Verification of Magnitude and Phase Responses in Fixed-Point Digital Filters

In the digital signal processing (DSP) area, one of the most important tasks is digital filter design. Currently, this procedure is performed with the aid of computational tools, which generally assume filter coefficients represented with floating-point arithmetic. Nonetheless, during the implementation phase, which is often done in digital signal processors or field programmable gate arrays, the representation of the obtained coefficients can be carried out through integer or fixed-point arithmetic, which often results in unexpected behavior or even unstable filters. The present work addresses this issue and proposes a verification methodology based on the digital-system verifier (DSVerifier), with the goal of checking fixed-point digital filters w.r.t. implementation aspects. In particular, DSVerifier checks whether the number of bits used in coefficient representation will result in a filter with the same features specified during the design phase. Experimental results show that errors regarding frequency response and overflow are likely to be identified with the proposed methodology, which thus improves overall system's reliability

An insight into polarization states of solid-state organic lasers

The polarization states of lasers are crucial issues both for practical applications and fundamental research. In general, they depend in a combined manner on the properties of the gain material and on the structure of the electromagnetic modes. In this paper, we address this issue in the case of solid-state organic lasers, a technology which enables to vary independently gain and mode properties. Different kinds of resonators are investigated: in-plane micro-resonators with Fabry-Perot, square, pentagon, stadium, disk, and kite shapes, and external vertical resonators. The degree of polarization P is measured in each case. It is shown that although TE modes prevail generally (P>0), kite-shaped micro-laser generates negative values for P, i.e. a flip of the dominant polarization which becomes mostly TM polarized. We at last investigated two degrees of freedom that are available to tailor the polarization of organic lasers, in addition to the pump polarization and the resonator geometry: upon using resonant energy transfer (RET) or upon pumping the laser dye to an higher excited state. We then demonstrate that significantly lower P factors can be obtained.Comment: 12 pages, 12 figure

Reconstruction of seasonal temperature variability in the tropical Pacific Ocean from the shell of the scallop, <i>Comptopallium radula</i>

International audienceWe investigated the oxygen isotope composition (d18O) of shell striae from juvenile Comptopallium radula (Mollusca; Pectinidae) specimens collected live in New Caledonia. Bottom-water temperature and salinity were monitored in-situ throughout the study period. External shell striae form with a 2-day periodicity in this scallop, making it possible to estimate the date of precipitation for each calcite sample collected along a growth transect. The oxygen isotope composition of shell calcite (d18Oshell calcite) measured at almost weekly resolution on calcite accreted between August 2002 and July 2003 accurately tracks bottom-water temperatures. A new empirical paleotemperature equation for this scallop species relates temperature and d18Oshell calcite: t(°C)=20.00(+/-0.61)-3.66(+/-0.39)x(d18Oshell calcite VPDB -d18Owater VSMOW) The mean absolute accuracy of temperature estimated using this equation is 1.0 °C at temperatures between 20 and 30 °C. Uncertainties regarding the precise timing of CaCO3 deposition and the actual variations in d18Owater at our study sites probably contribute to this error. Comparison with a previously published empirical paleotemperature equation indicates that C. radula calcite is enriched in 18O by ~0.7‰ relative to equilibrium. Given the direction of this offset and the lack of correlation between shell growth rate and d18Oshell calcite, this disequilibrium is unlikely to be related to kinetic isotope effects. We suggest that this enrichment reflects (1) a relatively low pH in the scallop's marginal extrapallial fluid (EPF), (2) an isotopic signature of the EPF different from that of seawater, or (3) Rayleigh fractionation during the biocalcification process. Relative changes in d18Oshell calcite reflect seawater temperature variability at this location and we suggest that the shell of C. radula may be useful as an archive of past seawater temperatures

A generative machine learning surrogate model of plasma turbulence

State-of-the-art techniques in generative artificial intelligence are employed for the first time to construct a surrogate model for plasma turbulence that enables long time transport simulations. The proposed GAIT (Generative Artificial Intelligence Turbulence) model is based on the coupling of a convolutional variational auto-encoder, that encodes precomputed turbulence data into a reduce latent space, and a deep neural network and decoder that generate new turbulence states 400 times faster than the direct numerical integration. The model is applied to the Hasegawa-Wakatani (HW) plasma turbulence model, that is closely related to the quasigeostrophic model used in geophysical fluid dynamics. Very good agreement is found between the GAIT and the HW models in the spatio-temporal Fourier and Proper Orthogonal Decomposition spectra as well as in the flow topology characterized by the Okubo-Weiss decomposition. Agreement is also found in the probability distribution function of particle displacements and the effective turbulent diffusivity

Bayesian inversion of synthetic AVO data to assess fluid and shale content in sand-shale media

Reservoir characterization of sand-shale sequences has always challenged geoscientists due to the presence of anisotropy in the form of shale lenses or shale layers. Water saturation and volume of shale are among the fundamental reservoir properties of interest for sand-shale intervals, and relate to the amount of fluid content and accumulating potentials of such media. This paper suggests an integrated workflow using synthetic data for the characterization of shaley-sand media based on anisotropic rock physics (T-matrix approximation) and seismic reflectivity modelling. A Bayesian inversion scheme for estimating reservoir parameters from amplitude vs. offset (AVO) data was used to obtain the information about uncertainties as well as their most likely values. The results from our workflow give reliable estimates of water saturation from AVO data at small uncertainties, provided background sand porosity values and isotropic overburden properties are known. For volume of shale, the proposed workflow provides reasonable estimates even when larger uncertainties are present in AVO data

Catalytic living ring-opening metathesis polymerization

In living ring-opening metathesis polymerization (ROMP), a transition-metal–carbene complex polymerizes ring-strained olefins with very good control of the molecular weight of the resulting polymers. Because one molecule of the initiator is required for each polymer chain, however, this type of polymerization is expensive for widespread use. We have now designed a chain-transfer agent (CTA) capable of reducing the required amount of metal complex while still maintaining full control over the living polymerization process. This new method introduces a degenerative transfer process to ROMP. We demonstrate that substituted cyclohexene rings are good CTAs, and thereby preserve the ‘living’ character of the polymerization using catalytic quantities of the metal complex. The resulting polymers show characteristics of a living polymerization, namely narrow molecular-weight distribution, controlled molecular weights and block copolymer formation. This new technique provides access to well- defined polymers for industrial, biomedical and academic use at a fraction of the current costs and significantly reduced levels of residual ruthenium catalyst

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

SWATH-MS as a strategy for CHO host cell protein identification and quantification supporting the characterization of mAb purification platforms

Funding Information: This work was supported by Sanofi. Funding Information: Authors acknowledge the support from the UniMS team, all MS data were generated by the UniMS–Mass Spectrometry Unit, iBET/ITQB, Oeiras, Portugal. The authors also acknowledge Miguel Antunes and Inês Isidro from iBET Data Science team for their contribution to data analysis. The authors acknowledge the experimental work from Emmanuel Fofie, Céline Hemet and Didier Duthé from Sanofi on chromatographic runs. The authors are grateful to Jason Walther for revising the manuscript and English proofreading. Publisher Copyright: © 2024 The AuthorsHost cell proteins (HCPs) are process-related impurities expressed by the host cells during biotherapeutics’ manufacturing, such as monoclonal antibodies (mAbs). Some challenging HCPs evade clearance during the downstream processing and can be co-purified with the molecule of interest, which may impact product stability, efficacy, and safety. Therefore, HCP content is a critical quality attribute to monitor and quantify across the bioprocess. Here we explored a mass spectrometry (MS)-based proteomics tool, the sequential window acquisition of all theoretical fragment-ion spectra (SWATH) strategy, as an orthogonal method to traditional ELISA. The SWATH workflow was applied for high-throughput individual HCP identification and quantification, supporting characterization of a mAb purification platform. The design space of HCP clearance of two polishing resins was evaluated through a design of experiment study. Absolute quantification of high-risk HCPs was achieved (reaching 1.8 and 4.2 ppm limits of quantification, for HCP A and B respectively) using HCP-specific synthetic heavy labeled peptide calibration curves. Profiling of other HCPs was also possible using an average calibration curve (using labeled peptides from different HCPs). The SWATH approach is a powerful tool for HCP assessment during bioprocess development enabling simultaneous monitoring and quantification of different individual HCPs and improving process understanding of their clearance.publishersversionpublishe

Metathesis of Fatty Acid Ester Derivatives in 1,1-Dialkyl and 1,2,3-Trialkyl Imidazolium Type Ionic Liquids

The self-metathesis of methyl oleate and methyl ricinoleate was carried out in the presence of ruthenium alkylidene catalysts 1–4 in [bmim] and [bdmim][X] type ionic liquids (RTILs) (X = PF6−, BF4− and NTf2−) using the gas chromatographic technique. Best catalytic performance was obtained in [bdmim][X] type ionic liquids when compared with [bmim][X] type ionic liquids. Catalyst recycling studies were also carried out in the room temperature ionic liquids (RTILs) with catalysts 1–4 in order to explore their possible industrial application