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This article deals with flow regime (FR) identification and gas holdup prediction in a bubble column (BC) of 0.1 m inner diameter operated with aqueous solutions of 2-pentanol at ambient conditions. The hydrodynamic behavior of mixtures of deionized water (DW) and 2-pentanol with different volume concentrations (0.5-2.0 vol. %) was examined. A new identification method based on an error analysis was proposed. By means of the local well-pronounced minima in the new dimensionless error ratio, three transition velocities (at 0.044, 0.055 and 0.077 m/s) were reliably identified. The first critical velocity was fully predictable by an empirical correlation. Overall gas holdups were also successfully predicted in both homogeneous and transition FRs of BC operation. One of the main empirical correlations was modified in order to predict the overall gas holdups recorded in different aqueous solutions of 2-pentanol. Only one parameter was fitted for every mixture investigated. The average relative error was very low.

The design of multiphase reaction and separation processes, such as for example catalytic hydrogenations, distillation and absorption processes, extraction processes, wastewater treatment, and many more, require a profound understanding of the multiphase fluid dynamics inside reactors and contactors. As Computational Multiphase Fluid Dynamics is still not fully mature to simulate complex two-phase and three-phase flow with overlaying heat and mass transfer as well as chemical reaction with sufficient accuracy there is a constant need for advanced experimental and measurement techniques; may it be for the provision of operational, design or thermodynamic parameters or for the validation of codes. In this talk we report on three different novel measurement techniques for this purpose. The presentation shall exemplarily demonstrate how advanced measurement and imaging techniques can be used to study opaque two-phase and three-phase flows in lab environment and potentially also in the field. We report on a) the use of ultrafast X-ray tomography and wire-mesh sensors for the study of reactive bubbly flow in a bubble column, b) the application of a large flow profiler in studying two-phase flow on a distillation column tray, and c) a method to obtain gas dispersion parameters in gas-liquid contactors using modulated gas flow.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

Background: Stage I epithelial ovarian cancer (EOC) encompasses five histologically different subtypes of tumors confined to the ovaries with a generally favorable prognosis. Despite the intrinsic heterogeneity, all stage I EOCs are treated with complete resection and adjuvant therapy in most of the cases. Owing to the lack of robust prognostic markers, this often leads to overtreatment. Therefore, a better molecular characterization of stage I EOCs could improve the assessment of the risk of relapse and the refinement of optimal treatment options. Materials and methods: 205 stage I EOCs tumor biopsies with a median follow-up of eight years were gathered from two independent Italian tumor tissue collections, and the genome distribution of somatic copy number alterations (SCNAs) was investigated by shallow whole genome sequencing (sWGS) approach. Results: Despite the variability in SCNAs distribution both across and within the histotypes, we were able to define three common genomic instability patterns, namely stable, unstable, and highly unstable. These patterns were based on the percentage of the genome affected by SCNAs and on their length. The genomic instability pattern was strongly predictive of patients’ prognosis also with multivariate models including currently used clinico-pathological variables. Conclusions: The results obtained in this study support the idea that novel molecular markers, in this case genomic instability patterns, can anticipate the behavior of stage I EOC regardless of tumor subtype and provide valuable prognostic information. Thus, it might be propitious to extend the study of these genomic instability patterns to improve rational management of this disease.

The uniformity of the gas distribution in bubble columns strongly depends on the gas sparger design. For example, not all holes of a perforated plate sparger with relatively high fractional free area are active at the same time. This is true especially at low gas flow rates. Consequently, the random activation of the holes causes gas maldistribution in the radial as well as in the axial directions. Contrary, needle spargers provide rather uniform distribution at the same operating conditions. Since dispersion phenomena depend on the gas holdup gradient, the gas maldistribution is expected to affect the dispersion. Surprisingly, only few publications address the possible influence of the sparger on gas dispersion. An exception is the study of Kölbel [1]. They measured the axial gas dispersion coefficient in a bubble column using a monolithic type of sparger. Here, the obtained gas dispersion coefficients run through a minimum while increasing the gas superficial velocity. Contrary, literature frequently reports axial dispersion coefficients that increase monotonously with the gas superficial velocity (e.g., [2], [3]). The objective of the present study was to resolve this discrepancy. Experiments were performed in a 100 mm ID column using three different spargers, namely: a perforated plate sparger with (a) 50 holes of 0.6 mm diameter corresponding to a fractional free area of 0.18%, (b) with 38 holes of 1.0 mm and 12 holes of 1.5 mm corresponding to a fractional free area of 0.66%, and (c) a needle sparger made of 31 needles with 0.8 mm inner diameter each. Axial dispersion was experimentally measured applying the gas flow modulation technique, which is a tracer-free approach explained by Marchini et al. [4, 5]. The results showed that the above mentioned minimum found by Kölbel [1] is reproducible for spargers with high fractional free area. Figure 1 reports the determined axial dispersion coefficients as a function of the gas superficial velocity for all considere

Dispersion phenomena significantly influence the residence time of the fluid phases in gas-liquid contactors and, thus, their yield. With the axial dispersion model (ADM), the effect of dispersion is considered during the process design. However, this requires a reliable quantification of the axial dispersion coefficients. A novel non-intrusive approach to determine the axial gas dispersion coefficient in bubble columns was recently pronounced by Hampel [1], called gas flow modulation technique (GFM). This approach is based on an imposed marginal sinusoidal modulation on the constant gas inlet flow. This leads to a modulation of the gas holdup in the bubble column, called holdup wave. Along the column axial direction, the gas dispersion damps the rising holdup wave in amplitude and shifts its phase. Amplitude damping and phase shift can be non-invasively determined, e.g., using gamma-ray densitometry to relate it to the value of the axial dispersion coefficient using the ADM. Figure 1 shows the principle of GFM and a simplified scheme of the experimental setup. Döß et al. [2] applied the GFM to bubble columns for the first time, although only for a narrow range of operating conditions in a 100 mm ID bubble column. The present study proves the applicability of the GFM to larger columns and for a wider range of gas superficial velocities and liquid properties. Experiments were performed in columns of 100, 150 and 330 mm ID at gas superficial velocities ranging from 17 to 47 mm/s. Air was used as the gas phase. Water, aqueous solutions with 2% wt. ethanol and 30% wt. glycerin were used as the liquid phase. This study, together with the uncertainty analyses recently performed by Marchini et al. [3, 4], qualifies the GFM as a viable non-invasive alternative to traditional tracer studies, for measuring the axial gas dispersion coefficient in bubble columns.

Commonly, structured packings are operated in film flow. In this case, the entire surface of the packing is completely covered by the liquid to make maximum use of the available surface area on the elements. However, perfect wetting of the packing is usually difficult to achieve. Moreover, when film flow is targeted, the interfacial area cannot exceed the geometric surface area provided by the packing. Thus, other flow configurations must be alternatively considered increasing the interfacial area potentially available for mass transfer. Droplet flow is one way to achieve this goal. Considering the extreme case of a spherical droplet in contact with the packing on a single infinitesimally small point. For equal volume of droplet and film, the interfacial area in this case is almost five times higher compared to film flow. The developed work is meant to characterize flow structures alternative to the classical film flow over structured packings to determine potential improvement in mass transfer performances. To achieve changes in the flow structure, the surface of the packings elements was modified. In particular, surface treatments were used to improve the hydrophobic properties of the surface. In this way, the formation of liquid droplets on the surface was promoted. A preliminary literature review allowed the selection of self-assembled monolayers (SAMs) as surface modification methods due to the simplicity of performing the treatment. A characterization campaign of the modified surfaces was carried out. Smooth metal sheets specimens of which the packings are made were used for the investigation of contact angles via optical techniques. Behavior of obtained droplets and rivulets as well as their tendency to coalesce were also analyzed. Subsequently, the mass transfer performance of the modified packings was compared with that of the standard packings by air-led stripping of isobutyl acetate from an aqueous solution. A model was developed in this work for droplet

The accurate identification of the transition velocities Utrans in bubble columns (BCs) is very important for their effective design, operation and scale-up. In this work, a novel parameter (new hybrid index (NHI)) has been developed and successfully applied to gas holdup and pressure fluctuations recorded in various BCs operated with water and aqueous solutions of alcohols (ethanol and iso-propanol). The first Utrans has been identified on the basis of a well-pronounced local NHI minimum, whereas the second Utrans has been distinguished by the point, from which the NHI profile levels off. It has been concluded that the main Utrans depend on the type of gas-liquid system and sparger used. A set of several Utrans has been reported.

The gas flow modulation technique (GFM) is a novel non-invasive approach for measuring the axial gas dispersion coefficient in bubble columns. The approach overcomes the limitations of traditional tracer-based techniques, qualifying it as a promising candidate for measurements in an industrial setting. The current work elaborates systematic guidelines for selecting the experimental parameters for the GFM. These guidelines are crucial for its successful application. In addition, a novel approach is proposed for confidently extracting the values and the uncertainty limits of the axial gas dispersion coefficient. Afterwards, we show the application of these guidelines in the frame of a case study that serves the purpose to illustrate their application and to demonstrate their usefulness.

Weeping is known to significantly reduce tray and point efficiencies in distillation tray columns. Recently, an analytical method was developed to simultaneously determine tray and point efficiencies in case of weeping. The approach, however, is based on the assumption of uniformly distributed weeping, while experimental studies generally reveal non-uniform weeping. In this study, the effect of several non-homogeneous weeping distributions on tray and point efficiencies is evaluated. In particular, state-of-the-art non-uniform weeping distributions, which have low spatial resolution, have been compared with arbitrarily assumed high resolution weeping distributions. The results illustrate that accurately quantifying the weeping distribution on the tray, allows to significantly improve the accuracy of calculated tray and point efficiencies.

The gas flow modulation technique is a recently proposed approach for measuring the axial gas dispersion coefficient in bubble columns. This study presents a quantitative analysis of the experimental uncertainty associated with gamma-ray densitometry and ensemble-averaging of the data. The considered uncertainty sources are the statistics of the photon counting process, a mismatch between the modelled and the real radiation propagation due to the spatial extent of the detector, and a potential mismatch between modulation and sampling frequencies. The analysis is based on a numerical gamma-ray propagation model and a Monte Carlo approach to account for statistical uncertainty. The proposed algorithm supports the selection of an optimal total scanning time based on detector size, modulation parameters, involved fluids and column and source parameters. The analysis reveals that a mismatch between the modulation and sampling frequencies is most critical while the impact of the other considered uncertainty sources is rather marginal.

The gas flow modulation technique (GFM) is a recently proposed approach for measuring the axial gas dispersion coefficient in bubble columns. It bases on a time-resolved measurement of the modulated gas holdup at different axial positions in the column and a subsequent calculation of the axial dispersion coefficient from amplitude damping and the phase lag of a gas holdup wave. In recent studies holdup has been measured with gamma-ray densitometry, which is advantageous in terms of measurement accuracy. However, the application of radiative measurement techniques in industrial settings poses several logistical and safety challenges. This study investigates the potential of non-radiative measurement techniques in the context of GFM. In particular, differential pressure sensors, conductivity needle probes and optical probes are considered. The results obtained using these alternative techniques are compared with gamma-ray measurements. The comparison qualifies differential pressure sensors as a particular viable alternative to gamma-ray densitometry.

The gas flow modulation technique is a recently proposed approach for measuring the axial gas dispersion coefficient in bubble columns. The approach uses a marginal sinusoidal distrubance on the gas inlet flow and relates the propagation of such disturbance in the column's axial direction to the axial gas dispersion coefficient. The approach requires to measure sinusoidally changing gas holdup in time with high accuracy. The presented data set was used to experimentally validate a newly developed simualtion algorithm for predicting the effect of various uncertainty sources on the measured holdup wave. The algorithm is able to predict the uncertianty related to the applycation of gamma-ray densitometry and of the data ensable-averaging approach. Experiments were preformed using an elliptical rotating disc able to mimik a controlled "material holdup wave", similar to the gas holdup wave measured in gas flow modulation.

The data were used to exemplify the application of Gas Flow Modulation (GFM) for measuring the axial gas dispersion coefficient in bubble column reactors operated at ambient conditions. For more details, please refer to the atteched PDF.

Collected data refer to gas flow modulation measurements in a D=100 mm bubble column. The axial holdup wave is determined at three axial positions using different sensing stategies (gamma-ray densitometry, differential pressure sensors, transmittance optical probes and conductivity needle probes). Average gas holdup as well as amplitude damping and phase-shift have been determined at three different gas flow rates in the homogeneous regime. A description of the experimental setup is provided in the file "Experimental_setup.pdf". An overview of the performed experiments is provided in the Excel file "DataDescription.xlsx"

isomiRs, the sequence-variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In this study we explored for the first time the expression of isomiRs across different stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multi-centric retrospective cohort of tumor biopsies (n=215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs. Among them, 42 isomiRs showed a clear histotype specific pattern, confirming our previously identified miRNA markers (miR192/194 and miR30a-3p/5p for mucinous and clear cell subtypes respectively) and uncovering new biomarkers for all the five subtypes. Using integrative models, we found that the 38% of these miRNA expression alterations is the result of copy number variations while the 17% of differential transcriptional activities. Our work represents the first attempt to characterize isomiRs expression in stage I EOC within and across subtypes and to contextualize their alterations in the framework of the large genomic heterogeneity of this tumor.

Myxoid liposarcoma (MLPS) is a rare soft-tissue sarcoma characterised by the expression of FUS-DDIT3 chimera. Trabectedin has shown significant clinical anti-tumour activity against MLPS. To characterise the molecular mechanism of trabectedin sensitivity and of resistance against it, we integrated genomic and transcriptomic data from treated mice bearing ML017 or ML017/ET, two patient-derived MLPS xenograft models, sensitive to and resistant against trabectedin, respectively. Longitudinal RNA-Seq analysis of ML017 showed that trabectedin acts mainly as a transcriptional regulator: 15 days after the third dose trabectedin modulates the transcription of 4883 genes involved in processes that sustain adipocyte differentiation. No such differences were observed in ML017/ET. Genomic analysis showed that prolonged treatment causes losses in 4p15.2, 4p16.3 and 17q21.3 cytobands leading to acquired-resistance against the drug. The results dissect the complex mechanism of action of trabectedin and provide the basis for novel combinatorial approaches for the treatment of MLPS that could overcome drug-resistance.

Stage III/IV epithelial ovarian cancer (EOC) is a systemic disease. The clonal relationship among different tumor lesions at diagnosis (spatial heterogeneity) and how tumor clonal architecture evolves over time (temporal heterogeneity) have not yet been defined. Such knowledge would help to develop new target-based strategies, as biomarkers which can adjudge the success of therapeutic intervention should be independent of spatial and temporal heterogeneity. The work described in this paper addresses spatial and temporal heterogeneity in a cohort of 71 tumor biopsies using targeted NGS technology. These samples were taken from twelve high grade serous (HGS) and seven non HSG-EOC, both at the time of primary surgery when the tumor was naïve to chemotherapy and after chemotherapy. Matched tumor lesions growing in the ovary or at other anatomical sites show very different mutational landscapes with branched tumor evolution. Mutations in ATM, ATR,TGFB3,VCAM1 and COL3A1 genes were shared across all lesions. BRCA1 and BRCA2 genes were frequently mutated in synchronous lesions of non HGS-EOC. Relapsed disease seems to originate from resistant clones originally present at the time of primary surgery rather than from resistance acquired de novo during platinum based therapy. Overall the work suggests that EOC continues to evolve. More detailed mapping of genetic lesions is necessary to improve therapeutic strategies.

The ICARUS T600 liquid argon (LAr) time projection chamber (TPC) underwent a major overhaul at CERN in 2016-2017 to prepare for the operation at FNAL in the Short Baseline Neutrino (SBN) program. This included a major upgrade of the photo-multiplier system and of the TPC wire read-out electronics. The full TPC wire read-out electronics together with the new wire biasing and interconnection scheme are described. The design of a new signal feed-through flange is also a fundamental piece of this overhaul whose major feature is the integration of all electronics components onto the signal flange. Initial functionality tests of the full TPC electronics chain installed in the T600 detector at FNAL are also described.

Importance: The low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease. Objective: To determine whether the presence of the clonal pathogenic TP53 variant detected in matched primary tumor biopsies can be identified in DNA purified from Papanicolaou test samples collected from women with HGS-EOC years before the diagnosis. Design, Setting, and Participants: This cohort study was conducted among a single-center cohort of women with histologically confirmed diagnosis of HGS-EOC recruited at San Gerardo Hospital, Monza, Italy, from October 15, 2015, to January 4, 2019. Serial dilutions of DNA derived from tumor samples and DNA extracted from healthy women's Papanicolaou test samples were analyzed to define the sensitivity and specificity of droplet digital polymerase chain reaction assays designed to detect the TP53 variants identified in tumors. All available brush-based Papanicolaou test slides performed up to 6 years before diagnosis were investigated at the Mario Negri Institute, Milano, Italy. Data were analyzed from October 2018 to December 2019. Main Outcomes and Measures: The presence of tumor pathogenic TP53 variants was assessed by the droplet digital polymerase chain reaction approach in DNA purified from Papanicolaou test samples obtained from the same patients before diagnosis during cervical cancer screenings. Results: Among 17 included patients (median [interquartile range] age at diagnosis, 60 [53-69] years), Papanicolaou tests withdrawn before diagnosis presented tumor-matched TP53 variants in 11 patients (64%). In 2 patients for whom longitudinal Papanicolaou tests were available, including 1 patient with Papanicolaou tests from 25 and 49 months before diagnosis and 1 patient with Papanicolaou tests from 27 and 68 months before diagnosis, the TP53 clonal variant was detected at all

Bubble columns are industrial equipment used for promoting the contact between the gas and the liquid phase. In the column, the gas phase rises in form of bubbles in a pool of liquid. The fraction of the column’s volume occupied by the gas is called gas holdup. Bubble column applications include bioreactors, production of food and beverage as well as of crucial chemicals. The Axial Dispersion Model is the most accepted model for describing the gas flow in bubble columns. In this model, all phenomena deviating from plug-flow conditions are combined and indicated as dispersion. Knowledge of the axial dispersion coefficient is crucial for designing bubble column reactors. This study provides a new non-invasive approach for measuring axial gas dispersion coefficients in bubble column reactors and the application of the new approach at different operating conditions.

The knowledge of the tray efficiency value is crucial for a correct design of tray columns [1]. In the last decades, several models have been developed for predicting the tray efficiency value, given the point efficiency. Validation of these models requires determining both tray and point efficiency experimentally. The tray efficiencies are mostly determined by sampling the incoming and exiting streams of liquid and gas over the tray. On the contrary, experimentally determining point efficiencies is technically challenging and thus, their value is often derived from correlations or small-scale experiments (e.g. Oldershaw columns). Only few studies on the experimental determination of point efficiencies on large-scale distillation trays exist (e.g. [2], [3]). The physical systems used in these studies pose several technical restrictions and safety concerns. For these reasons, a setup designed ad hoc for point efficiency studies is mostly needed. Recently Marchini et al. [4] proposed the stripping of isobutyl acetate from an aqueous solution using air as a physical system,which was proven to offer several advantages over the traditional ones and to be readily integrated into existing cold fluid air/water mockups without any major modification. The authors also showed how the tray-to-point efficiency ratio can be determined based on the liquid concentration distribution on the tray, accounting for liquid mixing phenomena in both the axial and transversal directions. In this study, the tray and point efficiency values of an 800 mm dia. distillation sieve tray were determined at different gas and liquid flow rates by sampling the liquid at different deck locations for subsequent UV-spectroscopy, obtaining the liquid concentration distribution (Figure 1).

This study proposes a novel non-intrusive approach for measuring axial liquid dispersion coefficients in trickle-bed reactors. The approach is based on the flow modulation technique (FMT), which replaces traditional tracer substance injections with a marginal sinusoidal modulation superimposed on the liquid inlet flow. The modulation causes a sinusoidal variation of the liquid holdup in time, i.e. liquid holdup wave. Downstream the inlet, the holdup wave gets damped in amplitude and shifted in phase due to dispersion. Amplitude damping and phase shift are experimentally measured and related to the value of the axial dispersion coefficient using a one-dimensional dispersion model. Recently, the flow modulation has been applied to investigate the axial gas dispersion coefficient in bubble columns. In this study, the approach is adapted to measure liquid dispersion in co-current gas-liquid trickle-bed reactors. In addition, the consequences of the assumptions requested by the axial dispersion model are discussed. Furthermore, the impact of the experimental flow modulation parameters on sensitivity and uncertainty of the dispersion coefficient is analyzed.

The gas flow modulation technique has recently been proposed as a novel method for determining the axial gas dispersion coefficient in bubble columns. The approach is based on a marginal sinusoidal modulation of the gas inlet flow rate that acts as a virtual tracer. Axial gas dispersion is then inversely calculated from amplitude damping and phase shift via an analytical solution of the axial dispersion model. The proposed study provides an analysis of the inherent uncertainties related to the assumptions of constant axial gas dispersion coefficient and bubble rise velocity, which are crucial for implementing the method. Besides, the sensitivity of the approach is assessed as function of the modulation parameters, the bubble rise velocity and the axial gas dispersion coefficient. Eventually, the possibility of tailoring the modulation parameters depending on the expected value of the axial gas dispersion coefficient to increase the sensitivity and to reduce the uncertainty is also assessed.

We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal window to acquire through plasma sample analysis a real-time picture of those emerging molecular lesions that will drive and sustain the growth of relapsed disease and ultimately will confer resistance. In this proof of principle study, the same genomic libraries obtained at the diagnosis (T0), TRm and TRc were further analyzed by targeted resequencing approach to sequence the coding region of a panel of 65 genes to provide longitudinal analysis of clonal evolution as a novel strategy to support clinical decisions for the second-line treatment. Experiments were performed on plasma and tumor tissues withdrawn on a selection of previously analyzed cohorts of cases (i.e., 33 matched primary and synchronous lesions and 43 plasma samples from 18 patients). At T0, the median concordance of mutations shared by each tumor tissue biopsy and its matched plasma sample was 2.27%. This finding confirms the limit of a single tumor biopsy to be representative of the entire disease, while plasma analysis can recapitulate most of the main molecular lesions of the disease. A comparable scenario was observed during longitudinal analysis, where, with the exception of the TP53 gene and germline mutations in BRCA1/2 genes, no other gene shared the same locus specific gene mutation across T0, TRm and TRc time points. This high level of temporal heterogeneity has important implications for planning second-line treatment. For example, in three out of 13 cases, plasma ctDNA analysis at TRm or TRc reported acquired novel variants in the TP53BP1 gene not present at T0. In particular, patient 21564, potentially eligible for PARP-inhibitor (PARPi) treatment at the time of diagno