Extended treatment with MY-NEOVAX, personalized neoantigen-enhanced oncolytic viruses, for two end-stage cancer patients.

Neoantigen vaccines involving multi-peptides and poly-epitope-encoding RNA or DNA have undergone early phase clinical testing with modest reported antitumor effects [ 1]. The less-than-expected activity of these neoantigenic vaccines may correspond with the development of immune escape mechanisms. One permutation on neoantigen vaccines, which may counter or prevent these adaptive immune escape mechanisms, are 'personalized' oncolytic viruses that encode one or more tumor-specific transgenes. Herein, positive therapeutic effects for MY-NEOVAX™, personalized neoantigen-enhanced oncolytic adenoviruses, are described for two heavily pretreated end-stage patients, one with high-grade metastatic neuroendocrine carcinoma of the pancreas and the other with colorectal cancer metastatic to the brain, liver and lungs. To date, treatment benefit has exceeded 12 months without dose-limiting toxicities or related serious adverse events and with documented radiologic stabilization and improved performance status

Undescended retropharyngeal parathyroid adenoma with adjacent thymic tissue in a 13-year-old boy with primary hyperparathyroidism.

We describe a rare presentation of a symptomatic parathyroid adenoma located in an ectopic retropharyngeal position in a 13-year-old boy. Preoperative CT scan and MRI demonstrated the ectopic location of the parathyroid adenoma. The patient underwent successful parathyroidectomy with cure of his hyperparathyroidism. On pathologic exam, the specimen was made up of a parathyroid adenoma and adjacent thymic tissue, indicating that it was likely an undescended lower parathyroid gland arising from the third pharyngeal pouch. Ectopic retropharyngeal parathyroid adenomas are very rare and to our knowledge, none have been previously described in adolescents

Optimal path shape for range-only underwater target localization using a Wave Glider

Underwater localization using acoustic signals is one of the main components in a navigation system for an autonomous underwater vehicle (AUV) as a more accurate alternative to dead-reckoning techniques. Although different methods based on the idea of multiple beacons have been studied, other approaches use only one beacon, which reduces the system’s costs and deployment complexity. The inverse approach for single-beacon navigation is to use this method for target localization by an underwater or surface vehicle. In this paper, a method of range-only target localization using a Wave Glider is presented, for which simulations and sea tests have been conducted to determine optimal parameters to minimize acoustic energy use and search time, and to maximize location accuracy and precision. Finally, a field mission is presented, where a Benthic Rover (an autonomous seafloor vehicle) is localized and tracked using minimal human intervention. This mission shows, as an example, the power of using autonomous vehicles in collaboration for oceanographic research.Peer ReviewedPostprint (author's final draft

High quality factor copper inductors integrated in deep dry-etched quartz substrates

This paper reports on an inductor fabrication method capable to deliver high quality factor (Q) and high self-resonance frequency (SRF) devices using quartz insulating substrates and thick high-conductivity copper lines. Inductors are key devices in RF circuits that, when fabricated on traditional semiconductor substrates, suffer from poor RF performances due to thin metallization and substrate related losses. Many previous works revealed that RF performances are strongly dependent on the limited metallization thickness and on the conductivity of the substrate. In this paper we demonstrate a new fabrication process to improve the Q factor of spiral inductors by patterning thick high conductive metal layers directly in a dielectric substrate. Moreover, we develop and validate accurate equivalent circuit modeling and parameter extraction for the characterization of the fabricated device

High quality factor copper inductors integrated in deep dry-etched quartz substrates

This paper reports on an inductor fabrication method capable to deliver high quality factor (Q) and high self-resonance frequency (SRF) devices using quartz insulating substrates and thick high-conductivity copper lines. Inductors are key devices in RF circuits that, when fabricated on traditional semiconductor substrates, suffer from poor RF performances due to thin metallization and substrate related losses. Many previous works revealed that RF performances are strongly dependent on the limited metallization thickness and on the conductivity of the substrate. In this paper we demonstrate a new fabrication process to improve the Q factor of spiral inductors by patterning thick high conductive metal layers directly in a dielectric substrate. Moreover, we develop and validate accurate equivalent circuit modeling and parameter extraction for the characterization of the fabricated device

Petrological Insights into Shifts in Eruptive Styles at Volcán Llaima (Chile)

Tephra and lava pairs from two summit eruptions (ad 2008 and 1957) and a flank fissure eruption (∼ ad 1850) are compared in terms of textures, phenocryst contents, and mineral zoning patterns to shed light on processes responsible for the shifts in eruption style during typical eruptive episodes at Volcán Llaima (Andean Southern Volcanic Zone, Chile). The mineralogy and whole-rock compositions of tephra and lavas are similar within eruptive episodes, suggesting a common magma reservoir for Strombolian paroxysms and lava effusion. The zoning profiles and textures of plagioclase record successive and discrete intrusions of volatile-rich mafic magma accompanied by mixing of these recharge magmas with the resident basaltic-andesitic crystal mushes that are commonly present at shallow levels in the Llaima system. Each recharge event destabilizes the plagioclase in equilibrium with the resident crystal mush melt and stabilizes relatively An-rich plagioclase, as is recorded by the numerous resorption zones. Lavas typically have ∼15-20 vol. % more phenocrysts than the tephra. Differences in plagioclase and olivine textures and zoning, combined with different phenocryst contents, indicate that a greater volume fraction of recharge magma is present in the explosively erupted magma than in subsequent effusively erupted magma. We propose that Strombolian paroxysms at Volcán Llaima are triggered by interactions with large volume fractions of recharge magma, which decrease the bulk viscosity and increase the volatile contents of the erupted magmas, leading to the conditions required for the fragmentation of basaltic-andesite. Lava effusion ensues from reduced interactions with the recharge magma, after it has partially degassed and crystallized, thereby impeding rapid ascent. This process could be operating at other steady-state basaltic volcanoes, wherein shallow reservoirs are periodically refilled by fresh, volatile-rich magma

Heterogeneous grain growth and vertical mass transfer within a snow layer under a temperature gradient

Inside a snow cover, metamorphism plays a key role in snow evolution at different scales. This study focuses on the impact of temperature gradient metamorphism on a snow layer in its vertical extent. To this end, two cold-laboratory experiments were conducted to monitor a snow layer evolving under a temperature gradient of 100 K m−1 using X-ray tomography and environmental sensors. The first experiment shows that snow evolves differently in the vertical: in the end, coarser depth hoar is found in the center part of the layer, with covariance lengths about 50 % higher compared to the top and bottom areas. We show that this heterogeneous grain growth could be related to the temperature profile, to the associated crystal growth regimes, and to the local vapor supersaturation. In the second experiment, a non-disturbing sampling method was applied to enable a precise observation of the basal mass transfer in the case of dry boundary conditions. An air gap, characterized by a sharp drop in density, developed at the base and reached more than 3 mm after a month. The two reported phenomena, heterogeneous grain growth and basal mass loss, create heterogeneities in snow – in terms of density, grain and pore size, and ice morphology – from an initial homogeneous layer. Finally, we report the formation of hard depth hoar associated with an increase in specific surface area (SSA) observed in the second experiment with higher initial density. These microscale effects may strongly impact the snowpack behavior, e.g., for snow transport processes or snow mechanics.</p

MEK inhibitors cobimetinib and trametinib, regressed a gemcitabine-resistant pancreatic-cancer patient-derived orthotopic xenograft (PDOX).

A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p.o., 14 consecutive days, n = 7); carfilzomib (2 mg/kg, i.v., twice a week for 2 weeks, n = 7); bortezomib (1 mg/kg, i.v., twice a week for 2 weeks, n = 7); MK-1775 (20 mg/kg, p.o., 14 consecutive days, n = 7); BEZ-235 (45 mg/kg, p.o., 14 consecutive days, n = 7); vorinostat (50 mg/kg, i.p., 14 consecutive days, n = 7). Only the MEK inhibitors, cobimetinib and trametinib, regressed tumor growth, and they were more significantly effective than other therapies (p &lt; 0.0001, respectively), thereby demonstrating the precision of the PDOX models of PDAC and its potential for individualizing pancreatic-cancer therapy

Structure of the specific combining ability between two species of Eucalyptus. II. A clustering approach and a multiplicative model

International audienceThe Eucalyptus breeding program of URPPI (a partnership between CIRAD-Fore t, Centre National de la Recherche Forestie re du Congo, and Unite dÕAforestation Industrielle du Congo) consists of a re- ciprocal recurrent selection scheme developed in the Congo between the two species Eucalyptus urophylla and Eucalyptus grandis. Two approaches are proposed in order to model and predict the speciÞc combining ability (SCA) between these species. The clustering ap- proach uses a simultaneous clustering procedure of the two species based on SCA and reveals heterotic groups coherent with the geographical origins of E. urophylla genotypes. The second approach uses a multiplicative model to partition the SCA into three multiplicative terms explaining 95% of the interactio

EXAFS Debye-Waller factors issued from Car-Parrinello molecular dynamics: Application to the fit of oxaliplatin and derivatives

One of the main pitfalls in EXAFS fitting is correlation among parameters, which can lead to unreli- able fits. The use of theoretical Debye-Waller factors (DWs) is a promising way to reduce the number of fitted parameters. When working with molecular dynamics, it is not only possible to evaluate DWs from the statistical distributions issued from the trajectory but also to estimate the distribution an- harmonicity, and to compute simulated average EXAFS spectra that can be fitted as experimental ones, in order to assess the ability of EXAFS fitting to recover information on DWs, as well as other structural and spectroscopical parameters. The case studied is oxaliplatin, a third generation anticancer drug. The structural information and the simulated average spectra were derived from a Car-Parrinello molecular dynamics (CP-MD) trajectory of a compound closely related to oxaliplatin. We present the DWs issued from this simulation and their use, by taking their theoretical absolute values (no DW fitted) or their ratios (one DW fitted). In this second approach, the fit of oxaliplatin experimental spectra leads to DWs values very close to the theoretical ones. This shows that the CP-MD trajectory provides a good representation of the distance distributions for oxaliplatin. Trans- ferability of oxaliplatin DWs, for all relevant single and multiple scattering paths, to closely related compounds is proven for the case of bis(oxalato)platinum(II) and bis(ethylene diamine)platinum(II).Ministerio de Ciencia e Innovación CTQ2011-25932Junta de Andalucía P06-FQM-0148