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Discovery of new protective malaria antigens will enable the development of novel vaccine formulations with potentially higher efficacy. While several high-throughput experimental approaches enable the identification of novel immunogens, none so far has been designed to selectively identify protective antigens. Here, we propose that sieve analysis conducted on the whole genome (SAWG) can be used specifically for this purpose. We review available medium- to high-throughput methods for antigen identification and contextualize the need for the identification of protective antigens. We then provide the rationale for why SAWG is ideally suited for the identification of protective antigens in recombining pathogens with large genome size, describe conditions for optimal use, and discuss potential pitfalls. Most importantly, this approach can be applied to the discovery of new protective targets in any recombining organism for which there is a whole organism-based vaccine that can be safely deployed in a disease-endemic region.

The ENCODE Consortium’s efforts to annotate noncoding cis -regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, noncoding CRISPR screens offer a systematic approach to investigate cis -regulatory mechanisms. The ENCODE4 Functional Characterization Centers conducted 108 screens in human cell lines, comprising >540,000 perturbations across 24.85 megabases of the genome. Using 332 functionally confirmed CRE–gene links in K562 cells, we established guidelines for screening endogenous noncoding elements with CRISPR interference (CRISPRi), including accurate detection of CREs that exhibit variable, often low, transcriptional effects. Benchmarking five screen analysis tools, we find that CASA produces the most conservative CRE calls and is robust to artifacts of low-specificity single guide RNAs. We uncover a subtle DNA strand bias for CRISPRi in transcribed regions with implications for screen design and analysis. Together, we provide an accessible data resource, predesigned single guide RNAs for targeting 3,275,697 ENCODE SCREEN candidate CREs with CRISPRi and screening guidelines to accelerate functional characterization of the noncoding genome. This analysis provides 108 noncoding CRISPR screens collated by the ENCODE4 consortium and establishes experimental guidelines for future CRISPRi screens characterizing functional cis -regulatory elements.

Theoretical and experimental studies have revealed that energy dissipation and release play an important role in the deformation and failure of coal rocks. To determine the relationship between energy transformation and coal failure, the mechanical behaviors of coal specimens taken from a 600-m deep mine were investigated by conventional triaxial compression tests using five different confining pressures. Each coal specimen was scanned by microfocus computed tomography before and after testing to examine the crack patterns. Sieve analysis was used to measure the post-failure coal fragments, and a fractal model was developed for describing the size distribution of the fragments. Based on the test results, a damage evolution model of the rigidity degeneration of coal before the peak strength was also developed and used to determine the initial damage and critical damage variables. It was found that the peak strength increased with increasing confining pressure, but the critical damage variable was almost invariant. More new cracks were initiated in the coal specimens when there was no confining pressure or the pressure was too high. The parameters of failure energy ratio β and stress drop coefficient α are further proposed to describe the failure mode of coal under different confining pressures. The test results revealed that β was approximately linearly related to the fractal dimension of the coal fragments and that a higher failure energy ratio corresponded to a larger fractal dimension and more severe failure. The stress drop coefficient α decreased approximately exponentially with increasing confining pressure, and could be used to appropriately describe the evolution of the coal failure mode from brittle to ductile with increasing confining pressure. A large β and small α under a high confining pressure were noticed during the tests, which implied that the failure of the coal was a kind of pseudo-ductile failure. Brittle failure occurred when the confining pressure was unloaded—an observation that is important for the safety assessment of deep mines, where a high in situ stress might result in brittle failure of the coal seam, or sudden outburst.

The online real-time particle size analysis of the microencapsules manufacturing process using the continuous solvent evaporation method was performed using focused beam reflectance measurement (FBRM). In this paper, we use FBRM measurements to investigate the effects of polymer type and compare the size distributions to those obtained using other sizing methods such as optical microscope and laser diffraction. FBRM was also utilized to measure the length-weighted chord length distribution (CLD) and particle size distribution (PSD) online during particle solidification, which could not be done with laser diffraction or nested sieve analysis. The chord lengths and CLD data were taken at specific times using an online FBRM probe mounted below the microparticle. The timing of the FBRM determinations was coordinated with the selection of microparticle samples for particle size analysis by optical microscope and laser diffraction calculation as a reference. For all three produced batches tested, FBRM, laser diffraction, and sieve analysis yielded similar results. Hardening time for the transformation of emulsion droplets into solid microparticles occurred within the first 10.5, 19, 25, 30, and 55 min, according to FBRM results. The FBRM CLDs revealed that a larger particle size mean resulted in a longer CLD and a lower peak of particle number. The FBRM data revealed that the polymer type had a significant impact on microparticle CLD and the transformation process.

Polymethyl methacrylate is a synthetic polymer which is known for its durability and initial setting time. This research project helps to investigate the effect of partial replacement of polymethyl methacrylate on the compressive strength of concrete cubes. Further, this study aims to explore the role of polymethyl methacrylate as a sustainable alternative of traditional cement concrete, thereby reducing the impact of carbon footprint into the environment by the production of cement. in this work 54 number of concrete cubes along replacement of cement with different proportions (0%, 2%, 4%, 6%, 8% & 10%) of PMMA have been casted in the laboratory, All the casted concrete cube has been tested after 3 days, 14 days & 28 days. After the testing, the result indicates that replacement of 4% of cement gives higher compressive strength of the cubes as recorded 21.91% from nominal cube, but the strength goes down with the lower percentage of replacement. In conclusion the 6% replacement of PMMA with cement gives the optimum and 4% gives the maximum strength ratio used for casting the concrete cubes. It is also noticed that PMMA makes more homogeneous mixture as compared to nominal mix, So, it can be preferred for further research in different aspect of concrete structure.

Sample selection means the act of picking a sample from a material that is representative of the whole. This method is just as important as the testing itself. To establish the minimum weight of an aggregate sample, regardless of whether it was taken in the field or in the laboratory, the maximum particle size is the determining factor. It is certain that the weight will be more than the quantity required for testing. A significant factor that affects the weight of the aggregate sample is the amount of precision that is sought for the test. Within the scope of this investigation, total aggregate sample was modeled by employing a multi-linear approximation function for Fuller’s curve. Aggregate particles are classified into classes according to their median diameter, and each class is simulated independently from the others. The root mean square error (RMSE) of the discrepancies between the target and sample curve was analyzed for two selected samples of total aggregate; this analysis was carried out as part of a stochastic analysis that involved one hundred realizations in the sampling process. An equation has been proposed that relate the maximum predicted RMSE with maximum aggregate size and sample weight by predicting the error for any diameter and sample weight through controlling the allowable error, the weight of sample aggregate can be found for each maximum diameter of aggregate. It was found for Iraqi standard the maximum RMSE not exceeded 2.3% for different diameter.

Effective interpretation of genome function and genetic variation requires a shift from epigenetic mapping of cis -regulatory elements (CREs) to characterization of endogenous function. We developed hybridization chain reaction fluorescence in situ hybridization coupled with flow cytometry (HCR–FlowFISH), a broadly applicable approach to characterize CRISPR-perturbed CREs via accurate quantification of native transcripts, alongside CRISPR activity screen analysis (CASA), a hierarchical Bayesian model to quantify CRE activity. Across >325,000 perturbations, we provide evidence that CREs can regulate multiple genes, skip over the nearest gene and display activating and/or silencing effects. At the cholesterol-level-associated FADS locus, we combine endogenous screens with reporter assays to exhaustively characterize multiple genome-wide association signals, functionally nominate causal variants and, importantly, identify their target genes. HCR–FlowFISH is a new approach to characterize CRISPR-perturbed cis -regulatory elements (CREs) via accurate quantification of native transcripts, alongside CRISPR activity screen analysis (CASA), a hierarchical Bayesian model to quantify CRE activity.

Preserving historic buildings requires renovation using compatible plasters that closely resemble the original ones. However, achieving this likeness requires a thorough characterization of the original plaster. This article explores the challenges of characterizing historic lime-based plasters from two architecturally interesting buildings in the Czech Republic dating back to the first half of the 20th century. Key issues include the determination of the binder-to-aggregate ratio, the fine aggregate particle size distribution, the mineralogical composition, and the degree of lime plaster carbonation. Experimental methods include X-ray diffraction analysis (XRD), pH-value determination, hydrochloric acid dissolution of binder components, sieve analysis, thermogravimetric analysis (TG), and differential scanning calorimetry (DSC). The tested plasters are compared, and the effectiveness of various approaches is evaluated. The binder-to-aggregate ratios are approximately 1:5. The plaster from one of the buildings was almost pure (lime binder + aggregate), while the second one contained other components, such as calcium silicate hydrates, gypsum, and magnesium phases.

CRISPR base editing screens enable analysis of disease-associated variants at scale; however, variable efficiency and precision confounds the assessment of variant-induced phenotypes. Here, we provide an integrated experimental and computational pipeline that improves estimation of variant effects in base editing screens. We use a reporter construct to measure guide RNA (gRNA) editing outcomes alongside their phenotypic consequences and introduce base editor screen analysis with activity normalization (BEAN), a Bayesian network that uses per-guide editing outcomes provided by the reporter and target site chromatin accessibility to estimate variant impacts. BEAN outperforms existing tools in variant effect quantification. We use BEAN to pinpoint common regulatory variants that alter low-density lipoprotein (LDL) uptake, implicating previously unreported genes. Additionally, through saturation base editing of LDLR , we accurately quantify missense variant pathogenicity that is consistent with measurements in UK Biobank patients and identify underlying structural mechanisms. This work provides a widely applicable approach to improve the power of base editing screens for disease-associated variant characterization. BEAN is a Bayesian approach for analyzing base editing screens with improved effect size quantification and variant classification. Applied to low-density lipoprotein (LDL)-associated common variants and saturation base editing of LDLR , BEAN identifies new LDL uptake genes and offers insights into variant structure–pathogenicity mechanisms.

The paper presents the characteristics of unplasticized PVC composites modified with biofiller obtained from the waste eggshells of hen eggs. The composites obtained by extrusion contained from 10 phr to 40 phr of biofiller. The filler was characterized using the SEM, TG, and sieve analysis methods. The influence of the filler on the processing properties was determined using plastographometric and MFR tests. Fundamental analysis of mechanical properties was also performed, i.e., Charpy impact strength and determination of tensile properties. The mechanical properties were supported with dynamical mechanical thermal analysis, time of thermal stability, and thermogravimetric analysis. Structure analysis was also performed using SEM and X-ray microcomputed tomography (micro-CT). The processing properties of the tested composites do not give grounds for disqualifying such material from traditional processing PVC mixtures. Notably, the biofiller significantly improves thermal stability. Ground eggshells (ES) work as scavengers for the Cl radicals released in the first stage, which delays the PVC chain’s decay. Additionally, a significant increase in the value of the modulus of elasticity and softening point (VST) of the composites concerning PVC was found. Ground hen eggshells can be used as an effective filler for PVC composites.