under semi-continuous system, similar pattern of result was achieved in Chlorella sp. DWOET (8.58 ± 0.49% glipid/gdry wt) with 1.11-fold higher than DWET (7.72 ± 0.54% glipid/gdry wt), if treated at 14 V/cm and recycled at 2.3 µm3 /s for 3000s. This corresponded to lipid oxidation that might have occurred during the ET method. The fatty acid methyl ester (FAME) composition of Chlorella sp. DWOET and DWET contained predominantly methyl linolenate (C18:3) and methyl palmitate (C16:0). The concentrations of methyl palmitate attained in Chlorella sp. DWOET and DWET were 0.049 ± 0.005 g/m3 and 0.045 ± 0.005 g/m3 , respectively.

The feasibility study on Chlorella sp. lipid extraction using an electrolysis treatment (ET) as pre-treatment was investigated. Stainless steel was used as the anode and cathode material. The ET method was conducted in a batch or continuous system with or without air aeration and recycling flow. The total lipid in Chlorella sp. AWET and AWET were not analysed due to small sample volume. Approximately same amount of lipids were attained from Chlorella sp. BWOET (7.97 ± 0.43% glipid/gdry wt) and BWET (7.95 ± 0.37% glipid/gdry wt) if treated at 5 V/cm and aerated at 16.7 µm3 /s for 1800s. Whereas, if Chlorella sp. was treated at 13 V/cm and aerated at 16.7 µm3 /s for 1800 s, the total lipid obtained in Chlorella sp. CWOET (8.18 ± 0.49% glipid/gdry wt) was 1.13-fold higher than CWET (7.22 ± 0.47% glipid/gdry wt). Meanwhile under semi-continuous system, similar pattern of result was achieved in Chlorella sp. DWOET (8.58 ± 0.49% glipid/gdry wt) with 1.11-fold higher than DWET (7.72 ± 0.54% glipid/gdry wt), if treated at 14 V/cm and recycled at 2.3 µm3 /s for 3000s. This corresponded to lipid oxidation that might have occurred during the ET method. The fatty acid methyl ester (FAME) composition of Chlorella sp. DWOET and DWET contained predominantly methyl linolenate (C18:3) and methyl palmitate (C16:0). The concentrations of methyl palmitate attained in Chlorella sp. DWOET and DWET were 0.049 ± 0.005 g/m3 and 0.045 ± 0.005 g/m3 , respectively.

The feasibility study on Chlorella sp. lipid extraction using an electrolysis treatment (ET) as pre-treatment was investigated. Stainless steel was used as the anode and cathode material. The ET method was conducted in a batch or continuous system with or without air aeration and recycling flow. The total lipid in Chlorella sp. AWET and AWET were not analysed due to small sample volume. Approximately same amount of lipids were attained from Chlorella sp. BWOET (7.97 ± 0.43% glipid/gdry wt) and BWET (7.95 ± 0.37% glipid/gdry wt) if treated at 5 V/cm and aerated at 16.7 µm3 /s for 1800s. Whereas, if Chlorella sp. was treated at 13 V/cm and aerated at 16.7 µm3 /s for 1800 s, the total lipid obtained in Chlorella sp. CWOET (8.18 ± 0.49% glipid/gdry wt) was 1.13-fold higher than CWET (7.22 ± 0.47% glipid/gdry wt). Meanwhile under semi-continuous system, similar pattern of result was achieved in Chlorella sp. DWOET (8.58 ± 0.49% glipid/gdry wt) with 1.11-fold higher than DWET (7.72 ± 0.54% glipid/gdry wt), if treated at 14 V/cm and recycled at 2.3 µm3 /s for 3000s. This corresponded to lipid oxidation that might have occurred during the ET method. The fatty acid methyl ester (FAME) composition of Chlorella sp. DWOET and DWET contained predominantly methyl linolenate (C18:3) and methyl palmitate (C16:0). The concentrations of methyl palmitate attained in Chlorella sp. DWOET and DWET were 0.049 ± 0.005 g/m3 and 0.045 ± 0.005 g/m3 , respectively.

Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to androgen receptor inhibition in metastatic castration-resistant prostate cancer (mCRPC) and whether ETS fusions predict response. Patients and Methods Patients underwent metastatic site biopsy and were stratified by ETS status and randomly assigned to abiraterone plus prednisone without (arm A) or with veliparib (arm B). Primary objectives were: confirmed prostate-specific antigen (PSA) response rate (RR) and whether ETS fusions predicted response. Secondary objectives were: safety, measurable disease RR (mRR), progression-free survival (PFS), and molecular biomarker analysis. A total of 148 patients were randomly assigned to detect a 20% PSA RR improvement. Results A total of 148 patients with mCRPC were randomly assigned: arm A, n = 72; arm B, n = 76. There were no differences in PSA RR (63.9% v 72.4%; P = .27), mRR (45.0% v 52.2%; P = .51), or median PFS (10.1 v 11 months; P = .99). ETS fusions did not predict response. Exploratory analysis of tumor sequencing (80 patients) revealed: 41 patients (51%) were ETS positive, 20 (25%) had DNA-damage repair defect (DRD), 41 (51%) had AR amplification or copy gain, 34 (43%) had PTEN mutation, 33 (41%) had TP53 mutation, 39 (49%) had PIK3CA pathway activation, and 12 (15%) had WNT pathway alteration. Patients with DRD had significantly higher PSA RR (90% v 56.7%; P = .007) and mRR (87.5% v 38.6%; P = .001), PSA decline ≥ 90% (75% v 25%; P = .001), and longer median PFS (14.5 v 8.1 months; P = .025) versus those with wild-type tumors. Median PFS was longer in patients with normal PTEN (13.5 v 6.7 months; P = .02), TP53 (13.5 v 7.7 months; P = .01), and PIK3CA (13.8 v 8.3 months; P = .03) versus those with mutation or activation. In multivariable analysis adjusting for clinical covariates, DRD association with PFS remained significant. Conclusion Veliparib and ETS status did not affect response. Exploratory analysis

Background: For metastatic germ cell tumour patients with intermediate prognosis (IPGCT) according to the IGCCCG classification 5-year overall survival (OS) rates of 79% were described, but recent data suggest significant changes. Patients and methods: To compare the outcome of current IPGCT with former patients and to find new prognosticators a retrospective observational study was performed. Eligibility criteria were: age ≥16 years, diagnosed between 1979 and 2014. Primary end-point was the 5-year OS rate. Results: This database includes 707 IPGCT: group 1 was diagnosed 1979–1996 (n = 237), and group 2 1997–2014 (n = 470). Median follow-up was 8.6 years (IQR: 14.4). Group 1 and 2 received first-line treatment with BEP (median 4 cycles; range 1–6) in 99% (group 1) and 95% (group 2), respectively. The proportion of first-line chemotherapy responders (CR and marker negative PR) was similar: 94% (group 1) and 96% (group 2), respectively (P = 0.290), but OS was superior in group 2 with a 5-year OS rate of 89% compared with 83% in group 1 (P = 0.035). In refractory disease, high-dose chemotherapy and treatment beyond second line was performed more often in group 2. A lactate dehydrogenase (LDH) cut-off value of 2 ULN (P = 0.002; HR 2.121) and alpha-fetoprotein (AFP) levels of 6200 IU/ml (P = 0.032; HR 2.155) pre-chemotherapy were independent prognosticators for OS in a multivariate analysis. Conclusion: Outcome of IPGCT has improved and is now closer to the good prognosis category. LDH and AFP levels represent potential markers to stratify IPGCT before treatment initiation.

This dissertation focuses on designing, fabricating and testing antennas that are suitable for operation within the V/W bands. In particular, this work focuses on the design of slotted rectangular waveguide antenna arrays and cross slotted waveguide fed horn antennas. These structures are known for their high efficiency and high circularly polarized gain that can be implemented in satellite and terrestrial communication links. In addition, such designs can be implemented in radar applications that operate infrequency bands around 72 GHz or 84 GHz bands. Such antenna structures are inexpensive to fabricate since they can simply be machined using high precision conventional methods (like milling) and laser cutting when suitable. In particular, this dissertation discusses two designs involving cross-slotted waveguides. The first one consists of an array of cross slotted rectangular waveguide antennas exhibiting radiation beams with Left Hand or Right Hand circular polarization. The array is composed of 8x16 elements and generates a circularly polarized gain of 25 dB over the frequency range 84.2 – 85.7 GHz. The array also exhibits a cross polarization discrimination of more than 20 dB and an isolation of more than 20 dB between the feeding ports. A new type of z-arm shaped cross slots is introduced that fits on the broad-wall of a conventional rectangular waveguide. The feeding network is also optimized to regulate the power and the phase of each rectangular waveguide element in order to increase the gain of the antenna array. This dissertation also presents the theoretical analysis of the second design which is a cross slotted waveguide polarizer. The polarizer achieves a RHCP or LHCP by altering the feeding ports. The polarizer feeds different conical horns or pyramidal horns without affecting their characteristics. The efficiency of the polarizer is improved by combining the power of different crossed slots using square waveguide combiners. Other mo

Lately, research on biodiesel production as a renewable and sustainable energy has become increasingly apparent due to the fact that fossil fuel is decreasing and the concern of global warming issues. The third generation of biofuel, which is microalgaebased biodiesel had gained interest over the last decade. The ability of microalgae to grow in various conditions is one of its advantages as the potential and promising feedstock for biodiesel. Microalgae can be cultivated in three modes such as photoautotrophic, heterotrophic and mixotrophic culture mode. Unlike photoautotrophic mode where light is required, the heterotrophic mode mainly utilized carbon compounds to grow. On the other hand, the mixotrophic mode is the condition where light and carbon compounds are supplied for microalgae culturing. This paper investigates the cell growth of Chlorella sp. cultivated in photoautotrophic, heterotrophic and mixotrophic culture mode. It was found that Chlorella sp. was capable of producing the highest cell concentration of 6.67 ± 0.56 x 106 cell mL-1 in the photoautotrophic mode for 23 days of cultivation period. This was 1.3 times and 3.2 times greater than the cell concentration in mixotrophic (5.02 ± 0.49 x 106 cell mL-1) and heterotrophic (2.03 ± 0.29 x 106 cell mL-1) culture, respectively. On the contrary, the highest specific growth rate obtained in the study was from heterotrophic mode (0.32 ± 0.04 day-1) followed by photoautotrophic and mixotrophic mode with 0.26 ± 0.05 day-1 and 0.20 ± 0.04 day-1, respectively. Chlorella sp. cell grew well under the photoautotrophic and mixotrophic mode. However, the insufficient of glucose level had contributed to lower cells productivity in the heterotrophic culture. Therefore, the mixotrophic mode could also be an alternative pathway in microalgae cultivation for biodiesel production if the glucose supplied was adequate and at the suitable level.

Lately, research on biodiesel production as a renewable and sustainable energy has become increasingly apparent due to the fact that fossil fuel is decreasing and the concern of global warming issues. The third generation of biofuel, which is microalgaebased biodiesel had gained interest over the last decade. The ability of microalgae to grow in various conditions is one of its advantages as the potential and promising feedstock for biodiesel. Microalgae can be cultivated in three modes such as photoautotrophic, heterotrophic and mixotrophic culture mode. Unlike photoautotrophic mode where light is required, the heterotrophic mode mainly utilized carbon compounds to grow. On the other hand, the mixotrophic mode is the condition where light and carbon compounds are supplied for microalgae culturing. This paper investigates the cell growth of Chlorella sp. cultivated in photoautotrophic, heterotrophic and mixotrophic culture mode. It was found that Chlorella sp. was capable of producing the highest cell concentration of 6.67 ± 0.56 x 106 cell mL-1 in the photoautotrophic mode for 23 days of cultivation period. This was 1.3 times and 3.2 times greater than the cell concentration in mixotrophic (5.02 ± 0.49 x 106 cell mL-1) and heterotrophic (2.03 ± 0.29 x 106 cell mL-1) culture, respectively. On the contrary, the highest specific growth rate obtained in the study was from heterotrophic mode (0.32 ± 0.04 day-1) followed by photoautotrophic and mixotrophic mode with 0.26 ± 0.05 day-1 and 0.20 ± 0.04 day-1, respectively. Chlorella sp. cell grew well under the photoautotrophic and mixotrophic mode. However, the insufficient of glucose level had contributed to lower cells productivity in the heterotrophic culture. Therefore, the mixotrophic mode could also be an alternative pathway in microalgae cultivation for biodiesel production if the glucose supplied was adequate and at the suitable level.

Lately, research on biodiesel production as a renewable and sustainable energy has become increasingly apparent due to the fact that fossil fuel is decreasing and the concern of global warming issues. The third generation of biofuel, which is microalgaebased biodiesel had gained interest over the last decade. The ability of microalgae to grow in various conditions is one of its advantages as the potential and promising feedstock for biodiesel. Microalgae can be cultivated in three modes such as photoautotrophic, heterotrophic and mixotrophic culture mode. Unlike photoautotrophic mode where light is required, the heterotrophic mode mainly utilized carbon compounds to grow. On the other hand, the mixotrophic mode is the condition where light and carbon compounds are supplied for microalgae culturing. This paper investigates the cell growth of Chlorella sp. cultivated in photoautotrophic, heterotrophic and mixotrophic culture mode. It was found that Chlorella sp. was capable of producing the highest cell concentration of 6.67 ± 0.56 x 106 cell mL-1 in the photoautotrophic mode for 23 days of cultivation period. This was 1.3 times and 3.2 times greater than the cell concentration in mixotrophic (5.02 ± 0.49 x 106 cell mL-1) and heterotrophic (2.03 ± 0.29 x 106 cell mL-1) culture, respectively. On the contrary, the highest specific growth rate obtained in the study was from heterotrophic mode (0.32 ± 0.04 day-1) followed by photoautotrophic and mixotrophic mode with 0.26 ± 0.05 day-1 and 0.20 ± 0.04 day-1, respectively. Chlorella sp. cell grew well under the photoautotrophic and mixotrophic mode. However, the insufficient of glucose level had contributed to lower cells productivity in the heterotrophic culture. Therefore, the mixotrophic mode could also be an alternative pathway in microalgae cultivation for biodiesel production if the glucose supplied was adequate and at the suitable level.

Lately, research on biodiesel production as a renewable and sustainable energy has become increasingly apparent due to the fact that fossil fuel is decreasing and the concern of global warming issues. The third generation of biofuel, which is microalgaebased biodiesel had gained interest over the last decade. The ability of microalgae to grow in various conditions is one of its advantages as the potential and promising feedstock for biodiesel. Microalgae can be cultivated in three modes such as photoautotrophic, heterotrophic and mixotrophic culture mode. Unlike photoautotrophic mode where light is required, the heterotrophic mode mainly utilized carbon compounds to grow. On the other hand, the mixotrophic mode is the condition where light and carbon compounds are supplied for microalgae culturing. This paper investigates the cell growth of Chlorella sp. cultivated in photoautotrophic, heterotrophic and mixotrophic culture mode. It was found that Chlorella sp. was capable of producing the highest cell concentration of 6.67 ± 0.56 x 106 cell mL-1 in the photoautotrophic mode for 23 days of cultivation period. This was 1.3 times and 3.2 times greater than the cell concentration in mixotrophic (5.02 ± 0.49 x 106 cell mL-1) and heterotrophic (2.03 ± 0.29 x 106 cell mL-1) culture, respectively. On the contrary, the highest specific growth rate obtained in the study was from heterotrophic mode (0.32 ± 0.04 day-1) followed by photoautotrophic and mixotrophic mode with 0.26 ± 0.05 day-1 and 0.20 ± 0.04 day-1, respectively. Chlorella sp. cell grew well under the photoautotrophic and mixotrophic mode. However, the insufficient of glucose level had contributed to lower cells productivity in the heterotrophic culture. Therefore, the mixotrophic mode could also be an alternative pathway in microalgae cultivation for biodiesel production if the glucose supplied was adequate and at the suitable level.

Lately, research on biodiesel production as a renewable and sustainable energy has become increasingly apparent due to the fact that fossil fuel is decreasing and the concern of global warming issues. The third generation of biofuel, which is microalgaebased biodiesel had gained interest over the last decade. The ability of microalgae to grow in various conditions is one of its advantages as the potential and promising feedstock for biodiesel. Microalgae can be cultivated in three modes such as photoautotrophic, heterotrophic and mixotrophic culture mode. Unlike photoautotrophic mode where light is required, the heterotrophic mode mainly utilized carbon compounds to grow. On the other hand, the mixotrophic mode is the condition where light and carbon compounds are supplied for microalgae culturing. This paper investigates the cell growth of Chlorella sp. cultivated in photoautotrophic, heterotrophic and mixotrophic culture mode. It was found that Chlorella sp. was capable of producing the highest cell concentration of 6.67 ± 0.56 x 106 cell mL-1 in the photoautotrophic mode for 23 days of cultivation period. This was 1.3 times and 3.2 times greater than the cell concentration in mixotrophic (5.02 ± 0.49 x 106 cell mL-1) and heterotrophic (2.03 ± 0.29 x 106 cell mL-1) culture, respectively. On the contrary, the highest specific growth rate obtained in the study was from heterotrophic mode (0.32 ± 0.04 day-1) followed by photoautotrophic and mixotrophic mode with 0.26 ± 0.05 day-1 and 0.20 ± 0.04 day-1, respectively. Chlorella sp. cell grew well under the photoautotrophic and mixotrophic mode. However, the insufficient of glucose level had contributed to lower cells productivity in the heterotrophic culture. Therefore, the mixotrophic mode could also be an alternative pathway in microalgae cultivation for biodiesel production if the glucose supplied was adequate and at the suitable level.

The advent of CubeSats has revolutionized the space research industry. The small physical size and constraints owing to outer space applications present significant challenges for antenna engineers to come up with innovative solutions. This paper presents a novel wide band antenna high gain antenna which is capable of deploying from a CubeSat platform.

Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2. Moreover, the effect of the most promising compounds on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein expression in lipopolysaccharide (LPS)-activated rat monocytes was also investigated. The results revealed that some of the synthesized compounds showed anti-inflammatory and/or analgesic activity with less ulcerogenic potential than the reference drug diclofenac sodium and are well tolerated by experimental animals. Moreover, they significantly inhibited iNOS and COX-2 protein expression induced by LPS stimulation. Compounds 16b and 18 were proved to display anti-inflammatory activity superior to diclofenac sodium and analgesic activity equivalent to it with minimal ulcerogenic potential.

Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2. Moreover, the effect of the most promising compounds on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein expression in lipopolysaccharide (LPS)-activated rat monocytes was also investigated. The results revealed that some of the synthesized compounds showed anti-inflammatory and/or analgesic activity with less ulcerogenic potential than the reference drug diclofenac sodium and are well tolerated by experimental animals. Moreover, they significantly inhibited iNOS and COX-2 protein expression induced by LPS stimulation. Compounds 16b and 18 were proved to display anti-inflammatory activity superior to diclofenac sodium and analgesic activity equivalent to it with minimal ulcerogenic potential.

Background Daucus carota L.ssp.carota (wild carrot), an herb used in folk medicine worldwide, was recently demonstrated to exhibit anticancer activity. In this study we examined the anticancer effect of Daucus carota oil extract (DCOE) fractions on the human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7 and clarified the mechanism of action. Methods and results Using the WST assay, the pentane fraction (F1) and 1:1 pentane:diethyl ether fraction (F2) were shown to possess the highest cytotoxicity against both cell lines. Flow cytometric analysis revealed that both fractions induced the accumulation of cells in the sub-G1 phase, increase in apoptotic cell death and chromatin condensation. The increase in apoptosis in response to treatment was also apparent in the increase in BAX and the decrease in Bcl-2 levels as well as the proteolytic cleavage of both caspase-3 and PARP as revealed by Western blot. Furthermore, treatment of MDA-MB-231 cells with either fraction significantly reduced the level of phosphorylated Erk but did not show any effect on phosphorylated Akt. The combined treatment with a potent PI3K inhibitor (wortmannin) and F1 or F2 fraction had a synergistic inhibitory effect on cell survival which shows that these two drugs work on different pathways. Conclusions These results suggest that the pentane-based fractions of DCOE possess potential anti-cancer activity that is mainly mediated through the Erk pathway.

Background Daucus carota L.ssp.carota (wild carrot), an herb used in folk medicine worldwide, was recently demonstrated to exhibit anticancer activity. In this study we examined the anticancer effect of Daucus carota oil extract (DCOE) fractions on the human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7 and clarified the mechanism of action. Methods and results Using the WST assay, the pentane fraction (F1) and 1:1 pentane:diethyl ether fraction (F2) were shown to possess the highest cytotoxicity against both cell lines. Flow cytometric analysis revealed that both fractions induced the accumulation of cells in the sub-G1 phase, increase in apoptotic cell death and chromatin condensation. The increase in apoptosis in response to treatment was also apparent in the increase in BAX and the decrease in Bcl-2 levels as well as the proteolytic cleavage of both caspase-3 and PARP as revealed by Western blot. Furthermore, treatment of MDA-MB-231 cells with either fraction significantly reduced the level of phosphorylated Erk but did not show any effect on phosphorylated Akt. The combined treatment with a potent PI3K inhibitor (wortmannin) and F1 or F2 fraction had a synergistic inhibitory effect on cell survival which shows that these two drugs work on different pathways. Conclusions These results suggest that the pentane-based fractions of DCOE possess potential anti-cancer activity that is mainly mediated through the Erk pathway.

Evidence shows that exposure to environmental enrichment (EE) or to a highly palatable diet can reduce the response to chronic stress in rats. To further explore the relationships between EE, dietary intake and stress, male Sprague-Dawley rats were fed one of two diets for 5 weeks: high carbohydrate (HC) or "Cafeteria" (CAF) (offering a choice of highly palatable cafeteria food). Also, they were housed in cages with or without EE. After the first two weeks, half of the animals from each group were stressed daily using a chronic variable stress (CVS) paradigm, while the other half were kept undisturbed until the end of the experiment. The effects of stress, EE and diet on animal adiposity, serum lipids, and stress hormones were analyzed. Results showed increases in liver weight and intra-abdominal fat associated with the CAF diet and an increase in bodyweight gain associated with both the CAF diet and EE. Stressed animals showed increased serum corticosterone (CORT) levels compared to non-stressed animals (P<0.001). In addition, there was a significant interaction between diet and EE (P=0.02) on serum CORT levels: the CVS-induced increase in CORT was attenuated in the presence of EE and the CAF diet independently and in a synergistic manner. Our study thus provides evidence that the availability of a positive rearing environment combined with highly palatable food renders rats more resilient to the effects of CVS.

The effects of acute and chronic (10 wk) red or white wine consumption on fasted and postprandial lipemia in the rat model are reported. Fasted rats, in the acute study, were loaded intragastrically with 5 ml of an olive oil emulsion (30% w/v) in the presence or absence of wine (8% v/v ethanol), and either mesenteric lymph or blood was collected 3 h postprandially. Animals in the chronic study received either red or white wine in drinking water for a period of 10 wk (3% v/v ethanol). Blood samples were collected from animals in either the fasted state or after fat–wine loading. Postprandially, wine delayed gastric emptying, reduced lymph triacylglycerol (TAG) secretion concomitantly with increased number and decreased chylomicron (CM) size, and increased plasma TAG and CM concentrations. Phospholipid and cholesterol contents of CM, but not very-low-density lipoprotein (VLDL), were increased, indicating enhanced liver bile secretion; however, a significant increase in plasma VLDL concentration was observed. In the chronic study, a wine–fat load resulted in increased high-density lipoprotein (HDL) cholesterol concentration and less pronounced postprandial hypertriglyceridemia and hyperchylomicronemia. In the fasted state, plasma TAG and total apolipoprotein B concentrations were not modified in these animals, and an increase in HDL and a decrease in low-density lipoprotein (LDL)/HDL cholesterol ratios were observed. No liver function or intestinal lipid absorption impairment was observed. In conclusion, unlike binge drinking, chronic moderate wine consumption appears to have a cardioprotective effect in the fasted state, an effect attenuated by the observed temporary postprandial hyperchylomicronemia and hypertriglyceridemia resulting from a direct effect of alcohol on CM size and number.

This paper discusses the design of a new conical log spiral antenna that can operate at UHF frequencies. The antenna constitutes a suitable candidate for deployment on top of a 6U CubeSat system. The conical log spiral is designed to operate between 300 MHz and 600 MHz and exhibit circular polarization as well as an acceptable gain. The antenna is also required to satisfy size constraints by being compactly folded during launch and deployed successfully once in orbit.

A concept for a deployable high-performance antenna for CubeSats is presented. The detailed design of a conical log-spiral antenna with wideband operation between 250 500 MHz, a gain of above 5 dB, and circular polarization is performed using electromagnetic simulations. A structural concept using dual-matrix composites with soft hinge regions, allowing the antenna to be packaged into small volumes, is developed. An antenna prototype is fabricated using Astroquartz fibers in an epoxy matrix; a high-strain silicone matrix is used in the hinge regions. Structural and electromagnetic analyses are conducted and show good agreement with predicted performance thus demonstrating the validity of the proposed antenna concept.

Daucus carota L. ssp. carota (Apiacea, wild carrot, Queen Anne's lace) has been used in folk medicine throughout the world and recently was shown to possess anticancer and antioxidant activities. This study aims to determine the anticancer activity of the pentane fraction (F1) and the 1:1 pentane:diethyl ether fraction (F2) of the Daucus Carota oil extract (DCOE) against human colon adenocarcinoma cell lines (HT-29 and Caco-2). Treatment of cells with various concentrations of F1 or F2 fractions produced a dose-dependent inhibition of cell proliferation. Flow cytometric analysis indicated that both fractions induced sub-G1 phase accumulation and increased apoptotic cell death. Western blot revealed the activation of caspase-3, PARP cleavage, and a considerable increase in Bax and p53 levels, and a decrease in Bcl-2 level. Treatment of HT-29 cells with either fraction markedly decreased the levels of both phosphorylated Erk and Akt. Furthermore, the combined treatment of F1 or F2 with wortmannin showed no added inhibition of cell survival suggesting an effect of F1 or F2 through the phosphatidyl inositol 3-kinase (PI3K) pathway. This study proposes that DCOE fractions (F1 and F2) inhibit cell proliferation by inducing cell cycle arrest and apoptosis in HT-29 cells through the suppression of mitogen-activated protein kinase (MAPK)/Erk and PI3K/Akt pathways.

Tragopogon porrifolius (white salsify) is an edible plant commonly used in folk medicine in Lebanon and neighbouring countries. This study investigates the effect of the aqueous extract of the aerial part of T. porrifolius on lipemia and appetite regulation using a rat model. Food intake, abdominal fat percentage, blood lipid profile, liver weight and liver enzymes were assessed following 4 weeks of extract intake via drinking water (50, 100, or 250 mg/kg body weight) in standard high-carbohydrate and high-fat dietary conditions. In a separate study, the short term effect of a preload of T. porrifolius extract on food intake was evaluated. Results showed that consumption of the plant extract for a period of four weeks resulted in a marked improvement of the lipid profile (triglycerides, total cholesterol, LDL and HDL cholesterol). Body weight, food intake and intra-abdominal fat were also lower in animals given the plant extract (100 and 250 mg/kg). In addition, T. porrifolius extract preload produced a dose dependent decrease in food intake observed over 24 h. The intake of T. porrifolius aqueous extract therefore improved lipemia and increased satiety in rats with no visible adverse effects.