User data dissemination concepts for earth resources

Domestic data dissemination networks for earth-resources data in the 1985-1995 time frame were evaluated. The following topics were addressed: (1) earth-resources data sources and expected data volumes, (2) future user demand in terms of data volume and timeliness, (3) space-to-space and earth point-to-point transmission link requirements and implementation, (4) preprocessing requirements and implementation, (5) network costs, and (6) technological development to support this implementation. This study was parametric in that the data input (supply) was varied by a factor of about fifteen while the user request (demand) was varied by a factor of about nineteen. Correspondingly, the time from observation to delivery to the user was varied. This parametric evaluation was performed by a computer simulation that was based on network alternatives and resulted in preliminary transmission and preprocessing requirements. The earth-resource data sources considered were: shuttle sorties, synchronous satellites (e.g., SEOS), aircraft, and satellites in polar orbits

User data dissemination concepts for earth resources: Executive summary

The impact of the future capabilities of earth-resources data sensors (both satellite and airborne) and their requirements on the data dissemination network were investigated and optimum ways of configuring this network were determined. The scope of this study was limited to the continental U.S.A. (including Alaska) and to the 1985-1995 time period. Some of the conclusions and recommendations reached were: (1) Data from satellites in sun-synchronous polar orbits (700-920 km) will generate most of the earth-resources data in the specified time period. (2) Data from aircraft and shuttle sorties cannot be readily integrated in a data-dissemination network unless already preprocessed in a digitized form to a standard geometric coordinate system. (3) Data transmission between readout stations and central preprocessing facilities, and between processing facilities and user facilities are most economically performed by domestic communication satellites. (4) The effect of the following factors should be studied: cloud cover, expanded coverage, pricing strategies, multidiscipline missions

Anti-Gag Cytolytic T Lymphocytes Specific for an Alternative Translational Reading Frame-Derived Epitope and Resistance Versus Susceptibility to Retrovirus-Induced Murine AIDS in F1 Mice

Murine AIDS (MAIDS) develops in susceptible mouse strains after infection with the LP-BM5 murine leukemia virus complex that contains causative defective, and ecotropic helper, retroviruses. We previously demonstrated that the MAIDSresistant H-2d strains BALB/cByJ and C57BL/KsJ generate MHC class I (Kd ) restricted virus-specific CD81 cytolytic T lymphocytes (CTLs) that lyse cells expressing either defective or ecotropic gag proteins. In contrast, the congenic BALB.B and closely related C57BL/6J MAIDS-susceptible H-2b strains were unable to serve as a source of gag-specific CTLs (Schwarz and Green, 1994), suggesting that anti-gag CTLs might provide a basis for resistance to MAIDS. Although its susceptibility to MAIDS was unknown, the (BALB/c 3 C57BL/6J) F1 (CBY6F1) strain could also produce H-2d -, but not H-2b -, restricted, anti-gag CTLs (Schwarz and Green, 1994). Because of this correlation between anti-gag CTLs and resistance to MAIDS, it was important to provide more direct evidence in support of CTL-mediated protection and to determine both the fine specificity of CByB6F1 anti-gag CTLs, in comparison with the resistant C57BL/Ks and BALB/c strains, and the susceptibility of this F1 strain to LP-BM5-induced MAIDS. We report here that no symptoms of MAIDS were observed in CBY6F1 (H-2d3b ) mice. For F2 mice, in contrast to the high susceptibility of H-2b/b mice, 77% of H-2d/d and 81% of H-2b/d F2 mice did not exhibit MAIDS after LP-BM5 infection. These results are in contrast to other published studies that concluded that susceptibility, rather than resistance, is dominant in F1 (resistant 3 susceptible or susceptible 3 resistant) mice. We also show that CBY6F1 anti-gag CTLs exhibit a fine specificity shared by the MAIDS-resistant BALB/c and C57BL/Ks strains, that is, the immunodominant gag epitope, SYNTGRFPPL, encoded by an alternative open reading frame. Together with our direct demonstration here that in vivo monoclonal antibody (mAb) depletion of CD81 T cells converts genetically resistant mice to MAIDS susceptibility, these data on the ability to mount anti-ORF2/SYNTGRFPPL, gag-specific CTL responses strongly suggest that CTLs are a primary factor in determining MAIDS resistance. Accordingly, given the Kd -restricted nature of the CTLs, the main genetic determinant of resistance appeared to be the codominant expression of the resistant H-2d haplotype. Interestingly, however, 19% of H-2d/b and 23% of the H-2d/d F2 mice had at least one clinical aspect of MAIDS, suggesting that a non-MHC genetic determinant(s) can negatively influence T-cell protection and thus disease outcome

Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34+ hematopoietic stem and progenitor cells. Within the hematopoietic system, we show that HK3 is predominantly expressed in cells of myeloid origin. CRISPR/Cas9 mediated gene disruption revealed that loss of HK3 has no effect on glycolytic activity in AML cell lines while knocking out HK2 significantly reduced basal glycolysis and glycolytic capacity. Instead, loss of HK3 but not HK2 led to increased sensitivity to ATRA-induced cell death in AML cell lines. We found that HK3 knockout (HK3-null) AML cells showed an accumulation of reactive oxygen species (ROS) as well as DNA damage during ATRA-induced differentiation. RNA sequencing analysis confirmed pathway enrichment for programmed cell death, oxidative stress, and DNA damage response in HK3-null AML cells. These signatures were confirmed in ATAC sequencing, showing that loss of HK3 leads to changes in chromatin configuration and increases the accessibility of genes involved in apoptosis and stress response. Through isoform-specific pulldowns, we furthermore identified a direct interaction between HK3 and the proapoptotic BCL-2 family member BIM, which has previously been shown to shorten myeloid life span. Our findings provide evidence that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation

Switching-On Survival and Repair Response Programs in Islet Transplants by Bone Marrow–Derived Vasculogenic Cells

OBJECTIVE—Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow–derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature

A search for radio emission from Galactic supersoft X-ray sources

We have made a deep search for radio emission from all the northern hemisphere supersoft X-ray sources using the VLA and MERLIN telescopes, at 5 and 8.4 GHz. Three previously undetected sources: T Pyx, V1974 Cygni and RX J0019.8+2156 were imaged in quiescence using the VLA in order to search for any persistent emission. No radio emission was detected in any of the VLA fields down to a typical 1 sigma RMS noise of 20 uJy/beam, however, 17 new point sources were detected in the fields with 5 GHz fluxes between 100 and 1500 uJy giving an average 100 uJy-source density of around 200 per square degree, comparable to what was found in the MERLIN HDF survey. The persistent source AG Draconis was observed by MERLIN to provide a confirmation of previous VLA observations and to investigate the source at a higher resolution. The core is resolved at the milliarcsec scale into two components which have a combined flux of around 1 mJy. It is possible that we are detecting nebulosity which is becoming resolved out by the higher MERLIN resolution. We have investigated possible causes of radio emission from a wind environment, both directly from the secondary star, and also as a consequence of the high X-ray luminosity from the white dwarf. There is an order of magnitude discrepancy between observed and modelled values which can be explained by the uncertainty in fundamental quantities within these systems.Comment: Accepted for publication in MNRAS, 7 pages, 1 figur

Low-mass X-ray binaries in the bulge of the Milky Way

We study the population of low-mass X-ray binaries (LMXBs) in the Galactic bulge using the deep survey of this region by the IBIS telescope aboard the INTEGRAL observatory. Thanks to the increased sensitivity with respect to previous surveys of this field, we succeeded to probe the luminosity function (LF) of LMXBs down to ~7e34 erg/sec in the 17-60keV energy band. The slope dlog N/dlog L=-0.96+/0.20 measured in the 1e35-1e37 erg/sec range confirms that the LMXB LF flattens below L_x<1e37 erg/sec with respect to higher luminosities. We discuss the origin of the observed LF flattening. We demonstrate that the spatial distribution of persistent LMXBs in the Galactic Center/Galactic bulge region is consistent with a model of stellar mass distribution that includes the nuclear stellar disk component in the innermost degree of the Galaxy. The spatial distribution of transient LMXBs detected in the Galactic Center region indicates an increased fraction of transient sources in the innermost degree of the Galaxy with respect to outer regions.Comment: 10 pages, 8 figures, Submitted to A&

Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration

The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types

A drug targeting only p110α can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types

Genetic alterations in PI3K (phosphoinositide 3-kinase) signalling are common in cancer and include deletions in PTEN (phosphatase and tensin homologue deleted on chromosome 10), amplifications of PIK3CA and mutations in two distinct regions of the PIK3CA gene. This suggests drugs targeting PI3K, and p110α in particular, might be useful in treating cancers. Broad-spectrum inhibition of PI3K is effective in preventing growth factor signalling and tumour growth, but suitable inhibitors of p110α have not been available to study the effects of inhibiting this isoform alone. In the present study we characterize a novel small molecule, A66, showing the S-enantiomer to be a highly specific and selective p110α inhibitor. Using molecular modelling and biochemical studies, we explain the basis of this selectivity. Using a panel of isoform-selective inhibitors, we show that insulin signalling to Akt/PKB (protein kinase B) is attenuated by the additive effects of inhibiting p110α/p110β/p110δ in all cell lines tested. However, inhibition of p110α alone was sufficient to block insulin signalling to Akt/PKB in certain cell lines. The responsive cell lines all harboured H1047R mutations in PIK3CA and have high levels of p110α and class-Ia PI3K activity. This may explain the increased sensitivity of these cells to p110α inhibitors. We assessed the activation of Akt/PKB and tumour growth in xenograft models and found that tumours derived from two of the responsive cell lines were also responsive to A66 in vivo. These results show that inhibition of p110α alone has the potential to block growth factor signalling and reduce growth in a subset of tumours