A gorilla adenovirus-based vaccine against Zika virus induces durable immunity and confers protection in pregnancy

The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD

CXCL12 retargeting of an adenovirus vector to cancer cells using a bispecific adapter

Ad vectors are promising delivery vehicles for cancer therapeutic interventions. However, their application is limited by promiscuous tissue tropism and hepatotoxicity. This limitation can be avoided by altering the native tropism of Ads so that they can be redirected to the target cells through alternate cellular receptors. The CXCR4 chemokine receptor belongs to a large superfamily of G-protein-coupled receptors and is known to be upregulated in a wide variety of cancers, including breast cancer and melanoma. These receptors have been associated with cancer cell survival, progression, and metastasis. In the current study, an Ad to cancer cells overexpressing CXCR4 by using a bispecific adapter, sCAR-CXCL12, was retargeted. The sCAR-CXCL12 adapter contained the soluble ectodomain form of the native Ad5 receptor (sCAR), which was fused to a mature human chemokine ligand, CXCL12, through a short peptide linker. A dramatic increase in the infectivity of cancer cells using a targeted Ad vector compared with an untargeted vector was observed. Furthermore, sCAR-CXCL12 attenuated Ad infection of liver ex vivo and in vivo and enhanced Ad vector infection of xenograft tumors implanted in immunodeficient SCID-bg mice. Thus, the sCAR-CXCL12 adapter could be used to retarget Ad vectors to chemokine receptor-positive tumors

HSV-1 Virions Engineered for Specific Binding to Cell Surface Receptors

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High resolution AMI Large Array imaging of spinning dust sources: spatially correlated 8 micron emission and evidence of a stellar wind in L675

We present 25 arcsecond resolution radio images of five Lynds Dark Nebulae (L675, L944, L1103, L1111 & L1246) at 16 GHz made with the Arcminute Microkelvin Imager (AMI) Large Array. These objects were previously observed with the AMI Small Array to have an excess of emission at microwave frequencies relative to lower frequency radio data. In L675 we find a flat spectrum compact radio counterpart to the 850 micron emission seen with SCUBA and suggest that it is cm-wave emission from a previously unknown deeply embedded young protostar. In the case of L1246 the cm-wave emission is spatially correlated with 8 micron emission seen with Spitzer. Since the MIR emission is present only in Spitzer band 4 we suggest that it arises from a population of PAH molecules, which also give rise to the cm-wave emission through spinning dust emission.Comment: accepted MNRA

The blaSHV-5 gene is encoded in a compound transposon duplicated in tandem in Enterobacter cloacae

AbstractThe presence of blaSHV-5 is described in a compound transposon, duplicated in tandem and flanked by IS26 copies on a 70-kb conjugative plasmid (pHNM1), in an Enterobacter cloacae strain associated with a nosocomial outbreak that occurred in Mexico

PMS61 Health-Related Quality of Life After Vertebral Fracture: Differences Between the EQ-5D and Time-Trade-Off Instruments

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Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival

Proportionate flow shop games

htmlabstractIn a proportionate flow shop problem several jobs have to be processed through a fixed sequence of machines and the processing time of each job is equal on all machines. By identifying jobs with agents, whose costs linearly depend on the completion time of their jobs, and assuming an initial processing order on the jobs, we face two problems: the first one is how to obtain an optimal order that minimizes the total processing cost, the second one is how to allocate the cost savings obtained by ordering the jobs optimally. In this paper we focus on the allocation problem. PFS games are defined as cooperative games associated to proportionate flow shop problems. It is seen that PFS games have a nonempty core. Moreover, it is shown that PFS games are convex if the jobs are initially ordered in decreasing urgency. For this case an explicit game independent expression for the Shapley value is provid

Wide field CO J = 3->2 mapping of the Serpens Cloud Core

Context. Outflows provide indirect means to get an insight on diverse star formation associated phenomena. On scales of individual protostellar cores, outflows combined with intrinsic core properties can be used to study the mass accretion/ejection process of heavily embedded protostellar sources. Methods. An area comprising 460"x230" of the Serpens cloud core has been mapped in 12 CO J = 3\to 2 with the HARP-B heterodyne array at the James Clerk Maxwell Telescope; J = 3\to 2 observations are more sensitive tracers of hot outflow gas than lower J CO transitions; combined with the high sensitivity of the HARP-B receptors outflows are sharply outlined, enabling their association with individual protostellar cores. Results. Most of ~20 observed outflows are found to be associated with known protostellar sources in bipolar or unipolar configurations. All but two outflow/core pairs in our sample tend to have a projected orientation spanning roughly NW-SE. The overall momentum driven by outflows in Serpens lies between 3.2 and 5.1 x 10^(-1) M\odot km s^(-1), the kinetic energy from 4.3 to 6.7 x 10^(43) erg and momentum flux is between 2.8 and 4.4 x 10^(-4) M\odot km s^(-1) yr^(-1). Bolometric luminosities of protostellar cores based on Spitzer photometry are found up to an order of magnitude lower than previous estimations derived with IRAS/ISO data. Conclusions. We confirm the validity of the existing correlations between the momentum flux and bolometric luminosity of Class I sources for the homogenous sample of Serpens, though we suggest that they should be revised by a shift to lower luminosities. All protostars classified as Class 0 sources stand well above the known Class I correlations, indicating a decline in momentum flux between the two classes.Comment: 15 pages, 10 figures, accepted for publication in A&