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We examine the ability of two dynamic turbulence closure models to simulate the diurnal development of convection and the transition from dry to shallow cumuli and then to deep convection. The dynamic models are compared with the conventional Smagorinsky scheme at a range of cloud‐resolving and grey‐zone resolutions. The dynamic schemes include the Lagrangian‐averaged, scale‐dependent dynamic Smagorinsky model and a Lagrangian‐averaged, dynamic mixed model. The conventional Smagorinsky model fails to reproduce the shallow convection stage beyond the large‐eddy simulation regime, continuously building up the convective available potential energy that eventually leads to an unrealistic deep convection phase. The dynamic Smagorinsky model significantly improves the representation of shallow and deep convection; however, it exhibits issues similar to the conventional scheme at coarser resolutions. In contrast, the dynamic mixed model closely follows the large‐eddy simulation results across the range of sub‐kilometre simulations. This is achieved by the combined effect of an adaptive length scale and the inclusion of the Leonard terms, which can produce counter‐gradient fluxes through the backscatter of energy from the subgrid to the resolved scales and enable appropriate non‐local contributions. A further sensitivity test on the inclusion of the Leonard terms on all hydrometeor fluxes reveals the strong interaction between turbulent transport and microphysics and the possible need for further optimisation of the dynamic mixed model coefficients together with the microphysical representation. [ABSTRACT FROM AUTHOR]

Background: The utilization of chemical preservatives holds the promise of effectively controlling microbial growth in soft cheese Aim: The first trial aimed to compare the effectiveness of LBA and K-Sorbate in controlling the proliferation of S. aureus, E. coli and mold in white soft cheese. The subsequent part of the study explored the inhibitory effects of K-Sorbate, nisin, and LBA on mold populations in cheese whey. Methods: Two sets of soft cheese were produced. One set was contaminated with S. aureus, while the other with E. coli, each at concentrations of 1 log CFU/mL and 1 log CFU/100 mL. Different concentrations of LBA were incorporated into these sets of cheese. Similar cheese samples were treated with K-Sorbate. For the subsequent part of the study, why was manufactured and divided into groups which inoculated with LBA with different concentrations, K-Sorbate and nisin. Results: With higher S. aureus inoculation, by day 18, the positive control exhibited growth exceeding 5 log CFU/g. In contrast, the LBA treatment dropped below LOD and K-Sorbate yielded 4.8 log CFU/g. While with lower S. aureus inoculation, the +ve control reach3 log CFU/g, while LBA treatment fell below LOD by the day 14, and K-Sorbate reached 2.9 log CFU/g. For E. coli inoculation, with higher concentrations, by day 18, the positive control exceeded 5 log CFU/g. Conversely, LBA treatment greatly decreased and K-Sorbate treatment measured 5.1 log CFU/g. With lower E. coli concentrations, the positive control surpassed 3 log CFU/g, yet LBA treatment dropped below LOD by the day 3. Mold counts indicated some inhibition with the K-Sorbate treatment, while control groups showed growth. LBA treatments exhibit noticeable growth inhibition. About the other part of the study the outcomes demonstrated that while growth of mold occurred in the control group, inhibitory effects were apparent in the treatment groups, and significant distinctions existed between K-Sorbate, nisin, LBA treatments, and the control group. Conclusion Our findings suggest that LBA has the potential to effectively control the growth of E. coli, S. aureus and mold in soft cheese. Moreover, LBA displays greater preservative efficacy compared to K-Sorbate and nisin. [Open Vet J 2024; 14(1.000): 594-603]

Navon letters and composite faces are two fascinating demonstrations of hierarchical organization in perception. Many researchers believe that the two types of stimuli and their associated tasks gauge comparable holisticmechanisms. This belief is so common that the two paradigms are now being applied in tandem to measure impaired holistic processing in prosopagnosic patients. But are Navon letters and composite faces processed in a similar fashion? In the present study we take a closer look at their apparent affinity. We gain novel insights into their underlying mechanisms by fitting parameters of the linear ballistic accumulator (LBA) model to empirical correct and incorrect response times (RTs). The results reveal major differences in processing between the two tasks. We conclude that despite the presence of a compelling surface similarity, Navon compound letters and composite faces tap into separate psychological processes. [ABSTRACT FROM AUTHOR]

Navon letters and composite faces are two fascinating demonstrations of hierarchical organization in perception. Many researchers believe that the two types of stimuli and their associated tasks gauge comparable holistic mechanisms. This belief is so common that the two paradigms are now being applied in tandem to measure impaired holistic processing in prosopagnosic patients. But are Navon letters and composite faces processed in a similar fashion? In the present study we take a closer look at their apparent affinity. We gain novel insights into their underlying mechanisms by fitting parameters of the linear ballistic accumulator (LBA) model to empirical correct and incorrect response times (RTs). The results reveal major differences in processing between the two tasks. We conclude that despite the presence of a compelling surface similarity, Navon compound letters and composite faces tap into separate psychological processes.

Shells of revolution under axisymmetric conditions exhibit a circumferentially uniform pre‐buckling stress state and are important fundamental systems which often serve as reference systems for those under more complex conditions. Given this status, work is continuing on a careful and complete characterization of their buckling response with the aid of the Reference Resistance Design (RRD) framework for the ultimate benefit of the EN 1993‐1‐6 Eurocode on the strength of stability of metal shells. The situation is greatly complicated by the fact that while modern finite element software packages offer axisymmetric shell elements in an efficient 2D modelling plane, these are not capable of detecting bifurcation buckling into non‐axisymmetric modes which are often critical for slender systems. Reverting to a full 3D plane is possible, but grossly inefficient and the explicitly modelled circumferential direction is parasitic and detrimental to the overall solution quality. AQUINAS is an accessible and intuitive toolbox developed by the Authors in MATLAB for the efficient analysis of axisymmetric shell structures, aiming to reintroduce a modelling capability that was once standard in the field. Data input is entirely object‐oriented and matrix assembly is parallelized with pre‐compiled C++ routines, with users being able to take direct advantage of MATLAB's visualization properties. The software natively supports the LA, LBA, MNA, GMNIA etc. Eurocode analysis taxonomy. This paper demonstrates the current capabilities of the toolbox, describes the extensive programme of verification against existing established solutions that has been performed, and illustrates its ability to efficiently compute very detailed capacity curves using the EN 1993‐1‐6 capacity curve framework. [ABSTRACT FROM AUTHOR]

Most data analyses rely on models. To complement statistical models, psychologists have developed cognitive models, which translate observed variables into psychologically interesting constructs. Response time models, in particular, assume that response time and accuracy are the observed expression of latent variables including 1) ease of processing, 2) response caution, 3) response bias, and 4) non-decision time. Inferences about these psychological factors, hinge upon the validity of the models' parameters. Here, we use a blinded, collaborative approach to assess the validity of such model-based inferences. Seventeen teams of researchers analyzed the same 14 data sets. In each of these two-condition data sets, we manipulated properties of participants' behavior in a two-alternative forced choice task. The contributing teams were blind to the manipulations, and had to infer what aspect of behavior was changed using their method of choice. The contributors chose to employ a variety of models, estimation methods, and inference procedures. Our results show that, although conclusions were similar across different methods, these "modeler's degrees of freedom" did affect their inferences. Interestingly, many of the simpler approaches yielded as robust and accurate inferences as the more complex methods. We recommend that, in general, cognitive models become a typical analysis tool for response time data. In particular, we argue that the simpler models and procedures are sufficient for standard experimental designs. We finish by outlining situations in which more complicated models and methods may be necessary, and discuss potential pitfalls when interpreting the output from response time models.

Antibody–drug conjugates (ADCs) are a new class of biotherapeutics, consisting of a cytotoxic payload covalently bound to an antibody by a linker. Ligand-binding assay (LBA) and liquid chromatography-mass spectrometry (LC-MS) are the favored techniques for the analysis of ADCs in biomatrices. The goal of our review is to provide current strategies related to a series of bioanalytical assays for pharmacokinetics (PK) and anti-drug antibody (ADA) assessments. Furthermore, the strengths and limitations of LBA and LC-MS platforms are compared. Finally, potential factors that affect the performance of the developed assays are also provided. It is hoped that the review can provide valuable insights to bioanalytical scientists on the use of an integrated analytical strategy involving LBA and LC–MS for the bioanalysis of ADCs and related immunogenicity evaluation. [ABSTRACT FROM AUTHOR]

The article describes the analysis of a work operation on a virtual model of a production workplace. In order for the virtual workplace to correspond to reality as much as possible, 3D scanning was used to create a digital model of the part that the worker is manipulating. Tecnomatix Jack software was used to create a virtual workplace model and simulate worker movements. The operation was analyzed by four different methods, namely RULA analysis, OWAS analysis, Comfort Assessment analysis and Lower Back analysis. The results of all analyzes for the same task show that the job is not properly designed and it is necessary to propose workplace changes to eliminate the identified problems. [ABSTRACT FROM AUTHOR]

Dicyemids and orthonectids were traditionally classified in a group called Mesozoa, but their placement in a single clade has been contested and their position(s) within Metazoa is uncertain. Here, we assembled a comprehensive matrix of Lophotrochozoa (Metazoa) and investigated the position of Dicyemida (= Rhombozoa) and Orthonectida, employing multiple phylogenomic approaches. We sequenced seven new transcriptomes and one draft genome from dicyemids (Dicyema, Dicyemennea) and two transcriptomes from orthonectids (Rhopalura). Using these and published data, we assembled and analysed contamination-filtered datasets with up to 987 genes. Our results recover Mesozoa monophyletic and as a close relative of Platyhelminthes or Gnathifera. Because of the tendency of the long-branch mesozoans to group with other long-branch taxa in our analyses, we explored the impact of approaches purported to help alleviate long-branch attraction (e.g. taxon removal, coalescent inference, gene targeting). None of these were able to break the association of Orthonectida with Dicyemida in the maximum-likelihood trees. Contrastingly, the Bayesian analysis and site-specific frequency model in maximum-likelihood did not recover a monophyletic Mesozoa (but only when using a specific 50 gene matrix). The classic hypothesis on monophyletic Mesozoa is possibly reborn and should be further tested. [ABSTRACT FROM AUTHOR]

Adaptive Control of Thought-Rational (ACT-R) and theLinear Ballistic Accumulator (LBA) were compared in amodel mimicry simulation of the Psychomotor VigilanceTask (PVT), a simple, reaction time (RT) task requiringsustained attention. The models use different formalisms tocapture the full response profile of the PVT. The parameterswere varied systematically to illustrate the ranges of themodels’ predictions, to assess the models’ estimationproperties, and to determine which parameters in the modelscorrespond with each other. Both models produced skewedRT distributions typical of empirical data, including falsestarts and lapses. The simulation study demonstrated that bothmodels and their parameters are recoverable. Lastly, isolatedparameters in the LBA model captured the effects of varyingparameters in the ACT-R model, but the reverse was notalways true. These interesting correspondences acrossdifferent modeling formalisms suggest the possibility ofintegrating ACT-R and the LBA in future work

Antibody–drug conjugates (ADCs) are a new class of biotherapeutics, consisting of a cytotoxic payload covalently bound to an antibody by a linker. Ligand-binding assay (LBA) and liquid chromatography-mass spectrometry (LC-MS) are the favored techniques for the analysis of ADCs in biomatrices. The goal of our review is to provide current strategies related to a series of bioanalytical assays for pharmacokinetics (PK) and anti-drug antibody (ADA) assessments. Furthermore, the strengths and limitations of LBA and LC-MS platforms are compared. Finally, potential factors that affect the performance of the developed assays are also provided. It is hoped that the review can provide valuable insights to bioanalytical scientists on the use of an integrated analytical strategy involving LBA and LC–MS for the bioanalysis of ADCs and related immunogenicity evaluation.

Implementation of immunocapture LC-MS methods to characterize the pharmacokinetic profile of large molecule drugs has become a widely used technique over the past decade. As the pharmaceutical industry strives for speediness into clinical development without jeopardizing quality, robust assays with generic application across the pipeline are becoming instrumental in bioanalysis, especially in early-stage development. This review highlights the capabilities and challenges involved in hybrid immunocapture LC-MS techniques and its continued applications in nonclinical and clinical pharmacokinetic assay design. This includes a comparison of LC-MS-based approaches to conventional ligand-binding assays and the driving demands in large molecule drug portfolios including growing sensitivity requirements and the unique challenges of new modalities requiring innovation in the bioanalytical laboratory.

In this paper we establish a baseline for the chemical and petrographic characterization of indigenous LBA/EIA funerary urns from south-western Iberia. In this we focus primarily on the morphological category of biconical vases, one of the most iconic vessel types known from Tartessian burial sites. In comparison to other types of ceramic urn vessels from archeological sites of the Orientalizing period in Andalusia, biconical vases are relatively rare, but are generally recognized as the earliest type of funerary vessel within the Tartessian sequence, clearly pre-dating the introduction of new ceramic technologies in the wake of the Phoenician colonization. Eleven samples of biconical vases from the key site of Setefilla are analyzed through XRF and thin-section petrography, in order to determine the chemical composition and technological properties of the samples. To contextualize the results from the chemical analyses, sixteen further samples from other hand-made vessel types, also from Setefilla, are likewise analyzed through XRF. The results indicate a high level of homogeneity in the make-up of biconical vases and a somewhat different chemical signature from other types of hand-made vessel. It remains to be established if minor variations that exist in the petrographic make-up of biconical vases follow a chronological gradient or if they are related to other factors. [ABSTRACT FROM AUTHOR]

Tropical vegetation is a major source of global land surface evapotranspiration, and can thus play a major role in global hydrological cycles and global atmospheric circulation. Accurate prediction of tropical evapotranspiration is critical to our understanding of these processes under changing climate. We examined the controls on evapotranspiration in tropical vegetation at 21 pan-tropical eddy covariance sites, conducted a comprehensive and systematic evaluation of 13 evapotranspiration models at these sites, and assessed the ability to scale up model estimates of evapotranspiration for the test region of Amazonia. Net radiation was the strongest determinant of evapotranspiration (mean evaporative fraction was 0.72) and explained 87% of the variance in monthly evapotranspiration across the sites. Vapor pressure deficit was the strongest residual predictor (14%), followed by normalized difference vegetation index (9%), precipitation (6%) and wind speed (4%). The radiation-based evapotranspiration models performed best overall for three reasons: (1) the vegetation was largely decoupled from atmospheric turbulent transfer (calculated from Ω decoupling factor), especially at the wetter sites; (2) the resistance-based models were hindered by difficulty in consistently characterizing canopy (and stomatal) resistance in the highly diverse vegetation; (3) the temperature-based models inadequately captured the variability in tropical evapotranspiration. We evaluated the potential to predict regional evapotranspiration for one test region: Amazonia. We estimated an Amazonia-wide evapotranspiration of 1370mmyr-1, but this value is dependent on assumptions about energy balance closure for the tropical eddy covariance sites; a lower value (1096mmyr-1) is considered in discussion on the use of flux data to validate and interpolate models. © 2009 The Authors Journal compilation © 2009 Blackwell Publishing Ltd.

We used frequency-domain reflectometry to make continuous, high-resolution measurements for 22 months of the soil moisture to a depth of 10 m in an Amazonian rain forest. We then used these data to determine how soil moisture varies on diet, seasonal and multi-year timescales, and to better understand the quantitative and mechanistic relationships between soil moisture and forest evapotranspiration. The mean annual precipitation at the site was over 1900 mm. The field capacity was approximately 0.53 m3 m-3 and was nearly uniform with soil depth. Soil moisture decreased at all levels during the dry season, with the minimum of 0.3g m3 m-3 at 3 in beneath the surface. The moisture in the upper 1 m showed a strong diel cycle with daytime depletion due to evapotranspiration. The moisture beneath 1 m declined during both day and night due to the combined effects of evapotranspiration, drainage and a nighttime upward movement of water. The depth of active water withdrawal changed markedly over the year. The upper 2 m of soil supplied ∼56% of the water used for evapotranspiration in the wet season and ∼28% of the water used in the dry season. The zone of active water withdrawal extended to a depth of at least 10 m. The day-to-day rates of moisture withdrawal from the upper 10 m of soil during rain-free periods agreed well with simultaneous measurements of whole-forest evapotranspiration made by the eddy covariance technique. The forest at the site was well adapted to the normal cycle of wet and dry seasons, and the dry season had only a small effect on the rates of land-atmosphere water vapour exchange. Copyright © 2006 John Wiley & Sons, Ltd.

We used the eddy covariance technique from July 2000 to July 2001 to measure the fluxes of sensible heat, water vapor, and CO2 between an old-growth tropical forest in eastern Amazonia and the atmosphere. Precipitation varied seasonally, with a wet season from mid-December 2000 to July 2001 characterized by successive rainy days, wet soil, and, relative to the dry season, cooler temperatures, greater cloudiness, and reduced incoming solar and net radiation. Average evapotranspiration decreased from 3.96 ± 0.65 mm/d during the dry season to 3.18 ± 0.76 mm/d during the wet season, in parallel with decreasing radiation and decreasing water vapor deficit. The average Bowen ratio was 0.17 ± 0.10, indicating that most of the incoming radiation was used for evaporation. The Bowen ratio was relatively low during the early wet season (December–March), as a result of increased evaporative fraction and reduced sensible heat flux. The seasonal decline in Bowen ratio and increase in evaporative fraction coincided with an increase in ecosystem CO2 assimilation capacity, which we attribute to the growth of new leaves. The evaporative fraction did not decline as the dry season progressed, implying that the forest did not become drought stressed. The roots extracted water throughout the top 250 cm of soil, and water redistribution, possibly by hydraulic lift, partially recharged the shallow soil during dry season nights. The lack of drought stress during the dry season was likely a consequence of deep rooting, and possibly vertical water movement, which allowed the trees to maintain access to soil water year round.

The Large-scale Biosphere–Atmosphere Experiment in Amazonia (LBA) is a multinational, interdisciplinary research program led by Brazil. Ecological studies in LBA focus on how tropical forest conversion, regrowth, and selective logging influence carbon storage, nutrient dynamics, trace gas fluxes, and the prospect for sustainable land use in the Amazon region. Early results from ecological studies within LBA emphasize the variability within the vast Amazon region and the profound effects that land-use and land-cover changes are having on that landscape. The predominant land cover of the Amazon region is evergreen forest; nonetheless, LBA studies have observed strong seasonal patterns in gross primary production, ecosystem respiration, and net ecosystem exchange, as well as phenology and tree growth. The seasonal patterns vary spatially and interannually and evidence suggests that these patterns are driven not only by variations in weather but also by innate biological rhythms of the forest species. Rapid rates of deforestation have marked the forests of the Amazon region over the past three decades. Evidence from ground-based surveys and remote sensing show that substantial areas of forest are being degraded by logging activities and through the collapse of forest edges. Because forest edges and logged forests are susceptible to fire, positive feedback cycles of forest degradation may be initiated by land-use-change events. LBA studies indicate that cleared lands in the Amazon, once released from cultivation or pasture usage, regenerate biomass rapidly. However, the pace of biomass accumulation is dependent upon past land use and the depletion of nutrients by unsustainable land-management practices. The challenge for ongoing research within LBA is to integrate the recognition of diverse patterns and processes into general models for prediction of regional ecosystem function.

We used two independent approaches, biometry and micrometeorology, to determine the net ecosystem production (NEP) of an old growth forest in Pará, Brazil. Biometric inventories indicated that the forest was either a source or, at most, a modest sink of carbon from 1984 to 2000 (+0.8 ± 2 Mg C·ha−1·yr−1; a positive flux indicates carbon loss by the forest, a negative flux indicates carbon gain). Eddy covariance measurements of CO2 exchange were made from July 2000 to July 2001 using both open- and closed-path gas analyzers. The annual eddy covariance flux calculated without correcting for the underestimation of flux on calm nights indicated that the forest was a large carbon sink (−3.9 Mg C·ha−1·yr−1). This annual uptake is comparable to past reports from other Amazonian forests, which also were calculated without correcting for calm nights. The magnitude of the annual integral was relatively insensitive to the selection of open- versus closed-path gas analyzer, averaging time, detrending, and high-frequency correction. In contrast, the magnitude of the annual integral was highly sensitive to the treatment of calm nights, changing by over 4 Mg C·ha−1·yr−1 when a filter was used to replace the net ecosystem exchange (NEE) during nocturnal periods with u* < 0.2 m/s. Analyses of the relationship between nocturnal NEE and u* confirmed that the annual sum needs to be corrected for the effect of calm nights, which resulted in our best estimate of the annual flux (+0.4 Mg C·ha−1·yr−1). The observed sensitivity of the annual sum to theu* filter is far greater than has been previously reported for temperate and boreal forests. The annual carbon balance determined by eddy covariance is therefore less certain for tropical than temperate forests. Nonetheless, the biometric and micrometeorological measurements in tandem provide strong evidence that the forest was not a strong, persistent carbon sink during the study interval.

We used eddy covariance to measure the net exchange of CO2between theatmosphere and an old-growth tropical forest in Para ́, Brazil from 1 July 2000 to 1 July2001. The mean air temperature and daily temperature range varied little year-round; therainy season lasted from late December to around July. Daytime CO2uptake under highirradiance averaged 16–19mmol·m22·s21. Light was the main controller of CO2exchange,accounting for 48% of the half-hour-to-half-hour variance. The rate of canopy photosyn-thesis at a given irradiance was lower in the afternoon than the morning. This photosyntheticinhibition was probably caused by high evaporative demand, high temperature, an intrinsiccircadian rhythm, or a combination of the three. Wood increment increased from Januaryto May, suggesting greater rates of carbon sequestration during the wet season. However,the daily net CO2exchange measured by eddy covariance revealed the opposite trend, withgreater carbon accumulation during the dry season. A reduction in respiration during thedry season was an important cause of this seasonal pattern. The surface litter was desiccatedin the dry season, and the seasonal pattern of respiration appears to be a direct result ofreduced forest floor decomposition during drought. In contrast, canopy photosynthesis wasnot directly reduced by the dry season, probably because deep rooting allows the forest toavoid drought stress

Accurate assessments of the CO2 fluxes between the terrestrial ecosystems and the atmosphere are pressingly needed for the climate change and carbon cycle studies. The Collatz et al. parameterization of leaf photosynthesis-stomatal conductance has been widely applied in land surface parameterization schemes for simulating the land surface CO2 fluxes. The study in this paper developed an analytical solution approach for the Collatz et al.'s parameterization for stable solution and computational efficiency. This analytical approach is then applied to the simplified biosphere model (SSiB), enhancing its capability of simulating land surface CO2 fluxes. The enhanced SSiB model is tested with field observation data sets from two Amazonian field experiments (ABRACOS missions and Manaus Eddy Covariance Study). Simulations of the land surface fluxes of latent heat, sensible heat and soil heat by the enhanced SSiB agree very well with observations with correlation coefficients being larger than 0.80. However, the correlation coefficient for the daily means Of CO2 fluxes is only 0.42 for the Manaus data set. A day-time, "square wave" in the simulated CO2 flux diurnal curves is found. The discrepancies between simulation and observation were found to be the results of incorrect parameter setup or improper leaf to canopy scaling strategy. A modification to the scaling strategy improves significantly the accuracy of the photosynthesis-stomatal conductance model. (C) 2002 Elsevier Science B.V. All rights reserved.

The urgency and importance of organizing a global effort to harmonize clinical assay validation specific to the vaccine industry was identified during the drafting of the 2020 White Paper in Bioanalysis due to the lack of clarity and regulatory guidance/guidelines in vaccine immunoassay validation. Indeed, the Workshop on Recent Issues in Bioanalysis (WRIB) issues the White Paper in Bioanalysis yearly, which is one of the high-profile articles of the Bioanalysis Journal focused on detailed discussions and recommendations on vaccine assay validation. Since 2017, participation in the WRIB working groups by vaccine assay validation experts and regulators has rapidly increased due to its unique format where industry leaders and regulators can meet and exchange ideas on topics of interest to both groups. In early 2021, Vaccine manufacturers approached WRIB for sponsoring/supporting the authorship and publication of an overarching vaccine assay validation document based on the 2017-2020 discussions and consensus starting from immunogenicity assays first and followed by future papers on molecular and cell-based assay validation. Using industry and WRIB vaccine network, a vaccine immunogenicity assay validation working group was assembled consisting of 16 companies. The work on the first white paper started officially in April 2021 focusing on Vaccine LBA Validation (Part 1), and the drafting of Vaccine LBA Development (Part 2) and Vaccine LBA Monitoring & Transfer (Part 3) are presently ongoing and expected to be published shortly after this paper. Moreover, recommendations on Vaccine Cell-Based Assays Validation (ELISpot and Flow cytometry) and Vaccine Molecular Assays Validation (PCR, NGS, NanoString) are also on the WRIB publications agenda and the drafting is planned to start in mid-2024. For too long, vaccine scientists have not had a clear validation guidance for clinical vaccine immunogenicity assays. We hope that this common effort will help close this regulatory gap.

Aim: Endogenous interferents can cause nonselectivity in ligand binding pharmacokinetic assays, leading to inaccurate quantification of drug concentrations. We describe the development of a Gyrolab immunoassay to quantify a new modality, CB307 and discuss strategies implemented to overcome matrix effects and achieve selectivity at the desired sensitivity. Results: Matrix effects were mitigated using strategies including increasing minimum required dilution (MRD) and lower limit of quantification, optimization of antibody orientation, assay buffer and solid phase. Conclusion: The strategies described resulted in a selective method for CB307 in disease state matrix that met bioanalytical method validation (BMV) guidance and is currently used to support clinical pharmacokinetic sample analysis in the first-in-human POTENTIA clinical study (NCT04839991) as a secondary clinical end point.

Aim: To demonstrate the importance of critical reagent characterization for immunogenicity assay development for multi-specific drugs using two case studies. Methods: Bridging anti-drug antibody (ADA) assay with acid-dissociated samples were used for both cases. Results: In the first case study, the unexpected interference in an ADA assay from clinical samples was identified; a model was created to replicate the issue, and an anti-target antibody was identified to mitigate the target interference. In the second case study, an issue due to non-specific binding of a domain-specific confirmatory reagent was identified, and various mitigation techniques were evaluated. Conclusion: A thorough characterization of the critical reagents helped identify the issues with these ADA case studies and provided strategies for resolving them.

Background: The utilization of chemical preservatives holds the promise of effectively controlling microbial growth in soft cheese., Aim: The first trial aimed to compare the effectiveness of lactobionic acid (LBA) and K-Sorbate in controlling the proliferation of Staphylococcus aureus, Escherichia coli, and mold in white soft cheese. The subsequent part of the study explored the inhibitory effects of K-Sorbate, nisin, and LBA on mold populations in cheese whey., Methods: Two sets of soft cheese were produced. One set was contaminated with S. aureus , while the other was with E. coli , each at concentrations of 1 log CFU/ml and 1 log CFU/100 ml. Different concentrations of LBA were incorporated into these sets of cheese. Similar cheese samples were treated with K-Sorbate. For the subsequent part of the study, it was manufactured and divided into groups that inoculated with LBA with different concentrations, K-Sorbate, and nisin., Results: With higher S. aureus inoculation, by day 18, the positive control exhibited growth exceeding 5 log CFU/g. In contrast, the LBA treatment dropped below limit of detection (LOD) and K-Sorbate yielded 4.8 log CFU/g. While with lower S. aureus inoculation, the positive control reached log CFU/g, while LBA treatment fell below LOD by day 14, and K-Sorbate reached 2.9 log CFU/g. For E. coli inoculation, with higher concentrations, by day 18, the positive control exceeded 5 log CFU/g. Conversely, LBA treatment greatly decreased and K-Sorbate treatment measured 5.1 log CFU/g. With lower E. coli concentrations, the positive control surpassed 3 log CFU/g, yet LBA treatment dropped below LOD by day 3. Mold counts indicated some inhibition with the K-Sorbate treatment, while control groups showed growth. LBA treatments exhibit noticeable growth inhibition. About the other part of the study, the outcomes demonstrated that while growth of mold occurred in the control group, inhibitory effects were apparent in the treatment groups, and significant distinctions existed between K-Sorbate, nisin, LBA treatments, and the control group., Conclusion: Our findings suggest that LBA has the potential to effectively control the growth of E. coli, S. aureus, and mold in soft cheese. Moreover, LBA displays greater preservative efficacy compared to K-Sorbate and nisin., Competing Interests: The authors declare that they have no competing interests.

According to recent assessments, tropical woodlands contribute about half of all global natural non-methane volatile organic compound (VOC) emissions. Large uncertainties exist especially about fluxes of compounds other than isoprene and monoterpenes. During the Large-Scale Biosphere/Atmosphere Experiment in Amazonia - Cooperative LBA Airborne Regional Experiment 1998 (LBA-CLAIRE-98) campaign, we measured the atmospheric mixing ratios of different species of VOC at a ground station at Balbina, Amazonia. The station was located 100 km north of Manaus, SE of the Balbina reservoir, with 200-1000 km of pristine forest in the prevailing wind directions. Sampling methods included DNPH-coated cartridges for carbonyls and cartridges filled with graphitic carbons of different surface characteristics for other VOCs. The most prominent VOC species present in air were formaldehyde and isoprene, each up to several ppb. Concentrations of methylvinyl ketone as well as methacroleine, both oxidation products of isoprene, were relatively low, indicating a very low oxidation capacity in the lower atmospheric boundary layer, which is in agreement with a daily ozone maximum of

Résumé: Les traitements antirétroviraux actuels permettent un contrôle efficace de la réplication du VIH mais en cas d'arrêt thérapeutique, un rebond de charge virale se produit dans la grande majorité des cas. L'intégration du génome viral dans le génome cellulaire explique cette persistance du VIH dans tous les tissus de l'organisme, bien qu'à des niveaux très variables, liés notamment à la densité en lymphocytes T CD4+, principales cibles du virus, et à leur durée de vie. Les organes lymphoïdes secondaires, et en particulier les ganglions, montrent les niveaux d'infection les plus élevés. Il existe différentes méthodes de caractérisation du réservoir, qui ne détectent pas toutes les mêmes formes virales, et sont complémentaires pour comprendre son établissement lors de la primo-infection et sa dynamique d'évolution. Au niveau sanguin, la diminution de l'ADN VIH, qui quantifie les formes intégrées et non intégrées du génome viral, total est d'autant plus forte et prolongée que les antirétroviraux ont été initiés précocement. Le traitement précoce prévient l'augmentation progressive des formes intégrées d'ADN VIH, les plus stables, et préserve les cellules immunitaires de l'infection. Mieux comprendre la physiopathologie de l'infection chez les individus contrôleurs naturels et les contrôleurs post-traitement peut également aider à la mise au point de nouvelles stratégies thérapeutiques visant la rémission, voire la guérison. Current antiretroviral therapy allows the control of HIV replication but a relapse occurs most of the time in case of treatment interruption. The viral genome integration explains this persistence of HIV in all body tissues, at very variable levels depending on their density of CD4+ T-cells, HIV main target. Secondary lymphoid tissues are the most infected organs. Several techniques can be used to characterize the reservoir, detecting different forms of the virus. They are complementary to decipher the establishment of HIV reservoir during the primary infection and its dynamics afterwards. In peripheral blood, the earlier the initiation of treatment, the more important is the decrease in total HIV DNA. Early treatment prevents the progressive increase in stable integrated forms of HIV DNA and preserves immune cells from infection. A better understanding of HIV infection in controllers will also aid in the development of new therapeutic strategies targeting the reservoir. [ABSTRACT FROM AUTHOR]

Characterization of pharmacokinetic (PK) properties and target tissue distribution of therapeutic fusion proteins (TFPs) are critical in supporting in vivo efficacy. We evaluated the pharmacokinetic profile of an investigational TFP consisting of human immunoglobulin G4 fused to the modified interferon alpha by orthogonal bioanalytical assays and applied minimal physiologically based pharmacokinetic (PBPK) modeling to characterize the TFP pharmacokinetics in mouse. The conventional ligand binding assay (LBA), immunocapture-liquid chromatography/tandem mass spectrometry (IC-LC/MS) detecting the human IgG4 peptide or the interferon alpha peptide were developed to measure the TFP concentrations in mouse plasma and tumor. The minimal PBPK model incorporated a tumor compartment model was used for data fitting. The plasma clearance measured by LBA and IC-LC/MS was comparable in the range of 0.5−0.6 mL/h/kg. However, the tumor exposure measured by the generic human IgG4 IC-LC/MS was significantly underestimated compared with the interferon alpha specific IC-LC/MS and LBA. Furthermore, the minimal PBPK model simultaneously captured the relationship between plasma and tissue exposure. We proposed the streamlined practical strategy to characterize the plasma exposure and tumor distribution of a TFP by both LBA and IC-LC/MS. The minimal PBPK modeling was established for better understanding of pharmacokinetic profile of investigational TFPs in the biotherapeutic discovery.

The 14th Japan Bioanalysis Forum Symposium was held at Tower Hall Funabori, Japan from 1-3 March 2023. The conference theme, 'Bringing Together - the Expertise of Bioanalysis', aimed to enable people from various fields to gather, learn and collaborate together for the common goal of delivering medicines to patients faster. Approximately 360 participants from various fields, including pharmaceutical industries, contractors, academia and regulatory authorities, gathered at an in-person symposium which had an online participation option, for the first time in 4 years. The symposium offered a wide range of topics including ICH M10, new modalities, biomarkers, immunogenicity, electronization and patient-centric sampling. The latest research results were provided from domestic and overseas scientists. This report summarizes the major topics.

Lactobionic acid (LBA) is a fine chemical largely applied in the food, chemical, cosmetics and pharmaceutical industries. Here, its production from ricotta cheese whey (RCW), or scotta, the main by-product obtained from ricotta cheese production process and currently employed mainly for cattle feed, was evaluated. Among seven bacterial species tested, only two Pseudomonas taetrolens strains were selected after preliminary screening in shake-flasks. When autoclaved RCW was used, a lactobionic acid titer of 34.25 ± 2.86 g/l, with a conversion yield (defined as mol LBA/mol of consumed lactose%) of up to 85 ± 7.0%, was obtained after 48 h of batch fermentation in 3 L stirred tank bioreactor. This study is a preliminary investigation on the potential industrial use of scotta as a substrate for bacterial growth and lactobionic acid production that details the possible biotechnological valorization pathways and feasibility of the process. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the performance of MOD16 and GLEAM evapotranspiration (ET) datasets in nine eddy covariance monitoring sites. Data from both ET products were downloaded and its daily means calculated. Evapotranspiration estimations were then compared to the observed ET in the eddy covariance monitoring sites from the Large-Scale Biosphere-Atmosphere Experiment in the Amazon (LBA). We performed a statistical analysis using the correlation coefficient (R), the root mean square error (RMSE) and BIAS. Results indicate that, in general, both products can represent the observed ET in the eddy covariance flux towers. MOD16 and GLEAM showed similar values to the calculated statistics when ET estimates were compared to observed ET. Model estimates and eddy covariance flux towers are subject to uncertainties that influence the analysis of remotely-sensed ET products. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the performance of MOD16 and GLEAM evapotranspiration (ET) datasets in nine eddy covariance monitoring sites. Data from both ET products were downloaded and its daily means calculated. Evapotranspiration estimations were then compared to the observed ET in the eddy covariance monitoring sites from the Large-Scale Biosphere-Atmosphere Experiment in the Amazon (LBA). We performed a statistical analysis using the correlation coefficient (R), the root mean square error (RMSE) and BIAS. Results indicate that, in general, both products can represent the observed ET in the eddy covariance flux towers. MOD16 and GLEAM showed similar values to the calculated statistics when ET estimates were compared to observed ET. Model estimates and eddy covariance flux towers are subject to uncertainties that influence the analysis of remotely-sensed ET products. [ABSTRACT FROM AUTHOR]

A pin made of a copper-based alloy, found at Tapada da Ajuda (Lisbon, Portugal), a site dated to the beginning of the Late Bronze Age, was analyzed by X-ray fluorescence (XRF) spectroscopy and examined by microscopy. The results of this study and the unusual manufacturing technique of the pin are presented and discussed in this paper. Typology and production technique of this object seem to indicate a Central European origin. [ABSTRACT FROM AUTHOR]

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Long Branch Attraction (LBA) is a well-known artifact in phylogenetic reconstruction when dealing with branch length heterogeneity. Here we show another phenomenon, Short Branch Attraction (SBA), which occurs when BLAST searches, a phenetic analysis, are used as a surrogate method for phylogenetic analysis. This error also results from branch length heterogeneity, but this time it is the short branches that are attracting. The SBA artifact is reciprocal and can be returned 100% of the time when multiple branches differ in length by a factor of more than two. SBA is an intended feature of BLAST searches, but becomes an issue, when top scoring BLAST hit analyses are used to infer Horizontal Gene Transfers (HGTs), assign taxonomic category with environmental sequence data in phylotyping, or gather homologous sequences for building gene families. SBA can lead researchers to believe that there has been a HGT event when only vertical descent has occurred, cause slowly evolving taxa to be over-represented and quickly evolving taxa to be under-represented in phylotyping, or systematically exclude quickly evolving taxa from analyses. SBA also contributes to the changing results of top scoring BLAST hit analyses as the database grows, because more slowly evolving taxa, or short branches, are added over time, introducing more potential for SBA. SBA can be detected by examining reciprocal best BLAST hits among a larger group of taxa, including the known closest phylogenetic neighbors. Therefore, one should look for this phenomenon when conducting best BLAST hit analyses as a surrogate method to identify HGTs, in phylotyping, or when using BLAST to gather homologous sequences. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are a unique class of biotherapeutics of inherent heterogeneity and correspondingly complex absorption, distribution, metabolism, and excretion (ADME) properties. Herein, we consider the contribution of various components of ADCs such as various classes of warheads, linkers, and conjugation strategies on ADME of ADCs. Understanding the metabolism and disposition of ADCs and interpreting exposure-efficacy and exposure-safety relationships of ADCs in the context of their various catabolites is critical for design and subsequent development of a clinically successful ADCs. Sophisticated bioanalytical assays are required for the assessments of intact ADC, total antibody, released warhead and relevant metabolites. Both ligand-binding assays (LBA) and hybrid LBA-liquid chromatography coupled with tandem mass spectrometry (LBA-LC-MS/MS) methods have been employed to assess pharmacokinetics (PK) of ADCs. Future advances in bioanalytical techniques will need to address the rising complexity of this biotherapeutic modality as more innovative conjugation strategies, antibody scaffolds and novel classes of warheads are employed for the next generation of ADCs. This review reflects our considerations on ADME of ADCs and provides a perspective on the current bioanalytical strategies for pharmacokinetic assessments of ADCs.

Os aerossóis atmosféricos respondem por uma das maiores incertezas na investigação dos cenários de mudança climática. A margem de erro associada às estimativas nas contribuições dos aerossóis no balanço energético global ainda é elevada, particularmente no que diz respeito ao chamado "efeito indireto". Ainda que o nível de compreensão científico, acerca do efeito indireto tenha avançado significativamente nos últimos anos, este ainda é muito baixo, quando comparado com o entendimento que se tem do papel dos gases de efeito estufa. Particularmente no Brasil, as medidas realizadas dentro do contexto LBA-SMOCC-EMfiN! (Large-Scale Biosphere-Atmosphere Experiment in Amazonia - Smoke Aerosols, Clouds, Rainfall and Climate - Experimento de Microfísica de Nuvens) possibilitaram uma base de dados ampla sobre aerossóis e microfísica de nuvens. Neste trabalho, apresentamos uma revisão de alguns dos principais resultados relacionados a essa base de dados, tanto via análise de resultados experimentais, quanto via modelagem numérica. Conclui-se que alterações significativas no processo de desenvolvimento da precipitação podem ocorrer em associação com a grande quantidade de aerossóis produzidos em queimadas, mas que diversas questões, principalmente referentes ao papel dos núcleos de condensação gigantes e núcleos de gelo ainda precisam ser elucidadas.Atmospheric aerosols account for some of the largest uncertainties regarding climate change scenarios. The uncertainties associated to the estimates of the aerosol contributions in the global energy budget is still very high, particularly concerning the so-called "indirect effect". Hence, although the level of scientific understanding on the role of aerosols in climate have advanced significantly in the last few years, it is still very low in comparison to the well established knowledge concerning the effect of greenhouse gases. Particularly in Brazil, the measurements taken during the LBA-SMOCC-EMfiN! (Large-Scale Biosphere-Atmosphere Experiment inAmazonia - SmokeAerosols, Clouds, Rainfall and Climate - Experimento de Microfísica de Nuvens) provided a comprehensive data base on aerosols and cloud microphysics. In this work, we review some of the major results related to such data base, via both analysis of experimental data and numerical modeling. We conclude that significant changes in precipitation development may occur in association with the large amount of aerosols launched into the atmosphere by forest fires but that several questions, especially those ones concerning giant cloud condensation nuclei and ice nuclei, have to be clarified.

Increasing adoption of location-based services and smartphones leads to optimistic forecasts for location-based mobile advertising (LBA).This study investigates the development of emerging LBA in Singapore by examining stakeholders’ perspectives and shaping forces in the socio-technical subsystems (i.e., technology, market/industry, and government/regulation). In addition to document analysis, it conducts in-depth interviews with key industry players in the LBA value chain, policy-makers, and smartphone consumers in order to identify drivers and challenges in this nascent mobile business. The socio-technical analyses show that LBA in Singapore is technology-ready with government support and industry pull, while conservative advertisers, negative consumer attitudes, and insufficient regulations hinder LBA's diffusion. The results reveal that LBA at an early adopter stage in Singapore has a relatively convergent and competitive value chain, as telcos play a crucial part in creating and distributing LBA services. With a newly launched Personal Data Protection Act, smartphone consumers still show concerns about personal privacy, data security, and intrusive spam. Technical implementation and LBA effectiveness are major inhibitors for advertisers' adoption. The Singapore case offers market and regulatory implications for other mobile-advanced countries to develop mobile marketing, location-based services, and LBA. [ABSTRACT FROM AUTHOR]