Dissipative processes in superfluid quark matter

We present some results about dissipative processes in fermionic superfluids that are relevant for compact stars. At sufficiently low temperatures the transport properties of a superfluid are dominated by phonons. We report the values of the bulk viscosity, shear viscosity and thermal conductivity of phonons in quark matter at extremely high density and low temperature. Then, we present a new dissipative mechanism that can operate in compact stars and that is named "rocket term". The effect of this dissipative mechanism on superfluid r-mode oscillations is sketched.Comment: 6 pages, 1 figure. Prepared for QCD@work 2010 - International Workshop on QCD - Theory and Experiment, 20-23 June 2010, Martina Franca - Valle d'Itria - Ital

On-line product quality and process failure monitoring in freeze-drying of pharmaceutical products

This is an Author's Accepted Manuscript of Domenico Colucci, José M. Prats-Montalbán, Alberto Ferrer & Davide Fissore (2021) On-line product quality and process failure monitoring in freeze-drying of pharmaceutical products, Drying Technology, 39:2, 134-147, DOI: 10.1080/07373937.2019.1614949 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/07373937.2019.1614949[EN] In this work the information provided by a noninvasive imaging sensor was used to develop two algorithms for real time fault detection and product quality monitoring during the Vacuum Freeze-Drying of single dose pharmaceuticals. Two algorithms based on multivariate statistical techniques, namely Principal Component Analysis and Partial Least Square Regression, were developed and compared. Five batches obtained under Normal Operating Conditions were used to train a reference model of the process; the classification abilities of these algorithms were tested on five more batches simulating different kind of faults. Good classification performances have been obtained with both algorithms. Coupling the information obtained from an infrared camera with that of other variables obtained from the PLC of the equipment, and from the textural analysis performed on the RGB images of the product, strongly improves the performances of the algorithms. The proposed algorithms can account for the heterogeneity of the batch and aim to reduce the off-specification products.This research work was partially supported by the Spanish Ministry of Economy, Industry and Competitiveness under the project DPI2017-82896-C2-1-R.Colucci, D.; Prats-Montalbán, JM.; Ferrer, A.; Fissore, D. (2021). On-line product quality and process failure monitoring in freeze-drying of pharmaceutical products. 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Infrared Thermography for Monitoring of Freeze-Drying Processes: Instrumental Developments and Preliminary Results. Journal of Pharmaceutical Sciences, 103(7), 2088-2097. doi:10.1002/jps.24017Van Bockstal, P.-J., Corver, J., De Meyer, L., Vervaet, C., & De Beer, T. (2018). Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring during Continuous Freeze-Drying of Unit Doses. Analytical Chemistry, 90(22), 13591-13599. doi:10.1021/acs.analchem.8b03788Lietta, E., Colucci, D., Distefano, G., & Fissore, D. (2019). On the Use of Infrared Thermography for Monitoring a Vial Freeze-Drying Process. Journal of Pharmaceutical Sciences, 108(1), 391-398. doi:10.1016/j.xphs.2018.07.025Velardi, S. A., & Barresi, A. A. (2008). Development of simplified models for the freeze-drying process and investigation of the optimal operating conditions. Chemical Engineering Research and Design, 86(1), 9-22. doi:10.1016/j.cherd.2007.10.007Pearson, K. (1901). LIII. 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Industrial & Engineering Chemistry Research, 57(15), 5338-5350. doi:10.1021/acs.iecr.7b04911Bharati, M. H., & MacGregor, J. F. (1998). Multivariate Image Analysis for Real-Time Process Monitoring and Control. Industrial & Engineering Chemistry Research, 37(12), 4715-4724. doi:10.1021/ie980334lPrats-Montalbán, J. M., de Juan, A., & Ferrer, A. (2011). Multivariate image analysis: A review with applications. Chemometrics and Intelligent Laboratory Systems, 107(1), 1-23. doi:10.1016/j.chemolab.2011.03.002Duchesne, C., Liu, J. J., & MacGregor, J. F. (2012). Multivariate image analysis in the process industries: A review. Chemometrics and Intelligent Laboratory Systems, 117, 116-128. doi:10.1016/j.chemolab.2012.04.003Colucci, D., Prats-Montalbán, J. M., Fissore, D., & Ferrer, A. (2019). Application of multivariate image analysis for on-line monitoring of a freeze-drying process for pharmaceutical products in vials. 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Application of multivariate image analysis for on-line monitoring of a freeze-drying process for pharmaceutical products in vials

[EN] A new Process Analytical Technology (PAT) has been developed and tested for on-line process monitoring of a vacuum freeze-drying process. The sensor uses an infrared camera to obtain thermal images of the ongoing process and multivariate image analysis (MIA) to extract the information. A reference model was built and different kind of anomalous events were simulated to test the capacity of the system to promptly identify them. Two different data structures and two different algorithms for the imputation of the missing information have been tested and compared. Results show that the MIA-based PAT system is able to efficiently detect on-line undesired events occurring during the vacuum freeze-drying process.The authors would like to acknowledge Elena Lietta for her support in the experimental investigation. This research work was partially supported by the Spanish Ministry of Economy, Industry and Competitiveness under the project DPI2017-82896-C2-1-R.Colucci, D.; Prats-Montalbán, JM.; Fisore, D.; Ferrer, A. (2019). Application of multivariate image analysis for on-line monitoring of a freeze-drying process for pharmaceutical products in vials. Chemometrics and Intelligent Laboratory Systems. 187:19-27. https://doi.org/10.1016/j.chemolab.2019.02.004S192718

R-mode oscillations and rocket effect in rotating superfluid neutron stars. I. Formalism

We derive the hydrodynamical equations of r-mode oscillations in neutron stars in presence of a novel damping mechanism related to particle number changing processes. The change in the number densities of the various species leads to new dissipative terms in the equations which are responsible of the {\it rocket effect}. We employ a two-fluid model, with one fluid consisting of the charged components, while the second fluid consists of superfluid neutrons. We consider two different kind of r-mode oscillations, one associated with comoving displacements, and the second one associated with countermoving, out of phase, displacements.Comment: 10 page

Dry-aged beef steaks: effect of dietary supplementation with Pinus taeda hydrolyzed lignin on sensory profile, colorimetric and oxidative stability

Flavor is one of the main factors involved in consumer meat-purchasing decision and use of natural antioxidants in animal feeding had a great appeal for consumers. The aim of this trial is to evaluate the effect of Pinus taeda hydrolyzed lignin (PTHL) feed addition on oxidative stability, volatile compounds characteristics, and sensory attributes of 35 days dry-aged beef steaks. Forty steer six months old were randomly divided into a control group (CON; n = 20) and an experimental group (PTHL; n = 20). Both groups were fed ad libitum for 120 days with the same TMR and only the PTHL group received PTHL supplement. Samples of LT muscle were removed from carcasses and dry aged for 35 days at 2 °C, 82% of humidity, and 0.4 m/s of ventilation and then analyzed. Meat of CON group showed lower yellowness (p < 0.01) and higher TBARS (p < 0.01) values. Moreover, CON meat showed higher volatile aldehydes and lower sulfur compounds (p < 0.01), with higher unpleasant odor (p < 0.05) and meaty odor (p < 0.01) score revealed by sensory assessors. PTHL inclusion in beef diet delayed the oxidative mechanisms in 35 days dry-aged steaks, resulting in an improved colorimetric, volatolomic, and sensory profile

DNaseI Hypersensitivity and Ultraconservation Reveal Novel, Interdependent Long-Range Enhancers at the Complex Pax6 Cis-Regulatory Region

The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6(Sey/Sey) mice

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

VSSP-activated macrophages mediate senescence and tumor inhibition in a preclinical model of advanced prostate cancer

: Androgen deprivation therapy (ADT) is a standard therapy for prostate cancer (PCa). Though disseminated disease is initially sensitive to ADT, an important fraction of the patients progresses to castration-resistant prostate cancer (CRPC). For this reason, the identification of novel effective therapies for treating CRPC is needed. Immunotherapeutic strategies focused on macrophages as antitumor effectors, directly enhancing their tumoricidal potential at the tumor microenvironment or their adoptive transfer after ex vivo activation, have arisen as promising therapies in several cancer types. Despite several approaches centered on the activation of tumor-associated macrophages (TAMs) in PCa are under investigation, to date there is no evidence of clinical benefit in patients. In addition, the evidence of the effectiveness of macrophage adoptive transfer on PCa is poor. Here we find that VSSP, an immunomodulator of the myeloid system, decreases TAMs and inhibits prostatic tumor growth when administered to castrated Pten-deficient prostate tumor-bearing mice. In mice bearing castration-resistant Ptenpc-/-; Trp53pc-/- tumors, VSSP administration showed no effect. Nevertheless, adoptive transfer of macrophages activated ex vivo with VSSP inhibited Ptenpc-/-; Trp53pc-/- tumor growth through reduction of angiogenesis and tumor cell proliferation and induction of senescence. Taken together, our results highlight the rationale of exploiting macrophage functional programming as a promising strategy for CRPC therapy, with particular emphasis on ex vivo-activated proinflammatory macrophage adoptive transfer. Video abstract

Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer

Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that senescent tumor cells rely on the anti-apoptotic gene Mcl-1 for their survival. Mcl-1 is upregulated in senescent tumor cells, including cells expressing low levels of Bcl-2, an established target for senolytic therapy. While treatment with the Bcl-2 inhibitor Navitoclax results in the reduction of metastases in tumor bearing mice, treatment with the Mcl-1 inhibitor S63845 leads to complete elimination of senescent tumor cells and metastases. These findings provide insights on the mechanism by which senescent tumor cells survive and reveal a vulnerability that can be exploited for cancer therapy.ISSN:2041-172