Applying a Digital Twin and wastewater analysis for robust validation of COVID-19 pandemic forecasts: insights from Catalonia.

Monitoring SARS-CoV-2 spread is challenging due to asymptomatic infections, numerous variants, and population behavior changes from non-pharmaceutical interventions. We developed a Digital Twin model to simulate SARS-CoV-2 evolution in Catalonia. Continuous validation ensures our model's accuracy. Our system uses Catalonia Health Service data to quantify cases, hospitalizations, and healthcare impact. These data may be under-reported due to screening policy changes. To improve our model's reliability, we incorporate data from the Catalan Surveillance Network of SARS-CoV-2 in Sewage (SARSAIGUA). This paper shows how we use sewage data in the Digital Twin validation process to identify discrepancies between model predictions and real-time data. This continuous validation approach enables us to generate long-term forecasts, gain insights into SARS-CoV-2 spread, reassess assumptions, and enhance our understanding of the pandemic's behavior in Catalonia.

Profiling wastewater characteristics in intra-urban catchments using online monitoring stations.

This study aims to investigate the differences in intra-urban catchments with different characteristics through real-time wastewater monitoring. Monitoring stations were installed in three neighbourhoods of Barcelona to measure flow, total chemical oxygen demand (COD), pH, conductivity, temperature, and bisulfide (HS-) for 1 year. Typical wastewater profiles were obtained for weekdays, weekends, and holidays in the summer and winter seasons. The results reveal differences in waking up times and evening routines, commuting behaviour during weekends and holidays, and water consumption. The pollutant profiles contribute to a better understanding of pollution generation in households and catchment activities. Flows and COD correlate well at all stations, but there are differences in conductivity and HS- at the station level. The article concludes by discussing the operational experience of the monitoring stations.

The Microwave Temperature and Humidity Profiler: Description and Preliminary Results.

This manuscript presents the Microwave Temperature and Humidity Profiler (MTHP), a dual-band spectroradiometer designed for measuring multi-incidence angle temperature and humidity atmospheric profiles from an aircraft platform. The MTHP bands are at 60 GHz for measuring the oxygen complex lines, therefore at this band, MTHP has a hyperspectral radiometer able to provide 2048 channels over an 8 GHz bandwidth, and 183 GHz for measuring water vapor, which only uses four channels since this absorption band's spectral richness is simpler. The MTHP builds upon the Microwave Temperature Profiler (MTP) with the inclusion of the hyperspectral radiometer. The instrument's design, components, and calibration methods are discussed in detail, with a focus on the three-point calibration scheme involving internal calibration loads and static air temperature readings. Preliminary results from the Technological Innovation into Iodine and GV aircraft Environmental Research (TI3GER) campaign are presented, showcasing the instrument's performance during flights across diverse geographical regions. The manuscript presents successful antenna temperature measurements at 60 GHz and 183 GHz. The hyperspectral measurements are compared with a simulated antenna temperature using the Atmospheric Radiative Transfer Simulator (ARTS) showing an agreement better than R2 > 0.88 for three of the flights analyzed. Additionally, the manuscript draws attention to potential Radio Frequency Interference (RFI) effects observed during a specific flight, underscoring the instrument's sensitivity to external interference. This is the first-ever airborne demonstration of a broadband and hyperspectral multi-incidence angle 60 GHz measurement. Future work on the MTHP could result in an improved spatial resolution of the atmospheric temperature vertical profile and, hence, help in estimating the Planetary Boundary Layer (PBL) with better accuracy. The MTHP and its hyperspectral multi-incidence angle at 60 GHz have the potential to be a valuable tool for investigating the PBL's role in atmospheric dynamics, offering insights into its impact on Earth's energy, water, and carbon cycles.

The first polarimetric GNSS-Reflectometer instrument in space improves the SMAP mission's sensitivity over densely vegetated areas.

The Soil Moisture Active Passive (SMAP) mission has dramatically benefited our knowledge of the Earth's surface processes. The SMAP mission was initially designed to provide complementary L-band measurements from a radiometer and a radar, producing geophysical measurements at a finer spatial resolution than the radiometer alone. Both instruments, sensitive to the geophysical parameters in the swath, provided independent measurements at different spatial resolutions. A few months after SMAP's launch, the radar transmitter's high-power amplifier suffered an anomaly, and the instrument could no longer return data. During recovery activities, the SMAP mission switched the radar receiver frequency facilitating the reception of Global Positioning System (GPS) signals scattered off the Earth's surface, and enabling the radar to become the first spaceborne polarimetric Global Navigation Satellite System - Reflectometry (GNSS-R) instrument. With more than 7 years of continued measurements, SMAP GNSS-R data are the most extensive existing GNSS-R dataset and the only one providing GNSS-R polarimetric measurements. We demonstrate that the SMAP polarimetric GNSS-R reflectivity, derived from Stokes parameters mathematical formulation, can enhance the radiometer data over dense vegetation areas, recovering some of the original SMAP radar capability to contribute to the science products and pioneering the first polarimetric GNSS-R mission.

The Catalan Surveillance Network of SARS-CoV-2 in Sewage: design, implementation, and performance.

Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard ( https://sarsaigua.icra.cat ). After 20 months of monitoring (July 20-March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.

BMS Derivatives C7-Linked to ß-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides.

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (ß-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time.

Computational Study of the Addition of Methanethiol to 40+ Michael Acceptors as a Model for the Bioconjugation of Cysteines.

A long series of Michael acceptors are studied computationally as potential alternatives to the maleimides that are used in most antibody-drug conjugates to link Cys of mAbs with cytotoxic drugs. The products of the reaction of methanethiol (CH3SH/MeSH, as a simple model of Cys) with N-methylated ethynesulfonamide, 2-ethynylpyridinium ion, propynamide, and methyl ethynephosphonamidate (that is, with HC≡C-EWG) are predicted by the M06-2X/6-311+G(d,p) method to be thermodynamically more stable, in relation to their precursors, than that of MeSH with N-methylmaleimide and, in general, with H2C═CH-EWG; calculations with AcCysOMe and tBuSH are also included. However, for the addition of the anion (MeS-), which is the reactive species, the order changes and N-methylated 2-vinylpyridinium ion, 2,3-butadienamide, and maleimide may give more easily the anionic adducts than several activated triple bonds; moreover, the calculated ΔG⧧ values increase following the order HC≡C-SO2NHMe, N-methylmaleimide, HC≡C-PO(OMe)NHMe, and HC≡C-CONHMe. In other words, MeS- is predicted to react more rapidly with maleimides than with ethynephosphonamidates and with propynamides, in agreement with the experimental results. New mechanistic details are disclosed regarding the advantageous use of some amides, especially of ethynesulfonamides, which, however, are more prone to double additions and exchange reactions.

Circulating Non-Esterified Fatty Acids as Biomarkers for Fat Content and Composition in Pigs.

Circulating non-esterified fatty acids (NEFA) can reflect the composition of dietary fat or adipose tissues depending on the fasting conditions. Therefore, circulating NEFA may be valuable as biomarkers for meat quality traits, such as intramuscular fat content and fatty acid composition in finishing pigs. Genetic variants that regulate lipid metabolism can also modulate the circulating NEFA. We conducted an experiment with 150 heavy Duroc pigs to evaluate fluctuations in the circulating NEFA composition due to age, fasting duration and two genetic polymorphisms, one in the leptin receptor (LEPR; rs709596309) and one in the stearoyl-CoA desaturase (SCD; rs80912566) gene. Circulating NEFA were more saturated and less monounsaturated than the subcutaneous and intramuscular adipose tissues. Absolute circulating NEFA content was more influenced by fasting duration than age. The SCD polymorphism did not impact NEFA content or composition. The LEPR polymorphism affected the content but not the fatty acid composition. Circulating oleic acid NEFA content after a short fasting was positively correlated with intramuscular fat content and, after a long fasting, with intramuscular oleic acid content. We conclude that circulating NEFA reflect environmental and genetic metabolic changes but are of limited value as biomarkers for intramuscular fat content and fatty acid composition.

(Z)-Oxopropene-1,3-diyl, a Linker for the Conjugation of the Thiol Group of Cysteine with Amino-Derivatized Drugs.

We have developed a conjugation reaction based on the thia-Michael addition to activated triple bonds, which can be an alternative to maleimides, the most commonly used reagents to link thiol groups (of Cys) to drugs and labels. An amino group is converted into its propynamide and, in aqueous media at 37 °C and pH 7.4, Cys derivatives are added. The oxopropene-1,3-diyl linker is formed with excellent Z selectivity without secondary reactions. No exchange with other thiols is observed.

Linoleic acid metabolic pathway allows for an efficient increase of intramuscular fat content in pigs.

BACKGROUND: Intramuscular fat (IMF) content is a relevant trait for high-quality meat products such as dry-cured ham, but increasing IMF has the undesirable correlated effect of decreasing lean growth. Thus, there is a need to find selection criteria for IMF independent from lean growth. In pigs, the proportion of linoleic (C18:2) and arachidonic (C20:4) acids decline with fat deposition and therefore they can be considered as indicators of fatness. The aim of this research was to estimate the genetic variation for C18:2 and C20:4 in IMF and their genetic correlations with IMF and lean growth traits, with the objective to assess their potential as specific biomarkers of IMF. The analysis was conducted using a full-pedigreed Duroc resource line with 91,448 records of body weight and backfat thickness (BT) at 180 days of age and 1371 records of fatty acid composition in the muscle gluteus medius. RESULTS: The heritability estimates for C18:2 and C20:4 in IMF, whether expressed in absolute (mg/g of muscle) or in relative (mg/g of fatty acid) terms, as well as for their ratio (C20:4/C18:2), were high (> 0.40), revealing that the C18:2 to C20:4 pathway is subjected to substantial genetic influence. Litter effects were not negligible, with values ranging from 8% to 15% of the phenotypic variance. The genetic correlations of C18:2 and C20:4 with IMF and BT were negative (- 0.75 to - 0.66, for IMF, and - 0.64 to - 0.36, for BT), if expressed in relative values, but almost null (- 0.04 to 0.07), if expressed in absolute values, except for C18:2 with IMF, which was highly positive (0.88). The ratio of C20:4 to C18:2 also displayed a stronger genetic correlation with IMF (- 0.59) than with BT (- 0.10). CONCLUSIONS: The amount of C18:2 in muscle can be used as an IMF-specific biomarker. Selection for the absolute amount of C18:2 is expected to deliver a similar response outcome as selection for IMF at restrained BT. Further genetic analysis of the C18:2 metabolic pathway may provide new insights into differential fat deposition among adipose tissues and on candidate genes for molecular markers targeting specifically for one of them.

Preparation of canine C-reactive protein serum reference material: A feasibility study.

BACKGROUND: The availability of a species-specific reference material is essential for the harmonization of results obtained in different laboratories by different methods. OBJECTIVES: We describe the preparation of a canine C-reactive protein (cCRP) serum reference material containing purified cCRP stabilized in a serum matrix. The material can be used by manufacturers to assign values to their calibrator and control materials. METHODS: The serum matrix was obtained using blood collected from healthy dogs, stabilized and submitted for a delipidation process. The reference material was prepared by diluting purified cCRP in the serum matrix containing 1.0 mol/L HEPES buffer, 3.0 mmol/L calcium chloride, 80,000 kUI/L aprotinin, and 1.0 mmol/L benzamidine hydrochloride monohydrate at a pH of 7.2, and dispensing (0.5 mL) the matrix into vials that were then frozen. RESULTS: The pilot batch of 200 vials was shown to be homogeneous and stable after a stability study at various temperatures and over a total time of 110 days. The prepared material was submitted to an assignment value study. Eight laboratories from different European countries participated by using the same reagents for an immunoturbidimetric method adapted for different analyzers. The obtained cCRP concentration in the reference material was 78.5 mg/L with an expanded uncertainty (k = 2) of 4.2 mg/L. CONCLUSIONS: Canine C-reactive protein serum reference material has been produced that allows harmonization of results obtained by different methods and different laboratories, thus reducing the possibility of errors and misunderstandings.

Formal Total Synthesis of Amphidinolide E.

A formal total synthesis of the cytotoxic macrolide amphidinolide E is reported. The strategic steps are three Julia-Kocienski reactions (J-K), for the formation of the C5-C6, C9-C10, and C17-C18 double bonds, a Suzuki-Molander C21-C22 bond formation reaction, and a Kita-Trost macrolactonization. The "instability" of the two dienic systems and of the stereocenter at C2 (allylic methine, α to the carboxy group) and the protecting groups at C17-OH and C18-OH have posed difficult challenges. Each Julia-Kocienski olefination has been systematically optimized to provide the highest possible E/Z ratios.

Tosvinyl and besvinyl as protecting groups of imides, azinones, nucleosides, sultams, and lactams. Catalytic conjugate additions to tosylacetylene.

The use of the 2-(4-methylphenylsulfonyl)ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsv-protected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimination mechanism using pyrrolidine or sodium dodecanethiolate as nucleophiles.

Modulation of the fibrillogenesis inhibition properties of two transthyretin ligands by halogenation.

The amyloidogenic protein transthyretin (TTR) is thought to aggregate into amyloid fibrils by tetramer dissociation which can be inhibited by a number of small molecule compounds. Our analysis of a series of crystallographic protein-inhibitor complexes has shown no clear correlation between the observed molecular interactions and the in vitro activity of the inhibitors. From this analysis, it emerged that halogen bonding (XB) could be mediating some key interactions. Analysis of the halogenated derivatives of two well-known TTR inhibitors has shown that while flufenamic acid affinity for TTR was unchanged by halogenation, diflunisal gradually improves binding up to 1 order of magnitude after iodination through interactions that can be interpreted as a suboptimal XB (carbonyl Thr106: I...O distance 3.96-4.05 Å; C-I...O angle 152-156°) or as rather optimized van der Waals contacts or as a mixture of both. These results illustrate the potential of halogenation strategies in designing and optimizing TTR fibrillogenesis inhibitors.

Nucleophile-catalyzed additions to activated triple bonds. Protection of lactams, imides, and nucleosides with MocVinyl and related groups.

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

PAU-SA: a synthetic aperture interferometric radiometer test bed for potential improvements in future missions.

The Soil Moisture and Ocean Salinity (SMOS) mission is an Earth Explorer Opportunity mission from the European Space Agency (ESA). Its goal is to produce global maps of soil moisture and ocean salinity using the Microwave Imaging Radiometer by Aperture Synthesis (MIRAS). The purpose of the Passive Advanced Unit Synthetic Aperture (PAU-SA) instrument is to study and test some potential improvements that could eventually be implemented in future missions using interferometric radiometers such as the Geoestacionary Atmosferic Sounder (GAS), the Precipitation and All-weather Temperature and Humidity (PATH) and the Geostationary Interferometric Microwave Sounder (GIMS). Both MIRAS and PAU-SA are Y-shaped arrays with uniformly distributed antennas, but the receiver topology and the processing unit are quite different. The purpose of this work is to identify the elements in the MIRAS's design susceptible of improvement and apply them in the PAU-SA instrument demonstrator, to test them in view of these future interferometric radiometer missions.

A general analysis of the impact of digitization in microwave correlation radiometers.

This study provides a general framework to analyze the effects on correlation radiometers of a generic quantization scheme and sampling process. It reviews, unifies and expands several previous works that focused on these effects separately. In addition, it provides a general theoretical background that allows analyzing any digitization scheme including any number of quantization levels, irregular quantization steps, gain compression, clipping, jitter and skew effects of the sampling period.

New passive instruments developed for ocean monitoring at the remote sensing lab-universitat politècnica de catalunya.

Lack of frequent and global observations from space is currently a limiting factor in many Earth Observation (EO) missions. Two potential techniques that have been proposed nowadays are: (1) the use of satellite constellations, and (2) the use of Global Navigation Satellite Signals (GNSS) as signals of opportunity (no transmitter required). Reflectometry using GNSS opportunity signals (GNSS-R) was originally proposed in 1993 by Martin-Neira (ESA-ESTEC) for altimetry applications, but later its use for wind speed determination has been proposed, and more recently to perform the sea state correction required in sea surface salinity retrievals by means of L-band microwave radiometry (T(B)). At present, two EO space-borne missions are currently planned to be launched in the near future: (1) ESA's SMOS mission, using a Y-shaped synthetic aperture radiometer, launch date November 2nd, 2009, and (2) NASA-CONAE AQUARIUS/SAC-D mission, using a three beam push-broom radiometer. In the SMOS mission, the multi-angle observation capabilities allow to simultaneously retrieve not only the surface salinity, but also the surface temperature and an "effective" wind speed that minimizes the differences between observations and models. In AQUARIUS, an L-band scatterometer measuring the radar backscatter (σ(0)) will be used to perform the necessary sea state corrections. However, none of these approaches are fully satisfactory, since the effective wind speed captures some sea surface roughness effects, at the expense of introducing another variable to be retrieved, and on the other hand the plots (T(B)-σ(0)) present a large scattering. In 2003, the Passive Advance Unit for ocean monitoring (PAU) project was proposed to the European Science Foundation in the frame of the EUropean Young Investigator Awards (EURYI) to test the feasibility of GNSS-R over the sea surface to make sea state measurements and perform the correction of the L-band brightness temperature. This paper: (1) provides an overview of the Physics of the L-band radiometric and GNSS reflectometric observations over the ocean, (2) describes the instrumentation that has been (is being) developed in the frame of the EURYI-funded PAU project, (3) the ground-based measurements carried out so far, and their interpretation in view of placing a GNSS-reflectometer as secondary payload in future SMOS follow-on missions.

Calibration of correlation radiometers using pseudo-random noise signals.

The calibration of correlation radiometers, and particularly aperture synthesis interferometric radiometers, is a critical issue to ensure their performance. Current calibration techniques are based on the measurement of the cross-correlation of receivers' outputs when injecting noise from a common noise source requiring a very stable distribution network. For large interferometric radiometers this centralized noise injection approach is very complex from the point of view of mass, volume and phase/amplitude equalization. Distributed noise injection techniques have been proposed as a feasible alternative, but are unable to correct for the so-called "baseline errors" associated with the particular pair of receivers forming the baseline. In this work it is proposed the use of centralized Pseudo-Random Noise (PRN) signals to calibrate correlation radiometers. PRNs are sequences of symbols with a long repetition period that have a flat spectrum over a bandwidth which is determined by the symbol rate. Since their spectrum resembles that of thermal noise, they can be used to calibrate correlation radiometers. At the same time, since these sequences are deterministic, new calibration schemes can be envisaged, such as the correlation of each receiver's output with a baseband local replica of the PRN sequence, as well as new distribution schemes of calibration signals. This work analyzes the general requirements and performance of using PRN sequences for the calibration of microwave correlation radiometers, and particularizes the study to a potential implementation in a large aperture synthesis radiometer using an optical distribution network.