Sources of emergency water supplies in Santa Clara County, California

USGS Publications Warehouse

Akers, J.P.

1977-01-01

Water distribution systems in Santa Clara County, Calif., may be damaged and rendered inoperable by a large earthquake or other disaster. In such an event, individual agencies may have to implement emergency measures to supply water for drinking, firefighting, decontamination, or other purposes. In Santa Clara County, 128 wells have been identified as potential water-supply sources in emergencies. The criteria used to select the wells are: yield of at least 3 liters per second (50 gallons per minute), good water quality, ready accessibility, and available emergency power. Purification methods of small water supplies are described. (Woodard-USGS)

The new Heavy-ion MCP-based Ancillary Detector DANTE for the CLARA-PRISMA Setup

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valiente-Dobon, J. J.; Gadea, A.; Corradi, L.

2006-08-14

The CLARA-PRISMA setup is a powerful tool for spectroscopic studies of neutron-rich nuclei produced in multi-nucleon transfer and deep-inelastic reactions. It combines the large acceptance spectrometer PRISMA with the {gamma}-ray array CLARA. At present, the ancillary heavy-ion detector DANTE, based on Micro-Channel Plates to be installed at the CLARA-PRISMA setup, is being constructed at LNL. DANTE will open the possibility of measuring {gamma}-{gamma} Doppler-corrected coincidences for the events outside the acceptance of PRISMA. In this presentation, it is described the heavy-ion detector DANTE, as well as the performances of the first prototype.

Preparation and characterization of human recombinant protein 1/Clara cell M(r) 10,000 protein.

PubMed

Okutani, R; Itoh, Y; Yamada, T; Yamaguchi, T; Singh, G; Yagisawa, H; Kawai, T

1996-09-01

Protein 1, which is identical to human Clara cell M(r) 10(4) protein, is a homodimeric, low molecular mass protein (M(r) 14,000) and an effective inhibitor of phospholipase A2 activity. We have expressed this protein in E. coli and characterized its physiochemical and biological properties. Using a pET expression system, about 1.7 mg of purified recombinant protein 1 was obtained from 250 ml of E. coli culture. The amino-terminal sequence of recombinant protein 1 up to the 20th residue was identical to that of native protein 1 except for an extra methionine at the amino-terminus. On reversed-phase HPLC, recombinant protein 1 eluted at the same retention time as native protein 1. The dose-response curves of recombinant protein 1 and native protein 1 in an enzyme-linked immunosorbent assay for protein 1 were identical. Recombinant protein 1 inhibited both porcine pancreas and cobra venom phospholipase A2 activities. These results indicated that recombinant protein 1 is structurally and biologically identical to native protein 1. We found that recombinant protein 1 also inhibits phosphatidylinositol-specific phospholipase C activity.

First light measurements of the Total Solar Irradiance experiment CLARA on NORSAT-1

NASA Astrophysics Data System (ADS)

Schmutz, Werner

2016-07-01

NORSAT-1 is a Norwegian micro-satellite, which will be launched April 22, 2016. (In the future at the time of writing this abstract.) The satellite carries two scientific instruments and an AIS receiver for performing ship detection from space. One of the scientific instruments is a Compact Light-weight Absolute RAdiometer (CLARA) and the other is a Langmuir Probe instrument comprising four probes mounted on booms. The latter experiment will measure electron density and the platform's floating potential along the orbit. The University of Oslo provides the Langmuir probes. The radiometer experiment CLARA has been built by PMOD/WRC funded through the Swiss PRODEX program. It will measure Total Solar Irradiance with an instrument of novel design that is optimized for minimizing mass and size by still ensuring highest measuring accuracy and thermal stability. The radiometers of CLARA have been fully characterized as well as calibrated at the TRF facility. It is expected that the first light accuracy of the absolute measurement of Total Solar Irradiance will be better than pm0.3 W/m^{2, allowing to probe the current TSI composite for its absolute level. The presentation will give an overview of the CLARA instrument and its calibration. It is expected that at the time of the COSPAR conference the first light TSI value of CLARA/NORSAT-1 is ready for publication. Together with a previous absolute TSI measurements available for July 27, 2010 measured by PREMOS/PICARD the new absolute TSI measurement will be used to test the accuracy of long term TSI trend given by the relative TSI composite.

Escaping Slavery: "Sweet Clara and the Freedom Quilt."

ERIC Educational Resources Information Center

Miller, Sue Ann

This lesson uses the picture book "Sweet Clara and the Freedom Quilt" by Deborah Hopkinson and an interactive website to enhance third- through fifth-grade students' understanding of the Underground Railroad and slavery, development of reading comprehension skills, and application of mapping skills. During three 45-60 minute lessons,…

Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3.

PubMed

Urry, Zoe L; Richards, David F; Black, Cheryl; Morales, Maria; Carnés, Jerónimo; Hawrylowicz, Catherine M; Robinson, Douglas S

2014-05-29

Allergen immunotherapy (SIT) is the only treatment for allergic disease capable of modifying disease long term. To reduce the risk of anaphylaxis from SIT, allergen-extracts have been modified by polymerisation with glutaraldehyde to reduce IgE binding. It is suggested that these allergoid extracts also have reduced T cell activity, which could compromise clinical efficacy. Effective SIT is thought to act through regulatory T cells (Tregs) rather than activation of effector T cells. There is no published data on the activity of modified extracts on Tregs. We compared the capacity of modified (depigmented-polymerised) versus unmodified (native) allergen extracts of grass pollen and house dust mite to stimulate proliferation/cytokine production and to modulate Treg/effector T cell frequency in cultures of peripheral blood mononuclear cells (PBMC), from volunteers sensitised to both allergens in vitro. Depigmented-polymerised allergen extracts stimulated less proliferation of PBMC, and reduced effector cell numbers after 7 days in culture than did native extracts. However, the frequency of Foxp3+ Tregs in cultures were similar to those seen with native extract so that ratios of regulatory to effector T cells were significantly increased in cultures stimulated with depigmented-polymerised extracts. Addition of 1α, 25-dihydroxyvitamin D3 further favoured Treg, and reduced effector cytokine production, but not interleukin-10. Depigmented-polymerised allergen extracts appear to favour Treg expansion over activation of effector T cells and this may relate to their demonstrated efficacy and safety in SIT. 1α, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT.

Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3

PubMed Central

2014-01-01

Background Allergen immunotherapy (SIT) is the only treatment for allergic disease capable of modifying disease long term. To reduce the risk of anaphylaxis from SIT, allergen-extracts have been modified by polymerisation with glutaraldehyde to reduce IgE binding. It is suggested that these allergoid extracts also have reduced T cell activity, which could compromise clinical efficacy. Effective SIT is thought to act through regulatory T cells (Tregs) rather than activation of effector T cells. There is no published data on the activity of modified extracts on Tregs. Results We compared the capacity of modified (depigmented-polymerised) versus unmodified (native) allergen extracts of grass pollen and house dust mite to stimulate proliferation/cytokine production and to modulate Treg/effector T cell frequency in cultures of peripheral blood mononuclear cells (PBMC), from volunteers sensitised to both allergens in vitro. Depigmented-polymerised allergen extracts stimulated less proliferation of PBMC, and reduced effector cell numbers after 7 days in culture than did native extracts. However, the frequency of Foxp3+ Tregs in cultures were similar to those seen with native extract so that ratios of regulatory to effector T cells were significantly increased in cultures stimulated with depigmented-polymerised extracts. Addition of 1α, 25-dihydroxyvitamin D3 further favoured Treg, and reduced effector cytokine production, but not interleukin-10. Conclusions Depigmented-polymerised allergen extracts appear to favour Treg expansion over activation of effector T cells and this may relate to their demonstrated efficacy and safety in SIT. 1α, 25-dihydroxyvitamin D3 further reduces effector T cell activation by allergen extracts and may be a useful adjuvant for SIT. PMID:24884430

Coyote Creek (Santa Clara County) Pilot Revegetation Project

Treesearch

John T. Stanley; L. R. Silva; H. C. Appleton; M. S. Marangio; W. J. Lapaz; B. H. Goldner

1989-01-01

The Santa Clara Valley Water District, located in Northern California, is currently evaluating a pilot riparian revegetation project on a 1.6 ha (4 ac) site adjacent to Coyote Creek in the south San Francisco Bay Area. Specific techniques used during the design, site preparation and installation of 3640 plants (including seed planting locations) are described. This...

Natural Law, Santa Clara, and the Supreme Court.

ERIC Educational Resources Information Center

Rodgers, Raymond S.; Lujan, Phillip

The court case, "Santa Clara Pueblo, et al. v. Julia Martinez, et al.," is the subject of this paper. It gives the background of the case of a woman whose children were refused admittance to tribal rolls because of an ordinance prohibiting the enrollment of children whose father is not a tribal member. The paper gives the arguments of…

133. AERIAL VIEW OF CLARA BARTON PARKWAY AND I495 INTERCHANGE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

133. AERIAL VIEW OF CLARA BARTON PARKWAY AND I-495 INTERCHANGE LOOKING EAST. - George Washington Memorial Parkway, Along Potomac River from McLean to Mount Vernon, VA, Mount Vernon, Fairfax County, VA

Cultural Contact through Musical Poetry in Clara Janes's "Kampa"

ERIC Educational Resources Information Center

Faszer-McMahon, Debra

2009-01-01

Clara Janes's "Kampa" is a love song dedicated to the renowned Czech poet Vladimir Holan. The work includes a musical and lyrical composition performed on tape, and its unconventional musical mode offers an alternative to divisions between western and non-western literary and musical forms. The poetry of "Kampa" presents musical methods of…

Mapping Typha Domingensis in the Cienega de Santa Clara Using Satellite Images, Global Positioning System, and Spectrometry

USGS Publications Warehouse

Sanchez, Richard D.; Burnett, Earl E.; Croxen, Fred

2000-01-01

The Cienega de Santa Clara, Sonora, Mexico, a brackish wetland area created near the delta of the Colorado River from drainage effluent flowing from the United States since 1977, may undergo changes owing to the operation of the Yuma Desalting Plant in the United States. This has become the largest wetland in the delta region containing rare and endangered species, yet little is known about the environmental impact of these changes. The water quality of the marsh is of growing concern to the Bureau of Reclamation (BOR) which operates the Desalting Plant. Consequently, the BOR solicited the U.S. Geological Survey to investigate the limits and usefulness of satellite, global positioning system (GPS), and spectra data to map the Typha domingensis (cattail) of the Cienega de Santa Clara. Typha domingensis was selected by the BOR as the Cienega de Santa Clara indicator species to best predict the environmental effects of effl uent from the Yuma Desalting Plant. The successful base mapping of Typha domingensis will provide a viable tool for long-term monitoring and stress detection in the Cienega de Santa Clara.

Santa Clara Valley water district multi-aquifer monitoring-well site, Coyote Creek Outdoor Classroom, San Jose, California

USGS Publications Warehouse

Hanson, R.T.; Newhouse, M.W.; Wentworth, C.M.; Williams, C.F.; Noce, T.E.; Bennett, M.J.

2002-01-01

The U.S. Geological Survey (USGS), in cooperation with the Santa Clara Valley Water District (SCVWD), has completed the first of several multiple-aquifer monitoring-well sites in the Santa Clara Valley. This site monitors ground-water levels and chemistry in the one of the major historic subsidence regions south of San Jose, California, at the Coyote Creek Outdoor Classroom (CCOC) (fig. 1) and provides additional basic information about the geology, hydrology, geochemistry, and subsidence potential of the upper- and lower-aquifer systems that is a major source of public water supply in the Santa Clara Valley. The site also serves as a science education exhibit at the outdoor classroom operated by SCVWD.

Hydrogeologic framework of the Santa Clara Valley, California

USGS Publications Warehouse

Hanson, Randall T.

2015-01-01

The hydrologic framework of the Santa Clara Valley in northern California was redefined on the basis of new data and a new hydrologic model. The regional groundwater flow systems can be subdivided into upper-aquifer and lower-aquifer systems that form a convergent flow system within a basin bounded by mountains and hills on three sides and discharge to pumping wells and the southern San Francisco Bay. Faults also control the flow of groundwater within the Santa Clara Valley and subdivide the aquifer system into three subregions.After decades of development and groundwater depletion that resulted in substantial land subsidence, Santa Clara Valley Water District (SCVWD) and the local water purveyors have refilled the basin through conservation and importation of water for direct use and artificial recharge. The natural flow system has been altered by extensive development with flow paths toward major well fields. Climate has not only affected the cycles of sedimentation during the glacial periods over the past million years, but interannual to interdecadal climate cycles also have affected the supply and demand components of the natural and anthropogenic inflows and outflows of water in the valley. Streamflow has been affected by development of the aquifer system and regulated flow from reservoirs, as well as conjunctive use of groundwater and surface water. Interaquifer flow through water-supply wells screened across multiple aquifers is an important component to the flow of groundwater and recapture of artificial recharge in the Santa Clara Valley. Wellbore flow and depth-dependent chemical and isotopic data indicate that flow into wells from multiple aquifers, as well as capture of artificial recharge by pumping of water-supply wells, predominantly is occurring in the upper 500 ft (152 m) of the aquifer system. Artificial recharge represents about one-half of the inflow of water into the valley for the period 1970–1999. Most subsidence is occurring below 250 ft

Discovery of ammocrypta clara (western sand darter) in the Upper Ohio River of West Virginia

USGS Publications Warehouse

Cincotta, Dan A.; Welsh, Stuart A.

2010-01-01

Ammocrypta clara Jordan and Meek (western sand darter) occurs primarily in the western portions of Mississippi River system, but also has been reported from a Lake Michigan drainage and a few eastern Texas Gulf Slope rivers. Additional range records depict a semi-disjunct distribution within the Ohio River drainage, including collections from Wabash River in Indiana, the Cumberland, Green, Kentucky and Big Sandy rivers of Kentucky, and the upper Tennessee River in Tennessee and Virginia. This paper documents the occurrence of A. clara from the upper Ohio River drainage within the lower Elk River, West Virginia, based on collections from 1986, 1991, 1995, 2005 and 2006. The Elk River population, consistent with those of other Ohio River drainages, has slightly higher counts for numbers of dorsal-fin rays, scales below lateral line and lateral line scales when compared to data from populations outside of the Ohio River drainage. Modal counts of meristic characters are similar among populations, except for higher modal counts of lateral line scales in the Ohio River population. The discovery of the Elk River population extends the range distribution of A. clara in the Eastern Highlands region, documents wide distributional overlap and additional sympatry with its sister species,A. pellucida (eastern sand darter), and softens support for an east-west Central Highlands vicariance hypothesis for the present distribution of A. clara and A. pellucida.

Structural superposition in fault systems bounding Santa Clara Valley, California

USGS Publications Warehouse

Graymer, Russell W.; Stanley, Richard G.; Ponce, David A.; Jachens, Robert C.; Simpson, Robert W.; Wentworth, Carl M.

2015-01-01

Santa Clara Valley is bounded on the southwest and northeast by active strike-slip and reverse-oblique faults of the San Andreas fault system. On both sides of the valley, these faults are superposed on older normal and/or right-lateral normal oblique faults. The older faults comprised early components of the San Andreas fault system as it formed in the wake of the northward passage of the Mendocino Triple Junction. On the east side of the valley, the great majority of fault displacement was accommodated by the older faults, which were almost entirely abandoned when the presently active faults became active after ca. 2.5 Ma. On the west side of the valley, the older faults were abandoned earlier, before ca. 8 Ma and probably accumulated only a small amount, if any, of the total right-lateral offset accommodated by the fault zone as a whole. Apparent contradictions in observations of fault offset and the relation of the gravity field to the distribution of dense rocks at the surface are explained by recognition of superposed structures in the Santa Clara Valley region.

Expression of Clara cell 10-kDa protein and trefoil factor family 1 in patients with chronic rhinosinusitis and nasal polyps

PubMed Central

Wang, Yuanyuan; Wang, Zong-Feng; Zhang, Zhili; Su, Yi

2018-01-01

The current study measured the expression of Clara cell 10-kDa protein (CC10) and trefoil factor family 1 (TFF1) in the sinus mucosa of patients exhibiting chronic rhinosinusitis (CRS) and nasal polyps (NP). CC10 and TFF1 expression in the sinus mucosa of the control group and patients with CRS and NP was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The correlation between CC10 and TFF1 expression was further analyzed using Spearman's correlation analysis. The expression of TFF1 was significantly increased in the sinus mucosa of patients with CRS and NP, whereas CC10 expression was significantly decreased compared with controls. Spearman's correlation analysis identified a negative correlation between CC10 and TFF1 expression in the sinus mucosa of patients with CRS and NP. The results of immunohistochemistry and RT-qPCR were consistent with each other. Hematoxylin and eosin staining revealed notable lesions in the mucous membranes, goblet cells and cilia of sinus mucosa samples from patients with CRS and NP. The negative correlation between CC10 and TFF1 expression during the progression of CRS and NP suggest that CC10 and TFF1 may serve important roles in its pathogenesis. PMID:29456658

Spatially explicit West Nile virus risk modeling in Santa Clara County, California

USDA-ARS?s Scientific Manuscript database

A previously created Geographic Information Systems model designed to identify regions of West Nile virus (WNV) transmission risk is tested and calibrated in Santa Clara County, California. American Crows that died from WNV infection in 2005 provide the spatial and temporal ground truth. Model param...

Structure and Velocities of the Northeastern Santa Cruz Mountains and the Western Santa Clara Valley, California, from the SCSI-LR Seismic Survey

USGS Publications Warehouse

Catchings, R.D.; Goldman, M.R.; Gandhok, G.

2006-01-01

Introduction: The Santa Clara Valley is located in the southern San Francisco Bay area of California and generally includes the area south of the San Francisco Bay between the Santa Cruz Mountains on the southwest and the Diablo Ranges on the northeast. The area has a population of approximately 1.7 million including the city of San Jose, numerous smaller cities, and much of the high-technology manufacturing and research area commonly referred to as the Silicon Valley. Major active strands of the San Andreas Fault system bound the Santa Clara Valley, including the San Andreas fault to the southwest and the Hayward and Calaveras faults to the northeast; related faults likely underlie the alluvium of the valley. This report focuses on subsurface structures of the western Santa Clara Valley and the northeastern Santa Cruz Mountains and their potential effects on earthquake hazards and ground-water resource management in the area. Earthquake hazards and ground-water resources in the Santa Clara Valley are important considerations to California and the Nation because of the valley's preeminence as a major technical and industrial center, proximity to major earthquakes faults, and large population. To assess the earthquake hazards of the Santa Clara Valley better, the U.S. Geological Survey (USGS) has undertaken a program to evaluate potential earthquake sources and potential effects of strong ground shaking within the valley. As part of that program, and to better assess water resources of the valley, the USGS and the Santa Clara Valley Water District (SCVWD) began conducting collaborative studies to characterize the faults, stratigraphy, and structures beneath the alluvial cover of the Santa Clara Valley in the year 2000. Such geologic features are important to both agencies because they directly influence the availability and management of groundwater resources in the valley, and they affect the severity and distribution of strong shaking from local or regional

A spatial analysis of the Burrowing Owl (Speotyto cunicularia) population in Santa Clara County, California, using a geographic information system

Treesearch

Janice Taylor Buchanan

1997-01-01

A small population of Burrowing Owls (Speotyto cunicularia) is found in the San Francisco Bay Area, particularly in Santa Clara County. These owls utilize habitat that is dispersed throughout this heavily urbanized region. In an effort to establish a conservation plan for Burrowing Owls in Santa Clara County, a spatial analysis of owl distribution...

31 flavors to 50 shades of grey: battling Phytophthoras in native habitats managed by the Santa Clara Valley Water District

Treesearch

Janet Hillman; Tedmund J. Swiecki; Elizabeth A. Bernhardt; Heather K. Mehl; Tyler B. Bourret; David Rizzo

2017-01-01

The Santa Clara Valley Water District (District) is a wholesale water supplier for 1.8 million people in Santa Clara County, California. Capital, water utility, and stream maintenance projects result in extensive, long-term mitigation requirements in riparian, wetland, and upland habitats throughout the county. In 2014, several restoration sites on the valley floor and...

Spatially Explicit West Nile Virus Risk Modeling in Santa Clara County, CA

USDA-ARS?s Scientific Manuscript database

A geographic information systems model designed to identify regions of West Nile virus (WNV) transmission risk was tested and calibrated with data collected in Santa Clara County, California. American Crows that died from WNV infection in 2005, provided spatial and temporal ground truth. When the mo...

SRTM Perspective View with Landsat Overlay: Santa Paula, and Santa Clara River Valley, California

NASA Image and Video Library

2000-12-14

Rectangular fields of the agriculturally rich Santa Clara River Valley are visible in this perspective view generated by using data from the Shuttle Radar Topography Mission and an enhanced Landsat image.

Evaluation of animal control measures on pet demographics in Santa Clara County, California, 1993-2006.

PubMed

Kass, Philip H; Johnson, Karen L; Weng, Hsin-Yi

2013-01-01

The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes. A prospective cross-sectional study of 1000 households was implemented in 2005 to evaluate characteristics of the owned and unowned population of dogs and cats in Santa Clara County, California. The same population was previously studied 12 years earlier. During this time period, the county instituted in 1994 and then subsequently disestablished a municipal spay/neuter voucher program for cats. Dog intakes declined from 1992-2005, as they similarly did for an adjacent county (San Mateo). However, cat intakes declined significantly more in Santa Clara County than San Mateo, with an average annual decline of approximately 700 cats for the 12 year period. Time series analysis showed a greater than expected decline in the number of cats surrendered to shelters in Santa Clara County during the years the voucher program was in effect (1994-2005). The net savings to the county by reducing the number of cat shelter intakes was estimated at approximately $1.5 million. The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes.

Groundwater quality in the Santa Clara River Valley, California

USGS Publications Warehouse

Burton, Carmen A.; Landon, Matthew K.; Belitz, Kenneth

2011-01-01

The Santa Clara River Valley (SCRV) study unit is located in Los Angeles and Ventura Counties, California, and is bounded by the Santa Monica, San Gabriel, Topatopa, and Santa Ynez Mountains, and the Pacific Ocean. The 460-square-mile study unit includes eight groundwater basins: Ojai Valley, Upper Ojai Valley, Ventura River Valley, Santa Clara River Valley, Pleasant Valley, Arroyo Santa Rosa Valley, Las Posas Valley, and Simi Valley (California Department of Water Resources, 2003; Montrella and Belitz, 2009). The SCRV study unit has hot, dry summers and cool, moist winters. Average annual rainfall ranges from 12 to 28 inches. The study unit is drained by the Ventura and Santa Clara Rivers, and Calleguas Creek. The primary aquifer system in the Ventura River Valley, Ojai Valley, Upper Ojai Valley, and Simi Valley basins is largely unconfined alluvium. The primary aquifer system in the remaining groundwater basins mainly consists of unconfined sands and gravels in the upper portion and partially confined marine and nonmarine deposits in the lower portion. The primary aquifer system in the SCRV study unit is defined as those parts of the aquifers corresponding to the perforated intervals of wells listed in the California Department of Public Health (CDPH) database. Public-supply wells typically are completed in the primary aquifer system to depths of 200 to 1,100 feet below land surface (bls). The wells contain solid casing reaching from the land surface to a depth of about 60-700 feet, and are perforated below the solid casing to allow water into the well. Water quality in the primary aquifer system may differ from the water in the shallower and deeper parts of the aquifer. Land use in the study unit is approximately 40 percent (%) natural (primarily shrubs, grassland, and wetlands), 37% agricultural, and 23% urban. The primary crops are citrus, avocados, alfalfa, pasture, strawberries, and dry beans. The largest urban areas in the study unit are the cities of

Clara Barton High School Bilingual Program. O.E.E. Evaluation Report, 1982-1983.

ERIC Educational Resources Information Center

Collazo-Levy, Dora; Sica, Michael

In 1982-83, the program evaluated here provided tutorial and supportive services to approximately 50 Spanish-speaking students of limited English proficiency (LEP) in grades 9-12 at Clara Barton High School, Brooklyn, New York. The program's main objective was to enable LEP students to function successfully in terms of language achievement and…

Clara Barton High School. Bilingual Project. O.E.E. Evaluation Report, 1981-1982.

ERIC Educational Resources Information Center

Shore, Rima; And Others

The report evaluates the Bilingual-Bicultural Project conducted in 1981-82 at Clara Barton High School, in Brooklyn, New York, for 50 Spanish speaking students with limited English proficiency (LEP). The project was designed to provide tutorial support to LEP students and to enable them to be placed in one of the more challenging health profession…

3D basin structure of the Santa Clara Valley constrained by ambient noise tomography

NASA Astrophysics Data System (ADS)

Cho, H.; Lee, S. J.; Rhie, J.; Kim, S.

2017-12-01

The basin structure is an important factor controls the intensity and duration of ground shaking due to earthquake. Thus it is important to study the basin structure for better understanding seismic hazard and also improving the earthquake preparedness. An active source seismic survey is the most appropriate method to determine the basin structure in detail but its applicability, especially in urban areas, is limited. In this study, we tested the potential of an ambient noise tomography, which can be a cheaper and more easily applicable method compared to a traditional active source survey, to construct the velocity model of the basin. Our testing region is the Santa Clara Valley, which is one of the major urban sedimentary basins in the States. We selected this region because continuous seismic recordings and well defined velocity models are available. Continuous seismic recordings of 6 months from short-period array of Santa Clara Valley Seismic Experiment are cross-correlated with 1 hour time window. And the fast marching method and the subspace method are jointly applied to construct 2-D group velocity maps between 0.2 - 4.0 Hz. Then, shear wave velocity model of the Santa Clara Valley is calculated up to 5 km depth using bayesian inversion technique. Although our model cannot depict the detailed structures, it is roughly comparable with the velocity model of the US Geological Survey, which is constrained by active seismic surveys and field researches. This result indicate that an ambient noise tomography can be a replacement, at least in part, of an active seismic survey to construct the velocity model of the basin.

Numerical model of a tracer test on the Santa Clara River, Ventura County, California

USGS Publications Warehouse

Nishikawa, Tracy; Paybins, Katherine S.; Izbicki, John A.; Reichard, Eric G.

1999-01-01

To better understand the flow processes, solute-transport processes, and ground-water/surface-water interactions on the Santa Clara River in Ventura County, California, a 24-hour fluorescent-dye tracer study was performed under steady-state flow conditions on a 45-km reach of the river. The study reach includes perennial (uppermost and lowermost) subreaches and ephemeral subreaches of the lower Piru Creek and the middle Santa Clara River. The tracer-test data were used to calibrate a one-dimensional flow model (DAFLOW) and a solute-transport model (BLTM). The dye-arrival times at each sample location were simulated by calibrating the velocity parameters in DAFLOW. The simulations of dye transport indicated that (1) ground-water recharge explains the loss of mass in the ephemeral middle subreaches, and (2) groundwater recharge does not explain the loss of mass in the perennial uppermost and lowermost subreaches. The observed tracer curves in the perennial subreaches were indicative of sorptive dye losses, transient storage, and (or) photodecay - these phenomena were simulated using a linear decay term. However, analysis of the linear decay terms indicated that photodecay was not a dominant source of dye loss.To better understand the flow processes, solute-transport processes, and ground-water/surface-water interactions on the Santa Clara River in Ventura County, California, a 24-hour fluorescent-dye tracer study was performed under steady-state flow conditions on a 45-km reach of the river. The study reach includes perennial (uppermost and lowermost) subreaches and ephemeral subreaches of the lower Piru Creek and the middle Santa Clara River. The tracer-test data were used to calibrate a one-dimension-al flow model (DAFLOW) and a solute-transport model (BLTM). The dye-arrival times at each sample location were simulated by calibrating the velocity parameters in DAFLOW. The simulations of dye transport indicated that (1) ground-water recharge explains the loss of

Repair of tracheal epithelium by basal cells after chlorine-induced injury

PubMed Central

2012-01-01

Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10), but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion The data are

Housing Patterns in Relation to Educational Achievement. Project SIMU School: Santa Clara County Component.

ERIC Educational Resources Information Center

Baker, William P.; Hoffmann, Glenn W.

This paper focuses attention on the critical importance of zoning and housing to education. It covers the causes of undersirable housing patterns, the apparent effects of these patterns on educational achievement, and possibilities for positive action to reverse the negative effects. Although examples are drawn from Santa Clara County, the thesis…

Ephemeral stream reaches preserve the evolutionary and distributional history of threespine stickleback in the Santa Clara and Ventura River watersheds of southern California

USGS Publications Warehouse

Richmond, Jonathan Q.; Jacobs, David K.; Backlin, Adam R.; Swift, Camm C.; Dellith, Chris; Fisher, Robert N.

2015-01-01

Much remains to be understood about the evolutionary history and contemporary landscape genetics of unarmored threespine stickleback in southern California, where populations collectively referred to as Gasterosteus aculeatus williamsoni have severely declined over the past 70+ years and are now endangered. We used mitochondrial sequence and microsatellite data to assess the population genetics and phylogeography of unarmored populations sampled immediately downstream from the type locality of G. a. williamsoni in the upper Santa Clara River, and assessed their distinctiveness with respect to low-armor populations in the downstream sections of the river and the adjacent Ventura River. We also characterized the geographic limits of different plate morphs and evaluated the congruence of those boundaries with barriers to dispersal in both river systems and to neutral genetic variation. We show substantial population structuring within the upper reach of the Santa Clara River, but little partitioning between the lower Santa Clara and Ventura Rivers—we attribute these patterns to different ancestry between spatially subdivided populations within the same drainage, a predominance of downstream gene flow, and ability for coastal dispersal between the Santa Clara and Ventura Rivers. We also show that alleles from introduced low-plate stock have infiltrated a native population in at least one upper Santa Clara River tributary, causing this formerly unarmored population to become gradually low-plated over a 30 + year time period. Measures of genetic diversity, census surveys, and severe habitat disturbance all indicate that unarmored stickleback near the type locality are currently at high risk of extinction.

Modeling the Cienega de Santa Clara, Sonora, Mexico

NASA Astrophysics Data System (ADS)

Huckelbridge, K. H.; Hidalgo, H.; Dracup, J.; Ibarra Obando, S. E.

2002-12-01

The Cienega de Santa Clara is a created wetland located in the Colorado River Delta (CRD), in Sonora, Mexico. It is sustained by agricultural return flows from the Wellton-Mohawk Irrigation District in Arizona and the Mexicali Valley in Mexico. As one of the few wetlands remaining in the CRD, it provides critical habitat for several species of fish and birds, including several endangered species such as the desert pupfish (Cyprinodon macularius) and the Yuma clapper rail (Rallus longirostris yumanensis). However, this habitat may be in jeopardy if the quantity and quality of the agricultural inflows are significantly altered. This study seeks to develop a model that describes the dynamics of wetland hydrology, vegetation, and water quality as a function of inflow variability and salinity loading. The model is divided into four modules set up in sequence. For a given time step, the sequence begins with the first module, which utilizes basic diffusion equations to simulate mixing processes in the shallow wetland when the flow and concentration of the inflow deviate from the baseline. The second module develops a vegetated-area response to the resulting distribution of salinity in the wetland. Using the new area of vegetation cover determined by the second module and various meteorological variables, the third module calculates the evapotranspiration rate for the wetland, using the Penman-Montieth equation. Finally, the fourth module takes the overall evapotranspiration rate, along with precipitation, inflow and outflow and calculates the new volume of the wetland using a water balance. This volume then establishes the initial variables for the next time step. The key outputs from the model are salinity concentration, area of vegetation cover, and wetland volume for each time step. Results from this model will illustrate how the wetland's hydrology, vegetation, and water quality are altered over time under various inflow scenarios. These outputs can ultimately be used

Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts.

PubMed

Cellot, Giada; Cilia, Emanuele; Cipollone, Sara; Rancic, Vladimir; Sucapane, Antonella; Giordani, Silvia; Gambazzi, Luca; Markram, Henry; Grandolfo, Micaela; Scaini, Denis; Gelain, Fabrizio; Casalis, Loredana; Prato, Maurizio; Giugliano, Michele; Ballerini, Laura

2009-02-01

Carbon nanotubes have been applied in several areas of nerve tissue engineering to probe and augment cell behaviour, to label and track subcellular components, and to study the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote neuronal electrical activity in networks of cultured cells, but the ways in which they affect cellular function are still poorly understood. Here, we show, using single-cell electrophysiology techniques, electron microscopy analysis and theoretical modelling, that nanotubes improve the responsiveness of neurons by forming tight contacts with the cell membranes that might favour electrical shortcuts between the proximal and distal compartments of the neuron. We propose the 'electrotonic hypothesis' to explain the physical interactions between the cell and nanotube, and the mechanisms of how carbon nanotubes might affect the collective electrical activity of cultured neuronal networks. These considerations offer a perspective that would allow us to predict or engineer interactions between neurons and carbon nanotubes.

Field-trip guide to the southeastern foothills of the Santa Cruz Mountains in Santa Clara County, California

USGS Publications Warehouse

Stoffer, Philip W.; Messina, Paula

2002-01-01

This field trip is an introduction to the geology of the southeastern foothills of the Santa Cruz Mountains in southern Santa Clara County. Seven stops include four short hikes to access rock exposures and views of the foothills east of Loma Prieta Peak between Gilroy and San José. Field-trip destinations highlight the dominant rock types of the "Franciscan assemblage" including outcrops of serpentinite, basalt, limestone, ribbon chert, graywacke sandstone, and shale. General discussions include how the rocks formed, and how tectonism and stream erosion have changed the landscape through time. All field trip stops are on public land; most are near reservoir dams of the Santa Clara Valley Water District. In addition, stops include examination of an Ohlone Indian heritage site and the New Almaden Mining Museum.

Lake warming favours small-sized planktonic diatom species

PubMed Central

Winder, Monika; Reuter, John E.; Schladow, S. Geoffrey

2008-01-01

Diatoms contribute to a substantial portion of primary production in the oceans and many lakes. Owing to their relatively heavy cell walls and high nutrient requirements, planktonic diatoms are expected to decrease with climate warming because of reduced nutrient redistribution and increasing sinking velocities. Using a historical dataset, this study shows that diatoms were able to maintain their biovolume with increasing stratification in Lake Tahoe over the last decades; however, the diatom community structure changed. Increased stratification and reduced nitrogen to phosphorus ratios selected for small-celled diatoms, particularly within the Cyclotella genus. An empirical model showed that a shift in phytoplankton species composition and cell size was consistent within different depth strata, indicating that altered nutrient concentrations were not responsible for the change. The increase in small-celled species was sufficient to decrease the average diatom size and thus sinking velocity, which strongly influences energy transfer through the food web and carbon cycling. Our results show that within the diverse group of diatoms, small-sized species with a high surface area to volume ratio were able to adapt to a decrease in mixing intensity, supporting the hypotheses that abiotic drivers affect the size structure of planktonic communities and that warmer climate favours small-sized diatom cells. PMID:18812287

Tissue-specific expression of the gene coding for human Clara cell 10-kD protein, a phospholipase A2-inhibitory protein.

PubMed Central

Peri, A; Cordella-Miele, E; Miele, L; Mukherjee, A B

1993-01-01

Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibitor, is suggested to be the human counterpart of rabbit uteroglobin (UG). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be useful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before designing gene transfer experiments. Since the UG gene in the rabbit is expressed in many other organs besides the lung and the endometrium, we investigated the organ and tissue specificity of human cc10kD gene expression using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, to that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene before its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological function(s). Images PMID:8227325

[Anatomical Vitamin C-Research during National Socialism and the Post-war Period: Max Clara's Human Experiments at the Munich Anatomical Institute].

PubMed

Schûtz, Mathias; Schochow, Maximilian; Waschke, Jens; Marckmann, Georg; Steger, Florian

2014-01-01

In autumn of 1942, Max Clara (1899-1966) became chairman of the anatomical institute Munich. There, he intensified his research concerning the proof of vitamin C with the bodies of executed prisoners which were delivered by the Munich-Stadelheim prison. This research on human organs was pursued by applying ascorbic acid (Cebion) to prisoners before their execution. The paper investigates this intensified and radicalized anatomical research through human experiments, which Max Clara conducted in Munich and published from Istanbul during the postwar years, as well as its scientific references from the Nazi period.

Daily variation in fine and ultrafine particulate air pollution and urinary concentrations of lung Clara cell protein CC16

PubMed Central

Timonen, K; Hoek, G; Heinrich, J; Bernard, A; Brunekreef, B; de Hartog, J; Hameri, K; Ibald-Mulli, A; Mirme, A; Peters, A; Tiittanen, P; Kreyling, W; Pekkanen, J

2004-01-01

Background: Daily variations in ambient particulate air pollution have been associated with respiratory mortality and morbidity. Aims: To assess the associations between urinary concentration of lung Clara cell protein CC16, a marker for lung damage, and daily variation in fine and ultrafine particulate air pollution. Methods: Spot urinary samples (n = 1249) were collected biweekly for six months in subjects with coronary heart disease in Amsterdam, Netherlands (n = 37), Erfurt, Germany (n = 47), and Helsinki, Finland (n = 47). Ambient particulate air pollution was monitored at a central site in each city. Results: The mean 24 hour number concentration of ultrafine particles was 17.3x103 cm–3 in Amsterdam, 21.1x103 cm–3 in Erfurt, and 17.0x103 cm–3 in Helsinki. The mean 24 hour PM2.5 concentrations were 20, 23, and 13 µg/m3, respectively. Daily variation in ultrafine particle levels was not associated with CC16. In contrast, CC16 concentration seemed to increase with increasing levels of PM2.5 in Helsinki, especially among subjects with lung disorders. No clear associations were observed in Amsterdam and Erfurt. In Helsinki, the CC16 concentration increased by 20.2% (95% CI 6.9 to 33.5) per 10 µg/m3 increase in PM2.5 concentration (lag 2). The respective pooled effect estimate was 2.1% (95% CI –1.3 to 5.6). Conclusion: The results suggest that exposure to particulate air pollution may lead to increased epithelial barrier permeability in lungs. PMID:15477284

78 FR 67336 - Habitat Conservation Plan for the United Water Conservation District, Santa Clara River Watershed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... incidental take permits for United's construction, operations, and maintenance of water management facilities... maintenance of the Freeman Diversion; diversion of water from the Santa Clara River; vegetation management... current and future water management activities. United intends to request a 50-year permit covering five...

Circadian Timing in the Lung; A Specific Role for Bronchiolar Epithelial Cells

PubMed Central

Gibbs, J. E.; Beesley, S.; Plumb, J.; Singh, D.; Farrow, S.; Ray, D. W.; Loudon, A. S. I.

2015-01-01

In addition to the core circadian oscillator, located within the suprachiasmatic nucleus, numerous peripheral tissues possess self-sustaining circadian timers. In vivo these are entrained and temporally synchronized by signals conveyed from the core oscillator. In the present study, we examine circadian timing in the lung, determine the cellular localization of core clock proteins in both mouse and human lung tissue, and establish the effects of glucocorticoids (widely used in the treatment of asthma) on the pulmonary clock. Using organotypic lung slices prepared from transgenic mPER2::Luc mice, luciferase levels, which report PER2 expression, were measured over a number of days. We demonstrate a robust circadian rhythm in the mouse lung that is responsive to glucocorticoids. Immunohistochemical techniques were used to localize specific expression of core clock proteins, and the glucocorticoid receptor, to the epithelial cells lining the bronchioles in both mouse and human lung. In the mouse, these were established to be Clara cells. Murine Clara cells retained circadian rhythmicity when grown as a pure population in culture. Furthermore, selective ablation of Clara cells resulted in the loss of circadian rhythm in lung slices, demonstrating the importance of this cell type in maintaining overall pulmonary circadian rhythmicity. In summary, we demonstrate that Clara cells are critical for maintaining coherent circadian oscillations in lung tissue. Their coexpression of the glucocorticoid receptor and core clock components establishes them as a likely interface between humoral suprachiasmatic nucleus output and circadian lung physiology. PMID:18787022

Perspectives of Mobile Versus Fixed Mammography in Santa Clara County, California: A Focus Group Study.

PubMed

Chen, Yi-Ren; Chang-Halpenny, Christine; Kumarasamy, Narmadan A; Venegas, Angela; Braddock Iii, Clarence H

2016-02-12

Our aim was to examine underserved women's perceptions on mobile versus fixed mammography in Santa Clara, California through a focus group study.  Research has shown that medically underserved women have higher breast cancer mortality rates correlated with under-screening and a disproportional rate of late-stage diagnosis. The Community Health Partnership in Santa Clara County, California runs the Community Mammography Access Project (CMAP) that targets nearly 20,000 medically underserved women over the age of 40 in the county through the collaborative effort of an existing safety net of healthcare providers. However, little data exists on the advantages or disadvantages of mobile mammography units from the patient perspective.   We assessed underserved women's perspectives on mammography services in Santa Clara County through two focus groups from women screened at mobile or fixed site programs. Patients were recruited from both CMAP clinics and a county hospital, and focus group data were analyzed using content analysis.  We found that women from both the mobile and fixed sites shared similar motivating factors for getting a mammogram. Both groups recognized that screening was uncomfortable but necessary for good health and had positive feedback about their personal physicians. However, mobile participants, in particular, appreciated the atmosphere of mobile screening, reported shorter wait times, and remarked on the good communication from the clinic staff and empathetic treatment they received. However, mobile participants also expressed concern about the quality of films at mobile sites due to delayed initial reading of the films.   Mobile mammography offers a unique opportunity for women of underserved populations to access high satisfaction screenings, and it encourages a model similar to CMAP in other underserved areas. However, emphasis should be placed on providing a warm and welcoming environment for patients and ensuring the quality of

Small cell carcinoma with concomitant adenocarcinoma arising in a Barrett's oesophagus: report of a case with a favourable behaviour.

PubMed

Bibeau, Frédéric; Chateau, Marie-Christine; Guiu, Michel; Assenat, Eric; Azria, David; Lavaill, Rosy; Ychou, Marc; Boissière-Michot, Florence

2008-01-01

Most Barrett's oesophagus-associated cancers are adenocarcinomas which occur in a pure form. They are rarely combined with another type of malignancy, such as endocrine tumours. Within the endocrine spectrum, small cell carcinomas (SmCC) usually have a highly aggressive behaviour with a poor prognosis. We report a case of composite SmCC and adenocarcinoma in the setting of a Barrett's oesophagus, in a 54-year-old man. This tumour was identified on a surgical specimen after neoadjuvant treatment with radiotherapy and 5-FU-Cis-platin based chemotherapy. The SmCC component was positive for chromogranin A, synaptophysin, neural cell adhesion molecule and neuron-specific enolase and negative for high molecular weight cytokeratin. The adenocarcinoma component showed a converse phenotype. In our case, the origin of the SmCC component could be explained by the numerous chromogranin A-positive cells observed in the Barrett's oesophagus or by the potential progenitor cells that may be located in the submucosal oesophageal gland ducts and the Barrett's metaplasia. Our report is thus indicative of the high and totipotential risk of Barrett's oesophagus. Moreover, it is particular because of its favourable behaviour, with a 6-year disease-free survival, after neoadjuvant chemoradiation, surgery and postoperative chemotherapy.

Ambient Noise Monitoring of the Santa Clara and San Gabriel Aquifers

NASA Astrophysics Data System (ADS)

Clements, T.; Denolle, M.

2016-12-01

Ambient noise cross-correlation is an effective technique to monitor temporal changes in the properties of the solid earth. The technique has had particular success in monitoring over time scales differing by orders of magnitude, with precursors to volcanic eruptions occurring over days [Brenguier, et al., 2008, Nature] and post-seismic relaxation in fault zones occurring over years [Brenguier, et al., 2008, Science]. Recently, the technique was extended to investigate the interaction of the solid earth and climate via ice sheet melt [Mordret et al.,2016]. In that vein, we use ambient noise cross-correlation to monitor basin-scale aquifers. The technique is amenable to studying aquifers, as it has potential for high spatial resolution, on the scale of a basin and can monitor aquifer recharge/draw down on timescales from large, single-day storms to multi-year droughts. Geodetics studies have previously recorded both long term, in the Santa Clara Valley [Chaussard et al., 2014, Schmidt and Burgmann, 2003], and short-term, in the San Gabriel Valley [King et al. 2007], ground uplift due to aquifer recharge. We use the Moving Window Cross Spectral technique [Clarke et al., 2011] to monitor wave-speed perturbation in the Santa Clara valley over the period 2001-2016 and San Gabriel Basin over the period 1995-2016. Preliminary results, using stations from the Berkeley Digital Seismograph Network and the USGS Northern California Regional Network, show that seismic velocities vary 0.1% intra-annually. We explore the temporal variations, along with correlations in observed ground water data, precipitation and geodesic measurements to deduce the poroelastic properties of the aquifers during the last two El-Nino and recent droughts in California.

β-Catenin Dosage Is a Critical Determinant of Tracheal Basal Cell Fate Determination

PubMed Central

Brechbuhl, Heather M.; Ghosh, Moumita; Smith, Mary Kathryn; Smith, Russell W.; Li, Bilan; Hicks, Douglas A.; Cole, Brook B.; Reynolds, Paul R.; Reynolds, Susan D.

2011-01-01

The purpose of this study was to determine whether β-catenin regulates basal cell fate determination in the mouse trachea. Analysis of TOPGal transgene reporter activity and Wnt/β-catenin pathway gene expression suggested a role for β-catenin in basal cell proliferation and differentiation after naphthalene-mediated Clara-like and ciliated cell depletion. However, these basal cell activities occurred simultaneously, limiting precise determination of the role(s) played by β-catenin. This issue was overcome by analysis of β-catenin signaling in tracheal air-liquid interface cultures. The cultures could be divided into two phases: basal cell proliferation and basal cell differentiation. A role for β-catenin in basal cell proliferation was indicated by activation of the TOPGal transgene on proliferation days 3 to 5 and by transient expression of Myc (alias c-myc). Another peak of TOPGal transgene activity was detected on differentiation days 2 to 10 and was associated with the expression of Axin 2. These results suggest a role for β-catenin in basal to ciliated and basal to Clara-like cell differentiation. Genetic stabilization of β-catenin in basal cells shortened the period of basal cell proliferation but had a minor effect on this process. Persistent β-catenin signaling regulated basal cell fate by driving the generation of ciliated cells and preventing the production of Clara-like cells. PMID:21703416

76 FR 72972 - Notice of Realty Action: Competitive Sale of Public Land in Santa Clara County, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

...; CACA 50168] Notice of Realty Action: Competitive Sale of Public Land in Santa Clara County, CA AGENCY... the proposed sale must be received by the BLM on or before January 12, 2012. ADDRESSES: Written comments concerning the proposed sale should be sent to the Field Manager, BLM, Hollister Field Office, 20...

Water resources development in Santa Clara Valley, California: insights into the human-hydrologic relationship

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reynolds, Jesse L.

2000-06-01

Groundwater irrigation is critical to food production and, in turn, to humankind's relationship with its environment. The development of groundwater in Santa Clara Valley, California during the early twentieth century is instructive because (1) responses to unsustainable resource use were largely successful; (2) the proposals for the physical management of the water, although not entirely novel, incorporated new approaches which reveal an evolving relationship between humans and the hydrologic cycle; and (3) the valley serves as a natural laboratory where natural (groundwater basin, surface watershed) and human (county, water district) boundaries generally coincide. Here, I investigate how water resources developmentmore » and management in Santa Clara Valley was influenced by, and reflective of, a broad understanding of water as a natural resource, including scientific and technological innovations, new management approaches, and changing perceptions of the hydrologic cycle. Market demands and technological advances engendered reliance on groundwater. This, coupled with a series of dry years and laissez faire government policies, led to overdraft. Faith in centralized management and objective engineering offered a solution to concerns over resource depletion, and a group dominated by orchardists soon organized, fought for a water conservation district, and funded an investigation to halt the decline of well levels. Engineer Fred Tibbetts authored an elaborate water salvage and recharge plan that optimized the local water resources by integrating multiple components of the hydrologic cycle. Informed by government investigations, groundwater development in Southern California, and local water law cases, it recognized the limited surface storage possibilities, the spatial and temporal variability, the relatively closed local hydrology, the interconnection of surface and subsurface waters, and the value of the groundwater basin for its storage, transportation, and

76 FR 68784 - Notice of Realty Action: Direct Sale of Public Land in Santa Clara County, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

...] Notice of Realty Action: Direct Sale of Public Land in Santa Clara County, CA AGENCY: Bureau of Land... regarding the proposed sale must be received by the BLM on or before December 22, 2011. ADDRESSES: Written comments concerning the proposed sale should be sent to the Field Manager, BLM Hollister Field Office, 20...

Modeling and validation of a 3D velocity structure for the Santa Clara Valley, California, for seismic-wave simulations

USGS Publications Warehouse

Hartzell, S.; Harmsen, S.; Williams, R.A.; Carver, D.; Frankel, A.; Choy, G.; Liu, P.-C.; Jachens, R.C.; Brocher, T.M.; Wentworth, C.M.

2006-01-01

A 3D seismic velocity and attenuation model is developed for Santa Clara Valley, California, and its surrounding uplands to predict ground motions from scenario earthquakes. The model is developed using a variety of geologic and geophysical data. Our starting point is a 3D geologic model developed primarily from geologic mapping and gravity and magnetic surveys. An initial velocity model is constructed by using seismic velocities from boreholes, reflection/refraction lines, and spatial autocorrelation microtremor surveys. This model is further refined and the seismic attenuation is estimated through waveform modeling of weak motions from small local events and strong-ground motion from the 1989 Loma Prieta earthquake. Waveforms are calculated to an upper frequency of 1 Hz using a parallelized finite-difference code that utilizes two regions with a factor of 3 difference in grid spacing to reduce memory requirements. Cenozoic basins trap and strongly amplify ground motions. This effect is particularly strong in the Evergreen Basin on the northeastern side of the Santa Clara Valley, where the steeply dipping Silver Creek fault forms the southwestern boundary of the basin. In comparison, the Cupertino Basin on the southwestern side of the valley has a more moderate response, which is attributed to a greater age and velocity of the Cenozoic fill. Surface waves play a major role in the ground motion of sedimentary basins, and they are seen to strongly develop along the western margins of the Santa Clara Valley for our simulation of the Loma Prieta earthquake.

Epstein-Barr virus-driven B Cell Proliferation with CD4+ T Cell Expansion: A Lymphomatoid Granulomatosis-like Disease Related to Hyperinterleukin-10 Secretion of Remarkably Favourable Outcome with Rituximab.

PubMed

Cervera, P; Guihot, A; Gorochov, G; Lassoued, K; Coppo, P

2015-12-01

Granulomatous lymphomatosis is an Epstein-Barr virus (EBV)-driven B cell proliferation associated with an exuberant CD4(+) T cell reaction with usually histopathological pictures of angiocentrism. So far, the characteristics of CD4(+) T cells in granulomatous lymphomatosis and the mechanism leading to their expansion remain poorly explored. We report a 56-year-old female with a past history of cold agglutinin disease, which was successfully treated with 4 weekly infusions of rituximab. She presented one year later with features of granulomatous lymphomatosis that resulted in severe lung and bone marrow infiltration. We provide evidence that CD4(+) T cell expansion was oligoclonal, involved anergic cells and did not result from an EBV-driven stimulation. Rather, it resulted possibly from a high production of interleukin-10 by immunoblastic EBV-positive B cells. The outcome was remarkably favourable with rituximab and steroids. Our results suggest that an EBV-driven B cell proliferation should be investigated in patients presenting with a CD4(+) T cells alveolitis or other systemic manifestations resulting from a CD4(+) T cell expansion. These features should prompt to introduce an immunosuppressive therapy including steroids and rituximab. Our results deserve further investigations to confirm our pathophysiological hypotheses in CD4(+) T cell expansions associated with EBV-driven B cell proliferations and to assess whether granulomatous lymphomatosis could result from comparable mechanisms. © 2015 The Foundation for the Scandinavian Journal of Immunology.

Status and understanding of groundwater quality in the Santa Clara River Valley, 2007-California GAMA Priority Basin Project

USGS Publications Warehouse

Burton, Carmen A.; Montrella, Joseph; Landon, Matthew K.; Belitz, Kenneth

2011-01-01

Groundwater quality in the approximately 460-square-mile Santa Clara River Valley study unit was investigated from April through June 2007 as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project is conducted by the U.S. Geological Survey (USGS) in collaboration with the California State Water Resources Control Board and the Lawrence Livermore National Laboratory. The Santa Clara River Valley study unit contains eight groundwater basins located in Ventura and Los Angeles Counties and is within the Transverse and Selected Peninsular Ranges hydrogeologic province. The Santa Clara River Valley study unit was designed to provide a spatially unbiased assessment of the quality of untreated (raw) groundwater in the primary aquifer system. The assessment is based on water-quality and ancillary data collected in 2007 by the USGS from 42 wells on a spatially distributed grid, and on water-quality data from the California Department of Public Health (CDPH) database. The primary aquifer system was defined as that part of the aquifer system corresponding to the perforation intervals of wells listed in the CDPH database for the Santa Clara River Valley study unit. The quality of groundwater in the primary aquifer system may differ from that in shallow or deep water-bearing zones; for example, shallow groundwater may be more vulnerable to surficial contamination. Eleven additional wells were sampled by the USGS to improve understanding of factors affecting water quality.The status assessment of the quality of the groundwater used data from samples analyzed for anthropogenic constituents, such as volatile organic compounds (VOCs) and pesticides, as well as naturally occurring inorganic constituents, such as major ions and trace elements. The status assessment is intended to characterize the quality of untreated groundwater resources in the primary aquifers of the Santa Clara River Valley study unit

Favoured local structures in liquids and solids: a 3D lattice model.

PubMed

Ronceray, Pierre; Harrowell, Peter

2015-05-07

We investigate the connection between the geometry of Favoured Local Structures (FLS) in liquids and the associated liquid and solid properties. We introduce a lattice spin model - the FLS model on a face-centered cubic lattice - where this geometry can be arbitrarily chosen among a discrete set of 115 possible FLS. We find crystalline groundstates for all choices of a single FLS. Sampling all possible FLS's, we identify the following trends: (i) low symmetry FLS's produce larger crystal unit cells but not necessarily higher energy groundstates, (ii) chiral FLS's exhibit peculiarly poor packing properties, (iii) accumulation of FLS's in supercooled liquids is linked to large crystal unit cells, and (iv) low symmetry FLS's tend to find metastable structures on cooling.

Liquefaction Hazard Maps for Three Earthquake Scenarios for the Communities of San Jose, Campbell, Cupertino, Los Altos, Los Gatos, Milpitas, Mountain View, Palo Alto, Santa Clara, Saratoga, and Sunnyvale, Northern Santa Clara County, California

USGS Publications Warehouse

Holzer, Thomas L.; Noce, Thomas E.; Bennett, Michael J.

2008-01-01

Maps showing the probability of surface manifestations of liquefaction in the northern Santa Clara Valley were prepared with liquefaction probability curves. The area includes the communities of San Jose, Campbell, Cupertino, Los Altos, Los Gatos Milpitas, Mountain View, Palo Alto, Santa Clara, Saratoga, and Sunnyvale. The probability curves were based on complementary cumulative frequency distributions of the liquefaction potential index (LPI) for surficial geologic units in the study area. LPI values were computed with extensive cone penetration test soundings. Maps were developed for three earthquake scenarios, an M7.8 on the San Andreas Fault comparable to the 1906 event, an M6.7 on the Hayward Fault comparable to the 1868 event, and an M6.9 on the Calaveras Fault. Ground motions were estimated with the Boore and Atkinson (2008) attenuation relation. Liquefaction is predicted for all three events in young Holocene levee deposits along the major creeks. Liquefaction probabilities are highest for the M7.8 earthquake, ranging from 0.33 to 0.37 if a 1.5-m deep water table is assumed, and 0.10 to 0.14 if a 5-m deep water table is assumed. Liquefaction probabilities of the other surficial geologic units are less than 0.05. Probabilities for the scenario earthquakes are generally consistent with observations during historical earthquakes.

Moderate DNA damage promotes metabolic flux into PPP via PKM2 Y-105 phosphorylation: a feature that favours cancer cells.

PubMed

Kumar, Bhupender; Bamezai, Rameshwar N K

2015-08-01

Pyruvate kinase M2, an important metabolic enzyme, promotes aerobic glycolysis (Warburg effect) to facilitate cancer cell proliferation. Unravelling the status of this important glycolytic pathway enzyme under sub-lethal doses of etoposide, a commonly used anti-proliferative genotoxic drug to induce mild/moderate DNA damage in HeLa cells as a model system and discern its effect on: PKM2 expression, phosphorylation, dimer: tetramer ratio, activity and associated effects, was pertinent. Protein expression and phosphorylation of PKM2 from HeLa cells was estimated using Western blotting. Same protein lysate was also used to estimate total pyruvate kinase activity and the total dimer: tetramer content evaluated using glycerol gradient ultra-centrifugation. Intracellular PEP was estimated manually using standard curve; while NADPH was assessed by NADPH estimation kit. Unpaired t test and two-way-ANOVA was used for statistical analysis. A relative decrease in PKM2 expression and a subsequent dose and time dependent increase in Y105-phosphorylation were observed. A concomitant increase in PKM2 dimer content and Y105-phosphorylation responsible for reduced PKM2 activity promoted PEP accumulation and NADPH production, representing increased metabolic flux into PPP, a feature that favours cancer cells. It was apparent that the sub-lethal doses of etoposide induced inadequate damage to DNA in cancer cells in culture promoted pro-survival conditions due to Y105-phosphorylation of PKM2, its stable dimerization and inactivation, a unique association not known earlier, indicating what might happen in tumour revivals or recurrences.

Santa Clara County Survey of Drug, Alcohol, and Tobacco Use among Students in Grades 5, 7, 9, 11.

ERIC Educational Resources Information Center

Constantine, Norm; And Others

This report presents findings from the Santa Clara County (California) survey of Drug, Alcohol, and Tobacco Use among Students in Grades 5, 7, 9, and 11 administered during the spring of 1991 to 5,180 students in 51 randomly selected county schools. An executive summary discusses sampling error, sample demographics, and findings on drug use…

Map showing locations of damaging landslides in Santa Clara County, California, resulting from 1997-98 El Nino rainstorms

USGS Publications Warehouse

Ellis, William L.; Harp, Edwin L.; Arnal, Caroline H.; Godt, Jonathan W.

1999-01-01

Heavy rainfall associated with a strong El Nino caused over $150 million in landslide damage in the 10-county San Francisco Bay region during the winter and spring of 1998. A team of USGS scientists collected information on landslide locations and damage costs. About $7.6 million in damages were assessed in Santa Clara County.

Tar Creek study, Sargent oil field, Santa Clara County, California

USGS Publications Warehouse

Wagner, David L.; Fedasko, Bill; Carnahan, J.R.; Brunetti, Ross; Magoon, Leslie B.; Lillis, Paul G.; Lorenson, T.D.; Stanley, Richard G.

2002-01-01

Field work in the Tar Creek area of Sargent oil field was performed June 26 to 28, 2000. The Santa Clara County study area is located in Sections, 30, 31, and 32, Township 11 South, Range 4 East, M.D.B&M; and in Sections 25 and 36, Township 11 South, Range 3 East, M.D.B.&M., north and south of Tar Creek, west of Highway 101. The work was a cooperative effort of the California Department of Conservation's Division of Oil, Gas, and Geothermal Resources (DOGGR), California Geological Survey (CGS), and the United States Geological Survey (USGS). The purpose of the project was to map the stratigraphy and geologic structure (David Wagner, CGS); sample oil for age dating (Les Magoon, USGS); and search for undocumented wells plus conduct a GPS survey of the area (Bill Fedasko, J.P. Carnahan, and Ross Brunetti, DOGGR)

Predictors of favourable outcome in inflammatory Crohn's disease. A retrospective observational study.

PubMed

Zabana, Yamile; Garcia-Planella, Esther; van Domselaar, Manuel; Mañosa, Míriam; Gordillo, Jordi; López-Sanromán, Antonio; Cabré, Eduard; Domènech, Eugeni

2013-12-01

No studies have specifically searched for predictors of a favourable outcome that would allow a conservative therapeutic approach in adult Crohn's disease (CD). To identify predictors of a favourable disease course over time at CD diagnosis. We identified and included all patients diagnosed with CD between January 1994 and December 2003, who had CD with an inflammatory pattern and no perianal disease at diagnosis, and who were followed up for at least 5 years. Clinical and therapeutic features until December 2008 and losses to follow-up were identified. We defined a favourable outcome as the absence of stricturing and penetrating complications of the disease (including perianal disease), together with the absence of need for anti-TNF therapy or resectional surgery during follow up. One hundred and forty-five patients were included and followed up for a median of 96 months (IQR, 79-140). At diagnosis, location was ileal in 39%, colonic in 28%, and ileocolonic in 32%; 50% of the patients were active smokers, and 41% used immunomodulators. Eighty-two patients (57%) met the criteria for a favourable outcome at the end of follow-up. The only factor associated with a favourable outcome was isolated colonic involvement (P=0.022), with 73% of these patients meeting the criteria for a favourable outcome. A favourable outcome of initially uncomplicated CD is not easily predicted at disease diagnosis by means of clinical or epidemiologic factors. Nevertheless, patients with isolated colonic disease are less likely to have an aggressive course. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

NASA Satellite Captures Super Bowl Cities - Santa Clara, CA

NASA Image and Video Library

2017-12-08

Landsat 7 image of the Santa Clara area acquired Nov 16, 2015. Landsat 7 is a U.S. satellite used to acquire remotely sensed images of the Earth's land surface and surrounding coastal regions. It is maintained by the Landsat 7 Project Science Office at the NASA Goddard Space Flight Center in Greenbelt, MD...Landsat satellites have been acquiring images of the Earth’s land surface since 1972. Currently there are more than 2 million Landsat images in the National Satellite Land Remote Sensing Data Archive. For more information visit: landsat.usgs.gov/..To learn more about the Landsat satellite go to:.landsat.gsfc.nasa.gov/ Credit: NASA/GSFC/Landsat 7 NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

IgV H mutations in blastoid mantle cell lymphoma characterize a subgroup with a tendency to more favourable clinical outcome.

PubMed

Cogliatti, Sergio B; Bertoni, Francesco; Zimmermann, Dieter R; Henz, Samuel; Diss, Tim C; Ghielmini, Michele; Schmid, Ulrico

2005-07-01

Mantle cell lymphoma (MCL) is associated with a very unfavourable clinical course. This is particularly true for mantle cell lymphoma of the blastoid subtype (MCL-b). In order to define prognostic factors, we analysed the impact of immunoglobulin heavy chain variable (IgV H) gene somatic hypermutations on clinical outcome in a series of 21 cases of morphologically, phenotypically, and genotypically well-characterized MCL-b. Testing and estimation were performed using log-rank statistics and displayed on Kaplan-Meier graphs. Thirteen of 21 cases of MCL-b revealed a homology rate of > or = 99% compared to IgV H germ-line sequences in the databases and were scored as non-mutated. Eight of 21 cases (38%) of MCL-b were mutated. In MCL-b the mutation frequency was usually low and the mutation pattern was only rarely antigen-selected, in contrast to a control group of 11 cases with morphologically almost identical, but phenotypically and genotypically clearly distinguishable, diffuse large B cell lymphoma, derived, most likely, from germinal centre B cells. In our series of 21 MCL-b, positive IgV H mutational status, irrespective of varying homology thresholds, had no statistically significant prognostic impact on event-free or overall survival. However, mutated MCL-b tended to present more frequently at an earlier stage and without bone marrow involvement and to show lower rates of relapse and death, resulting in a more favourable clinical outcome. Copyright 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

76 FR 16812 - Notice of Realty Action: Modified Competitive Bid Sale of Public Land in Santa Clara County, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

...: Modified Competitive Bid Sale of Public Land in Santa Clara County, CA AGENCY: Bureau of Land Management... County, California, for not less than the appraised fair market value of $41,000. The sale will be... proposed sale must be received by the BLM on or before May 9, 2011. The adjoining landowners have until 3 p...

Suffering for her art: the chronic pain syndrome of pianist Clara Wieck-Schumann.

PubMed

Altenmüller, Eckart; Kopiez, Reinhard

2010-01-01

Clara Schumann was an outstanding pianist, systematically trained as a child prodigy by her father Friedrich Wieck. Married to the composer Robert Schumann she gave birth to 8 children, however, was able to continue performing regularly in public. After the mental breakdown of her husband, she had to increase her public performance activities due to the need to earn a living for her large family. In this time, the first pains in the right arm occurred, which at the beginning were of shorter duration, however increasingly required prolonged periods of rest. Later, when attempting to work on the highly demanding piano works of Johannes Brahms, especially on his first piano concerto, she developed chronic pain, which forced her to interrupt any concert activities for more than 1 year. Obviously, Brahms' modern treatment of the piano in an almost orchestral way imposed technical difficulties which Clara Schumann was not properly prepared to deal with. Finally, she underwent a multimodal pain therapy in the private sanatorium of Dr. Esmarch, which consisted of an integrated interdisciplinary approach comprising pain medication, psychotherapy, physiotherapy and modification of playing habits. She fully recovered and successfully continued her career as an internationally renowned concert pianist. The case report impressively demonstrates the stressors an outstanding female elite musician had to cope with in the 19th century. Furthermore, it is a convincing example of how the intuition and mere experience of a sensitive and understanding doctor lead to the right conclusions and to a modern multimodal pain therapy in chronic overuse injury. Furthermore the case report demonstrates the important role of prevention, including physical exercises, self-awareness, and reasonable practice schedules. Copyright (c) 2010 S. Karger AG, Basel.

Favouring butyrate production for a new generation biofuel by acidogenic glucose fermentation using cells immobilised on γ-alumina.

PubMed

Syngiridis, Kostas; Bekatorou, Argyro; Kandylis, Panagiotis; Larroche, Christian; Kanellaki, Maria; Koutinas, Athanasios A

2014-06-01

The effect of γ-alumina as a fermentation advancing tool and as carrier for culture immobilisation, regarding VFAs and ethanol production during acidogenic fermentation of glucose, was examined at various process conditions (sugar concentration, pH) and operation modes (continuous with and without effluent recirculation and batch). The results showed that at high initial pH (8.9) the continuous acidogenic fermentation of glucose led to high yields of VFAs and favoured the accumulation of butyric acid. The batch process on the other hand at pH 6.5, favoured the ethanol-type fermentation. The results indicate that in the frame of technology development for new generation biofuels, using γ-alumina as a process advancing tool at optimum process conditions (pH, initial glucose concentration and mode of operation), the produced VFAs profile and ethanol concentration may be manipulated. Copyright © 2014. Published by Elsevier Ltd.

Predicted liquefaction in the greater Oakland area and northern Santa Clara Valley during a repeat of the 1868 Hayward Fault (M6.7-7.0) earthquake

USGS Publications Warehouse

Holzer, Thomas L.; Noce, Thomas E.; Bennett, Michael J.

2010-01-01

Probabilities of surface manifestations of liquefaction due to a repeat of the 1868 (M6.7-7.0) earthquake on the southern segment of the Hayward Fault were calculated for two areas along the margin of San Francisco Bay, California: greater Oakland and the northern Santa Clara Valley. Liquefaction is predicted to be more common in the greater Oakland area than in the northern Santa Clara Valley owing to the presence of 57 km2 of susceptible sandy artificial fill. Most of the fills were placed into San Francisco Bay during the first half of the 20th century to build military bases, port facilities, and shoreline communities like Alameda and Bay Farm Island. Probabilities of liquefaction in the area underlain by this sandy artificial fill range from 0.2 to ~0.5 for a M7.0 earthquake, and decrease to 0.1 to ~0.4 for a M6.7 earthquake. In the greater Oakland area, liquefaction probabilities generally are less than 0.05 for Holocene alluvial fan deposits, which underlie most of the remaining flat-lying urban area. In the northern Santa Clara Valley for a M7.0 earthquake on the Hayward Fault and an assumed water-table depth of 1.5 m (the historically shallowest water level), liquefaction probabilities range from 0.1 to 0.2 along Coyote and Guadalupe Creeks, but are less than 0.05 elsewhere. For a M6.7 earthquake, probabilities are greater than 0.1 along Coyote Creek but decrease along Guadalupe Creek to less than 0.1. Areas with high probabilities in the Santa Clara Valley are underlain by young Holocene levee deposits along major drainages where liquefaction and lateral spreading occurred during large earthquakes in 1868 and 1906.

Paleomagnetic record determined in cores from deep research wells in the Quaternary Santa Clara basin, California

USGS Publications Warehouse

Mankinen, Edward A.; Wentworth, Carl M.

2016-01-01

The Mono Lake (ca. 32 ka), Pringle Falls (ca. 210 ka), and Big Lost (ca. 565 ka) geomagnetic excursions all seem to be represented in the Santa Clara Valley wells. Possible correlations to the Laschamp (ca. 40 ka) and Blake (ca. 110 ka) excursions are also noted. Three additional excursions that have apparently not been previously reported from western North America occur within cycle 6 (between 536 and 433 ka), near the base of cycle 5 (after 433 ka), and near the middle of cycle 2 (before ca. 75 ka).

Indian Health Service Training Center, Training Course TC-72-2 (April 17-May 5, 1972): Pueblo de Santa Clara - A Description of the Perceived Health Needs of the People of Santa Clara Pueblo and the Management Processes Involved in the Delivery of Health Services to Them.

ERIC Educational Resources Information Center

Public Health Service (DHEW), Washington, DC. Div. of Indian Health.

Members of the Health Services Management class conducted a descriptive study of the perceived health problems of the people of Santa Clara Pueblo and the management processes involved in the delivery of health services to them. Data were obtained from personal interviews with 38 Tribal members, 9 officals, 6 employees working primarily in the…

Nutrient contributions to the Santa Barbara Channel, California, from the ephemeral Santa Clara River

USGS Publications Warehouse

Warrick, J.A.; Washburn, L.; Brzezinski, Mark A.; Siegel, D.A.

2005-01-01

The Santa Clara River delivers nutrient rich runoff to the eastern Santa Barbara Channel during brief (???1-3 day) episodic events. Using both river and oceanographic measurements, we evaluate river loading and dispersal of dissolved macronutrients (silicate, inorganic N and P) and comment on the biological implications of these nutrient contributions. Both river and ocean observations suggest that river nutrient concentrations are inversely related to river flow rates. Land use is suggested to influence these concentrations, since runoff from a subwatershed with substantial agriculture and urban areas had much higher nitrate than runoff from a wooded subwatershed. During runoff events, river nutrients were observed to conservatively mix into the buoyant, surface plume immediately seaward of the Santa Clara River mouth. Dispersal of these river nutrients extended 10s of km into the channel. Growth of phytoplankton and nutrient uptake was low during our observations (1-3 days following runoff), presumably due to the very low light levels resulting from high turbidity. However, nutrient quality of runoff (Si:N:P = 16:5:1) was found to be significantly different than upwelling inputs (13:10:1), which may influence different algal responses once sediments settle. Evaluation of total river nitrate loads suggests that most of the annual river nutrient fluxes to the ocean occur during the brief winter flooding events. Wet winters (such as El Nin??o) contribute nutrients at rates approximately an order-of-magnitude greater than "average" winters. Although total river nitrate delivery is considerably less than that supplied by upwelling, the timing and location of these types of events are very different, with river discharge (upwelling) occurring predominantly in the winter (summer) and in the eastern (western) channel. ?? 2004 Elsevier Ltd. All rights reserved.

Endoreduplication and fruit growth in tomato: evidence in favour of the karyoplasmic ratio theory.

PubMed

Chevalier, Christian; Bourdon, Matthieu; Pirrello, Julien; Cheniclet, Catherine; Gévaudant, Frédéric; Frangne, Nathalie

2014-06-01

The growth of a plant organ depends upon the developmental processes of cell division and cell expansion. The activity of cell divisions sets the number of cells that will make up the organ; the cell expansion activity then determines its final size. Among the various mechanisms that may influence the determination of cell size, endopolyploidy by means of endoreduplication appears to be of great importance in plants. Endoreduplication is widespread in plants and supports the process of differentiation of cells and organs. Its functional role in plant cells is not fully understood, although it is commonly associated with ploidy-dependent cell expansion. During the development of tomato fruit, cells from the (fleshy) pericarp tissue become highly polyploid, reaching a DNA content barely encountered in other plant species (between 2C and 512C). Recent investigations using tomato fruit development as a model provided new data in favour of the long-standing karyoplasmic ratio theory, stating that cells tend to adjust their cytoplasmic volume to the nuclear DNA content. By establishing a highly structured cellular system where multiple physiological functions are integrated, endoreduplication does act as a morphogenetic factor supporting cell growth during tomato fruit development. © The Author 2013. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

PubMed

Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

2016-04-01

Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

Favourable and Unfavourable Conditions for Children's Confidence Judgments

ERIC Educational Resources Information Center

Roebers, Claudia M.; von der Linden, Nicole; Howie, Pauline

2007-01-01

Two studies are presented in which favourable and unfavourable conditions for children's meta-cognitive monitoring processes are examined. Previously reported findings have shown that especially children's uncertainty monitoring (in contrast to certainty monitoring) poses specific problems for children in their elementary school years. When…

M/V Santa Clara I - Board of Inquiry Report Concerning The Loss of Hazardous Materials Near the New Jersey Coast on 3 January 1992

DOT National Transportation Integrated Search

1992-05-18

This report examines the circumstances surrounding the loss of 4 containers of arsenic trioxide, a hazardous substance, overboard from the Panamanian M/V SANTA CLARA I during heavy weather approximately 40 miles off the New Jersey coast on January 3,...

Effect of controlled human exposure to diesel exhaust and allergen on airway surfactant protein D, myeloperoxidase and club (Clara) cell secretory protein 16.

PubMed

Biagioni, B J; Tam, S; Chen, Y-W R; Sin, D D; Carlsten, C

2016-09-01

Air pollution is a major cause of global morbidity and mortality. Air pollution and aeroallergens aggravate respiratory illness, but the variable effects of air pollutants and allergens in the lung are poorly understood. To determine the effects of diesel exhaust (DE) and bronchial allergen challenge as single and dual exposures on aspects of innate immunity in the airway as reflected by surfactant protein D (SPD), myeloperoxidase (MPO) and club (Clara) cell secretory protein 16 (CC16) in 18 atopic individuals. In this double-blind, randomized crossover study, atopic individuals were exposed to DE or filtered air, followed by endobronchial allergen or saline 1 hour after inhalational exposure. Bronchoalveolar lavage, bronchial washings, nasal lavage and blood samples were obtained 48 hours after exposures and assayed for CC16, MPO and SPD by ELISA. In bronchial samples, the concentration of SPD increased from 53.3 to 91.8 ng/mL after endobronchial allergen, with no additional contribution from DE. MPO also increased significantly in response to allergen (6.8 to 14.7 ng/mL), and there was a small additional contribution from exposure to DE. The concentration of CC16 decreased from 340.7 to 151.0 ng/mL in response to DE, with minor contribution from allergen. These changes were not reflected in nasal lavage fluid or plasma samples. These findings suggest that allergen and DE variably influence different aspects of the innate immune response of the lung. SPD and MPO, known markers of allergic inflammation in the lung, are strongly increased by allergen while DE has a minor effect therein. DE induces a loss of CC16, a protective protein, while allergen has a minor effect therein. Results support site- and exposure-specific responses in the human lung upon multiple exposures. © 2016 John Wiley & Sons Ltd.

Subsurface and petroleum geology of the southwestern Santa Clara Valley ("Silicon Valley"), California

USGS Publications Warehouse

Stanley, Richard G.; Jachens, Robert C.; Lillis, Paul G.; McLaughlin, Robert J.; Kvenvolden, Keith A.; Hostettler, Frances D.; McDougall, Kristin A.; Magoon, Leslie B.

2002-01-01

Gravity anomalies, historical records of exploratory oil wells and oil seeps, new organic-geochemical results, and new stratigraphic and structural data indicate the presence of a concealed, oil-bearing sedimentary basin beneath a highly urbanized part of the Santa Clara Valley, Calif. A conspicuous isostatic-gravity low that extends about 35 km from Palo Alto southeastward to near Los Gatos reflects an asymmetric, northwest-trending sedimentary basin comprising low-density strata, principally of Miocene age, that rest on higher-density rocks of Mesozoic and Paleogene(?) age. Both gravity and well data show that the low-density rocks thin gradually to the northeast over a distance of about 10 km. The thickest (approx 4 km thick) accumulation of low-density material occurs along the basin's steep southwestern margin, which may be controlled by buried, northeast-dipping normal faults that were active during the Miocene. Movement along these hypothetical normal faults may been contemporaneous (approx 17–14 Ma) with sedimentation and local dacitic and basaltic volcanism, possibly in response to crustal extension related to passage of the northwestward-migrating Mendocino triple junction. During the Pliocene and Quaternary, the normal faults and Miocene strata were overridden by Mesozoic rocks, including the Franciscan Complex, along northeastward-vergent reverse and thrust faults of the Berrocal, Shannon, and Monte Vista Fault zones. Movement along these fault zones was accompanied by folding and tilting of strata as young as Quaternary and by uplift of the modern Santa Cruz Mountains; the fault zones remain seismically active. We attribute the Pliocene and Quaternary reverse and thrust faulting, folding, and uplift to compression caused by local San Andreas Fault tectonics and regional transpression along the Pacific-North American Plate boundary. Near the southwestern margin of the Santa Clara Valley, as many as 20 exploratory oil wells were drilled between 1891

Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes.

PubMed

Kurowski, Marcin; Jurczyk, Janusz; Jarzębska, Marzanna; Moskwa, Sylwia; Makowska, Joanna S; Krysztofiak, Hubert; Kowalski, Marek L

2014-04-15

Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens. The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively. Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well. Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes

Tracing ground-water movement by using the stable isotopes of oxygen and hydrogen, upper Penitencia Creek alluvial fan, Santa Clara Valley, California

USGS Publications Warehouse

Muir, K.S.; Coplen, Tyler B.

1981-01-01

Starting in 1965 the Santa Clara Valley Water District began importing about i00,000 acre-feet per year of northern California water. About one-half of this water was used to artificially recharge the Upper Penitencia Creek alluvial fan in Santa Clara Valley. In order to determine the relative amounts of local ground water and recharged imported water being pumped from the wells, stable isotopes of oxygen and hydrogen were used to trace the movement of the imported water in the alluvial fan. To trace the movement of imported water in the Upper Penitencia Creek alluvial fan, well samples were selected to give areal and depth coverage for the whole fan. The stable isotopes of oxygen-16, oxygen-18, and deuterium were measured in the water samples of imported water and from the wells and streams in the Santa Clara Valley. The d18oand dD compositions of the local runoff were about -6.00 o/oo (parts per thousand) and -40 o/oo, respectively; the average compositions for the local native ground-water samples were about -6.1 o/oo and -41 o/oo, respectively; and the average compositions of the imported water samples were -10.2 o/oo and -74 o/oo, respectively. (The oxygen isotopic composition of water samples is reported relative to Standard Mean Ocean Water, in parts per thousand.) The difference between local ground water and recharged imported water was about 4.1 o/oo in d18o and 33 o/oo in dL. The isotopic data indicate dilution of northern California water with local ground water in a downgradient direction. Two wells contain approximately 74 percent northern California water, six wells more than 50 percent. Data indicate that there may be a correlation between the percentage of northern California water and the depth or length of perforated intervals in wells.

Fuel cell commercialization — beyond the 'Notice of Market Opportunity for Fuel Cells' (NOMO)

NASA Astrophysics Data System (ADS)

Serfass, J. A.; Glenn, D. R.

1992-01-01

The Notice of Market Opportunity for Fuel Cells (NOMO) was released in Oct. 1988 by the American Public Power Association. Its goal was to identify a manufacturer for commercializing a multi-megawatt fuel cell power plant with attractive cost and performance characteristics, supported by a realistic, yet aggressive commercialization plan, leading to mid-1990s application. Energy Research Corporation's program to commercialize its 2-MW internal-reforming carbonate fuel cell was selected. The program was refined in the development of the Principles and Framework for Commercializing Direct Fuel Cell Power Plants, which defines buyer responsibilities for promotion and coordination of information development, supplier responsibilities for meeting certain milestones and for sharing the results of success in a royalty agreement, and risk management features. Twenty-three electric and gas utilities in the US and Canada have joined the Fuel Cell Commercialization Group to support the buyers' obligations in this program. The City of Santa Clara, CA; Electric Power Research Institute; Los Angeles Department of Water and Power; Southern California Gas Company; Southern California Edison; National Rural Electric Cooperative Association; and Pacific Gas & Electric, have formed the Santa Clara Demonstration Group to build the first 2-MW power plant. The preliminary design for this demonstration is nearly complete. Integrated testing of a 20-kW stack with the complete balance-of-plant, has been successfully accomplished by Pacific Gas & Electric at its test facility in San Ramon, CA.

Mono Lake excursion recorded in sediment of the Santa Clara Valley, California

USGS Publications Warehouse

Mankinen, Edward A.; Wentworth, Carl M.

2004-01-01

Two intervals recording anomalous paleomagnetic inclinations were encountered in the top 40 meters of research drill hole CCOC in the Santa Clara Valley, California. The younger of these two intervals has an age of 28,090 ± 330 radiocarbon years B.P. (calibrated age ∼32.8 ka). This age is in excellent agreement with the latest estimate for the Mono Lake excursion at the type locality and confirms that the excursion has been recorded by sediment in the San Francisco Bay region. The age of an anomalous inclination change below the Mono Lake excursion was not directly determined, but estimates of sedimentation rates indicate that the geomagnetic behavior it represents most likely occurred during the Mono Lake/Laschamp time interval (∼45–28 ka). If true, it may represent one of several recurring fluctuations of magnetic inclination during an interval of a weak geomagnetic dipole, behavior noted in other studies in the region.

The veil of ignorance can favour biological cooperation.

PubMed

Queller, David C; Strassmann, Joan E

2013-01-01

Lack of information is a constraint but ignorance can sometimes assist the evolution of cooperation by constraining selfishness. We discuss examples involving both ignorance of role or pay-off and ignorance of relatedness. Ignorance can favour cooperative traits like grouping and warning coloration and reduce conflicts from meiotic drive, imprinting, greenbeards and various forms of nepotism.

The veil of ignorance can favour biological cooperation

PubMed Central

Queller, David C.; Strassmann, Joan E.

2013-01-01

Lack of information is a constraint but ignorance can sometimes assist the evolution of cooperation by constraining selfishness. We discuss examples involving both ignorance of role or pay-off and ignorance of relatedness. Ignorance can favour cooperative traits like grouping and warning coloration and reduce conflicts from meiotic drive, imprinting, greenbeards and various forms of nepotism. PMID:24132090

Revisiting surface albedo changes over Greenland since 1980s using satellite data from GLASS, CLARA, MODIS, and Landsat

NASA Astrophysics Data System (ADS)

He, T.; Liang, S.; Zhang, Y.

2017-12-01

Massive melting events over Greenland have been observed over the past few decades. Accompanying the melting events are the surface albedo changes, which had temporal and spatial variations. Albedo changes over Greenland during the past few decades have been reported in previous studies with the help of satellite observations; however, magnitudes and timing in albedo trends differ greatly in those studies. This has limited our understanding of albedo change mechanisms over Greenland. In this study, we present an analysis of surface albedo change over Greenland since 1980s combining four satellite albedo datasets, namely MODIS, GLASS, CLARA, and Landsat. MODIS, GLASS, and CLARA albedo data are publicly available and Landsat albedos were derived in our earlier study trying to bridge the scale difference between coarse resolution data and ground measurements available from early 1980s. Inter-comparisons were made among the satellite albedos and against ground measurements. We have several new findings. First, trends in surface albedo change among the satellite albedo datasets generally agree with each other and with ground measurements. Second, all datasets showed negative albedo trends after 2000, but magnitudes differ greatly. Third, trends before 2000 from coarse resolution data are not significant but Landsat data observed positive albedo changes. Fourth, the turning point of albedo trend was found to be earlier than 2000. Those findings may bring new research topics on timing and magnitude, and an improved understanding mechanisms of the albedo changes over Greenland during the past few decades.

Near-Surface Structure and Velocities of the Northeastern Santa Cruz Mountains and the Western Santa Clara Valley, California, From Seismic Imaging

USGS Publications Warehouse

Catchings, R.D.; Gandhok, G.; Goldman, M.R.; Steedman, Clare

2007-01-01

Introduction The Santa Clara Valley (SCV) is located in the southern San Francisco Bay area of California and is bounded by the Santa Cruz Mountains to the southwest, the Diablo Ranges to the northeast, and the San Francisco Bay to the north (Fig. 1). The SCV, which includes the City of San Jose, numerous smaller cities, and much of the high-technology manufacturing and research area commonly referred to as the Silicon Valley, has a population in excess of 1.7 million people (2000 U. S. Census;http://quickfacts.census.gov/qfd/states/06/06085.html The SCV is situated between major active faults of the San Andreas Fault system, including the San Andreas Fault to the southwest and the Hayward and Calaveras faults to the northeast, and other faults inferred to lie beneath the alluvium of the SCV (CWDR, 1967; Bortugno et al., 1991). The importance of the SCV as a major industrial center, its large population, and its proximity to major earthquake faults are important considerations with respect to earthquake hazards and water-resource management. The fault-bounded alluvial aquifer system beneath the valley is the source of about one-third of the water supply for the metropolitan area (Hanson et al., 2004). To better address the earthquake hazards of the SCV, the U.S. Geological Survey (USGS) has undertaken a program to evaluate potential seismic sources, the effects of strong ground shaking, and stratigraphy associated with the regional aquifer system. As part of that program and to better understand water resources of the valley, the USGS and the Santa Clara Valley Water District (SCVWD) began joint studies to characterize the faults, stratigraphy, and structures beneath the SCV in the year 2000. Such features are important to both agencies because they directly influence the availability and management of groundwater resources in the valley, and they affect the severity and distribution of strong shaking from local and regional earthquakes sources that may affect

Statistical analysis and mathematical modeling of a tracer test on the Santa Clara River, Ventura County, California

USGS Publications Warehouse

Paybins, Katherine S.; Nishikawa, Tracy; Izbicki, John A.; Reichard, Eric G.

1998-01-01

To better understand flow processes, solute-transport processes, and ground-water/surface-water interactions on the Santa Clara River in Ventura County, California, a 24-hour fluorescent-dye tracer study was performed under steady-state flow conditions on a 28-mile reach of the river. The study reach includes perennial (uppermost and lowermost) subreaches and ephemeral subreaches of the lower Piru Creek and the middle Santa Clara River. Dye was injected at a site on Piru Creek, and fluorescence of river water was measured continuously at four sites and intermittently at two sites. Discharge measurements were also made at the six sites. The time of travel of the dye, peak dye concentration, and time-variance of time-concentration curves were obtained at each site. The long tails of the time-concentration curves are indicative of sources/sinks within the river, such as riffles and pools, or transient bank storage. A statistical analysis of the data indicates that, in general, the transport characteristics follow Fickian theory. These data and previously collected discharge data were used to calibrate a one-dimensional flow model (DAFLOW) and a solute-transport model (BLTM). DAFLOW solves a simplified form of the diffusion-wave equation and uses empirical relations between flow rate and cross-sectional area, and flow rate and channel width. BLTM uses the velocity data from DAFLOW and solves the advection-dispersion transport equation, including first-order decay. The simulations of dye transport indicated that (1) ground-water recharge explains the loss of dye mass in the middle, ephemeral, subreaches, and (2) ground-water recharge does not explain the loss of dye mass in the uppermost and lowermost, perennial, subreaches. This loss of mass was simulated using a linear decay term. The loss of mass in the perennial subreaches may be caused by a combination of photodecay or adsorption/desorption.

Neogene contraction between the San Andreas fault and the Santa Clara Valley, San Francisco Bay region, California

USGS Publications Warehouse

McLaughlin, R.J.; Langenheim, V.E.; Schmidt, K.M.; Jachens, R.C.; Stanley, R.G.; Jayko, A.S.; McDougall, K.A.; Tinsley, J.C.; Valin, Z.C.

1999-01-01

In the southern San Francisco Bay region of California, oblique dextral reverse faults that verge northeastward from the San Andreas fault experienced triggered slip during the 1989 M7.1 Loma Prieta earthquake. The role of these range-front thrusts in the evolution of the San Andreas fault system and the future seismic hazard that they may pose to the urban Santa Clara Valley are poorly understood. Based on recent geologic mapping and geophysical investigations, we propose that the range-front thrust system evolved in conjunction with development of the San Andreas fault system. In the early Miocene, the region was dominated by a system of northwestwardly propagating, basin-bounding, transtensional faults. Beginning as early as middle Miocene time, however, the transtensional faulting was superseded by transpressional NE-stepping thrust and reverse faults of the range-front thrust system. Age constraints on the thrust faults indicate that the locus of contraction has focused on the Monte Vista, Shannon, and Berrocal faults since about 4.8 Ma. Fault slip and fold reconstructions suggest that crustal shortening between the San Andreas fault and the Santa Clara Valley within this time frame is ~21%, amounting to as much as 3.2 km at a rate of 0.6 mm/yr. Rates probably have not remained constant; average rates appear to have been much lower in the past few 100 ka. The distribution of coseismic surface contraction during the Loma Prieta earthquake, active seismicity, late Pleistocene to Holocene fluvial terrace warping, and geodetic data further suggest that the active range-front thrust system includes blind thrusts. Critical unresolved issues include information on the near-surface locations of buried thrusts, the timing of recent thrust earthquake events, and their recurrence in relation to earthquakes on the San Andreas fault.

Compaction of forest soil by logging machinery favours occurrence of prokaryotes.

PubMed

Schnurr-Pütz, Silvia; Bååth, Erland; Guggenberger, Georg; Drake, Harold L; Küsel, Kirsten

2006-12-01

Soil compaction caused by passage of logging machinery reduces the soil air capacity. Changed abiotic factors might induce a change in the soil microbial community and favour organisms capable of tolerating anoxic conditions. The goals of this study were to resolve differences between soil microbial communities obtained from wheel-tracks (i.e. compacted) and their adjacent undisturbed sites, and to evaluate differences in potential anaerobic microbial activities of these contrasting soils. Soil samples obtained from compacted soil had a greater bulk density and a higher pH than uncompacted soil. Analyses of phospholipid fatty acids demonstrated that the eukaryotic/prokaryotic ratio in compacted soils was lower than that of uncompacted soils, suggesting that fungi were not favoured by the in situ conditions produced by compaction. Indeed, most-probable-number (MPN) estimates of nitrous oxide-producing denitrifiers, acetate- and lactate-utilizing iron and sulfate reducers, and methanogens were higher in compacted than in uncompacted soils obtained from one site that had large differences in bulk density. Compacted soils from this site yielded higher iron-reducing, sulfate-reducing and methanogenic potentials than did uncompacted soils. MPN estimates of H2-utilizing acetogens in compacted and uncompacted soils were similar. These results indicate that compaction of forest soil alters the structure and function of the soil microbial community and favours occurrence of prokaryotes.

Simulation of ground-water/surface-water flow in the Santa Clara-Calleguas ground-water basin, Ventura County, California

USGS Publications Warehouse

Hanson, Randall T.; Martin, Peter; Koczot, Kathryn M.

2003-01-01

Ground water is the main source of water in the Santa Clara-Calleguas ground-water basin that covers about 310 square miles in Ventura County, California. A steady increase in the demand for surface- and ground-water resources since the late 1800s has resulted in streamflow depletion and ground-water overdraft. This steady increase in water use has resulted in seawater intrusion, inter-aquifer flow, land subsidence, and ground-water contamination. The Santa Clara-Calleguas Basin consists of multiple aquifers that are grouped into upper- and lower-aquifer systems. The upper-aquifer system includes the Shallow, Oxnard, and Mugu aquifers. The lower-aquifer system includes the upper and lower Hueneme, Fox Canyon, and Grimes Canyon aquifers. The layered aquifer systems are each bounded below by regional unconformities that are overlain by extensive basal coarse-grained layers that are the major pathways for ground-water production from wells and related seawater intrusion. The aquifer systems are bounded below and along mountain fronts by consolidated bedrock that forms a relatively impermeable boundary to ground-water flow. Numerous faults act as additional exterior and interior boundaries to ground-water flow. The aquifer systems extend offshore where they crop out along the edge of the submarine shelf and within the coastal submarine canyons. Submarine canyons have dissected these regional aquifers, providing a hydraulic connection to the ocean through the submarine outcrops of the aquifer systems. Coastal landward flow (seawater intrusion) occurs within both the upper- and lower-aquifer systems. A numerical ground-water flow model of the Santa Clara-Calleguas Basin was developed by the U.S. Geological Survey to better define the geohydrologic framework of the regional ground-water flow system and to help analyze the major problems affecting water-resources management of a typical coastal aquifer system. Construction of the Santa Clara-Calleguas Basin model required

Frequency dependence limits divergent evolution by favouring rare immigrants over residents.

PubMed

Bolnick, Daniel I; Stutz, William E

2017-06-08

Two distinct forms of natural selection promote adaptive biological diversity. Divergent selection occurs when different environments favour different phenotypes, leading to increased differences between populations. Negative frequency-dependent selection occurs when rare variants within a population are favoured over common ones, increasing diversity within populations. These two diversifying forces promote genetic variation at different spatial scales, and may act in opposition, but their relative effects remain unclear because they are rarely measured concurrently. Here we show that negative frequency-dependent selection within populations can favor rare immigrants over locally adapted residents. We reciprocally transplanted lake and stream ecotypes of threespine stickleback into lake and stream habitats, while manipulating the relative abundance of residents versus immigrants. We found negative frequency-dependence: survival was highest for the locally rare ecotype, rather than natives. Also, individuals with locally rare major histocompatibility complex (MHC) class IIb genotypes were infected by fewer parasites. This negative frequency-dependent selection will tend to favour rare immigrants over common residents, amplifying the effect of migration and undermining the efficacy of divergent natural selection to drive population differences. The only signal of divergent selection was a tendency for foreign fish to have higher parasite loads than residents, after controlling for MHC genotype rarity. Frequency-dependent ecological interactions have long been thought to promote speciation. Our results suggest a more nuanced view in which negative frequency dependence alters the fate of migrants to promote or constrain evolutionary divergence between populations.

EVAR using the Nellix Sac-anchoring endoprosthesis: treatment of favourable and adverse anatomy.

PubMed

Krievins, D K; Holden, A; Savlovskis, J; Calderas, C; Donayre, C E; Moll, F L; Katzen, B; Zarins, C K

2011-07-01

The study aimed to review the results of endovascular aneurysm repair (EVAR) using a novel sac-anchoring endoprosthesis in patients with favourable and adverse anatomy. This is a prospective, multicentre, clinical trial. The Nellix endoprosthesis consists of dual, balloon-expandable endoframes, surrounded by polymer-filled endobags, which obliterate the aneurysm sac and maintain endograft position. The study reviewed worldwide clinical experience and Core Lab evaluation of computed tomography (CT) scans. From 2008 to 2010, 34 patients (age 71 ± 8 years, abdominal aortic aneurysm (AAA) diameter 5.8 ± 0.8 cm) were treated at four clinical sites. Seventeen patients (50%) met the inclusion criteria for Food and Drug Administration (FDA)-approved endografts (favourable anatomy); 17 (50%) had one or more adverse anatomic feature: neck length <10 mm (24%), neck angle >60° (9%) and iliac diameter >23 mm (38%). Device deployment was successful in all patients; iliac aneurysm treatment preserved hypogastric patency. Perioperative mortality was 1/34 (2.9%); one patient died at 10 months of congestive heart failure (CHF); one patient had a secondary procedure at 15 months. During 15 ± 6 months follow-up, there were no differences in outcome between favourable and adverse anatomy patients. Follow-up CT extending up to 2 years revealed no change in aneurysm size or endograft position and no new endoleaks. Favourable and adverse anatomy patients can be successfully treated using the Nellix sac-anchoring endoprosthesis. Early results are promising but longer-term studies are needed. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Precision-cut vibratome slices allow functional live cell imaging of the pulmonary neuroepithelial body microenvironment in fetal mice.

PubMed

Schnorbusch, Kathy; Lembrechts, Robrecht; Brouns, Inge; Pintelon, Isabel; Timmermans, Jean-Pierre; Adriaensen, Dirk

2012-01-01

We recently developed an ex vivo lung slice model that allows for confocal live cell imaging (LCI) of neuroepithelial bodies (NEBs) in postnatal mouse lungs (postnatal days 1-21 and adult). NEBs are morphologically well-characterized, extensively innervated groups of neuroendocrine cells in the airway epithelium, which are shielded from the airway lumen by 'Clara-like' cells. The prominent presence of differentiated NEBs from early embryonic development onwards, strongly suggests that NEBs may exert important functions during late fetal and neonatal life. The main goal of the present study was to adapt the current postnatal LCI lung slice model to enable functional studies of fetal mouse lungs (gestational days 17-20).In vibratome lung slices of prenatal mice, NEBs could be unequivocally identified with the fluorescent stryryl pyridinium dye 4-Di-2-ASP. Changes in the intracellular free calcium concentration and in mitochondrial membrane potential could be monitored using appropriate functional fluorescent indicators (e.g. Fluo-4).It is clear that the described fetal mouse lung slice model is suited for LCI studies of Clara cells, ciliated cells, and the NEB microenvironment, and offers excellent possibilities to further unravel the significance of NEBs during the prenatal and perinatal period.

SRTM Perspective View with Landsat Overlay: Santa Paula, and Santa Clara River Valley, California

NASA Technical Reports Server (NTRS)

2000-01-01

Rectangular fields of the agriculturally rich Santa Clara River Valley are visible in this perspective view generated using data from the Shuttle Radar Topography Mission and an enhanced Landsat image. The Santa Clara River, which lends its name to this valley, flows from headwaters near Acton, California, 160 km (100 miles) to the Pacific Ocean, and is one of only two natural river systems remaining in southern California. In the foreground of this image, the largely dry riverbed can be seen as a bright feature as it winds its way along the base of South Mountain. The bright region at the right end of this portion of the valley is the city of Santa Paula, California. Founded in 1902, this small, picturesque town at the geographic center of Ventura County is referred to as the 'Citrus Capital of the World.' The city is surrounded by orange, lemon, and avocado groves and is a major distribution point for citrus fruits in the United States. The bright, linear feature in the center of the valley is State Highway 126, the valley's 'main drag.' For visualization purposes, topographic heights displayed in this image are exaggerated two times. Colors, from Landsat data, approximate natural color.

The elevation data used in this image was acquired by SRTM aboard the Space Shuttle Endeavour, launched on February 11, 2000. SRTM used the same radar instrument that comprised the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) that flew twice on Endeavour in 1994. SRTM was designed to collect three-dimensional measurements of Earth's land surface. To collect the 3-D SRTM data, engineers added a mast 60 meters (about 200 feet)long, installed additional C-band and X-band antennas, and improved tracking and navigation devices. The mission is a cooperative project between the NASA, the National Imagery and Mapping Agency (NIMA) of the U.S. Department of Defense, and the German and Italian space agencies. It is managed by NASA's Jet Propulsion Laboratory

Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases.

PubMed

Rajput, Ashish B; Turbin, Dmitry A; Cheang, Maggie Cu; Voduc, David K; Leung, Sam; Gelmon, Karen A; Gilks, C Blake; Huntsman, David G

2008-01-01

We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) infiltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this finding in a larger cohort of invasive breast cancer patients and examine the relationship between the presence of MCs and other clinical and pathological features. Clinically annotated tissue microarrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase techniques to identify and quantify MCs. For statistical analysis, we applied a split-sample validation technique. Breast cancer specific survival was analyzed by Kaplan-Meier [KM] method and log rank test was used to compare survival curves. Survival analysis by KM method showed that the presence of stromal MCs was a favourable prognostic factor in the training set (P = 0.001), and the validation set group (P = 0.006). X-tile plot generated to define the optimal number of MCs showed that the presence of any number of stromal MCs predicted good prognosis. Multivariate analysis showed that the MC effect in the training set (Hazard ratio [HR] = 0.804, 95% Confidence interval [CI], 0.653-0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683-1.049, P = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2 status. This study concludes that stromal MC infiltration in invasive breast cancer is an independent good prognostic marker and reiterates the critical role of local inflammatory responses in breast cancer progression.

Clara Harrison Town and the origins of the first institutional commitment law for the "feebleminded": psychologists as expert diagnosticians.

PubMed

Farreras, Ingrid G

2014-11-01

The first law providing for the commitment of "feeble-minded" individuals in the United States was passed in 1915, in the state of Illinois. House Bill 655 not only allowed for the permanent, involuntary institutionalization of feeble-minded individuals, but it shifted the commitment and discharge authority from the institution superintendents to the courts. Clara Harrison Town, a student of Lightner Witmer, and the state psychologist at the second largest institution for feeble-minded individuals in the country, was instrumental in this law passing and in ensuring that psychologists, for the first time, be viewed as court "experts" when testifying as to the feeble mindedness of individuals.

[A case of favourable outcome of the treatment of extremely severe acute poisoning with methanol].

PubMed

Batotsyrenov, B V; Livanov, G A; Vasil'ev, S A; Fedorov, A V; Antrianov, A Iu

2013-01-01

A case of favourable outcome of the treatment of extremely severe acute poisoning after prolonged exposure to lethal doses of methanol is reported. The complex treatment included urgent and effective elimination of the poison (multiple gastric lavage, hemodialysis), antidote therapy (administration of ethanol), correction of decompensated metabolic acidosis (alkali therapy and infusion therapy with reamberin). These measures had beneficial effect on the clinical course of poisoning and ensured its favourable outcome.

Serine protease allergen favours Th2 responses via PAR-2 and STAT3 activation in murine model.

PubMed

Agrawal, K; Arora, N

2018-03-01

Protease activity of Per a 10 favours Th2 responses by differential regulation of IL-12p70 and IL-23 cytokine subunits. This study aimed to elucidate the underlying mechanism of differential regulation of IL-12p70 and IL-23. PAR-2 activation was blocked in murine model by administering SAM11 before each sensitization. CD11c + p-STAT3 + cells were measured in lungs by flow cytometry. BMDCs were pretreated with SAM11 or isotype control or stattic and stimulated with Per a 10. p-STAT3 levels were measured using Western blot. Transcript levels of IL-12p35, IL-12/23p40 and IL-23p19 were measured using RT-PCR. Cytokine levels were analysed using ELISA. Protease activity of Per a 10 increased p-STAT3 levels in mouse lungs, which was reduced upon PAR-2 blockage. Percentage of p-STAT3 + CD11c + cells was higher in Per a 10-administered mice and was reduced upon PAR-2 blockage. IL-12p35 and IL-12p70 levels were higher, and IL-23p19 and IL-23 levels were lower in both SAM11-treated mice and BMDCs indicating a role of PAR-2-mediated signalling. IL-4, TSLP, IL-17A, EPO activity, total cell count and specific IgE and IgG1 levels were lower in SAM11-administered mice. Inhibiting STAT3 activation via stattic also leads to lower levels of IL-23p19 and IL-23 and higher levels of IL-12p35. Per a 10 leads to PAR-2 activation on BMDCs resulting in downstream activation of STAT3 to regulate the balance between IL-12/IL-23 subunits causing a cytokine milieu rich in IL-23 to favour Th2 polarization. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Determinants of favourable opinions about euthanasia in a sample of French physicians.

PubMed

Dany, Lionel; Baumstarck, Karine; Dudoit, Eric; Duffaud, Florence; Auquier, Pascal; Salas, Sébastien

2015-11-05

The question whether euthanasia should be legalised has led to substantial public debate in France. The objective of this study in a sample of French physicians was to establish the potential determinants of a favourable opinion about euthanasia in general and when faced with a specific situation as embodied in the Humbert affair. The study was a cross-sectional survey investigating two different samples of medical doctors: (1) those specialised in palliative care and affiliated to the French Society for Patient Accompaniment and Palliative Care; (2) medical interns (medical doctors in training course) in a French medical university (Marseille). A questionnaire was sent (email) to each voluntary participant including sociodemographics, professional status, mention of believing in God, and opinion about euthanasia (the question was designed to assess the general opinion about euthanasia and the opinion about a specific case, the Vincent Humbert' case (a man who was rendered quadriplegic, blind, and mute after an accident and has requested euthanasia). A total of 413 physicians participated in the research (participation rate: 48.5%). Less than half of the population were favourable to euthanasia in general and almost two-thirds of the population were favourable to Vincent Humbert's request for euthanasia. Based on the multivariate analysis, individuals believing in God and being a medical intern were significant independent factors linked to having a favourable opinion about euthanasia in general and about the Vincent Humbert's request. There is still no study in France on the development of opinion about euthanasia and its impact. The issue goes beyond the strictly professional sphere and involves broader socio-political stakes. These stakes do not necessarily take into account medical practices and experiences or the desires of end-of-life patients. The professional upheaval that the future French legal framework will doubtlessly trigger will require further

Analysis of alluvial hydrostratigraphy using indicator geostatistics, with examples from Santa Clara Valley, California

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-03-01

Current trends in hydrogeology seek to enlist sedimentary concepts in the interpretation of permeability structures. However, existing conceptual models of alluvial deposition tend to inadequately account for the heterogeneity caused by complex sedimentological and external factors. This dissertation presents three analyses of alluvial hydrostratigraphy using indicator geostatistics. This approach empirically acknowledges both the random and structured qualities of alluvial structures at scales relevant to site investigations. The first analysis introduces the indicator approach, whereby binary values are assigned to borehole-log intervals on the basis of inferred relative permeability; it presents a case study of indicator variography at a well-documented ground-watermore » contamination site, and uses indicator kriging to interpolate an aquifer-aquitard sequence in three dimensions. The second analysis develops an alluvial-architecture context for interpreting semivariograms, and performs comparative variography for a suite of alluvial sites in Santa Clara Valley, California. The third analysis investigates the use of a water well perforation indicator for assessing large-scale hydrostratigraphic structures within relatively deep production zones.« less

Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases

PubMed Central

Rajput, Ashish B.; Turbin, Dmitry A.; Cheang, Maggie CU; Voduc, David K.; Leung, Sam; Gelmon, Karen A.; Gilks, C. Blake

2007-01-01

Purpose We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) infiltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this finding in a larger cohort of invasive breast cancer patients and examine the relationship between the presence of MCs and other clinical and pathological features. Experimental design Clinically annotated tissue microarrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase techniques to identify and quantify MCs. For statistical analysis, we applied a split-sample validation technique. Breast cancer specific survival was analyzed by Kaplan–Meier [KM] method and log rank test was used to compare survival curves. Results Survival analysis by KM method showed that the presence of stromal MCs was a favourable prognostic factor in the training set (P = 0.001), and the validation set group (P = 0.006). X-tile plot generated to define the optimal number of MCs showed that the presence of any number of stromal MCs predicted good prognosis. Multivariate analysis showed that the MC effect in the training set (Hazard ratio [HR] = 0.804, 95% Confidence interval [CI], 0.653–0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683–1.049, P = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2 status. Conclusions This study concludes that stromal MC infiltration in invasive breast cancer is an independent good prognostic marker and reiterates the critical role of local inflammatory responses in breast cancer progression. PMID:17431762

Hospital characteristics and favourable neurological outcome among patients with out-of-hospital cardiac arrest in Osaka, Japan.

PubMed

Matsuyama, Tasuku; Kiyohara, Kosuke; Kitamura, Tetsuhisa; Nishiyama, Chika; Nishiuchi, Tatsuya; Hayashi, Yasuyuki; Kawamura, Takashi; Ohta, Bon; Iwami, Taku

2017-01-01

To assess the association between favourable neurological outcome and hospital characteristics such as hospital volume and number of critical care centres (CCMCs) after out-of-hospital cardiac arrest (OHCA). This retrospective, population-based observational study conducted in Osaka Prefecture, Japan included adult patients with OHCA, aged ≥18 years who were transported to acute care hospitals between January 2005 and December 2012. We divided acute care hospitals into CCMCs or non-CCMCs, the latter of which were divided into the following three groups according to the annual average number of transported OHCA cases: low-volume (≤10 cases), middle-volume (11-39 cases), and high-volume (≥40 cases) groups. Random effects logistic regression models, with hospital treated as a random effect, were used to assess factors potentially associated with a favourable neurological outcome. A total of 44,474 patients were eligible. The proportions of favourable neurological outcome from OHCA were 0.9% (31/3559) in the low-volume group, 1.2% (106/9171) in the middle-volume group, 1.6% (222/14,007) in the high-volume group, and 4.3% (766/17,737) in the CCMC group (P<0.001). In the multivariable analysis, transport to CCMCs was significantly associated with favourable neurological outcome, compared with transport to non-CCMCs (adjusted odds ratio 1.63; 95% confidence interval, 1.60-1.66). Among the non-CCMC group, there was no significant relationship between hospital volume and favourable neurological outcome. In this population, transport of OHCA patients to CCMCs led to significantly higher one-month survival rates with favourable neurological outcome from OHCA, whereas no significant association was noted among the hospitals with different volumes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Santa Clara Strength of Religious Faith Questionnaire: Psychometric analysis in older adults

PubMed Central

Cummings, Jeremy P.; Carson, Cody S.; Shrestha, Srijana; Kunik, Mark E.; Armento, Maria E.; Stanley, Melinda A.; Amspoker, Amber B.

2014-01-01

Objectives To assist researchers and clinicians considering using the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) with older-adult samples, the current study analyzed the psychometrics of SCSRFQ scores in two older-adult samples. Method Adults age 55 or older who had formerly participated in studies of cognitive-behavioral therapy for anxiety and/or depression were recruited to complete questionnaires. In Study 1 (N = 66), the authors assessed the relations between the SCSRFQ and other measures of religiousness/spirituality, mental health, and demographic variables, using bivariate correlations and nonparametric tests. In Study 2 (N = 223), the authors also conducted confirmatory and exploratory factor analyses of the SCSRFQ, as well as an Item Response Theory analysis. Results The SCSRFQ was moderately to highly positively correlated with all measures of religiousness/spirituality. Relations with mental health were weak and differed across samples. Ethnic minorities scored higher than White participants on the SCSRFQ, but only in Study 2. Factor analyses showed that a single-factor model fit the SCSRFQ best. According to Item Response Theory analysis, SCSRFQ items discriminated well between participants with low-to-moderate levels of the construct but provided little information at higher levels. Conclusion Although the SCSRFQ scores had adequate psychometric characteristics, the measure’s usefulness may be limited in samples of older adults. PMID:24892461

Darwin's Arguments in Favour of Natural Selection and against Special Creationism

ERIC Educational Resources Information Center

Nola, Robert

2013-01-01

In many places in "The Origin of Species", Darwin compares his own theory of Natural Selection favourably with Special Creationism which comes off as a bad second best. He does this using some version of the argument form known as "Inference to the Best Explanation". The first part of this paper is methodological. It considers Whewell's notion of…

Evidence for the existence of Pd-107 in the early solar system. [from Santa Clara iron meteorite data

NASA Technical Reports Server (NTRS)

Kelly, W. R.; Wasserburg, G. J.

1978-01-01

Measurements of the concentration and isotopic composition of Ag and Pd in the Santa Clara iron meteorite suggest that in situ decay of Pd-107 occurred in the meteorite or its parent body. The initial solar ratio of Pd-107/Pd-110 is estimated from the observed ratio of excess Ag-107/Pd-110, and the value of the Pd ratio is incompatible with an interval of approximately 100,000,000 years between the end of nucleosynthesis and the formation of planetary objects but is compatible with a later injection of material. The inferred existence of Pd-107 and Al-26 indicates that the late injection included freshly synthesized material of both intermediate and low atomic weight on a similar time scale. The significance of the Pd-107/Ag-107 chronometer is considered.

Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

NASA Astrophysics Data System (ADS)

Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of the mediastinum: A favourable response to treatment and review of the literature.

PubMed

Ghandi, Narges; Ghanadan, Alireza; Azizian, Mohammad-Reza; Hejazi, Pardis; Aghazadeh, Nessa; Tavousi, Parvin; Daneshpazhooh, Maryam

2015-05-01

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder that occurs in association with an underlying neoplasm. Inflammatory myofibroblastic tumour (IMT) is a rare low-grade sarcoma of fibroblasts and myofibroblasts associated with inflammatory cells, most commonly occurring in the lung. In this study, a case of PNP associated with IMT of the mediastinum is reported. The patient had a favourable outcome following surgical resection and treatment with a systemic steroid, azathioprine, and i.v. immunoglobulin. The occurrence of PNP with sarcomas, specifically IMT, is noteworthy although it is not well studied in the existing literature. © 2014 The Australasian College of Dermatologists.

Seasonal trends of atmospheric nitrogen dioxide and sulfur dioxide over North Santa Clara, Cuba.

PubMed

Alejo, Daniellys; Morales, Mayra C; de la Torre, Jorge B; Grau, Ricardo; Bencs, László; Van Grieken, René; Van Espen, Piet; Sosa, Dismey; Nuñez, Vladimir

2013-07-01

Atmospheric nitrogen dioxide (NO2) and sulfur dioxide (SO2) levels were monitored simultaneously by means of Radiello passive samplers at six sites of Santa Clara city, Cuba, in the cold and the warm seasons in 2010. The dissolved ionic forms of NO2 and SO2 as nitrate and sulfite plus sulfate, respectively, were determined by means of ion chromatography. Analysis of NO2 as nitrite was also performed by UV-Vis spectrophotometry. For NO2, significant t tests show good agreement between the results of IC and UV-Vis methods. The NO2 and SO2 concentrations peaked in the cold season, while their minimum levels were experienced in the warm season. The pollutant levels do not exceed the maximum allowable limit of the Cuban Standard 39:1999, i.e., 40 μg/m(3) and 50 μg/m(3) for NO2 and SO2, respectively. The lowest pollutant concentrations obtained in the warm season can be attributed to an increase in their removal via precipitation (scavenging) while to the decreased traffic density and industrial emission during the summer holidays (e.g., July and August).

A Bone Health Intervention for Chinese Immigrants in Santa Clara County.

PubMed

Zou, Joanne; Hampton, Michelle DeCoux; Shade, Kate; Kaku, Leonard

Among Chinese immigrants, osteoporosis is undertreated, misdiagnosed, and a leading cause of fragility fractures. In orthopaedic surgery departments, prevention education and health behavior change programs are necessary to improve their bone health. The purpose of this study was to examine the effectiveness of an osteoporosis prevention education program on participants' self-efficacy with regard to exercise and nutrition when provided by an orthopaedic surgery team during an annual Chinese Health Fair in Santa Clara County, CA. This pilot study used a single-group pretest and posttest design. Chinese immigrants at risk of osteoporosis were recruited during a 1-day health fair. The Bone Health Intervention (BHI) included orthopaedic surgeon consultation, visual aids including osteoporosis images and bone models, a video that included a discussion on calcium and vitamin D in the Chinese diet and culturally-acceptable exercise, and osteoporosis educational handouts. The Osteoporosis Self-Efficacy Scale (OSES) was utilized to measure participants' confidence in the ability to participate in self-care behaviors related to physical activity and calcium intake before and after the intervention. Paired t tests were used to compare participants' OSES scores pre- and postintervention. There was a significant increase in mean OSES scores postintervention, indicating that the intervention could be an effective method of increasing participants' self-efficacy regarding calcium intake and time spent in exercising. These results indicate that a culturally meaningful education program can potentially reduce fragility fracture risk. Orthopaedic health providers are ideal candidates to deliver preventive care education to improve outcomes for Chinese immigrants.

Analysis of the stormwater drainage of the historic walls of Cartagena de Indias between the bastions of San Lucas, Santa Catalina and Santa Clara

NASA Astrophysics Data System (ADS)

Utria, A.; Saba, M.; Quiñones-Bolaños, E.

2017-12-01

The city walls of Cartagena between the Baluarte of San Lucas and Santa Clara reflects the consequences of poor stormwater drainage. In the present investigation the current drainage state of this area have been evaluated, assessing its sizing and conditions to be then modelled through SWMM 5 software for return periods of 5, 10, 15 and 20 years respectively. Finally, it has been determined that the physical deterioration of the drainage elements justifies the malfunction of the whole system, therefore cleaning and periodic maintenance of the drainage elements is strongly suggested.

Autologous serum supplement favours in vitro regenerative paracrine factors synthesis.

PubMed

Haque, Nazmul; Kasim, Noor Hayaty Abu; Kassim, Noor Lide Abu; Rahman, Mohammad Tariqur

2017-08-01

Foetal bovine serum (FBS) is often the serum supplement of choice for in vitro human cell culture. This study compares the effect of FBS and autologous human serum (AuHS) supplement in human peripheral blood mononuclear cell (PBMC) culture to prepare secretome. The PBMC (n = 7) were cultured either in RPMI-1640 containing L-glutamine and 50 units/ml Penicillin-Streptomycin (BM) or in BM with either AuHS or FBS. Viability, proliferation and differentiation of PBMC were evaluated. Paracrine factors present in the secretomes (n = 6) were analysed using ProcartaPlex Human Cytokine panel (17 plex). Ingenuity Pathway Analysis (IPA) was performed to predict activation or inhibition of biological functions related to tissue regeneration. The viability of PBMC that were cultured with FBS supplement was significantly reduced at 96 h compared to those at 0 and 24 h (P < .05). While the reduction of the viability of PBMC that were cultured with AuHS supplement was not significantly different compared to those at 0 and 24 h. The FBS secretomes prepared at 24 h was found to contain significantly higher amount of EGF (P < .05) compared to that in AuHS or BM secretome. The AuHS secretomes contained significantly higher amount of HGF at 24 (P < .05) and 96 h (P < .01), and VEGF-A at 24 h (P < .05) compared to those in the FBS secretomes. SDF-1 was not detected in the FBS secretomes prepared at either 24 or 96 hours. Double immunocytochemical staining revealed a marked increase in co-localization of SDF-1 and its receptor in PBMC that were cultured with AuHS supplement compared to that cultured with FBS supplement. In secretome preparation, AuHS supplement favours synthesis of paracrine factors that are needed for regenerative therapy. © 2017 John Wiley & Sons Ltd.

COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis

PubMed Central

2014-01-01

Background Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. Methods The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. Results COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. Conclusions COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis. PMID:24950702

Changes in cloud properties over East Asia deduced from the CLARA-A2 satellite data record

NASA Astrophysics Data System (ADS)

Benas, Nikos; Fokke Meirink, Jan; Hollmann, Rainer; Karlsson, Karl-Göran; Stengel, Martin

2017-04-01

Studies on cloud properties and processes, and their role in the Earth's changing climate, have advanced during the past decades. A significant part of this advance was enabled by satellite measurements, which offer global and continuous monitoring. Lately, a new satellite-based cloud data record was released: the CM SAF cLoud, Albedo and surface RAdiation dataset from AVHRR data - second edition (CLARA-A2) includes high resolution cloud macro- and micro-physical properties derived from the AVHRR instruments on board NOAA and MetOp polar orbiters. Based on this data record, an analysis of cloud property changes over East Asia during the 12-year period 2004-2015 was performed. Significant changes were found in both optical and geometric cloud properties, including increases in cloud liquid water path and top height. The Cloud Droplet Number Concentration (CDNC) was specifically studied in order to gain further insight into possible connections between aerosol and cloud processes. To this end, aerosol and cloud observations from MODIS, covering the same area and period, were included in the analysis.

Cell-specific modulation of surfactant proteins by ambroxol treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seifart, Carola; Clostermann, Ursula; Seifart, Ulf

2005-02-15

Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNAmore » content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.« less

A Psychometric Evaluation of the Santa Clara Strength of Religious Faith Questionnaire among Students from Poland and Chile.

PubMed

Wnuk, Marcin

2017-01-01

This study verifies the psychometric properties of the Santa Clara Strength of Religious Faith Questionnaire (SCSORFQ). This measure consists of 10 items regarding strength of religious faith, regardless of religious denomination or affiliation. Participants were 177 students from Chile and 393 students from Poland. The SCSORFQ method is a reliable measure with good internal consistency evaluated by the α-Cronbach coefficient. Factor analysis statistically confirmed the unidimensional structure of the SCSORFQ. The strength of religious faith in both student groups was moderate to strong correlated with public or private aspects of religiousness and strong correlated with spiritual experiences. It was weakly correlated with the cognitive indicator of well-being as satisfaction with life as well as with existential variables like hope and meaning of life. The results confirm that the SCSORFQ is psychometrically sound and is therefore recommended for use by researchers studying the construct of religiousness.

Physical subdivision and description of the water-bearing sediments of the Santa Clara Valley, California

USGS Publications Warehouse

Wentworth, Carl M.; Jachens, Robert C.; Williams, Robert A.; Tinsley, John C.; Hanson, Randall T.

2015-01-01

Maps and cross sections show the elevations of cycle boundaries and the underlying bedrock surface, the varying thicknesses of the cycles and of their fine tops and coarse bottoms, and the aggregate thickness of coarse layers in those bottom intervals. Coarse sediment is more abundant toward some parts of the basin margin and in the southern part of the basin. Cycle boundary surfaces are relatively smooth, and their shapes are consistent with having been intercycle topographic surfaces. The underlying bedrock surface has a relief of more than 1,200 feet and deepens toward the center of the basin and the west edge of the fault-bounded Evergreen Basin, which is concealed beneath the east side of the Quaternary basin. The absence of consistent abrupt changes in thicknesses or boundary elevations across the basin or in cross section indicates that the interior of the basin is largely unfaulted, with the Silver Creek strand of the San Andreas system at the west edge of the Evergreen Basin being the sole exception. The east and west margins of the Santa Clara Basin, in contrast, are marked by reverse and thrust fault systems.

Development of a local-scale urban stream assessment method using benthic macroinvertebrates: An example from the Santa Clara Basin, California

USGS Publications Warehouse

Carter, J.L.; Purcell, A.H.; Fend, S.V.; Resh, V.H.

2009-01-01

Research that explores the biological response to urbanization on a site-specific scale is necessary for management of urban basins. Recent studies have proposed a method to characterize the biological response of benthic macroinvertebrates along an urban gradient for several climatic regions in the USA. Our study demonstrates how this general framework can be refined and applied on a smaller scale to an urbanized basin, the Santa Clara Basin (surrounding San Jose, California, USA). Eighty-four sampling sites on 14 streams in the Santa Clara Basin were used for assessing local stream conditions. First, an urban index composed of human population density, road density, and urban land cover was used to determine the extent of urbanization upstream from each sampling site. Second, a multimetric biological index was developed to characterize the response of macroinvertebrate assemblages along the urban gradient. The resulting biological index included metrics from 3 ecological categories: taxonomic composition ( Ephemeroptera, Plecoptera, and Trichoptera), functional feeding group (shredder richness), and habit ( clingers). The 90th-quantile regression line was used to define the best available biological conditions along the urban gradient, which we define as the predicted biological potential. This descriptor was then used to determine the relative condition of sites throughout the basin. Hierarchical partitioning of variance revealed that several site-specific variables (dissolved O2 and temperature) were significantly related to a site's deviation from its predicted biological potential. Spatial analysis of each site's deviation from its biological potential indicated geographic heterogeneity in the distribution of impaired sites. The presence and operation of local dams optimize water use, but modify natural flow regimes, which in turn influence stream habitat, dissolved O2, and temperature. Current dissolved O2 and temperature regimes deviate from natural

Demographic factors associated with perceptions about water safety and tap water consumption among adults in Santa Clara County, California, 2011.

PubMed

van Erp, Brianna; Webber, Whitney L; Stoddard, Pamela; Shah, Roshni; Martin, Lori; Broderick, Bonnie; Induni, Marta

2014-06-12

The objective of this study was to examine differences in tap water consumption and perceptions of bottle versus tap water safety for Hispanics and non-Hispanic whites, as well as associations with other demographic characteristics. Data are from the Santa Clara County, California, Dietary Practices Survey (2011; N = 306). We used logistic regression to examine associations between demographic characteristics and 1) perceptions that bottled water is safer than tap and 2) primarily consuming tap water. Hispanics were less likely than non-Hispanic whites to primarily drink tap water (OR = 0.33; 95% CI, 0.11-0.99), although there was no significant difference in perceptions that bottled water is safer between these groups (OR = 0.50; 95% CI, 0.11-2.27). Hispanics may be an important population for interventions promoting tap water consumption.

The H II galaxy Hubble diagram strongly favours Rh = ct over ΛCDM

NASA Astrophysics Data System (ADS)

Wei, Jun-Jie; Wu, Xue-Feng; Melia, Fulvio

2016-12-01

We continue to build support for the proposal to use H II galaxies (HIIGx) and giant extragalactic H II regions (GEHR) as standard candles to construct the Hubble diagram at redshifts beyond the current reach of Type Ia supernovae. Using a sample of 25 high-redshift HIIGx, 107 local HIIGx, and 24 GEHR, we confirm that the correlation between the emission-line luminosity and ionized-gas velocity dispersion is a viable luminosity indicator, and use it to test and compare the standard model ΛCDM and the Rh = ct universe by optimizing the parameters in each cosmology using a maximization of the likelihood function. For the flat ΛCDM model, the best fit is obtained with Ω _m= 0.40_{-0.09}^{+0.09}. However, statistical tools, such as the Akaike (AIC), Kullback (KIC) and Bayes (BIC) Information Criteria favour Rh = ct over the standard model with a likelihood of ≈94.8-98.8 per cent versus only ≈1.2-5.2 per cent. For wCDM (the version of ΛCDM with a dark-energy equation of state wde ≡ pde/ρde rather than wde = wΛ = -1), a statistically acceptable fit is realized with Ω _m=0.22_{-0.14}^{+0.16} and w_de= -0.51_{-0.25}^{+0.15} which, however, are not fully consistent with their concordance values. In this case, wCDM has two more free parameters than Rh = ct, and is penalized more heavily by these criteria. We find that Rh = ct is strongly favoured over wCDM with a likelihood of ≈92.9-99.6 per cent versus only 0.4-7.1 per cent. The current HIIGx sample is already large enough for the BIC to rule out ΛCDM/wCDM in favour of Rh = ct at a confidence level approaching 3σ.

Targeting the impact of agri-environmental policy - Future scenarios in two less favoured areas in Portugal.

PubMed

Jones, Nadia; Fleskens, Luuk; Stroosnijder, Leo

2016-10-01

Targeting agri-environmental measures (AEM) improves their effectiveness in the delivery of public goods, provided the necessary coordination with other incentives. In less favoured areas (LFA) measures focusing on the conservation of extensive farming contribute to sustainable land management in these areas. In this paper we investigate the implementation of a possible AEM supporting the improvement of permanent pastures coordinated with the extensive livestock and single farm payments actually in place. Through applying a spatially-explicit mixed integer optimisation model we simulate future land use scenarios for two less favoured areas in Portugal (Centro and Alentejo) considering two policy scenarios: a 'targeted AEM', and a 'non-targeted AEM'. We then compare the results with a 'basic policy' option (reflecting a situation without AEM). This is done with regard to landscape-scale effects on the reduction of fire hazard and erosion risk, as well as effects on farm income. The results show that an AEM for permanent pastures would be more cost-effective for erosion and fire hazard mitigation if implemented within a spatially targeted framework. However when cost-effectiveness is assessed with other indicators (e.g. net farm income and share of grazing livestock) 'non-targeted AEM' implementation delivers the best outcome in Alentejo. In Centro the implementation of an AEM involves important losses of income compared to the 'basic policy'. 'Targeted AEM' tends to favour farms in very marginal conditions, i.e. targeting is demonstrated to perform best in landscapes where spatial heterogeneity is higher. The results also show the risk of farm abandonment in the two studied less favoured areas: in all three scenarios more than 30% of arable land is deemed to be abandoned. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

PubMed

Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria

2015-03-01

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI. © 2015 European Society of Endocrinology.

Drought Effects on Riparian Vegetation in the Santa Clara River Basin Using Airborne Imaging Spectroscopy

NASA Astrophysics Data System (ADS)

Schmidt, C.; Miller, D.; Roberts, D. A.

2017-12-01

Riparian forests are groundwater-dependent ecosystems that are highly sensitive to changes in the water table. As climate change continues, droughts are likely to become more frequent and severe in Southern California, threatening the persistence of these ecosystems. From 2012 to 2017, California experienced the most severe drought in the past century, providing a case study to assess drought impacts. Using imagery collected by the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) from 2013 and 2016, we evaluated changes in riparian forest health in a central section of the Santa Clara River Basin, a multi-use river located just north of Los Angeles. We used Constrained Reference Endmember Selection (CRES) to select reference endmembers of green vegetation (GV), non-photosynthetic vegetation (NPV), and rock/soil. We used spectral mixture analysis to estimate endmember fractions. We assessed changes in green vegetation cover and canopy water content at key monitoring sites based on the Relative GV Fraction, the Normalized Difference Water Index, and the Water Band Index. Preliminary results showed a decrease in the GV fraction and an increase in the NPV fraction, indicating an overall decline in riparian forest health as a result of drought. Our results demonstrate the spatial extent of drought effects in groundwater dependent ecosystems.

Stem cells are dispensable for lung homeostasis but restore airways after injury.

PubMed

Giangreco, Adam; Arwert, Esther N; Rosewell, Ian R; Snyder, Joshua; Watt, Fiona M; Stripp, Barry R

2009-06-09

Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contributions of progenitor (Clara) and bronchiolar stem cells to epithelial maintenance and repair. In normal and moderately injured airways chimeric patches were small in size and not associated with previously described stem cell niches. This finding suggested that single, randomly distributed progenitor cells maintain normal epithelial homeostasis. In contrast we found that repair following severe lung injury resulted in the generation of rare, large clonal cell patches that were associated with stem cell niches. This study provides evidence that epithelial stem cells are dispensable for normal airway homeostasis. We also demonstrate that stem cell activation and robust clonal cellular expansion occur only during repair from severe lung injury.

Direct fuel cell power plants: the final steps to commercialization

NASA Astrophysics Data System (ADS)

Glenn, Donald R.

Since the last paper presented at the Second Grove Fuel Cell Symposium, the Energy Research Corporation (ERC) has established two commercial subsidiaries, become a publically-held firm, expanded its facilities and has moved the direct fuel cell (DFC) technology and systems significantly closer to commercial readiness. The subsidiaries, the Fuel Cell Engineering Corporation (FCE) and Fuel Cell Manufacturing Corporation (FCMC) are perfecting their respective roles in the company's strategy to commercialize its DFC technology. FCE is the prime contractor for the Santa Clara Demonstration and is establishing the needed marketing, sales, engineering, and servicing functions. FCMC in addition to producing the stacks and stack modules for the Santa Clara demonstration plant is now upgrading its production capability and product yields, and retooling for the final stack scale-up for the commercial unit. ERC has built and operated the tallest and largest capacities-to-date carbonate fuel cell stacks as well as numerous short stacks. While most of these units were tested at ERC's Danbury, Connecticut (USA) R&D Center, others have been evaluated at other domestic and overseas facilities using a variety of fuels. ERC has supplied stacks to Elkraft and MTU for tests with natural gas, and RWE in Germany where coal-derived gas were used. Additional stack test activities have been performed by MELCO and Sanyo in Japan. Information from some of these activities is protected by ERC's license arrangements with these firms. However, permission for limited data releases will be requested to provide the Grove Conference with up-to-date results. Arguably the most dramatic demonstration of carbonate fuel cells in the utility-scale, 2 MW power plant demonstration unit, located in the City of Santa Clara, California. Construction of the unit's balance-of-plant (BOP) has been completed and the installed equipment has been operationally checked. Two of the four DFC stack sub-modules, each

Physiological adaptations to weight loss and factors favouring weight regain

PubMed Central

Greenway, F L

2015-01-01

Obesity is a major global health problem and predisposes individuals to several comorbidities that can affect life expectancy. Interventions based on lifestyle modification (for example, improved diet and exercise) are integral components in the management of obesity. However, although weight loss can be achieved through dietary restriction and/or increased physical activity, over the long term many individuals regain weight. The aim of this article is to review the research into the processes and mechanisms that underpin weight regain after weight loss and comment on future strategies to address them. Maintenance of body weight is regulated by the interaction of a number of processes, encompassing homoeostatic, environmental and behavioural factors. In homoeostatic regulation, the hypothalamus has a central role in integrating signals regarding food intake, energy balance and body weight, while an ‘obesogenic' environment and behavioural patterns exert effects on the amount and type of food intake and physical activity. The roles of other environmental factors are also now being considered, including sleep debt and iatrogenic effects of medications, many of which warrant further investigation. Unfortunately, physiological adaptations to weight loss favour weight regain. These changes include perturbations in the levels of circulating appetite-related hormones and energy homoeostasis, in addition to alterations in nutrient metabolism and subjective appetite. To maintain weight loss, individuals must adhere to behaviours that counteract physiological adaptations and other factors favouring weight regain. It is difficult to overcome physiology with behaviour. Weight loss medications and surgery change the physiology of body weight regulation and are the best chance for long-term success. An increased understanding of the physiology of weight loss and regain will underpin the development of future strategies to support overweight and obese individuals in their

Ciliated cells of pseudostratified airway epithelium do not become mucous cells after ovalbumin challenge.

PubMed

Pardo-Saganta, Ana; Law, Brandon M; Gonzalez-Celeiro, Meryem; Vinarsky, Vladimir; Rajagopal, Jayaraj

2013-03-01

Mucous cell metaplasia is a hallmark of airway diseases, such as asthma and chronic obstructive pulmonary disease. The majority of human airway epithelium is pseudostratified, but the cell of origin of mucous cells has not been definitively established in this type of airway epithelium. There is evidence that ciliated, club cell (Clara), and basal cells can all give rise to mucus-producing cells in different contexts. Because pseudostratified airway epithelium contains distinct progenitor cells from simple columnar airway epithelium, the lineage relationships of progenitor cells to mucous cells may be different in these two epithelial types. We therefore performed lineage tracing of the ciliated cells of the murine basal cell-containing airway epithelium in conjunction with the ovalbumin (OVA)-induced murine model of allergic lung disease. We genetically labeled ciliated cells with enhanced Yellow Fluorescent Protein (eYFP) before the allergen challenge, and followed the fate of these cells to determine whether they gave rise to newly formed mucous cells. Although ciliated cells increased in number after the OVA challenge, the newly formed mucous cells were not labeled with the eYFP lineage tag. Even small numbers of labeled mucous cells could not be detected, implying that ciliated cells make virtually no contribution to the new goblet cell pool. This demonstrates that, after OVA challenge, new mucous cells do not originate from ciliated cells in a pseudostratified basal cell-containing airway epithelium.

Activation of microRNA-494-targeting Bmi1 and ADAM10 by silibinin ablates cancer stemness and predicts favourable prognostic value in head and neck squamous cell carcinomas

PubMed Central

Chang, Yu-Chao; Lai, Yu-Chi; Hu, Fang-Wei; Yu, Cheng-Chia

2015-01-01

Tumor initiating cells (TICs) possessing cancer stemness were shown to be enriched after therapy, resulting in the relapse and metastasis of head and neck squamous cell carcinomas (HNC). An effective therapeutic approach suppressing the HNC-TICs would be a potential method to improve the treatments for HNC. We observed that the treatment of silibinin (SB) dose dependently down-regulated the ALDH1 activity, CD133 positivity, stemness signatures expression, self-renewal property, and chemoresistance in ALDH1+CD44+ HNC-TICs. Using miRNA-microarray and mechanistic studies, SB increased the expression of microRNA-494 (miR-494) and both Bmi1 and ADAM10 were identified as the novel targets of miR-494. Moreover, overexpression of miR-494 results in a reduction in cancer stemness. However, knockdown of miR-494 in CD44−ALDH1−non-HNC-TICs enhanced cancer stemness and oncogenicity, while co-knockdown of Bmi1 and ADAM10 effectively reversed these phenomena. Mice model showed that SB treatment by oral gavage to xenograft tumors reduced tumor growth and prolonged the survival time of tumor-bearing mice by activation of miR-494-inhibiting Bmi1/ADAM10 expression. Survival analysis indicated that a miR494highBmi1lowADAM10low phenotype predicted a favourable clinical outcome. We conclude that the inhibition of tumor aggressiveness in HNC-TICs by SB was mediated by up-regulation miR-494, suggesting that SB would be a valuable anti-cancer drug for treatment of HNC. PMID:26090866

Inference of Eco-geomorphic Processes Using Integrated Historical Data for a Rapidly Changing Mediterranean-climate River Corridor: Lower Santa Clara River, California

NASA Astrophysics Data System (ADS)

Beller, E. E.; Grossinger, R. M.; Downs, P. W.; Orr, B. K.

2010-12-01

Environmental conservation demands reach-specific data as the basis for place-based restoration and management measures. However, areas such as the lower Santa Clara River valley have been subject to intensive modification since the at least the nineteenth century, but without regular hydrogeomorphic or ecological monitoring (e.g., flow gauging, repeat topographic surveys, vegetation mapping) until the mid-twentieth century. This gap has limited data on former river corridor form and understanding of historical eco-geomorphic processes. The result is a lack of consensus about the range of potential riparian and aquatic habitats to consider as restoration targets, their appropriate relative distribution, and the relationship between such ecological targets and physical processes on the river, past and present. To address this data gap on the lower Santa Clara River, we initiated an effort to extend the documentation of river characteristics beyond readily available early data sets (such as aerial photography from 1927) by integrating historical cartographic, textual, and visual accounts to create a heterogeneous but substantial dataset describing hydrologic, geomorphic, and riparian characteristics back to 1769 - the date of the first non-native exploration of the region. We collected over 1,000 documents, including General Land Office survey data, early maps from the county surveyor, and traveler’s accounts of the region, evaluating each source for its accuracy and reliability. These data were synthesized to evaluate the location and composition of riparian areas that persisted despite substantial flood events and impacts of rapidly changing land use, and to determine aspects of the former hydrology of the river affecting riparian pattern that are still relevant today. The data also indicate the general resilience of mainstem channel form in response to these events in contrast to the present-day eco-geomorphic system, which is far more sensitive to change. Used

Impact of oligodendroglial component in glioblastoma (GBM-O): Is the outcome favourable than glioblastoma?

PubMed

Goda, Jayant S; Lewis, Shirley; Agarwal, Aditi; Epari, Sridhar; Churi, Shraddha; Padmavati, A; Gupta, Tejpal; Shetty, Prakash; Moiyadi, Aliasgar; Jalali, Rakesh

2015-08-01

Prognosis of patients with glioblastoma with oligodendroglial component (GBM-O) is not well defined. We report our experience of patients of GBM-O treated at our center. Between January 2007 and August 2013, out of 817 consecutive patients with glioblastoma (GBM), 74 patients with GBM-O were identified in our prospectively maintained database. An experienced neuropathologist revaluated the histopathology of all these 74 patients and the diagnosis of GBM-O was eventually confirmed in 57 patients. Patients were uniformly treated with maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolamide (TMZ). At a median follow up of 16 months, median overall survival (OS) and progression free survival (PFS) of the entire cohort was 23 months and 13 months respectively. Near total excision was performed in 30/57 (52.6%). On univariate analysis, age < 50 years was a significant favourable prognostic factor for OS (p = 0.009) and PFS (p = 0.017), while patients with near total resection had a significantly better PFS (p = 0.017), patients who completed a minimum of 6 cycles of adjuvant TMZ had significantly better OS (p = 0.000) and PFS (p = 0.003). On multivariate analysis, none of the above factors were significant except for patient who had completed a minimum of 6 cycles of TMZ (OS; p = 0.000 & PFS; p = 0.015). A comparative analysis of GBM-O patients with a similarly treated cohort of 105 GBM patients during the same period revealed significantly better median OS in favour of GBM-O (p = 0.01). Our experience suggests patients with GBM-O have a more favourable clinical outcome as compared to GBM. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparisons of shear-wave slowness in the Santa Clara Valley, California using blind interpretations of data from invasive and noninvasive methods

USGS Publications Warehouse

Boore, D.M.; Asten, M.W.

2008-01-01

Many groups contributed to a blind interpretation exercise for the determination of shear-wave slowness beneath the Santa Clara Valley. The methods included invasive methods in deep boreholes as well as noninvasive methods using active and passive sources, at six sites within the valley (with most investigations being conducted at a pair of closely spaced sites near the center of the valley). Although significant variability exists between the models, the slownesses from the various methods are similar enough that linear site amplifications estimated in several ways are generally within 20% of one another. The methods were able to derive slownesses that increase systematically with distance from the valley edge, corresponding to a tendency for the sites to be underlain by finer-grained materials away from the valley edge. This variation is in agreement with measurements made in the boreholes at the sites.

Pulse compression favourable aperiodic infrared imaging approach for non-destructive testing and evaluation of bio-materials

NASA Astrophysics Data System (ADS)

Mulaveesala, Ravibabu; Dua, Geetika; Arora, Vanita; Siddiqui, Juned A.; Muniyappa, Amarnath

2017-05-01

In recent years, aperiodic, transient pulse compression favourable infrared imaging methodologies demonstrated as reliable, quantitative, remote characterization and evaluation techniques for testing and evaluation of various biomaterials. This present work demonstrates a pulse compression favourable aperiodic thermal wave imaging technique, frequency modulated thermal wave imaging technique for bone diagnostics, especially by considering the bone with tissue, skin and muscle over layers. In order to find the capabilities of the proposed frequency modulated thermal wave imaging technique to detect the density variations in a multi layered skin-fat-muscle-bone structure, finite element modeling and simulation studies have been carried out. Further, frequency and time domain post processing approaches have been adopted on the temporal temperature data in order to improve the detection capabilities of frequency modulated thermal wave imaging.

An evolutionary concept of polycystic ovarian disease: does evolution favour reproductive success over survival?

PubMed

Gleicher, Norbert; Barad, David

2006-05-01

Polycystic ovarian disease (PCOD) is currently considered as possibly the most frequent cause of female infertility. It is also closely associated with syndrome XX, which, in turn, is closely linked with premature and excessive mortality. Considering these adverse effects on reproductive success and human survival, the evolutionary survival of PCOD, itself considered by many to be a genetically transmitted condition, would, on first glance, appear surprising, since evolution usually discriminates against both of these traits. However, an analysis of some recently reported characteristics of the condition calls for the reconsideration of PCOD as a condition which, from an evolutionary viewpoint, favours decreased reproductive success. Indeed, the reported observations that patients with PCOD will resume spontaneous ovulation with even relatively minor weight loss, and experience later menopause than controls, suggests exactly the opposite. Under an evolutionary concept, PCOD can thus be seen as a 'fertility storage condition' which in fact favours human reproductive success and allows the human species to maintain fertility even during adverse environmental circumstances, such as famines.

Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Keisha M.; Franzi, Lisa M.; Last, Jerold A., E-mail: jalast@ucdavis.edu

2013-01-01

Our previous work has shown that coarse particulate matter (PM{sub 10-2.5}) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24 hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stressmore » in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At 1 hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1 ± 3.2 pg/mL to 83.9 ± 12.2 pg/mL was observed a half-hour after PM instillation. By 1 hour after PM instillation, isoprostane values had returned to 30.4 ± 7.6 pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1 hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.5–1 hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure. -- Highlights: ► We studied very early events (0.5–1 hour

SPDEF regulates goblet cell hyperplasia in the airway epithelium

PubMed Central

Park, Kwon-Sik; Korfhagen, Thomas R.; Bruno, Michael D.; Kitzmiller, Joseph A.; Wan, Huajing; Wert, Susan E.; Khurana Hershey, Gurjit K.; Chen, Gang; Whitsett, Jeffrey A.

2007-01-01

Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID:17347682

Women Favour Dyadic Relationships, but Men Prefer Clubs: Cross-Cultural Evidence from Social Networking

PubMed Central

David-Barrett, Tamas; Rotkirch, Anna; Carney, James; Behncke Izquierdo, Isabel; Krems, Jaimie A.; Townley, Dylan; McDaniell, Elinor; Byrne-Smith, Anna; Dunbar, Robin I. M.

2015-01-01

The ability to create lasting, trust-based friendships makes it possible for humans to form large and coherent groups. The recent literature on the evolution of sociality and on the network dynamics of human societies suggests that large human groups have a layered structure generated by emotionally supported social relationships. There are also gender differences in adult social style which may involve different trade-offs between the quantity and quality of friendships. Although many have suggested that females tend to focus on intimate relations with a few other females, while males build larger, more hierarchical coalitions, the existence of such gender differences is disputed and data from adults is scarce. Here, we present cross-cultural evidence for gender differences in the preference for close friendships. We use a sample of ∼112,000 profile pictures from nine world regions posted on a popular social networking site to show that, in self-selected displays of social relationships, women favour dyadic relations, whereas men favour larger, all-male cliques. These apparently different solutions to quality-quantity trade-offs suggest a universal and fundamental difference in the function of close friendships for the two sexes. PMID:25775258

Women favour dyadic relationships, but men prefer clubs: cross-cultural evidence from social networking.

PubMed

David-Barrett, Tamas; Rotkirch, Anna; Carney, James; Behncke Izquierdo, Isabel; Krems, Jaimie A; Townley, Dylan; McDaniell, Elinor; Byrne-Smith, Anna; Dunbar, Robin I M

2015-01-01

The ability to create lasting, trust-based friendships makes it possible for humans to form large and coherent groups. The recent literature on the evolution of sociality and on the network dynamics of human societies suggests that large human groups have a layered structure generated by emotionally supported social relationships. There are also gender differences in adult social style which may involve different trade-offs between the quantity and quality of friendships. Although many have suggested that females tend to focus on intimate relations with a few other females, while males build larger, more hierarchical coalitions, the existence of such gender differences is disputed and data from adults is scarce. Here, we present cross-cultural evidence for gender differences in the preference for close friendships. We use a sample of ∼112,000 profile pictures from nine world regions posted on a popular social networking site to show that, in self-selected displays of social relationships, women favour dyadic relations, whereas men favour larger, all-male cliques. These apparently different solutions to quality-quantity trade-offs suggest a universal and fundamental difference in the function of close friendships for the two sexes.

Favourable results of Mohs micrographic surgery for basal cell carcinoma.

PubMed

Gniadecki, Robert; Glud, Martin; Mortensen, Kia; Bang, Bo; Biskup, Edyta; Omland, Silje Haukali

2015-12-01

Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing of the surrounding healthy skin, and it also offers higher cure rates than standard tumour excision with a predefined margin of healthy skin. The superiority of MMS relies on the fact that the entire (100%) margin of the excised tissue is examined microscopically for residual tumour in contrast to the traditional histopathological examination, in which 2% of the margin is examined. In Denmark, MMS was first introduced by us in 2012. In the present study, we retrospectively included all patients who underwent MMS from May 2012 to June 2015. A total of 231 patients with 263 BCC were included. The mean age was 66.1 years. The most common localisations were the forehead (31.3%), the nose (31.0%) and the cheek (14.7%). Primary BCC comprised 54.0%; the remaining cases were relapses, most frequently after curettage (36.9%), radiotherapy (18.9%) and photodynamic therapy (11.7%). MMS leads to 40% smaller skin defects than standard excisions with 4 or 6 mm margins. Closure of skin defects was achieved by side-to-side closure in 49% and by local flaps in 40%. There were no relapses during the observation time. The safety, cosmetic and functional outcome were excellent. We recommend that MMS be included in the Danish BCC treatment guidelines, especially for high-risk BCC in the face, in line with standard practice in Europe and the United States. none. not relevant.

Climate change and habitat conversion favour the same species.

PubMed

Frishkoff, Luke O; Karp, Daniel S; Flanders, Jon R; Zook, Jim; Hadly, Elizabeth A; Daily, Gretchen C; M'Gonigle, Leithen K

2016-09-01

Land-use change and climate change are driving a global biodiversity crisis. Yet, how species' responses to climate change are correlated with their responses to land-use change is poorly understood. Here, we assess the linkages between climate and land-use change on birds in Neotropical forest and agriculture. Across > 300 species, we show that affiliation with drier climates is associated with an ability to persist in and colonise agriculture. Further, species shift their habitat use along a precipitation gradient: species prefer forest in drier regions, but use agriculture more in wetter zones. Finally, forest-dependent species that avoid agriculture are most likely to experience decreases in habitable range size if current drying trends in the Neotropics continue as predicted. This linkage suggests a synergy between the primary drivers of biodiversity loss. Because they favour the same species, climate and land-use change will likely homogenise biodiversity more severely than otherwise anticipated. © 2016 John Wiley & Sons Ltd/CNRS.

Effects of early developmental conditions on innate immunity are only evident under favourable adult conditions in zebra finches

NASA Astrophysics Data System (ADS)

de Coster, Greet; Verhulst, Simon; Koetsier, Egbert; de Neve, Liesbeth; Briga, Michael; Lens, Luc

2011-12-01

Long-term effects of unfavourable conditions during development can be expected to depend on the quality of the environment experienced by the same individuals during adulthood. Yet, in the majority of studies, long-term effects of early developmental conditions have been assessed under favourable adult conditions only. The immune system might be particularly vulnerable to early environmental conditions as its development, maintenance and use are thought to be energetically costly. Here, we studied the interactive effects of favourable and unfavourable conditions during nestling and adult stages on innate immunity (lysis and agglutination scores) of captive male and female zebra finches ( Taeniopygia guttata). Nestling environmental conditions were manipulated by a brood size experiment, while a foraging cost treatment was imposed on the same individuals during adulthood. This combined treatment showed that innate immunity of adult zebra finches is affected by their early developmental conditions and varies between both sexes. Lysis scores, but not agglutination scores, were higher in individuals raised in small broods and in males. However, these effects were only present in birds that experienced low foraging costs. This study shows that the quality of the adult environment may shape the long-term consequences of early developmental conditions on innate immunity, as long-term effects of nestling environment were only evident under favourable adult conditions.

Impact of cardiopulmonary resuscitation duration on neurologically favourable outcome after out-of-hospital cardiac arrest: A population-based study in Japan.

PubMed

Matsuyama, Tasuku; Kitamura, Tetsuhisa; Kiyohara, Kosuke; Nishiyama, Chika; Nishiuchi, Tatsuya; Hayashi, Yasuyuki; Kawamura, Takashi; Ohta, Bon; Iwami, Taku

2017-04-01

The optimal cardiopulmonary resuscitation (CPR) duration for patients with out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to assess the association between CPR duration and outcome after OHCA. This prospective, population-based observational study conducted in Osaka, Japan enrolled 6981 adult patients with non-traumatic witnessed OHCA who achieved return of spontaneous circulation (ROSC) from January 2005 through December 2012. CPR duration was defined as the time of CPR initiation by emergency medical service personnel to the ROSC in pre-hospital settings or after hospital admission. The primary outcome was one-month survival with neurologically favourable outcome (cerebral performance category scale 1 or 2). Overall, median CPR duration was 25min (interquartile range: 15-34) and the proportion of neurologically favourable outcome was 12.5% (875/6,981). The proportion of neurologically favourable outcome among the CPR duration ≥31min group was significantly lower compared with that among the 0-5min group (55.1% [320/581] versus 2.2% [54/2424], adjusted odds ratio [AOR] 0.04; 95% confidence interval [CI] 0.03-0.05 in all patients, 78.4% [240/306] versus 11.4% [30/264], AOR 0.04; 95% CI 0.02-0.06 in the shockable group, 29.1% [80/275] versus 1.1% [24/2160], and AOR 0.03; 95% CI 0.02-0.05 in the non-shockable group). The cumulative proportion for neurologically favourable outcome reached 99% after 44, 41, and 43min of CPR in all patients, the shockable group, and the non-shockable group, respectively. The proportion of patients with neurologically favourable outcome declined with increasing CPR duration, but some OHCA patients could benefit from prolonged CPR duration >30min. Copyright © 2017 Elsevier B.V. All rights reserved.

Low vascularity predicts favourable outcomes in leiomyoma patients treated with uterine artery embolization.

PubMed

Tang, Yixin; Chen, Chunlin; Duan, Hui; Ma, Ben; Liu, Ping

2016-10-01

To investigate the clinical factors predicting outcomes of leiomyoma treated with uterine artery embolization (UAE). A total of 183 uterine leiomyoma patients undergoing UAE were retrospectively analyzed. Patient age, characteristics of vascular supply in magnetic resonance imaging (MRI)/digital subtraction angiography (DSA), number, size and location of leiomyoma were recorded. Leiomyoma regrowth, new leiomyoma appearance and recurrence of any previously reported symptoms were carefully monitored over a mean follow-up of 30 months (median 32 months, range 12-80). Potential recurrence risk factors were analyzed by univariate and multivariate cox regression analysis. Twenty-three recurrences were recorded. The difference in the vascularity classification systems between MRI and DSA was not statistically significant (P = 0.059). High vascularity in MRI, high vascularity in DSA and multiple leiomyoma showed a significant risk of recurrence using univariate and multivariate analysis (P = 0.004, P < 0.001 and P = 0.023, respectively). The other factors were not significantly associated with leiomyoma recurrence (P > 0.05). Low vascularity and solitary leiomyoma indicated favourable outcomes in patients treated with UAE. • Low vascularity and solitary mass predicted favourable outcomes in UAE-treated patients. • MRI might provide information on vascularity in leiomyoma before UAE. • Variations in vascular supply, age, size, location were not associated with recurrence.

Shaded relief aeromagnetic map of the Santa Clara Valley and vicinity, California

USGS Publications Warehouse

Roberts, Carter W.; Jachens, Robert C.

2003-01-01

This aeromagnetic map covers the southern portion of San Francisco Bay, the Santa Clara Valley and surrounding mountains, part of which has been modelled in threedimensions (Jachens and other, 2001). The magnetic anomaly map has been compiled from existing digital data. Data was obtained from six aeromagnetic surveys that were flown at different times, spacings and elevations. The International Geomagnetic Reference Field (IGRF) for the date of each survey had been removed in the initial processing. The resulting residual magnetic anomalies were analytically continued onto a common surface 305 m (1000 ft) above terrain. Portions of each survey were substantially above the specified flight height listed in the table. The surveys were then merged together using a commercial software package called Oasis Montage. The gray lines on the map indicate the extent of each survey. The program used these regions of overlap to determine the best fit between surveys. Black dots show probable edges of magnetic bodies defined by the maximum horizontal gradient determined using a computer program by Blakely (1995). Crystalline rocks generally contain sufficient magnetic minerals to cause variations in the Earth’s magnetic field that can be mapped by aeromagnetic surveys. Sedimentary rocks are generally weakly magnetized and consequently have a small effect on the magnetic field: thus a magnetic anomaly map can be used to “see through” the sedimentary rock cover and can convey information on lithologic contrasts and structural trends related to the underlying crystalline basement (see Nettleton,1971; Blakely, 1995). Faults often cut magnetic bodies and offset magnetic anomalies can thus be used to help determine fault motion. Serpentinite, which is highly magnetic, is often found along faults. On this map areas of low magnetic anomalies are shown in blues and green while highs are shown in reds and magentas. Faults are from Brabb and others, 1998a,1998b, Graymer and others

Family characteristics predicting favourable changes in 10 and 11-year-old children's lifestyle-related health behaviours during an 18-month follow-up.

PubMed

Ray, Carola; Roos, Eva

2012-02-01

Lifestyle-related health behaviours such as screen time, physical activity, sleep duration, and food intake tend to change into non-favourable directions when children become young adolescents. Cross-sectional studies show that family characteristics are important determinants for children's health behaviours. This study examined whether family characteristics such as parenting practices at meals and family involvement predict a more favourable change in children's lifestyle-related health behaviours during an 18-month follow-up. 745 children in school grades 4 and 5 (response rate 65%) filled in a baseline questionnaire in the autumn of 2006. A follow-up was conducted in the spring of 2008 (91%). Several health behaviours had changed in a non-favourable direction. Baseline parenting practices at meals and family involvement predicted some of the changes in the lifestyle-related health behaviours in 2008. Parenting practices at meals predicted a smaller increase in TV, DVD viewing time, and a smaller decrease in fruit intake. Amongst family involvement determinants, less time alone at home after school predicted a smaller increase in screen time, a smaller decrease in sleep duration, and a smaller increase in soft drink intake. For conclusion several family characteristics predicted favourable changes in children's lifestyle-related health behaviours. Copyright © 2011 Elsevier Ltd. All rights reserved.

The response time threshold for predicting favourable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest.

PubMed

Ono, Yuichi; Hayakawa, Mineji; Iijima, Hiroaki; Maekawa, Kunihiko; Kodate, Akira; Sadamoto, Yoshihiro; Mizugaki, Asumi; Murakami, Hiromoto; Katabami, Kenichi; Sawamura, Atsushi; Gando, Satoshi

2016-10-01

It is well established that the period of time between a call being made to emergency medical services (EMS) and the time at which the EMS arrive at the scene (i.e. the response time) affects survival outcomes in patients who experience out-of-hospital cardiac arrest (OHCA). However, the relationship between the response time and favourable neurological outcomes remains unclear. We therefore aimed to determine a response time threshold in patients with bystander-witnessed OHCA that is associated with positive neurological outcomes and to assess the relationship between the response time and neurological outcomes in patients with OHCA. This study was a retrospective, observational analysis of data from 204,277 episodes of bystander-witnessed OHCA between 2006 and 2012 in Japan. We used classification and regression trees (CARTs) and receiver operating characteristic (ROC) curve analyses to determine the threshold of response time associated with favourable neurological outcomes (Cerebral Performance Category 1 or 2) 1 month after cardiac arrest. Both CARTs and ROC analyses indicated that a threshold of 6.5min was associated with improved neurological outcomes in all bystander-witnessed OHCA events of cardiac origin. Furthermore, bystander cardiopulmonary resuscitation (CPR) prolonged the threshold of response time by 1min (up to 7.5min). The adjusted odds ratio for favourable neurological outcomes in patients with OHCA who received care within ≤6.5min was 1.935 (95% confidential interval: 1.834-2.041, P<0.001). A response time of ≤6.5min was closely associated with favourable neurological outcomes in all bystander-witnessed patients with OHCA. Bystander CPR prolonged the response time threshold by 1min. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Experimental study of neutron-rich nuclei near the N = 82 closed shell using the {sub 40}{sup 96}Zr+{sub 50}{sup 124}Sn reaction with GASP and PRISMA-CLARA arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodríguez, W.; Torres, D. A.; Cristancho, F.

2014-11-11

In this contribution an experimental study of the deep-inelastic reaction {sub 40}{sup 96}Zr+{sub 50}{sup 124}Sn at 530 MeV, using the GASP and PRISMA-CLARA arrays, is presented. The experiments populate a wealth of projectile-like and target-like binary fragments, in a large neutron-rich region around N ≥ 50 and Z ≈ 40. Preliminary results on the study of the yrast and near-yrast states for {sup 95}Nb will be shown, along with a comparison of the experimental yields obtained in the experiments.

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

PubMed Central

Hong, Kyung U.; Reynolds, Susan D.; Watkins, Simon; Fuchs, Elaine; Stripp, Barry R.

2004-01-01

Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury. PMID:14742263

Prognostic significance of surfactant protein A, surfactant protein D, Clara cell protein 16, S100 protein, trefoil factor 3, and prostatic secretory protein 94 in idiopathic pulmonary fibrosis, sarcoidosis, and chronic pulmonary obstructive disease.

PubMed

Doubková, Martina; Karpíšek, Michal; Mazoch, Jiri; Skřičková, Jana; Doubek, Michael

2016-10-07

Identification of serum and bronchoalveolar lavage fluid (BALF) biomarkers may facilitate diagnosis and prognostication in various lung disorders. Serum and BALF levels of surfactant protein A (SP-A), surfactant protein D (SP-D), Clara cell protein 16 (CC16), S100 protein, trefoil factor 3 (TFF3), and prostatic secretory protein 94 (PSP94) were evaluated in 94 consecutive patients (idiopathic pulmonary fibrosis (IPF; n=18), sarcoidosis (n=25), chronic obstructive pulmonary disease (COPD; n=51)), and in 155 healthy controls. Biomarkers were measured at diagnosis and compared with disease characteristics. Both uniparametric and multiparametric analyses were used. Seven significant correlations were found: 1) BALF PSP94 level correlated with prognosis of sarcoidosis (P=0.035); 2) BALF SP-D level with pulmonary functions in IPF (P=0.032); 3) BALF SP-D and TFF3 with IPF mortality (P=0.049 and 0.017, respectively); 4) serum TFF3 level with COPD mortality (P=0.006,); 5) serum SP-A with pulmonary functions impairment in IPF (P=0.011); 6) serum SP-D level was associated with HRCT interstitial score in IPF (P=0.0346); and 7) serum SP-A was associated with staging of COPD according to spirometry (P<0.001). Moreover, our analysis showed that some biomarker levels differed significantly among the diseases: 1) BALF SP-D level differed between sarcoidosis and IPF; 2) serum SP-A level differed among IPF, sarcoidosis, COPD and was also different from healthy controls; 3) serum S100A6, S100A11 levels differed among IPF, sarcoidosis, COPD from healthy controls 4) serum SP-D, CC16, TFF-3 levels distinguished IPF patients from healthy controls; and 5) serum CC16, TFF3, PSP94 distinguished COPD patients from healthy controls. Our study shows that some of selected biomarkers should have prognostic value in the analysed lung disorders. On the other hand, these biomarkers do not appear to be unequivocally suitable for differential diagnosis of these disorders.

Germ cell tumour growth patterns originating from clear cell carcinomas of the ovary and endometrium: a comparative immunohistochemical study favouring their origin from somatic stem cells.

PubMed

Nogales, Francisco F; Prat, Jaime; Schuldt, Maolly; Cruz-Viruel, Nelly; Kaur, Baljeet; D'Angelo, Emanuela; Matias-Guiu, Xavier; Vidal, August; McCluggage, W Glenn; Oosterhuis, J Wolter

2018-03-01

To report a series of 11 ovarian and one endometrial neoplasm in elderly patients with mixed clear cell tumour and germ cell tumour (GCT) components, to compare their immunohistochemical profiles and demonstrate a putative stem cell population. The clear cell tumours included 11 clear cell carcinomas (CCC) and one borderline clear cell tumour, while the GCT always included glandular yolk sac tumour (YST). In four cases, there were also foci of teratoma with immature neuroepithelial and endodermal tissues and undifferentiated areas showing true embryoids. To distinguish between the clear cell and YST components, the following antibodies were used: HNF1-β, napsin-A, cytokeratin 7 (CK7), PAX8, EMA, AFP, SALL4, villin, glypican-3 (GPC-3), GATA3, HepPar-1, OCT4, CDX2, CD30 and SOX2. HNF1-β, CK7, EMA and GPC-3 were often expressed in both components. Other markers had higher specificity for each cellular lineage; napsin-A and PAX8 were expressed only in CCC, while SALL4, villin, AFP and HepPar-1 were positive in the glandular YST component but negative in the clear cell component. OCT4 expression occurred in six of 10 cases and consistently in teratoma (four of four). There is considerable immunophenotypical overlap between the two components in these mixed neoplasms, and a panel of markers should be used to facilitate the distinction. We propose that OCT4-expressing somatic cancer cells differentiate into GCT and represent spontaneously induced pluripotent stem cells, possibly conditioned by age-related epigenetic factors. These neoplasms have features of prepubertal type GCT showing lack of 12p gain, preponderance of YST and coexistence with immature neuroectoderm. However, there may also be undifferentiated stem cell areas with embryoid bodies, of the type seen in postpubertal testicular GCT, but lacking a complete embryonal carcinoma immunophenotype. © 2017 John Wiley & Sons Ltd.

Favourable Changes of the Risk-Benefit Ratio in Alpine Skiing

PubMed Central

Burtscher, Martin; Ruedl, Gerhard

2015-01-01

During the past five decades recreational alpine skiing has become increasingly safer. The numerous annual media reports on ski injuries have to be interpreted on the basis of the tremendous numbers of skiers. These favourable changes seem primarily be due to the introduction of short carving skis, more rigid and comfortable ski boots, the use of protective gear like helmets, and the optimized preparation of ski slopes. The associated health benefits from skiing, especially arising from its association with a healthier life style, and possibly also from effects related to hypoxia preconditioning and increasing subjective vitality by natural elements clearly outweigh the health hazards. Technical improvements will likely help further reducing the injury risk. At least hypothetically, each individual skier could help to prevent injuries by the development of an appropriate physical fitness and responsible behaviour on ski slopes thereby optimizing the risk-benefit ratio of alpine skiing. PMID:26035659

Use of tobacco retail permitting to reduce youth access and exposure to tobacco in Santa Clara County, California.

PubMed

Coxe, Nicole; Webber, Whitney; Burkhart, Janie; Broderick, Bonnie; Yeager, Ken; Jones, Laura; Fenstersheib, Marty

2014-10-01

To target youth smoking, the impact of a local tobacco retail permit was evaluated on the number and location of tobacco retailers, and on the level of enforcement and compliance with tobacco sales regulations from 2010 to 2012 within unincorporated Santa Clara County, California. Geographic Information Systems (GIS) mapping of each of 36 tobacco retailers pre- and post-intervention, observational surveys of tobacco retail environments pre- and post-intervention, and post-intervention enforcement surveys to measure location of sales, level of enforcement action, and compliance with laws governing sale of tobacco products were conducted. Eleven (30.6%) of the initial 36 retailers selling tobacco at the start of the intervention stopped selling tobacco post intervention. Of these 11 retailers, one was within 500feet of another retailer, and three were within 1000feet of a K-12 school. Ten (91%) of the retailers who stopped selling tobacco were non-traditional retailers. An immediate reduction in the number of stores selling tobacco occurred following implementation of tobacco retail permitting. Post-implementation, all retailers who underwent compliance checks were in compliance with laws prohibiting sales of tobacco to minors. Compliance with laws governing the sale of tobacco has potential to reduce access and use of tobacco products by youth. Published by Elsevier Inc.

Water quality of Calero Reservoir, Santa Clara County, California, 1981-83

USGS Publications Warehouse

Clifton, D.G.; Gloege, I.S.

1987-01-01

Data were collected from December 1980 to September 1983 to describe water quality conditions of Calero Reservoir and the Almaden-Calero canal, Santa Clara County, California. Results show that water in Calero Reservoir and the canal generally met water quality criteria, as identified by the California Regional Water Quality Control Board San Francisco Bay Region, for municipal and domestic supply, water contact and non-contact recreation, warm water fish habitat, wildlife habitat, and fish spawning. Water temperature profiles show that Calero Reservoir can be classified as a warm monomictic reservoir. Water transparency profiles showed rapid attenuation of light with depth in the water column. The depth of the euphotic zone ranged from .5 m to 5.0 m. In winter and spring, light-extinction values generally were high throughout the water column; in summer and fall, values generally were high near the reservoir bottom. Dissolved oxygen concentrations were < 5.0 mg/L in about 22% of the measurements. Median pH values were 7.9 in the reservoir and 8.4 in the canal. Mean specific conductance values were 299 microsiemens/cm at 25 C in the reservoir and 326 in the canal. Calcium and magnesium were the dominant cations and bicarbonate the dominant anion in Calero Reservoir. Concentrations of total recoverable mercury in the bottom sediments in Calero Reservoir ranged from 0.06 to 0.85 mg/kg, but concentrations in the water column were was generally < 1 mg/L. Mean total nitrogen concentration in the Reservoir was 1.00 mg/L, much of it in dissolved form (mean concentration was 0.85 mg/L). Mean total organic nitrogen concentration in Calero Reservoir was 0.65 mg/L, and mean total nitrate concentration was 0.21 mg/L. Mean total phosphorus and dissolved orthophosphorous concentrations were 0.05 and 0.019 mg/L, respectively. Net primary productivity in the euphotic zone ranged from -2,000 to 10,000 mg of oxygen/sq m/day; the median value was 930. Carlson 's trophic-state index

Evolution of trust and trustworthiness: social awareness favours personality differences

PubMed Central

McNamara, John M.; Stephens, Philip A.; Dall, Sasha R.X.; Houston, Alasdair I.

2008-01-01

Interest in the evolution and maintenance of personality is burgeoning. Individuals of diverse animal species differ in their aggressiveness, fearfulness, sociability and activity. Strong trade-offs, mutation–selection balance, spatio-temporal fluctuations in selection, frequency dependence and good-genes mate choice are invoked to explain heritable personality variation, yet for continuous behavioural traits, it remains unclear which selective force is likely to maintain distinct polymorphisms. Using a model of trust and cooperation, we show how allowing individuals to monitor each other's cooperative tendencies, at a cost, can select for heritable polymorphisms in trustworthiness. This variation, in turn, favours costly ‘social awareness’ in some individuals. Feedback of this sort can explain the individual differences in trust and trustworthiness so often documented by economists in experimental public goods games across a range of cultures. Our work adds to growing evidence that evolutionary game theorists can no longer afford to ignore the importance of real world inter-individual variation in their models. PMID:18957369

Sexual selection favours male parental care, when females can choose

PubMed Central

Alonzo, Suzanne H.

2012-01-01

Explaining the evolution of male care has proved difficult. Recent theory predicts that female promiscuity and sexual selection on males inherently disfavour male care. In sharp contrast to these expectations, male-only care is often found in species with high extra-pair paternity and striking variation in mating success, where current theory predicts female-only care. Using a model that examines the coevolution of male care, female care and female choice; I show that inter-sexual selection can drive the evolution of male care when females are able to bias mating or paternity towards parental males. Surprisingly, female choice for parental males allows male care to evolve despite low relatedness between the male and the offspring in his care. These results imply that predicting how sexual selection affects parental care evolution will require further understanding of why females, in many species, either do not prefer or cannot favour males that provide care. PMID:22171082

Can eccentric arterial plaques alone cause flow stagnation points and favour thrombus incorporation?

PubMed Central

Beneli, Cristina T; Barbosa, Priscila F; Floriano, Elaine M; Abreu, Mônica A; Ramalho, Fernando S; Júnior, Jorge Elias; Rossi, Marcos A; Ramos, Simone G

2009-01-01

We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas. PMID:19563612

Expect the unexpected: favourable outcome in Munchausen by proxy syndrome.

PubMed

Klepper, Jörg; Heringhaus, Anja; Wurthmann, Cornelius; Voit, Thomas

2008-09-01

Munchausen by proxy syndrome (MBPS) is a form of child abuse wherein the mother fabricates or produces illness in her child. The condition is hard to diagnose and few successful interventions have been described. Long-term outcome is associated with high family disruption, reabuse, mortality and morbidity. We report on a six-month-old girl that experienced eight hospital admissions within five months. Symptoms of repeated vomiting, bloody diarrhoea and acute life-threatening events (ALTE) were never substantiated. Finally, blood in diapers and napkins presented by the mother was shown to be of maternal origin. When confronted, the mother agreed to psychiatric admission. Following five months of treatment, her mental state stabilised and she entered supported living. She remained separated from the child, who was given to the father and developed normally on close paediatric follow-up. We report a definite diagnosis and successful intervention in MBPS. The case highlights characteristic features of this entity and illustrates that a favourable outcome depends on early intervention with separation of the child and perpetrator, as well as concomitant long-term psychiatric treatment.

Ground water/surface water responses to global climate simulations, Santa Clara-Calleguas Basin, Ventura, California

USGS Publications Warehouse

Hanson, R.T.; Dettinger, M.D.

2005-01-01

Climate variations can play an important, if not always crucial, role in successful conjunctive management of ground water and surface water resources. This will require accurate accounting of the links between variations in climate, recharge, and withdrawal from the resource systems, accurate projection or predictions of the climate variations, and accurate simulation of the responses of the resource systems. To assess linkages and predictability of climate influences on conjunctive management, global climate model (GCM) simulated precipitation rates were used to estimate inflows and outflows from a regional ground water model (RGWM) of the coastal aquifers of the Santa ClaraCalleguas Basin at Ventura, California, for 1950 to 1993. Interannual to interdecadal time scales of the El Nin??o Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) climate variations are imparted to simulated precipitation variations in the Southern California area and are realistically imparted to the simulated ground water level variations through the climate-driven recharge (and discharge) variations. For example, the simulated average ground water level response at a key observation well in the basin to ENSO variations of tropical Pacific sea surface temperatures is 1.2 m/??C, compared to 0.9 m/??C in observations. This close agreement shows that the GCM-RGWM combination can translate global scale climate variations into realistic local ground water responses. Probability distributions of simulated ground water level excursions above a local water level threshold for potential seawater intrusion compare well to the corresponding distributions from observations and historical RGWM simulations, demonstrating the combination's potential usefulness for water management and planning. Thus the GCM-RGWM combination could be used for planning purposes and - when the GCM forecast skills are adequate - for near term predictions.

Geologic map of the Palo Alto and part of the Redwood Point 7-1/2' quadrangles, San Mateo and Santa Clara counties, California

USGS Publications Warehouse

Pampeyan, Earl H.

1993-01-01

The Palo Alto and southern part of the Redwood Point 7-1/2' quadrangles cover an area on the San Francisco peninsula between San Francisco Bay and the Santa Cruz Mountains. San Francisquito and Los Trancos Creeks, in the southeastern part of the map area, form the boundary between San Mateo and Santa Clara Counties. The area covered by the geologic map extends from tidal and marsh lands at the edge of the bay southward across a gently sloping alluvial plain to the foothills of the northern Santa Cruz Mountains. The foothills are separated from the main mass of the mountains by two northwest-striking faults, the San Andreas and Pilarcitos, that cross the southwest corner of the map area (fig. 1). The map and adjoining areas are here divided into three structural blocks juxtaposed along these faults, adopting the scheme of Nilsen and Brabb (1979): (1) the San Francisco Bay block lying east of the San Andreas Fault Zone; (2) the Pilarcitos block lying between the San Andreas and Pilarcitos Faults; and (3) the La Honda block that includes the main mass of the Santa Cruz Mountains lying west of the Pilarcitos Fault. The west boundary of the La Honda block is the Seal Cove-San Gregorio Fault. Pre-late Pleistocene Cenozoic rocks of the foothills have been compressed into northwest-striking folds, which have been overridden by Mesozoic rocks along southwest-dipping low-angle faults. Coarse- to fine-grained upper Pleistocene and Holocene alluvial and estuarine deposits, eroded from the foothills and composing the alluvial plain, are essentially undeformed. Most of the alluvial plain, including some parts of the marsh land that borders the bay, has been covered by residential and commercial developments, and virtually all of the remaining marsh land has been diked off and used as salt evaporating ponds. The map area includes parts of the municipalities of San Carlos, Redwood City, Atherton, Woodside, Portola Valley, Menlo Park, and East Palo Alto in San Mateo County; and

Multiple cores of Gleason score 6 correlate with favourable findings at radical prostatectomy

PubMed Central

Ellis, Carla L.; Walsh, Patrick C.; Partin, Alan W.; Epstein, Jonathan I.

2014-01-01

Objective To establish whether the good prognosis of Gleason score 6 (GS6) is maintained in the setting of multiple involved cores. Patients and Methods In total, 6156 men (from 1 April 2000 to 30 April 2007) with GS6 on biopsy underwent radical prostatectomy (RP) at our institution. The number of positive cores was correlated with the outcome at RP. Results More positive cores correlated with less organ-confined disease (P < 0.001), positive margins (P < 0.012), increasing RP grade (P < 0.001) and increased seminal vesicles/lymph node involvement (P = 0.012). For men with data available, the actuarial risk of being biochemically free of disease at 5 years was 93.2% when ≤6 cores were positive (812 men followed to 5 years) vs 89.1% if >6 cores were positive (41 men followed to 2 years) (P = 0.6). Although the predicted ‘cure rate’ of >75% probability of a tumour showing no evidence of biochemical recurrence at 10 years after RP was statistically different between cases with ≤6 vs >6 positive cores (P < 0.0001), the outcome in both groups was still favourable (90.5% vs 84%). Partin-like tables were generated factoring in the number of positive cores to predict organ-confined disease as a guide for urologists to perform nerve-sparing surgery. For example, with T1c disease, there was a ≥75% probability of organ-confined disease with one to three positive cores regardless of prostate-specific antigen (PSA) level, and the same probability was present with four to six positive cores and a PSA level of 0–4 ng/mL. Conclusion A low Gleason score on biopsy is a powerful prognostic finding, such that this favourable outcome is maintained even in the setting of multiple positive cores with GS6. PMID:23350787

Multiple cores of Gleason score 6 correlate with favourable findings at radical prostatectomy.

PubMed

Ellis, Carla L; Walsh, Patrick C; Partin, Alan W; Epstein, Jonathan I

2013-06-01

To establish whether the good prognosis of Gleason score 6 (GS6) is maintained in the setting of multiple involved cores. In total, 6156 men (from 1 April 2000 to 30 April 2007) with GS6 on biopsy underwent radical prostatectomy (RP) at our institution. The number of positive cores was correlated with the outcome at RP. More positive cores correlated with less organ-confined disease (P < 0.001), positive margins (P < 0.012), increasing RP grade (P < 0.001) and increased seminal vesicles/lymph node involvement (P = 0.012). For men with data available, the actuarial risk of being biochemically free of disease at 5 years was 93.2% when ≤6 cores were positive (812 men followed to 5 years) vs 89.1% if >6 cores were positive (41 men followed to 2 years) (P = 0.6). Although the predicted 'cure rate' of >75% probability of a tumour showing no evidence of biochemical recurrence at 10 years after RP was statistically different between cases with ≤6 vs >6 positive cores (P < 0.0001), the outcome in both groups was still favourable (90.5% vs 84%). Partin-like tables were generated factoring in the number of positive cores to predict organ-confined disease as a guide for urologists to perform nerve-sparing surgery. For example, with T1c disease, there was a ≥75% probability of organ-confined disease with one to three positive cores regardless of prostate-specific antigen (PSA) level, and the same probability was present with four to six positive cores and a PSA level of 0-4 ng/mL. A low Gleason score on biopsy is a powerful prognostic finding, such that this favourable outcome is maintained even in the setting of multiple positive cores with GS6. © 2013 BJU International.

The voice of Holland: Dutch public and patient's opinion favours single-port laparoscopy.

PubMed

Fransen, Sofie Af; Broeders, Epm; Stassen, Lps; Bouvy, Nd

2014-07-01

Single-port laparoscopy is prospected as the future of minimal invasive surgery. It is hypothesised to cause less post operative pain, with a shorter hospitalisation period and improved cosmetic results. Population- and patient-based opinion is important for the adaptation of new techniques. This study aimed to assess the opinion and perception of a healthy population and a patient population on single-port laparoscopy compared with conventional laparoscopy. An anonymous 33-item questionnaire, describing conventional and single-port laparoscopy, was given to 101 patients and 104 healthy volunteers. The survey participants (median age 44 years; range 17-82 years) were asked questions about their personal situation and their expectations and perceptions of the two different surgical techniques; conventional multi-port laparoscopy and single-port laparoscopy. A total of 72% of the participants had never heard of single-port laparoscopy before. The most important concern in both groups was the risk of surgical complications. When complication risks remain similar, 80% prefers single-port laparoscopy to conventional laparoscopy. When the risk of complications increases from 1% to 10%, 43% of all participants prefer single-port laparoscopy. A total of 70% of the participants are prepared to receive treatment in another hospital if single-port surgery is not performed in their hometown hospital. The preference for single-port approach was higher in the female population. Although cure and safety remain the main concerns, the population and patients group have a favourable perception of single-port surgery. The impact of public opinion and patient perception towards innovative techniques is undeniable. If the safety of the two different procedures is similar, this study shows a positive attitude of both participant groups in favour of single-port laparoscopy. However, solid scientific proof for the safety and feasibility of this new surgical technique needs to be obtained

Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis.

PubMed

Serce, Nuran Bektas; Boesl, Andreas; Klaman, Irina; von Serényi, Sonja; Noetzel, Erik; Press, Michael F; Dimmler, Arno; Hartmann, Arndt; Sehouli, Jalid; Knuechel, Ruth; Beckmann, Matthias W; Fasching, Peter A; Dahl, Edgar

2012-12-13

Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the

Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis

PubMed Central

2012-01-01

Background Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Methods Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. Results SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. Conclusions The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour

Colonic stem cell data are consistent with the immortal model of stem cell division under non-random strand segregation.

PubMed

Walters, K

2009-06-01

Colonic stem cells are thought to reside towards the base of crypts of the colon, but their numbers and proliferation mechanisms are not well characterized. A defining property of stem cells is that they are able to divide asymmetrically, but it is not known whether they always divide asymmetrically (immortal model) or whether there are occasional symmetrical divisions (stochastic model). By measuring diversity of methylation patterns in colon crypt samples, a recent study found evidence in favour of the stochastic model, assuming random segregation of stem cell DNA strands during cell division. Here, the effect of preferential segregation of the template strand is considered to be consistent with the 'immortal strand hypothesis', and explore the effect on conclusions of previously published results. For a sample of crypts, it is shown how, under the immortal model, to calculate mean and variance of the number of unique methylation patterns allowing for non-random strand segregation and compare them with those observed. The calculated mean and variance are consistent with an immortal model that incorporates non-random strand segregation for a range of stem cell numbers and levels of preferential strand segregation. Allowing for preferential strand segregation considerably alters previously published conclusions relating to stem cell numbers and turnover mechanisms. Evidence in favour of the stochastic model may not be as strong as previously thought.

Air pollution and emergency room visits for asthma in Santa Clara County, California.

PubMed Central

Lipsett, M; Hurley, S; Ostro, B

1997-01-01

During the winters of 1986-1987 through 1991-1992, rainfall throughout much of Northern California was subnormal, resulting in intermittent accumulation of air pollution, much of which was attributable to residential wood combustion (RWC). This investigation examined whether there was a relationship between ambient air pollution in Santa Clara County, California and emergency room visits for asthma during the winters of 1988-1989 through 1991-1992. Emergency room (ER) records from three acute-care hospitals were abstracted to compile daily visits for asthma and a control diagnosis (gastroenteritis) for 3-month periods during each winter. Air monitoring data included daily coefficient of haze (COH) and every-other-day particulate matter with aerodynamic diameter equal to or less than 10 microns (PM10, 24-hr average), as well as hourly nitrogen dioxide and ozone concentrations. Daily COH measurements were used to predict values for missing days of PM10 to develop a complete PM10 time series. Daily data were also obtained for temperature, precipitation, and relative humidity. In time-series analyses using Poisson regression, consistent relationships were found between ER visits for asthma and PM10. Same-day nitrogen dioxide concentrations were also associated with asthma ER visits, while ozone was not. Because there was a significant interaction between PM10 and minimum temperature in this data set, estimates of relative risks (RRs) for PM10-associated asthma ER visits were temperature-dependent. A 60 micrograms/m3 change in PM10 (2-day lag) corresponded to RRs of 1.43 (95% CI = 1.18-1.69) at 20 degrees F, representing the low end of the temperature distribution, 1.27 (95% CI = 1.13-1.42) at 30 degrees F, and 1.11 (95% CI = 1.03-1.19) at 41 degrees F, the mean of the observed minimum temperature. ER visits for gastroenteritis were not significantly associated with any pollutant variable. Several sensitivity analyses, including the use of robust regressions and of

Mesenchymal stem cells and cardiac repair

PubMed Central

Nesselmann, Catharina; Ma, Nan; Bieback, Karen; Wagner, Wolfgang; Ho, Anthony; Konttinen, Yrjö T; Zhang, Hao; Hinescu, Mihail E; Steinhoff, Gustav

2008-01-01

Accumulating clinical and experimental evidence indicates that mesenchymal stem cells (MSCs) are promising cell types in the treatment of cardiac dysfunction. They may trigger production of reparative growth factors, replace damaged cells and create an environment that favours endogenous cardiac repair. However, identifying mechanisms which regulate the role of MSCs in cardiac repair is still at work. To achieve the maximal clinical benefits, ex vivo manipulation can further enhance MSC therapeutic potential. This review focuses on the mechanism of MSCs in cardiac repair, with emphasis on ex vivo manipulation. PMID:18684237

Do Refuge Plants Favour Natural Pest Control in Maize Crops?

PubMed Central

Quispe, Reinaldo; Mazón, Marina; Rodríguez-Berrío, Alexander

2017-01-01

The use of non-crop plants to provide the resources that herbivorous crop pests’ natural enemies need is being increasingly incorporated into integrated pest management programs. We evaluated insect functional groups found on three refuges consisting of five different plant species each, planted next to a maize crop in Lima, Peru, to investigate which refuge favoured natural control of herbivores considered as pests of maize in Peru, and which refuge plant traits were more attractive to those desirable enemies. Insects occurring in all the plants, including the maize crop itself, were sampled weekly during the crop growing cycle, from February to June 2011. All individuals collected were identified and classified into three functional groups: herbivores, parasitoids, and predators. Refuges were compared based on their effectiveness in enhancing the populations of predator and parasitoid insects of the crop enemies. Refuges A and B were the most effective, showing the highest richness and abundance of both predators and parasitoids, including several insect species that are reported to attack the main insect pests of maize (Spodoptera frugiperda and Rhopalosiphum maidis), as well as other species that serve as alternative hosts of these natural enemies. PMID:28718835

Breaks in Pavement and Pipes as Indicators of Range-Front Faulting Resulting from the 1989 Loma Prieta Earthquake near the Southwest Margin of the Santa Clara Valley, California

USGS Publications Warehouse

Schmidt, Kevin M.; Ellen, Stephen D.; Haugerud, Ralph A.; Peterson, David M.; Phelps, Geoffery A.

1995-01-01

Damage to pavement and near-surface utility pipes, caused by the October 17, 1989, Loma Prieta earthquake, provide indicators for ground deformation in a 663 km2 area near the southwest margin of the Santa Clara Valley, California. The spatial distribution of 1284 sites of such damage documents the extent and distribution of detectable ground deformation. Damage was concentrated in four zones, three of which are near previously mapped faults. The zone through Los Gatos showed the highest concentration of damage, as well as evidence for pre- and post-earthquake deformation. Damage along the foot of the Santa Cruz Mountains reflected shortening that is consistent with movement along reverse faults in the region and with the hypothesis that tectonic strain is distributed widely across numerous faults in the California Coast Ranges.

An exploration of men's experiences of undergoing active surveillance for favourable-risk prostate cancer: A mixed methods study protocol.

PubMed

Ruane-McAteer, Eimear; O'Sullivan, Joe; Porter, Sam; Venderbos, Lionne; Prue, Gillian

2016-08-02

Prostate cancer is one of the most common male cancers worldwide. Active Surveillance (AS) has been developed to allow men with lower risk disease to postpone or avoid the adverse side effects associated with curative treatments until the disease progresses. Despite the medical benefits of AS, it is reported that living with untreated cancer can create a significant emotional burden for patients. The aim of this study is to gain insight into the experiences of men eligible to undergo AS for favourable-risk PCa. This study has a mixed-methods sequential explanatory design consisting of two phases: quantitative followed by qualitative. Phase 1 has a multiple point, prospective, longitudinal exploratory design. Ninety men diagnosed with favourable-risk prostate cancer will be assessed immediately post-diagnosis (baseline) and followed over a period of 12 months, in intervals of 3 month. Ninety age-matched men with no cancer diagnosis will also be recruited using peer nomination and followed up in the same 3 month intervals. Following completion of Phase 1, 10-15 AS participants who have reported both the best and worst psychological functioning will be invited to participate in semi-structured qualitative interviews. Phase 2 will facilitate further exploration of the quantitative results and obtain a richer understanding of participants' personal interpretations of their illness and psychological wellbeing. To our knowledge, this is the first study to utilise early baseline measures; include a healthy comparison group; calculate sample size through power calculations; and use a mixed methods approach to gain a deeper more holistic insight into the experiences of men diagnosed with favourable-risk prostate cancer.

Geologic, water-chemistry, and hydrologic data from multiple-well monitoring sites and selected water-supply wells in the Santa Clara Valley, California, 1999-2003

USGS Publications Warehouse

Newhouse, M.W.; Hanson, R.T.; Wentworth, C.M.; Everett, Rhett; Williams, C.F.; Tinsley, J.C.; Noce, T.E.; Carkin, B.A.

2004-01-01

To better identify the three-dimensional geohydrologic framework of the Santa Clara Valley, lithologic, geologic, geophysical, geomechanical, hydraulic, and water-chemistry data were collected from eight ground-water multiple-well monitoring sites constructed in Santa Clara County, California, as part of a series of cooperative studies between the U.S. Geological Survey and the Santa Clara Valley Water District. The data are being used to update and improve the three-dimensional geohydrologic framework of the basin and to address issues related to water supply, water chemistry, sequence stratigraphy, geology, and geological hazards. This report represents a compilation of data collected from 1999 to 2003, including location and design of the monitoring sites, cone penetrometer borings, geologic logs, lithologic logs, geophysical logs, core analysis, water-chemistry analysis, ground-water-level measurements, and hydraulic and geomechanical properties from wells and core samples. Exploratory cone penetrometer borings taken in the upper 17 to 130 feet at six of the monitoring sites identified the base of Holocene as no deeper than 75 feet in the central confined area and no deeper than 35 feet in the southern unconfined areas of the valley. Generalized lithologic characterization from the monitoring sites indicates about four to six different aquifer units separated by relatively fine-grained units occur within the alluvial deposits shallower than 860 feet deep. Analysis of geophysical logs indicates that coarse-grained units varied in thickness between 10 and 25 feet in the southeastern unconfined area of the valley and between 50 and 200 feet in the south-central and southwestern areas of the valley. Deviations from temperature-gradient logs indicate that the majority of horizontal ground-water flow occurs above a depth of 775 feet in the south central and above 510 feet in the southeastern areas of the valley. Bulk physical properties from more than 1,150 feet of

Simulated ground motion in Santa Clara Valley, California, and vicinity from M≥6.7 scenario earthquakes

USGS Publications Warehouse

Harmsen, Stephen C.; Hartzell, Stephen

2008-01-01

Models of the Santa Clara Valley (SCV) 3D velocity structure and 3D finite-difference software are used to predict ground motions from scenario earthquakes on the San Andreas (SAF), Monte Vista/Shannon, South Hayward, and Calaveras faults. Twenty different scenario ruptures are considered that explore different source models with alternative hypocenters, fault dimensions, and rupture velocities and three different velocity models. Ground motion from the full wave field up to 1 Hz is exhibited as maps of peak horizontal velocity and pseudospectral acceleration at periods of 1, 3, and 5 sec. Basin edge effects and amplification in sedimentary basins of the SCV are observed that exhibit effects from shallow sediments with relatively low shear-wave velocity (330 m/sec). Scenario earthquakes have been simulated for events with the following magnitudes: (1) M 6.8–7.4 Calaveras sources, (2) M 6.7–6.9 South Hayward sources, (3) M 6.7 Monte Vista/Shannon sources, and (4) M 7.1–7.2 Peninsula segment of the SAF sources. Ground motions are strongly influenced by source parameters such as rupture velocity, rise time, maximum depth of rupture, hypocenter, and source directivity. Cenozoic basins also exert a strong influence on ground motion. For example, the Evergreen Basin on the northeastern side of the SCV is especially responsive to 3–5-sec energy from most scenario earthquakes. The Cupertino Basin on the southwestern edge of the SCV tends to be highly excited by many Peninsula and Monte Vista fault scenarios. Sites over the interior of the Evergreen Basin can have long-duration coda that reflect the trapping of seismic energy within this basin. Plausible scenarios produce predominantly 5-sec wave trains with greater than 30 cm/sec sustained ground-motion amplitude with greater than 30 sec duration within the Evergreen Basin.

Intrapulmonary administration of CCL21 gene-modified dendritic cells reduces tumor burden in spontaneous murine bronchoalveolar cell carcinoma.

PubMed

Yang, Seok-Chul; Batra, Raj K; Hillinger, Sven; Reckamp, Karen L; Strieter, Robert M; Dubinett, Steven M; Sharma, Sherven

2006-03-15

The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing secondary lymphoid chemokine (CCL21) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. The transgenic mice (CC-10 TAg) express the SV40 large T antigen (TAg) under the Clara cell promoter, develop bilateral, multifocal, and pulmonary adenocarcinomas, and die at 4 months as a result of progressive pulmonary tumor burden. A single intratracheal administration of CCL21 gene-modified dendritic cells (DC-AdCCL21) led to a marked reduction in tumor burden with extensive mononuclear cell infiltration of the tumors. The reduction in tumor burden was accompanied by the enhanced elaboration of type 1 cytokines [IFN-gamma, interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor] and antiangiogenic chemokines (CXCL9 and CXCL10) but a concomitant decrease in the immunosuppressive molecules (IL-10, transforming growth factor-beta, prostaglandin E(2)) in the tumor microenvironment. The DC-AdCCL21 therapy group revealed a significantly greater frequency of tumor-specific T cells releasing IFN-gamma compared with the controls. Continuous therapy with weekly intranasal delivery of DC-AdCCL21 significantly prolonged median survival by >7 weeks in CC-10 TAg mice. Both innate natural killer and specific T-cell antitumor responses significantly increased following DC-AdCCL21 therapy. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of intrapulmonary-administered DC-AdCCL21 in regulation of tumor immunity and genetic immunotherapy for lung cancer.

Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission.

PubMed

Thomas, Xavier; de Botton, Stéphane; Chevret, Sylvie; Caillot, Denis; Raffoux, Emmanuel; Lemasle, Emilie; Marolleau, Jean-Pierre; Berthon, Céline; Pigneux, Arnaud; Vey, Norbert; Reman, Oumedaly; Simon, Marc; Recher, Christian; Cahn, Jean-Yves; Hermine, Olivier; Castaigne, Sylvie; Celli-Lebras, Karine; Ifrah, Norbert; Preudhomme, Claude; Terré, Christine; Dombret, Hervé

2017-04-10

Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment × SCT interaction term. Results At 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment × SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles. Conclusion These results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission.

Cell-Specific Oxidative Stress and Cytotoxicity after Wildfire Coarse Particulate Matter Instillation into Mouse Lung

PubMed Central

Williams, Keisha M.; Franzi, Lisa M.; Last, Jerold A.

2012-01-01

Our previous work has shown that coarse particulate matter (PM10-2.5) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24 hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stress in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At one hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1±3.2 pg/mL to 83.9±12.2 pg/mL was observed a half-hour after PM instillation. By one hour after PM instillation, isoprostane values had returned to 30.4±7.6pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1 hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.5-1 hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure. PMID:23142465

Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung.

PubMed

Williams, Keisha M; Franzi, Lisa M; Last, Jerold A

2013-01-01

Our previous work has shown that coarse particulate matter (PM(10-2.5)) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stress in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At 1hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1±3.2pg/mL to 83.9±12.2pg/mL was observed a half-hour after PM instillation. By 1hour after PM instillation, isoprostane values had returned to 30.4±7.6pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.5-1hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of tracer tests completed in 1999 and 2000 on the upper Santa Clara River, Los Angeles and Ventura Counties, California

USGS Publications Warehouse

Cox, Marisa H.; Mendez, Gregory O.; Kratzer, Charles R.; Reichard, Eric G.

2003-01-01

The interaction of surface water and hyporheic water along the Santa Clara River in Los Angeles and Ventura Counties, California, was evaluated by conducting tracer tests and analyzing water-quality data under different flow conditions in October 1999 and May 2000. Tracer and water-quality samples were collected at multiple river and hyporheic sites as well as at the Los Angeles County Sanitation Districts Saugus and Valencia Water Reclamation Plants. These water reclamation plants provide the main source of base flow in the river. Rhodamine WT dye was injected into the river to determine river traveltimes and to indicate when Lagrangian water-quality sampling could be performed at each site. Sodium bromide was injected into the river at a constant rate at the water reclamation plants to evaluate the surface-water and shallow ground-water interactions in the hyporheic zone. In the upper reach of the study area, which extends 2.9 river miles downstream from the Saugus Water Reclamation Plant, traveltime was 3.2 hours during May 2000. In the lower reach, which extends 14.1 river miles downstream from the Valencia Water Reclamation Plant, traveltime was 9.6 hours during October 1999 and 7.1 hours during May 2000. The sodium bromide tracer was detected at both hyporheic locations sampled during October 1999, and at two of the three hyporheic locations sampled during May 2000. On the basis of Rhodamine dye tests, flow curves were constructed from the discharge measurements in the Valencia reach. Flow-curve results indicate net gains in flow throughout most, but not all, of the upper parts of the reach and net losses in flow at the lower part of the reach. Lagrangian water-quality sampling provides information on the changes in chemistry as the water flows downstream from the water reclamation plants. Along both reaches there is an increase in sulfate (40-60 mg/L in the Saugus reach and 160 mg/L in the Valencia reach) and a decrease in chloride (about 45 mg/L in the

Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.

PubMed

Sharma, Sherven; Batra, Raj K; Yang, Seok Chul; Hillinger, Sven; Zhu, Li; Atianzar, Kimberly; Strieter, Robert M; Riedl, Karen; Huang, Min; Dubinett, Steven M

2003-11-01

The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing interleukin (IL)-7 (DC-AdIL-7) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg), expressing the SV40 large T antigen under the Clara cell promoter, develop bilateral multifocal pulmonary adenocarcinomas and die at 4 months as a result of progressive pulmonary tumor burden. Injection of DC-AdIL-7 in the axillary lymph node region (ALNR) weekly for 3 weeks led to a marked reduction in tumor burden with extensive lymphocytic infiltration of the tumors and enhanced survival. The antitumor responses were accompanied by the enhanced elaboration of interferon (IFN)-gamma and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-gamma-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-gamma (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-beta, prostaglandin E(2) (PGE(2)), and the proangiogenic modulator vascular endothelial growth factor (VEGF) decreased in response to DC-AdIL-7 treatment. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of DC-AdIL-7 in regulation of tumor immunity and its use in lung cancer genetic immunotherapy.

Reduced Ang2 expression in aging endothelial cells.

PubMed

Hohensinner, P J; Ebenbauer, B; Kaun, C; Maurer, G; Huber, K; Wojta, J

2016-06-03

Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. Copyright © 2016 Elsevier Inc. All rights reserved.

Identifying the environmental conditions favouring West Nile Virus outbreaks in Europe.

PubMed

Marcantonio, Matteo; Rizzoli, Annapaola; Metz, Markus; Rosà, Roberto; Marini, Giovanni; Chadwick, Elizabeth; Neteler, Markus

2015-01-01

West Nile Virus (WNV) is a globally important mosquito borne virus, with significant implications for human and animal health. The emergence and spread of new lineages, and increased pathogenicity, is the cause of escalating public health concern. Pinpointing the environmental conditions that favour WNV circulation and transmission to humans is challenging, due both to the complexity of its biological cycle, and the under-diagnosis and reporting of epidemiological data. Here, we used remote sensing and GIS to enable collation of multiple types of environmental data over a continental spatial scale, in order to model annual West Nile Fever (WNF) incidence across Europe and neighbouring countries. Multi-model selection and inference were used to gain a consensus from multiple linear mixed models. Climate and landscape were key predictors of WNF outbreaks (specifically, high precipitation in late winter/early spring, high summer temperatures, summer drought, occurrence of irrigated croplands and highly fragmented forests). Identification of the environmental conditions associated with WNF outbreaks is key to enabling public health bodies to properly focus surveillance and mitigation of West Nile virus impact, but more work needs to be done to enable accurate predictions of WNF risk.

Oxidative stress favours herpes virus infection in vertebrates: a meta-analysis.

PubMed

Sebastiano, Manrico; Chastel, Olivier; de Thoisy, Benoît; Eens, Marcel; Costantini, David

2016-08-01

Herpes viruses are responsible for a variety of pathological effects in humans and in both wild and domestic animals. One mechanism that has been proposed to facilitate replication and activity of herpes viruses is oxidative stress (OS). We used meta-analytical techniques to test the hypotheses that (1) herpes virus infection causes OS and (2) supplementation of antioxidants reduces virus load, indicating that replication is favoured by a state of OS. Results based on studies on mammals, including humans, and birds show that (1) OS is indeed increased by herpes virus infection across multiple tissues and species, (2) biomarkers of OS may change differently between tissues, and (3) the effect size does not differ among different virus strains. In addition, the increase of oxidative damage in blood (tissue commonly available in ecological studies) was similar to that in the tissues most sensitive to the herpes virus. Our results also show that administration of antioxidants reduces virus yield, indicating that a condition of OS is favorable for the viral replication. In addition, some antioxidants may be more efficient than others in reducing herpes virus yield. Our results point to a potential mechanism linking herpes virus infection to individual health status.

Reach-scale channel sensitivity to multiple human activities and natural events: Lower Santa Clara River, California, USA

NASA Astrophysics Data System (ADS)

Downs, Peter W.; Dusterhoff, Scott R.; Sears, William A.

2013-05-01

Understanding the cumulative impact of natural and human influences on the sensitivity of channel morphodynamics, a relative measure between the drivers for change and the magnitude of channel response, requires an approach that accommodates spatial and temporal variability in the suite of primary stressors. Multiple historical data sources were assembled to provide a reach-scale analysis of the lower Santa Clara River (LSCR) in Ventura County, California, USA. Sediment supply is naturally high due to tectonic activity, earthquake-generated landslides, wildfires, and high magnitude flow events during El Niño years. Somewhat typically for the region, the catchment has been subject to four reasonably distinct land use and resource management combinations since European-American settlement. When combined with analysis of channel morphological response (quantifiable since ca. 1930), reach-scale and temporal differences in channel sensitivity become apparent. Downstream reaches have incised on average 2.4 m and become narrower by almost 50% with changes focused in a period of highly sensitive response after about 1950 followed by forced insensitivity caused by structural flood embankments and a significant grade control structure. In contrast, the middle reaches have been responsive but are morphologically resilient, and the upstream reaches show a mildly sensitive aggradational trend. Superimposing the natural and human drivers for change reveals that large scale stressors (related to ranching and irrigation) have been replaced over time by a suite of stressors operating at multiple spatial scales. Lower reaches have been sensitive primarily to 'local' scale impacts (urban growth, flood control, and aggregate mining) whereas, upstream, catchment-scale influences still prevail (including flow regulation and climate-driven sediment supply factors). These factors illustrate the complexity inherent to cumulative impact assessment in fluvial systems, provide evidence for a

Upweighting rare favourable alleles increases long-term genetic gain in genomic selection programs.

PubMed

Liu, Huiming; Meuwissen, Theo H E; Sørensen, Anders C; Berg, Peer

2015-03-21

The short-term impact of using different genomic prediction (GP) models in genomic selection has been intensively studied, but their long-term impact is poorly understood. Furthermore, long-term genetic gain of genomic selection is expected to improve by using Jannink's weighting (JW) method, in which rare favourable marker alleles are upweighted in the selection criterion. In this paper, we extend the JW method by including an additional parameter to decrease the emphasis on rare favourable alleles over the time horizon, with the purpose of further improving the long-term genetic gain. We call this new method dynamic weighting (DW). The paper explores the long-term impact of different GP models with or without weighting methods. Different selection criteria were tested by simulating a population of 500 animals with truncation selection of five males and 50 females. Selection criteria included unweighted and weighted genomic estimated breeding values using the JW or DW methods, for which ridge regression (RR) and Bayesian lasso (BL) were used to estimate marker effects. The impacts of these selection criteria were compared under three genetic architectures, i.e. varying numbers of QTL for the trait and for two time horizons of 15 (TH15) or 40 (TH40) generations. For unweighted GP, BL resulted in up to 21.4% higher long-term genetic gain and 23.5% lower rate of inbreeding under TH40 than RR. For weighted GP, DW resulted in 1.3 to 5.5% higher long-term gain compared to unweighted GP. JW, however, showed a 6.8% lower long-term genetic gain relative to unweighted GP when BL was used to estimate the marker effects. Under TH40, both DW and JW obtained significantly higher genetic gain than unweighted GP. With DW, the long-term genetic gain was increased by up to 30.8% relative to unweighted GP, and also increased by 8% relative to JW, although at the expense of a lower short-term gain. Irrespective of the number of QTL simulated, BL is superior to RR in maintaining

[Regulation of age-dependent phenomena. Influence of C6-substituted purines on cell aggregation and cell migration in primary cultures of lense epithelial cells].

PubMed

Glässer, D; Iwig, M; Weber, E

1975-01-01

The existence of an age dependent latent period of cell emigration has been proved in the primary culture of epithelial cells of bovine lenses. The previously described aggregation phenomenon as well as the latent period of the cell emigration increase with the age of the sponsor animals. Extracellular adenine and other C6-substituted purines, isolated from the cells themselves and added to the medium, act the same way on the lens cells in the primary culture as the increasing age of the sponsor animals. Adenine stimulates cell aggregation and inhibits the adhesion of the cells to the substratum, the cell flattening and the cell migration. The adenine action has been proved down to a concentration of 3 X 10(-6) M. During the primary culture, the lens cells gradually los the adenine sensitivity. The adenine action also occurs on single cells, isolated by trypsination, it differs from the reaction of ouabain and can be removed at low concentration by washing procedures. The results favour the suggestion C6-substituted purines to be involved in cell ageing.

(Why) Does Evolution Favour Embryogenesis?

PubMed

Rensing, Stefan A

2016-07-01

Complex multicellular organisms typically possess life cycles in which zygotes (formed by gamete fusion) and meiosis occur. Canonical animal embryogenesis describes development from zygote to birth. It involves polarisation of the egg/zygote, asymmetric cell divisions, establishment of axes, symmetry breaking, formation of organs, and parental nutrition (at least in early stages). Similar developmental patterns have independently evolved in other eukaryotic lineages, including land plants and brown algae. The question arises whether embryo-like structures and associated developmental processes recurrently emerge because they are local optima of the evolutionary landscape. To understand which evolutionary principles govern complex multicellularity, we need to analyse why and how similar processes evolve convergently - von Baer's and Haeckel's phylotypic stage revisited in other phyla. Copyright © 2016 Elsevier Ltd. All rights reserved.

Silk fibroin scaffolds enhance cell commitment of adult rat cardiac progenitor cells.

PubMed

Di Felice, Valentina; Serradifalco, Claudia; Rizzuto, Luigi; De Luca, Angela; Rappa, Francesca; Barone, Rosario; Di Marco, Patrizia; Cassata, Giovanni; Puleio, Roberto; Verin, Lucia; Motta, Antonella; Migliaresi, Claudio; Guercio, Annalisa; Zummo, Giovanni

2015-11-01

The use of three-dimensional (3D) cultures may induce cardiac progenitor cells to synthesize their own extracellular matrix (ECM) and sarcomeric proteins to initiate cardiac differentiation. 3D cultures grown on synthetic scaffolds may favour the implantation and survival of stem cells for cell therapy when pharmacological therapies are not efficient in curing cardiovascular diseases and when organ transplantation remains the only treatment able to rescue the patient's life. Silk fibroin-based scaffolds may be used to increase cell affinity to biomaterials and may be chemically modified to improve cell adhesion. In the present study, porous, partially orientated and electrospun nanometric nets were used. Cardiac progenitor cells isolated from adult rats were seeded by capillarity in the 3D structures and cultured inside inserts for 21 days. Under this condition, the cells expressed a high level of sarcomeric and cardiac proteins and synthesized a great quantity of ECM. In particular, partially orientated scaffolds induced the synthesis of titin, which is a fundamental protein in sarcomere assembly. Copyright © 2013 John Wiley & Sons, Ltd.

Cell Division and Evolution of Biological Tissues

NASA Astrophysics Data System (ADS)

Rivier, Nicolas; Arcenegui-Siemens, Xavier; Schliecker, Gudrun

A tissue is a geometrical, space-filling, random cellular network; it remains in this steady state while individual cells divide. Cell division (fragmentation) is a local, elementary topological transformation which establishes statistical equilibrium of the structure. Statistical equilibrium is characterized by observable relations (Lewis, Aboav) between cell shapes, sizes and those of their neighbours, obtained through maximum entropy and topological correlation extending to nearest neighbours only, i.e. maximal randomness. For a two-dimensional tissue (epithelium), the distribution of cell shapes and that of mother and daughter cells can be obtained from elementary geometrical and physical arguments, except for an exponential factor favouring division of larger cells, and exponential and combinatorial factors encouraging a most symmetric division. The resulting distributions are very narrow, and stationarity severely restricts the range of an adjustable structural parameter

Gut microbiota modulate T cell trafficking into human colorectal cancer.

PubMed

Cremonesi, Eleonora; Governa, Valeria; Garzon, Jesus Francisco Glaus; Mele, Valentina; Amicarella, Francesca; Muraro, Manuele Giuseppe; Trella, Emanuele; Galati-Fournier, Virginie; Oertli, Daniel; Däster, Silvio Raffael; Droeser, Raoul A; Weixler, Benjamin; Bolli, Martin; Rosso, Raffaele; Nitsche, Ulrich; Khanna, Nina; Egli, Adrian; Keck, Simone; Slotta-Huspenina, Julia; Terracciano, Luigi M; Zajac, Paul; Spagnoli, Giulio Cesare; Eppenberger-Castori, Serenella; Janssen, Klaus-Peter; Borsig, Lubor; Iezzi, Giandomenica

2018-02-06

Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Favourable rotational alignment outcomes in PSI knee arthroplasty: A Level 1 systematic review and meta-analysis.

PubMed

Mannan, A; Smith, T O

2016-03-01

Implant malposition in total knee arthroplasty (TKA) often results in unsatisfactory outcomes. Rotational malalignment leads to impaired patellar tracking, stability and joint biomechanics. Patient-specific instrumentation aims to improve three-dimensional implant positioning while reducing overall costs of instrumentation. A PRISMA compliant search of all relevant literature between 2000 and 2014 was performed. The primary outcome of interest was deviation from a neutral femoral and tibial axial alignment of patient-specific instrumentation (PSI) vs conventional instrumentation. Femoral rotation was measured with reference to the transepicondylar axis. Tibial rotation was reported with reference to the anterior tibial tuberosity and a "best fit" with the anterior tibial cortex. Six randomised studies met the inclusion criteria reporting on a total of 444 knees. Computed tomography (CT) based PSI systems were used exclusively in three studies, and two further studies in association with magnetic resonance imaging (MRI). MRI was used exclusively in one study. Mean femoral rotation in the conventional group was: -1.7 to 1.6° (vs -1.7 to 1° in the PSI group). Meta-analysis demonstrated a significant treatment effect favouring PSI with increased accuracy in "three-degree outliers" with femoral rotation: Z=2.07, P=0.04. A single study reported tibial rotational outcomes with no significant difference demonstrated in conventional instrumentation vs PSI. This Level 1 meta-analysis demonstrates favourable femoral rotational alignment outcomes in PSI knee arthroplasty. Only limited data is available for tibial rotational outcomes. Further studies with standardised "gold-standard" measurement criteria are required to clarify tibial rotational outcomes in PSI TKA. 1. Copyright © 2015 Elsevier B.V. All rights reserved.

Is pollen removal or seed set favoured by flower longevity in a hummingbird-pollinated Salvia species?

PubMed Central

Aximoff, Izar Araujo; Freitas, Leandro

2010-01-01

Background and Aims The period between the beginning of anthesis and flower senescence modulates the transport of pollen by pollinators among conspecific flowers, and its length may therefore influence reproductive success. This study evaluated whether floral longevity favours pollen removal from the anthers over fecundity (seed set) in an ornithophilous species that does not undergo pollen limitation. Methods Field investigations were conducted on floral longevity, nectar production, pollinator behaviour, and variations in fruit set (FS), mean number of seeds per fruit (MSF) and pollen removal by hummingbirds (PR) during the anthesis of Salvia sellowiana in south-east Brazil. Key Results Anthesis of flowers exposed to pollinators lasted 4 d, as well as on flowers with pollen removed from the anthers or deposited on the stigma. The longevity of bagged flowers was significantly higher (approx. 9 d). FS and PR reached 87·2 and 90 %, respectively, in natural conditions. PR increased gradually over the period of anthesis; however, FS and MSF reached their maxima in the first hours of anthesis. Nectar production was continuous, but the secretion rate was reduced after pollination. The removal of nectar from non-pollinated flowers stimulated its production. Conclusions The longevity of anthesis in S. sellowiana seems to be related to the mechanism of gradual dispensing of pollen, resulting in greater male reproductive success. This is in agreement with the pollen-donation hypothesis. The small number of ovules (four) of S. sellowiana and the high frequency and the foraging mode of its pollinators may favour the selection for floral longevity driven by male fitness in this system. PMID:20622254

Hydrodynamic patterns favouring sea urchin recruitment in coastal areas: A Mediterranean study case.

PubMed

Farina, S; Quattrocchi, G; Guala, I; Cucco, A

2018-05-11

In invertebrate fisheries, sea urchin harvesting continues to grow with dramatic consequences for benthic ecosystems. The identification of areas with a marked natural recruitment and the mechanisms regulating it is crucial for the conservation of benthic communities and for planning the sustainable harvesting. This study evaluates the spatial distribution and density of recruits of the edible sea urchin Paracentrotus lividus along the Sinis + Peninsula (Sardinia) and explores its significant relationships with the local oceanographic features. Our results reveal that recruitment is favoured in areas with slow currents and high levels of confinement and trapping of the water masses. Analysis of the residual circulation indicates that the presence of local standing circulation structures promotes the sea urchin recruitment process. Our findings emphasize the importance of managing local sea urchin harvesting as a system of populations with their demographic influence mainly dependent on the most important ecological driver that is the recruitment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Psychosocial group rehabilitation for lonely older people: favourable processes and mediating factors of the intervention leading to alleviated loneliness.

PubMed

Savikko, Niina; Routasalo, Pirkko; Tilvis, Reijo; Pitkälä, Kaisu

2010-03-01

Loneliness among community-dwelling older people is a common problem, with serious health consequences. The favourable processes and mediating factors of a psychosocial group rehabilitation intervention in alleviating older people's loneliness were evaluated. Altogether, 117 lonely, home-dwelling individuals (aged ≥75 years) participated in a psychosocial group rehabilitation intervention. The content comprised (i) art and inspiring activities, (ii) group exercise and discussions or (iii) therapeutic writing and group therapy. The psychosocial group rehabilitation intervention was evaluated from the group leaders' diaries and by observing the groups. Experiences of loneliness and social participation were collected by postintervention questionnaires from the participants. Data were analysed using methodological triangulation. Doing things together and sharing experiences with their peers inspired lively discussions, created a feeling of togetherness and led to participants' empowerment and increased self-esteem. The intervention socially activated the participants, and their feelings of loneliness had been alleviated during the intervention. Several common favourable processes and mediating factors were identified in the psychosocial group rehabilitation intervention that led to alleviation of loneliness among older people. Relevance to clinical practice.  The psychosocial group rehabilitation intervention gives nurses an effective tool to support older people's psychosocial resources by activating them and alleviating their loneliness. © 2009 Blackwell Publishing Ltd.

A Survey of Italian Physicians' Opinion about Stem Cells Research: What Doctors Prefer and What the Law Requires

PubMed Central

Frati, Paola; Pacchiarotti, Arianna; D'Errico, Stefano

2014-01-01

To evaluate the Italian physicians' knowledge/information level about the therapeutic potential of stem cells, the research choice between embryonic and cordonal stem cells, and the preference between autologous and heterologous storage of cordonal stem cells, we performed a national survey. The questionnaire—distributed to 3361 physicians—involved physicians of different religious orientations and of different medical specialities. Most of the physicians involved (67%) were Catholics, and the majority were gynaecologists and paediatricians (43%) who are mainly in charge to inform future mothers about the possibility of cordonal stem cells conservation. The majority of the physicians interviewed do not have specific knowledge about stem cells (59%), most of them having only generic information (92%). The largest part of physicians prefer to use umbilical cord blood cells rather than embryonic stem cells. Nevertheless, a large percentage of physicians were in favour of embryo research, especially when embryos are supernumerary (44% versus 34%). Eighty-seven % of the physicians interviewed proved to have a general knowledge about stem cells and believe in their therapeutic potential. They prefer research on cordonal stem cells rather than on embryo stem cells. Although they are in favour of heterologous stem cells donation, they still prefer cryopreservation for personal use. PMID:24877099

Reduced Ang2 expression in aging endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at; Ebenbauer, B.; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna

Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of agingmore » before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.« less

[A case of favourable outcome of severe acute intoxication with an animal poison after a bite by the monocled cobra].

PubMed

Livanov, G A; Batotsyrenkov, B V; Lodiagin, A N; Andrianov, A Iu; Kuznetsov, O A; Loladze, A T; Baranov, D V

2014-01-01

This paper reports a case of severe acute intoxication with an animal poison after a bite by the monocled cobra. Combined treatment including artificial lung ventilation, infusion-detoxication and desensitizing (hormonal) therapy, hemosorption, correction of metabolic disorders with cytoflavin, antibacterial therapy had positive effect on the patient's condition and ensured the favourable outcome ofpotentially lethal poisoning without the use ofa specific anti-snake venom serum.

Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease

PubMed Central

Mendez, Ivar; Sanchez-Pernaute, Rosario; Cooper, Oliver; Viñuela, Angel; Ferrari, Daniela; Björklund, Lars; Dagher, Alain; Isacson, Ole

2008-01-01

We report the first post-mortem analysis of two patients with Parkinson’s disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive 18F-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (n = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3–4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation. PMID:15872020

Using Spring Water Nitrate to Monitor Spatiotemporal Trends in Nitrogen Deposition for the Santa Clara Valley Habitat Plan

NASA Astrophysics Data System (ADS)

Weiss, S. B.; Hastings, M. G.

2016-12-01

Atmospheric nitrogen deposition is a major acute threat to biodiversity, but has rarely been addressed in regulatory conservation plans. The Santa Clara Valley Habitat Plan is a Habitat Conservation Plan/Natural Communities Conservation Plan (HCP/NCCP) that addresses development impacts on 19 covered species, most of which inhabit nutrient-poor serpentine grasslands that are highly sensitive to N-deposition with a critical load of 6 kg-N ha-1 year-1. Increased N-deposition from highway improvements and development was a major regulatory nexus, and a novel nitrogen fee based on car trips generated is one of the funding mechanisms, driving a need for cost-effective and robust monitoring of N-deposition trends over the 50-year plan and beyond. In the high deposition zone (10-20 kg-N ha-1 year-1), spring water nitrate levels up to 25 ppm (as NO3-) were measured in baseflow, levels higher than any reported for non-agricultural sites in California. Nitrate measurements follow measured and modeled deposition gradients, and are affected by catchment soils, geomorphology, and vegetation. Existing knowledge of local nitrogen deposition using passive samplers, CMAQ models, N-cycling measurements, and emissions inventories/projections are used to generate hypotheses that can be tested with a combination of spring water nitrate sampled through the year and across deposition gradients, N and O isotopic analysis including 17O to trace atmospheric nitrate, modeled recharge rates, and groundwater dating. A set of sentinel springs for long-term monitoring will be identified and sampled on an interval commensurate with shallow groundwater residence times. The unique characteristics of serpentine grasslands (low productivity, shallow soils, highly fractured bedrock, and numerous springs) provide a model system for tracing N-deposition and its effects on protected species.

First Report of Awake Craniotomy of a Famous Musician: Suprasellar Tumor Surgery of Pianist Clara Haskil in 1942.

PubMed

Gasenzer, Elena Romana; Kanat, Ayhan; Neugebauer, Edmund A M

2017-05-01

Clara Haskil (January 7, 1895-December 7, 1960) was one of the most famous female pianists of the 20th century. In her life and work she set new standards in piano playing. However, her career was beset by poor health and the adversities of two world wars. In her lifetime Haskil had three major disorders: juvenile scoliosis requiring treatment in her adolescence, a tumor of the sellar region requiring surgery at age 47 years, and a traumatic brain injury causing her death at the age of 65. Her medical history illustrates the development of surgical methods and rehabilitation in medicine before and after World War II. At an early age, she spent a year in a nursing home for orthopedic diseases due to scoliosis. In 1942, when she was 47 years old, she displayed the first symptoms of a suprasellar brain tumor: headache and hemianopsia. The famous surgeon Marcel David performed surgery on her without general anesthesia while Haskil mentally played a Mozart piano concerto as a neuronal representation to control her memory and mental abilities. Only 3 months after that operation she played a Mozart piano concerto at a concert that began her career as a great interpreter of Mozart. Her neurologic rehabilitation was remarkable and highlighted new methods in the field. In 1960, she traveled to Brussels for a concert. In the train station she stumbled on the stairs and hit her head on one of the steps. Skull fracture and intracranial hematoma were diagnosed. Doctors tried to operate on her but she lost consciousness and died. Haskil created new styles in piano playing, and her medical history offers indications of new concepts in neurosurgery. Georg Thieme Verlag KG Stuttgart · New York.

Ground-water/surface-water responses to global climate simulations, Santa Clara-Calleguas basin, Ventura County, California, 1950-93

USGS Publications Warehouse

Hanson, Randall T.; Dettinger, Michael D.

2005-01-01

Climate variations can play an important, if not always crucial, role in successful conjunctive management of ground water and surface water resources. This will require accurate accounting of the links between variations in climate, recharge, and withdrawal from the resource systems, accurate projection or predictions of the climate variations, and accurate simulation of the responses of the resource systems. To assess linkages and predictability of climate influences on conjunctive management, global climate model (GCM) simulated precipitation rates were used to estimate inflows and outflows from a regional ground water model (RGWM) of the coastal aquifers of the Santa Clara-Calleguas Basin at Ventura, California, for 1950 to 1993. Interannual to interdecadal time scales of the El Niño Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) climate variations are imparted to simulated precipitation variations in the Southern California area and are realistically imparted to the simulated ground water level variations through the climate-driven recharge (and discharge) variations. For example, the simulated average ground water level response at a key observation well in the basin to ENSO variations of tropical Pacific sea surface temperatures is 1.2 m/°C, compared to 0.9 m/°C in observations. This close agreement shows that the GCM-RGWM combination can translate global scale climate variations into realistic local ground water responses. Probability distributions of simulated ground water level excursions above a local water level threshold for potential seawater intrusion compare well to the corresponding distributions from observations and historical RGWM simulations, demonstrating the combination's potential usefulness for water management and planning. Thus the GCM-RGWM combination could be used for planning purposes and — when the GCM forecast skills are adequate — for near term predictions.

Protist predation can favour cooperation within bacterial species

PubMed Central

Friman, Ville-Petri; Diggle, Stephen P.; Buckling, Angus

2013-01-01

Here, we studied how protist predation affects cooperation in the opportunistic pathogen bacterium Pseudomonas aeruginosa, which uses quorum sensing (QS) cell-to-cell signalling to regulate the production of public goods. By competing wild-type bacteria with QS mutants (cheats), we show that a functioning QS system confers an elevated resistance to predation. Surprisingly, cheats were unable to exploit this resistance in the presence of cooperators, which suggests that resistance does not appear to result from activation of QS-regulated public goods. Instead, elevated resistance of wild-type bacteria was related to the ability to form more predation-resistant biofilms. This could be explained by the expression of QS-regulated resistance traits in densely populated biofilms and floating cell aggregations, or alternatively, by a pleiotropic cost of cheating where less resistant cheats are selectively removed from biofilms. These results show that trophic interactions among species can maintain cooperation within species, and have further implications for P. aeruginosa virulence in environmental reservoirs by potentially enriching the cooperative and highly infective strains with functional QS system. PMID:23945212

VIP modulates the pro-inflammatory maternal response, inducing tolerance to trophoblast cells

PubMed Central

Fraccaroli, Laura; Alfieri, Julio; Larocca, Luciana; Calafat, Mario; Roca, Valeria; Lombardi, Eduardo; Ramhorst, Rosanna; Leirós, Claudia Pérez

2009-01-01

Background and purpose Successful embryo implantation is followed by a local pro-inflammatory and Th1 response, subsequently controlled by a Th2 response. Vasoactive intestinal peptide (VIP) has anti-inflammatory effects and promotes tolerogenic/Th2 responses while favouring embryonic development. We investigated the potential regulatory role of VIP on human trophoblast cells, maternal pro-inflammatory responses and trophoblast-maternal leukocyte interactions. Experimental approach We tested VIP effects directly on a trophoblast cell line (Swan 71 cells) and after co-culture with maternal peripheral blood mononuclear cells (PBMCs) as models of the feto-maternal dialogue. We also co-cultured maternal and paternal PBMCs to test effects of endogenous VIP on maternal alloresponses. Key results Swan 71 cells express VPAC1 receptors and VIP induced their proliferation and the expression of leukaemia inhibitor factor, a pro-implantatory marker. After interaction with trophoblast cells, VIP increased Foxp3, the proportion of CD4+CD25+Foxp3+ cells within maternal PBMCs and transforming growth factor β expression. Also, during the trophoblast-maternal PBMCs interaction, VIP reduced pro-inflammatory mediators [interleukin (IL)-6, monocyte chemoattractant protein 1, nitric oxide], while increasing IL-10. Trophoblast cells produced VIP which dose-dependently suppressed allomaternal responses, accompanied by reduced expression of the T cell transcription factor, T-bet. Conclusions and implications Vasoactive intestinal peptide induced pro-implantatory markers and trophoblast cell proliferation, while controlling the initial pro-inflammatory response, by increasing maternal regulatory T cells and anti-inflammatory cytokines. As an autocrine regulatory peptide VIP might contribute to fetal survival through two mechanisms; a direct trophic effect on trophoblast cells and an immunomodulatory effect that favours tolerance to fetal antigens. PMID:19133995

Atherosclerosis is a vascular stem cell disease caused by insulin.

PubMed

Traunmüller, Friederike

2018-07-01

The present article proposes the hypothesis that when multipotent vascular stem cells are exposed to excessive insulin in a rhythmic pattern of sharply rising and falling concentrations, their differentiation is misdirected toward adipogenic and osteogenic cell lineages. This results in plaque-like accumulation of adipocytes with fat and cholesterol deposition from adipocyte debris, and osteogenic (progenitor) cells with a calcified matrix in advanced lesions. The ingrowth of capillaries and infiltration with macrophages, which upon uptake of lipids turn into foam cells, are unspecific pro-resolving reactions. Epidemiological, histopathological, pharmacological, and experimental evidence in favour of this hypothesis is summarised. Copyright © 2018. Published by Elsevier Ltd.

Can favourable psychosocial working conditions in midlife moderate the risk of work exit for chronically ill workers? A 20-year follow-up of the Whitehall II study.

PubMed

Fleischmann, Maria; Carr, Ewan; Stansfeld, Stephen A; Xue, Baowen; Head, Jenny

2018-03-01

To investigate if favourable psychosocial working conditions can reduce the risk of work exit and specifically for workers with chronic disease. Men and women (32%) aged 35-55, working and having no chronic disease at baseline of the Whitehall II study of London-based civil servants were selected (n=9040). We observed participants' exit from work through retirement, health-related exit and unemployment, new diagnosis of chronic disease (ie, coronary heart disease, diabetes, stroke and cancer) and their psychosocial working conditions in midlife. Using cause-specific Cox models, we examined the association of chronic disease and favourable psychosocial working conditions and their interaction, with the three types of work exit. We adjusted for gender, occupational grade, educational level, remaining in civil service, spouse's employment status and mental health. Chronic disease significantly increased the risk of any type of work exit (HR 1.27) and specifically the risk of health-related exit (HR 2.42). High skill discretion in midlife reduced the risk of any type of work exit (HR 0.90), retirement (HR 0.91) and health-related exit (HR 0.68). High work social support in midlife decreased the risk of health-related exit (HR 0.79) and unemployment (HR 0.71). Favourable psychosocial working conditions in midlife did not attenuate the association between chronic disease and work exit significantly. The chronically ill have increased risks of work exit, especially through health-related exit routes. Chronic disease is an obstacle to extended working lives. Favourable working conditions directly relate to reduced risks of work exit. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effect of TRAIL molecule on cell viability in in vitro beta cell culture.

PubMed

Tekmen, I; Ozyurt, D; Pekçetin, C; Buldan, Z

2007-06-01

Insulin-dependent diabetes mellitus (IDDM) is an organ-specific autoimmune disorder triggered by autoreactive T cells directed to pancreas beta-cell antigens. In this disorder, more than 90% of beta cells are destroyed. Cell death may be mediated via soluble or membrane-bound cell death ligands. One of these ligands may be tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-alpha superfamily. In the present study, we examined whether TRAIL had cytotoxic effects on adult rat pancreas beta cell cultures and INS1-E rat insulinoma cell line cultures or not. In this study, cell destruction models were built with TRAIL concentrations of 10, 100 and 1000 ng. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used for evaluating cell viability. It was detected that cell cultures with TRAIL added showed no differences statistically when compared with control cultures containing no toxic additions. These results showed that TRAIL did not have significant cytotoxic effects on pancreas beta cell culture and INS-1E rat insulinoma cell line cultures. Detection of the expression of TRAIL receptors and natural apoptosis inhibitor proteins will be favourable to investigate the resistance mechanisms to TRAIL-induced cell death in this cell culture system.

Morphometry, ultrastructure, myosin isoforms, and metabolic capacities of the "mini muscles" favoured by selection for high activity in house mice.

PubMed

Guderley, Helga; Houle-Leroy, Philippe; Diffee, Gary M; Camp, Dana M; Garland, Theodore

2006-07-01

Prolonged selective breeding of mice (Mus musculus) for high levels of voluntary wheel running has favoured an unusual phenotype ("mini muscles"), apparently caused by a single Mendelian recessive allele, in which most hind-limb muscles are markedly reduced in mass, but have increased mass-specific activities of mitochondrial enzymes. We examined whether these changes reflect changes in fibre size, number or ultrastructure in normal and "mini-muscle" mice within the two (of four) selectively bred lines (lab designations L3 and L6) that exhibit the phenotype at generations 26 and 27. In both lines, the gastrocnemius and plantaris muscles are smaller in mass (by >50% and 20%, respectively) in affected individuals. The mass-specific activities of mitochondrial enzymes in the gastrocnemius and plantaris muscles were increased in the mini phenotype in both lines, with stronger effects in the gastrocnemius muscle. In the gastrocnemius, the % myosin heavy chain (MHC) IIb was reduced by 50% in L3 and by 30% in L6, whereas the % MHC IIa and I were higher, particularly in L3. Fibre number in the plantaris muscle did not significantly differ between mini and normal muscles, although muscle mass was a significant positive correlate of fibre number. Small fibres were more abundant in mini than normal muscles in L3. Mitochondrial volume density was significantly higher in mini than normal muscle fibres in L3, but not in L6. Microscopy revealed a surprising attribute of the mini muscles: an abundance of small, minimally differentiated, myofibril-containing cells positioned in a disorderly fashion, particularly in the surface layer. We hypothesise that these unusual cells may be satellite cells or type IIb fibres that did not complete their differentiation. Together, these observations suggest that mice with the mini phenotype have reduced numbers of type IIb fibres in many of their hind-limb muscles, leading to a decrease in mass and an increase in mass-specific aerobic capacity

Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte-dendritic cell cross-talk.

PubMed

Cabillic, F; Bouet-Toussaint, F; Toutirais, O; Rioux-Leclercq, N; Fergelot, P; de la Pintière, C Thomas; Genetet, N; Patard, J-J; Catros-Quemener, V

2006-12-01

Anti-tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC-Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC-Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide +/- heat shock (Tu H(2)O(2) +/- HS) treated cells. DC-Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)-6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL-6 levels (n = 4), DC-Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H(2)O(2) + HS, DC-Tu stimulation resulted in improved CTL activity. H(2)O(2) + HS treatment induced post-apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL-6, VEGF, transforming growth factor (TGF)-beta1] and induced HSP70 expression. Taken together, data show that reduction in IL-6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti-tumour CTL response.

Analysis of seismic waves crossing the Santa Clara Valley using the three-component MUSIQUE array algorithm

NASA Astrophysics Data System (ADS)

Hobiger, Manuel; Cornou, Cécile; Bard, Pierre-Yves; Le Bihan, Nicolas; Imperatori, Walter

2016-10-01

We introduce the MUSIQUE algorithm and apply it to seismic wavefield recordings in California. The algorithm is designed to analyse seismic signals recorded by arrays of three-component seismic sensors. It is based on the MUSIC and the quaternion-MUSIC algorithms. In a first step, the MUSIC algorithm is applied in order to estimate the backazimuth and velocity of incident seismic waves and to discriminate between Love and possible Rayleigh waves. In a second step, the polarization parameters of possible Rayleigh waves are analysed using quaternion-MUSIC, distinguishing retrograde and prograde Rayleigh waves and determining their ellipticity. In this study, we apply the MUSIQUE algorithm to seismic wavefield recordings of the San Jose Dense Seismic Array. This array has been installed in 1999 in the Evergreen Basin, a sedimentary basin in the Eastern Santa Clara Valley. The analysis includes 22 regional earthquakes with epicentres between 40 and 600 km distant from the array and covering different backazimuths with respect to the array. The azimuthal distribution and the energy partition of the different surface wave types are analysed. Love waves dominate the wavefield for the vast majority of the events. For close events in the north, the wavefield is dominated by the first harmonic mode of Love waves, for farther events, the fundamental mode dominates. The energy distribution is different for earthquakes occurring northwest and southeast of the array. In both cases, the waves crossing the array are mostly arriving from the respective hemicycle. However, scattered Love waves arriving from the south can be seen for all earthquakes. Combining the information of all events, it is possible to retrieve the Love wave dispersion curves of the fundamental and the first harmonic mode. The particle motion of the fundamental mode of Rayleigh waves is retrograde and for the first harmonic mode, it is prograde. For both modes, we can also retrieve dispersion and ellipticity

Blind shear-wave velocity comparison of ReMi and MASW results with boreholes to 200 m in Santa Clara Valley: Implications for earthquake ground-motion assessment

USGS Publications Warehouse

Stephenson, W.J.; Louie, J.N.; Pullammanappallil, S.; Williams, R.A.; Odum, J.K.

2005-01-01

Multichannel analysis of surface waves (MASW) and refraction microtremor (ReMi) are two of the most recently developed surface acquisition techniques for determining shallow shear-wave velocity. We conducted a blind comparison of MASW and ReMi results with four boreholes logged to at least 260 m for shear velocity in Santa Clara Valley, California, to determine how closely these surface methods match the downhole measurements. Average shear-wave velocity estimates to depths of 30, 50, and 100 m demonstrate that the surface methods as implemented in this study can generally match borehole results to within 15% to these depths. At two of the boreholes, the average to 100 m depth was within 3%. Spectral amplifications predicted from the respective borehole velocity profiles similarly compare to within 15 % or better from 1 to 10 Hz with both the MASW and ReMi surface-method velocity profiles. Overall, neither surface method was consistently better at matching the borehole velocity profiles or amplifications. Our results suggest MASW and ReMi surface acquisition methods can both be appropriate choices for estimating shearwave velocity and can be complementary to each other in urban settings for hazards assessment.

Acute inhalation toxicity of 3-methylfuran in the mouse: pathology, cell kinetics, and respiratory rate effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haschek, W.M.; Boyd, M.R.; Hakkinen, P.J.

1984-01-01

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in male BALB/c mice by morphologic examination of animals killed at varying timepoints following a 1-hr exposure to an initial chamber concentration of 14 to 37 mumol/liter (343 to 906 ppm). In addition, respiratory rate measurements and cell kinetics were used to assess quantitatively pulmonary damage and repair. Necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen 1 day following exposure and was followed by regeneration, which was virtually complete, within 21 days. Cell kinetic studies showed peak bronchiolar cell proliferation at 3 days with a labeling index (LI) of 5.0%more » compared to 0.4% in controls. An increase in parenchymal cell proliferation was also noted coincident with a mild interstitial pneumonitis. This parenchymal proliferation, peaking at 10 days with an LI of 1.4% compared to 0.2% in controls, consisted primarily of type II epithelial and endothelial cell proliferation indicating possible delayed damage and repair of type I epithelial and endothelial cells. The respiratory rate showed an initial transient increase followed by a more prolonged decrease with eventual return to control levels. 3MF toxicity was also evidenced by a necrotizing suppurative rhinitis, centrilobular hepatic necrosis, lymphocyte necrosis in the thymus and spleen, sialoadenitis, and otitis media.« less

Favourable prognosis of cystadeno- over adenocarcinoma of the pancreas after curative resection.

PubMed

Ridder, G J; Maschek, H; Klempnauer, J

1996-06-01

This report details nine patients after curative surgical resection of histologically proven mucinous cystadenocarcinoma of the pancreas and compares the prognosis with ductal adenocarcinomas. Cystadenocarcinomas represented 2.1% (10/ 466) of a total of 466 patients who underwent surgical exploration and 5.5%, of all curatively resected carcinomas of the exocrine pancreas at Hanover Medical School from 1971 to 1994. Forty percent of adenocarcinomas and 90% of cystadenocarcinomas were resectable. A curative R0 resection was possible in all patients with cystadenocarcinoma and 85 % with adenocarcinoma. Six of the patients with cystadenocarcinoma were female and three were male. Their median age was 54 +/- 12 years (range: 44 to 81 years). Four cystic neoplasms were located in the head, one in the head and body, three in the tail, and one in the body and tail of the pancreas. There was no hospital mortality in this group. The prognosis after resection of cystadenocarcinomas was significantly better compared to ductal adenocarcinomas of the pancreas. The Kaplan-Meier survival was 89% vs 52% after 1 year, and 56% vs 13% at 5 years. Our results indicate the favourable prognosis of cystadeno- over ductal adenocarcinomas of the pancreas in a cohort of patients with curative tumour resection.

Future Climate Change Will Favour Non-Specialist Mammals in the (Sub)Arctics

PubMed Central

Hof, Anouschka R.; Jansson, Roland; Nilsson, Christer

2012-01-01

Arctic and subarctic (i.e., [sub]arctic) ecosystems are predicted to be particularly susceptible to climate change. The area of tundra is expected to decrease and temperate climates will extend further north, affecting species inhabiting northern environments. Consequently, species at high latitudes should be especially susceptible to climate change, likely experiencing significant range contractions. Contrary to these expectations, our modelling of species distributions suggests that predicted climate change up to 2080 will favour most mammals presently inhabiting (sub)arctic Europe. Assuming full dispersal ability, most species will benefit from climate change, except for a few cold-climate specialists. However, most resident species will contract their ranges if they are not able to track their climatic niches, but no species is predicted to go extinct. If climate would change far beyond current predictions, however, species might disappear. The reason for the relative stability of mammalian presence might be that arctic regions have experienced large climatic shifts in the past, filtering out sensitive and range-restricted taxa. We also provide evidence that for most (sub)arctic mammals it is not climate change per se that will threaten them, but possible constraints on their dispersal ability and changes in community composition. Such impacts of future changes in species communities should receive more attention in literature. PMID:23285098

Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dairou, Julien; Petit, Emile; Ragunathan, Nilusha

2009-05-01

Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and {beta}-naphthylamine ({beta}-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating thatmore » inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H{sub 2}O{sub 2} or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.« less

Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

PubMed

Zumsteg, Zachary S; Zelefsky, Michael J; Woo, Kaitlin M; Spratt, Daniel E; Kollmeier, Marisa A; McBride, Sean; Pei, Xin; Sandler, Howard M; Zhang, Zhigang

2017-11-01

To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR

Meteorological Situations Favouring the Development of Dust Plumes over Iceland

NASA Astrophysics Data System (ADS)

Schepanski, K.; Szodry, K.

2017-12-01

The knowledge on mineral dust emitted at high latitudes is limited, but its impact on the polar environments is divers. Within a warming climate, dust emitted from regions in cold climates is expected to increase due to the retreat of the ice sheet and increasing melting rates. Therefore, and for its extensive impacts on different aspects of the climate system, a better understanding of the atmospheric dust life-cycle at high latitudes/cold climates in general, and the spatio-temporal distribution of dust sources in particular, are essential. At high-latitudes, glacio-fluvial sediments as found on river flood plains e.g. supplied by glaciers are prone to wind erosion when dry and bare. In case of the occurrence of strong winds, sediments are blown out and dust plumes develop. As dust uplift is controlled by soil surface characteristics, the availability of suitable sediments, and atmospheric conditions, an interannual variability in dust source activity is expected. We investigated atmospheric circulation patterns that favour the development of dust plumes over Iceland, which presents a well-known dust source at high latitudes. Using the atmosphere model COSMO (COnsortium for Small-scale MOdeling), we analysed the wind speed distribution over the Iceland region for identified and documented dust cases. As one outcome of the study, the position of the Icelandic low, the anticyclones located over Northern Europe, and the resulting pressure gradients are of particular relevance. The interaction of the synoptic-scale winds with the Icelandic orography may locally enhance the wind speeds and thus foster local dust emission. Results from this study suggest that the atmospheric circulation determined by the pressure pattern is of particular relevance for the formation of dust plumes entering the North Atlantic.

The Quaternary Silver Creek Fault Beneath the Santa Clara Valley, California

USGS Publications Warehouse

Wentworth, Carl M.; Williams, Robert A.; Jachens, Robert C.; Graymer, Russell W.; Stephenson, William J.

2010-01-01

The northwest-trending Silver Creek Fault is a 40-km-long strike-slip fault in the eastern Santa Clara Valley, California, that has exhibited different behaviors within a changing San Andreas Fault system over the past 10-15 Ma. Quaternary alluvium several hundred meters thick that buries the northern half of the Silver Creek Fault, and that has been sampled by drilling and imaged in a detailed seismic reflection profile, provides a record of the Quaternary history of the fault. We assemble evidence from areal geology, stratigraphy, paleomagnetics, ground-water hydrology, potential-field geophysics, and reflection and earthquake seismology to determine the long history of the fault in order to evaluate its current behavior. The fault formed in the Miocene more than 100 km to the southeast, as the southwestern fault in a 5-km-wide right step to the Hayward Fault, within which the 40-km-long Evergreen pull-apart basin formed. Later, this basin was obliquely cut by the newly recognized Mt. Misery Fault to form a more direct connection to the Hayward Fault, although continued growth of the basin was sufficient to accommodate at least some late Pliocene alluvium. Large offset along the San Andreas-Calaveras-Mt Misery-Hayward Faults carried the basin northwestward almost to its present position when, about 2 Ma, the fault system was reorganized. This led to near abandonment of the faults bounding the pull-apart basin in favor of right slip extending the Calaveras Fault farther north before stepping west to the Hayward Fault, as it does today. Despite these changes, the Silver Creek Fault experienced a further 200 m of dip slip in the early Quaternary, from which we infer an associated 1.6 km or so of right slip, based on the ratio of the 40-km length of the strike-slip fault to a 5-km depth of the Evergreen Basin. This dip slip ends at a mid-Quaternary unconformity, above which the upper 300 m of alluvial cover exhibits a structural sag at the fault that we interpret as

Understanding cell cycle and cell death regulation provides novel weapons against human diseases.

PubMed

Wiman, K G; Zhivotovsky, B

2017-05-01

Cell division, cell differentiation and cell death are the three principal physiological processes that regulate tissue homoeostasis in multicellular organisms. The growth and survival of cells as well as the integrity of the genome are regulated by a complex network of pathways, in which cell cycle checkpoints, DNA repair and programmed cell death have critical roles. Disruption of genomic integrity and impaired regulation of cell death may both lead to uncontrolled cell growth. Compromised cell death can also favour genomic instability. It is becoming increasingly clear that dysregulation of cell cycle and cell death processes plays an important role in the development of major disorders such as cancer, cardiovascular disease, infection, inflammation and neurodegenerative diseases. Research achievements in these fields have led to the development of novel approaches for treatment of various conditions associated with abnormalities in the regulation of cell cycle progression or cell death. A better understanding of how cellular life-and-death processes are regulated is essential for this development. To highlight these important advances, the Third Nobel Conference entitled 'The Cell Cycle and Cell Death in Disease' was organized at Karolinska Institutet in 2016. In this review we will summarize current understanding of cell cycle progression and cell death and discuss some of the recent advances in therapeutic applications in pathological conditions such as cancer, neurological disorders and inflammation. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Identification of cancer initiating cells in K-Ras driven lung adenocarcinoma.

PubMed

Mainardi, Sara; Mijimolle, Nieves; Francoz, Sarah; Vicente-Dueñas, Carolina; Sánchez-García, Isidro; Barbacid, Mariano

2014-01-07

Ubiquitous expression of a resident K-Ras(G12V) oncogene in adult mice revealed that most tissues are resistant to K-Ras oncogenic signals. Indeed, K-Ras(G12V) expression only induced overt tumors in lungs. To identify these transformation-permissive cells, we induced K-Ras(G12V) expression in a very limited number of adult lung cells (0.2%) and monitored their fate by X-Gal staining, a surrogate marker coexpressed with the K-Ras(G12V) oncoprotein. Four weeks later, 30% of these cells had proliferated to form small clusters. However, only SPC(+) alveolar type II (ATII) cells were able to form hyperplastic lesions, some of which progressed to adenomas and adenocarcinomas. In contrast, induction of K-Ras(G12V) expression in lung cells by intratracheal infection with adenoviral-Cre particles generated hyperplasias in all regions except the proximal airways. Bronchiolar and bronchioalveolar duct junction hyperplasias were primarily made of CC10(+) Clara cells. Some of them progressed to form benign adenomas. However, only alveolar hyperplasias, exclusively made up of SPC(+) ATII cells, progressed to yield malignant adenocarcinomas. Adenoviral infection induced inflammatory infiltrates primarily made of T and B cells. This inflammatory response was essential for the development of K-Ras(G12V)-driven bronchiolar hyperplasias and adenomas, but not for the generation of SPC(+) ATII lesions. Finally, activation of K-Ras(G12V) during embryonic development under the control of a Sca1 promoter yielded CC10(+), but not SPC(+), hyperplasias, and adenomas. These results, taken together, illustrate that different types of lung cells can generate benign lesions in response to K-Ras oncogenic signals. However, in adult mice, only SPC(+) ATII cells were able to yield malignant adenocarcinomas.

Relationships of field habitat measurements, visual habitat indices, and land cover to benthic macroinvertebrates in urbanized streams of the Santa Clara Valley, California

USGS Publications Warehouse

Fend, S.V.; Carter, J.L.; Kearns, F.R.

2005-01-01

We evaluated several approaches for measuring natural and anthropogenic habitat characteristics to predict benthic macroinvertebrate assemblages over a range of urban intensity at 85 stream sites in the Santa Clara Valley, California. Land cover was summarized as percentage urban land cover and impervious area within upstream buffers and the upstream subwatersheds. Field measurements characterized water chemistry, channel slope, sediment, and riparian canopy. In . addition to applying the visual-based habitat assessment in U.S. Environmental Protection Agency's rapid bioassessment protocol, we developed a simplified urban habitat assessment index based on turbidity, fine sediment deposition, riparian condition, and channel modification. Natural and anthropogenic habitat variables covaried along longitudinal stream gradients and were highly correlated with elevation. At the scale of the entire watershed, benthic macroinvertebrate measures were equally correlated with variables expressing natural gradients and urbanization effects. When natural gradients were reduced by partitioning sites into ecoregion subsection groupings, habitat variables most highly correlated with macroinvertebrate measures differed between upland and valley floor site groups. Among the valley floor sites, channel slope and physical modification of channel and riparian habitats appeared more important than upstream land cover or water quality in determining macroinvertebrate richness and ordination scores. Among upland sites, effects of upstream reservoir releases on habitat quality appeared important. Rapid habitat evaluation methods appeared to be an effective method for describing habitat features important to benthic macroinvertebrates when adapted for the region and the disturbance of interest. ?? 2005 by the American Fisheries Society.

Neuroimmune Interactions, Low-Dose Sarin Inhalation, and Gulf War Syndrome

DTIC Science & Technology

2012-10-01

antibody-forming cell qPCR real-time PCR CORT corticosterone Introduction Cigarette smoking is a major health risk factor and contributes to over...and PTK activities in splenic T cells One of the earliest effects of TCR ligation is the activation of PTK, including Src-like kinases Fyn and Lck...development of Clara and goblet cells without causing significant lung inflammation, and the SS-induced effects on alveolar architecture are

Evolutionary conservation advice for despotic populations: habitat heterogeneity favours conflict and reduces productivity in Seychelles magpie robins.

PubMed

López-Sepulcre, Andrés; Kokko, Hanna; Norris, Ken

2010-11-22

Individual preferences for good habitat are often thought to have a beneficial stabilizing effect for populations. However, if individuals preferentially compete for better-quality territories, these may become hotspots of conflict. We show that, in an endangered species, this process decreases the productivity of favoured territories to the extent that differences in productivity between territories disappear. Unlike predictions from current demographic theory on site-dependent population regulation (ideal despotic distribution), we show that population productivity is reduced if resources are distributed unevenly in space. Competition for high-quality habitat can thus have detrimental consequences for populations even though it benefits individuals. Manipulating conflict (e.g. by reducing variation in habitat quality) can therefore prove an effective conservation measure in species with strong social or territorial conflict.

January 2016 extensive summer melt in West Antarctica favoured by strong El Niño

DOE PAGES

Nicolas, Julien P.; Vogelmann, Andrew M.; Scott, Ryan C.; ...

2017-06-15

Over the past two decades the primary driver of mass loss from the West Antarctic Ice Sheet (WAIS) has been warm ocean water underneath coastal ice shelves, not a warmer atmosphere. Yet, surface melt occurs sporadically over low-lying areas of the WAIS and is not fully understood. Here we report on an episode of extensive and prolonged surface melting observed in the Ross Sea sector of the WAIS in January 2016. A comprehensive cloud and radiation experiment at the WAIS ice divide, downwind of the melt region, provided detailed insight into the physical processes at play during the event. Themore » unusual extent and duration of the melting are linked to strong and sustained advection of warm marine air toward the area, likely favoured by the concurrent strong El Niño event. Finally, the increase in the number of extreme El Niño events projected for the twenty-first century could expose the WAIS to more frequent major melt events.« less

January 2016 extensive summer melt in West Antarctica favoured by strong El Niño

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicolas, Julien P.; Vogelmann, Andrew M.; Scott, Ryan C.

Over the past two decades the primary driver of mass loss from the West Antarctic Ice Sheet (WAIS) has been warm ocean water underneath coastal ice shelves, not a warmer atmosphere. Yet, surface melt occurs sporadically over low-lying areas of the WAIS and is not fully understood. Here we report on an episode of extensive and prolonged surface melting observed in the Ross Sea sector of the WAIS in January 2016. A comprehensive cloud and radiation experiment at the WAIS ice divide, downwind of the melt region, provided detailed insight into the physical processes at play during the event. Themore » unusual extent and duration of the melting are linked to strong and sustained advection of warm marine air toward the area, likely favoured by the concurrent strong El Niño event. Finally, the increase in the number of extreme El Niño events projected for the twenty-first century could expose the WAIS to more frequent major melt events.« less

January 2016 extensive summer melt in West Antarctica favoured by strong El Niño

NASA Astrophysics Data System (ADS)

Nicolas, Julien P.; Vogelmann, Andrew M.; Scott, Ryan C.; Wilson, Aaron B.; Cadeddu, Maria P.; Bromwich, David H.; Verlinde, Johannes; Lubin, Dan; Russell, Lynn M.; Jenkinson, Colin; Powers, Heath H.; Ryczek, Maciej; Stone, Gregory; Wille, Jonathan D.

2017-06-01

Over the past two decades the primary driver of mass loss from the West Antarctic Ice Sheet (WAIS) has been warm ocean water underneath coastal ice shelves, not a warmer atmosphere. Yet, surface melt occurs sporadically over low-lying areas of the WAIS and is not fully understood. Here we report on an episode of extensive and prolonged surface melting observed in the Ross Sea sector of the WAIS in January 2016. A comprehensive cloud and radiation experiment at the WAIS ice divide, downwind of the melt region, provided detailed insight into the physical processes at play during the event. The unusual extent and duration of the melting are linked to strong and sustained advection of warm marine air toward the area, likely favoured by the concurrent strong El Niño event. The increase in the number of extreme El Niño events projected for the twenty-first century could expose the WAIS to more frequent major melt events.

Using a Triple Helix Approach to Examine Interactions and Dynamics of Innovation in Less-Favoured Regions: The Case of the Portuguese Polytechnic of Guarda

ERIC Educational Resources Information Center

Natário, Manuela; Braga, Ascensão; Daniel, Ana; Rosa, Cecília; Salgado, Miguel

2017-01-01

Using the Triple Helix model, this article examines the contribution of a higher education institution, the Polytechnic of Guarda (PG), located in an inland, a less-favoured region of Portugal, to territorial innovation dynamics. The main goal is to explore how the interaction and cooperation between the three helices of the Guarda region (PG,…

Remote Sensing of Ground Deformation for Monitoring Groundwater Management Practices: Application to the Santa Clara Valley During the 2012-2015 California Drought

NASA Astrophysics Data System (ADS)

Chaussard, Estelle; Milillo, Pietro; Bürgmann, Roland; Perissin, Daniele; Fielding, Eric J.; Baker, Brett

2017-10-01

Groundwater management typically relies on water-level data and spatially limited deformation measurements. While interferometric synthetic aperture radar has been used to study hydrological deformation, its limited temporal sampling can lead to biases in rapidly changing systems. Here we use 2011-2017 COSMO-SkyMed data with revisit intervals as short as 1 day to study the response of the Santa Clara Valley (SCV) aquifer in California to the unprecedented 2012-2015 drought. Cross-correlation and independent component analyses of deformation time series enable tracking water through the aquifer system. The aquifer properties are derived prior to and during the drought to assess the success of water-resource management practices. Subsidence due to groundwater withdrawal dominates during 2011-2017, limited to the confined aquifer and west of the Silver Creek Fault, similar to predrought summer periods. Minimum water levels and elevations were reached in mid-2014, but thanks to intensive groundwater management efforts the basin started to rebound in late 2014, during the deepening drought. By 2017, water levels were back to their predrought levels, while elevations had not yet fully rebounded due to the delayed poroelastic response of aquitards and their large elastic compressibility. As water levels did not reach a new lowstand, the drought led to only elastic and recoverable changes in the SCV. The SCV lost 0.09 km3 during the drought while seasonal variations amount to 0.02 km3. Analysis of surface loads due to water mass changes in the aquifer system suggests that groundwater drawdowns could influence the stress on nearby faults.

18. Photocopy of undated illustration in unidentified publication. CEILING AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. Photocopy of undated illustration in unidentified publication. CEILING AND REREDOS PRESERVED IN 1884 RESTORATION - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

29. Photocopy of October 25, 1926, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. Photocopy of October 25, 1926, photograph in San Francisco Chronicle Library. VIEW INSIDE RUINED TOWERS - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

33. Photocopy of circa 1930 photograph in San Francisco Chronicle ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

33. Photocopy of circa 1930 photograph in San Francisco Chronicle Library. FACADE OF RESTORED MISSION (FIFTH CHURCH) - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

34. Photocopy of circa 1930 photograph in San Francisco Chronicle ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

34. Photocopy of circa 1930 photograph in San Francisco Chronicle Library. CLOSE VIEW OF RESTORED MISSION FACADE - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

28. Photocopy of October 25, 1926, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. Photocopy of October 25, 1926, photograph in San Francisco Chronicle Library. RUINS OF TOWERS, LOOKING NORTH - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

Rechargeable alkaline manganese dioxide cells. A test report

NASA Astrophysics Data System (ADS)

Farrington, Michael D.

The rechargeable alkaline MnO 2 (RAM) system has now been commercially available for several years. The Canadian Department of National Defence is interested in determining if the low cost RAM system is technically capable of replacing existing cells and batteries now in use. A preliminary study identified sufficient candidate batteries in use within the Department whose performance requirements compared favourably with RAM manufacturers' claims. Further study was warranted. Replacement cost savings could be significant. A study is now in progress that is aimed at determining how well the RAM technology actually performs. This paper presents test results that illustrate how RAM cells compare to primary alkaline cells and nickel/cadmium. The majority of the work is focused on the 'AA' size products from Rayovac and Pure Energy: tests were also conducted on Rayovac 'D' cells.

Tumour necrosis factor (TNF)-mediated NF-κB activation facilitates cellular invasion of non-professional phagocytic epithelial cell lines by Trypanosoma cruzi.

PubMed

Pinto, Andrea M T; Sales, Paula C M; Camargos, Elizabeth R S; Silva, Aristóbolo M

2011-10-01

At the site of infection, pro-inflammatory cytokines locally produced by macrophages infected with Trypanosoma cruzi can activate surrounding non-professional phagocytes such as fibroblasts, epithelial and endothelial cells, which can be further invaded by the parasite. The effect of secreted soluble factors on the invasion of these cells remains, however, to be established. We show here that two epithelial cell lines become significantly susceptible to the infection by the Y strain of T. cruzi after tumour necrosis factor (TNF) treatment. The increase in the invasion was correlated with the increasing concentration of recombinant TNF added to cultures of HEK293T or LLC-MK2 cells. Supernatants taken from PMA-differentiated human monocytes infected with T. cruzi also increased the permissiveness of epithelial cells to subsequent infection with the parasite, which was inhibited by a TNF monoclonal antibody. Furthermore, the permissiveness induced by TNF was inhibited by TPCK, and led to significant decrease in the number of intracellular parasites, providing evidence that activation of NF-κB induced by TNF favours the invasion of the epithelial cell lines by T. cruzi through yet an unidentified mechanism. Our data indicate that soluble factors released from macrophages early in the infection favours T. cruzi invasion of non-professional phagocytic cells. © 2011 Blackwell Publishing Ltd.

Antibody distance from the cell membrane regulates antibody effector mechanisms

PubMed Central

Cleary, Kirstie L.S.; Chan, H.T. Claude; James, Sonja; Glennie, Martin J.; Cragg, Mark S.

2017-01-01

Immunotherapy using monoclonal antibodies (mAb) such as rituximab is an established means of treating haematological malignancies. Antibodies can elicit a number of mechanisms to delete target cells, including complement dependent cytotoxicity (CDC), antibody dependent cellular cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). The inherent properties of the target molecule help define which of these mechanisms are more important for efficacy. However, why mAb binding to different epitopes within the same target elicits different levels of therapeutic activity, is often unclear. To specifically address whether distance from the target cell membrane influences the aforementioned effector mechanisms, a panel of fusion proteins consisting of a CD20 or CD52 epitope attached to various CD137 scaffold molecules were generated. The CD137 scaffold was modified through the removal or addition of cysteine-rich extracellular domains, to produce a panel of chimeric molecules which held the target epitope at different distances along the protein. It was shown that CDC and ADCC favoured a membrane proximal epitope, whilst ADCP favoured an epitope positioned further away. These findings were then confirmed using reagents targeting the membrane proximal or distal domains of CD137 itself before investigating these properties in vivo where a clear difference in the splenic clearance of transfected tumour cells was observed. Together, this work demonstrates how altering the position of the antibody epitope is able to change the effector mechanisms engaged and facilitates the selection of mAbs designed to delete target cells through specific effector mechanisms and provide more effective therapeutic agents. PMID:28404636

A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

PubMed Central

Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

2016-01-01

A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells

PubMed Central

Kobayashi, Hideki; Butler, Jason M.; O'Donnell, Rebekah; Kobayashi, Mariko; Ding, Bi-Sen; Bonner, Bryant; Chiu, Vi K.; Nolan, Daniel J.; Shido, Koji; Benjamin, Laura; Rafii, Shahin

2010-01-01

Endothelial cells establish an instructive vascular niche that reconstitutes haematopoietic stem and progenitor cells (HSPCs) through release of specific paracrine growth factors, known as angiocrine factors. However, the mechanism by which endothelial cells balance the rate of proliferation and lineage-specific differentiation of HSPCs is unknown. Here, we demonstrate that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Conversely, co-activation of Akt-stimulated endothelial cells with p42/44 MAPK shifts the balance towards maintenance and differentiation of the HSPCs. Selective activation of Akt1 in the endothelial cells of adult mice increased the number of colony forming units in the spleen and CD34−Flt3− KLS HSPCs with LT-HSC activity in the bone marrow, accelerating haematopoietic recovery. Therefore, the activation state of endothelial cells modulates reconstitution of HSPCs through the upregulation of angiocrine factors, with Akt–mTOR-activated endothelial cells supporting the self-renewal of LT-HSCs and expansion of HSPCs, whereas MAPK co-activation favours maintenance and lineage-specific differentiation of HSPCs. PMID:20972423

Soft γ-ray selected radio galaxies: favouring giant size discovery

NASA Astrophysics Data System (ADS)

Bassani, L.; Venturi, T.; Molina, M.; Malizia, A.; Dallacasa, D.; Panessa, F.; Bazzano, A.; Ubertini, P.

2016-09-01

Using the recent INTEGRAL/IBIS and Swift/BAT surveys we have extracted a sample of 64 confirmed plus three candidate radio galaxies selected in the soft gamma-ray band. The sample covers all optical classes and is dominated by objects showing a Fanaroff-Riley type II radio morphology; a large fraction (70 per cent) of the sample is made of `radiative mode' or high-excitation radio galaxies. We measured the source size on images from the NRAO VLA Sky Survey, the Faint Images of the Radio Sky at twenty-cm and the Sydney University Molonglo Sky Survey images and have compared our findings with data in the literature obtaining a good match. We surprisingly found that the soft gamma-ray selection favours the detection of large size radio galaxies: 60 per cent of objects in the sample have size greater than 0.4 Mpc while around 22 per cent reach dimension above 0.7 Mpc at which point they are classified as giant radio galaxies (GRGs), the largest and most energetic single entities in the Universe. Their fraction among soft gamma-ray selected radio galaxies is significantly larger than typically found in radio surveys, where only a few per cent of objects (1-6 per cent) are GRGs. This may partly be due to observational biases affecting radio surveys more than soft gamma-ray surveys, thus disfavouring the detection of GRGs at lower frequencies. The main reasons and/or conditions leading to the formation of these large radio structures are still unclear with many parameters such as high jet power, long activity time and surrounding environment all playing a role; the first two may be linked to the type of active galactic nucleus discussed in this work and partly explain the high fraction of GRGs found in the present sample. Our result suggests that high energy surveys may be a more efficient way than radio surveys to find these peculiar objects.

30. Photocopy of October 1926 photograph in San Francisco CallBulletin ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

30. Photocopy of October 1926 photograph in San Francisco Call-Bulletin Library. ARTICLES SAVED FROM THE FIRE OF OCTOBER 23, 1926 - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

23. Photocopy of October 23, 1926, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

23. Photocopy of October 23, 1926, photograph in San Francisco Call-Bulletin Library. NORTH TOWER DURING FIRE OF OCTOBER 23, 1926 - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

Generation of a human airway epithelium derived basal cell line with multipotent differentiation capacity

PubMed Central

2013-01-01

Background As the multipotent progenitor population of the airway epithelium, human airway basal cells (BC) replenish the specialized differentiated cell populations of the mucociliated airway epithelium during physiological turnover and repair. Cultured primary BC divide a limited number of times before entering a state of replicative senescence, preventing the establishment of long-term replicating cultures of airway BC that maintain their original phenotype. Methods To generate an immortalized human airway BC cell line, primary human airway BC obtained by brushing the airway epithelium of healthy nonsmokers were infected with a retrovirus expressing human telomerase (hTERT). The resulting immortalized cell line was then characterized under non-differentiating and differentiating air-liquid interface (ALI) culture conditions using ELISA, TaqMan quantitative PCR, Western analysis, and immunofluorescent and immunohistochemical staining analysis for cell type specific markers. In addition, the ability of the cell line to respond to environmental stimuli under differentiating ALI culture was assessed. Results We successfully generated an immortalized human airway BC cell line termed BCi-NS1 via expression of hTERT. A single cell derived clone from the parental BCi-NS1 cells, BCi-NS1.1, retains characteristics of the original primary cells for over 40 passages and demonstrates a multipotent differentiation capacity into secretory (MUC5AC, MUC5B), goblet (TFF3), Clara (CC10) and ciliated (DNAI1, FOXJ1) cells on ALI culture. The cells can respond to external stimuli such as IL-13, resulting in alteration of the normal differentiation process. Conclusion Development of immortalized human airway BC that retain multipotent differentiation capacity over long-term culture should be useful in understanding the biology of BC, the response of BC to environmental stress, and as a target for assessment of pharmacologic agents. PMID:24298994

22. Photocopy of October 23, 1926, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. Photocopy of October 23, 1926, photograph in San Francisco Call-Bulletin Library. UPPER PART OF FACADE DURING FIRE OF OCTOBER 23, 1926 - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

25. Photocopy of October 23, 1926, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. Photocopy of October 23, 1926, photograph in San Francisco Call-Bulletin Library. VIEW FROM THE SOUTHEAST DURING FIRE OF OCTOBER 23, 1926 - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

24. Photocopy of October 23, 1926, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. Photocopy of October 23, 1926, photograph in San Francisco Call-Bulletin Library. VIEW FROM THE WEST DURING FIRE OF OCTOBER 23, 1926 - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

32. Photocopy of May 14, 1928, photograph in San Francisco ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. Photocopy of May 14, 1928, photograph in San Francisco CHRONICLE Library. INTERIOR DURING SOLEMN PONTIFICAL MASS OF DEDICATION ON May 14, 1928 - Mission Santa Clara de Asis, Franklin & Grant Streets, Santa Clara, Santa Clara County, CA

CYP2F2-generated metabolites, not styrene oxide, are a key event mediating the mode of action of styrene-induced mouse lung tumors.

PubMed

Cruzan, G; Bus, J; Hotchkiss, J; Harkema, J; Banton, M; Sarang, S

2012-02-01

Styrene induces lung tumors in mice but not in rats. Although metabolism of styrene to 7,8-styrene oxide (SO) by CYP2E1 has been suggested as a mediator of styrene toxicity, lung toxicity is not attenuated in CYP2E1 knockout mice. However, styrene and/or SO metabolism by mouse lung Clara cell-localized CYP2F2 to ring-oxidized cytotoxic metabolite(s) has been postulated as a key metabolic gateway responsible for both lung toxicity and possible tumorigenicity. To test this hypothesis, the lung toxicity of styrene and SO was evaluated in C57BL/6 (WT) and CYP2F2⁻/⁻ knockout mice treated with styrene (400 mg/kg/day, gavage, or 200 or 400 mg/kg/day, ip) or S- or R-SO (200 mg/kg/day, ip) for 5 days. Styrene treated WT mice displayed significant necrosis and exfoliation of Clara cells, and cumulative BrdU-labeling index of S-phase cells was markedly increased in terminal bronchioles of WT mice exposed to styrene or S- or RSO. In contrast, Clara and terminal bronchiole cell toxicity was not observed in CYP2F2⁻/⁻ mice exposed to either styrene or SO. This study clearly demonstrates that the mouse lung toxicity of both styrene and SO is critically dependent on metabolism by CYP2F2. Importantly, the human isoform of CYP2F, CYP2F1, is expressed at much lower levels and likely does not catalyze significant styrene metabolism, supporting the hypothesis that styrene-induced mouse lung tumors may not quantitatively, or possibly qualitatively, predict lung tumor potential in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids

PubMed Central

Madeddu, Denise; Cerino, Giulia; Falco, Angela; Frati, Caterina; Gallo, Diego; Deriu, Marco A.; Falvo D’Urso Labate, Giuseppe; Quaini, Federico; Audenino, Alberto; Morbiducci, Umberto

2016-01-01

A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection, increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future. PMID:27144306

A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids.

PubMed

Massai, Diana; Isu, Giuseppe; Madeddu, Denise; Cerino, Giulia; Falco, Angela; Frati, Caterina; Gallo, Diego; Deriu, Marco A; Falvo D'Urso Labate, Giuseppe; Quaini, Federico; Audenino, Alberto; Morbiducci, Umberto

2016-01-01

A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection, increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.

Mutation Analysis in Cultured Cells of Transgenic Rodents

PubMed Central

Zheng, Albert; Bates, Steven E.; Tommasi, Stella

2018-01-01

To comply with guiding principles for the ethical use of animals for experimental research, the field of mutation research has witnessed a shift of interest from large-scale in vivo animal experiments to small-sized in vitro studies. Mutation assays in cultured cells of transgenic rodents constitute, in many ways, viable alternatives to in vivo mutagenicity experiments in the corresponding animals. A variety of transgenic rodent cell culture models and mutation detection systems have been developed for mutagenicity testing of carcinogens. Of these, transgenic Big Blue® (Stratagene Corp., La Jolla, CA, USA, acquired by Agilent Technologies Inc., Santa Clara, CA, USA, BioReliance/Sigma-Aldrich Corp., Darmstadt, Germany) mouse embryonic fibroblasts and the λ Select cII Mutation Detection System have been used by many research groups to investigate the mutagenic effects of a wide range of chemical and/or physical carcinogens. Here, we review techniques and principles involved in preparation and culturing of Big Blue® mouse embryonic fibroblasts, treatment in vitro with chemical/physical agent(s) of interest, determination of the cII mutant frequency by the λ Select cII assay and establishment of the mutation spectrum by DNA sequencing. We describe various approaches for data analysis and interpretation of the results. Furthermore, we highlight representative studies in which the Big Blue® mouse cell culture model and the λ Select cII assay have been used for mutagenicity testing of diverse carcinogens. We delineate the advantages of this approach and discuss its limitations, while underscoring auxiliary methods, where applicable. PMID:29337872

[Multifocal Langerhans cell histiocytosis of bone: late revelation in a 76-year-old woman].

PubMed

Lahiani, D; Hammami, B K; Maâloul, I; Frikha, M; Baklouti, S; Jlidi, R; Ben Jemaâ, M

2008-03-01

Langerhans cell histiocytosis or histiocytosis X has a variable course from a self-limited eosinophilic granuloma to an aggressive disseminated disease. It mainly affects children. We report a 76-year-old woman with multifocal bone histiocytosis X, involving the rachis, an iliac bone and the skull. The diagnosis has been established by histological exam. Outcome was favourable after chemotherapy.

Evaluation of thermodynamically favourable operating conditions for production of hydrogen in three different reforming technologies

NASA Astrophysics Data System (ADS)

Seo, Y.-S.; Shirley, A.; Kolaczkowski, S. T.

With the aid of thermodynamic analysis using AspenPlus™, the characteristics of three different types of reforming process are investigated. These include: steam-methane reforming (SMR), partial oxidation (POX) and autothermal reforming (ATR). Thereby, favourable operating conditions are identified for each process. The optimum steam-to-carbon (S:C) ratio of the SMR reactor is found to be 1.9. The optimum air ratio of the POX reactor is 0.3 at a preheat temperature of 312 °C. The optimum air ratio and S:C ratio of the ATR reactor are 0.29 and 0.35, respectively at a preheat temperature of 400 °C. Simulated material and energy balances show that the CH 4 flow rates required to generate 1 mol s -1 of hydrogen are 0.364 mol s -1 for POX, 0.367 mol s -1 for ATR and 0.385 mol s -1 for the SMR. These results demonstrate that the POX reforming system has the lowest energy cost to produce the same amount of hydrogen from CH 4.

Low-Dose Curcumin Stimulates Proliferation, Migration and Phagocytic Activity of Olfactory Ensheathing Cells

PubMed Central

Tello Velasquez, Johana; Watts, Michelle E.; Todorovic, Michael; Nazareth, Lynnmaria; Pastrana, Erika; Diaz-Nido, Javier; Lim, Filip; Ekberg, Jenny A. K.; Quinn, Ronald J.; John, James A. St

2014-01-01

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies. PMID:25360677

Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells.

PubMed

Ricciardi, M; Zanotto, M; Malpeli, G; Bassi, G; Perbellini, O; Chilosi, M; Bifari, F; Krampera, M

2015-03-17

Epithelial-to-mesenchymal transition (EMT) has a central role in cancer progression and metastatic dissemination and may be induced by local inflammation. We asked whether the inflammation-induced acquisition of mesenchymal phenotype by neoplastic epithelial cells is associated with the onset of mesenchymal stromal cell-like immune-regulatory properties that may enhance tumour immune escape. Cell lines of lung adenocarcinoma (A549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induction by either the supernatant of mixed-lymphocyte reactions or inflammatory cytokines. EMT occurrence following inflammatory priming elicited multiple immune-regulatory effects in cancer cells resulting in NK and T-cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase, but not Fas ligand pathway, was involved at least in part in these effects, as shown by the use of specific inhibitors. EMT induced by inflammatory stimuli confers to cancer cells some mesenchymal stromal cell-like immune-modulatory properties, which could be a cue for cancer progression and metastatic dissemination by favouring immune escape.

Does a person selectively recall the good or the bad from their personal past? It depends on the recall target and the person's favourability of self-views.

PubMed

Ritchie, Timothy D; Sedikides, Constantine; Skowronski, John J

2017-09-01

In three studies, participants remembered real-life behaviours at Time 1 and attempted to recall them at Time 2. When the recall target was the self, a positivity bias emerged: self-positivity. In Study 3, self-positivity extended to an individual (target) who was liked by the participant, but did it not extend to a disliked target. For this latter target, a negativity bias emerged. For recall targets that were participants' acquaintances, self-positivity in recall was also eliminated in Studies 1 and 3, and a negativity bias in recall emerged in Study 2. Finally, in Study 2 (but not Study 3), the favourability of participants' self-view predicted the magnitude of the self-positivity in self-recall, but it did not predict valence effects in other-recall. Taken together, the results indicate that the link between behaviour valence and recall is moderated by the recall target and the favourability of one's self-view.

Material- and feature-dependent effects on cell adhesion to micro injection moulded medical polymers.

PubMed

Choi, Seong Ying; Habimana, Olivier; Flood, Peter; Reynaud, Emmanuel G; Rodriguez, Brian J; Zhang, Nan; Casey, Eoin; Gilchrist, Michael D

2016-09-01

Two polymers, polymethylmethacrylate (PMMA) and cyclic olefin copolymer (COC), containing a range of nano- to micron- roughness surfaces (Ra 0.01, 0.1, 0.4, 1.0, 2.0, 3.2 and 5.0μm) were fabricated using electrical discharge machining (EDM) and replicated using micro injection moulding (μIM). Polymer samples were characterized using optical profilometry, atomic force microscopy (AFM) and water surface contact angle. Cell adhesion tests were carried out using bacterial Pseudomonas fluorescens and mammalian Madin-Darby Canine Kidney (MDCK) cells to determine the effect of surface hydrophobicity, surface roughness and stiffness. It is found that there are features which gave insignificant differences (feature-dependent effect) in cell adhesion, albeit a significant difference in the physicochemical properties (material-dependent effect) of substrata. In bacterial cell adhesion, the strongest feature-dependence is found at Ra 0.4μm surfaces, with material-dependent effects strongest at Ra 0.01μm. Ra 0.1μm surfaces exhibited strongest feature-dependent effects and Ra 5.0μm has strongest material-dependent effects on mammalian cell adhesion. Bacterial cell adhesion is found to be favourable to hydrophobic surfaces (COC), with the lowest adhesion at Ra 0.4μm for both materials. Mammalian cell adhesion is lowest in Ra 0.1μm and highest in Ra 1.0μm, and generally favours hydrophilic surfaces (PMMA). These findings can be used as a basis for developing medical implants or microfluidic devices using micro injection moulding for diagnostic purposes, by tuning the cell adhesion on different areas containing different surface roughnesses on the diagnostic microfluidic devices or medical implants. Copyright © 2016 Elsevier B.V. All rights reserved.

The offshore export of sand during exceptional discharge from California rivers

USGS Publications Warehouse

Warrick, Jonathan A.; Barnard, Patrick L.

2012-01-01

Littoral cells along active tectonic margins receive large inputs of sand and gravel from coastal watersheds and commonly lose this sediment to submarine canyons. One hypothesis is that the majority of coarse (sand and gravel) river sediment discharge will be emplaced within and immediately “resupply” local littoral cells. A competing hypothesis is that the infrequent, large floods that supply the majority of littoral sediment may discharge water-sediment mixtures within negatively buoyant hyperpycnal plumes that transport sediment offshore of the littoral cell. Here we summarize pre- and post-flood surveys of two wave-dominated California (United States) river deltas during record to near-record floods to help evaluate these hypotheses: the 1982–1983 delta at the San Lorenzo River mouth and the 2005 delta at the Santa Clara River mouth. Flood sedimentation at both deltas resulted in several meters of aggradation and hundreds of meters of offshore displacement of isobaths. One substantial difference between these deltas was the thick (>2 m) aggradation of sand on the inner shelf of the Santa Clara River delta that contained substantial amounts (∼50%) of littoral-grade sediment. Once deposited on the inner shelf, only a fraction (∼20%) of this river sand was observed to migrate toward the beach over the following 5 yr. Furthermore, simple hypopycnal plume behavior could not explain deposition of this sand on the inner shelf. Thus, during an exceptional flood a substantial amount of littoral-grade sand was exported offshore of the littoral system at the Santa Clara River mouth—likely from hyperpycnal plume processes—and was deposited on the inner shelf.

On measuring cell confluence in phase contrast microscopy

NASA Astrophysics Data System (ADS)

Dempsey, K. P.; Richardson, J. B.; Lam, K. P.

2014-03-01

A principal focus highlighting recent advances in cell based therapies concerns the development of effective treatments for osteoarthritis. Earlier clinicaltrials have shown that 80% of patients receiving mesenchymal stem cell(MSC) based treatment have improved their quality of life by alleviating pain whilst extending the life of their natural joints. The current challenge facing researchers is to identify the biological differences between the treatments that have worked and those which have shown little improvement. One possible candidate for the difference in treatment prognosis is an examination of the proliferation of the ( type) cells as they grow. To further understanding of the proliferation and differentiation of MSC, non-invasive live cell imaging techniques have been developed which capture important cell events and dynamics in cell divisions over an extended period of time. An automated image analysis procedure capable of tracking cell confluence over time has also been implemented, providing an objective and realistic estimation of cell growth within continuous live cell cultures. The proposed algorithm accounts for the halo artefacts that occur in phase microscopy. In addition to a favourable run-time performance, the method was also validated using continuous live MSC cultures, with consistent and meaningful results.

Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells.

PubMed

Lee, Shih-Han; Appleby, Vanessa; Jeyapalan, Jennie N; Palmer, Roger D; Nicholson, James C; Sottile, Virginie; Gao, Erning; Coleman, Nicholas; Scotting, Paul J

2011-02-01

Germ cell tumours (GCTs) are a diverse group of neoplasms all of which are generally believed to arise from germ cell progenitors (PGCs). Even those that form in the nervous system are likewise believed to be PGC-derived, despite being found a great distance from the normal location of germ cells. The primary evidence in favour of this model for the origins of intracranial GCTs is that they share molecular features with other GCTs. Those features include shared gene expression and a lack of methylation of imprinted genes, including SNRPN. Contrary to this model, we have proposed that endogenous neural stem cells of the brain are a more likely origin for these tumours. We show here that the lack of methylation of SNRPN that has previously been taken to indicate an origin for GCTs from PGCs is also seen in neural stem cells of mice and humans. We believe that, in the light of these and other recent observations, endogenous neural precursors of the brain are a more plausible origin for intracranial GCTs than are misplaced PGCs.

Hypoxia enhances the malignant nature of bladder cancer cells and concomitantly antagonizes protein O-glycosylation extension

PubMed Central

Lima, Luís; Azevedo, Rita; Soares, Janine; Cotton, Sofia; Parreira, Beatriz; Neves, Manuel; Amaro, Teresina; Tavares, Ana; Teixeira, Filipe; Palmeira, Carlos; Rangel, Maria; Silva, André M.N.; Reis, Celso A.; Santos, Lúcio Lara; Oliveira, Maria José; Ferreira, José Alexandre

2016-01-01

Invasive bladder tumours express the cell-surface Sialyl-Tn (STn) antigen, which stems from a premature stop in protein O-glycosylation. The STn antigen favours invasion, immune escape, and possibly chemotherapy resistance, making it attractive for target therapeutics. However, the events leading to such deregulation in protein glycosylation are mostly unknown. Since hypoxia is a salient feature of advanced stage tumours, we searched into how it influences bladder cancer cells glycophenotype, with emphasis on STn expression. Therefore, three bladder cancer cell lines with distinct genetic and molecular backgrounds (T24, 5637 and HT1376) were submitted to hypoxia. To disclose HIF-1α-mediated events, experiments were also conducted in the presence of Deferoxamine Mesilate (Dfx), an inhibitor of HIF-1α proteasomal degradation. In both conditions all cell lines overexpressed HIF-1α and its transcriptionally-regulated protein CA-IX. This was accompanied by increased lactate biosynthesis, denoting a shift toward anaerobic metabolism. Concomitantly, T24 and 5637 cells acquired a more motile phenotype, consistent with their more mesenchymal characteristics. Moreover, hypoxia promoted STn antigen overexpression in all cell lines and enhanced the migration and invasion of those presenting more mesenchymal characteristics, in an HIF-1α-dependent manner. These effects were reversed by reoxygenation, demonstrating that oxygen affects O-glycan extension. Glycoproteomics studies highlighted that STn was mainly present in integrins and cadherins, suggesting a possible role for this glycan in adhesion, cell motility and invasion. The association between HIF-1α and STn overexpressions and tumour invasion was further confirmed in bladder cancer patient samples. In conclusion, STn overexpression may, in part, result from a HIF-1α mediated cell-survival strategy to adapt to the hypoxic challenge, favouring cell invasion. In addition, targeting STn-expressing glycoproteins may

Analyses of atypical glandular cells re-defined by the 2006 Bethesda System: histologic outcomes and clinical implication of follow-up management.

PubMed

Ulker, V; Numanoglu, C; Akyol, A; Kuru, O; Akbayir, O; Erim, A; Ongut, C

2013-01-01

To evaluate the histopathology and the long-term follow-up outcome of women who had atypical glandular cells on Pap smears. All women with atypical glandular cells (AGC) who underwent colposcopic and histopathologic evaluation between January 2005 and October 2010 were reviewed. Patient data were examined up to October 2012, allowing for at least two years of follow-up for all patients. Forty-four women with AGC Pap test underwent histologic follow-up during the study period. Overall, upon reclassification of smears, 35 (79.5%) cases were diagnosed with AGC "not otherwise specified" (NOS) and nine (20.5%) with AGC "favour neoplasia". Seven out of nine patients (77.7%) with AGC "favour neoplasia" had significant pathology. On the other hand, only 11 out of 35 cases (31.4%) with AGC "NOS" had significant pathology. Significant correlation was found between AGC "favour neoplasia" smears and a significant pathology (p: 0.01). Of the 44 patients, 18 (40.9%) had significant pathology. Eight patients (18.2%) had low grade cervical intraepithelial neoplasia (CIN 1), four (9%) had high-grade cervical intraepithelial neoplasia (CIN 2/3), one (2.2%) had microinvasive squamous cell carcinoma of uterine cervix, one (2.2%) had cervical adenocarcinoma in situ, one (2.2%) had cervical adenocarcinoma, one (2.2%) had endometrial adenocarcinoma, and two (4.5%) had endometrial hyperplasia. Reporting AGC in the population is clinically significant due to the high prevalence of underlying preinvasive and invasive diseases (40.9%). The subtypes of the AGC category are significant predictor of such lesions.

Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma.

PubMed

Saha, Shilpi; Bhattacharjee, Pushpak; Guha, Deblina; Kajal, Kirti; Khan, Poulami; Chakraborty, Sreeparna; Mukherjee, Shravanti; Paul, Shrutarshi; Manchanda, Rajkumar; Khurana, Anil; Nayak, Debadatta; Chakrabarty, Rathin; Sa, Gaurisankar; Das, Tanya

2015-08-01

Adverse side effects of chemotherapy during cancer treatment have shifted considerable focus towards therapies that are not only targeted but are also devoid of toxic side effects. We evaluated the antitumorigenic activity of sulphur, and delineated the molecular mechanisms underlying sulphur-induced apoptosis in non-small cell lung carcinoma (NSCLC) cells. A search for the underlying mechanism revealed that the choice between the two cellular processes, NFκBp65-mediated survival and p53-mediated apoptosis, was decided by the competition for a limited pool of transcriptional coactivator protein p300 in NSCLC cells. In contrast, sulphur inhibited otherwise upregulated survival signaling in NSCLC cells by perturbing the nuclear translocation of p65NFκB, its association with p300 histone acetylase, and subsequent transcription of Bcl-2. Under such anti-survival condition, induction of p53-p300 cross-talk enhanced the transcriptional activity of p53 and intrinsic mitochondrial death cascade. Overall, the findings of this preclinical study clearly delineated the molecular mechanism underlying the apoptogenic effect of the non-toxic homeopathic remedy, sulphur, in NSCLC cells.

Cell-fate determination by ubiquitin-dependent regulation of translation.

PubMed

Werner, Achim; Iwasaki, Shintaro; McGourty, Colleen A; Medina-Ruiz, Sofia; Teerikorpi, Nia; Fedrigo, Indro; Ingolia, Nicholas T; Rape, Michael

2015-09-24

Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3(KBTBD8)) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.

Sox17 drives functional engraftment of endothelium converted from non-vascular cells

PubMed Central

Schachterle, William; Badwe, Chaitanya R.; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M.; Rafii, Shahin

2017-01-01

Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function. PMID:28091527

Sox17 drives functional engraftment of endothelium converted from non-vascular cells.

PubMed

Schachterle, William; Badwe, Chaitanya R; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M; Rafii, Shahin

2017-01-16

Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.

Role of bentonite clays on cell growth.

PubMed

Cervini-Silva, Javiera; Ramírez-Apan, María Teresa; Kaufhold, Stephan; Ufer, Kristian; Palacios, Eduardo; Montoya, Ascención

2016-04-01

Bentonites, naturally occurring clays, are produced industrially because of their adsorbent capacity but little is known about their effects on human health. This manuscript reports on the effect of bentonites on cell growth behaviour. Bentonites collected from India (Bent-India), Hungary (Bent-Hungary), Argentina (Bent-Argentina), and Indonesia (Bent-Indonesia) were studied. All four bentonites were screened in-vitro against two human cancer cell lines [U251 (central nervous system, glioblastoma) and SKLU-1 (lung adenocarcinoma)] supplied by the National Cancer Institute (USA). Bentonites induced growth inhibition in the presence of U251 cells, and growth increment in the presence of SKLU-1 cells, showing that interactions between bentonite and cell surfaces were highly specific. The proliferation response for U251 cells was explained because clay surfaces controlled the levels of metabolic growth components, thereby inhibiting the development of high-grade gliomas, particularly primary glioblastomas. On the other hand, the proliferation response for SKLU-1 was explained by an exacerbated growth favoured by swelling, and concomitant accumulation of solutes, and their hydration and transformation via clay-surface mediated reactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Excessive Weight Favours Skin Physiology - Up to a Point: Another Expression of the Obesity Paradox.

PubMed

Monteiro Rodrigues, Luís Monteiro; Palma, Lídia; Santos, Osvaldo; Almeida, Maria Angélica; Bujan, Julia; Tavares, Liliana

2017-01-01

Recently classified as an epidemic by the WHO, obesity (as well as the state of being overweight) clearly affects significant populations across all ages. The relationship between obesity and some diseases (e.g. cardiovascular ones) is known, although many paradoxes remain to be explained. Very little information is available, however, regarding its impact on skin physiology and skin disease. This study aims to examine the influence of excessive weight on epidermal hydration and transepidermal water loss, key variables of skin water balance and skin biomechanics. A convenience sample of 89 healthy female volunteers was selected and divided into 4 groups, according to their BMI (body mass index), as normal (control), overweight, obese (I and II), and morbid. Skin physiology was quantitatively assessed in all individuals in 4 anatomical areas using non-invasive biometrical analysis by reference instrumentation. Descriptive and comparative statistics were applied, adopting a confidence level of 95%. A non-linear alteration for all variables was detected as a function of BMI. Results suggest that excessive weight might favour skin performance within certain limits, reflecting a particular adaptation of the skin to the weight gain and body contour. © 2017 S. Karger AG, Basel.

2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52) – a novel type of 5-lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo

PubMed Central

Greiner, C; Hörnig, C; Rossi, A; Pergola, C; Zettl, H; Schubert-Zsilavecz, M; Steinhilber, D; Sautebin, L; Werz, O

2011-01-01

BACKGROUND AND PURPOSE 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5-LO inhibitor 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH We evaluated the efficacy of HZ52 in vivo using carrageenan-induced pleurisy in rats and platelet-activating factor (PAF)-induced lethal shock in mice. We also characterized 5-LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5-LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS HZ52, 1.5 mg·kg−1 i.p., prevented carrageenan-induced pleurisy accompanied by reduced LTB4 levels and protected mice (10 mg·kg−1, i.p.) against PAF-induced shock. Detailed analysis in cell-based and cell-free assays revealed that inhibition of 5-LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca2+. CONCLUSIONS AND IMPLICATIONS HZ52 is a promising new type of 5-LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5-LO inhibitory mechanism different from classical 5-LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers. PMID:21506958

Tocopherol production in plant cell cultures.

PubMed

Caretto, Sofia; Nisi, Rossella; Paradiso, Annalisa; De Gara, Laura

2010-05-01

Tocopherols, collectively known as vitamin E, are lipophilic antioxidants, essential dietary components for mammals and exclusively synthesized by photosynthetic organisms. Of the four forms (alpha, beta, gamma and delta), alpha-tocopherol is the major vitamin E form present in green plant tissues, and has the highest vitamin E activity. Synthetic alpha-tocopherol, being a racemic mixture of eight different stereoisomers, always results less effective than the natural form (R,R,R) alpha-tocopherol. This raises interest in obtaining this molecule from natural sources, such as plant cell cultures. Plant cell and tissue cultures are able to produce and accumulate valuable metabolites that can be used as food additives, nutraceuticals and pharmaceuticals. Sunflower cell cultures, growing under heterotrophic conditions, were exploited to establish a suitable in vitro production system of natural alpha-tocopherol. Optimization of culture conditions, precursor feeding and elicitor application were used to improve the tocopherol yields of these cultures. Furthermore, these cell cultures were useful to investigate the relationship between alpha-tocopherol biosynthesis and photomixotrophic culture conditions, revealing the possibility to enhance tocopherol production by favouring sunflower cell photosynthetic properties. The modulation of alpha-tocopherol levels in plant cell cultures can provide useful hints for a regulatory impact on tocopherol metabolism.

Harmful and favourable ultraviolet conditions for human health over Northern Eurasia

NASA Astrophysics Data System (ADS)

Chubarova, Nataly; Zhdanova, Ekaterina

2014-05-01

We provide the analysis of the spatial and temporal distribution of ultraviolet (UV) radiation over Northern Eurasia taking into account for both its detrimental (erythema and eye-damage effects) and favourable (vitamin D synthesis) influence on human health. The UV effects on six different skin types are considered in order to cover the variety of skin types of European and Asian inhabitants. To better quantifying the vitamin D irradiance threshold we accounted for an open body fraction S as a function of effective air temperature. The spatial and temporal distribution of UV resources was estimated by radiative transfer (RT) modeling (8 stream DISORT RT code) with 1x 1 degree grid and monthly resolution. For this purpose special datasets of main input geophysical parameters (total ozone content, aerosol characteristics, surface UV albedo, UV cloud modification factor) have been created over the territory of Northern Eurasia, which can be of separate interest for the different multidisciplinary scientific applications over the PEEX domain. The new approaches were used to retrieve aerosol and cloud transmittance from different satellite and re-analysis datasets for calculating the solar UV irradiance at ground. Using model simulations and some experimental data we provide the altitude parameterization for different types of biologically active irradiance in mountainous area taking into account not only for the effects of molecular scattering but for the altitude dependence of aerosol parameters and surface albedo. Based on the new classification of UV resources (Chubarova, Zhdanova, 2013) we show that the distribution of harmful (UV deficiency and UV excess) and favorable UV conditions is regulated by various geophysical parameters (mainly, total ozone, cloudiness and open body fraction) and can significantly deviate from latitudinal dependence. The interactive tool for providing simulations of biologically active irradiance and its attribution to the different

Autologous intravenous bone marrow mononuclear cell therapy for patients with subacute ischaemic stroke: A pilot study

PubMed Central

Prasad, Kameshwar; Mohanty, Sujata; Bhatia, Rohit; Srivastava, M.V.P.; Garg, Ajay; Srivastava, Achal; Goyal, Vinay; Tripathi, Manjari; Kumar, Amit; Bal, Chandrashekar; Vij, Aarti; Mishra, Nalini Kant

2012-01-01

Background & objectives: Bone marrow mononuclear cell therapy has emerged as one of the option for the treatment of Stroke. Several preclinical studies have shown that the treatment with mononuclear cell (MNCs) can reduce the infarct size and improve the functional outcome. We evaluated the feasibility, safety and clinical outcome of administering bone marrow mononuclear cell (MNCs) intravenously to patients with subacute ischaemic stroke. Methods: In a non-randomized phase-I clinical study, 11 consecutive, eligible and consenting patients, aged 30-70 yr with ischaemic stroke involving anterior circulation within 7 to 30 days of onset of stroke were included. Bone marrow was aspirated from iliac crest and the harvested mononuclear cells were infused into antecubital vein. Outcomes measured for safety included immediate reactions after cell infusion and evidence of tumour formation at one year in whole body PET scan. Patients were followed at week 1, 4-6, 24 and 52 to determine clinical progress using National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), MRI, EEG and PET. Feasibility outcomes included target-dose feasibility. Favourable clinical outcome was defined as mRS score of 2 or less or BI score of 75 to 100 at six months after stem cell therapy. Results: Between September 2006 and April 2007, 11 patients were infused with bone-marrow mononuclear cells (mean 80 million with CD-34+ mean 0.92 million). Protocol was target-dose feasible in 9 patients (82%). FDG-PET scan at 24 and 52 wk in nine patients did not reveal evidence of tumour formation. Seven patients had favourable clinical outcome. Interpretation & conclusions: Intravenous bone marrow mononuclear cell therapy appears feasible and safe in patients with subacute ischaemic stroke. Further, a randomized controlled trial to examine its efficacy is being conducted. PMID:22960888

Living with strangers: direct benefits favour non-kin cooperation in a communally nesting bird.

PubMed

Riehl, Christina

2011-06-07

The greater ani (Crotophaga major), a Neotropical cuckoo, exhibits an unusual breeding system in which several socially monogamous pairs lay eggs in a single nest and contribute care to the communal clutch. Cooperative nesting is costly-females compete for reproduction by ejecting each other's eggs-but the potential direct or indirect fitness benefits that might accrue to group members have not been identified. In this study, I used molecular genotyping to quantify patterns of genetic relatedness and individual reproductive success within social groups in a single colour-banded population. Microsatellite analysis of 122 individuals in 49 groups revealed that group members are not genetic relatives. Group size was strongly correlated with individual reproductive success: solitary pairs were extremely rare and never successful, and nests attended by two pairs were significantly more likely to be depredated than were nests attended by three pairs. Egg loss, a consequence of reproductive competition, was greater in large groups and disproportionately affected females that initiated laying. However, early-laying females compensated for egg losses by laying larger clutches, and female group members switched positions in the laying order across nesting attempts. The greater ani, therefore, appears to be one of the few species in which cooperative breeding among unrelated individuals is favoured by direct, shared benefits that outweigh the substantial costs of reproductive competition.

Favourable IFNL3 genotypes are associated with spontaneous clearance and are differentially distributed in Aboriginals in Canadian HIV-hepatitis C co-infected individuals.

PubMed

Moqueet, Nasheed; Infante-Rivard, Claire; Platt, Robert W; Young, Jim; Cooper, Curtis; Hull, Mark; Walmsley, Sharon; Klein, Marina B

2015-03-20

Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected whites and Aboriginals from the Canadian Co-infection Cohort. HCV treatment-naïve individuals with at least two HCV RNA tests were included (n = 538). A spontaneous clearance case was defined as someone with two consecutive HCV RNA-negative tests, at least six months apart. Data were analyzed using Cox proportional hazards adjusted for sex and ethnicity. Advantageous variants and haplotypes were more common in Aboriginals than Caucasians: 57% vs. 46% had the rs12979860 CC genotype, respectively; 58% vs. 48%, rs8103142 TT; 74% vs. 67%, the rs12979860 C allele; and 67% vs. 64% the TCT haplotype with three favourable alleles. The adjusted Hazard Ratios (95% CI) for spontaneous clearance were: rs12979860: 3.80 (2.20, 6.54); rs8099917: 5.14 (2.46, 10.72); and rs8103142: 4.36 (2.49, 7.62). Even after adjusting for rs12979860, Aboriginals and females cleared HCV more often, HR (95% CI) = 1.53 (0.89, 2.61) and 1.42 (0.79, 2.53), respectively. Our results suggest that favourable IFNL3 genotypes are more common among Aboriginals than Caucasians, and may partly explain the higher HCV clearance rates seen among Aboriginals.

Cyclin D1 negatively regulates the expression of differentiation genes in HT-29 M6 mucus-secreting colon cancer cells.

PubMed

Mayo, Clara; Mayol, Xavier

2009-08-28

HT-29 M6 colon cancer cells differentiate to a mucus-secreting phenotype in culture. We found that the pattern of cyclin D1 expression in HT-29 M6 cells did not correlate with instances of cell proliferation but was specifically induced during a dedifferentiation process following disaggregation of epithelial cell layers, even under conditions that did not allow cell cycle reentrance. Interestingly, ectopic expression of cyclin D1 in differentiated cells led to the inhibition of the transcriptional activity of differentiation gene promoters, such as the mucin MUC1. We thus propose that the overexpression of cyclin D1 found in colon cancer favours tumour dedifferentiation as one mechanism of tumour progression.

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract.

PubMed

Manickam, Cordelia; Nwanze, Chiadika; Ram, Daniel R; Shah, Spandan V; Smith, Scott; Jones, Rhianna; Hueber, Brady; Kroll, Kyle; Varner, Valerie; Goepfert, Paul; Jost, Stephanie; Reeves, R Keith

2018-05-03

Recently, a seemingly novel innate immune cell subset bearing features of natural killer and B cells was identified in mice. So-called NKB cells appear as first responders to infections, but whether this cell population is truly novel or is in fact a subpopulation of B cells and exists in higher primates remains unclear. The objective of this study was to identify NKB cells in primates and study the impact of HIV/SIV infections. NKB cells were quantified in both naïve and lentivirus infected rhesus macaques and humans by excluding lineage markers (CD3, CD127), and positive Boolean gating for CD20, NKG2A/C and/or NKp46. Additional phenotypic measures were conducted by RNA-probe and traditional flow cytometry. Circulating cytotoxic NKB cells were found at similar frequencies in humans and rhesus macaques (range, 0.01-0.2% of total lymphocytes). NKB cells were notably enriched in spleen (median, 0.4% of lymphocytes), but were otherwise systemically distributed in tonsil, lymph nodes, colon, and jejunum. Expression of immunoglobulins was highly variable, but heavily favoured IgM and IgA rather than IgG. Interestingly, NKB cell frequencies expanded in PBMC and colon during SIV infection, as did IgG expression, but were generally unaltered in HIV-infected humans. These results suggest a cell type expressing both natural killer and B-cell features exists in rhesus macaques and humans and are perturbed by HIV/SIV infection. The full functional niche remains unknown, but the unique phenotype and systemic distribution could make NKB cells unique targets for immunotherapeutics or vaccine strategies.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro.

PubMed

Palethorpe, Helen M; Leach, Damien A; Need, Eleanor F; Drew, Paul A; Smith, Eric

2018-04-10

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo , providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro

PubMed Central

Palethorpe, Helen M.; Leach, Damien A.; Need, Eleanor F.; Drew, Paul A.; Smith, Eric

2018-01-01

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo, providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome. PMID:29721186

Analysis of conditions favourable for small vertical axis wind turbines between building passages in urban areas of Sweden

NASA Astrophysics Data System (ADS)

Awan, Muhammad Rizwan; Riaz, Fahid; Nabi, Zahid

2017-05-01

This paper presents the analysis of installing the vertical axis wind turbines between the building passages on an island in Stockholm, Sweden. Based on the idea of wind speed amplification due to the venture effect in passages, practical measurements were carried out to study the wind profile for a range of passage widths in parallel building passages. Highest increment in wind speed was observed in building passages located on the periphery of sland as wind enters from free field. Wind mapping was performed in the island to choose the most favourable location to install the vertical axis wind turbines (VAWT). Using the annual wind speed data for location and measured amplification factor, energy potential of the street was calculated. This analysis verified that small vertical axis wind turbines can be installed in the passage centre line provided that enough space is provided for traffic and passengers.

Cell cycle arrest in the jewel wasp Nasonia vitripennis in larval diapause.

PubMed

Shimizu, Yuta; Mukai, Ayumu; Goto, Shin G

2018-04-01

Insects enter diapause to synchronise their life cycle with biotic and abiotic environmental conditions favourable for their development, reproduction, and survival. One of the most noticeable characteristics of diapause is the blockage of ontogeny. Although this blockage should occur with the cessation of cellular proliferation, i.e. cell cycle arrest, it was confirmed only in a few insect species and information on the molecular pathways involved in cell cycle arrest is limited. In the present study, we investigated developmental and cell cycle arrest in diapause larvae of the jewel wasp Nasonia vitripennis. Developmental and cell cycle arrest occur in the early fourth instar larval stage of N. vitripennis under short days. By entering diapause, the S fraction of the cell cycle disappears and approximately 80% and 20% of cells arrest their cell cycle in the G0/G1 and G2 phases, respectively. We further investigated expression of cell cycle regulatory genes and some housekeeping genes to dissect molecular mechanisms underlying the cell cycle arrest. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomechanical cell regulatory networks as complex adaptive systems in relation to cancer.

PubMed

Feller, Liviu; Khammissa, Razia Abdool Gafaar; Lemmer, Johan

2017-01-01

Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis. Some of the non-genetic factors that may also favour cancerization are dysregulation in epithelial-mesenchymal interactions, in cell-to-cell communication, in extracellular matrix turnover, in extracellular matrix-to-cell interactions and in mechanotransduction pathways. Persistent increase in extracellular matrix stiffness, for whatever reason, has been shown to play an important role in cell transformation, and later in cancer cell invasion. In this article we review certain cell regulatory networks driving carcinogenesis, focussing on the role of mechanical stresses modulating structure and function of cells and their extracellular matrices.

Advances in ethanol production using immobilized cell systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Margaritis, A.; Merchant, F.J.A.

The application of immobilized cell systems for the production of ethanol has resulted in substantial improvements in the efficiency of the process when compared to the traditional free cell system. In this review, the various methods of cell immobilization employed in ethanol production systems have been described in detail. Their salient features, performance characteristics, advantages and limitations have been critically assessed. More recently, these immobilized cell systems have also been employed for the production of ethanol from non-conventional feedstocks such as Jerusalem artichoke extracts, cheese whey, cellulose, cellobiose and xylose. Ethanol production by immobilized yeast and bacterial cells has beenmore » attempted in various bioreactor types. Although most of these studies have been carried out using laboratory scale prototype bioreactors, it appears that only fluidized bed, horizontally packed bed bioreactors and tower fermenters may find application on scale-up. Several studies have indicated that upon immobilization, yeast cells performing ethanol fermentation exhibit more favourable physiological and metabolic properties. This, in addition to substantial improvements in ethanol productivities by immobilized cell systems, is indicative of the fact that future developments in the production of ethanol and alcoholic beverages will be directed towards the use of immobilized cell systems. 291 references.« less

Preferential invasion of mitotic cells by Salmonella reveals that cell surface cholesterol is maximal during metaphase.

PubMed

Santos, António J M; Meinecke, Michael; Fessler, Michael B; Holden, David W; Boucrot, Emmanuel

2013-07-15

Cell surface-exposed cholesterol is crucial for cell attachment and invasion of many viruses and bacteria, including the bacterium Salmonella, which causes typhoid fever and gastroenteritis. Using flow cytometry and 3D confocal fluorescence microscopy, we found that mitotic cells, although representing only 1-4% of an exponentially growing population, were much more efficiently targeted for invasion by Salmonella. This targeting was not dependent on the spherical shape of mitotic cells, but was instead SipB and cholesterol dependent. Thus, we measured the levels of plasma membrane and cell surface cholesterol throughout the cell cycle using, respectively, brief staining with filipin and a fluorescent ester of polyethylene glycol-cholesterol that cannot flip through the plasma membrane, and found that both were maximal during mitosis. This increase was due not only to the rise in global cell cholesterol levels along the cell cycle but also to a transient loss in cholesterol asymmetry at the plasma membrane during mitosis. We measured that cholesterol, but not phosphatidylserine, changed from a ∼2080 outerinner leaflet repartition during interphase to ∼5050 during metaphase, suggesting this was specific to cholesterol and not due to a broad change of lipid asymmetry during metaphase. This explains the increase in outer surface levels that make dividing cells more susceptible to Salmonella invasion and perhaps to other viruses and bacteria entering cells in a cholesterol-dependent manner. The change in cholesterol partitioning also favoured the recruitment of activated ERM (Ezrin, Radixin, Moesin) proteins at the plasma membrane and thus supported mitotic cell rounding.

Nanoliter reactors improve multiple displacement amplification of genomes from single cells.

PubMed

Marcy, Yann; Ishoey, Thomas; Lasken, Roger S; Stockwell, Timothy B; Walenz, Brian P; Halpern, Aaron L; Beeson, Karen Y; Goldberg, Susanne M D; Quake, Stephen R

2007-09-01

Since only a small fraction of environmental bacteria are amenable to laboratory culture, there is great interest in genomic sequencing directly from single cells. Sufficient DNA for sequencing can be obtained from one cell by the Multiple Displacement Amplification (MDA) method, thereby eliminating the need to develop culture methods. Here we used a microfluidic device to isolate individual Escherichia coli and amplify genomic DNA by MDA in 60-nl reactions. Our results confirm a report that reduced MDA reaction volume lowers nonspecific synthesis that can result from contaminant DNA templates and unfavourable interaction between primers. The quality of the genome amplification was assessed by qPCR and compared favourably to single-cell amplifications performed in standard 50-microl volumes. Amplification bias was greatly reduced in nanoliter volumes, thereby providing a more even representation of all sequences. Single-cell amplicons from both microliter and nanoliter volumes provided high-quality sequence data by high-throughput pyrosequencing, thereby demonstrating a straightforward route to sequencing genomes from single cells.

The contribution of B-cell proliferation to spleen enlargement in Babesia microti-infected mice.

PubMed Central

Inchley, C J

1987-01-01

Flow cytofluorimetric analysis showed that B-cell proliferation makes a major contribution to the enlargement and increased cellularity of the spleen, which are characteristic of Babesia microti infections in mice. Expansion of the B-cell population was accompanied by modulation of the cell surface, which affected most B lymphocytes, and which was detected as a reduction in the density of surface immunoglobulin. This effect was noted as early as Day 7, shortly after the appearance of parasites in the circulation and the onset of gross spleen changes. In contrast to the results for B cells, the frequency of splenic T cells declined, and when the data were transformed into absolute numbers it became clear that only limited T-cell proliferation had occurred. There was no evidence to suggest that the balance of T-cell subsets was shifted in favour of suppressor T cells. The relationships of these results to reports of immunosuppression by this parasite are discussed. Images Figure 2 Figure 5 PMID:3493207

Regulatory landscape for cell therapy--EU view.

PubMed

McBlane, James W

2015-09-01

This article addresses regulation of cell therapies in the European Union (EU), covering cell sourcing and applications for clinical trials and marketing authorisation applications. Regulatory oversight of cell sourcing and review of applications for clinical trials with cell therapies are handled at national level, that is, separately with each country making its own decisions. For clinical trials, this can lead to different decisions in different countries for the same trial. A regulation is soon to come into force that will address this and introduce a more efficient clinical trial application process. However, at the marketing authorisation stage, the process is pan-national: the Committee for Human Medicinal Products (CHMP) is responsible for giving the final scientific opinion on all EU marketing authorisation applications for cell therapies: favourable scientific opinions are passed to the European Commission (EC) for further consultation and, if successful, grant of a marketing authorisation valid in all 28 EU countries. In its review of applications for marketing authorisations (MAAs) for cell therapies, the CHMP is obliged to consult the Committee for Advanced Therapies (CAT), who conduct detailed scientific assessments of these applications, with assessment by staff from national regulatory authorities and specialist advisors to the regulators. Copyright © 2015.

Zinc ions regulate opening of tight junction favouring efflux of macromolecules via the GSK3β/snail-mediated pathway.

PubMed

Xiao, Ruyue; Yuan, Lan; He, Weijiang; Yang, Xiaoda

2018-01-24

Zinc is an essential trace element presenting in particularly high concentration in the brain. In some regions, e.g. lateral amygdala, subiculum and hippocampus, rapidly-exchangeable zinc may transiently reach even up to 600 μM. To explore the possible roles of high-concentration Zn 2+ in regulating the blood-brain barrier (BBB), we investigated the effects of Zn 2+ on the functions and structures of the tight junction (TJ) with an in vitro model of a Madin-Darby canine kidney (MDCK) cell monolayer. The experimental results indicated that high concentrations (>200 μM) of Zn 2+ can affect the TJ integrity in a polarized manner. Basolateral addition of Zn 2+ led to reversible TJ opening with pore paths of r ∼ 2 nm or more depending on Zn 2+ concentration. The efflux/influx ratios of different sized probes were found to be ∼4.6 for FD4 (M W 4000) and ∼1.8 for Eu-DTPA (M W 560), suggesting that the Zn 2+ -induced paracelluar channels favour efflux especially for macromolecules. Further mechanistic studies revealed that the elevated intracellular Zn 2+ taken from the basolateral side can increase phosphorylation of glycogen synthase kinase (GSK) 3β, primarily due to the inhibition of calcineurin (CaN), thus resulting in the elevation of the snail transcriptional repressors. Subsequently, Zn 2+ can cause the down-regulation of claudin-1, breakage of occludin and ZO-1 rings, and collapse of basolateral F-actin structures. These overall factors result in the formation of a trumpet-like paracellular channel, which allows asymmetric solute permeation. The ERK1/2 and JNK1/2 pathways may also be involved in the Zn 2+ -induced TJ opening process, while the activation of matrix metalloproteinase was not observed. Our results may suggest a potential role of zinc in regulation of BBB permeability associated with brain clearance of metabolites through the glymphatic system.

Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion.

PubMed

Ganier, Olivier; Schnerch, Dominik; Nigg, Erich A

2018-06-01

Centrosome aberrations disrupt tissue architecture and may confer invasive properties to cancer cells. Here we show that structural centrosome aberrations, induced by overexpression of either Ninein-like protein (NLP) or CEP131/AZI1, sensitize polarized mammalian epithelia to basal cell extrusion. While unperturbed epithelia typically dispose of damaged cells through apical dissemination into luminal cavities, certain oncogenic mutations cause a switch in directionality towards basal cell extrusion, raising the potential for metastatic cell dissemination. Here we report that NLP-induced centrosome aberrations trigger the preferential extrusion of damaged cells towards the basal surface of epithelial monolayers. This switch in directionality from apical to basal dissemination coincides with a profound reorganization of the microtubule cytoskeleton, which in turn prevents the contractile ring repositioning that is required to support extrusion towards the apical surface. While the basal extrusion of cells harbouring NLP-induced centrosome aberrations requires exogenously induced cell damage, structural centrosome aberrations induced by excess CEP131 trigger the spontaneous dissemination of dying cells towards the basal surface from MDCK cysts. Thus, similar to oncogenic mutations, structural centrosome aberrations can favour basal extrusion of damaged cells from polarized epithelia. Assuming that additional mutations may promote cell survival, this process could sensitize epithelia to disseminate potentially metastatic cells. © 2018 The Authors.

Adhesion and migration of CHO cells on micropatterned single layer graphene

NASA Astrophysics Data System (ADS)

Keshavan, S.; Oropesa-Nuñez, R.; Diaspro, A.; Canale, C.; Dante, S.

2017-06-01

Cell patterning technology on single layer graphene (SLG) is a fairly new field that can find applications in tissue engineering and biomaterial/biosensors development. Recently, we have developed a simple and effective approach for the fabrication of patterned SLG substrates by laser micromachining, and we have successfully applied it for the obtainment of geometrically ordered neural networks. Here, we exploit the same approach to investigate the generalization of the cell response to the surface cues of the fabricated substrates and, contextually, to quantify cell adhesion on the different areas of the patterns. To attain this goal, we tested Chinese hamster ovary (CHO) cells on PDL-coated micropatterned SLG substrates and quantified the adhesion by using single cell force spectroscopy (SCFS). Our results indicate higher cell adhesion on PDL-SLG, and, consequently, an initial CHO cell accumulation on the graphene areas, confirming the neuronal behaviour observed previously; interestingly, at later time point in culture, cell migration was observed towards the adjacent SLG ablated regions, which resulted more favourable for cell proliferation. Therefore, our findings indicate that the mechanism of interaction with the surface cues offered by the micropatterned substrates is strictly cell-type dependent.

Favourable outcome in a child with symptomatic diagnosis of Glutaric aciduria type 1 despite vertical HIV infection and minor head trauma.

PubMed

Thomas, Angeline; Dobbels, Els F M; Springer, Priscilla E; Ackermann, Christelle; Cotton, Mark F; Laughton, Barbara

2018-04-01

The first case of Glutaric aciduria Type 1(GA1) in an African child was reported in 2001. GA1 has a prevalence of 1:5000 in black South Africans. Although early diagnosis is essential for a favourable outcome, newborn screening is not routine in South Africa where an estimated 320,000 children have HIV infection. Neurodevelopmental delay and encephalopathy are complications of both HIV and GA1. In such a setting it is important to recognise that HIV and GA1 can occur simultaneously. We present an HIV-infected South African male child of Xhosa descent with macrocephaly who commenced combination antiretroviral therapy (ART) at 8 weeks of age in a clinical trial which included a neurodevelopmental sub-study. He developed short-lived focal seizures at 16 months after minor head trauma. Neurological examination was normal. Neuroimaging showed temporal lobe atrophy, subtle hyperintense signal change in the globus pallidus, and focal haemosiderosis in the right Sylvian fissure region. As findings were not in keeping with HIV encephalopathy, a urine metabolic screen was undertaken which suggested GA1. Genetic testing confirmed Arg293Trp mutation. He began L-carnitine and a low protein diet as a restricted diet was not practicable. At 21 months he developed pulmonary tuberculosis, requiring 6 months treatment. He did not develop any neurologic motor symptoms. Serial neurodevelopmental and neuropsychological test scores until 9 years were similar to healthy neighbourhood controls, except for mild language delay at 3½ years. Detection of GA1, probably facilitated through participation in a clinical trial, was pivotal for a favourable outcome. The concomitant use of ART and anti-tuberculous therapy in a child with GA1 appears safe.

Downstream effects of ROCK signaling in cultured human corneal stromal cells: microarray analysis of gene expression.

PubMed

Harvey, Stephen A K; Anderson, Susan C; SundarRaj, Nirmala

2004-07-01

Rho-associated coiled-coil-containing protein kinase (ROCK) is a downstream target of Rho GTPase signaling and regulates the assembly of stress fibers. Previous reports indicate that Rho/ROCK signaling is involved in the regulation of several cellular processes, some of which may be cell-type specific and are probably critical to corneal stromal cell activation. The present study identified ROCK-regulated gene expression in corneal stromal cells. Corneal stromal cells derived from eyes of three different donors were cultured to yield the following designated phenotypes: baseline fibroblasts (DMEM with 10% serum), activated fibroblasts (10% serum+bFGF+heparin), and myofibroblasts (1% serum+TGF-beta 1). Cells were exposed to the ROCK inhibitor Y-27632 or vehicle for 12 hours, and transcript levels altered by ROCK inhibition were identified with oligonucleotide microarrays (GeneChips; Affymetrix, Santa Clara, CA). In these phenotypes, Y-27632 caused marked (twofold or more) increases or decreases in 14/4, 12/3, and 15/10 transcripts. In both fibroblast groups Y-27632-treatment increased expression of endothelin receptors and of parathyroid hormone-like hormone. The upregulation of alpha-smooth muscle actin in myofibroblasts was attenuated by Y-27632. Combining data from all groups identified ROCK-supported (Y-27632 inhibitable) expression of 10 transcripts, including ribonucleotide reductase M2, the cyclin B1-CDC2-CKS2 system, and four mitotic spindle-associated proteins. ROCK inhibition causes broad inhibition of DNA synthesis and mitosis and causes changes that are different between (bFGF-activated) fibroblasts and (TGF-beta 1-induced) myofibroblasts. Thus, Rho/ROCK signaling regulates both common and distinct downstream events in corneal stromal cells activated (differentiated) to fibroblast or myofibroblast phenotype.

Evaluation of the Spies™ modalities image quality

PubMed Central

Emiliani, Esteban; Talso, Michele; Baghdadi, Mohammed; Barreiro, Aarón; Orosa, Andrea; Serviàn, Pol; Gavrilov, Pavel; Proietti, Silvia; Traxer, Olivier

2017-01-01

Introduction The Spies™ system (Karl-Storz®) was introduced into digital ureteroscopy to improve endoscopic vision. To date, there is no data to either indicate which of the Spies modalities is better for improving diagnosis and treatment procedures, nor to compare the modalities in terms of image quality. The aim of this study was to evaluate and compare the image quality of five Spies™ modalities (SM) to the standard white light in an in-vitro model. Materials and Methods Two standardized grids and 3 stones of different composition were recorded in white light and the 5SM (Clara, Chroma, Clara+Chroma), Spectra A and B) using 4 standardized aqueous scenarios. Twelve templates were done in order to simultaneously compare the same objective in the different modalities. Six urologists, five medical students, five urology residents, and five persons not involved with urology evaluated each video on a scale of 1 (very bad) to 5 (very good). Results Comparing white light to SM, subjects scored better the quality of Clara and Clara+Chroma than white light (p=0.0139 and p<0.05) and scored worse Spectra A and B (p=0.0005 and p=0.0023)). When comparing Clara to the other SM, it was ranked equivalent to Clara+Chroma (p=0.67) and obtained a higher rank than Chroma, Spectra A and B (p<0.05, p=0.0001 and p=0.0001). In the multivariate analysis mean scores were higher among urologists. Conclusion In all analyzed scenarios, the subjects ranked Clara and Clara+Chroma as the modalities with better image quality compared to white light. PMID:28338307

Evaluation of the Spies TM modalities image quality.

PubMed

Emiliani, Esteban; Talso, Michele; Baghdadi, Mohammed; Barreiro, Aaron; Orosa, Andrea; Serviàn, Pol; Gavrilov, Pavel; Proietti, Silvia; Traxer, Olivier

2017-01-01

The Spies™ system (Karl-Storz®) was introduced into digital ureteroscopy to improve endoscopic vision. To date, there is no data to either indicate which of the Spies modalities is better for improving diagnosis and treatment procedures, nor to compare the modalities in terms of image quality. The aim of this study was to evaluate and compare the image quality of five Spies™ modalities (SM) to the standard white light in an in-vitro model. Two standardized grids and 3 stones of different composition were recorded in white light and the 5SM (Clara, Chroma, Clara+Chroma), Spectra A and B) using 4 standardized aqueous scenarios. Twelve templates were done in order to simultaneously compare the same objective in the different modalities. Six urologists, five medical students, five urology residents, and five persons not involved with urology evaluated each video on a scale of 1 (very bad) to 5 (very good). Comparing white light to SM, subjects scored better the quality of Clara and Clara+Chroma than white light (p=0.0139 and p<0.05) and scored worse Spectra A and B (p=0.0005 and p=0.0023). When comparing Clara to the other SM, it was ranked equivalent to Clara+Chroma (p=0.67) and obtained a higher rank than Chroma, Spectra A and B (p<0.05, p=0.0001 and p=0.0001). In the multivariate analysis mean scores were higher among urologists. In all analyzed scenarios, the subjects ranked Clara and Clara+Chroma as the modalities with better image quality compared to white light. Copyright® by the International Brazilian Journal of Urology.

Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities.

PubMed

Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

2015-01-01

To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye.

Nanostructuring of Aluminum Alloy Powders by Cryogenic Attrition with Hydrogen-Free Process Control Agent

DTIC Science & Technology

2015-02-01

Nanostructuring of Aluminum Alloy Powders by Cryogenic Attrition with Hydrogen-Free Process Control Agent by Frank Kellogg , Clara Hofmeister...Process Control Agent Frank Kellogg Bowhead Science and Technology Clara Hofmeister Advanced Materials Processing and Analysis Center...NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Frank Kellogg , Clara Hofmeister, Anit Giri, and Kyu Cho 5d. PROJECT NUMBER 5e

Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study.

PubMed

Boers, Inge; Muskiet, Frits Aj; Berkelaar, Evert; Schut, Erik; Penders, Ria; Hoenderdos, Karine; Wichers, Harry J; Jong, Miek C

2014-10-11

The main goal of this randomized controlled single-blinded pilot study was to study whether, independent of weight loss, a Palaeolithic-type diet alters characteristics of the metabolic syndrome. Next we searched for outcome variables that might become favourably influenced by a Paleolithic-type diet and may provide new insights in the pathophysiological mechanisms underlying the metabolic syndrome. In addition, more information on feasibility and designing an innovative dietary research program on the basis of a Palaeolithic-type diet was obtained. Thirty-four subjects, with at least two characteristics of the metabolic syndrome, were randomized to a two weeks Palaeolithic-type diet (n = 18) or an isoenergetic healthy reference diet, based on the guidelines of the Dutch Health Council (n = 14). Thirty-two subjects completed the study. Measures were taken to keep bodyweight stable. As primary outcomes oral glucose tolerance and characteristics of the metabolic syndrome (abdominal circumference, blood pressure, glucose, lipids) were measured. Secondary outcomes were intestinal permeability, inflammation and salivary cortisol. Data were collected at baseline and after the intervention. Subjects were 53.5 (SD9.7) year old men (n = 9) and women (n = 25) with mean BMI of 31.8 (SD5.7) kg/m2. The Palaeolithic-type diet resulted in lower systolic blood pressure (-9.1 mmHg; P = 0.015), diastolic blood pressure (-5.2 mmHg; P = 0.038), total cholesterol (-0.52 mmol/l; P = 0.037), triglycerides (-0.89 mmol/l; P = 0.001) and higher HDL-cholesterol (+0.15 mmol/l; P = 0.013), compared to reference. The number of characteristics of the metabolic syndrome decreased with 1.07 (P = 0.010) upon the Palaeolithic-type diet, compared to reference. Despite efforts to keep bodyweight stable, it decreased in the Palaeolithic group compared to reference (-1.32 kg; P = 0.012). However, favourable effects remained after post-hoc adjustments for this

Organic farming favours insect-pollinated over non-insect pollinated forbs in meadows and wheat fields.

PubMed

Batáry, Péter; Sutcliffe, Laura; Dormann, Carsten F; Tscharntke, Teja

2013-01-01

The aim of this study was to determine the relative effects of landscape-scale management intensity, local management intensity and edge effect on diversity patterns of insect-pollinated vs. non-insect pollinated forbs in meadows and wheat fields. Nine landscapes were selected differing in percent intensively used agricultural area (IAA), each with a pair of organic and conventional winter wheat fields and a pair of organic and conventional meadows. Within fields, forbs were surveyed at the edge and in the interior. Both diversity and cover of forbs were positively affected by organic management in meadows and wheat fields. This effect, however, differed significantly between pollination types for species richness in both agroecosystem types (i.e. wheat fields and meadows) and for cover in meadows. Thus, we show for the first time in a comprehensive analysis that insect-pollinated plants benefit more from organic management than non-insect pollinated plants regardless of agroecosystem type and landscape complexity. These benefits were more pronounced in meadows than wheat fields. Finally, the community composition of insect-pollinated and non-insect-pollinated forbs differed considerably between management types. In summary, our findings in both agroecosystem types indicate that organic management generally supports a higher species richness and cover of insect-pollinated plants, which is likely to be favourable for the density and diversity of bees and other pollinators.

Organic Farming Favours Insect-Pollinated over Non-Insect Pollinated Forbs in Meadows and Wheat Fields

PubMed Central

Batáry, Péter; Sutcliffe, Laura; Dormann, Carsten F.; Tscharntke, Teja

2013-01-01

The aim of this study was to determine the relative effects of landscape-scale management intensity, local management intensity and edge effect on diversity patterns of insect-pollinated vs. non-insect pollinated forbs in meadows and wheat fields. Nine landscapes were selected differing in percent intensively used agricultural area (IAA), each with a pair of organic and conventional winter wheat fields and a pair of organic and conventional meadows. Within fields, forbs were surveyed at the edge and in the interior. Both diversity and cover of forbs were positively affected by organic management in meadows and wheat fields. This effect, however, differed significantly between pollination types for species richness in both agroecosystem types (i.e. wheat fields and meadows) and for cover in meadows. Thus, we show for the first time in a comprehensive analysis that insect-pollinated plants benefit more from organic management than non-insect pollinated plants regardless of agroecosystem type and landscape complexity. These benefits were more pronounced in meadows than wheat fields. Finally, the community composition of insect-pollinated and non-insect-pollinated forbs differed considerably between management types. In summary, our findings in both agroecosystem types indicate that organic management generally supports a higher species richness and cover of insect-pollinated plants, which is likely to be favourable for the density and diversity of bees and other pollinators. PMID:23382979

A critical review of which children with acute myeloid leukaemia need stem cell procedures.

PubMed

Hasle, Henrik

2014-07-01

The last decades have seen parallel improvements in chemotherapy-based and haematopoietic stem cell transplantation (HSCT) regimens for acute myeloid leukaemia (AML) in children. There has been no consensus on indication for HSCT. Reserving HSCT for high-risk and relapsed patients spare many patients from the long-term toxicity of this treatment. The results of matched unrelated donor HSCT equal family donor transplantation and the presence of a matched sibling should no longer be a transplant indication. Minimal residual disease measured by flow cytometry may identify poor responders benefitting from HSCT in first complete remission (CR1) and those with a favourable response to induction therapy who do not need HSCT even with adverse cytogenetic aberrations. FLT3-internal tandem duplication without NPM1 mutation has a very high relapse rate despite favourable response and HSCT is indicated in CR1 in these cases. Finding the optimal indications for HSCT is a delicate balance between risk of relapse and late effects. © 2014 John Wiley & Sons Ltd.

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

PubMed

Gonzalez-Serna, A; Ferrando-Martinez, S; Tarancon-Diez, L; De Pablo-Bernal, R S; Dominguez-Molina, B; Jiménez, J L; Muñoz-Fernández, M Á; Leal, M; Ruiz-Mateos, E

2017-12-20

NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.

Atopic dermatitis induces the expansion of thymus-derived regulatory T cells exhibiting a Th2-like phenotype in mice.

PubMed

Moosbrugger-Martinz, Verena; Tripp, Christoph H; Clausen, Björn E; Schmuth, Matthias; Dubrac, Sandrine

2016-05-01

Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility, immune hyper-responsiveness of the skin and environmental factors. Although the important role of abnormal immune reactivity in the pathogenesis of AD is widely accepted, the role of regulatory T cells (Tregs) remains elusive. We found that the Treg population is expanded in a mouse model of AD, i.e. mice topically treated with vitamin D3 (VitD). Moreover, mice with AD-like symptoms exhibit increased inducible T-cell costimulator (ICOS)-, cytotoxic T-lymphocyte antigen-4 (CTLA-4)- and Glycoprotein-A repetitions predominant receptor (GARP)-expressing Tregs in skin-draining lymph nodes. Importantly, the differentiation of Tregs into thymus-derived Tregs is favoured in our mouse model of AD. Emigrated skin-derived dendritic cells are required for Treg induction and Langerhans cells are responsible for the biased expansion of thymus-derived Tregs . Intriguingly, thymus-derived Tregs isolated from mice with AD-like symptoms exhibit a Th2 cytokine profile. Thus, AD might favour the expansion of pathogenic Tregs able to produce Th2 cytokines and to promote the disease instead of alleviating symptoms. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

NASA Astrophysics Data System (ADS)

Khetan, Sudhir; Guvendiren, Murat; Legant, Wesley R.; Cohen, Daniel M.; Chen, Christopher S.; Burdick, Jason A.

2013-05-01

Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

USAF Advanced Terrestrial Energy Study. Volume 4. Analysis, Data, and Bibliography.

DTIC Science & Technology

1983-04-01

OBJECTIVE OF THIS PROGRAM IS T0 DEVELOP A METHODOLOGY FOR PREDICTING LON(.o-TERM FUEL CELL PERFORM4ANCE FROM S"ORT-TEIM VESTING. APPLYING THE PERVURbATION...ION PROGRAM WAS DEVELOPED FOR ACTUALLY INSTALLINGP THE FUEL CELL POWER PLANT AT THE SANTA CLARA SIE DE SCh1PT ORS6 AIR POLLUTION DATtMENT;AUXILIARY...IV OF THE CERAMIC TECHNOLUGY READINESS PROGRAM TITL IMDNU) ADVANCED MATER IALS FUR ALTERNATIVE FUEL CAPABLE DIRECTLY FIRED HEAT ENGINES 36 - - - . r

T helper type 17 cells contribute to anti-tumour immunity and promote the recruitment of T helper type 1 cells to the tumour.

PubMed

Nuñez, Sarah; Saez, Juan Jose; Fernandez, Dominique; Flores-Santibañez, Felipe; Alvarez, Karla; Tejon, Gabriela; Ruiz, Paulina; Maldonado, Paula; Hidalgo, Yessia; Manriquez, Valeria; Bono, Maria Rosa; Rosemblatt, Mario; Sauma, Daniela

2013-05-01

T helper type 17 (Th17) lymphocytes are found in high frequency in tumour-burdened animals and cancer patients. These lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, have a well-defined role in the development of inflammatory and autoimmune pathologies; however, their function in tumour immunity is less clear. We explored possible opposing anti-tumour and tumour-promoting functions of Th17 cells by evaluating tumour growth and the ability to promote tumour infiltration of myeloid-derived suppressor cells (MDSC), regulatory T cells and CD4(+)  interferon-γ(+) cells in a retinoic acid-like orphan receptor γt (RORγt) -deficient mouse model. A reduced percentage of Th17 cells in the tumour microenvironment in RORγt-deficient mice led to enhanced tumour growth, that could be reverted by adoptive transfer of Th17 cells. Differences in tumour growth were not associated with changes in the accumulation or suppressive function of MDSC and regulatory T cells but were related to a decrease in the proportion of CD4(+) T cells in the tumour. Our results suggest that Th17 cells do not affect the recruitment of immunosuppressive populations but favour the recruitment of effector Th1 cells to the tumour, thereby promoting anti-tumour responses. © 2012 Blackwell Publishing Ltd.

Circadian rhythm of a Silene species favours nocturnal pollination and constrains diurnal visitation

PubMed Central

Prieto-Benítez, Samuel; Dötterl, Stefan; Giménez-Benavides, Luis

2016-01-01

Background and Aims Traits related to flower advertisement and reward sometimes vary in a circadian way, reflecting phenotypic specialization. However, specialized flowers are not necessarily restricted to specialized pollinators. This is the case of most Silene species, typically associated with diurnal or nocturnal syndromes of pollination but usually showing complex suites of pollinators. Methods A Silene species with mixed floral features between diurnal and nocturnal syndromes was used to test how petal opening, nectar production, scent emission and pollination success correlate in a circadian rhythm, and whether this is influenced by environmental conditions. The effect of diurnal and nocturnal visitation rates on plant reproductive success is also explored in three populations, including the effect of the pollinating seed predator Hadena sancta. Key Results The result showed that repeated petal opening at dusk was correlated with nectar secretion and higher scent production during the night. However, depending on environmental conditions, petals remain opened for a while in the morning, when nectar and pollen still were available. Pollen deposition was similarly effective at night and in the morning, but less effective in the afternoon. These results were consistent with field studies. Conclusions The circadian rhythm regulating floral attractiveness and reward in S. colorata is predominantly adapted to nocturnal flower visitors. However, favourable environmental conditions lengthen the optimal daily period of flower attraction and pollination towards morning. This allows the complementarity of day and night pollination. Diurnal pollination may help to compensate the plant reproductive success when nocturnal pollinators are scarce and when the net outcome of H. sancta shifts from mutualism to parasitism. These results suggest a functional mechanism explaining why the supposed nocturnal syndrome of many Silene species does not successfully predict their

Degradable Organically-Derivatized Polyoxometalate with Enhanced Activity against Glioblastoma Cell Line

NASA Astrophysics Data System (ADS)

She, Shan; Bian, Shengtai; Huo, Ruichao; Chen, Kun; Huang, Zehuan; Zhang, Jiangwei; Hao, Jian; Wei, Yongge

2016-09-01

High efficacy and low toxicity are critical for cancer treatment. Polyoxometalates (POMs) have been reported as potential candidates for cancer therapy. On accounts of the slow clearance of POMs, leading to long-term toxicity, the clinical application of POMs in cancer treatment is restricted. To address this problem, a degradable organoimido derivative of hexamolybdate is developed by modifying it with a cleavable organic group, leading to its degradation. Of note, this derivative exhibits favourable pharmacodynamics towards human malignant glioma cell (U251), the ability to penetrate across blood brain barrier and low toxicity towards rat pheochromocytoma cell (PC12). This line of research develops an effective POM-based agent for glioblastoma inhibition and will pave a new way to construct degradable anticancer agents for clinical cancer therapy.

Deliberation favours social efficiency by making people disregard their relative shares: evidence from USA and India

PubMed Central

Corgnet, Brice; Espín, Antonio M.; Hernán-González, Roberto

2017-01-01

Groups make decisions on both the production and the distribution of resources. These decisions typically involve a tension between increasing the total level of group resources (i.e. social efficiency) and distributing these resources among group members (i.e. individuals' relative shares). This is the case because the redistribution process may destroy part of the resources, thus resulting in socially inefficient allocations. Here we apply a dual-process approach to understand the cognitive underpinnings of this fundamental tension. We conducted a set of experiments to examine the extent to which different allocation decisions respond to intuition or deliberation. In a newly developed approach, we assess intuition and deliberation at both the trait level (using the Cognitive Reflection Test, henceforth CRT) and the state level (through the experimental manipulation of response times). To test for robustness, experiments were conducted in two countries: the USA and India. Despite absolute-level differences across countries, in both locations we show that: (i) time pressure and low CRT scores are associated with individuals' concerns for their relative shares and (ii) time delay and high CRT scores are associated with individuals' concerns for social efficiency. These findings demonstrate that deliberation favours social efficiency by overriding individuals' intuitive tendency to focus on relative shares. PMID:28386421

Blood pressure targets in type 2 diabetes. Evidence against or in favour of an aggressive approach.

PubMed

Mancia, Giuseppe; Grassi, Guido

2018-03-01

When associated with high blood pressure, type 2 diabetes mellitus is characterised by a high risk of adverse cardiovascular (CV) and renal outcomes. However, both can be effectively reduced by antihypertensive treatment. Current guidelines on the treatment of hypertension emphasize the need to effectively treat high blood pressure in diabetic individuals, but their recommendations differ in terms of the optimal target blood pressure value to aim for in order to maximise CV and renal protection. In some guidelines the recommended target blood pressure values are <140/90 mmHg (systolic/diastolic), whereas in others, blood pressure values close or even less than 130/80 mmHg are recommended. This paper will discuss the evidence for and against a conservative or more aggressive blood pressure target for treated diabetic hypertensive individuals based on the evidence provided by randomised trials, trial meta-analyses and large observational studies. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90 mmHg, and that values approaching 130/80 mmHg should be recommended. However, evidence in favour of even lower systolic values, i.e. <130 mmHg, is limited and is definitively against a reduction to <120 mmHg.

Protein and cell micropatterning and its integration with micro/nanoparticles assembly.

PubMed

Yap, F L; Zhang, Y

2007-01-15

Micropatterning of proteins and cells has become very popular over the past decade due to its importance in the development of biosensors, microarrays, tissue engineering and cellular studies. This article reviews the techniques developed for protein and cell micropatterning and its biomedical applications. The prospect of integrating micro and nanoparticles with protein and cell micropatterning is discussed. The micro/nanoparticles are assembled into patterns and form the substrate for proteins and cell attachment. The assembled particles create a micro or nanotopography, depending on the size of the particles employed. The nonplanar structure can increase the surface area for biomolecules attachment and therefore enhance the sensitivity for detection in biosensors. Furthermore, a nanostructured substrate can influence the conformation and functionality of protein attached to it, while cellular response in terms of morphology, adhesion, proliferation, differentiation, etc. can be affected by a surface expressing micro or nanoscale structures. Proteins and cells tend to lose their normal functions upon attachment to substrate. By recognizing the types of topography that are favourable for preserving proteins and cell behaviour, and integrating it with micropattering will lead to the development of functional protein and cell patterns.

CAR T-cell immunotherapy: The path from the by-road to the freeway?

PubMed

Whilding, Lynsey M; Maher, John

2015-12-01

Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Polyphase enrichment and redistribution processes in silver-rich mineral associations of the hydrothermal fluorite-barite-(Ag-Cu) Clara deposit, SW Germany

NASA Astrophysics Data System (ADS)

Keim, Maximilian F.; Walter, Benjamin F.; Neumann, Udo; Kreissl, Stefan; Bayerl, Richard; Markl, Gregor

2018-03-01

The silver-copper sulfide mineralization associated with the fluorite-barite vein system at the Clara deposit in SW Germany shows large scale vertical zoning. Low to moderate silver contents prevail in the upper 350 m, whereas high silver contents occur in the subsequent 450 m of the currently known vein system. This change in Ag tenor is related to conspicuous mineralogical changes with depth. A detailed petrographic and fluid inclusion study identifies evidence for five subsequent hydrothermal and one alteration stage—all contributing to mineralogical diversity. The vertical Ag zoning, however, is attributed only to the first of these stages. During this first stage, increasing oxidation of ascending hydrothermal fluids (90-160 °C, 24.2-26.7 wt% NaCl+CaCl2) led to the formation of high-Ag tetrahedrite-tennantite in the lower parts and basically Ag-free enargite in the upper parts of the vein system. The subsequent hydrothermal stage led to significant mineralogical changes, but inherited the pre-existing Ag zonation. In this second hydrothermal stage, which was related to fluids similar in composition to those of the first stage (70-125 °C, 23.1-26.5 wt% NaCl+CaCl2), dissolution of high Ag-tetrahedrite-tennantite resulted in the formation of complex Ag-sulfosalts together with moderately Ag-bearing tetrahedrite-tennantite and chalcopyrite. The first two stages were formed by fluid mixing of a sedimentary and a hot basement fluid. The influx of fluids with high Ag, Bi and Pb activity during stage 3 and 5 resulted in the local replacement of earlier Ag-sulfosalts by galena and Ag-(Bi)-sulfosalts. The fourth stage is marked by partial dissolution of sulfides and sulfosalts by a late, hot, undiluted basement fluid (250 °C, 18.7-20.9 wt% NaCl+CaCl2) precipitating fluorite, barite and quartz. Finally, supergene alteration lead to the dissolution of silver-bearing phases and the precipitation of acanthite and native silver. The study illustrates, how metal tenor

Experiment ueber den Einflusse von Metaboliten und Antimetaboliten am Modell von Trichomonas Vaginalis. IV. Mitteilung: Vitamine, die das Wachstum von Trichomonas Vaginalis Beguenstigen (Experiments on the Influence of Metabolites and Antimetabolites on the Model of Trichomonas Vaginalis. IV. Communication: Vitamins Favouring the Growth of Trichomonas Vaginalis),

DTIC Science & Technology

A number of vitamins have been investigated for their influence upon Trichomonas vaginalis . At a concentration of 0.20 mg ml vitamin A has...stimulating action upon the growth of Trichomonas vaginalis . Vitamin D2 has been shown to favour Trichomonas multiplication in all experimental series...Vitamin D3 generally favours the Trichomonas vaginalis population. Addition of vitamin E resulted in enhanced multiplication of Trichomonas and longer

Allogeneic stem cell transplantation using lymphoablative rather than myeloablative conditioning regimen for relapsed or refractory lymphomas.

PubMed

Yoon, Jae-Ho; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Kim, Hee-Je; Min, Chang-Ki; Lee, Jong-Wook; Min, Woo-Sung; Cho, Seok-Goo

2017-03-01

In relapsed or refractory non-Hodgkin lymphoma (NHL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides graft-versus-lymphoma activity resulting in fewer incidences of relapse. However, therapy-related mortality (TRM) remains an important challenge. We attempted to introduce our reduced-intensity conditioning (RIC) regimen. From 2007 to 2013, we treated 28 relapsed or refractory NHLs with allo-HSCT. All were pre-conditioned with fludarabine [FLU, 180 mg/body surface area (BSA)/6 days] and melphalan (MEL, 70 mg/BSA/1 day); 25 (all but 3) were additionally treated with total body irradiation (TBI, 800 cGy/4Fx/2 days). Peripheral blood stem cells were collected from matched siblings (n = 10) or suitably matched unrelated (n = 18) donors. There were eight diffuse large B-cell lymphomas, seven peripheral T-cell lymphoma not otherwise specified, give lymphoblastic lymphomas, two mantle cell lymphomas, and six various other lymphomas. Of these patients, 10 relapsed after auto-HSCT, 5 relapsed after chemotherapy, and 13 were refractory lymphomas. After allo-HSCT, complete remission was achieved in 22 (78.5%) patients. After a median follow-up of 24.8 months, 3-year overall survival and disease-free survival were 62.4 and 59.2% and the 3-year TRM and relapse incidence were 14.9 and 28.6% respectively. Acute and chronic graft-versus-host diseases (GVHDs) were identified in 17 (≥Grade II in 12 patients) and 18 patients respectively, and the group with chronic GVHD showed favourable survival outcomes. In relapsed or refractory NHL, RIC-allo-HSCT using FLU + MEL + 800 cGy TBI showed favourable survival outcomes with acceptable TRM and relapse incidence. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T cell – Th17 Balance

PubMed Central

George, Mariam Mathew; Vignesh, Kavitha Subramanian; Landero Figueroa, Julio A.; Caruso, Joseph A.; Deepe, George S.

2016-01-01

Zn is an essential metal for development and maintenance of both the innate and adaptive compartments of the immune system. Zn homeostasis impacts maturation of dendritic cells (DCs) that are important in shaping T cell responses. The mechanism by which Zn regulates the tolerogenic phenotype of DCs remains largely unknown. In this study, we investigated the effect of Zn on DC phenotype and the generation of forkhead box P3 (FoxP3+) regulatory T cells (Tregs) using a model of Histoplasma capsulatum fungal infection. Exposure of bone marrow derived DCs to Zn in vitro induced a tolerogenic phenotype by diminishing surface major histocompatibility complex (MHC)II and promoting the tolerogenic markers, programmed death-ligand (PD-L)1, PD-L2 and the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO). Zn triggered tryptophan degradation by IDO and kynurenine production by DCs and strongly suppressed the proinflammatory response to stimulation by toll like receptor (TLR) ligands. In vivo, Zn supplementation and subsequent H. capsulatum infection supressed MHCII on DCs, enhanced PD-L1 and PD-L2 expression on MHCIIlo DCs and skewed the Treg - Th17 balance in favour of FoxP3+ Tregs while decreasing Th17 cells. Thus, Zn shapes the tolerogenic potential of DCs in vitro and in vivo and promotes Tregs during fungal infection. PMID:27465530

Baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

PubMed

Viecelli, Andrea K; Pascoe, Elaine M; Polkinghorne, Kevan R; Hawley, Carmel M; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Johnson, David W; Kerr, Peter G; Mori, Trevor A; Scaria, Anish; Hooi, Seong L; Ong, Meng L; Irish, Ashley B

2016-03-01

The Fish oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial investigated whether 3 months of omega-3 polyunsaturated fatty acids, either alone or in combination with aspirin, will effectively reduce primary access failure of de novo arteriovenous fistulae. This report presents the baseline characteristics of all study participants, examines whether study protocol amendments successfully increased recruitment of a broader and more representative haemodialysis cohort, including patients already receiving aspirin, and contrasts Malaysian participants with those from Australia, New Zealand and the United Kingdom (UK). This international, randomized, double-blind, placebo-controlled trial included patients older than 19 years with stage 4 or 5 chronic kidney disease currently receiving, or planned within 12 months to receive haemodialysis. Participants (n = 568) were overweight (28.6 ± 7.3 kg/m(2) ), relatively young (54.8 ± 14.3 years), and predominantly male (63%) with a high prevalence of diabetes mellitus (46%) but low rate of ischaemic heart disease (8%). Sixty one percent were planned for lower arm arteriovenous fistula creation. Malaysian participants (n = 156) were younger (51.8 ± 13.6 years vs 57.1 ± 14.2 years, P < 0.001) with a higher prevalence of diabetes mellitus (65% vs 43%, P < 0.001), but less ischaemic heart disease (5% vs 14%, P < 0.01) compared with the combined Australian, New Zealand and UK cohort (n = 228). Protocol modifications allowing for inclusion of patients receiving aspirin increased the prevalence of co-morbidities compared with the original cohort. The FAVOURED study participants, while mostly similar to patients in contemporary national registry reports and comparable recent clinical trials, were on average younger and had less ischaemic heart disease. These differences were reduced as a consequence of including patients already receiving aspirin. © 2015 Asian

Cells anticipate periodic events

NASA Astrophysics Data System (ADS)

Nakagaki, Toshiyuki

2009-03-01

We show that an amoeboid organism can anticipate the timing of periodic events. The plasmodium of the true slime mold Physarum polycephalum moves rapidly under favourable conditions, but stops moving when transferred to less-favourable conditions. Plasmodia exposed to unfavourable conditions, presented in three consecutive pulses at constant intervals, reduced their locomotive speed in response to each episode. When subsequently subjected to favourable conditions, the plasmodia spontaneously reduced their locomotive speed at the time point when the next unfavourable episode would have occurred. This implied anticipation of impending environmental change. After this behaviour had been evoked several times, the locomotion of the plasmodia returned to normal; however, the anticipatory response could subsequently be induced by a single unfavourable pulse, implying recall of the memorized periodicity. We explored the mechanisms underlying these behaviours from a dynamical systems perspective. Our results hint at the cellular origins of primitive intelligence and imply that simple dynamics might be sufficient to explain its emergence.

Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities

PubMed Central

Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

2015-01-01

Purpose: To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Methods: Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Results: Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. Conclusion: In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye. PMID:26425316

The effect of unfavourable and favourable social comparisons on paranoid ideation: An experimental study.

PubMed

Ascone, Leonie; Jaya, Edo S; Lincoln, Tania M

2017-09-01

Low social rank is associated with paranoia, but there is a lack of evidence for causality. We tested the effects of social comparisons on negative affect and paranoia with an online social rank paradigm, and whether striving to avoid inferiority or fears of social rejection moderated paranoid reactions. Female students (N = 172) were randomly exposed to one of two validated online profiles depicting a same-aged, high (unfavourable comparison) vs. low rank (favourable comparison) female student. Moderators were assessed at baseline. Social rank, anxiety, sadness and paranoia were assessed pre and post profile-exposure. There was a large effect of the experimental manipulation on social rank (p < 0.001, η 2 partial  = 0.191). The manipulations had no effects on anxiety and paranoia (p > 0.38). Sadness was significantly altered (p = 0.016, η 2 partial  = 0.033). There were significant moderation effects between the experimental conditions and insecure striving (trend-level) as well as fears of rejection. Our findings may be biased (overestimation of effects) as students are likely to be more competitive compared to the general population. Our rank manipulations did not alter paranoia. This suggests that changes in the cognitive representation of social rank alone - without triggering a strong emotional response - do not suffice to evoke paranoia. Although our results do not support the notion that threats to social rank cause paranoid symptoms, they suggest that threats to social rank are more likely to trigger paranoid states in those who are insecure in regard to their social position. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stroma: the forgotten cells of innate immune memory.

PubMed

Crowley, Thomas; Buckley, Christopher D; Clark, Andrew R

2018-05-05

All organisms are constantly exposed to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. Whilst the innate immune system is the front line of response to each stimulant, it has been traditionally considered to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure. This concept of "innate immune memory" has been known for nearly a century, and is accepted amongst myeloid biologists. In recent years, other innate immune cells, such as natural killer cells, have been shown to display memory, suggesting innate immune memory is a trait common to several cell types. Over the last thirty years, evidence has slowly accumulated in favour of not only haematopoietic cells, but also stromal cells, being imbued with memory following inflammatory episodes. A recent publication showing this also to be true in epithelial cells suggests innate immune memory to be widespread, if underappreciated, in non-haematopoietic cells. In this review, we will examine the evidence supporting the existence of innate immune memory in stromal cells. We will also discuss the ramifications of memory in long-lived tissue-resident cells. Finally, we will pose questions we feel to be important in the understanding of these forgotten cells in the field of innate memory. This article is protected by copyright. All rights reserved. © 2018 British Society for Immunology.

Challenges and opportunities in the manufacture and expansion of cells for therapy.

PubMed

Maartens, Joachim H; De-Juan-Pardo, Elena; Wunner, Felix M; Simula, Antonio; Voelcker, Nicolas H; Barry, Simon C; Hutmacher, Dietmar W

2017-10-01

Laboratory-based ex vivo cell culture methods are largely manual in their manufacturing processes. This makes it extremely difficult to meet regulatory requirements for process validation, quality control and reproducibility. Cell culture concepts with a translational focus need to embrace a more automated approach where cell yields are able to meet the quantitative production demands, the correct cell lineage and phenotype is readily confirmed and reagent usage has been optimized. Areas covered: This article discusses the obstacles inherent in classical laboratory-based methods, their concomitant impact on cost-of-goods and that a technology step change is required to facilitate translation from bed-to-bedside. Expert opinion: While traditional bioreactors have demonstrated limited success where adherent cells are used in combination with microcarriers, further process optimization will be required to find solutions for commercial-scale therapies. New cell culture technologies based on 3D-printed cell culture lattices with favourable surface to volume ratios have the potential to change the paradigm in industry. An integrated Quality-by-Design /System engineering approach will be essential to facilitate the scaled-up translation from proof-of-principle to clinical validation.

High-efficiency dye-sensitized solar cells with ferrocene-based electrolytes.

PubMed

Daeneke, Torben; Kwon, Tae-Hyuk; Holmes, Andrew B; Duffy, Noel W; Bach, Udo; Spiccia, Leone

2011-03-01

Dye-sensitized solar cells based on iodide/triiodide (I(-)/I(3)(-)) electrolytes are viable low-cost alternatives to conventional silicon solar cells. However, as well as providing record efficiencies of up to 12.0%, the use of I(-)/I(3)(-) in such solar cells also brings about certain limitations that stem from its corrosive nature and complex two-electron redox chemistry. Alternative redox mediators have been investigated, but these generally fall well short of matching the performance of conventional I(-)/I(3)(-) electrolytes. Here, we report energy conversion efficiencies of 7.5% (simulated sunlight, AM1.5, 1,000 W m(-2)) for dye-sensitized solar cells combining the archetypal ferrocene/ferrocenium (Fc/Fc(+)) single-electron redox couple with a novel metal-free organic donor-acceptor sensitizer (Carbz-PAHTDTT). These Fc/Fc(+)-based devices exceed the efficiency achieved for devices prepared using I(-)/I(3)(-) electrolytes under comparable conditions, revealing the great potential of ferrocene-based electrolytes in future dye-sensitized solar cells applications. This improvement results from a more favourable matching of the redox potential of the ferrocene couple with that of the new donor-acceptor sensitizer.

ARC-2010-ACD10-0005-064

NASA Image and Video Library

2010-01-23

NASA Ames Research Center 70 Year Anniversary Gala Dinner held at Santa Clara University, Santa Clara, California with special guest speaker Nichelle Nichols of Star Trek fame. with Dale Compton and Meredith Moore

ARC-2010-ACD10-0005-052

NASA Image and Video Library

2010-01-23

NASA Ames Research Center 70 Year Anniversary Gala Dinner held at Santa Clara University, Santa Clara, California with special guest speaker Nichelle Nichols of Star Trek fame. with Lew Braxton, Pete Worden and ____

N. River Street, east side of street at Sound End ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

N. River Street, east side of street at Sound End - River Street Historic District, Bounded by West Saint James Street, West Santa Clara Street, Pleasant Street, & Guadalupe River, San Jose, Santa Clara County, CA

Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.

PubMed

Ohta, K; Yamashita, N; Tajima, M; Miyasaka, T; Nakano, J; Nakajima, M; Ishii, A; Horiuchi, T; Mano, K; Miyamoto, T

1999-11-01

Inhaled pollutants were recently shown to be responsible for an increased incidence of airway allergic diseases, including asthma. A common feature of all forms of asthma is airway hyperresponsiveness. Our purpose was to elucidate the effects of diesel exhaust particulate (DEP), one of the most prevalent inhaled pollutants, on airway responsiveness. A/J and C57Bl/6 mice were used; the former are genetically predisposed to be hyperresponsive to acetylcholine, whereas the latter are not. DEP was administered intranasally for 2 weeks, after which pulmonary function was analyzed by whole-body plethysmography. Intranasal administration of DEP increased airway responsiveness to acetylcholine in both A/J and C57Bl/6 mice and induced displacement of ciliated epithelial cells by mucus-secreting Clara cells. The effect was mediated by M(3) muscarinic receptors. Acetylcholine-evoked bronchial constriction was reversed by administration of terbutaline, a beta(2)-adrenergic antagonist, which is also characteristic of human asthma. Intranasal administration of antibody raised against GM-CSF abolished DEP-evoked increases in airway responsiveness and Clara cell hyperplasia. The antibody raised against IL-4 also inhibited DEP-evoked increases in airway responsiveness. However, it was to a lesser extent compared with antibody against GM-CSF. In addition, DEP stimulated GM-CSF messenger RNA expression in the lung. DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.

Red blood cell transfusion for people undergoing hip fracture surgery.

PubMed

Brunskill, Susan J; Millette, Sarah L; Shokoohi, Ali; Pulford, E C; Doree, Carolyn; Murphy, Michael F; Stanworth, Simon

2015-04-21

transfusion thresholds in postoperative morbidity for the following complications: thromboembolism (RR 1.15 favouring a restrictive threshold, 95% CI 0.56 to 2.37; four trials; 2416 participants), stroke (RR 2.40 favouring a restrictive threshold, 95% CI 0.85 to 6.79; four trials; 2416 participants), wound infection (RR 1.61 favouring a restrictive threshold, 95% CI 0.77 to 3.35; three trials; 2332 participants), respiratory infection (pneumonia) (RR 1.35 favouring a restrictive threshold, 95% CI 0.95 to 1.92; four trials; 2416 participants) and new diagnosis of congestive heart failure (RR 0.77 favouring a liberal threshold, 95% CI 0.48 to 1.23; three trials; 2332 participants). There was very low quality evidence of a lower risk of myocardial infarction in the liberal compared with the restrictive transfusion threshold group (RR 0.59, 95% CI 0.36 to 0.96; three trials; 2217 participants). Assuming an illustrative baseline risk of myocardial infarction of 24 per 1000 participants in the restricted threshold group, this result was compatible with between one and 15 fewer myocardial infarctions in the liberal threshold group. We found low quality evidence of no difference in mortality, functional recovery or postoperative morbidity between 'liberal' versus 'restrictive' thresholds for red blood cell transfusion in people undergoing surgery for hip fracture. Although further research may change the estimates of effect, the currently available evidence does not support the use of liberal red blood cell transfusion thresholds based on a 10 g/dL haemoglobin trigger in preference to more restrictive transfusion thresholds based on lower haemoglobin levels or symptoms of anaemia in these people. Future research needs to address the effectiveness of red blood cell transfusions at different time points in the surgical pathway, whether pre-operative, peri-operative or postoperative. In particular, such research would need to consider people who are symptomatic or haemodynamically

Evolutionary process of Bos taurus cattle in favourable versus unfavourable environments and its implications for genetic selection

PubMed Central

O'Neill, Christopher J; Swain, David L; Kadarmideen, Haja N

2010-01-01

The evolutionary processes that have enabled Bos taurus cattle to establish around the globe are at the core to the future success of livestock production. Our study focuses on the history of cattle domestication including the last 60 years of B. taurus breeding programmes in both favourable and unfavourable environments and its consequences on evolution and fitness of cattle. We discuss the emergence of ‘production diseases’ in temperate production systems and consider the evolutionary genetics of tropical adaptation in cattle and conclude that the Senepol, N'Dama, Adaptaur and Criollo breeds, among others with similar evolutionary trajectories, would possess genes capable of improving the productivity of cattle in challenging environments. Using our own experimental evidence from northern Australia, we review the evolution of the Adaptaur cattle breed which has become resistant to cattle tick. We emphasize that the knowledge of interactions between genotype, environment and management in the livestock systems will be required to generate genotypes for efficient livestock production that are both economically and environmentally sustainable. Livestock producers in the 21st century will have less reliance on infrastructure and veterinary products to alleviate environmental stress and more on the animal's ability to achieve fitness in a given production environment. PMID:25567936

Evolutionary process of Bos taurus cattle in favourable versus unfavourable environments and its implications for genetic selection.

PubMed

O'Neill, Christopher J; Swain, David L; Kadarmideen, Haja N

2010-09-01

The evolutionary processes that have enabled Bos taurus cattle to establish around the globe are at the core to the future success of livestock production. Our study focuses on the history of cattle domestication including the last 60 years of B. taurus breeding programmes in both favourable and unfavourable environments and its consequences on evolution and fitness of cattle. We discuss the emergence of 'production diseases' in temperate production systems and consider the evolutionary genetics of tropical adaptation in cattle and conclude that the Senepol, N'Dama, Adaptaur and Criollo breeds, among others with similar evolutionary trajectories, would possess genes capable of improving the productivity of cattle in challenging environments. Using our own experimental evidence from northern Australia, we review the evolution of the Adaptaur cattle breed which has become resistant to cattle tick. We emphasize that the knowledge of interactions between genotype, environment and management in the livestock systems will be required to generate genotypes for efficient livestock production that are both economically and environmentally sustainable. Livestock producers in the 21st century will have less reliance on infrastructure and veterinary products to alleviate environmental stress and more on the animal's ability to achieve fitness in a given production environment.

Professionals' positive perceptions of fathers are associated with more favourable attitudes towards including them in family interventions.

PubMed

de Montigny, Francine; Gervais, Christine; Meunier, Sophie; Dubeau, Diane

2017-12-01

This Université du Québec en Outaouais study examined professionals' attitudes towards fathers, their perceived self-efficacy when working with them and their perceptions of the importance of including fathers in family interventions. Professionals in Québec, Canada, working in childcare fields such as education, social services, health, community services and management answered a self-report questionnaire between 2013 and 2015. The 296 respondents (90% females) had a mean age of 39 (20-65), were from urban, semi-urban and rural settings and provided services to families with children up to five years of age. Social service professionals perceived fathers more negatively than did other professionals. Even though male professionals perceived fathers more negatively, they felt more confident working with them than did their female counterparts. Positive perceptions of fathers were associated with more favourable attitudes towards including them in family interventions, and this association was mediated by the professionals' perceptions of their own self-efficacy. The most negative attitudes were reported by social service professionals. Male professionals viewed fathers more negatively but were more confident working with them than were female colleagues. Improving professionals' perceptions of fathers could help to promote their inclusion in family interventions. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

South front and west side, storage (bldg. no. 217) and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

South front and west side, storage (bldg. no. 217) and refrigeration shop (bldg. no. 216) to right, looking northeast. - Agnews State Hospital, Truck Garage, Fourth Street near Avenue A, Santa Clara, Santa Clara County, CA

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

PubMed Central

Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

2015-01-01

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

Ecological symmetry breaking can favour the evolution of altruism in an action-response game.

PubMed

Di Paolo, E A

2000-03-21

The evolution of altruistic behaviour is studied in a simple action-response game with a tunable degree of conflict of interest. It is shown that for the continuous, mixed-medium approach no stable polymorphism favours altruism. Ecological dynamics are explored with the addition of a spatial dimension and a local energy variable. A continuous spatial model with finite local range does not introduce any substantial difference in the results with respect to the level of altruism. However, the model illustrates how ecological coupling may lead to the formation of stable spatial patterns in the form of discrete and isolated clusters of players as a consequence of inverse density dependence. A discrete, individual-based model is built in which local interactions are also modelled as occurring within a finite neighbourhood of each individual and spatial positions are not restricted as in lattice models. This model shows substantially different results. A high level of altruism is observed for low (but positive) degrees of conflict and this level decreases linearly for higher degrees of conflict. The evolution of altruism is explained by studying the broken symmetries introduced by the spatial clusters themselves, mainly between their central and peripheral regions which, in combination with the discrete and the stochastic nature of the model, result in the stabilization of strategies in which players behave altruistically towards the same type. As a consequence of the activity of the players, energy resources at the centre of an altruistic cluster are very depleted; so much so that, for low conflict, fitter non-altruistic mutants may initially invade only to become locally extinct due to their less efficient use of energy as their numbers increase. In peripheral regions invader may subsist; however, for geometrical reasons long-lasting genealogies tend to originate only at the centre of a cluster. Copyright 2000 Academic Press.

Higher maternal education is associated with favourable growth of young children in different countries

PubMed Central

Lakshman, Rajalakshmi; Zhang, Jing; Zhang, Jianduan; Koch, Felix S; Marcus, Claude; Ludvigsson, Johnny; Ong, Ken K; Sobko, Tanja

2013-01-01

Background Childhood growth affects long-term health and could contribute to health inequalities that persist throughout life. Methods We compared growth data of 4-6 year old children born 1997-2002 in UK (n=15,168), Sweden (n=6,749) and rural China (n=10,327). Standard deviation scores (SDS) were calculated against the WHO Standard. Obesity and overweight were defined by International Obesity Taskforce cut-offs, and stunting, underweight and thinness by height, weight or BMI < −2 SDS. Associations with maternal education were standardised by calculating the Slope Index of Inequality (SII). Results Mean SDS height, weight and BMI in UK (−0.01; 0.42; 0.62, respectively) and Sweden (0.45; 0.59; 0.45) were higher than in China (−0.98, −0.82, −0.29). Higher maternal education was consistently associated with taller offspring height SDS (SII: UK 0.25; Sweden 0.17; China 1.06). Underweight and stunting were less common in UK (prevalence: 0.6% and 2.2%, respectively) and Sweden (0.3% and 0.6%) than in China (9.5% and 16.4%), where these outcomes were inversely associated with maternal education (SII: −25.8% and −12.7%). Obesity prevalence in UK, Sweden and China was 4.8%, 3.7% and 0.4%, respectively. Maternal education was inversely associated with offspring obesity in UK (SII: −3.3%) and Sweden (−2.8%), but not in China (+0.3%). Conclusions Higher maternal education was associated with more favourable growth in young children: lower obesity and overweight in UK and Sweden, and lower stunting and underweight in rural China. Public health strategies to optimize growth in early childhood need to acknowledge socioeconomic factors, but possibly with a different emphasis in different settings. PMID:23450064

Higher maternal education is associated with favourable growth of young children in different countries.

PubMed

Lakshman, Rajalakshmi; Zhang, Jing; Zhang, Jianduan; Koch, Felix S; Marcus, Claude; Ludvigsson, Johnny; Ong, Ken K; Sobko, Tanja

2013-07-01

Childhood growth affects long-term health and could contribute to health inequalities that persist throughout life. We compared growth data of 4-year-old to 6-year-old children born 1997-2002 in UK (n=15,168), Sweden (n=6749) and rural China (n=10,327). SD scores (SDS) were calculated against the WHO Growth Standard. Obesity and overweight were defined by the International Obesity Taskforce cut-offs, and stunting, underweight and thinness by height, weight or body mass index (BMI)<-2 SDS. Associations with maternal education were standardised by calculating the Slope Index of Inequality (SII). Mean SDS height, weight and BMI in the UK (-0.01, 0.42, 0.62, respectively) and Sweden (0.45, 0.59, 0.45) were higher than in China (-0.98, -0.82, -0.29). Higher maternal education was consistently associated with taller offspring height SDS (SII: UK 0.25; Sweden 0.17; China 1.06). Underweight and stunting were less common in the UK (prevalence: 0.6% and 2.2%, respectively) and Sweden (0.3% and 0.6%) than in China (9.5% and 16.4%), where these outcomes were inversely associated with maternal education (SII: -25.8% and -12.7%). Obesity prevalence in the UK, Sweden and China was 4.8%, 3.7% and 0.4%, respectively. Maternal education was inversely associated with offspring obesity in the UK (SII: -3.3%) and Sweden (-2.8%), but not in China (+0.3%). Higher maternal education was associated with more favourable growth in young children: lower obesity and overweight in the UK and Sweden, and lower stunting and underweight in rural China. Public health strategies to optimise growth in early childhood need to acknowledge socioeconomic factors, but possibly with a different emphasis in different settings.

Innate signaling by mycobacterial cell wall components and relevance for development of adjuvants for subunit vaccines.

PubMed

Tima, Hermann Giresse; Huygen, Kris; Romano, Marta

2016-11-01

Pathogen recognition receptors (PRRs) recognize pathogen-associated molecular patterns, triggering the induction of inflammatory innate responses and contributing to the development of specific adaptive immune responses. Novel adjuvants have been developed based on agonists of PRRs. Areas covered: Lipid pathogen-associated molecular patterns (PAMPs) present in the cell wall of mycobacteria are revised, with emphasis on agonists of C-type lectin receptors, signaling pathways, and preclinical data supporting their use as novel adjuvants inducing cell-mediated immune responses. Their potential use as lipid antigens in novel tuberculosis subunit vaccines is also discussed. Expert commentary: Few adjuvants are licensed for human use and mainly favour antibody-mediated protective immunity. Use of lipid PAMPs that trigger cell-mediated immune responses could lead to the development of adjuvants for vaccines against intracellular pathogens and cancer.

Polyelectrolyte multi-layers assembly of SiCHA nanopowders and collagen type I on aminolysed PLA films to enhance cell-material interactions.

PubMed

Baba Ismail, Yanny Marliana; Ferreira, Ana Marina; Bretcanu, Oana; Dalgarno, Kenneth; El Haj, Alicia J

2017-11-01

This paper presents a new approach in assembling bone extracellular matrix components onto PLA films, and investigates the most favourable environment which can be created using the technique for cell-material interactions. Poly (lactic acid) (PLA) films were chemically modified by covalently binding the poly(ethylene imine) (PEI) as to prepare the substrate for immobilization of polyelectrolyte multilayers (PEMs) coating. Negatively charged polyelectrolyte consists of well-dispersed silicon-carbonated hydroxyapatite (SiCHA) nanopowders in hyaluronic acid (Hya) was deposited onto the modified PLA films followed by SiCHA in collagen type I as the positively charged polyelectrolyte. The outermost layer was finally cross-linked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrocholoride and N-hydroxysulfosuccinimide sodium salt (EDC/NHS) solutions. The physicochemical features of the coated PLA films were monitored via X-ray Photoelectron Spectroscopy (XPS) and Atomic Force Microscope (AFM). The amounts of calcium and collagen deposited on the surface were qualitatively and quantitatively determined. The surface characterizations suggested that 5-BL has the optimum surface roughness and highest amounts of calcium and collagen depositions among tested films. In vitro human mesenchymal stem cells (hMSCs) cultured on the coated PLA films confirmed that the coating materials greatly improved cell attachment and survival compared to unmodified PLA films. The cell viability, cell proliferation and Alkaline Phosphatase (ALP) expression on 5-BL were found to be the most favourable of the tested films. Hence, this newly developed coating materials assembly could contribute to the improvement of the bioactivity of polymeric materials and structures aimed to bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Opportunities and barriers to establishing a cell therapy programme in South Africa

PubMed Central

2013-01-01

The establishment of a cell therapy programme in South Africa has the potential to contribute to the alleviation of the country’s high disease burden and also to contribute to economic growth. South Africa has various positive attributes that favour the establishment of such a high-profile venture; however, there are also significant obstacles which need to be overcome. We discuss the positive and negative features of the current health biotechnology sector. The positive factors include a strong market pull and a highly innovative scientific and medical community, while the most problematic features include the lack of human resources and education and limited funding. The South African Government has undertaken to strengthen the biotechnology sector in general, but a focus on cell therapy is lacking. The next important step would be to provide financial, legal/ethical and other support for groups that are active and productive in this field through the development of a local cell therapy programme. PMID:23719318

Robotic multi-well planar patch-clamp for native and primary mammalian cells

PubMed Central

Milligan, Carol J; Li, Jing; Sukumar, Piruthivi; Majeed, Yasser; Dallas, Mark L; English, Anne; Emery, Paul; Porter, Karen E; Smith, Andrew M; McFadzean, Ian; Beccano-Kelly, Dayne; Bahnasi, Yahya; Cheong, Alex; Naylor, Jacqueline; Zeng, Fanning; Liu, Xing; Gamper, Nikita; Jiang, Lin-Hua; Pearson, Hugh A; Peers, Chris; Robertson, Brian; Beech, David J

2009-01-01

Multi-well robotic planar patch-clamp has become common in drug development and safety programmes because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. It has not, however, been adopted significantly in other important areas of ion channel research, where conventional patch-clamp remains the favoured method. Here we show the wider potential of the multi-well approach with the capability for efficient intracellular solution exchange, describing protocols and success rates for recording from a range of native and primary mammalian cells derived from blood vessels, arthritic joints, and the immune and central nervous systems. The protocol involves preparing a suspension of single cells to be dispensed robotically into 4-8 microfluidic chambers each containing a glass chip with a small aperture. Under automated control, giga-seals and whole-cell access are achieved followed by pre-programmed routines of voltage paradigms and fast extracellular or intracellular solution exchange. Recording from 48 chambers usually takes 1-6 hr depending on the experimental design and yields 16-33 cell recordings. PMID:19197268

Airborne Quercus pollen in SW Spain: Identifying favourable conditions for atmospheric transport and potential source areas.

PubMed

Maya-Manzano, José María; Fernández-Rodríguez, Santiago; Smith, Matt; Tormo-Molina, Rafael; Reynolds, Andrew M; Silva-Palacios, Inmaculada; Gonzalo-Garijo, Ángela; Sadyś, Magdalena

2016-11-15

The pollen grains of Quercus spp. (oak trees) are allergenic. This study investigates airborne Quercus pollen in SW Spain with the aim identifying favourable conditions for atmospheric transport and potential sources areas. Two types of Quercus distribution maps were produced. Airborne Quercus pollen concentrations were measured at three sites located in the Extremadura region (SW Spain) for 3 consecutive years. The seasonal occurrence of Quercus pollen in the air was investigated, as well as days with pollen concentrations ≥80Pm(-3). The distance that Quercus pollen can be transported in appreciable numbers was calculated using clusters of back trajectories representing the air mass movement above the source areas (oak woodlands), and by using a state-of-the-art dispersion model. The two main potential sources of Quercus airborne pollen captured in SW Spain are Q. ilex subsp. ballota and Q. suber. The minimum distances between aerobiological stations and Quercus woodlands have been estimated as: 40km (Plasencia), 66km (Don Benito), 62km (Zafra) from the context of this study. Daily mean Quercus pollen concentration can exceed 1,700Pm(-3), levels reached not less than 24 days in a single year. High Quercus pollen concentration were mostly associated with moderate wind speed events (6-10ms(-1)), whereas that a high wind speed (16-20ms(-1)) seems to be associated with low concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells.

PubMed

Muller, Mees; Heeck, Kier; Elemans, Coen P H

2016-01-01

Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500 nN/m), and have a 100-fold higher tip displacement threshold (< 10 μm vs. <400 nm). We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz) signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC.

Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells

PubMed Central

Muller, Mees; Heeck, Kier

2016-01-01

Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500 nN/m), and have a 100-fold higher tip displacement threshold (< 10 μm vs. <400 nm). We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz) signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC. PMID:27448330

Activated human primary NK cells efficiently kill colorectal cancer cells in 3D spheroid cultures irrespectively of the level of PD-L1 expression.

PubMed

Lanuza, Pilar M; Vigueras, Alan; Olivan, Sara; Prats, Anne C; Costas, Santiago; Llamazares, Guillermo; Sanchez-Martinez, Diego; Ayuso, José María; Fernandez, Luis; Ochoa, Ignacio; Pardo, Julián

2018-01-01

Haploidentical Natural Killer (NK) cells have been shown as an effective and safe alternative for the treatment of haematological malignancies with poor prognosis for which traditional therapies are ineffective. In contrast to haematological cancer cells, that mainly grow as single suspension cells, solid carcinomas are characterised by a tridimensional (3D) architecture that provide specific surviving advantages and resistance against chemo- and radiotherapy. However, little is known about the impact of 3D growth on solid cancer immunotherapy especially adoptive NK cell transfer. We have recently developed a protocol to activate ex vivo human primary NK cells using B lymphoblastic cell lines, which generates NK cells able to overcome chemoresistance in haematological cancer cells. Here we have analysed the activity of these allogeneic NK cells against colorectal (CRC) human cell lines growing in 3D spheroid culture and correlated with the expression of some of the main ligands regulating NK cell activity. Our results indicate that activated NK cells efficiently kill colorectal tumour cell spheroids in both 2D and 3D cultures. Notably, although 3D CRC cell cultures favoured the expression of the inhibitory immune checkpoint PD-L1, it did not correlate with increased resistance to NK cells. Finally, we have analysed in detail the infiltration of NK cells in 3D spheroids by microscopy and found that at low NK cell density, cell death is not observed although NK cells are able to infiltrate into the spheroid. In contrast, higher densities promote tumoural cell death before infiltration can be detected. These findings show that highly dense activated human primary NK cells efficiently kill colorectal carcinoma cells growing in 3D cultures independently of PD-L1 expression and suggest that the use of allogeneic activated NK cells could be beneficial for the treatment of colorectal carcinoma.

The functional performance of microencapsulated human pancreatic islet-derived precursor cells.

PubMed

Montanucci, Pia; Pennoni, Ilaria; Pescara, Teresa; Blasi, Paolo; Bistoni, Giovanni; Basta, Giuseppe; Calafiore, Riccardo

2011-12-01

We have examined long-term cultured, human islet-derived stem/precursor cells (hIPC). Whole human islets (HI) were obtained by multi-enzymatic digestion of cadaveric donor pancreases, plated on tissue flasks, and allowed to adhere and expand for several in vitro passages, in order to obtain hIPC. We detected specific stem cell markers (Oct-4, Sox-2, Nanog, ABCG2, Klf-4, CD117) in both intact HI and hIPC. Moreover, hIPC while retaining the expression of Glut-2, Pdx-1, CK-19, and ICA-512, started re-expressing Ngn3, thereby indicating acquisition of a specific pancreatic islet beta cell-oriented phenotype identity. The intrinsic plasticity of hIPC was documented by their ability to differentiate into various germ layer-derived cell phenotypes (ie, osteocytic, adipocytic and neural), including endocrine cells associated with insulin secretory capacity. To render hIPC suitable for transplantation we have enveloped them within our highly purified, alginate-based microcapsules. Upon intraperitoneal graft in NOD/SCID mice we have observed that the microcapsules acted as three-dimensional niches favouring post-transplant hIPC differentiation and acquisition of beta cell-like functional competence. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties.

PubMed

Hobbs, Joanne K; Prentice, Erica J; Groussin, Mathieu; Arcus, Vickery L

2015-10-01

Ancestral sequence reconstruction has been widely used to study historical enzyme evolution, both from biochemical and cellular perspectives. Two properties of reconstructed ancestral proteins/enzymes are commonly reported--high thermostability and high catalytic activity--compared with their contemporaries. Increased protein stability is associated with lower aggregation rates, higher soluble protein abundance and a greater capacity to evolve, and therefore, these proteins could be considered "superior" to their contemporary counterparts. In this study, we investigate the relationship between the favourable in vitro biochemical properties of reconstructed ancestral enzymes and the organismal fitness they confer in vivo. We have previously reconstructed several ancestors of the enzyme LeuB, which is essential for leucine biosynthesis. Our initial fitness experiments revealed that overexpression of ANC4, a reconstructed LeuB that exhibits high stability and activity, was only able to partially rescue the growth of a ΔleuB strain, and that a strain complemented with this enzyme was outcompeted by strains carrying one of its descendants. When we expanded our study to include five reconstructed LeuBs and one contemporary, we found that neither in vitro protein stability nor the catalytic rate was correlated with fitness. Instead, fitness showed a strong, negative correlation with estimated evolutionary age (based on phylogenetic relationships). Our findings suggest that, for reconstructed ancestral enzymes, superior in vitro properties do not translate into organismal fitness in vivo. The molecular basis of the relationship between fitness and the inferred age of ancestral LeuB enzymes is unknown, but may be related to the reconstruction process. We also hypothesise that the ancestral enzymes may be incompatible with the other, contemporary enzymes of the metabolic network.

Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis

PubMed Central

Thiesen, H.-J.; Steinbeck, F.; Maruschke, M.; Koczan, D.; Ziems, B.; Hakenberg, O. W.

2017-01-01

Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value. PMID

Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

PubMed

Thiesen, H-J; Steinbeck, F; Maruschke, M; Koczan, D; Ziems, B; Hakenberg, O W

2017-01-01

Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

The evolution of colour pattern complexity: selection for conspicuousness favours contrasting within-body colour combinations in lizards.

PubMed

Pérez I de Lanuza, G; Font, E

2016-05-01

Many animals display complex colour patterns that comprise several adjacent, often contrasting colour patches. Combining patches of complementary colours increases the overall conspicuousness of the complex pattern, enhancing signal detection. Therefore, selection for conspicuousness may act not only on the design of single colour patches, but also on their combination. Contrasting long- and short-wavelength colour patches are located on the ventral and lateral surfaces of many lacertid lizards. As the combination of long- and short-wavelength-based colours generates local chromatic contrast, we hypothesized that selection may favour the co-occurrence of lateral and ventral contrasting patches, resulting in complex colour patterns that maximize the overall conspicuousness of the signal. To test this hypothesis, we performed a comparative phylogenetic study using a categorical colour classification based on spectral data and descriptive information on lacertid coloration collected from the literature. Our results demonstrate that conspicuous ventral (long-wavelength-based) and lateral (short-wavelength-based) colour patches co-occur throughout the lacertid phylogeny more often than expected by chance, especially in the subfamily Lacertini. These results suggest that selection promotes the evolution of the complex pattern rather than the acquisition of a single conspicuous colour patch, possibly due to the increased conspicuousness caused by the combination of colours with contrasting spectral properties. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Implementing Simulation Design of Experiments and Remote Execution on a High Performance Computing Cluster

DTIC Science & Technology

2007-09-01

example, an application developed in Sun’s Netbeans [2007] integrated development environment (IDE) uses Swing class object for graphical user... Netbeans Version 5.5.1 [Computer Software]. Santa Clara, CA: Sun Microsystems. Process Modeler Version 7.0 [Computer Software]. Santa Clara, Ca

Alternative approaches to myeloid suppressor cell therapy in transplantation: comparing regulatory macrophages to tolerogenic DCs and MDSCs

PubMed Central

2012-01-01

Several types of myeloid suppressor cell are currently being developed as cell-based immunosuppressive agents. Despite detailed knowledge about the molecular and cellular functions of these cell types, expert opinions differ on how to best implement such therapies in solid organ transplantation. Efforts in our laboratory to develop a cell-based medicinal product for promoting tolerance in renal transplant patients have focused on a type of suppressor macrophage, which we call the regulatory macrophage (M reg). Our favoured clinical strategy is to administer donor-derived M regs to recipients one week prior to transplantation. In contrast, many groups working with tolerogenic dendritic cells (DCs) advocate post-transplant administration of recipient-derived cells. A third alternative, using myeloid-derived suppressor cells, presumably demands that cells are given around the time of transplantation, so that they can infiltrate the graft to create a suppressive environment. On present evidence, it is not possible to say which cell type and treatment strategy might be clinically superior. This review seeks to position our basic scientific and early-stage clinical studies of human regulatory macrophages within the broader context of myeloid suppressor cell therapy in transplantation. PMID:23369628

Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia

PubMed Central

Haiat, Stéphanie; Billard, Christian; Quiney, Claire; Ajchenbaum-Cymbalista, Florence; Kolb, Jean-Pierre

2006-01-01

B-cell chronic lymphocytic leukaemia (B-CLL) is the most prevalent leukaemia in Western countries and is characterized by the gradual accumulation in patients of small mature B cells. Since the vast majority of tumoral cells are quiescent, the accumulation mostly results from deficient apoptosis rather than from acute proliferation. Although the phenomenon is relevant in vivo, B-CLL cells die rapidly in vitro as a consequence of apoptosis, suggesting a lack of essential growth factors in the culture medium. Indeed, the rate of B-CLL cell death in vitro is modulated by different cytokines, some favouring the apoptotic process, others counteracting it. Two related members of the tumour necrosis factor family, BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand), already known for their crucial role in normal B-cell survival, differentiation and apoptosis, were recently shown to be expressed by B-CLL cells. These molecules are able to protect the leukaemic cells against spontaneous and drug-induced apoptosis via autocrine and/or paracrine pathways. This review will focus on the role of BAFF and APRIL in the survival of tumoral cells. It will discuss the expression of these molecules by B-CLL cells, their regulation, transduction pathways and their effects on leukaemic cells. The design of reagents able to counteract the effects of these molecules seems to be a new promising therapeutic approach for B-CLL and is already currently developed in the treatment of autoimmune diseases. PMID:16827889

Regional climate modulates the canopy mosaic of favourable and risky microclimates for insects.

PubMed

Pincebourde, Sylvain; Sinoquet, Herve; Combes, Didier; Casas, Jerome

2007-05-01

of the climatic regime experienced in open air outside canopies. Favourable and risky spots within the canopy do change as a function of the climatic conditions at the regional scale. The shifting nature of the mosaic of suitable and risky habitats may explain the observed uniform distribution of leaf miners within tree canopies.

Power output of microbial fuel cell emphasizing interaction of anodic binder with bacteria

NASA Astrophysics Data System (ADS)

Li, Hongying; Liao, Bo; Xiong, Juan; Zhou, Xingwang; Zhi, Huozhen; Liu, Xiang; Li, Xiaoping; Li, Weishan

2018-03-01

Electrochemically active biofilm is necessary for the electron transfer between bacteria and anodic electrode in microbial fuel cells and selecting the type of anodic electrode material that favours formation of electrochemically active biofilm is crucial for the microbial fuel cell operation. We report a new finding that the interaction of anodic binder with bacteria plays more important role than its hydrophilicity for forming an electrochemically active biofilm, which is emphasized by applying poly(bisphenol A-co-epichorohydrin) as an anodic binder of the microbial fuel cell based on carbon nanotubes as anodic electrode and Escherichia coli as bacterium. The physical characterizations and electrochemical measurements demonstrate that poly(bisphenol A-co-epichorohydrin) exhibits a strong interaction with bacteria and thus provides the microbial fuel cell with excellent power density output. The MFC using poly(bisphenol A-co-epichorohydrin) reaches a maximum power density output of 3.8 W m-2. This value is larger than that of the MFCs using polytetrafluoroethylene that has poorer hydrophilicity, or polyvinyl alcohol that has better hydrophilicity but exhibits weaker interaction with bacteria than poly(bisphenol A-co-epichorohydrin).

Expression of genes involved in mouse lung cell differentiation/regulation after acute exposure to photons and protons with or without low-dose preirradiation.

PubMed

Tian, Jian; Zhao, WeiLing; Tian, Sisi; Slater, James M; Deng, Zhiyong; Gridley, Daila S

2011-11-01

The goal of this study was to compare the effects of acute 2 Gy irradiation with photons (0.8 Gy/min) or protons (0.9 Gy/min), both with and without pre-exposure to low-dose/low-dose-rate γ rays (0.01 Gy at 0.03 cGy/h), on 84 genes involved in stem cell differentiation or regulation in mouse lungs on days 21 and 56. Genes with a ≥1.5-fold difference in expression and P < 0.05 compared to 0 Gy controls are emphasized. Two proteins specific for lung stem cells/progenitors responsible for local tissue repair were also compared. Overall, striking differences were present between protons and photons in modulating the genes. More genes were affected by protons than by photons (22 compared to 2 and 6 compared to 2 on day 21 and day 56, respectively) compared to 0 Gy. Preirradiation with low-dose-rate γ rays enhanced the acute photon-induced gene modulation on day 21 (11 compared to 2), and all 11 genes were significantly downregulated on day 56. On day 21, seven genes (aldh2, bmp2, cdc2a, col1a1, dll1, foxa2 and notch1) were upregulated in response to most of the radiation regimens. Immunoreactivity of Clara cell secretory protein was enhanced by all radiation regimens. The number of alveolar type 2 cells positive for prosurfactant protein C in irradiated groups was higher on day 56 (12.4-14.6 cells/100) than on day 21 (8.5-11.2 cells/100) (P < 0.05). Taken together, these results showed that acute photons and protons induced different gene expression profiles in the lungs and that pre-exposure to low-dose-rate γ rays sometimes had modulatory effects. In addition, proteins associated with lung-specific stem cells/progenitors were highly sensitive to radiation.

Real-Time Protein and Cell Binding Measurements on Hydroxyapatite Coatings

PubMed Central

Vilardell, A. M.; Cinca, N.; Jokinen, A.; Garcia-Giralt, N.; Dosta, S.; Cano, I. G.; Guilemany, J. M.

2016-01-01

Although a lot of in vitro and in vivo assays have been performed during the last few decades years for hydroxyapatite bioactive coatings, there is a lack of exploitation of real-time in vitro interaction measurements. In the present work, real-time interactions for a plasma sprayed hydroxyapatite coating were measured by a Multi-Parametric Surface Plasmon Resonance (MP-SPR), and the results were compared with standard traditional cell viability in vitro assays. MP-SPR is proven to be suitable not only for measurement of molecule–molecule interactions but also molecule–material interaction measurements and cell interaction. Although SPR is extensively utilized in interaction studies, recent research of protein or cell adsorption on hydroxyapatite coatings for prostheses applications was not found. The as-sprayed hydroxyapatite coating resulted in 62.4% of crystalline phase and an average thickness of 24 ± 6 μm. The MP-SPR was used to measure lysozyme protein and human mesenchymal stem cells interaction to the hydroxyapatite coating. A comparison between the standard gold sensor and Hydroxyapatite (HA)-plasma coated sensor denoted a clearly favourable cell attachment on HA coated sensor as a significantly higher signal of cell binding was detected. Moreover, traditional cell viability and proliferation tests showed increased activity with culture time indicating that cells were proliferating on HA coating. Cells show homogeneous distribution and proliferation along the HA surface between one and seven days with no significant mortality. Cells were flattened and spread on rough surfaces from the first day, with increasing cytoplasmatic extensions during the culture time. PMID:27618911

Control of cell interaction using quasi-monochromatic light with varying spatiotemporal coherence

NASA Astrophysics Data System (ADS)

Budagovsky, A. V.; Maslova, M. V.; Budagovskaya, O. N.; Budagovsky, I. A.

2017-02-01

By the example of plants, fungi and bacteria, we consider the possibility of controlling the interaction of cells, being in competitive, antagonistic, or parasitic relations. For this aim we used short-time irradiation (a few seconds or minutes) with the red (633 nm) quasi-monochromatic light having different spatiotemporal coherence. It is shown that the functional activity is mostly increased in the cells whose size does not exceed the coherence length and the correlation radius of the light field. Thus, in the case of cells essentially differing in size, it is possible to increase the activity of smaller cells, avoiding the stimulation of larger ones. For example, the radiation having relatively low coherence (Lcoh, rcor <= 10 μm) facilitates mainly the damage of large-size plant cells by pathogen fungi, while the exposure to light with less statistical regularity (Lcoh = 4 μm, rcor = 5 μm) inhibits the growth of the Fusarium microcera fungus, infected by the bacterium of the Pseudomonas species. The quasi-monochromatic radiation with sufficiently high spatiotemporal coherence stimulated all interacting species (bacteria, fungi, plants). In the considered biocenosis, the equilibrium was shifted towards the favour of organisms having the highest rate of cell division or the ones better using their adaptation potential.

Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.

PubMed

Gower, Barbara A; Chandler-Laney, Paula C; Ovalle, Fernando; Goree, Laura Lee; Azziz, Ricardo; Desmond, Renee A; Granger, Wesley M; Goss, Amy M; Bates, G Wright

2013-10-01

Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects β-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. Thirty women with PCOS. β-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. Paired t-test indicated that the lower-CHO diet induced significant decreases in basal β-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') β-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone. © 2013 John Wiley & Sons Ltd.

77 FR 61022 - Notice of Realty Action: Notice of Receipt of Conveyance of Mineral Interest Application, Santa...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... of Realty Action: Notice of Receipt of Conveyance of Mineral Interest Application, Santa Clara County... of the federally owned mineral interests underlying a 1,148.68 acre tract of land in Santa Clara County, California. Publication of this notice temporarily segregates the mineral interests in the land...

Regulation of c- and N-myc expression during induced differentiation of murine neuroblastoma cells.

PubMed

Larcher, J C; Vayssière, J L; Lossouarn, L; Gros, F; Croizat, B

1991-04-01

Using clones N1E-115 and N1A-103 from mouse neuroblastoma C1300, a comparative analysis of c- and N-myc gene expression was undertaken both in proliferating cells and in cultures exposed to conditions which induce differentiation. Under the latter conditions, while N1E-115 cells extend abundant neurites and express many biochemical features of mature neurons, clone N1A-103 stops dividing and expresses certain neurospecific markers but is unable to differentiate morphologically. In both clones, chemical agents, i.e. 1-methyl cyclohexane carboxylic acid (CCA) or dimethyl sulfoxide (DMSO), induce a decrease in c-myc expression. Similar results were found for N-myc gene in N1E-115 cells, but in contrast, in clone N1A-103, N-myc expression is increased with CCA and not modified with DMSO. Globally, this study favours the hypothesis that changes in c-myc expression would correspond to cell division blockade and differentiation, while modulations in N-myc are more closely related to an early phase of terminal differentiation.

Gut environment-induced intraepithelial autoreactive CD4+ T cells suppress central nervous system autoimmunity via LAG-3

PubMed Central

Kadowaki, Atsushi; Miyake, Sachiko; Saga, Ryoko; Chiba, Asako; Mochizuki, Hideki; Yamamura, Takashi

2016-01-01

The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of ‘induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS). They constitutively express Ctla4 and Tgfb1 and markedly upregulate Lag3 expression in the CNS, thereby inhibiting inflammation. We also demonstrate the suppressive capability of CD4+ IELs with alternative antigen specificities, their proliferation in response to gut-derived antigens and contribution of the microbiota and dietary aryl hydrocarbon receptor ligands to their induction. Thus, the gut environment favours the generation of autoreactive CD4+ T cells with unique regulatory functions, potentially important for preventing CNS autoimmunity. PMID:27198196

Post-fire environments are favourable for plant functioning of seeder and resprouter Mediterranean shrubs, even under drought.

PubMed

Parra, Antonio; Moreno, José M

2017-05-01

Understanding how drought affects seeder and resprouter plants during post-fire regeneration is important for the anticipation of Mediterranean vegetation vulnerability in a context of increasing drought and fire caused by climate change. A Mediterranean shrubland was subjected to various drought treatments (including 45% rainfall reduction, 7 months drought yr -1 ), before and after experimental burning, by means of a rainout-shelter system with an irrigation facility. Predawn shoot water potential (Ψ pd ), relative growth rate (RGR), specific leaf area (SLA) and bulk leaf carbon isotopic composition (δ 13 C) were monitored in the main woody species during the first 3 yr after fire. Cistus ladanifer seedlings showed higher Ψ pd , RGR and SLA, and lower δ 13 C, than unburned plants during the first two post-fire years. Seedlings under drought maintained relatively high Ψ pd , but suffered a decrease in Ψ pd and RGR, and an increase in δ 13 C, relative to control treatments. Erica arborea, E. scoparia and Phillyrea angustifolia resprouts had higher Ψ pd and RGR than unburned plants during the first post-fire year. Resprouters were largely unaffected by drought. Overall, despite marked differences between the two functional groups, post-fire environments were favourable for plant functioning of both seeder and resprouter shrubs, even under the most severe drought conditions implemented. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

PubMed Central

Mead, G. M.; Russell, M.; Clark, P.; Harland, S. J.; Harper, P. G.; Cowan, R.; Roberts, J. T.; Uscinska, B. M.; Griffiths, G. O.; Parmar, M. K.

1998-01-01

Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity. PMID:9792152

Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis

PubMed Central

Abrahamsson, Sofia V.; Angelini, Daniela F.; Dubinsky, Amy N.; Morel, Esther; Oh, Unsong; Jones, Joanne L.; Carassiti, Daniele; Reynolds, Richard; Salvetti, Marco; Calabresi, Peter A.; Coles, Alasdair J.; Battistini, Luca; Martin, Roland; Burt, Richard K.

2013-01-01

in the gut mucosa but expressing the central nervous system-homing receptor CCR6. Detection of mucosal-associated invariant T cells in post-mortem multiple sclerosis brain white matter active lesions confirmed their involvement in the disease pathology. Intracellular cytokine staining demonstrated interferon γ and interleukin 17 production and lack of interleukin 10 production, a pro-inflammatory profile. Mucosal-associated invariant T cell frequency did not change in patients treated with interferon β; and was more depleted after autologous haematopoietic stem cell transplantation than in patients who had received high-dose cyclophosphamide (n = 7) or alemtuzumab (n = 21) treatment alone, suggesting an additive or synergistic effect of the conditioning regime components. We propose that a favourably modified balance of regulatory and pro-inflammatory lymphocytes underlies the suppression of central nervous system inflammation in patients with multiple sclerosis following non-myeloablative autologous haematopoietic stem cell transplantation with a conditioning regimen consisting of cyclophosphamide and alemtuzumab. PMID:23864273

The Touch and Zap method for in vivo whole-cell patch recording of intrinsic and visual responses of cortical neurons and glial cells.

PubMed

Schramm, Adrien E; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J

2014-01-01

Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe "Touch and Zap", an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the "Touch". By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or "Zap", as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi

The Touch and Zap Method for In Vivo Whole-Cell Patch Recording of Intrinsic and Visual Responses of Cortical Neurons and Glial Cells

PubMed Central

Schramm, Adrien E.; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J.

2014-01-01

Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe “Touch and Zap”, an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the “Touch”. By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or “Zap”, as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi

The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

NASA Astrophysics Data System (ADS)

Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

2014-04-01

Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

Cell Based Associations: A procedure for considering scarce and mixed mineral occurrences in predictive mapping

NASA Astrophysics Data System (ADS)

Tourlière, Bruno; Pakyuz-Charrier, Evren; Cassard, Daniel; Barbanson, Luc; Gumiaux, Charles

2015-05-01

Cell Based Association is an innovative mineral favorability procedure designed to answer special needs of the mining industry in data wise critical situations where usual favorability methods may not yield satisfactory results. Those situations relate to input data quality (e.g. clustered points, mixed and scarce data, approximate location) or some assumptions that are considered unreasonable (e.g. map areas relevance, conditional independence). The principle of CBA consists in replacing polygons of geological units with a square cell grid (hence the 'cell-based'). Each cell contains a range of units ('association') that are binary coded in terms of their presence (1) or absence (0) within study area. The loss of resolution inherent to this procedure is compensated by the enriched information contained in each cell owing to the notion of (lithological) association. Lithological associations are considered as binary spectra and as such are classified using Ascendant Hierarchical Clustering (AHC) thus obtaining a synthetic map of lithological associations. The prospectivity map shows as favourable the cells of the same AHC classes that the ones including mineral occurrences. It was observed that CBA can distinguish between different ore deposit varieties from a blended mineral occurrences data set. CBA can theoretically include any spatialized data (e.g. geophysics, structural data) as an extra variable to specify classification and narrow favourable areas. Doing so would make it an independent favorability mapping procedure and is still under development. Cell size in a grid is a critical parameter of the procedure; it must be compatible with the looked-for phenomena and should have a sufficient lithological variability. In addition to its use for producing favorability maps, a CBA-derived map could help in understanding the background information contained in geological maps. CBA can also be applied to other fields, such as agriculture and urban planning

HER2 expression identifies dynamic functional states within circulating breast cancer cells.

PubMed

Jordan, Nicole Vincent; Bardia, Aditya; Wittner, Ben S; Benes, Cyril; Ligorio, Matteo; Zheng, Yu; Yu, Min; Sundaresan, Tilak K; Licausi, Joseph A; Desai, Rushil; O'Keefe, Ryan M; Ebright, Richard Y; Boukhali, Myriam; Sil, Srinjoy; Onozato, Maristela L; Iafrate, Anthony J; Kapur, Ravi; Sgroi, Dennis; Ting, David T; Toner, Mehmet; Ramaswamy, Sridhar; Haas, Wilhelm; Maheswaran, Shyamala; Haber, Daniel A

2016-09-01

Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER + /HER2 - primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2 + and HER2 - subpopulations: HER2 + circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2 - circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2 + and HER2 - circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2 + and HER2 - circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2 + state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2 - phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance.

Multistage carcinogenesis in cell culture.

PubMed

Rubin, H

2001-01-01

Rodent fibroblasts explanted from embryos to culture undergo a period of declining growth rate in serial passages leading to crisis, followed by the appearance of variants which can multiply indefinitely. If the "immortal" cell line was established by low density passage, i.e., 3T3 cells, it has a low saturation density and is non-tumorigenic. If it was established by high density passage, it has a high saturation density and is tumorigenic. The establishment of cells goes through successive stages, including increased capacity to multiply in low serum concentration, growth to high saturation density, growth in suspension, assisted tumour formation in susceptible hosts and unassisted tumour formation. Chromosome aberrations and aneuploidy occur long before the capacity to produce tumours appears. Contrary to conventional belief, human fibroblast populations also undergo a continuous loss of capacity to multiply from the time of explantation, with only the longest surviving clone reaching the Hayflick limit. Neoplastic transformation of rodent cells is strongly favoured by maintaining them in a quiescent state at confluence for prolonged periods, which results in genetic damage to the cells. It also produces a large variety of chromosomal aberrations in human cells and extends their replicative lifespan. Individual clones are more susceptible to spontaneous transformation than their heterogeneous parental cultures. The implications of these results for tumour development in vivo are that oncogenic genetic changes may be common under stressful conditions which restrict replication, and that such changes are maximized when a rogue clone reaches a critical size that reduces stabilizing interactions with neighbouring clones. An alternative explanation, described in the Addendum, which we retrospectively favor is that the easily transformed clones are a minority in the uncloned parental population. The reason they transform before the parental population is that when

Ovarian cancer stem cells: still an elusive entity?

PubMed

Lupia, Michela; Cavallaro, Ugo

2017-03-20

The cancer stem cell (CSC) model proposes that tumor development and progression are fueled and sustained by undifferentiated cancer cells, endowed with self-renewal and tumor-initiating capacity. Ovarian carcinoma, based on its biological features and clinical evolution, appears as a prototypical example of CSC-driven disease. Indeed, ovarian cancer stem cells (OCSC) would account not only for the primary tumor growth, the peritoneal spread and the relapse, but also for the development of chemoresistance, thus having profound implication for the treatment of this deadly disease. In the last decade, an increasing body of experimental evidence has supported the existence of OCSC and their pathogenic role in the disease. Nevertheless, the identification of OCSC and the definition of their phenotypical and functional traits have proven quite challenging, mainly because of the heterogeneity of the disease and of the difficulties in establishing reliable biological models. A deeper understanding of OCSC pathobiology will shed light on the mechanisms that underlie the clinical behaviour of OC. In addition, it will favour the design of innovative treatment regimens that, on one hand, would counteract the resistance to conventional chemotherapy, and, on the other, would aim at the eradication of OC through the elimination of its CSC component.

Induced pluripotent stem cells: Mechanisms, achievements and perspectives in farm animals

PubMed Central

Kumar, Dharmendra; Talluri, Thirumala R; Anand, Taruna; Kues, Wilfried A

2015-01-01

Pluripotent stem cells are unspecialized cells with unlimited self-renewal, and they can be triggered to differentiate into desired specialized cell types. These features provide the basis for an unlimited cell source for innovative cell therapies. Pluripotent cells also allow to study developmental pathways, and to employ them or their differentiated cell derivatives in pharmaceutical testing and biotechnological applications. Via blastocyst complementation, pluripotent cells are a favoured tool for the generation of genetically modified mice. The recently established technology to generate an induced pluripotency status by ectopic co-expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc allows to extending these applications to farm animal species, for which the derivation of genuine embryonic stem cells was not successful so far. Most induced pluripotent stem (iPS) cells are generated by retroviral or lentiviral transduction of reprogramming factors. Multiple viral integrations into the genome may cause insertional mutagenesis and may increase the risk of tumour formation. Non-integration methods have been reported to overcome the safety concerns associated with retro and lentiviral-derived iPS cells, such as transient expression of the reprogramming factors using episomal plasmids, and direct delivery of reprogramming mRNAs or proteins. In this review, we focus on the mechanisms of cellular reprogramming and current methods used to induce pluripotency. We also highlight problems associated with the generation of iPS cells. An increased understanding of the fundamental mechanisms underlying pluripotency and refining the methodology of iPS cell generation will have a profound impact on future development and application in regenerative medicine and reproductive biotechnology of farm animals. PMID:25815117

Soluble CD40-ligand (sCD40L, sCD154) plays an immunosuppressive role via regulatory T cell expansion in HIV infection

PubMed Central

Jenabian, M-A; Patel, M; Kema, I; Vyboh, K; Kanagaratham, C; Radzioch, D; Thébault, P; Lapointe, R; Gilmore, N; Ancuta, P; Tremblay, C; Routy, J-P

2014-01-01

CD40/CD40-ligand (CD40L) signalling is a key stimulatory pathway which triggers the tryptophan (Trp) catabolizing enzyme IDO in dendritic cells and is immunosuppressive in cancer. We reported IDO-induced Trp catabolism results in a T helper type 17 (Th17)/regulatory T cell (Treg) imbalance, and favours microbial translocation in HIV chronic infection. Here we assessed the link between sCD40L, Tregs and IDO activity in HIV-infected patients with different clinical outcomes. Plasmatic sCD40L and inflammatory cytokines were assessed in anti-retroviral therapy (ART)-naive, ART-successfully treated (ST), elite controllers (EC) and healthy subjects (HS). Plasma levels of Trp and its metabolite Kynurenine (Kyn) were measured by isotope dilution tandem mass spectrometry and sCD14 was assessed by enzyme-linked immunosorbent assay (ELISA). IDO-mRNA expression was quantified by reverse transcription–polymerase chain reaction (RT–PCR). The in-vitro functional assay of sCD40L on Treg induction and T cell activation were assessed on peripheral blood mononuclear cells (PBMCs) from HS. sCD40L levels in ART-naive subjects were significantly higher compared to ST and HS, whereas EC showed only a minor increase. In ART-naive alone, sCD40L was correlated with T cell activation, IDO-mRNA expression and CD4 T cell depletion but not with viral load. sCD40L was correlated positively with IDO enzymatic activity (Kyn/Trp ratio), Treg frequency, plasma sCD14 and inflammatory soluble factors in all HIV-infected patients. In-vitro functional sCD40L stimulation induced Treg expansion and favoured Treg differentiation by reducing central memory and increasing terminal effector Treg proportion. sCD40L also increased T cell activation measured by co-expression of CD38/human leucocyte antigen D-related (HLA-DR). These results indicate that elevated sCD40L induces immunosuppression in HIV infection by mediating IDO-induced Trp catabolism and Treg expansion. PMID:24924152

Soluble CD40-ligand (sCD40L, sCD154) plays an immunosuppressive role via regulatory T cell expansion in HIV infection.

PubMed

Jenabian, M-A; Patel, M; Kema, I; Vyboh, K; Kanagaratham, C; Radzioch, D; Thébault, P; Lapointe, R; Gilmore, N; Ancuta, P; Tremblay, C; Routy, J-P

2014-10-01

CD40/CD40-ligand (CD40L) signalling is a key stimulatory pathway which triggers the tryptophan (Trp) catabolizing enzyme IDO in dendritic cells and is immunosuppressive in cancer. We reported IDO-induced Trp catabolism results in a T helper type 17 (Th17)/regulatory T cell (Treg ) imbalance, and favours microbial translocation in HIV chronic infection. Here we assessed the link between sCD40L, Tregs and IDO activity in HIV-infected patients with different clinical outcomes. Plasmatic sCD40L and inflammatory cytokines were assessed in anti-retroviral therapy (ART)-naive, ART-successfully treated (ST), elite controllers (EC) and healthy subjects (HS). Plasma levels of Trp and its metabolite Kynurenine (Kyn) were measured by isotope dilution tandem mass spectrometry and sCD14 was assessed by enzyme-linked immunosorbent assay (ELISA). IDO-mRNA expression was quantified by reverse transcription-polymerase chain reaction (RT-PCR). The in-vitro functional assay of sCD40L on Treg induction and T cell activation were assessed on peripheral blood mononuclear cells (PBMCs) from HS. sCD40L levels in ART-naive subjects were significantly higher compared to ST and HS, whereas EC showed only a minor increase. In ART-naive alone, sCD40L was correlated with T cell activation, IDO-mRNA expression and CD4 T cell depletion but not with viral load. sCD40L was correlated positively with IDO enzymatic activity (Kyn/Trp ratio), Treg frequency, plasma sCD14 and inflammatory soluble factors in all HIV-infected patients. In-vitro functional sCD40L stimulation induced Treg expansion and favoured Treg differentiation by reducing central memory and increasing terminal effector Treg proportion. sCD40L also increased T cell activation measured by co-expression of CD38/human leucocyte antigen D-related (HLA-DR). These results indicate that elevated sCD40L induces immunosuppression in HIV infection by mediating IDO-induced Trp catabolism and Treg expansion. © 2014 British Society for Immunology.

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Science.gov Websites

Partnership Successes Photo of a hand holding an ecobee smart thermostat Bringing Comfort, Convenience, and adoption-a win-win for both homeowners and utilities. Learn more. Blue electric bus in California's Santa Clara Valley Evaluating Electric Bus Grid Integration Performance in California's Santa Clara Valley

Synoptic conditions favouring the occurrence of dust transport from Africa toward Sardinia Island.

NASA Astrophysics Data System (ADS)

Canu, Annalisa; Pellizzaro, Grazia; Pintus, Gabriella; Duce, Pierpaolo

2016-04-01

characterized by a low-pressure system over the Iberian Peninsula that extended towards Morocco and by the associated high-pressure system over the North-East Africa (Algeria, Tunisia and Libya) and Sicily. This synoptic structure (low pressure over North-Western Africa) forced the dusty air masses towards the Mediterranean basin, favouring the transport of African air masses towards the Sardinia island.

Epidermal 'alarm substance' cells of fishes maintained by non-alarm functions: possible defence against pathogens, parasites and UVB radiation.

PubMed

Chivers, Douglas P; Wisenden, Brian D; Hindman, Carrie J; Michalak, Tracy A; Kusch, Robin C; Kaminskyj, Susan G W; Jack, Kristin L; Ferrari, Maud C O; Pollock, Robyn J; Halbgewachs, Colin F; Pollock, Michael S; Alemadi, Shireen; James, Clayton T; Savaloja, Rachel K; Goater, Cameron P; Corwin, Amber; Mirza, Reehan S; Kiesecker, Joseph M; Brown, Grant E; Adrian, James C; Krone, Patrick H; Blaustein, Andrew R; Mathis, Alicia

2007-10-22

Many fishes possess specialized epidermal cells that are ruptured by the teeth of predators, thus reliably indicating the presence of an actively foraging predator. Understanding the evolution of these cells has intrigued evolutionary ecologists because the release of these alarm chemicals is not voluntary. Here, we show that predation pressure does not influence alarm cell production in fishes. Alarm cell production is stimulated by exposure to skin-penetrating pathogens (water moulds: Saprolegnia ferax and Saprolegnia parasitica), skin-penetrating parasites (larval trematodes: Teleorchis sp. and Uvulifer sp.) and correlated with exposure to UV radiation. Suppression of the immune system with environmentally relevant levels of Cd inhibits alarm cell production of fishes challenged with Saprolegnia. These data are the first evidence that alarm substance cells have an immune function against ubiquitous environmental challenges to epidermal integrity. Our results indicate that these specialized cells arose and are maintained by natural selection owing to selfish benefits unrelated to predator-prey interactions. Cell contents released when these cells are damaged in predator attacks have secondarily acquired an ecological role as alarm cues because selection favours receivers to detect and respond adaptively to public information about predation.

A unique 19F MRI agent for the tracking of non phagocytic cells in vivo.

PubMed

Moonshi, Shehzahdi S; Zhang, Cheng; Peng, Hui; Puttick, Simon; Rose, Stephen; Fisk, Nicholas M; Bhakoo, Kishore; Stringer, Brett W; Qiao, Greg G; Gurr, Paul A; Whittaker, Andrew K

2018-05-03

There is currently intense interest in new methods for understanding the fate of therapeutically-relevant cells, such as mesenchymal stem cells (MSCs). The absence of a confounding background signal and consequent unequivocal assignment makes 19F MRI one of the most attractive modalities for the tracking of injected cells in vivo. We describe here the synthesis of novel partly-fluorinated polymeric nanoparticles with small size and high fluorine content as MRI agents. The polymers, constructed from perfluoropolyether methacrylate (PFPEMA) and oligo(ethylene glycol) methacrylate (OEGMA) have favourable cell uptake profiles and excellent MRI performance. To facilitate cell studies the polymer was further conjugated with a fluorescent dye creating a dual-modal imaging agent. The efficacy of labelling of MSCs was assessed using 19F NMR, flow cytometry and confocal microscopy. The labelling efficiency of 2.6 ± 0.1 × 1012 19F atoms per cell, and viability of >90% demonstrates high uptake and good tolerance by the cells. This loading translates to a minimum 19F MRI detection sensitivity of ∼7.4 × 103 cells per voxel. Importantly, preliminary in vivo data demonstrate that labelled cells can be readily detected within a short acquisition scan period (12 minutes). Hence, these copolymers show outstanding potential for 19F MRI cellular tracking and for quantification of non-phagocytic and therapeutically-relevant cells in vivo.

High-dose interleukin2 - a 10-year single-site experience in the treatment of metastatic renal cell carcinoma: careful selection of patients gives an excellent outcome.

PubMed

Chow, S; Galvis, V; Pillai, M; Leach, R; Keene, E; Spencer-Shaw, A; Shablak, A; Shanks, J; Liptrot, T; Thistlethwaite, F; Hawkins, R E

2016-01-01

VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes. This is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into Favourable or Other categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with Favourable pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors. Among prospectively selected patients with Favourable pathology ( n  = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete

Hyaluronic acid effect on adipose-derived stem cells. Biological in vitro evaluation.

PubMed

Moreno, A; Martínez, A; Olmedillas, S; Bello, S; de Miguel, F

2015-01-01

To evaluate the in vitro effects of hyaluronic acid (HA) on adipose-derived stem cells (ASC) in order to consider the possibility of their combined used in the treatment of knee arthrosis. The ASC cells were grown both in the presence and absence of AH, and several studies were carried out: proliferation (WST8) and cell viability studies (Alamar Blue® and Trypan Blue), possible chondrogenic differentiation (collagen type 2 expression) by RT-PCR, AH receptor expression (CD44) by flow cytometry and RT-QPCR, and expression of inflammatory and anti-inflammatory factors (IL-6, TGFß, IL-10) by RT-QPCR. The number of ASC significantly increased after 7 days with HA (158±39%, p <0.05). Additionally, the cell viability of the ASC treated with HA after 1, 3, 5 and 7 days was similar to that of the control cells, being considered non-toxic. There were no changes observed in the expression of CD44 and chondrogenic differentiation. TGFß expression was not modified after AH treatment, but there was a 4-fold decrease in IL-6 expression and IL-10 expression increased up to 2-fold compared to control cells. Hyaluronic acid favours ASC proliferation without causing cellular toxicity, and inducing an anti-inflammatory profile in these cells. Hyaluronic acid appears to be a suitable vehicle for the intra-articular administration of mesenchymal stem cells. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases.

PubMed

Lescaudron, L; Naveilhan, P; Neveu, I

2012-01-01

Cell transplantation has been proposed as a means of replacing specific cell populations lost through neurodegenerative processes such as that seen in Parkinson's or Huntington's diseases. Improvement of the clinical symptoms has been observed in a number of Parkinson and Huntington's patients transplanted with freshly isolated fetal brain tissue but such restorative approach is greatly hampered by logistic and ethical concerns relative to the use of fetal tissue, in addition to potential side effects that remain to be controlled. In this context, stem cells that are capable of self-renewal and can differentiate into neurons, have received a great deal of interest, as demonstrated by the numerous studies based on the transplantation of neural stem/progenitor cells, embryonic stem cells or mesenchymal stem cells into animal models of Parkinson's or Huntington's diseases. More recently, the induction of pluripotent stem cells from somatic adult cells has raised a new hope for the treatment of neurodegenerative diseases. In the present article, we review the main experimental approaches to assess the efficiency of cell-based therapy for Parkinson's or Huntington's diseases, and discuss the recent advances in using stem cells to replace lost dopaminergic mesencephalic or striatal neurons. Characteristics of the different stem cells are extensively examined with a special attention to their ability of producing neurotrophic or immunosuppressive factors, as these may provide a favourable environment for brain tissue repair and long-term survival of transplanted cells in the central nervous system. Thus, stem cell therapy can be a valuable tool in regenerative medicine.

Novel fiber-based pure chitosan scaffold for tendon augmentation: biomechanical and cell biological evaluation.

PubMed

Nowotny, J; Aibibu, D; Farack, J; Nimtschke, U; Hild, M; Gelinsky, M; Kasten, P; Cherif, Ch

2016-07-01

One possibility to improve the mechanical properties after tendon ruptures is augmentation with a scaffold. Based on wet spinning technology, chitosan fibres were processed to a novel pure high-grade multifilament yarn with reproducible quality. The fibres were braided to obtain a 3D tendon scaffold. The CS fibres and scaffolds were evaluated biomechanically and compared to human supraspinatus (SSP) tendons. For the cytobiological characterization, in vitro cell culture experiments with human mesenchymal stem cells (hMSC) were performed. Three types of 3D circular braided scaffolds were fabricated. Significantly, higher ultimate stress values were measured for scaffold with larger filament yarn, compared to scaffold with smaller filament yarn. During cultivation over 28 days, the cells showed in dependence of isolation method and/or donor a doubling or tripling of the cell number or even a six-fold increase on the CS scaffold, which was comparable to the control (polystyrene) or in the case of cells obtained from human biceps tendon even higher proliferation rates. After 14 days, the scaffold surface was covered homogeneously with a cell layer. In summary, the present work demonstrates that braided chitosan scaffolds constitute a straightforward approach for designing tendon analogues, maintaining important flexibility in scaffold design and providing favourable mechanical properties of the resulting construct.

Bartonella entry mechanisms into mammalian host cells.

PubMed

Eicher, Simone C; Dehio, Christoph

2012-08-01

The Gram-negative genus Bartonella comprises arthropod-borne pathogens that typically infect mammals in a host-specific manner. Bartonella bacilliformis and Bartonella quintana are human-specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of Bartonella infections range from mild symptoms to life-threatening disease. Following transmission by blood-sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host-specific manner. Attachment to the extracellular matrix (ECM) and to nucleated cells is mediated by surface-exposed bacterial adhesins, in particular trimeric autotransporter adhesins (TAAs). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For Bartonella henselae and assumingly most other species, the infection process is aided at different steps by Bartonella effector proteins (Beps). They are injected into host cells through the type IV secretion system (T4SS) VirB/D4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by Trw, another T4SS, in a strictly host-specific manner, followed by pathogen-forced uptake involving the IalB invasin and subsequent replication and persistence within a membrane-bound intra-erythrocytic compartment. © 2012 Blackwell Publishing Ltd.

Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib.

PubMed

Hickinson, D Mark; Marshall, Gayle B; Beran, Garry J; Varella-Garcia, Marileila; Mills, Elizabeth A; South, Marie C; Cassidy, Andrew M; Acheson, Kerry L; McWalter, Gael; McCormack, Rose M; Bunn, Paul A; French, Tim; Graham, Alex; Holloway, Brian R; Hirsch, Fred R; Speake, Georgina

2009-06-01

Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an exploratory principal component analysis revealed a separation between the genomic profiles of sensitive and resistant cell lines. Subsequently, a hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A hypothesis-free analysis identified 46 gene transcripts that were strongly differentiated, seven of which had a known association with EGFR and head and neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed Affymetrix data, and EGFR gene mutation, amplification, and genomic gain correlated strongly with gefitinib sensitivity. We identified biomarkers that predict for in vitro responsiveness to gefitinib, seven of which have known association with EGFR and head and neck cancer. These in vitro predictive biomarkers may have potential utility in the clinic and warrant further investigation.

Immunomodulatory/inflammatory effects of geopropolis produced by Melipona fasciculata Smith in combination with doxorubicin on THP-1 cells.

PubMed

Oliveira, Lucas Pires Garcia; Conte, Fernanda Lopes; Cardoso, Eliza de Oliveira; Conti, Bruno José; Santiago, Karina Basso; Golim, Marjorie de Assis; Cruz, Maria Teresa; Sforcin, José Maurício

2016-12-01

Geopropolis (GEO) in combination with doxorubicin (DOX) reduced HEp-2 cells viability compared to GEO and DOX alone. A possible effect of this combination on the innate immunity could take place, and its effects were analysed on THP-1 cell - a human leukaemia monocytic cell line used as a model to study monocyte activity and macrophage activity, assessing cell viability, expression of cell markers and cytokine production. THP-1 cells were incubated with GEO, DOX and their combination. Cell viability was assessed by MTT assay, cell markers expression by flow cytometry and cytokine production by ELISA. GEO + DOX did not affect cell viability. GEO alone or in combination increased TLR-4 and CD80 but not HLA-DR and TLR-2 expression. GEO stimulated TNF-α production while DOX alone or in combination did not affect it. GEO alone or in combination inhibited IL-6 production. GEO exerted a pro-inflammatory profile by increasing TLR-4 and CD80 expression and TNF-α production, favouring the activation of the immune/inflammatory response. GEO + DOX did not affect cell viability and presented an immunomodulatory action. Lower concentrations of DOX combined to GEO could be used in cancer patients, avoiding side effects and benefiting from the biological properties of GEO. © 2016 Royal Pharmaceutical Society.

Mycosporine-like amino acids and xanthophyll-cycle pigments favour a massive spring bloom development of the dinoflagellate Prorocentrum minimum in Grande Bay (Argentina), an ozone hole affected area

NASA Astrophysics Data System (ADS)

Carreto, José I.; Carignan, Mario O.; Montoya, Nora G.; Cozzolino, Ezequiel; Akselman, Rut

2018-02-01

In Grande Bay (Southern Patagonian Shelf) in a eutrophic and recirculating area slightly stratified during spring, we observed an intense (up to 1 × 107 cells L- 1) and shallow, quasi mono-specific bloom of the dinoflagellate Prorocentrum minimum. Peridinin was the most abundant carotenoid, but the relative amounts of the xanthophyll cycle carotenoids (diadinoxanthin + diatoxanthin = DT) to light-harvesting pigments were high (DT/Chl a ratio = 0.32 and DT/peridinin ratio = 0.40). Shinorine, usujirene, palythene, mycosporine-serine-glycine methyl ester and palythenic acid were the primary mycosporine-like amino acids (MAAs), followed by mycosporine-glycine, palythine, and porphyra-334. The ΣMAAs/Chl a ratios (up to 27.9 nmol/nmol) were in the upper range reported either in nutrient-replete dinoflagellate cultures or natural populations. We monitored, from space (using satellite ocean colour data), the spatial and temporal bloom variability (from September 22 to October 31, 2005) using an approach to discriminate dinoflagellate from diatom blooms. The results indicated that an intense diatom bloom started in early spring but was rapidly replaced by an intense bloom of the dinoflagellate P. minimum, although the nutrient concentrations were apparently not limiting. The most notorious change in this period was a sharp increase in the levels of solar UVB radiation (UVB index 9.0) as a consequence of the overpass of the polar vortex over this area. We postulated that the synthesis and accumulation of MAAs and xanthophyll pigments, were competitive advantages for the opportunistic red tide dinoflagellate P. minimum over the sensitive diatoms, favouring the development of their surface blooms in this seasonally solar UVB radiation (UVBR) affected area.

XIAP as a Molecular Target for Therapeutic Intervention in Prostate Cancer

DTIC Science & Technology

2007-10-01

receptor corepressor Clara Hwang Æ Veda N. Giri Æ John C. Wilkinson Æ Casey W. Wright Æ Amanda S. Wilkinson Æ Kathleen A. Cooney Æ Colin S. Duckett Received...including BRCA1, histone deacetylases (HDAC), and members of the polycomb group (PcG) of proteins. Clara Hwang and Veda N. Giri contributed equally to

Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy

PubMed Central

Moffett, R. Charlotte; Vasu, Srividya; Thorens, Bernard; Drucker, Daniel J.; Flatt, Peter R.

2014-01-01

Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in islet and beta cell area, numbers of medium/large sized islets, with positive effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic insulin content. Alpha cell area and glucagon content were unchanged but prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1 and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This was associated with abolition of normal pregnancy-induced increases in plasma GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1. PMID:24927416

The composition of cell walls from grape skin in Vitis vinifera intraspecific hybrids.

PubMed

Apolinar-Valiente, Rafael; Gómez-Plaza, Encarna; Terrier, Nancy; Doco, Thierry; Ros-García, José María

2017-09-01

Monastrell is a red grape cultivar adapted to the dry environmental conditions of Murcia, SE Spain. Its berries seem to be characterized by a rigid cell wall structure, which could make difficult the winemaking process. Cabernet Sauvignon cultivar is used to complement Monastrell wines in this region owing to its high phenolic content with high extractability. This study explores the skin cell wall composition of grapes from plants resulting from intraspecific crosses of Vitis vinifera cultivars Monastrell × Cabernet Sauvignon. Moreover, the morphology of the cell wall material (CWM) from some representative samples was visualized by transmission optical microscopy. The total sugar content of CWM from nine out of ten genotypes of the progeny was lower than that from Monastrell. Seven out of ten genotypes showed lower phenolic content than Cabernet Sauvignon. The CWM from nine out of ten hybrids presented lower protein content than that from Monastrell. This study confirms that skin cell walls from Monastrell × Cabernet Sauvignon hybrid grapes presented major differences in composition compared with their parents. These data could help in the development of new cultivars adapted to the dry conditions of SE Spain and with a cell wall composition favouring extractability. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Cell type dependent morphological adaptation in polyelectrolyte hydrogels governs chondrogenic fate.

PubMed

Raghothaman, Deepak; Leong, Meng Fatt; Lim, Tze Chiun; Wan, Andrew C A; Ser, Zheng; Lee, Eng Hin; Yang, Zheng

2016-04-04

Repair of critical-size articular cartilage defects typically involves delivery of cells in biodegradable, 3D matrices. Differences in the developmental status of mesenchymal stem cells (MSCs) and terminally differentiated mature chondrocytes might be a critical factor in engineering appropriate 3D matrices for articular cartilage tissue engineering. This study examined the relationship between material-driven early cell morphological adaptations and chondrogenic outcomes, by studying the influence of aligned collagen type I (Col I) presentation on chondrocytes and MSC in interfacial polyelectrolyte complexation (IPC)-based hydrogels. In the absence of Col I, both chondrocytes and MSCs adopted rounded cell morphology and formed clusters, with chondrocyte clusters favoring the maintenance of hyaline phenotype, while MSC clusters differentiated to fibro-superficial zone-like chondrocytes. Encapsulated chondrocytes in IPC-Col I hydrogel adopted a fibroblastic morphology forming fibro-superficial zone-like phenotype, which could be reversed by inhibiting actin polymerization using cytochalasin D (CytD). In contrast, adoption of fibroblastic morphology by encapsulated MSCs in IPC-Col I facilitated superior chondrogenesis, generating a mature, hyaline neocartilage tissue. CytD treatment abrogated the elongation of MSCs and brought about a single cell-like state, resulting in insignificant chondrogenic differentiation, underscoring the essential requirement of providing matrix environments that are amenable to cell-cell interactions for robust MSC chondrogenic differentiation. Our study demonstrates that MSCs and culture-expanded chondrocytes favour differential microenvironmental niches and emphasizes the importance of designing biomaterials that meet cell type-specific requirements, in adopting chondrocyte or MSC-based approaches for regenerating hyaline, articular cartilage.

Heterosis May Result in Selection Favouring the Products of Long-Distance Pollen Dispersal in Eucalyptus

PubMed Central

Costa e Silva, João; Potts, Brad M.; Lopez, Gustavo A.

2014-01-01

Using native trees from near the northern and southern extremities of the relatively continuous eastern distribution of Eucalyptus globulus in Tasmania, we compared the progenies derived from natural open-pollination (OP) with those generated from within-region and long-distance outcrossing. Controlled outcrossing amongst eight parents - with four parents from each of the northern and southern regions - was undertaken using a diallel mating scheme. The progeny were planted in two field trials located within the species native range in southern Tasmania, and their survival and diameter growth were monitored over a 13-year-period. The survival and growth performances of all controlled cross types exceeded those of the OP progenies, consistent with inbreeding depression due to a combination of selfing and bi-parental inbreeding. The poorer survival of the northern regional (♀N♂N) outcrosses compared with the local southern regional outcrosses (♀S♂S) indicated differential selection against the former. Despite this mal-adaptation of the non-local ♀N♂N crosses at both southern sites, the survival of the inter-regional hybrids (♀N♂S and ♀S♂N) was never significantly different from that of the local ♀S♂S crosses. Significant site-dependent heterosis was detected for the growth of the surviving long-distance hybrids. This was expressed as mid-parent heterosis, particularly at the more northern planting site. Heterosis increased with age, while the difference between the regional ♀N♂N and ♀S♂S crosses remained insignificant at any age at either site. Nevertheless, the results for growth suggest that the fitness of individuals derived from long-distance crossing may be better at the more northern of the planting sites. Our results demonstrate the potential for early-age assessments of pollen dispersal to underestimate realised gene flow, with local inbreeding under natural open-pollination resulting in selection favouring the products of

Long-Term Harvest Residue Retention Could Decrease Soil Bacterial Diversities Probably Due to Favouring Oligotrophic Lineages.

PubMed

Zhang, Yaling; Zhang, Manyun; Tang, Li; Che, Rongxiao; Chen, Hong; Blumfield, Tim; Boyd, Sue; Nouansyvong, Mone; Xu, Zhihong

2018-03-01

Harvest residues contain large stores of carbon (C) and nitrogen (N) in forest plantations. Decomposing residues can release labile C and N into soil and thus provide substrates for soil bacterial communities. Previous studies showed that residue retention could increase soil C and N pools and activate bacterial communities in the short term (≤ 10 years). The current study examined the effects of a long-term (19-year) harvest residue retention on soil total and water and hot water extractable C and N pools, as well as bacterial communities via Illumina MiSeq sequencing. The experiment was established in a randomised complete block design with four replications, southeast Queensland of Australia, including no (R0), single (R1, 51 to 74 t ha -1 dry matter) and double quantities (R2, 140 t ha -1 dry matter) of residues retained. Generally, no significant differences existed in total C and N, as well as C and N pools extracted by water and hot water among the three treatments, probably due to negligible amounts of labile C and N released from harvest residues. Soil δ 15 N significantly decreased from R0 to R1 to R2, probably due to reduced N leaching with residue retention (P < 0.001). Residue retention increased the relative abundances of Actinobacteria (P = 0.016) and Spartobacteria (P < 0.001), whereas decreased Betaproteobacteria (P = 0.050). This favour for the oligotrophic groups probably caused the decrease in the bacterial diversity as revealed by Shannon index (P = 0.025). Hence, our study suggests that residue retention is not an appropriate management practice in the long term.

Alcohols potentiate the function of 5-HT3 receptor–channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state

PubMed Central

Zhou, Qing; Verdoorn, Todd A; Lovinger, David M

1998-01-01

5-HT3 receptor-mediated ion current was recorded from NCB-20 neuroblastoma cells using the whole-cell patch-clamp technique. Rapid drug superfusion was used to study the mechanism of alcohol potentiation of 5-HT3 receptor function and to analyse effects of alcohols on receptor-channel kinetics in detail.Trichloroethanol (TCEt) increased in a dose-dependent way the initial slope, 20–80 % rise time and measured desensitization rate of the current induced by low concentrations (1–2 μm) of 5-HT. Ethanol (EtOH) and butanol (ButOH) had similar effects on the 5-HT3 receptor-induced current.TCEt and ButOH decreased the measured desensitization rate of current induced by 10 μm 5-HT, a maximally effective concentration of agonist. These alcohols also increased the relative amplitude of steady state to peak current induced by 2 or 10 μm 5-HT, indicating a possible decrease in the intrinsic rate of desensitization.TCEt also decreased the deactivation rate of the current activated by 2 μm 5-HT after a short pulse of agonist application.Current sweeps generated by 1 μm 5-HT in the presence or absence of 10 mm TCEt or 100 mm EtOH were well fitted using a modified standard kinetic model derived from the nicotinic acetylcholine receptor. This analysis indicated that potentiation by alcohols could be accounted for by increases in the association rate constant coupled with decreases in the dissociation and desensitization rate constants.This study suggests that alcohols potentiate 5-HT3 receptor-mediated current by both increasing the rate of channel activation and stabilizing the open state by decreasing the rates of channel deactivation and desensitization. PMID:9518697

Wildfire in the valley of the wild roses

Treesearch

Linda Moon Stumpff

2015-01-01

Santa Clara Indian Pueblo lands are adjacent to the Jemez National Forest, Bandelier National Monument and Valles Caldera National Preserve. This paper explores Pueblo vulnerability and resilience after repeated and devastating fires in this century as a result of drought and climate change. Santa Clara Pueblo holds a rich store of traditional knowledge about the fire-...

Periodontal healing by periodontal ligament cell sheets in a teeth replantation model.

PubMed

Zhou, Yefang; Li, Yusheng; Mao, Ling; Peng, Hao

2012-02-01

Successful transplantation of avulsed teeth is to restore the attachment and regenerate the periodontal support. Different strategies have been applied in treatment from modification of teeth storage, antibiotic usage to peridontium tissue replacement. We developed a novel periodontal ligament cell-sheet delivery system to apply on delayed replanted teeth in promoting periodontal healing in a canine model. Autologous periodontal ligament (PDL) fibroblasts were isolated from extracted premolars of beagle dog. The cell-sheets were fabricated using normal culture dish after stimulation of extracellular matrix formation. Teeth were surgically extracted and attached soft tissues were removed. After root canal treatment, the root of teeth were wrapped by the PDL cell-sheets and replanted back to prior socket accordingly whilst teeth without cell sheets as a control. Eight weeks after surgery, the animals were sacrificed and decalcified specimens were prepared. Regeneration of periodontal tissue was evaluated through histology assay. Multi-layered PDL cell-sheet could be attached on tooth root and most cells on sheet-tooth constructs were viable before replantation. Minimum clinical signs of inflammation were observed in experiment. PDL cell-sheets group show significant higher occurrence of favourable healing (88.4%) than control group with low healing (5.3%). Periodontal ligament and cememtum tissue regeneration was observed in the experimental group, and the regenerated tissues showed high collagen type III, type I and fibronectin expression. The periodontal ligament cell-sheets fabricated through normal cell culture dish has a potential for regeneration of periodontal ligament and may become a novel therapy for avulsed teeth replantation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fabrication of mediator-free hybrid nano-interfaced electrochemical biosensor for monitoring cancer cell proliferation.

PubMed

Madhurantakam, Sasya; Jayanth Babu, K; Balaguru Rayappan, John Bosco; Krishnan, Uma Maheswari

2017-01-15

Glucose, a chief energy source in cellular metabolism, has a significant role in cell proliferation. Cancer cells utilize more glucose than normal cells to meet the energy demand arising due to their uncontrolled proliferation. The present work reports the development of a nano-interfaced amperometric biosensor for rapid and accurate monitoring of glucose utilization by cancer cells. A hybrid nano-interface comprising a blend of carbon nanotubes (CNTs) and graphene (GR) was employed to enhance the surface area of the working electrode and favour direct electron transfer. Glucose oxidase (GOx) immobilized on the interface serves as the sensing element due to its high selectivity and sensitivity towards glucose. Utilization of glucose was monitored at pre-determined time intervals in MiaPaCa-2 cancer cells. The results obtained from the amperometric technique were compared with the values obtained from a commercial glucometer. Alamar blue assay was performed to check the proliferation rate of the cells. A good correlation was obtained between the proliferation rate and glucose utilization. The designed biosensor was found to be unaffected by the presence of potential interferents and hence may serve as a novel in vitro tool to rapidly quantify the proliferation rates of cancer cells in response to different treatment strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

Monkey CV1 cell line expressing the sheep-goat SLAM protein: a highly sensitive cell line for the isolation of peste des petits ruminants virus from pathological specimens.

PubMed

Adombi, Caroline Mélanie; Lelenta, Mamadou; Lamien, Charles Euloge; Shamaki, David; Koffi, Yao Mathurin; Traoré, Abdallah; Silber, Roland; Couacy-Hymann, Emmanuel; Bodjo, Sanne Charles; Djaman, Joseph A; Luckins, Antony George; Diallo, Adama

2011-05-01

Peste des petits ruminants (PPR) is an important economically transboundary disease of sheep and goats caused by a virus which belongs to the genus Morbillivirus. This genus, in the family Paramyxoviridae, also includes the measles virus (MV), canine distemper virus (CDV), rinderpest virus (RPV), and marine mammal viruses. One of the main features of these viruses is the severe transient lymphopaenia and immunosuppression they induce in their respective hosts, thereby favouring secondary bacterial and parasitic infections. This lymphopaenia is probably accounted for by the fact that lymphoid cells are the main targets of the morbilliviruses. In early 2000, it was demonstrated that a transmembrane glycoprotein of the immunoglobulin superfamily which is present on the surface of lymphoid cells, the signalling lymphocyte activation molecule (SLAM), is used as cellular receptor by MV, CDV and RPV. Wild-type strains of these viruses can be isolated and propagated efficiently in non-lymphoid cells expressing this protein. The present study has demonstrated that monkey CV1 cells expressing goat SLAM are also highly efficient for isolating PPRV from pathological samples. This finding suggests that SLAM, as is in the case for MV, CDV and RPV, is also a receptor for PPRV. Copyright © 2011 Elsevier B.V. All rights reserved.

Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

PubMed

De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

2016-07-01

Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.

PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis.

PubMed

Hecht, Markus; Büttner-Herold, Maike; Erlenbach-Wünsch, Katharina; Haderlein, Marlen; Croner, Roland; Grützmann, Robert; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold V

2016-09-01

The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value. PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated. RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030). Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stem cells and their role in renal ischaemia reperfusion injury.

PubMed

Bagul, Atul; Frost, Jodie H; Drage, Martin

2013-01-01

Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

Establishing a public umbilical cord blood stem cell bank for South Africa: an enquiry into public acceptability.

PubMed

Meissner-Roloff, Madelein; Pepper, Michael S

2013-12-01

South Africa (SA) faces a large unmet need for bone marrow (BM) transplantation, which could be alleviated in part by establishing a public umbilical cord blood stem cell bank (UCB SCB). Umbilical cord blood is an increasingly utilised source of hematopoietic stem cells for BM transplantation in addition to BM or mobilized peripheral blood stem cells. Establishing a public UCB SCB would therefore be a positive step towards improving the quality of health care in SA by providing for an important unmet need. This study takes the form of an enquiry into the acceptability of establishing a public bank through an interview with and questionnaire completed by mothers-to-be in the antenatal clinic of a large public hospital in SA. Initial results are positive, with 85 % of the participants in favour of establishing a public UCB SCB in SA. This initial probe will serve as a model for a more comprehensive national enquiry into public support and acceptability in different clinics, hospitals and provinces in SA.

Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

PubMed Central

Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

2012-01-01

Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

Forced emigration, favourable outcomes.

PubMed

Pearn, J

2001-10-01

The discipline of public health and preventive medicine in Australia and New Zealand had its genesis in the advocacy of 18th and 19th century military pioneers. Military (Royal Navy and British Army) surgeons were posted to Australia as part of their non-discretionary duty. Civilian doctors emigrated variously for adventure, escapism and gold fever. One group, a particularly influential group disproportionate to their numbers, came in one sense as forced emigrants because of chronic respiratory disease in general, and tuberculosis in particular. Tuberculosis was an occupational hazard of 19th century medical and surgical practice throughout western Europe. This paper analyses six examples of such emigration which had, perhaps unforeseen at the time, significant results in the advancement of public health. Such emigration was in one sense voluntary, but in another was forced upon the victims in their quest for personal survival. In Australia, such medical individuals became leading advocates and successful catalysts for change in such diverse fields as social welfare, public health, the preventive aspects of medical practice, child health, nutrition and medical education. A number of such public health pioneers today have no physical memorials; but their influence is to be seen in the ethos of medical practice in Australia and New Zealand today. Their memory is further perpetuated in the names of Australian native wildflowers and trees that symbolise not only a healthy environment but the long-term investment, accrued with interest, of the institution of public health measures for which their advocacy achieved much success.

Devising work schedules for a collective: favouring intergenerational collaboration among counsellors in a shelter for female victims of conjugal violence.

PubMed

Chatigny, Céline

2011-01-01

The work activity of counsellors in shelters for female victims of conjugal violence is explored. The consortium of shelters requested the study because of complaints of worker stress, difficulties in management and high employee turnover. This qualitative and participatory community study involved a team of specialists in ergonomics and social work from the Centre de recherche interdisciplinaire sur la biologie, la santé, la sociélté et l'environnement (CINBIOSE), brought together by the Community Outreach Service of Université du Québec à Montréal (UQAM). Presented here are the study findings pertaining to training. Twenty-two semi-structured interviews and 80 hours of observation of work and training were conducted with counsellors from two contrasting shelters. Observations revealed an intense collaborative activity involving communication by many means. Nonetheless, young counsellors interviewed complained of having few opportunities to develop their counselling skills because they were isolated on evening, night and weekend shifts. In collaboration with the ergonomists, one shelter experimented with new ways of devising the work schedule to favour learning and training. By transforming the training mechanism, job status and work schedules, the shelter made the conditions more conducive to the development of counsellors' skills and health, while eliminating turnover for at least the two following years.

Targeting SYK kinase-dependent anti-apoptotic resistance pathway in B-lineage acute lymphoblastic leukaemia (ALL) cells with a potent SYK inhibitory pentapeptide mimic.

PubMed

Uckun, Fatih M; Ek, Rauf O; Jan, Shyi-Tai; Chen, Chun-Lin; Qazi, Sanjive

2010-05-01

The present study found that the pentapeptide mimic C-61, targeting the substrate binding P-site of SYK tyrosine kinase acted as a potent inducer of apoptosis in chemotherapy-resistant SYK-expressing primary leukemic B-cell precursors taken directly from relapsed B-precursor leukaemia (BPL) patients (but not SYK-deficient infant pro-B leukaemia cells), exhibited favourable pharmacokinetics in mice and non-human primates, and eradicated in vivo clonogenic leukaemia cells in severe combined immunodeficient mouse xenograft models of chemotherapy-resistant human BPL at dose levels non-toxic to mice and non-human primates. These in vitro and in vivo findings provide proof of principle for effective treatment of chemotherapy-resistant BPL by targeting SYK-dependent anti-apoptotic blast cell survival machinery with a SYK P-Site inhibitor. Further development of C-61 may provide the foundation for therapeutic innovation against chemotherapy-resistant BPL.

EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells.

PubMed

Galler, K M; Widbiller, M; Buchalla, W; Eidt, A; Hiller, K-A; Hoffer, P C; Schmalz, G

2016-06-01

To evaluate the effect of dentine conditioning on migration, adhesion and differentiation of dental pulp stem cells. Dentine discs prepared from extracted human molars were pre-treated with EDTA (10%), NaOCl (5.25%) or H2 O. Migration of dental pulp stem cells towards pre-treated dentine after 24 and 48 h was assessed in a modified Boyden chamber assay. Cell adhesion was evaluated indirectly by measuring cell viability. Expression of mineralization-associated genes (COL1A1, ALP, BSP, DSPP, RUNX2) in cells cultured on pre-treated dentine for 7 days was determined by RT-qPCR. Nonparametric statistical analysis was performed for cell migration and cell viability data to compare different groups and time-points (Mann-Whitney U-test, α = 0.05). Treatment of dentine with H2 O or EDTA allowed for cell attachment, which was prohibited by NaOCl with statistical significance (P = 0.000). Furthermore, EDTA conditioning induced cell migration towards dentine. The expression of mineralization-associated genes was increased in dental pulp cells cultured on dentine after EDTA conditioning compared to H2 O-pre-treated dentine discs. EDTA conditioning of dentine promoted the adhesion, migration and differentiation of dental pulp stem cells towards or onto dentine. A pre-treatment with EDTA as the final step of an irrigation protocol for regenerative endodontic procedures has the potential to act favourably on new tissue formation within the root canal. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells

PubMed Central

Wang, Zhongfang; Wan, Yanmin; Qiu, Chenli; Quiñones-Parra, Sergio; Zhu, Zhaoqin; Loh, Liyen; Tian, Di; Ren, Yanqin; Hu, Yunwen; Zhang, Xiaoyan; Thomas, Paul G.; Inouye, Michael; Doherty, Peter C.; Kedzierska, Katherine; Xu, Jianqing

2015-01-01

The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of different effector mechanisms across the spectrum of H7N9 disease and recovery. We find that a diversity of response mechanisms contribute to resolution and survival. Patients discharged within 2–3 weeks have early prominent H7N9-specific CD8+ T-cell responses, while individuals with prolonged hospital stays have late recruitment of CD8+/CD4+ T cells and antibodies simultaneously (recovery by week 4), augmented even later by prominent NK cell responses (recovery >30 days). In contrast, those who succumbed have minimal influenza-specific immunity and little evidence of T-cell activation. Our study illustrates the importance of robust CD8+ T-cell memory for protection against severe influenza disease caused by newly emerging influenza A viruses. PMID:25967273

Cell injury, retrodifferentiation and the cancer treatment paradox.

PubMed

Uriel, José

2015-09-01

This "opinion article" is an attempt to take an overview of some significant changes that have happened in our understanding of cancer status during the last half century and its evolution under the progressive influence of molecular biology. As an active worker in cancer research and developmental biology during most of this period, I would like to comment briefly on these changes and to give my critical appreciation of their outcome as it affects our knowledge of cancer development as well as the current treatment of the disease. A recall of my own contribution to the subject is also included. Two subjects are particularly developed: cell injury and cell-killing therapies. Cell injury, whatever its origin, has acquired the status of a pivotal event for the initiation of cancer emergence. It is postulated that cell injury, a potential case of cellular death, may also be the origin of a process of stepwise cell reversion (retrodifferentiation or retroprogrammation) leading, by division, mature or stem cells to progressive immaturity. The genetic instability and mutational changes that accompanies this process of cell injury and rejuvenation put normal cells in a status favourable to neoplastic transformation or may evolve cancer cells toward clones with higher malignant potentiality. Thus, cell injury suggests lifestyle as the major upstream initiator of cancer development although this not exclude randomness as an unavoidable contributor to the disease. Cell-killing agents (mainly cytotoxic drugs and radiotherapy) are currently used to treat cancer. At the same time, it is agreed that agents with high cell injury potential (ultraviolet light, ionising radiations, tobacco, environmental pollutants, etc.) contribute to the emergence of malignant tumours. This represents a real paradox. In spite of the progress accomplished in cancer survival, one is tempted to suggest that we have very few chances of really cure cancer as long as we continue to treat malignancies

Photoperiod length paces the temporal orchestration of cell cycle and carbon-nitrogen metabolism in Crocosphaera watsonii.

PubMed

Dron, Anthony; Rabouille, Sophie; Claquin, Pascal; Talec, Amélie; Raimbault, Virginie; Sciandra, Antoine

2013-12-01

We analysed the effect of photoperiod length (PPL) (16:8 and 8:16 h of light-dark regime, named long and short PPL, respectively) on the temporal orchestration of the two antagonistic, carbon and nitrogen acquisitions in the unicellular, diazotrophic cyanobacterium Crocosphaera watsonii strain WH8501 growing diazotrophically. Carbon and nitrogen metabolism were monitored at high frequency, and their patterns were compared with the cell cycle progression. The oxygen-sensitive N2 fixation process occurred mainly during the dark period, where photosynthesis cannot take place, inducing a light-dark cycle of cellular C : N ratio. Examination of circadian patterns in the cell cycle revealed that cell division occurred during the midlight period, (8 h and 4 h into the light in the long and short PPL conditions, respectively), thus timely separated from the energy-intensive diazotrophic process. Results consistently show a nearly 5 h time lag between the end of cell division and the onset of N2 fixation. Shorter PPLs affected DNA compaction of C. watsonii cells and also led to a decrease in the cell division rate. Therefore, PPL paces the growth of C. watsonii: a long PPL enhances cell division while a short PPL favours somatic growth (biomass production) with higher carbon and nitrogen cell contents. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

One pot synthesis of highly luminescent polyethylene glycol anchored carbon dots functionalized with a nuclear localization signal peptide for cell nucleus imaging.

PubMed

Yang, Lei; Jiang, Weihua; Qiu, Lipeng; Jiang, Xuewei; Zuo, Daiying; Wang, Dongkai; Yang, Li

2015-04-14

Strong blue fluorescent polyethylene glycol (PEG) anchored carbon nitride dots (CDs@PEG) with a high quantum yield (QY) of 75.8% have been synthesized by a one step hydrothermal treatment. CDs with a diameter of ca. 6 nm are well dispersed in water and present a graphite-like structure. Photoluminescence (PL) studies reveal that CDs display excitation-dependent behavior and are stable under various test conditions. Based on the as-prepared CDs, we designed novel cell nucleus targeting imaging carbon dots functionalized with a nuclear localization signal (NLS) peptide. The favourable biocompatibilities of CDs and NLS modified CDs (NLS-CDs) are confirmed by in vitro cytotoxicity assays. Importantly, intracellular localization experiments in MCF7 and A549 cells demonstrate that NLS-CDs could be internalized in the nucleus and show blue light, which indicates that CDs may serve as cell nucleus imaging probes.

Energy level alignment in TiO2/metal sulfide/polymer interfaces for solar cell applications.

PubMed

Lindblad, Rebecka; Cappel, Ute B; O'Mahony, Flannan T F; Siegbahn, Hans; Johansson, Erik M J; Haque, Saif A; Rensmo, Håkan

2014-08-28

Semiconductor sensitized solar cell interfaces have been studied with photoelectron spectroscopy to understand the interfacial electronic structures. In particular, the experimental energy level alignment has been determined for complete TiO2/metal sulfide/polymer interfaces. For the metal sulfides CdS, Sb2S3 and Bi2S3 deposited from single source metal xanthate precursors, it was shown that both driving forces for electron injection into TiO2 and hole transfer to the polymer decrease for narrower bandgaps. The energy level alignment results were used in the discussion of the function of solar cells with the same metal sulfides as light absorbers. For example Sb2S3 showed the most favourable energy level alignment with 0.3 eV driving force for electron injection and 0.4 eV driving force for hole transfer and also the most efficient solar cells due to high photocurrent generation. The energy level alignment of the TiO2/Bi2S3 interface on the other hand showed no driving force for electron injection to TiO2, and the performance of the corresponding solar cell was very low.

High-fibre enteral feeding results in improved anthropometrics and favourable gastrointestinal tolerance in malnourished children with growth failure.

PubMed

Kansu, Aydan; Durmaz Ugurcan, Ozlem; Arslan, Duran; Unalp, Aycan; Celtik, Coskun; Sarıoglu, Aysugul Alptekin

2018-06-01

The practical value of using fibre-enriched enteral feeding regimens to rehabilitate malnourished children remains inconclusive. This study determined the usage patterns, gastrointestinal tolerance, anthropometrics and safety of high-fibre enteral feeding in malnourished children with growth failure. This Turkish observational study between February 2013 and June 2015 comprised 345 paediatric patients from 17 centres with malnutrition-related growth failure, with a weight and height of <2 SD percentiles for their age. Changes in anthropometrics, gastrointestinal symptoms, defecation habits and safety data relating to adverse events were analysed during the six-month follow-up period. Most subjects (99.7%) were supplemented with enteral feeding. The absolute difference and 95% confidence interval values for the Z scores of height for age, weight for age, weight for height and body mass index for height increased significantly in four months to six months to 0.21 (0.09-0.32), 0.61 (0.51-0.70), 0.81 (0.56-1.06) and 0.70 (0.53-0.86), respectively (p < 0.001 for each). The percentage of patients with normal defecation frequency significantly increased from 70.3% to 92.8% at the four months to six months visit (p = 0.004). Adverse events occurred in 15 (4.3%) of patients. Using a six-month high-fibre enteral feeding was associated with favourable outcomes in anthropometrics, appetite, gastrointestinal tolerance and safety in malnourished children. ©2018 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Ground-Water Quality Data in the Santa Clara River Valley Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Montrella, Joseph; Belitz, Kenneth

2009-01-01

Ground-water quality in the approximately 460-square-mile Santa Clara River Valley study unit (SCRV) was investigated from April to June 2007 as part of the statewide Priority Basin project of the Ground-Water Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The study was designed to provide a spatially unbiased assessment of the quality of raw ground water used for public water supplies within SCRV, and to facilitate a statistically consistent basis for comparing water quality throughout California. Fifty-seven ground-water samples were collected from 53 wells in Ventura and Los Angeles Counties. Forty-two wells were selected using a randomized grid-based method to provide statistical representation of the study area (grid wells). Eleven wells (understanding wells) were selected to further evaluate water chemistry in particular parts of the study area, and four depth-dependent ground-water samples were collected from one of the eleven understanding wells to help understand the relation between water chemistry and depth. The ground-water samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOC], pesticides and pesticide degradates, potential wastewater-indicator compounds, and pharmaceutical compounds), a constituent of special interest (perchlorate), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), radioactive constituents, and microbial constituents. Naturally occurring isotopes (tritium, carbon-13, carbon-14 [abundance], stable isotopes of hydrogen and oxygen in water, stable isotopes of nitrogen and oxygen in nitrate, chlorine-37, and bromine-81), and dissolved noble gases also were measured to help identify the source

CD47-ligation induced cell death in T-acute lymphoblastic leukemia.

PubMed

Leclair, Pascal; Liu, Chi-Chao; Monajemi, Mahdis; Reid, Gregor S; Sly, Laura M; Lim, Chinten James

2018-05-10

CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue for targeted cancer therapies involves neutralizing the anti-phagocytic function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of CD47 receptor ligation is the direct induction of tumour cell death. While several mAbs and their derivatives with this property have been studied, the best characterized is the commercially available mAb B6H12, which requires immobilization for induction of cell death. Here, we describe a commercially available mAb, CC2C6, which induces T-cell acute lymphoblastic leukemia (ALL) cell death in soluble form. Soluble CC2C6 induces CD47-dependent cell death in a manner consistent with immobilized B6H12, which is characterized by mitochondrial deficiencies but is independent of caspase activation. Titration studies indicated that CC2C6 shares a common CD47-epitope with B6H12. Importantly, CC2C6 retains the anti-phagocytic neutralizing function, thus possessing dual anti-tumour properties. Although CD47-ligation induced cell death occurs in a caspase-independent manner, CC2C6 was found to stimulate increases in Mcl-1 and NOXA levels, two Bcl-2 family proteins that govern the intrinsic apoptosis pathway. Further analysis revealed that the ratio of Mcl-1:NOXA were minimally altered for cells treated with CC2C6, in comparison to cells treated with agents that induced caspase-dependent apoptosis which alter this ratio in favour of NOXA. Finally, we found that CC2C6 can synergize with low dose chemotherapeutic agents that induce classical apoptosis, giving rise to the possibility of an effective combination treatment with reduced long-term sequelae associated with high-dose chemotherapies in childhood ALL.

Antibacterial and anticancer PDMS surface for mammalian cell growth using the Chinese herb extract paeonol(4-methoxy-2-hydroxyacetophenone)

NASA Astrophysics Data System (ADS)

Jiao, Jiajia; Sun, Lili; Guo, Zaiyu; Hou, Sen; Holyst, Robert; Lu, Yun; Feng, Xizeng

2016-12-01

Polydimethylsiloxane (PDMS) is widely used as a cell culture platform to produce micro- and nano-technology based microdevices. However, the native PDMS surface is not suitable for cell adhesion and is always subject to bacterial pollution and cancer cell invasion. Coating the PDMS surface with antibacterial or anticancer materials often causes considerable harm to the non-cancer mammalian cells on it. We have developed a method to fabricate a biocompatible PDMS surface which not only promotes non-cancer mammalian cell growth but also has antibacterial and anticancer activities, by coating the PDMS surface with a Chinese herb extract, paeonol. Coating changes the wettability and the elemental composition of the PDMS surface. Molecular dynamic simulation indicates that the absorption of paeonol onto the PDMS surface is an energy favourable process. The paeonol-coated PDMS surface exhibits good antibacterial activity against both Gram-positive and Gram-negative bacteria. Moreover considerable antibacterial activity is maintained after the coated surface is rinsed or incubated in water. The coated PDMS surface inhibits bacterial growth on the contact surface and promotes non-cancer mammalian cell growth with low cell toxicity; meanwhile the growth of cancer cells is significantly inhibited. Our study will potentially guide PDMS surface modification approaches to produce biomedical devices.

One-pot synthesis of fluorescent nitrogen-doped carbon dots with good biocompatibility for cell labeling.

PubMed

Zhang, Zhengwei; Yan, Kun; Yang, Qiulian; Liu, Yanhua; Yan, Zhengyu; Chen, Jianqiu

2017-12-01

Here we report an easy and economical hydrothermal carbonization approach to synthesize the fluorescent nitrogen-doped carbon dots (N-CDs) that was developed using citric acid and triethanolamine as the precursors. The synthesis conditions were optimized to obtain the N-CDs with superior fluorescence performances. The as-prepared N-CDs are monodispersed sphere nanoparticles with good water solubility, and exhibited strong fluorescence, favourable photostability and excitation wavelength-dependent behavior. Furthermore, the in vitro cytotoxicity and cellular labeling of N-CDs were investigated using the rat glomerular mesangial cells. The results showed the N-CDs have more inconspicuous cytotoxicity and better biosafety in comparison with ZnSe quantum dots, although both targeted the cells successfully. Considering their admirable photostability, low toxicity and good compatibility, the as-obtained N-CDs could have potential applications in biosensors, cellular imaging, and other fields. Copyright © 2017 John Wiley & Sons, Ltd.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells.

PubMed

Setzler, Brian P; Zhuang, Zhongbin; Wittkopf, Jarrid A; Yan, Yushan

2016-12-06

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW -1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Setzler, Brian P.; Zhuang, Zhongbin; Wittkopf, Jarrid A.; Yan, Yushan

2016-12-01

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW-1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Lamellipodia-based migrations of larval epithelial cells are required for normal closure of the adult epidermis of Drosophila

PubMed Central

Bischoff, Marcus

2012-01-01

Cell migrations are an important feature of animal development. They are, furthermore, essential to wound healing and tumour progression. Despite recent progress, it is still mysterious how cell migration is spatially and temporally regulated during morphogenesis and how cell migration is coordinated with other cellular behaviours to shape tissues and organs. The formation of the abdominal epithelium of Drosophila during metamorphosis provides an attractive system to study morphogenesis. Here, the diploid adult histoblasts replace the polyploid larval epithelial cells (LECs). Using in vivo 4D microscopy, I show that, besides apical constriction and apoptosis, the LECs undergo extensive coordinated migrations. The migrations follow a transition from a stationary (epithelial) to a migratory mode. The migratory behaviour is stimulated by autocrine Dpp signalling. Directed apical lamellipodia-like protrusions propel the cells. Initially, planar cell polarity determines the orientation of LEC migration. While LECs are migrating they also constrict apically, and changes in activity of the small GTPase Rho1 can favour one behaviour over the other. This study shows that the LECs play a more active role in morphogenesis than previously thought, with their migrations contributing to abdominal closure. It furthermore provides insights into how the migratory behaviour of cells is regulated during morphogenesis. PMID:22230614

PAR1 activation affects the neurotrophic properties of Schwann cells.

PubMed

Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

2017-03-01

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of the phosphatidylinositol-3-kinase/Akt/target of rapamycin pathway during ambidensovirus infection of insect cells.

PubMed

Salasc, F; Mutuel, D; Debaisieux, S; Perrin, A; Dupressoir, T; Grenet, A-S Gosselin; Ogliastro, M

2016-01-01

The phosphatidylinositol-3-kinase (PI3K)/Akt/target of rapamycin (TOR) signalling pathway controls cell growth and survival, and is targeted by a number of viruses at different phases of their infection cycle to control translation. Whether and how insect viruses interact with this pathway remain poorly addressed. Here, we investigated the role of PI3K/Akt/TOR signalling during lethal infection of insect cells with an insect parvovirus. Using Junonia coenia densovirus (JcDV; lepidopteran ambidensovirus 1) and susceptible insect cells as experimental models, we first described JcDV cytopathology, and showed that viral infection affects cell size, cell proliferation and survival. We deciphered the role of PI3K/Akt/TOR signalling in the course of infection and found that non-structural (NS) protein expression correlates with the inhibition of TOR and the shutdown of cellular synthesis, concomitant with the burst of viral protein expression. Together, these results suggest that NS proteins control the cellular translational machinery to favour the translation of viral mRNAs at the expense of cellular mRNAs. As a consequence of TOR inhibition, cell autophagy is activated. These results highlight new functions for NS proteins in the course of multiplication of an insect parvovirus.

CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL

PubMed Central

Cutrona, G; Tasso, P; Dono, M; Roncella, S; Ulivi, M; Carpaneto, E M; Fontana, V; Comis, M; Morabito, F; Spinelli, M; Frascella, E; Boffa, L C; Basso, G; Pistoia, V; Ferrarini, M

2002-01-01

CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 cases, 93.2±4.5%, MRFI 211±82 CD10-positive cells) or low (11 cases, 11.5±6.2%, MRFI 10±7 CD10-negative cells) expression of CD10. CD10-positive acute lymphoblastic leukaemia cells were cycling cells with elevated c-myc levels and propensity to apoptosis, whereas CD10-negative acute lymphoblastic leukaemia cells had lower cycling capacities and c-myc levels, and were resistant to apoptosis in vitro. A close correlation between all these properties was demonstrated by the observations that the few CD10-positive cells found in the CD10-negative acute lymphoblastic leukaemia group displayed elevated c-myc and cycling capacities and were apoptosis prone. Moreover, exposure of CD10-positive acute lymphoblastic leukaemia B cells to a peptide nucleic acid anti-gene specific for the second exon of c-myc caused inhibition of c-myc expression and reduced cell cycling and apoptotic abilities as well as decreased CD10 expression. British Journal of Cancer (2002) 86, 1776–1785. doi:10.1038/sj.bjc.6600329 www.bjcancer.com © 2002 Cancer Research UK PMID:12087466

The role of meiotic cohesin REC8 in chromosome segregation in gamma irradiation-induced endopolyploid tumour cells.

PubMed

Erenpreisa, Jekaterina; Cragg, Mark S; Salmina, Kristine; Hausmann, Michael; Scherthan, Harry

2009-09-10

Escape from mitotic catastrophe and generation of endopolyploid tumour cells (ETCs) represents a potential survival strategy of tumour cells in response to genotoxic treatments. ETCs that resume the mitotic cell cycle have reduced ploidy and are often resistant to these treatments. In search for a mechanism for genome reduction, we previously observed that ETCs express meiotic proteins among which REC8 (a meiotic cohesin component) is of particular interest, since it favours reductional cell division in meiosis. In the present investigation, we induced endopolyploidy in p53-dysfunctional human tumour cell lines (Namalwa, WI-L2-NS, HeLa) by gamma irradiation, and analysed the sub-cellular localisation of REC8 in the resulting ETCs. We observed by RT-PCR and Western blot that REC8 is constitutively expressed in these tumour cells, along with SGOL1 and SGOL2, and that REC8 becomes modified after irradiation. REC8 localised to paired sister centromeres in ETCs, the former co-segregating to opposite poles. Furthermore, REC8 localised to the centrosome of interphase ETCs and to the astral poles in anaphase cells where it colocalised with the microtubule-associated protein NuMA. Altogether, our observations indicate that radiation-induced ETCs express features of meiotic cell divisions and that these may facilitate chromosome segregation and genome reduction.

Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study

PubMed Central

2010-01-01

Background Numerous epidemiological studies have demonstrated adverse health effects of a sedentary life style, on the one hand, and of acute and chronic exposure to traffic-related air pollution, on the other. Because physical exercise augments the amount of inhaled pollutants, it is not clear whether cycling to work in a polluted urban environment should be encouraged or not. To address this conundrum we investigated if a bicycle journey along a busy commuting road would induce changes in biomarkers of pulmonary and systematic inflammation in a group of healthy subjects. Methods 38 volunteers (mean age: 43 ± 8.6 years, 26% women) cycled for about 20 minutes in real traffic near a major bypass road (road test; mean UFP exposure: 28,867 particles per cm3) in Antwerp and in a laboratory with filtered air (clean room; mean UFP exposure: 496 particles per cm3). The exercise intensity (heart rate) and duration of cycling were similar for each volunteer in both experiments. Exhaled nitric oxide (NO), plasma interleukin-6 (IL-6), platelet function, Clara cell protein in serum and blood cell counts were measured before and 30 minutes after exercise. Results Percentage of blood neutrophils increased significantly more (p = 0.004) after exercise in the road test (3.9%; 95% CI: 1.5 to 6.2%; p = 0.003) than after exercise in the clean room (0.2%; 95% CI: -1.8 to 2.2%, p = 0.83). The pre/post-cycling changes in exhaled NO, plasma IL-6, platelet function, serum levels of Clara cell protein and number of total blood leukocytes did not differ significantly between the two scenarios. Conclusions Traffic-related exposure to particles during exercise caused a small increase in the distribution of inflammatory blood cells in healthy subjects. The health significance of this isolated change is unclear. PMID:20973949

Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study.

PubMed

Jacobs, Lotte; Nawrot, Tim S; de Geus, Bas; Meeusen, Romain; Degraeuwe, Bart; Bernard, Alfred; Sughis, Muhammad; Nemery, Benoit; Panis, Luc Int

2010-10-25

Numerous epidemiological studies have demonstrated adverse health effects of a sedentary life style, on the one hand, and of acute and chronic exposure to traffic-related air pollution, on the other. Because physical exercise augments the amount of inhaled pollutants, it is not clear whether cycling to work in a polluted urban environment should be encouraged or not. To address this conundrum we investigated if a bicycle journey along a busy commuting road would induce changes in biomarkers of pulmonary and systematic inflammation in a group of healthy subjects. 38 volunteers (mean age: 43 ± 8.6 years, 26% women) cycled for about 20 minutes in real traffic near a major bypass road (road test; mean UFP exposure: 28,867 particles per cm3) in Antwerp and in a laboratory with filtered air (clean room; mean UFP exposure: 496 particles per cm3). The exercise intensity (heart rate) and duration of cycling were similar for each volunteer in both experiments. Exhaled nitric oxide (NO), plasma interleukin-6 (IL-6), platelet function, Clara cell protein in serum and blood cell counts were measured before and 30 minutes after exercise. Percentage of blood neutrophils increased significantly more (p = 0.004) after exercise in the road test (3.9%; 95% CI: 1.5 to 6.2%; p = 0.003) than after exercise in the clean room (0.2%; 95% CI: -1.8 to 2.2%, p = 0.83). The pre/post-cycling changes in exhaled NO, plasma IL-6, platelet function, serum levels of Clara cell protein and number of total blood leukocytes did not differ significantly between the two scenarios. Traffic-related exposure to particles during exercise caused a small increase in the distribution of inflammatory blood cells in healthy subjects. The health significance of this isolated change is unclear.

Macrophages Modulate Migration and Invasion of Human Tongue Squamous Cell Carcinoma

PubMed Central

Pirilä, Emma; Väyrynen, Otto; Sundquist, Elias; Päkkilä, Kaisa; Nyberg, Pia; Nurmenniemi, Sini; Pääkkönen, Virve; Pesonen, Paula; Dayan, Dan; Vered, Marilena; Uhlin-Hansen, Lars; Salo, Tuula

2015-01-01

Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF

Air-dried cells from the anhydrobiotic insect, Polypedilum vanderplanki, can survive long term preservation at room temperature and retain proliferation potential after rehydration.

PubMed

Watanabe, Kazuyo; Imanishi, Shigeo; Akiduki, Gaku; Cornette, Richard; Okuda, Takashi

2016-08-01

Pv11, a cell line derived from the anhydrobiotic insect, Polypedilum vanderplanki, was preserved in a dry form (only 6% residual moisture) at room temperature for up to 251 days and restarted proliferating after rehydration. A previous study already reported survival of Pv11 cells after desiccation, but without subsequent proliferation. Here, the protocol was improved to increase survival and achieve proliferation of Pv11 cells after dry storage. The method basically included preincubation, desiccation and rehydration processes and each step was investigated. So far, preincubation in a 600 mM trehalose solution for 48 h before dehydration was the most favourable preconditioning to achieve successful dry preservation of Pv11 cells, allowing about 16% of survival after rehydration and subsequent cell proliferation. Although the simple air-dry method established for Pv11 cells here was not applicable for successful dry-preservation of other insect cell lines, Pv11 is the first dry-preservable animal cell line and will surely contribute not only to basic but also applied sciences. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Nephrectomy for infected stag horn calculus confounded by the presence of squamous cell carcinoma.

PubMed

Kondisetty, Sandeep; Borkar, Pallavi Vijay; Thomas, Appu

2017-09-27

Squamous cell carcinoma of kidney is a rare tumour of the many tumours seen in the kidney. It is usually associated with chronic irritation by a foreign body, which is mostly a stag horn calculus. Diagnosis of carcinoma in the presence of stag horn calculus is bizarre as it is seen in only <1% of patients. After imaging in this patient, the lymph nodes were enlarged and showed necrosis, which favoured the diagnosis of tuberculosis in a country where it is endemic. The pathological examination after surgery has amazed us by the presence of squamous cell carcinoma with lymph nodes positive with metastasis to vertebrae as the patient has presented to us with all symptoms of infection like pain and fever, which never made us think about malignancy preoperatively. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pregi, Nicolas; Wenker, Shirley; Vittori, Daniela

2009-02-01

The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-{alpha}. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-{alpha} or pretreated with 25 U/ml Epo for 12more » h before the addition of TNF-{alpha}. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-{kappa}B nuclear translocation, TNF-{alpha} induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-{kappa}B, through mechanisms involving Jak/STAT and PI3K signalling pathways.« less

Metabolic Conversion of Ceramides in HeLa Cells - A Cholesteryl Phosphocholine Delivery Approach

PubMed Central

Kjellberg, Matti A.; Lönnfors, Max; Slotte, J. Peter; Mattjus, Peter

2015-01-01

Ceramides can be delivered to cultured cells without solvents in the form of complexes with cholesteryl phosphocholine. We have analysed the delivery of three different radiolabeled D-erythro-ceramides (C6-Cer, C10-Cer and C16-Cer) to HeLa cells, and followed their metabolism as well as the cell viability. We found that all three ceramides were successfully taken up by HeLa cells when complexed to CholPC in an equimolar ratio, and show that the ceramides show different rates of cellular uptake and metabolic fate. The C6-Cer had the highest incorporation rate, followed by C10-Cer and C16-Cer, respectively. The subsequent effect on cell viability strongly correlated with the rate of incorporation, where C6-Cer had the strongest apoptotic effects. Low-dose (1 μM) treatment with C6-Cer favoured conversion of the precursor to sphingomyelin, whereas higher concentrations (25–100 μM) yielded increased conversion to C6-glucosylceramide. Similar results were obtained for C10-Cer. In the lower-dose C16-Cer experiments, most of the precursor was degraded, whereas at high-dose concentrations the precursor remained un-metabolized. Using this method, we demonstrate that ceramides with different chain lengths clearly exhibit varying rates of cellular uptake. The cellular fate of the externally delivered ceramides are clearly connected to their rate of incorporation and their subsequent effects on cell viability may be in part determined by their chain length. PMID:26599810

Stem cell research in Germany: ethics of healing vs. human dignity.

PubMed

Oduncu, Fuat S

2003-01-01

On 25 April 2002, the German Parliament has passed a strict new law referring to stem cell research. This law took effect on July 1, 2002. The so-called embryonic Stem Cell Act ("Stammzellgesetz-StZG") permits the import of embryonic stem (ES) cells isolated from surplus lvF-embryos for research reasons. The production itself of ES cells from human blastocysts has been prohibited by the German Embryo Protection Act of 1990, with the exception of the use of ES cells which exist already. The debate on the legitimate use of ES cells escalated, after the main German research funding agency, the Deutsche Forschungsgemeinschaft (DFG), unexpectedly published new guidelines recommending a restricted use of human ES cells for research. Meanwhile, the debate has ethically divided society, political parties, government and church members into a group supporting and a group rejecting ES cell research. The arguments in favour of such a research can be summarized as arguments derived from a new "ethics of healing" calling for a therapeutic imperative, whereas the arguments against can be summarized as arguments violating the fundamental principle of human dignity as they imply the destruction of human embryos. This article will try to present and evaluate various ethical arguments founded on the latest biological and medical data on the potential use of stem cell technologies. It will finally come to the conclusion that ES cell research is opposed to human dignity, since the procedures of isolating ES cells require the destruction and instrumentalization of human embryos. Human embryos are human beings at a very early stage of their development, fully possessing the ability of completing their development. At this very early stage, human embryos are extremely dependent and fragile, and thus vulnerable corporealities. Vulnerability and human dignity demand the protection of the embryo's corporeal integrity. Hence, this essay will try to propagate research with adult stem (AS

Surface deformation and shear flow in ligand mediated cell adhesion.

PubMed

Sircar, Sarthok; Roberts, Anthony J

2016-10-01

We present a unified, multiscale model to study the attachment/detachment dynamics of two deforming, charged, near spherical cells, coated with binding ligands and subject to a slow, homogeneous shear flow in a viscous, ionic fluid medium. The binding ligands on the surface of the cells experience both attractive and repulsive forces in an ionic medium and exhibit finite resistance to rotation via bond tilting. The microscale drag forces and couples describing the fluid flow inside the small separation gap between the cells, are calculated using a combination of methods in lubrication theory and previously published numerical results. For a selected range of material and fluid parameters, a hysteretic transition of the sticking probability curves (i.e., the function [Formula: see text]) between the adhesion phase (when [Formula: see text]) and the fragmentation phase (when [Formula: see text]) is attributed to a nonlinear relation between the total nanoscale binding forces and the separation gap between the cells. We show that adhesion is favoured in highly ionic fluids, increased deformability of the cells, elastic binders and a higher fluid shear rate (until a critical threshold value of shear rate is reached). Within a selected range of critical shear rates, the continuation of the limit points (i.e., the turning points where the slope of [Formula: see text] changes sign) predict a bistable region, indicating an abrupt switching between the adhesion and the fragmentation regimes. Although, bistability in the adhesion-fragmentation phase diagram of two deformable, charged cells immersed in an ionic aqueous environment has been identified by some in vitro experiments, but until now, has not been quantified theoretically.

Therapeutic Phlebotomy is Safe in Children with Sickle Cell Anaemia and can be Effective Treatment for Transfusional Iron Overload

PubMed Central

Aygun, Banu; Mortier, Nicole A.; Kesler, Karen; Lockhart, Alexandre; Schultz, William H.; Cohen, Alan R.; Alvarez, Ofelia; Rogers, Zora R.; Kwiatkowski, Janet L.; Miller, Scott T.; Sylvestre, Pamela; Iyer, Rathi; Lane, Peter A.; Ware, Russell E.

2015-01-01

SUMMARY Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (−8.7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment. PMID:25612463

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

PubMed Central

West, John D; Dorà, Natalie J; Collinson, J Martin

2015-01-01

In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed

R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5

PubMed Central

Cavarelli, Mariangela; Foglieni, Chiara; Rescigno, Maria; Scarlatti, Gabriella

2013-01-01

The gastrointestinal tract is a principal route of entry and site of persistence of human immunodeficiency virus type 1 (HIV-1). The intestinal mucosa, being rich of cells that are the main target of the virus, represents a primary site of viral replication and CD4+ T-cell depletion. Here, we show both in vitro and ex vivo that HIV-1 of R5 but not X4 phenotype is capable of selectively triggering dendritic cells (DCs) to migrate within 30 min between intestinal epithelial cells to sample virions and transfer infection to target cells. The engagement of the chemokine receptor 5 on DCs and the viral envelope, regardless of the genetic subtype, drive DC migration. Viruses penetrating through transient opening of the tight junctions likely create a paracellular gradient to attract DCs. The formation of junctions with epithelial cells may initiate a haptotactic process of DCs and at the same time favour cell-to-cell viral transmission. Our findings indicate that HIV-1 translocation across the intestinal mucosa occurs through the selective engagement of DCs by R5 viruses, and may guide the design of new prevention strategies. PMID:23606583

Dendritic cells regulate angiogenesis associated with liver fibrogenesis.

PubMed

Blois, Sandra M; Piccioni, Flavia; Freitag, Nancy; Tirado-González, Irene; Moschansky, Petra; Lloyd, Rodrigo; Hensel-Wiegel, Karin; Rose, Matthias; Garcia, Mariana G; Alaniz, Laura D; Mazzolini, Guillermo

2014-01-01

During liver fibrogenesis the immune response and angiogenesis process are fine-tuned resulting in activation of hepatic stellate cells that produce an excess of extracellular matrix proteins. Dendritic cells (DC) play a central role modulating the liver immunity and have recently been implicated to favour fibrosis regression; although their ability to influence the development of fibrogenesis is unknown. Therefore, we explored whether the depletion of DC during early stages of liver injury has an impact in the development of fibrogenesis. Using the CD11c.DTR transgenic mice, DC were depleted in two experimental models of fibrosis in vivo. The effect of anti-angiogenic therapy was tested during early stages of liver fibrogenesis. DC depletion accelerates the development of fibrosis and as a consequence, the angiogenesis process is boosted. We observed up-regulation of pro-angiogenic factors together with an enhanced vascular endothelial growth factor (VEGF) bioavailability, mainly evidenced by the decrease of anti-angiogenic VEGF receptor 1 (also known as sFlt-1) levels. Interestingly, fibrogenesis process enhanced the expression of Flt-1 on hepatic DC and administration of sFlt-1 was sufficient to abrogate the acceleration of fibrogenesis upon DC depletion. Thus, DC emerge as novel players during the development of liver fibrosis regulating the angiogenesis process and thereby influencing fibrogenesis.

Requirements and testing methods for surfaces of metallic bipolar plates for low-temperature PEM fuel cells

NASA Astrophysics Data System (ADS)

Jendras, P.; Lötsch, K.; von Unwerth, T.

2017-03-01

To reduce emissions and to substitute combustion engines automotive manufacturers, legislature and first users aspire hydrogen fuel cell vehicles. Up to now the focus of research was set on ensuring functionality and increasing durability of fuel cell components. Therefore, expensive materials were used. Contemporary research and development try to substitute these substances by more cost-effective material combinations. The bipolar plate is a key component with the greatest influence on volume and mass of a fuel cell stack and they have to meet complex requirements. They support bending sensitive components of stack, spread reactants over active cell area and form the electrical contact to another cell. Furthermore, bipolar plates dissipate heat of reaction and separate one cell gastight from the other. Consequently, they need a low interfacial contact resistance (ICR) to the gas diffusion layer, high flexural strength, good thermal conductivity and a high durability. To reduce costs stainless steel is a favoured material for bipolar plates in automotive applications. Steel is characterized by good electrical and thermal conductivity but the acid environment requires a high chemical durability against corrosion as well. On the one hand formation of a passivating oxide layer increasing ICR should be inhibited. On the other hand pitting corrosion leading to increased permeation rate may not occur. Therefore, a suitable substrate lamination combination is wanted. In this study material testing methods for bipolar plates are considered.

Lipidated promiscuous peptide augments the expression of MHC-II molecules on dendritic cells and activates T cells

PubMed Central

Gowthaman, Uthaman; Rai, Pradeep K.; Zeng, Weiguang; Jackson, David C.; Agrewala, Javed N.

2013-01-01

Background & objectives: In spite of the fact that BCG is the most widely used vaccine, tuberculosis (TB) continues to be a major killer disease in TB-endemic regions. Recently, many emerging evidences from the published literature indicate the role of environmental mycobacteria in blocking the processing and presentation of BCG antigens and thereby impairing with suboptimal generation of protective T cells. To surmount this problem associated with BCG, we constructed a novel lipopeptide (L91) by conjugating a promiscuous peptide consisting of CD4+ T-helper epitope of sequence of 91-110 of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys, an agonist of Toll-like receptor-2. Methods: Mice were immunized subcutaneously with 20 nmol of L91, followed by a booster with 10 nmol, after an interval of 21 days of primary immunization. Animals were sacrificed after seven days of post-booster immunization. L91 induced immune response was characterized by the expression of MHC-II and CD74 on the surface of dendritic cells (DCs) by flowcytometry. Cytokines (IL-4, IL-10, IFN-γ) secretion and anti-peptide antibodies were measured by ELISA. Results: Self-adjuvanting lipopeptide vaccine (L91) was directly bound to MHC-II molecules and without requiring extensive processing for its presentation to T cells. It stimulated and activated dendritic cells and augmented the expression of MHC-II molecules. Further, it activated effector CD4 T cells to mainly secrete interferon (IFN)-γ but not interleukin (IL)-4 and IL-10. L91 did not elicit anti-peptide antibodies. Interpretation & conclusions: The findings suggest that L91 evokes maturation and upregulation of MHC class II molecules and promotes better antigen presentation and, therefore, optimum activation of T cells. L91 mainly induces effector Th1 cells, as evidenced by predominant release of IFN-γ, consequently can mount favourable immune response against M. tuberculosis. As L91 does not provoke the generation of anti

Giant cell tumour 2nd metatarsal-Result with en-bloc excision and autologous fibular grafting.

PubMed

Agarwal, Saurabh; Chawla, Sumit; Agarwal, Sippy; Agarwal, Puneet

2015-12-01

Giant cell tumour (GCT) of the small bones is relatively uncommon tumour. It occurs most commonly in the distal portions of femur and radius and proximal end of tibia. GCT of small bones presents at advanced stages with major bony destruction. These tumours represent more aggressive course; associated with increased local recurrence rates (40%) and metastasis. Various treatment modalities like en-bloc resection, cryosurgery, intralesional curettage with burring/phenolization or bone cement are available. In our case en-bloc resection with reconstruction using nonvascular autogenous fibular strut graft was used in patient of 2nd metatarsal GCT and a favourable functional outcome was observed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs.

PubMed

Schadendorf, Dirk; Lebbé, Céleste; Zur Hausen, Axel; Avril, Marie-Françoise; Hariharan, Subramanian; Bharmal, Murtuza; Becker, Jürgen C

2017-01-01

Merkel cell carcinoma (MCC) is a rare skin cancer that is associated with Merkel cell polyomavirus infection in most cases. Incidence rates of MCC have increased in past decades. Risk factors for MCC include ultraviolet light exposure, immunosuppression and advanced age. MCC is an aggressive malignancy with frequent recurrences and a high mortality rate, although patient outcomes are generally more favourable if the patient is referred for treatment at an early stage. Although advances have been made recently in the MCC field, large gaps remain with regard to definitive biomarkers and prognostic indicators. Although MCC is chemosensitive, responses in advanced stages are mostly of short duration, and the associated clinical benefit on overall survival is unclear. Recent nonrandomised phase 2 clinical trials with anti-PD-L1/PD-1 antibodies have demonstrated safety and efficacy; however, there are still no approved treatments for patients with metastatic MCC. Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Heat loss distribution: Impedance and thermal loss analyses in LiFePO4/graphite 18650 electrochemical cell

NASA Astrophysics Data System (ADS)

Balasundaram, Manikandan; Ramar, Vishwanathan; Yap, Christopher; Lu, Li; Tay, Andrew A. O.; Palani, Balaya

2016-10-01

We report here thermal behaviour and various components of heat loss of 18650-type LiFePO4/graphite cell at different testing conditions. In this regard, the total heat generated during charging and discharging processes at various current rates (C) has been quantified in an Accelerating Rate Calorimeter experiment. Irreversible heat generation, which depends on applied current and internal cell resistance, is measured under corresponding charge/discharge conditions using intermittent pulse techniques. On the other hand, reversible heat generation which depends on entropy changes of the electrode materials during the cell reaction is measured from the determination of entropic coefficient at various states of charge/discharge. The contributions of irreversible and reversible heat generation to the total heat generation at both high and low current rates are evaluated. At every state of charge/discharge, the nature of the cell reaction is found to be either exothermic or endothermic which is especially evident at low C rates. In addition, electrochemical impedance spectroscopy measurements are performed on above 18650 cells at various states of charge to determine the components of internal resistance. The findings from the impedance and thermal loss analysis are helpful for understanding the favourable states of charge/discharge for battery operation, and designing better thermal management systems.

One-step pyrolysis route to three dimensional nitrogen-doped porous carbon as anode materials for microbial fuel cells

NASA Astrophysics Data System (ADS)

Bi, Linlin; Ci, Suqin; Cai, Pingwei; Li, Hao; Wen, Zhenhai

2018-01-01

The design and synthesis of low-cost and favourable anode materials is crucial to both power production efficiency and overall performance of microbial fuel cells (MFCs). Herein, we reported the preparation of three dimensional (3D) nitrogen-doped porous carbons (N/PCs) by one-step pyrolysis of solid mixture of sodium citrate and melamine. a variety of techniques, including electron microscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), etc., were applied to characterize the surface physicochemical properties of the products, featuring macroporous structure with rich nitrogen doping on the as-prepared N/PCs. When applied as anode materials of MFC, the N/PCs exhibits a maximum power density of 2777.7 mW m-2, approximately twice higher than that of the MFCs with the commercial carbon cloth (CC) as anode. The significantly improved performance of the N/PCs was attributed to the unique structure and properties, such as favourable porous structure, good electrical conductivity, and large pore volume (0.7 cm3 g-1) in the present N/PCs. Nitrogen dopant on the surface of porous carbon contributed to an increasing in biocompatibility, resulting in a suitable micro-environment for microbial growth and thus helps to decrease charge transfer resistance at the electrode interface.

Ecological mechanisms favouring behavioural diversification in the absence of morphological diversification: a theoretical examination using brook charr (Salvelinus fontinalis).

PubMed

De Kerckhove, Derrick; McLaughlin, Robert L; Noakes, David L G

2006-03-01

1. Behavioural diversification is thought to be an important initial step in the origin of resource polymorphisms. We developed a model for young brook charr (Salvelinus fontinalis Mitchill) to examine four mechanisms that could generate a U-shaped relationship between growth rate (fitness) and the proportion of time spent moving that would favour alternative foraging tactics in the absence of obvious differences in body size and shape. 2. Recently emerged brook charr of similar size and shape inhabit still-water pools along the sides of streams. Some individuals tend to sit and wait for crustacean prey at the pool substrate near the bank, while others tend to search actively for insect prey at the pool surface away from the bank. 3. The ecological mechanisms modelled were (i) the relationship between the rate of prey capture and the proportion of time spent moving is curvilinear, such that net rate of energy gain is maximized at two different levels of activity; (ii) switching between foraging locations and, hence, tactics involves lost opportunity and travel costs; (iii) switching between prey types and, hence, tactics involves a learning cost; and (iv) foraging success is status-dependent with individuals switching between tactics having a lower status than those specializing at a tactic. 4. Singly, no mechanism predicted the U-shaped relationship between growth rate and the proportion of time spent moving. Together, a U-shaped relationship was obtained, indicating that the behavioural diversification and diversifying selection observed in the field may be a consequence of multiple, subtle mechanisms.

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

PubMed

Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E; Stivala, Ernesto González; Carrasco, Andrés E; López, Silvia L

2014-01-01

In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

Candidate genes and favoured loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer's disease.

PubMed

Gurling, H

1986-01-01

It is argued that further research to achieve more detailed diagnostic systems in many psychiatric disorders is unlikely to be productive without taking genetic effects into account. Even when this is done, for example when carrying out segregation analysis to determine a mode of genetic transmission, mental illnesses often pose specific problems that preclude accurate analysis. Because techniques in molecular biology and genetics have made it possible to study gene effects in human disease systematically it should now be possible to specify the genes that are involved. When this has been achieved then a diagnostic system based on genetic causation can develop. This will have the advantage of helping to pinpoint environmental factors more accurately. Specific strategies will need to be adopted to overcome uncertain modes of inheritance, incomplete or non-penetrance of disease alleles and disease heterogeneity. Highly speculative hypotheses can be put forward for a locus causing Alzheimer's disease on a portion of the long arm of chromosome 21. For autism it is plausible that there is a disease locus at or near the fragile X site on the X chromosome. A locus for manic depression has been very tentatively mapped using DNA markers to chromosome 11 and in a small proportion of families DNA markers have also shown some evidence for X linkage. Schizophrenia does not seem to be associated with any favoured loci. Candidate genes for schizophrenia include those encoding dopamine, other neurotransmitter receptors or enzymes and various neuropeptides such as enkephalin and beta endorphin.

A novel surface modification approach for protein and cell microarrays

NASA Astrophysics Data System (ADS)

Kurkuri, Mahaveer D.; Driever, Chantelle; Thissen, Helmut W.; Voelcker, Nicholas H.

2007-01-01

Tissue engineering and stem cell technologies have led to a rapidly increasing interest in the control of the behavior of mammalian cells growing on tissue culture substrates. Multifunctional polymer coatings can assist research in this area in many ways, for example, by providing low non-specific protein adsorption properties and reactive functional groups at the surface. The latter can be used for immobilization of specific biological factors that influence cell behavior. In this study, glass slides were coated with copolymers of glycidyl methacrylate (GMA) and poly(ethylene glycol) methacrylate (PEGMA). The coatings were prepared by three different methods based on dip and spin coating as well as polymer grafting procedures. Coatings were characterized by X-ray photoelectron spectroscopy, surface sensitive infrared spectroscopy, ellipsometry and contact angle measurements. A fluorescently labelled protein was deposited onto reactive coatings using a contact microarrayer. Printing of a model protein (fluorescein labeled bovine serum albumin) was performed at different protein concentrations, pH, temperature, humidity and using different micropins. The arraying of proteins was studied with a microarray scanner. Arrays printed at a protein concentration above 50 μg/mL prepared in pH 5 phosphate buffer at 10°C and 65% relative humidity gave the most favourable results in terms of the homogeneity of the printed spots and the fluorescence intensity.

Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants.

PubMed

Nieto-Sampedro, Manuel

2003-11-01

Growth-promoting macroglia (aldynoglia) with growth properties and immunological markers similar to Schwann cells, are found in loci of the mammalian CNS where axon regeneration occurs throughout life, like the olfactory sytem, hypothalamus-hypophysis and the pineal gland. Contrary to Schwann cells, aldynoglia mingle freely with astrocytes and can migrate in brain and spinal cord. Transplantation of cultured and immunopurified olfactory ensheathing cells (OECs) in the spinal cord after multiple central rhizotomy, promoted sensory and central axon growth and partial functional restoration, judging by anatomical, electrophysiological and behavioural criteria. OEC transplants suppressed astrocyte reactivity, thus generally favouring axon growth after a lesion. However, the functional repair promoted by OEC transplants was partial in the best cases, depending on lesion type and location. Cyst formation after photochemical cord lesion was partially prevented but neither the corticospinal tract, interrupted by a mild contusion, nor the sectioned medial longitudinal fascicle, did regrow after OEC transplantation in the injured area.

Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

PubMed Central

Stephens, T. C.; Peacock, J. H.

1977-01-01

The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY. PMID:921888

Hoxb4 overexpression in CD4 memory phenotype T cells increases the central memory population upon homeostatic proliferation.

PubMed

Frison, Héloïse; Giono, Gloria; Thébault, Paméla; Fournier, Marilaine; Labrecque, Nathalie; Bijl, Janet J

2013-01-01

Memory T cell populations allow a rapid immune response to pathogens that have been previously encountered and thus form the basis of success in vaccinations. However, the molecular pathways underlying the development and maintenance of these cells are only starting to be unveiled. Memory T cells have the capacity to self renew as do hematopoietic stem cells, and overlapping gene expression profiles suggested that these cells might use the same self-renewal pathways. The transcription factor Hoxb4 has been shown to promote self-renewal divisions of hematopoietic stem cells resulting in an expansion of these cells. In this study we investigated whether overexpression of Hoxb4 could provide an advantage to CD4 memory phenotype T cells in engrafting the niche of T cell deficient mice following adoptive transfer. Competitive transplantation experiments demonstrated that CD4 memory phenotype T cells derived from mice transgenic for Hoxb4 contributed overall less to the repopulation of the lymphoid organs than wild type CD4 memory phenotype T cells after two months. These proportions were relatively maintained following serial transplantation in secondary and tertiary mice. Interestingly, a significantly higher percentage of the Hoxb4 CD4 memory phenotype T cell population expressed the CD62L and Ly6C surface markers, characteristic for central memory T cells, after homeostatic proliferation. Thus Hoxb4 favours the maintenance and increase of the CD4 central memory phenotype T cell population. These cells are more stem cell like and might eventually lead to an advantage of Hoxb4 T cells after subjecting the cells to additional rounds of proliferation.

Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair.

PubMed

Ahmed, Hanaa H; Toson, Elshahat A; El-Mezayen, Hatem A; Rashed, Laila A; Elsherbiny, Eslam S

2017-07-01

The current study sought to clarify the role of bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AD-MSCs) in repressing nephropathy in the experimental model. Moreover, the aim of this work was extended to compare between stem cells role and angiotensin converting enzyme inhibitor in kidney repair. Isolation and preparation of MSCs culture, flow cytometry using CD34, CD44 and CD105 cell surface markers, biochemical analyses for determination of serum creatinine, urea, transforming growth factor β (TGF-β), cystatin C (CYS-C) and urinary N-Acetyl-ß-D-Glucosaminidase (UNAG), and histopathological investigation of kidney tissue sections were performed. The results of the present study revealed that single intravenous infusion of MSCs either derived from bone marrow or adipose tissue was able to enhance renal reparative processes through significantly decreased serum creatinine, urea, TGF-β and CYS-C levels as well as UNAG level and significantly increase glomerular filtration rate. Additionally, the histopathological investigations of kidney tissues showed that MSCs have significant regenerative effects as evidenced by the decrease in focal inflammatory cells infiltration, focal interstitial nephritis and congested glomeruli as well as degenerated tubules. The current data provided distinct evidence about the favourable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation. © 2016 Asian Pacific Society of Nephrology.

Medical nutrition therapy administered by a dietitian yields favourable diabetes outcomes in individual with type 2 diabetes mellitus.

PubMed

Barakatun Nisak, M Y; Ruzita, A T; Norimah, A K; Kamaruddin, N A

2013-01-01

This prospective, single-group, pre-post design trial was conducted to evaluate the effect of individualised Medical Nutrition Therapy intervention administered by a dietitian in individuals with type 2 diabetes mellitus on glycaemic control, metabolic parameters and dietary intake. Subjects (n=104; age=56.4 ±9.9 years; 37% male; years of diagnosis = 6.3 ±4.9 years) treated with diet and on a stabile dose of oral anti-diabetic agents were given dietary advice by a dietitian for a 12 week period. Individualised dietary advice was based on Malaysian Medical Nutrition Therapy for adults with type 2 diabetes mellitus. The primary outcome measure was glycaemic control (fructosamine and HbA1c level) and the secondary outcome included measures of anthropometry, blood pressure, lipid profile, insulin levels dietary intake and knowledge on nutrition. At week 12, 100 subjects completed the study with a dropout rate of 3.8%. The post-Medical Nutrition Therapy results showed a significant reduction of fructosamine (311.5 ±50 to 297 ±44 umol/L; P< 0.001) and HbA1c (7.6 ±1.2 to 7.2 +1.1%, p<0.001) with pronounced reduction for subjects who had very high HbA1c levels of >9.3% at baseline. Waist circumference (90.7 ±10.2 to 89.1 ±9.8 cm, p<0.05), HDL-cholesterol (1.1 ±0.3 to 1.2 ±0.3 mmol/L, p<0.05), dietary intake and nutrition knowledge score (42 ±19 vs. 75 ±17%; p< 0.001) were significantly improved from the baseline. Individualised Medical Nutrition Therapy administered by a dietitian resulted in favourable diabetes outcomes, which were more apparent for individuals with higher than optimal HbA1c levels at the start of the study.

Renal cell carcinoma with Xp11.2 translocation in a 7-year-old boy.

PubMed

Jayasinghe, C; Siegler, N; Leuschner, I; Fleischhack, G; Born, M; Müller, A M

2010-05-01

More than 90% of pediatric renal tumors are nephroblastomas while renal cell carcinomas (RCC) are rare in children (< 5%). According to the clinical diagnoses of a nephroblastoma stage IV a 7-year-old boy with a kidney tumor and peripheral pulmonary lesion was preoperatively treated for 8 weeks with Vincristine, Actinomycin D and Adriamycin. The resected kidney displayed a RCC with Xp11.2 translocation. There was no tumor regression and the pulmonary lesion was no longer detectable. Hence chemotherapy was put to a halt. Fine needle aspiration biopsy (FNA) would have allowed to adjust the tumor subtype. Prognosis of pediatric RCC with translocation seems more favourable than without translocation though definitive evidence will only be possible by documentation in a clinical diagnose-related register.

Modeling the cost and benefit of proteome regulation in a growing bacterial cell

NASA Astrophysics Data System (ADS)

Sharma, Pooja; Pratim Pandey, Parth; Jain, Sanjay

2018-07-01

Escherichia coli cells differentially regulate the production of metabolic and ribosomal proteins in order to stay close to an optimal growth rate in different environments, and exhibit the bacterial growth laws as a consequence. We present a simple mathematical model of a growing-dividing cell in which an internal dynamical mechanism regulates the allocation of proteomic resources between different protein sectors. The model allows an endogenous determination of the growth rate of the cell as a function of cellular and environmental parameters, and reproduces the bacterial growth laws. We use the model and its variants to study the balance between the cost and benefit of regulation. A cost is incurred because cellular resources are diverted to produce the regulatory apparatus. We show that there is a window of environments or a ‘niche’ in which the unregulated cell has a higher fitness than the regulated cell. Outside this niche there is a large space of constant and time varying environments in which regulation is an advantage. A knowledge of the ‘niche boundaries’ allows one to gain an intuitive understanding of the class of environments in which regulation is an advantage for the organism and which would therefore favour the evolution of regulation. The model allows us to determine the ‘niche boundaries’ as a function of cellular parameters such as the size of the burden of the regulatory apparatus. This class of models may be useful in elucidating various tradeoffs in cells and in making in-silico predictions relevant for synthetic biology.

Expression pattern of immunosurveillance-related antigen in adult T cell leukaemia/lymphoma.

PubMed

Asano, Naoko; Miyoshi, Hiroaki; Kato, Takeharu; Shimono, Joji; Yoshida, Noriaki; Kurita, Daisuke; Sasaki, Yuya; Kawamoto, Keisuke; Ohshima, Koichi; Seto, Masao

2018-05-01

Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and β2 microglobulin (β2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL. We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for β2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and β2M in the cell membrane (HLA m+ β2M m+ ). No significant clinical differences other than prognosis were found between the HLA m+ β2M m+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1 high ) (P = 0.011) of the HLA m+ β2M m+ group than in the other groups. The HLA m+ β2M m+ group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLA m+ β2M m+ with miPD-L1 high had the most favourable prognosis among all groups. The membranous expression of HLA and β2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy. © 2018 John Wiley & Sons Ltd.

Cell cycle effect on the activity of deoxynucleoside analogue metabolising enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fyrberg, Anna; Albertioni, Freidoun; Lotfi, Kourosh

Deoxynucleoside analogues (dNAs) are cytotoxic towards both replicating and indolent malignancies. The impact of fluctuations in the metabolism of dNAs in relation to cell cycle could have strong implications regarding the activity of dNAs. Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) are important enzymes for phosphorylation/activation of dNAs. These drugs can be dephosphorylated/deactivated by 5'-nucleotidases (5'-NTs) and elevated activities of 5'-NTs and decreased dCK and/or dGK activities represent resistance mechanisms towards dNAs. The activities of dCK, dGK, and three 5'-NTs were investigated in four human leukemic cell lines in relationship to cell cycle progression and cytotoxicity of dNAs. Synchronization ofmore » cell cultures to arrest in G0/G1 by serum-deprivation was performed followed by serum-supplementation for cell cycle progression. The activities of dCK and dGK increased up to 3-fold in CEM, HL60, and MOLT-4 cells as they started to proliferate, while the activity of cytosolic nucleotidase I was reduced in proliferating cells. CEM, HL60, and MOLT-4 cells were also more sensitive to cladribine, cytarabine, 9-{beta}-D-arabinofuranosylguanine and clofarabine than K562 cells which demonstrated lower levels and less alteration of these enzymes and were least susceptible to the cytotoxic effects of most dNAs. The results suggest that, in the cell lines studied, the proliferation process is associated with a general shift in the direction of activation of dNAs by inducing activities of dCK/dGK and reducing the activity of cN-I which is favourable for the cytotoxic effects of cladribine, cytarabine and, 9-{beta}-D-arabinofuranosylguanine. These results emphasize the importance of cellular proliferation and dNA metabolism by both phosphorylation and dephosphorylation for susceptibility to dNAs. It underscores the need to understand the mechanisms of action and resistance to dNAs in order to increase efficacy of dNAs treatment by new

Mesenchymal stromal cells (MSCs) and colorectal cancer: a troublesome twosome for the anti-tumour immune response?

PubMed Central

O'Malley, Grace; Heijltjes, Madelon; Houston, Aileen M.; Rani, Sweta; Ritter, Thomas; Egan, Laurence J.; Ryan, Aideen E.

2016-01-01

The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis. PMID:27542276

Therapeutic phlebotomy is safe in children with sickle cell anaemia and can be effective treatment for transfusional iron overload.

PubMed

Aygun, Banu; Mortier, Nicole A; Kesler, Karen; Lockhart, Alexandre; Schultz, William H; Cohen, Alan R; Alvarez, Ofelia; Rogers, Zora R; Kwiatkowski, Janet L; Miller, Scott T; Sylvestre, Pamela; Iyer, Rathi; Lane, Peter A; Ware, Russell E

2015-04-01

Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (-8·7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment. © 2015 John Wiley & Sons Ltd.

Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation

PubMed Central

Kale, Sagar L.; Agrawal, Komal; Gaur, Shailendra Nath; Arora, Naveen

2017-01-01

Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies. Per a 10 exposure also leads to secretion of IL-33, TSLP and intracellular Ca2+ dependent increase in ATP levels. Further, in vivo experiments revealed that Per a 10 administration in mice elevated allergic inflammatory parameters along with high levels of IL-33, TSLP, IL-1α and uric acid in the mice lungs. We next demonstrated that Per a 10 cleaves CD23 (low affinity IgE receptor) from the surface of PBMCs and purified B cells and CD25 (IL-2 receptor) from the surface of PBMCs and purified T cells in an activity dependent manner, which might favour Th2 responses. In conclusion, protease activity of Per a 10 plays a significant role in initiation of allergic airway inflammation at the mucosal surfaces. PMID:28198394

Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells.

PubMed

Armstrong, J L; Ruiz, M; Boddy, A V; Redfern, C P F; Pearson, A D J; Veal, G J

2005-02-28

Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the key mechanism underlying the favourable clinical properties of 13-cis retinoic acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism is thought to contribute to resistance, and strategies to modulate this may increase the clinical efficacy of 13cisRA. The aim of this study was to test the hypothesis that retinoids, such as acitretin, which bind preferentially to cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the RA hydroxylase CYP26, such as R116010, can increase the intracellular availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 microM) or R116010 (1 or 10 microM) in combination with either 10 microM ATRA or 13cisRA induced a selective increase in intracellular levels of ATRA, while 13cisRA levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1. The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma.

HSV-1-induced activation of NF-κB protects U937 monocytic cells against both virus replication and apoptosis

PubMed Central

Marino-Merlo, Francesca; Papaianni, Emanuela; Medici, Maria Antonietta; Macchi, Beatrice; Grelli, Sandro; Mosca, Claudia; Borner, Christoph; Mastino, Antonio

2016-01-01

The transcription factor nuclear factor-kappa B (NF-κB) is a crucial player of the antiviral innate response. Intriguingly, however, NF-κB activation is assumed to favour herpes simplex virus (HSV) infection rather than restrict it. Apoptosis, a form of innate response to viruses, is completely inhibited by HSV in fully permissive cells, but not in cells incapable to fully sustain HSV replication, such as immunocompetent cells. To resolve the intricate interplay among NF-κB signalling, apoptosis and permissiveness to HSV-1 in monocytic cells, we utilized U937 monocytic cells in which NF-κB activation was inhibited by expressing a dominant-negative IκBα. Surprisingly, viral production was increased in monocytic cells in which NF-κB was inhibited. Moreover, inhibition of NF-κB led to increased apoptosis following HSV-1 infection, associated with lysosomal membrane permeabilization. High expression of late viral proteins and induction of apoptosis occurred in distinct cells. Transcriptional analysis of known innate response genes by real-time quantitative reverse transcription-PCR excluded a contribution of the assayed genes to the observed phenomena. Thus, in monocytic cells NF-κB activation simultaneously serves as an innate process to restrict viral replication as well as a mechanism to limit the damage of an excessive apoptotic response to HSV-1 infection. This finding may clarify mechanisms controlling HSV-1 infection in monocytic cells. PMID:27584793

Prostate Cancer Aggressiveness Gene in Hereditary Prostate Cancer

DTIC Science & Technology

2007-03-01

with REA, and estrogen receptor corepressor. Breast Canc Res Treat., in press (2007). This grant provided research support for Dr Veda Giri while...an estrogen receptor corepressor Clara Hwang Æ Veda N. Giri Æ John C. Wilkinson Æ Casey W. Wright Æ Amanda S. Wilkinson Æ Kathleen A. Cooney Æ Colin S...histone deacetylases (HDAC), and members of the polycomb group (PcG) of proteins. Clara Hwang and Veda N. Giri contributed equally to this work. C

Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells

PubMed Central

Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi

2015-01-01

Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. PMID:25910782

R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5.

PubMed

Cavarelli, Mariangela; Foglieni, Chiara; Rescigno, Maria; Scarlatti, Gabriella

2013-05-01

The gastrointestinal tract is a principal route of entry and site of persistence of human immunodeficiency virus type 1 (HIV-1). The intestinal mucosa, being rich of cells that are the main target of the virus, represents a primary site of viral replication and CD4(+) T-cell depletion. Here, we show both in vitro and ex vivo that HIV-1 of R5 but not X4 phenotype is capable of selectively triggering dendritic cells (DCs) to migrate within 30 min between intestinal epithelial cells to sample virions and transfer infection to target cells. The engagement of the chemokine receptor 5 on DCs and the viral envelope, regardless of the genetic subtype, drive DC migration. Viruses penetrating through transient opening of the tight junctions likely create a paracellular gradient to attract DCs. The formation of junctions with epithelial cells may initiate a haptotactic process of DCs and at the same time favour cell-to-cell viral transmission. Our findings indicate that HIV-1 translocation across the intestinal mucosa occurs through the selective engagement of DCs by R5 viruses, and may guide the design of new prevention strategies. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells.

PubMed

Li, Xiao-Hong; McGrath, Kristine C Y; Tran, Van H; Li, Yi-Ming; Mandadi, Sravan; Duke, Colin C; Heather, Alison K; Roufogalis, Basil D

2013-01-01

Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP) cation channel superfamily are candidate calcium influx channels. NF κ B activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in [Ca(2+)] i in HuH-7 cells. The increase in [Ca(2+)] i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca(2+)] i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NF κ B activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NF κ B activation was dependent on the calcium gradient and TRPV1. The rapid NF κ B activation by S-[6]-gingerol was associated with an increase in mRNA levels of NF κ B-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins.

Design and performance of a trickle-bed bioreactor with immobilized hybridoma cells.

PubMed

Phillips, H A; Scharer, J M; Bols, N C; Moo-Young, M

1992-01-01

A trickle-bed system employing inert matrices of vermiculite or polyurethane foam packed in the downcomer section of a split-flow air-lift reactor has been developed for hybridoma culture to enhance antibody productivity. This quiescent condition favoured occlusion and allowed the cells to achieve densities twelve fold greater (12.8 x 10(6) cells/ml reactor for polyurethane foam) than in free cell suspension. The reactor was operated in a cyclic batch mode whereby defined volumes of medium were periodically withdrawn and replaced with equal volumes of fresh medium. The pH of the medium was used as the indicator of the feeding schedule. Glucose, lactate and ammonia concentrations reached a stationary value after 5 days. With vermiculite packing, a monoclonal antibody (MAb) concentration of 2.4 mg/l was achieved after 12 days. The MAb concentration declined then increased to a value of 1.8 mg/l. In the polyurethane foam average monoclonal antibody (MAb) concentrations reached a stationary value of 1.1 mg/l in the first 20 days and increased to a new stationary state value of 2.1 mg/l for the remainder of the production. MAb productivity in the trickle-bed reactor was 0.3 mg/l.d (polyurethane foam) and 0.18 mg/l.d (vermiculite) in comparison to 0.12 mg/l.d for free cell suspension. This trickle-bed system seems to be an attractive way of increasing MAb productivity in culture.

[Cyclosporin A causes oxidative stress and mitochondrial dysfunction in renal tubular cells].

PubMed

Pérez de Hornedo, J; de Arriba, G; Calvino, M; Benito, S; Parra, T