Anticancer activity of OSW-1: Induction of apoptotic pathway in leukemia and autophagic death in pancreatic cancer through a calcium mediated mechanism

OSW-1 is a natural compound found in the bulbs of Orninithogalum saudersiae, a member of the lily family. This compound exhibits potent antitumor activity in vitro with the IC50 values in the low nanomolar concentration range and demonstrating its ability to kill drug resistant cancer cells. In an effort to discover the unknown mechanism of action of this novel compound as a potential anticancer agent, the main objective of this research project was to test the cytotoxicity of OSW-1 against various cancer lines, and to elucidate the biochemical and molecular mechanism(s) responsible for the anticancer activity of OSW-1. My initial investigation revealed that OSW-1 is effective in killing various cancer cells including pancreatic cancer cells and primary leukemia cells resistant to standard chemotherapeutic agents, and that non-malignant cells were less sensitive to this compound. Further studies revealed that in leukemia cells, OSW-1 causes a significant increase in cytosolic calcium and activates rapid calcium-dependent apoptosis by the intrinsic pathway. Additionally, OSW-1 treatment leads to the degradation of the ER chaperone GRP78/BiP implicated in the survival of cancer cells. Meanwhile, it shows a reduced sensitivity in respiration-deficient sub-clones of leukemia cells which had higher basal levels of Ca2+. Mechanistically, it was further demonstrated that cytosolic Ca2+ elevations were observed together with Na+ decreases in the cytosol, suggesting OSW-1 caused the calcium overload through inhibition of the Na+/Ca 2+exchanger (NCX). Although similar calcium disturbances were observed in pancreatic cancer cells, mechanistic studies revealed that autophagy served as an initial pro-survival mechanism subsequent to OSW-1 treatment but extended autophagy caused inevitable cell death. Furthermore, combination of OSW-1 with autophagy inhibitors significantly enhances the cytotoxicity against pancreatic cancer cells. Taken together, this study revealed the novel mechanism of OSW-1 which is through inhibition of the Na+/Ca2+ exchanger and provides a basis for using this compound in combination with other agents for the treatment of pancreatic cancer which is resistant to available anticancer drugs. ^

Hispanic incorporation and access to health care in Houston and Harris County, Texas: Adopting an Hispanic perspective to the Aday and Andersen model

This study examines Hispanic levels of incorporation and access to health care. Applying the Aday and Andersen framework for the study of access, the study examined the relationship between two levels of Hispanic incorporation into U.S. society, i.e., mainstream versus ethnic, and potential and realized measures of access to health care. Data for the study were drawn from a 1992 telephone survey of 600 randomly selected Hispanics in Houston and Harris County.^ The hypotheses tested were: (1) Hispanics who are incorporated into mainstream society are more likely to have better potential and realized access to health care than those who are incorporated into ethnic-group enclaves regardless of their socioeconomic status (SES), health status and health needs, and (2) there is no interaction between the levels of incorporation (mainstream or ethnic) and SES, health status, and health needs in predicting potential and realized access.^ The data analysis supported Hypothesis One for the two measures of potential access. The results of bivariate and multiple logistic regression analyses indicated that for Hispanics in Houston and Harris County, being in the "mainstream" incorporation category increased their potential access to care, having "health insurance" and a "regular place of care". For the selected measure of realized access, having a "regular check-up", the analysis did not demonstrate statistically significant differences in having a regular check-up among Hispanics incorporated in the ethnic or mainstream incorporation categories.^ Hypothesis Two, that there is no interaction between the levels of incorporation and socioeconomic characteristics, health status, and health needs in predicting potential and realized access among Hispanics was supported by the data. The results of the logistic regression analysis showed that, after adjusting for socioeconomic status, health status, and health needs, the association between "level of incorporation" and the two measures of potential access ("health insurance" and having a "usual place of care") was not modified by the control variables nor by their interaction with level of incorporation. That is, the effect of incorporation on Hispanics' health insurance coverage, and having a usual place of care, was homogenous across Hispanics with different SES and health status.^ The main research implication of this dissertation is the employment of a theoretical framework for the assessment of cultural factors essential to research on migrating heterogeneous subpopulations. It also provided strategies to solve practical and methodological difficulties in the secondary analyses of data on these populations. ^

Measuring value in cancer-related health care: A case study in head and neck cancer

In the current climate of escalating health care costs, defining value and accurately measuring it are two critical issues affecting not only the future of cancer care in particular but also the future of health care in general. Specifically, measuring and improving value in cancer-related health care are critical for continued advancements in research, management, and overall delivery of care. However, in oncology, most of this research has focused on value as it relates to insurance industry and payment reform, with little attention paid to value as the output of clinical interventions that encompass integrated clinical teams focusing on the entire cycle of care and measuring objective outcomes that are most relevant to patients. ^ In this study, patient-centered value was defined as health outcomes achieved per dollar spent, and calculated using objective functional outcomes and total care costs. The analytic sample comprised patients diagnosed with three common head and neck cancers—cancer of the larynx, oral cavity, and oropharynx—who were treated in an integrated tertiary care center over an approximately 10-year period. The results of this study provide initial empirical data that can be used to assess and ultimately to help improve the quality and value of head and neck cancer care, and more importantly they can be used by patients and clinicians to make better-informed decisions about care, particularly what therapeutic services and outcomes matter the most to patients.^

Fertilizer and Swine Manure Management Systems Impacts on Phosphorus in Soil and Subsurface Tile Drainage

Swine manure and fertilizer can be used to supply the nitrogen (N) and phosphorus (P) needs of crops. Excess P application sometimes applied with N-based manure for corn increases the risk of P loss and water quality impairment. Poor water quality in Iowa streams and lakes due to excess P has prompted questions about the impact of cropping and nutrient management systems on P loss from fields.

Ag Engineering and Agronomy Farm and Central Iowa Research Farms Summary

Includes Ag Engineering and Agronomy Farm Farm and Weather Summary, Central Iowa Farms Farm and Weather Summary and Project Lists

Integrated Data Sets of the EU FP5 Research Project ORFOIS: Origin and fate of biogenic particle fluxes in the ocean and their interactions with atmospheric CO2 concentrations as well as the marine sediment

For a reliable simulation of the time and space dependent CO2 redistribution between ocean and atmosphere an appropriate time dependent simulation of particle dynamics processes is essential but has not been carried out so far. The major difficulties were the lack of suitable modules for particle dynamics and early diagenesis (in order to close the carbon and nutrient budget) in ocean general circulation models, and the lack of an understanding of biogeochemical processes, such as the partial dissolution of calcareous particles in oversaturated water. The main target of ORFOIS was to fill in this gap in our knowledge and prediction capability infrastructure. This goal has been achieved step by step. At first comprehensive data bases (already existing data) of observations of relevance for the three major types of biogenic particles, organic carbon (POC), calcium carbonate (CaCO3), and biogenic silica (BSi or opal), as well as for refractory particles of terrestrial origin were collated and made publicly available.

(Table 1) Normalized difference vegetation index in control and warming plots, Abisco Research Station

Extreme winter warming events in the sub-Arctic have caused considerable vegetation damage due to rapid changes in temperature and loss of snow cover. The frequency of extreme weather is expected to increase due to climate change thereby increasing the potential for recurring vegetation damage in Arctic regions. Here we present data on vegetation recovery from one such natural event and multiple experimental simulations in the sub-Arctic using remote sensing, handheld passive proximal sensors and ground surveys. Normalized difference vegetation index (NDVI) recovered fast (2 years), from the 26% decline following one natural extreme winter warming event. Recovery was associated with declines in dead Empetrum nigrum (dominant dwarf shrub) from ground surveys. However, E. nigrum healthy leaf NDVI was also reduced (16%) following this winter warming event in experimental plots (both control and treatments), suggesting that non-obvious plant damage (i.e., physiological stress) had occurred in addition to the dead E. nigrum shoots that was considered responsible for the regional 26% NDVI decline. Plot and leaf level NDVI provided useful additional information that could not be obtained from vegetation surveys and regional remote sensing (MODIS) alone. The major damage of an extreme winter warming event appears to be relatively transitory. However, potential knock-on effects on higher trophic levels (e.g., rodents, reindeer, and bear) could be unpredictable and large. Repeated warming events year after year, which can be expected under winter climate warming, could result in damage that may take much longer to recover.

Soil characteristics and Collembola and Acari abundance in control and warming plots at Abisco Research Station

Extreme weather events can have negative impacts on species survival and community structure when surpassing lethal thresholds. Extreme winter warming events in the Arctic rapidly melt snow and expose ecosystems to unseasonably warm air (2-10 °C for 2-14 days), but returning to cold winter climate exposes the ecosystem to lower temperatures by the loss of insulating snow. Soil animals, which play an integral part in soil processes, may be very susceptible to such events depending on the intensity of soil warming and low temperatures following these events. We simulated week-long extreme winter warming events - using infrared heating lamps, alone or with soil warming cables - for two consecutive years in a sub-Arctic dwarf shrub heathland. Minimum temperatures were lower and freeze-thaw cycles were 2-11 times more frequent in treatment plots compared with control plots. Following the second event, Acari populations decreased by 39%; primarily driven by declines of Prostigmata (69%) and the Mesostigmatic nymphs (74%). A community-weighted vertical stratification shift occurred from smaller soil dwelling (eu-edaphic) Collembola species dominance to larger litter dwelling (hemi-edaphic) species dominance in the canopy-with-soil warming plots compared with controls. The most susceptible groups to these winter warming events were the smallest individuals (Prostigmata and eu-edaphic Collembola). This was not apparent from abundance data at the Collembola taxon level, indicating that life forms and species traits play a major role in community assembly following extreme events. The observed shift in soil community can cascade down to the micro-flora affecting plant productivity and mineralization rates. Short-term extreme weather events have the potential to shift community composition through trait composition with potentially large consequences for ecosystem development.

What factors affect the visibility of Argentinean publications in humanities and social sciences in Scopus? Some evidence beyond the geographic realm of research

Se analizan los patrones de publicación y citación en ciencias humanas y sociales en Scopus en el período 2003-2012, según el alcance geográfico de la investigación. Los resultados muestran que los temas de alcance nacional tienen un predominio del español como lengua de publicación y una marcada preferencia por la autoría única frente a los patrones observados en el grupo de otros temas, no situados geográficamente, donde el inglés y la colaboración institucional es más fuerte y está más consolidada. La citación no parece estar determinada solo por el alcance geográfico de las investigaciones, sino también por el idioma de publicación, la coautoría y los perfiles de las revistas donde se publica. Se espera que los resultados den lugar a una reflexión constructiva sobre la cultura investigadora y editorial y que sean útiles como referencia para establecer criterios de evaluación en las comisiones evaluadoras y las políticas editoriales a nivel nacional

What factors affect the visibility of Argentinean publications in humanities and social sciences in Scopus? Some evidence beyond the geographic realm of research

Se analizan los patrones de publicación y citación en ciencias humanas y sociales en Scopus en el período 2003-2012, según el alcance geográfico de la investigación. Los resultados muestran que los temas de alcance nacional tienen un predominio del español como lengua de publicación y una marcada preferencia por la autoría única frente a los patrones observados en el grupo de otros temas, no situados geográficamente, donde el inglés y la colaboración institucional es más fuerte y está más consolidada. La citación no parece estar determinada solo por el alcance geográfico de las investigaciones, sino también por el idioma de publicación, la coautoría y los perfiles de las revistas donde se publica. Se espera que los resultados den lugar a una reflexión constructiva sobre la cultura investigadora y editorial y que sean útiles como referencia para establecer criterios de evaluación en las comisiones evaluadoras y las políticas editoriales a nivel nacional

What factors affect the visibility of Argentinean publications in humanities and social sciences in Scopus? Some evidence beyond the geographic realm of research

Se analizan los patrones de publicación y citación en ciencias humanas y sociales en Scopus en el período 2003-2012, según el alcance geográfico de la investigación. Los resultados muestran que los temas de alcance nacional tienen un predominio del español como lengua de publicación y una marcada preferencia por la autoría única frente a los patrones observados en el grupo de otros temas, no situados geográficamente, donde el inglés y la colaboración institucional es más fuerte y está más consolidada. La citación no parece estar determinada solo por el alcance geográfico de las investigaciones, sino también por el idioma de publicación, la coautoría y los perfiles de las revistas donde se publica. Se espera que los resultados den lugar a una reflexión constructiva sobre la cultura investigadora y editorial y que sean útiles como referencia para establecer criterios de evaluación en las comisiones evaluadoras y las políticas editoriales a nivel nacional

Concentration of organic compounds in aerosols and surface waters of the East Atlantic and Antarctic

The data on content and composition of lipids and aliphatic hydrocarbons (HC) in aerosols and surface waters obtained during the spring-summer periods of 2001 and 2003 along the vessel route from the North Sea to the Antarctic and backwards are presented. It was shown that the distribution of organic compounds is caused by influence of zonal supply of eolian matter from land, anthropogenic, and marine autochtonous sources. Concentrations of organic compounds in the aerosols varied from 0.22 to 13.04 ng/m**3 for lipids and from 0.04 to 7.03 ng/m**3 for aliphatic HC; in surface waters, it from 9 to 84 and from 1 to 53 µg/l, respectively. There is correlation between fluxes of lithogenic fraction of the aerosols, HC, and lipids. Growth of productivity in the aquatic area increases levels of the HC in the surface waters but to a lower degree than HC supply with oil contamination.

Topographic model of Greenland (elevation lines in PanMap and ASCII format)

In this paper, a new high-resolution elevation model of Greenland, including the ice sheet as well as the ice free regions, is presented. It is the first published full coverage model, computed with an average resolution of 2 km and providing an unprecedented degree of detail. The topography is modeled from a wide selection of data sources, including satellite radar altimetry from Geosat and ERS 1, airborne radar altimetry and airborne laser altimetry over the ice sheet, and photogrammetric and manual map scannings in the ice free region. The ice sheet model accuracy is evaluated by omitting airborne laser data from the analysis and treating them as ground truth observations. The mean accuracy of the ice sheet elevations is estimated to be 12-13 m, and it is found that on surfaces of a slope between 0.2° and 0.8°, corresponding to approximately 50% of the ice sheet, the model presents a 40% improvement over models based on satellite altimetry alone. On coastal bedrock, the model is compared with stereo triangulated reference points, and it is found that the model accuracy is of the order of 25-35 m in areas covered by stereo photogrammetry scannings and between 200 and 250 m elsewhere.

Zooplankton and chlorophyll in upper water layers within research polygons in the Atlantic Ocean, June-September 2001

During Cruise 46 of R/V Akademik Mstislav Keldysh (from June to September 2001), vertical distributions of Radiolaria (Acantharia - Bac and Euradiolaria - Beur), mesozooplankton (from 0.2 to 3.0 mm size, Bm), and chlorophyll a (Cchl) in the epipelagic zone of the North Atlantic were studied. To examine the above-listed characteristics, samples were taken by Niskin 30 l bottles from 12-16 depth levels within the upper 100 to 200 m layer in the subarctic (48°11'N, 16°06'W) and subtropical (27°31'N, 75°51'W) waters, as well as in the transitional zone (41°44'N, 49°57'W). The latter proved to be characterized by the highest values of all averaged parameters examined by us within the upper 100 m layer (Bm - 365mg/m**3, Bac - 140 mg/m**3, Beur - 0.37 mg/m**3, and Cchl - 0.32 mg/m**3). For subarctic and subtropical waters corresponding characteristics were as follows: Bm - 123 and 53 mg/m**3, Bac - 0 and 0.06 mg/m**3, Beur - 0.17 and 0.19 mg/m**3, and Cchl - 0.27 and 0.05 mg/m**3, respectively. Percentage of Acantharia in total biomass of Radiolaria and zooplankton ranged from 0 to 39%, whereas that of Euradiolaria varied from 0.01 to 0.36%. Depth levels with maximum abundance of Acantharia were located above maxima of zooplankton and chlorophyll a or coincided with them. As for Euradiolaria, vertical profiles of their biomass were more diverse as compared with Acantharia. The latter group preferred more illuminated depth levels for its maximum development (10-100% of surface irradiance, E0) with respect to Euradiolaria (1-60% of E0). Possible reasons for this difference are discussed.