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Carbon and nitrogen are crucial elements for life and must be efficiently regenerated in a circular economy. Biomass streams at the end of their useful life, such as sewage sludge, are difficult to recycle even though they contain organic carbon and nitrogen components. Gasification is an emerging technology to utilize such challenging waste streams and produce syngas that can be further processed into, e.g., Fischer-Tropsch fuels, methane, or methanol. Here, the objective is to investigate if nitrogen can be recovered from product gas cleaning in a dual fluidized bed (DFB) after gasification of softwood pellets to form yeast biomass. Yeast biomass is a protein-rich product, which can be used for food and feed applications. An aqueous solution containing ammonium at a concentration of 66 mM was obtained and by adding other nutrients it enables the growth of the methylotrophic yeast Komagataella phaffii to form 6.2 g.L −1 dry yeast biomass in 3 days. To further integrate the process, it is discussed how methanol can be obtained from syngas by chemical catalysis, which is used as a carbon source for the yeast culture. Furthermore, different gas compositions derived from the gasification of biogenic feedstocks including sewage sludge, bark, and chicken manure are evaluated for their ability to yield methanol and yeast biomass. The different feedstocks are compared based on their potential to yield methanol and ammonia, which are required for the generation of yeast biomass. It was found that the gasification of bark and chicken manure yields a balanced carbon and nitrogen source for the formation of yeast biomass. Overall, a novel integrated process concept based on renewable, biogenic feedstocks is proposed connecting gasification with methanol synthesis to enable the formation of protein-rich yeast biomass.

Polymer fractions from a biological matrix have been well-characterized by vibrational spectroscopy, XPS, CP/MAS 13C NMR, MALDI-TOF mass spectrometry, thermal analysis, and SEM, and all the results had corroborated for the chemical extraction of β-glucan polymers grafted amino groups by peptide bonds (namely NH2-β-glucan) as well as a cyclic oligosaccharide. Our primary purpose was to explore the polysaccharide extraction parameters in the sample of Usnea lichen, mainly in terms of extraction time and concentration of the extractive alkaline solution, to investigate the chemical characterization of the polysaccharide fractions. The low-cost methodology adopted in this work was able to extract the materials of interest with the expected efficiency without the significant impact of chemicals on the environment. The chemical extraction of an NH2-bonded biopolymer can be a very interesting material for many applications since chemical functionalization is crucial to introducing specific properties for developing new materials. In this regard, the cyclic β-glucan described as a very porous material is highly desirable for various applications in the biomedical, biotechnological, and environmental areas.

Understanding the transition from quiescent primordial follicles to activated primary follicles is vital for characterizing ovarian folliculogenesis and improving assisted reproductive techniques. To date, no study has investigated preantral follicle crowding in the ovaries of livestock or characterized these crowds according to follicular morphology and ovarian location (portions and regions) in any species. Therefore, the present study aimed to assess the crowding (clustering and neighborhood) patterns of preantral follicles in the equine ovary according to mare age, follicular morphology and developmental stage, and spatial location in the ovary. Ovaries from mares (n = 8) were collected at an abattoir and processed histologically for evaluation of follicular clustering using the Morisita Index and follicular neighborhoods in ovarian sections. Young mares were found to have a large number of preantral follicles with neighbors (n = 2,626), while old mares had a small number (n = 305). Moreover, young mares had a higher number of neighbors per follicle (2.6 ± 0.0) than old mares (1.2 ± 0.1). Follicle clustering was shown to be present in all areas of the ovary, with young mares having more clustering overall than old mares and a tendency for higher clustering in the ventral region when ages were combined. Furthermore, follicles with neighbors were more likely to be morphologically normal (76.5 ± 6.5%) than abnormal (23.5 ± 6.5%). Additionally, morphologically normal activated follicles had increased odds of having neighbors than normal resting follicles, and these normal activated follicles had more neighbors (2.6 ± 0.1) than normal resting follicles (2.3 ± 0.1 neighbors). In the present study, it was demonstrated that preantral follicles do crowd in the mare ovary and that clustering/neighborhood patterns are dynamic and differ depending on mare age, follicular morphology, and follicular developmental stage.

Ovarian tissue collected by biopsy procedures allows the performance of many studies with clinical applications in the field of female fertility preservation. The aim of the present study was to investigate the influence of reproductive phase (anestrous vs. diestrous) and ovarian structures (antral follicles and corpus luteum) on the quality, class distribution, number, and density of preantral follicles, and stromal cell density. Ovarian fragments were harvested by biopsy pick-up procedures from mares and submitted to histological analysis. The mean preantral follicle and ovarian stromal cell densities were greater in the diestrous phase and a positive correlation of stromal cell density with the number and density of preantral follicles was observed. The mean area (mm2) of ovarian structures increased in the diestrous phase and had positive correlations with number of preantral follicles, follicle density, and stromal cell density. Biopsy fragments collected from ovaries containing an active corpus luteum had a higher follicle density, stromal cell density, and proportion of normal preantral follicles. In conclusion, our results showed: (1) the diestrous phase influenced positively the preantral follicle quality, class distribution, and follicle and stromal cell densities; (2) the area of ovarian structures was positively correlated with the follicle and stromal cell densities; and (3) the presence of an active corpus luteum had a positive effect on the quality of preantral follicles, and follicle and stromal densities. Therefore, herein we demonstrate that the presence of key ovarian structures favors the harvest of ovarian fragments containing an appropriate number of healthy preantral follicles.

In a phase 3 trial, the addition of neoadjuvant and adjuvant pembrolizumab to standard care improved event-free survival among participants with locally advanced head and neck cancer without affecting surgical outcomes.

A bstract Nelson-Barr theories solve the strong CP problem with CP spontaneously broken at Λ cp and transmitted to the CP conserving version of the SM through vector-like quarks (VLQs). For an arbitrary number of CP breaking scalars and VLQs, we perform the full one-loop matching calculations at Λ cp up to dimension five operators and the relevant matching calculations at the VLQ scale relevant to tracking the contributions to the parameter θ ¯ . In the EFT after the CP breaking scalars have been integrated out, we confirm that the running of θ ¯ at one-loop is induced by CP violating dimension five operators and similarly by dimension six operator after matching to the SMEFT. In the latter, an additional contribution enters in the matching to θ ¯ at tree-level due to a dimension five operator. Analyzing the experimental constraint from θ ¯ for generic settings, we see that a large separation between Λ cp and the VLQ scale already suppresses the one-loop contribution to θ ¯ sufficiently. We confirm that a simple extension based on a nonconventional CP has vanishing one-loop contribution to θ ¯ . Part of our results can be also applied to generic VLQ extensions of the SM.

This study aimed to evaluate the effect of whole-body vibrations (WBV) on ergonomics related to static posture during the operation of container handling machines (Portainer). A 3D numerical model of a seated man was developed using modal and harmonic analysis based on the finite element method (FEM), and implemented on the ANSYS platform to achieve this. Quantitative analyses of whole-body vibrations were carried out in actual workplaces at a port terminal in northeastern Brazil, considering the interaction between the human and the machine. A comparison was made between the real data collected at the operating sites and the values obtained from the developed model. Concerning vibration exposure, the results revealed a critical situation: in 86.2% of cases, the Acceleration of Resulting Normalized Exposure—A(8)—exceeded the alert level, and in 96.6% of cases, the Resulting Vibration Dose Value (VDV) also surpassed this threshold. Similarly, an alert level was exceeded in 97.0% of cases. According to the maximum limits established by Brazilian legislation, the acceleration from normalized exposure did not exceed the limit, while the resulting vibration dose value was surpassed in 20% of cases. The modal analysis results helped identify the critical directions of vibration response, thus supporting the assessment of human exposure effects and the structural performance of the system analyzed. The harmonic analysis showed good agreement between the model and the real acceleration data in the frequency range of 3 to 4 Hz.

Comprehensive studies on spatial distribution of preantral follicles in the ovary are scarce. Considering that preantral follicles represent the main ovarian reserve, harvesting of these follicles is crucial for the development/use of assisted reproductive techniques. Therefore, knowledge on follicle spatial distribution can be helpful for targeting areas with richer number of preantral follicles through biopsy procedures. The aim of this study was to assess the distribution and localization of equine preantral follicles according to: (i) age, (ii) ovarian portion (lateral and intermediary) and region (dorsal and ventral), (iii) distance from the geometric center, and (iv) follicular class. Ovaries from young and old mares (n = 8) were harvested in a slaughterhouse and submitted to histological processing for further evaluation. For data analyses, a novel methodology was developed according to the geometric center of each histological section for a precise determination of preantral follicle distribution. Results indicated that (i) equine preantral follicles are clustered and located near to the ovarian geometric center, and that aging induced their dispersion through the ovarian cortex; (ii) the distance from the geometric center was shorter for developing follicles than primordial; and (iii) secondary follicles were more distant from the geometric center but closer to the ovulation fossa. In conclusion, the spatial distribution of preantral follicles was successfully determined in the equine ovary and was affected by age, region, and portion.

Malaria is an infectious disease that affects over 216 million people worldwide, killing over 445,000 patients annually. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new drug candidates is a major global health priority. Aiming to make the drug discovery processes faster and less expensive, we developed binary and continuous Quantitative Structure-Activity Relationships (QSAR) models implementing deep learning for predicting antiplasmodial activity and cytotoxicity of untested compounds. Then, we applied the best models for a virtual screening of a large database of chemical compounds. The top computational predictions were evaluated experimentally against asexual blood stages of both sensitive and multi-drug-resistant Plasmodium falciparum strains. Among them, two compounds, LabMol-149 and LabMol-152, showed potent antiplasmodial activity at low nanomolar concentrations (EC50 <500 nM) and low cytotoxicity in mammalian cells. Therefore, the computational approach employing deep learning developed here allowed us to discover two new families of potential next generation antimalarial agents, which are in compliance with the guidelines and criteria for antimalarial target candidates.

Aspergillus fumigatus , one of the most important human-pathogenic fungal species, is able to cause aspergillosis, a heterogeneous group of diseases that presents a wide range of clinical manifestations. Invasive pulmonary aspergillosis is the most serious pathology in terms of patient outcome and treatment, with a high mortality rate ranging from 50% to 95% primarily affecting immunocompromised patients. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, there were several reports of evolution of clinical azole resistance in the last decade. Caspofungin, a noncompetitive β-1,3-glucan synthase inhibitor, has been used against A. fumigatus , but it is fungistatic and is recommended as second-line therapy for invasive aspergillosis. More information about caspofungin tolerance and resistance is necessary in order to refine antifungal strategies that target the fungal cell wall. Here, we screened a transcription factor (TF) deletion library for TFs that can mediate caspofungin tolerance and resistance. We have identified 11 TFs that are important for caspofungin sensitivity and/or for the c aspofungin p aradoxical e ffect (CPE). These TFs encode proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism or cell wall remodeling, and mitochondrial respiratory function. The study of those genes regulated by TFs identified in this work will provide a better understanding of the signaling pathways that are important for caspofungin tolerance and resistance. Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in A. fumigatus and new strategies are needed to combat invasive aspergillosis. Caspofungin is effective against other human-pathogenic fungal species, but it is fungistatic only against A. fumigatus . Resistance to caspofungin in A. fumigatus has been linked to mutations in the fksA gene that encodes the target enzyme of the drug β-1,3-glucan synthase. However, tolerance of high caspofungin concentrations, a phenomenon known as the c aspofungin p aradoxical e ffect (CPE), is also important for subsequent adaptation and drug resistance evolution. Here, we identified and characterized the transcription factors involved in the response to CPE by screening an A. fumigatus library of 484 null transcription factors (TFs) in CPE drug concentrations. We identified 11 TFs that had reduced CPE and that encoded proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism, and cell wall remodeling. One of these TFs, FhdA, was important for mitochondrial respiratory function and iron metabolism. The Δ fhdA mutant showed decreased growth when exposed to Congo red or to high temperature. Transcriptome sequencing (RNA-seq) analysis and further experimental validation indicated that the Δ fhdA mutant showed diminished respiratory capacity, probably affecting several pathways related to the caspofungin tolerance and resistance. Our results provide the foundation to understand signaling pathways that are important for caspofungin tolerance and resistance. IMPORTANCE Aspergillus fumigatus , one of the most important human-pathogenic fungal species, is able to cause aspergillosis, a heterogeneous group of diseases that presents a wide range of clinical manifestations. Invasive pulmonary aspergillosis is the most serious pathology in terms of patient outcome and treatment, with a high mortality rate ranging from 50% to 95% primarily affecting immunocompromised patients. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, there were several reports of evolution of clinical azole resistance in the last decade. Caspofungin, a noncompetitive β-1,3-glucan synthase inhibitor, has been used against A. fumigatus , but it is fungistatic and is recommended as second-line therapy for invasive aspergillosis. More information about caspofungin tolerance and resistance is necessary in order to refine antifungal strategies that target the fungal cell wall. Here, we screened a transcription factor (TF) deletion library for TFs that can mediate caspofungin tolerance and resistance. We have identified 11 TFs that are important for caspofungin sensitivity and/or for the c aspofungin p aradoxical e ffect (CPE). These TFs encode proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism or cell wall remodeling, and mitochondrial respiratory function. The study of those genes regulated by TFs identified in this work will provide a better understanding of the signaling pathways that are important for caspofungin tolerance and resistance.