Immunogenicity and Protection After Vaccination With a Modified Vaccinia Virus Ankara-Vectored Yellow Fever Vaccine in the Hamster Model

The highly efficacious live-attenuated 17D yellow fever (YF) vaccine is occasionally associated with rare life-threatening adverse events. Modified vaccinia virus Ankara (MVA), a non-replicating poxvirus, has been used as a vaccine platform to safely deliver various antigens. A MVA-based YF vaccine (MVA-BN-YF) was tested with and without a non-mineral oil adjuvant in a hamster model of lethal YF disease and protective efficacy of this vaccine was compared with the 17D vaccine. The vaccine candidate MVA-BN-YF generated a protective response in hamsters infected with YFV that was comparable to protection by the live 17D vaccine. Similar levels of neutralizing antibody were observed in animals vaccinated with either vaccine alone or vaccine with adjuvant. Significant improvement in survival, weight change, and serum alanine aminotransferase levels were observed in vaccinated hamsters when administered 42 and 14 days prior to challenge with Jimenez YF virus (YFV). Neutralizing antibodies induced by MVA-BN-YF were transferred to naïve hamsters prior to virus challenge. Passive administration of neutralizing antibody 24 h prior to virus infection resulted in significantly improved survival and weight change. A trend toward reduced liver enzyme levels was also observed. MVA-BN-YF, therefore, represents a safe alternative to vaccination with live-attenuated YFV

Total Face Approach (TFA): a novel 3D approach to describe the main cephalometric craniomaxillofacial parameters

The aim of this study is to propose a 3D skeletal classification and relative normal values of reference. Method: from a pool of 271 cone-beam computerized tomography images 108 chinsummit examinations of the skull were selected and divided into 3 traditional skeletal classes. The same Cone-beam Computerized Tomography (CBCT) images were then assessed using the cephalometric multiplanar analysis following the total face approach protocol. Results: the results of this study indicate standard 3D cephalometric norms for the vertical and sagittal evaluation of the skull. Conclusions: data obtained from our measurements allowed the creation of intervals supplying nosological classification that could be used in orthodontics, orthognatic surgery and implant surgery in fully edentulous patients

A radiation free alternative to CBCT volumetric rendering for soft tissue evaluation

Objective: The aim of the present study is to evaluate whether a “radiation free” method using 3D facial scan can replace Cone Beam Computed Tomography (CBCT) volumetric rendering of soft tissue of the patient to assess maxillofacial surgery outcomes and compare the reference points and angular measurements of patient facial soft tissue. Material and Methods: Facial soft tissue scan of the patient’s face, before and after orthognathic surgery and a CBCT of the skull for volumetric rendering of soft tissues were carried out. The 3D acquisitions were processed using Planmeca ProMax 3D ProFace® software (Planmeca USA, Inc.; Roselle, Illinois, USA). The participant were positioned in a natural position during the skull scannering. Three sagittal angular measurements were performed (Tr-NA, Tr-N-Pg, Ss-N-Pg) and two verticals (Go-N-Me, Tr-Or-Pg) on facial soft tissue scan and on the patient’s 3D soft tissue CBCT volumetric rendering. Results: A certain correspondence has been demonstrated between the measurements obtained on the Proface and those on the CBCT. Conclusion: A radiation free method was to be considered an important diagnostic tool that works in conditions of not subjecting the patient to harmful ionizing radiation and it was therefore particularly suitable for growing subjects. The soft tissue analysis based on the realistic facial scan has shown sufficient reliability and reproducibility even if further studies are needed to confirm the research result

The embedded clusters DBS 77, 78, 102, and 160-161 and their link with the interstellar medium

Aims. We report a study of the global properties of some embedded clusters placed in the fourth quadrant of the Milky Way to clarify some issues related with their location into the Galaxy and their stellar formation processes. Methods. We performed BVI photometric observations in the region of DBS 77, 78, 102, 160, and 161 clusters and infrared spectroscopy in DBS 77 region. They were complemented with JHK data from VVV survey combined with 2MASS catalogue, and used mid-infrared information from GLIMPSE catalogue. We also searched for HI data from SGPS and PMN radio surveys, and previous spectroscopic stellar classification. The spectroscopic and photometric information allowed us to estimate the spectral classification of the brightest stars of each studied region. On the other hand, we used the radio data to investigate the interstellar material parameters and the continuum sources probably associated with the respective stellar components. Results. We estimated the basic physical parameters of the clusters (reddening, distance, age, and initial mass function). We searched for HII regions located near to the studied clusters and we analyzed the possible link between them. In the particular case of DBS 160-161 clusters, we identified the HI bubble B332.5-0.1-42 located around them. We found that the mechanical energy injected to the interstellar medium by the more massive stars of this couple of clusters was enough to generate the bubble.Comment: 15 pages, 14 figures, 6 tables, accepted for publication in A&

The role of BRAF V600 mutation in melanoma

BRAF is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway. About 50 % of melanomas harbors activating BRAF mutations (over 90 % V600E). BRAFV600E has been implicated in different mechanisms underlying melanomagenesis, most of which due to the deregulated activation of the downstream MEK/ERK effectors. The first selective inhibitor of mutant BRAF, vemurafenib, after highly encouraging results of the phase I and II trial, was compared to dacarbazine in a phase III trial in treatment-naïve patients (BRIM-3). The study results showed a relative reduction of 63 % in risk of death and 74 % in risk of tumor progression. Considering all trials so far completed, median overall survival reached approximately 16 months for vemurafenib compared to less than 10 months for dacarbazine treatment. Vemurafenib has been extensively tested on melanoma patients expressing the BRAFV600E mutated form; it has been demonstrated to be also effective in inhibiting melanomas carrying the V600K mutation. In 2011, both FDA and EMA therefore approved vemurafenib for metastatic melanoma carrying BRAFV600 mutations. Some findings suggest that continuation of vemurafenib treatment is potentially beneficial after local therapy in a subset of patients with disease progression (PD). Among who continued vemurafenib >30 days after local therapy of PD lesion(s), a median overall survival was not reached, with a median follow-up of 15.5 months from initiation of BRAF inhibitor therapy. For patients who did not continue treatment, median overall survival from the time of disease progression was 1.4 months. A clinical phase I/II trial is evaluating the safety, tolerability and efficacy of vemurafenib in combination with the CTLA-4 inhibitor mAb ipilimumab. In the BRIM-7 trial vemurafenib is tested in association with GDC-0973, a potent and highly selective inhibitor of MEK1/2. Preliminary data seem to indicate that an additional inhibitor of mutated BRAF, GSK2118436, might be also active on a wider range of BRAF mutations (V600E-K-D-R); actually, treatment with such a compound is under evaluation in a phase III study among stage III-IV melanoma patients positive for BRAF mutations. Overall, BRAF inhibitors were well tolerated; common adverse events are arthralgia, rash, fatigue, alopecia, keratoacanthoma or cutaneous squamous-cell carcinoma, photosensitivity, nausea, and diarrhea, with some variants between different inhibitors

High Galactic latitude polarized emission at 1.4 GHz and implications for cosmic microwave background observations

We analyse the polarized emission at 1.4 GHz in a 3x3 deg^2 area at high Galactic latitude (b ~ -40deg). The region, centred in (RA=5h, Dec=-49deg), was observed with the Australia Telescope Compact Array radio-interferometer, whose 3-30 arcmin angular sensitivity range allows the study of scales appropriate for CMB Polarization (CMBP) investigations. The angular behavior of the diffuse emission is analysed through the E- and B-mode power spectra. These follow a power law $C^X_l \propto l^{\beta_X}$ with slopes \beta_E = -1.97 \pm 0.08 and \beta_B = -1.98 \pm 0.07. The emission is found to be about a factor 25 fainter than in Galactic plane regions. The comparison of the power spectra with other surveys indicates that this area is intermediate between strong and negligible Faraday rotation effects. A similar conclusion can be reached by analysing both the frequency and Galactic latitude behaviors of the diffuse Galactic emission of the 408-1411 MHz Leiden survey data. We present an analysis of the Faraday rotation effects on the polarized power spectra, and find that the observed power spectra can be enhanced by a transfer of power from large to small angular scales. The extrapolation of the spectra to 32 and 90GHz of the CMB window suggests that Galactic synchrotron emission leaves the CMBP E-mode uncontaminated at 32GHz. The level of the contamination at 90GHz is expected to be more than 4 orders of magnitude below the CMBP spectrum. Extrapolating to the relevant angular scales, this region also appears adequate for investigation of the CMBP B-modes for models with tensor/scalar fluctuation power ratio T/S>0.01. We also identify polarized point sources in the field, providing a 9 object list which is complete down to the polarized flux limit of S^p_lim = 2 mJy.Comment: 13 pages, 11 figures, accepted for publication in MNRA

The structure of atomic gas around the supernova remnant 3C 400.2

The interaction of the SNR 3C 400.2 with the interstellar medium is investigated on the basis of the HI observations using the Synthesis Radio Telescope at the Dominion Radio Astrophysical Observatory (DRAO). These new data show the existence of a dense atomic cloud associated with 3C 400.2 in the velocity range +14 to +42 km s -1 , and high velocity clouds probably accelerated by the supernova blast wave at  km s -1 and +69 km s -1 . We propose that the complex remnant 3C 400.2 is the result of a supernova explosion in a region of the interstellar medium containing a density discontinuity. A breakout phenomenon may explain the observed morphology in the different spectral regimes.Facultad de Ciencias Astronómicas y GeofísicasInstituto Argentino de Radioastronomí

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

The Parkes Galactic Meridian Survey (PGMS): observations and CMB polarization foreground analysis

We present observations and CMB foreground analysis of the Parkes Galactic Meridian Survey (PGMS), an investigation of the Galactic latitude behaviour of the polarized synchrotron emission at 2.3 GHz with the Parkes Radio Telescope. The survey consists of a 5-deg wide strip along the Galactic meridian l=254-deg extending from Galactic plane to South Galactic pole. We identify three zones distinguished by polarized emission properties: the disc, the halo, and a transition region connecting them. The halo section lies at latitudes |b| > 40-deg and has weak and smooth polarized emission mostly at large scale with steep angular power spectra of median slope $\beta_{\rm med} \sim -2.6$. The disc region covers the latitudes |b|<20-deg and has a brighter, more complex emission dominated by the small scales with flatter spectra of median slope $\beta_{\rm med} = -1.8$. The transition region has steep spectra as in the halo, but the emission increases toward the Galactic plane from halo to disc levels. The change of slope and emission structure at b \sim -20\degr is sudden, indicating a sharp disc-halo transition. The whole halo section is just one environment extended over 50-deg with very low emission which, once scaled to 70GHz, is equivalent to the CMB B-Mode emission for a tensor-to-scalar perturbation power ratio r_halo = 3.3 +/- 0.4 x 10^{-3}. Applying a conservative cleaning procedure, we estimate an r detection limit of $\delta r \sim 2\times 10^{-3}$ at 70~GHz (3-sigma C.L.) and, assuming a dust polariztion fraction <12%, $\delta r \sim 1\times 10^{-2}$ at 150~GHz. The 150-GHz limit matches the goals of planned sub-orbital experiments, which can therefore be conducted at this high frequency. The 70-GHz limit is close to the goal of proposed next generation space missions, which thus might not strictly require space-based platforms.Comment: 23 pages, 22 Figures. Accepted for publication on MNRAS. Some figures have been reduced in resolution. Replaced with the accepted version, 3 figures, more details on instrument performances, and map of polarization spectral index adde

Mucinous breast cancer: A narrative review of the literature and a retrospective tertiary single-centre analysis

We reviewed literature and our data to find out mucinous breast cancer's overall survival (OS), disease free survival (DFS) and if there are differences between pure mucinous breast cancer and mixed mucinous breast cancer in terms of OS and DFS