Molecular characterization of the immune modulatory function of matrix metalloproteinase-7, a factor in the tumour micromilieu

Matrix metalloproteinases are the components of the tumour microenvironment which play a crucial role in tumour progression. Matrix metalloproteinase-7 (MMP-7) is expressed in a variety of tumours and the expression is associated with an aggressive malignant phenotype and poor prognosis. A role for MMP-7 in the immune escape of tumours has been postulated, but the mechanisms are not clearly understood. The present study was focused on identifying physiological inactivators of MMP-7 and also to unravel the mechanisms involved in MMP-7 mediated immune escape. This study shows that human leukocyte elastase (HLE), secreted by polymorphonuclear leukocytes cleaves MMP-7 in the catalytic domain as revealed by N-terminal sequencing. Further analysis demonstrates that the activity of MMP-7 was drastically decreased after HLE treatment in a time and dose dependent manner. MMP-7 induces apoptosis resistance in tumour cells by cleaving CD95 and CD95L. The effect of HLE on MMP-7 mediated apoptosis resistance was analysed. In vitro stimulation of apoptosis by anti-Apo-1 (anti-CD95 antibody) and the chemotherapeutic drug doxorubicin is reduced by MMP-7. Also tumour specific cytotoxic T cells do not effectively kill tumour cells in the presence of MMP-7. This study revealed that HLE abrogates the negative effect of MMP-7 on apoptosis induced by CD95 stimulation, doxorubicin or cytotoxic T cells and restores apoptosis sensitivity of tumour cells. To gain insight into the possible immune modulatory functions of MMP-7, experiments were performed to identify new immune relevant substrates. The human T cell line, Jurkat, was selected for these studies. Hsc70 which is involved in uncoating of clathrin vesicles was found in the supernatants of the MMP-7 treated cells indicating a modulatory role of MMP-7 on endocytosis. Further studies demonstrated that MMP-7 leads to decreased clathrin staining in HEK293, HepG2, Jurkat, CD4+ T cells and dendritic cells. Results also show MMP-7 treatment increased surface expression of cytotoxic T lymphocyte associated protein-4 (CTLA-4) which accumulated due to inhibition of the clathrin mediated internalization in CD4+CD25+ cells.

Impact of SLM build parameters on the surface quality

Additive manufacturing by melting of metal powders is an innovative method to create one-offs and customized parts. Branches like dentistry, aerospace engineering and tool making were indicated and the manufacturing methods are established. Besides all the advantages, like freedom of design, manufacturing without a tool and the reduction of time-to-market, there are however some disadvantages, such as reproducibility or the surface quality. The surface quality strongly depends on the orientation of the component in the building chamber, the process parameters which are laser power and exposure time, but also on the so-called “hatch”-strategy, which includes the way the laser exposes the solid areas. This paper deals with the investigation and characterization of the surface quality of generated parts produced by SLM. Main process parameters including part orientation, part size and hatch strategies are investigated and monitored. The outcome is a recommendation of suitable hatch strategies depending on desired part properties. This includes metered values and takes into account process stability and reproducibility.

Relating in situ gas measurements to the surface outgassing properties of cometary nuclei

The sensitivity of the gas flow field to changes in different initial conditions has been studied for the case of a highly simplified cometary nucleus model. The nucleus model simulated a homogeneously outgassing sphere with a more active ring around an axis of symmetry. The varied initial conditions were the number density of the homogeneous region, the surface temperature, and the composition of the flow (varying amounts of H2O and CO2) from the active ring. The sensitivity analysis was performed using the Polynomial Chaos Expansion (PCE) method. Direct Simulation Monte Carlo (DSMC) was used for the flow, thereby allowing strong deviations from local thermal equilibrium. The PCE approach can be used to produce a sensitivity analysis with only four runs per modified input parameter and allows one to study and quantify non-linear responses of measurable parameters to linear changes in the input over a wide range. Hence the PCE allows one to obtain a functional relationship between the flow field properties at every point in the inner coma and the input conditions. It is for example shown that the velocity and the temperature of the background gas are not simply linear functions of the initial number density at the source. As probably expected, the main influence on the resulting flow field parameter is the corresponding initial parameter (i.e. the initial number density determines the background number density, the temperature of the surface determines the flow field temperature, etc.). However, the velocity of the flow field is also influenced by the surface temperature while the number density is not sensitive to the surface temperature at all in our model set-up. Another example is the change in the composition of the flow over the active area. Such changes can be seen in the velocity but again not in the number density. Although this study uses only a simple test case, we suggest that the approach, when applied to a real case in 3D, should assist in identifying the sensitivity of gas parameters measured in situ by, for example, the Rosetta spacecraft to the surface boundary conditions and vice versa.

Numerical study of the laser-tip coupling in surface plasmon assisted stacked-double-gate field emitter arrays

Recently, sub-wavelength-pitch stacked double-gate metal nanotip arrays have been proposed to realize high current, high brightness electron bunches for ultrabright cathodes for x-ray free-electron laser applications. With the proposed device structure, ultrafast field emission of photoexcited electrons is efficiently driven by vertical incident near infrared laser pulses, via near field coupling of the surface plasmon polariton resonance of the gate electrodes with the nanotip apex. In this work, in order to gain insight in the underlying physical processes, the authors report detailed numerical studies of the proposed device. The results indicate the importance of the interaction of the double-layer surface plasmon polariton, the position of the nanotip, as well as the incident angle of the near infrared laser pulses.

Distribution of benthic and planktic foraminifera in surface sediments of the Indian and Pakistan continental margin, Arabian Sea

During the Indian Ocean Expedition of the German research vessel "Meteor" and the following cruise with the Pakistani fishing vessel "Machhera" in February and March 1965, sediments were sampled from the shelf, continental slope and the Arabian Basin off Pakistan and India. The biostratigraphic studies are based on sedimentary material from 24 sediment cores up to 480 cm long and 100 grab samples. The faunal residues of the > 160 µ fraction (chiefly foraminifera and pteropods) were determined and counted in order to get an idea of the climatic conditions during the Late Quaternary of this region. Biostratigraphic correlations of these Late Quaternary deposits are only possible if the thanatocoenosis of the surface sediments are well known. The analysis of the benthonic foraminiferal populations resulted in the definition of several foraminiferal facies. The following sequence of forarniniferal facies, named after their most characteristic members, can be distinguished from the shelf to the deep-sea: 1. Ammonia-Florilus facies ; 2. Ammonia-Cancris facies; 3. Cassidulina-Cibicides facies; 4. Uvigerina-Cassidulina facies ; 5. Buliminacea facies ; 6. deepwater facies, partly with Bulimina aculeata or with Nonionidae. On the upper continental slope there is a zone extremely poor in benthonic foraminifera. In this water depth the oxygen minimum layer (0.05-0.02 ml/l) of the water column reaches the slope. Almost no connection can be observed between the living and the dead foraminiferal population of the same sample. The regional distribution of the planktonic foraminifera from plankton tows as well as from the surface sediments shows marked differences in the species composition of faunas from different regions within the area of investigation. That depends on oceanographic conditions such as upwelling, dissolution of carbonate at great depths etc. Based on the results of faunal analysis of samples from the recent sea-floor, a biostratigraphic subdivision of the sediments in the cores was established. The following biostratigraphically defined sections could be distinguished from the top of the sediment cores downwards : 1. Relatively cool climatic conditions are reflected by the foraminifera of the uppermost core sections. 2. The next section is characterized by much warmer conditions (Holocene climatic optimum). The C-14 ages of this interval range from 4000 to 10 000 years B.P. according to different authors. C-14 dates on the material investigated do not give reliable clues. 3. Foraminiferal populations adapted to much colder conditions can be observed in the underlying core section. The boundary between the warm climate reflected by the foraminifera of section 2 and the cold climate (section 3) is relatively sharp. It can be correlated from core to core over the whole area investigated. The cold climate sediments of section 3 are underlain by different cool-, warm- and cold-climate sediments which can only be correlated over very short distances. Since it appears certain that the last really cold conditions ended earlier in the Arabian Sea and its vicinity than in Europe it is recommended not to use the European stratigraphic terms for the Quaternary. Because of the lack of reliable absolute sediment ages for the cores no exact sedimentation rates can be given. According to rough estimates, however, the rates are 1-2 cm/1000 years in the deep basin and up to 40 cm/1000 years on the upper continental slope. Sedimentation rates are always larger near the mouth of the Indus-River than off South India at stations of about the same water depth. Planktonic gastropods (mainly pteropods) cannot be used for biostratigraphic purposes in the region under consideration. All of them seem to be displaced from the shelf. Their distribution there is given in.

Holocene sedimentation in the Strait of Otranto, Mediterranean Sea

An extensive radiograph study of 24 undisturbed, up to 206-cm long box and gravity cores from the western part of the Strait of Otranto revealed a great variety of primary bedding structures and secondary burrowing features. The regional distribution of the sediments according to their structural, textural, and compositional properties reflects the major morphologic subdivisions of the strait into shelf, slope, and trough bottom (e.g., the bottom of the northern end of the Corfu-Kephallinia Trough, which extends from the northeastern Ionian Sea into the Strait of Otranto): (1) The Apulian shelf (0 to -170m) is only partly covered by very poorly sorted, muddy sands without layering. These relict(?) sands are rich in organic carbonate debris and contain glauconite and reworked (?Pleistocene) ooids. (2) The slope sediments (-170 to -1,000 m) are poorly sorted, sandy muds with a high degree of burrowing. One core (OT 5) is laminated and shows slump structures. An origin of these slumped sediment masses from older deposits higher on the slope was inferred from their abnormal compaction, color, texture, organic content, and mineral composition. (3) Cores from the northern end of the Corfu-Kephallinia Trough (-980 to -1,060 m) display a few graded sand layers, 2-5 cm (maximum 30 cm) thick with parallel and ripple-cross-laminations, deposited by oceanic bottom or small-scale turbidity currents. They are intercalated with homogeneous lutite. (4) Hemipelagic sediments prevail in the more southerly part of the Corfu-Kephallinia Trough and on the "Apulian-Ionian Ridge", the southern submarine extension of the Apulian Peninsula. Below a core depth of 160 cm, these cores have a laminated ("varved") zone, representing an Early Holocene (Boreal-Atlanticum) "stagnation layer" (14C age approximately 9,000 years). The terrigenous components of the surface sediments as well as those of the deeper sand layers can be derived from the Apulian shelf and the Italian mainland (Cretaceous Apulian Plateau and Gargano Mountains, southern Apennines, volcanic province of the Monte Vulture). Indicated by the heavy mineral glaucophane, a minor proportion of the sedimentary material is probably of Alpine origin. If this portion is considered to be first-cycle clastic material it reaches the Strait of Otranto after a longitudinal transport of 700 km via the Adriatic Sea. The lack of phyllosilicates in the coarse- to medium-grained shelf samples might be explained by the activity of the "Apulian Current" (surface velocities up to 4 knots) which in the past possibly has affected the bottom almost down to depths of the shelf edge. The percentage of planktonic organisms, and also the plankton: benthos ratio in the sediments is a useful indicator for bathymetry (depth zonation).

Diatom assamblage in samples from sediment traps across the Pacific Sector of the Southern Ocean

An array of four sediment trap moorings recorded the particulate flux across the Antarctic Circumpolar Current (ACC) at 170 °W, between November 1996 and January 1998, as part of the US JGOFS-Antarctic Environment and Southern Ocean Process Study (AESOPS) program. The trap locations represent sampling within the Polar Frontal Zone, the Antarctic Polar Front, the Antarctic Zone and the Southern Antarctic Zone. Here we report observations from 1000 m below the sea-surface compared to seafloor and surface water distributions. Sub-sample splits from each trap were obtained and total diatom flux and species composition were determined. The diatom fluxes were quantified using both a dilution and a 'spike' method to allow for the rapid repeatability of measurements. Diatom flux was found to be highly seasonal across the ACC particularly at higher latitudes. Marine snow aggregates of intact diatom cells and chains were the major components of the biogenic flux. Siliceous particle size was noted to decrease with increasing latitude, which could be aligned with a shift of the diatom assemblage to small-size species/sea-ice affiliated species. A 'double-structured' diatom flux was recorded at the location of the Antarctic Polar Front trap, with a shift in the diatom assemblage from larger to smaller diatoms in the second flux episode. The sediment trap assemblage shows deviations from the surface water assemblage, while surface sediment samples indicate that significant dissolution occurs after 1000 m and at the sediment-water interface. Estimation of diatom biovolumes across the ACC shows that large diatoms have the potential to greatly impact biogenic fluxes to the ocean interior despite their low fluxes. Small species of the genus Fragilariopsis could potentially export as much Corg as Fragilariopsis kerguelensis near the retreating ice edge. However, their low abundance in the surface sediments also suggests that these diatoms are a shallow export species.

Organic-walled dinoflagellate cysts analysis and statistical analysis of 116 surface sediment samples from the eastern Indian Ocean

Assemblages of organic-walled dinoflagellate cysts (dinocysts) from 116 marine surface samples have been analysed to assess the relationship between the spatial distribution of dinocysts and modern local environmental conditions [e.g. sea surface temperature (SST), sea surface salinity (SSS), productivity] in the eastern Indian Ocean. Results from the percentage analysis and statistical methods such as multivariate ordination analysis and end-member modelling, indicate the existence of three distinct environmental and oceanographic regions in the study area. Region 1 is located in western and eastern Indonesia and controlled by high SSTs and a low nutrient content of the surface waters. The Indonesian Throughflow (ITF) region (Region 2) is dominated by heterotrophic dinocyst species reflecting the region's high productivity. Region 3 is encompassing the area offshore north-west and west Australia which is characterised by the water masses of the Leeuwin Current, a saline and nutrient depleted southward current featuring energetic eddies.

Phytoplankton in the surface desalted lens of the Kara Sea

Phytoplankton of a surface strongly desalinated water lens was investigated on the basis of materials collected during Cruise 57 of R/V Akademik Mstislav Keldysh in September 2007. The lens with salinity <18 psu had area of ca. 19000 sq. km and was located in the northwestern part of the Kara Sea near the eastern coast of Novaya Zemlya. It was a specific biotope that had been isolated from surrounding waters for more than three months. In the investigated area 66 algae species were identified. The maximal species diversity was found in the upper layers of the desalinated lens, where species number was 1.5 to 3 times higher than in other parts of the water column. Phytoplankton abundance in the upper layers of the lens was 1.5 to 4.5 times higher than in its lower part and generally higher than below the picnocline. Diatoms were the most abundant group in the upper layers of the lens, while flagellates dominated in the subpicnocline part of the water column. Maximal values of phytoplankton biomass were observed everywhere in the upper layers of the lens, where they were 1.2 to 3.7 times higher than in the lower part of the lens and 1.3 to 7.2 times higher than in the layer below the picnocline. Dinoflagellates generally gave the most contribution to total phytoplankton biomass. Phytoplankton of the desalinated surface lens in the northwestern part of the Kara Sea by its composition and quantitative parameters had the nearest resemblance to a phytocenosis that we observed two weeks later at a shallow desalinated shelf closely adjacent to the Ob estuary.

Age models of upper Pliocene samples of the North Atlantic

Abundance variations of six Pliocene species of discoasters have been analyzed over the time interval from 1.89 to 2.95 Ma at five contrasting sites in the North Atlantic: Deep Sea Drilling Project Sites 552 (56°N) and 607 (41°N) and Ocean Drilling Program 658 (20°N), 659 (18°N), and 662 (1°S). A sampling interval equivalent to approximately 3 k.y. was used. Total Discoaster abundance showed a reduction with increasing latitude and from the effects of upwelling. This phenomenon is most obvious in Discoaster brouweri, the only species that survived over the entire time interval studied. Prior to 2.38 Ma, Discoaster pentaradiatus and Discoaster surculus are important components of the Discoaster assemblage: Discoaster pentaradiatus increases slightly with latitude up to 41°N, and its abundance relative to D. brouweri increases up to 56°N; D. surculus increases in abundance with latitude and with upwelling conditions relative to both D. brouweri and D. pentaradiatus and is dominant to the latter species at upwelling Site 658 and at the highest latitude sites. Discoaster asymmetricus and Discoaster tamalis appear to increase in abundance with latitude relative to D. brouweri. Many of the abundance changes observed appear to be connected with the initiation of glaciation in the North Atlantic at 2.4 Ma. The long-term trend of decreasing Discoaster abundance probably reflects the fall of sea-surface temperatures. This trend of cooling is overprinted by short-term variations that are probably associated with orbital forcing. Evidence for the astronomical elements of eccentricity and obliquity periodicities were found at all sites; however, only at Sites 607, 659, and 662 were precessional periodicities detected. Furthermore, only at Site 659 was precession found to be dominant to obliquity. Abundance peaks of individual species were found to cross-correlate between sites. The distinct abundance fluctuations observed especially in the tropics suggest that temperature is not the only factor responsible for this variation. This study reveals for the first time the importance of productivity pressure on the suppression of Discoaster abundance.

Area-averaged mean seasonal cycles of chlorophyll-a concentration, sea surface temperature, alongshore wind stress, westward wind speed and dust component of the aerosol optical depth at 550 nm

Nutrient supply in the area off Northwest Africa is mainly regulated by two processes, coastal upwelling and deposition of Saharan dust. In the present study, both processes were analyzed and evaluated by different methods, including cross-correlation, multiple correlation, and event statistics, using remotely sensed proxies of the period from 2000 to 2008 to investigate their influence on the marine environment. The remotely sensed chlorophyll-a concentration was used as a proxy for the phytoplankton biomass stimulated by nutrient supply into the euphotic zone from deeper water layers and from the atmosphere. Satellite-derived alongshore wind stress and sea-surface temperature were applied as proxies for the strength and reflection of coastal upwelling processes. The westward wind and the dust component of the aerosol optical depth describe the transport direction of atmospheric dust and the atmospheric dust column load. Alongshore wind stress and induced upwelling processes were most significantly responsible for the surface chlorophyll-a variability, accounting for about 24% of the total variance, mainly in the winter and spring due to the strong north-easterly trade winds. The remotely sensed proxies allowed determination of time lags between biological response and its forcing processes. A delay of up to 16 days in the surface chlorophyll-a concentration due to the alongshore wind stress was determined in the northern winter and spring. Although input of atmospheric iron by dust storms can stimulate new phytoplankton production in the study area, only 5% of the surface chlorophyll-a variability could be ascribed to the dust component in the aerosol optical depth. All strong desert storms were identified by an event statistics in the time period from 2000 to 2008. The 57 strong storms were studied in relation to their biological response. Six events were clearly detected in which an increase of chlorophyll-a was caused by Saharan dust input and not by coastal upwelling processes. Time lags of <8 days, 8 days, and 16 days were determined. An increase in surface chlorophyll-a concentration of up to 2.4 mg m**3 after dust storms in which the dust component of the aerosol optical depth was up to 0.9 was observed.

Geochemistry of recent sediments of the East African continental margin, Arabian Sea

Chemical analyses have been carried out on 40 samples from the sediment surface and 210 samples from cores that were taken from the edge of the African continental block at the Arabian Sea (coasts of Somalia and Kenya, from Cape Guardafui to Mombasa) on the occasion of the Indian Ocean Expedition of the German research vessel "Meteor" during the years 1964/65. The carbonate content shows its maximum on the northern part of the continental shelf of Africa, where fossil reef debris furnish the detritic portion of carbonate. In the southern part of the continental shelf of Africa the portion of carbonate is low, as it is heavily diluted by the non-carbonatic detritus. It is also in the deep-sea that a lower carbonate content is encountered below the calcite compensation depth. Trace elements in the carbonates: On the shelf and in its vicinity Sr and Mg are enriched. The enrichment has been brought about by the portion of reef debris, as this latter contains aragonite (enrichment of Sr) as well as high-magnesium calcite. The greatest part of the slope contains carbonates that are poor in trace elements and mainly made up of foraminifera (and of coccoliths). Below the carbonate compensation depth another enrichment of Mg takes place in the carbonates, which is probably due to a selective dissolution of calcite in comparison to dolomite. The iron and manganese contents of the carbonates are high (iron higher in coast proximity, manganese higher in the depth), but not genuine, as they come about in the course of the extraction of the carbonates as a result of the dissolution of authigenic Mn-Fe-minerals. Non-carbonatic portion of the sediments: In coast proximity an enrichment of quartz comes about. Within the quartz-rich zone it is the elements V, Cr, Fe, Ti, and B that have been enriched in the non-carbonatic components. This enrichment must be attributed to an elevated content of heavy minerals. In the case of Ti and Fe the preliminary enrichment brought about by processes of lateritisation on the continent plays a certain role. Toward the deep-sea an enrichment of the elements Mn Ni, Cu, and Zn takes place; these enrichments must be explained by authigenic Mn-Fe-minerals. Within the Mn-rich zone a belt running parallel to the coast stands out that shows an increased Mn-enrichment. However, this increase in enrichment does not apply to the elements Ni, Cu, and Zn. It is probable that this latter increased enrichment comes about as a result of the migration of manganese to the sediment surface. (Within the sediments there prevail reductive conditions, in the presence of which Mn is capable of migration, whereas at the sediment surface its precipitation comes about under oxidizing conditions). The quantity of organic matter mainly is dependent on grain size and on the rate of sedimentation. On the shelf an impoverishment of organic matter is to be encountered, as the sediments are coarse-grained. In the depth the impoverishment must be explained on the strength of a small rate of sedimentation. Between those two ranges organic substance is enriched. P and N show an enrichment in comparison to Corg with this applying all the more the smaller the absolute quantity of Corg is. In this particular case one has to do with an enrichment coming about during the diagenetic processes of organic matter. A comparison with the sediments from the Indian and Pakistani continental border in Arabian Sea shows as follows: on the African continental border the coarse detrital material has been transported farther out to deep-sea, which has something to do with the greater inclination of the surface of sedimentation. Carbonate is found in greater abundance on the African side. Its chemical composition is influenced by reef-debris which is missing by Indian-Pakistani side. The content of organic matter is lower on the African side. Contrary to that, the enrichments of N and P compared to organic matter are of an equal order of magnitude on both sides of the Arabian Sea.