It remains unclear in the literature what is the cause of the so-called alkali-carbonate reaction (ACR) damage to concrete yet, a consensus is reached when considering dedolimitization as non-expansive. However, expansion and cracks as distress features are often attributed to alkali-silica reaction (ASR) when evidence of a reactive mineral is found in the aggregate. Evidently, different types of aggregates may produce different types and degrees of damage. Therefore, this work aims to assess the damage to concrete generated and propagated by the so-called ACR susceptible reactive Kingston coarse aggregate through mechanical testing (i.e., direct shear test), microscopy (the damage rating index – DRI), and other techniques. Distinct induced expansion levels (i.e., 0%, 0.05%, 0.12%, and 0.20%) were selected to compare the distress caused by ACR to concrete affected by ASR. Result show that the behaviour of ACR, namely as captured through the DRI, is inconsistent with that of ASR thus attesting to ACR being a distinct distress mechanism.

Quantitative polymerase chain reaction (qPCR) has emerged as an important bioanalytical method for assessing the pharmacokinetics of human cell-based medicinal products after xenotransplantation into immunodeficient mice. A particular challenge in bioanalytical qPCR studies is that the different tissues of the host organism can affect amplification efficiency and amplicon detection to varying degrees, and ignoring these matrix effects can easily cause a significant underestimation of the true number of target cells in a sample. Here we describe the development and drug regulatory-compliant validation of a TaqMan® qPCR assay for quantification of mesenchymal stromal cells in the range of 125 to 20,000 cells/200 µl lysate by amplification of a human-specific, highly repetitive αsatellite DNA sequence of the chromosome 17 centromere region HSSATA17. Assessment of matrix effects in 14 different mouse tissues and blood revealed a wide range of spike recovery rates across the different tissue types from 11 to 174%. Based on these observations, we propose to perform systematic spike-and-recovery experiments during assay validation and to correct for the effects of the different tissue matrices on cell quantification in subsequent bioanalytical studies by multiplying the back-calculated cell number by tissue-specific factors derived from the inverse of the validated percent recovery rate.

The doctoral defense is an important step in the doctoral journey and an essential requirement for obtaining the doctoral degree. Past research on the doctoral defense has focused solely on national practices. In this work, I investigate the potential link between the doctoral defense format based on its major and minor elements and the perception of the defense by the student. For this purpose, I first reviewed the different defense formats used internationally to extract the different elements of the doctoral defense, as well as the literature on students’ perceptions of the doctoral defense. Then, I carried out an international survey which received 297 responses, of which 204 completed surveys which I used for the analysis in this article. I first analyzed the outcomes of the survey using qualitative and quantitative methods, and then cross-correlated the outcomes of defense format to the outcomes of student perception. From this analysis, I observe that the defense elements that positively impact the students’ perception are: publication of the thesis before the defense, receiving committee feedback before the defense, knowing the recommendation of one or more committee members in advance, having the supervisor present in the audience or as part of the committee, using a dress code, and including a laudatio. The final conclusion of this work is threefold. The first conclusion is that the details of the defense format impact most the students’ perception. The second conclusion is that doctoral students on average value the defense as a positive experience. The third conclusion is that the defense format cannot influence two important aspects of how a student perceives the defense: the student’s inner life and lived experience during the defense, and the behavior of the committee members.

Establishment of diagnostic methods with low detection limits plays a critical role in the maintenance of early diagnosis, prevention of serious neurological complications, and control of the spread of ZIKA. In this study, we established the micro-droplet digital polymerase chain reaction (ddPCR) and real-time fluorescent quantification PCR (qPCR) protocols for the detection of Zika virus based on the NS5 gene. For the Zika standard plasmid, the standard curve of R² was 0.999, and the amplification efficiency was 92.203%, as determined by qPCR. Both ddPCR and qPCR were positive for cell culture of Zika nucleic acid.The minimum detection limit of ddPCR is 1–2 times lower than qPCR. Moreover, all tests of Dengue virus (1–4 serotypes) were negative in cell culture. Overall, these results suggested than ddPCR may have a lower limit of detection than qPCR.

Computed tomography (CT) offers detailed insights into the internal anatomy of patients, partic-ularly for spinal vertebrae examination. However, CT scans are associated with higher radiation exposure and cost compared to conventional X-ray imaging. In this study, we applied a Genera-tive Adversarial Network (GAN) framework to reconstruct 3D spinal vertebrae structures from synthetic biplanar X-ray images, specifically focusing on anterior and lateral views. The synthetic X-ray images were generated using the DRRGenerator module in 3D Slicer, by incorporating segmentations of spinal vertebrae in CT scans for the region of interest focussing. The approach leverages a novel feature fusion technique based on X2CT-GAN to combine information from both views and employs a combination of Mean Squared Error (MSE) loss and adversarial loss to train the generator, resulting in high-quality synthetic 3D spinal vertebrae CTs. A total of n=440 CT data were processed. We evaluated the performance of our model using multiple metrics, in-cluding Mean Absolute Error (MAE) (for each slice of the 3D volume [MAE0] and for the entire 3D volume [MAE]), Cosine Similarity, Peak Signal-to-Noise Ratio (PSNR), 3D Peak Sig-nal-to-Noise Ratio (PSNR-3D), and Structural Similarity Index (SSIM). The average PSNR was 28.394 dB, PSNR-3D was 27.432, SSIM was 0.468, cosine similarity was 0.484, MAE0 was 0.034, and MAE was 85.359. The results demonstrated the effectiveness of the approach in reconstruct-ing 3D spinal vertebrae structures from biplanar X-rays, although some limitations in accurately capturing the fine bone structures and maintaining the precise morphology of the vertebrae were present. This technique has the potential to enhance the diagnostic capabilities of low-cost X-ray machines while reducing radiation exposure and cost associated with CT scans, paving the way for future applications in spinal imaging and diagnosis.

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared 15 SCs and their derivatives (tetrahydrocannabinol [THC], naphthoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.

Pasmo (Septoria linicola) is a fungal disease causing major losses in seed yield and quality, and stem fibre quality in flax. Pasmo resistance (PR) is quantitative and has low heritability. To improve PR breeding efficiency, the accuracy of genomic prediction (GP) was evaluated using a diverse worldwide core collection of 370 accessions. Four marker sets, including three defined by 500, 134, and 67 previously identified quantitative trait loci (QTL) and one of 52,347 PR-correlated genome-wide single nucleotide polymorphisms, were used to build ridge regression best linear unbiased prediction (RR-BLUP) models using pasmo severity (PS) data collected from field experiments performed during five consecutive years. With five-fold random cross-validation, GP accuracy as high as 0.92 was obtained from the models using the 500 QTL when the average PS was used as the training dataset. GP accuracy increased with training population size, reaching values >0.9 with training population size greater than 185. Linear regression of the observed PS with the number of positive-effect QTL in accessions provided an alternative GP approach with an accuracy of 0.86. The results demonstrate the GP models based on marker information from all identified QTL and the 5-year PS average is highly effective for PR prediction.

Weed competitive ability (WCA) is a desirable key trait for the improvement of grain yield under direct-seeded rice (DSR) and the aerobic rice ecosystem. The present study targeted screening of 167 introgression lines (ILs) of a Green Super Rice (GSR) IR2-6 population derived from a cross between Weed Tolerant Rice 1 (WTR1) as the recipient parent and Y134 as the donor parent developed at IRRI for weed competitiveness in screen house conditions (SHC). The ILs were phenotyped for WCA traits such as early seed germination (ESG) and early seedling vigor (ESV) in Petri dishes and pot experiment conditions. The results of phenotypic variance revealed ESG-related traits, especially first germination count (1st GC) that positively correlated with second germination count (2nd GC), germination percentage (GP), total dry weight (TDW), total fresh weight (TFW), and vigor index (VI-1), whereas, in ESV, all the traits were positively correlated with each other except for three traits: root dry weight (RDW), 1st GC, and GP-2. The ESG and ESV traits are vital for weed competitiveness. A 6K SNP array was used to study the genetic association for the WCA traits. Forty-four QTLs for WCA traits were mapped on all chromosomes (except on chromosomes 4 and 8) through single marker analysis (SMA). Out of 44 QTLs, 29 were associated with ESG traits and 15 with ESV traits, with LOD scores of 2.93 to 8.03 and 2.93 to 5.04 and explained phenotypic variance ranging from 7.85% to 19.9% and from 7.85% to 13.2%, respectively. However, 31 QTLs were contributed by a negative additive allele from Y134, whereas a positive additive allele was contributed by WTR1 in 13 QTLs. Among them, two QTL hotspot regions were mapped on chromosome 11 (24.7-27.9 Mb) and chromosome 12 (14.8-17.4 Mb). The majority of the QTLs related to WCA traits were grouped into two QTL hotspots: QTL hotspot-I (qAFW11.1, qFC11.1, qFC11.2, qSC11.1, qGP-111.1, qGP-111.2, qTFGS11.1, qVI-111.1, and qVI-111.2) and QTL hotspot-II (qFC12.1, qFC12.2, qSC12.1, qFC12.2, qGP-112.1, qGP-112.2, qTFGS12.1, qTFGS12.2, qVI-112.1, qIV12.2, qFC12.1, and qGC12.2), and a few of them were co-localized on chromosomes 11 and 12. Further, we fine-tuned in the genomic regions of QTL hotspots and identified a total of 13 putative candidate genes on chromosomes 11 and 12 collectively. The present study is the first report on the genetic basis of WCA-related traits and the co-localized QTLs, which could be highly valuable in future breeding programs aiming to improve WCA in rice.

Enhanced food and nutrition security remains a primary goal for every community. Several interventions have been promoted in dry areas to improve issues on food and nutrition security. However, studies on the level of knowledge, cultural norms, perceptions and attitudes that are key drivers in adoption and uptake to highlight gaps and provide evidence for improvement are limited. This study investigated variables influencing the adoption and implementation of an integrated crop-dairy goat farming system in Elgeyo Marakwet. A descriptive cross-sectional survey entailing qualitative and quantitative approaches among farmers practicing integrated farming was undertaken. A thematic questionnaire was used to collect quantitative data, while key informant interviews and focus groups discussions were used in qualitative research. This study utilized the multi-stage sampling procedure to sample the farmers and sample size was calculated based on Krejcie and Morgan table. Data analysis for quantitative data was done using SPSS software while qualitative data utilized N-vivo software The findings show that farmers have knowledge on the integrated farming system. Age, level of education, land size, gender, perceptions and attitudes influence adoption. Small animals like dairy goats are associated to women in this community hence increasing their participation in access, control and decision making of agricultural resources. The key findings of this study provide baseline data that can form evidence to help inform policy on the indicators contributing to adoption of integrated crop-dairy goat systems to enhance food and nutrition security

Since the come up in the 70´s, various decentralized control methodologies have been developed to deal with the challenge of controlling complex and/or spatially distributed systems with multiple inputs and multiple outputs (MIMO), e.g., chemical plants, power systems, water systems, etc. In general, the use of distributed information and control structures requires to synthesize control laws in a constrained (decentralized) information structure. The article presents another version of the unified frequency domain robust decentralized controller design method [1]. The proposed design procedure is appropriate for uncertain dynamic MIMO systems given as a set of transfer function matrices. Its main framework is provided by the Equivalent Subsystems Method [1, 24] guaranteeing fulfillment of the necessary and sufficient stability condition of the overall closed-loop system if individual closed-loop equivalent subsystems are stable. Generating sets of equivalent subsystems for all transfer function matrices describing the uncertain MIMO plant allows to use the QFT method [19] to independently design local robust SISO controllers that constitute the resulting decentralized controller implemented on true subsystems. The developed design procedure is verified and illustrated on a case study on robust decentralized level controller design for a quadruple tank process [2, 24].

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits in a population. To date, a total of 267 QTL for 29 quantitative traits have been reported in 13 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, scaffold sequences, or pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but were mainly based on simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. This article provides methods with software tools and database files to uniquely map SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules. Using these methods, 195 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters. Mapping of QTL from different studies to the same reference enables comparisons and facilitates genome-wide QTL analysis, candidate gene scanning, and breeding applications.

The limited information available on the structure of complexes involving transcription factors and cognate DNA response elements represents a major obstacle in the quest to understand their mechanism of action at the molecular level. We implemented a concerted structural proteomics approach, which combined hydrogen-deuterium exchange (HDX), quantitative protein-protein and protein-nucleic acid cross-linking (XL), and homology analysis, to model the structure of the complex between the full-length DNA binding domain (DBD) of FOXO4 and its DNA binding element (DBE). The results confirmed that FOXO4-DBD assumes the characteristic forkhead topology shared by these types of transcription factors, but its binding mode differs significantly from those of other members of the family. The results showed that the binding interaction stabilized regions that were rather flexible and disordered in the unbound form. Surprisingly, the conformational effects were not limited only to the interface between bound components but extended also to distal regions that may be essential to recruiting additional factors to the transcription machinery. In addition to providing valuable new insights into the binding mechanism, this project provided an excellent evaluation of the merits of structural proteomics approaches in the investigation of systems that arematerial not directly amenable to traditional high-resolution techniques.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using the fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, 7 years apart. An age-related decrease in MPF was found in global WM, GM, and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%) and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Rice blast, caused by Magnaporthe oryzae, poses significant threat to rice production. Rice blast susceptibility has been observed in Japanese rice varieties with excellent eating quality. Enhancing blast resistance is essential to ensure minimal use of agricultural chemicals. Two types of blast resistance are observed: true resistance, which is a type of qualitative resistance expressed by a major gene, and field resistance, which is a type of quantitative resistance expressed by multiple micro-acting genes. ‘Resistance collapse’, in which a variety with a true resistance gene becomes diseased by blast fungus races compatible with the resistance gene, has been observed. Varieties carrying blast-resistance genes, such as Pb1 (panicle blast resistance 1), have been developed through DNA marker-assisted selection. In this review, we focus on the Pb1, which expresses strong quantitative resistance to panicle blast and has been widely used in Japan without showing ‘resistance collapse’ for 40 years. Pb1 is an ‘adult plant resistance gene’ that does not exert strong selection pressure on the blast population during the leaf blast stage, thus preventing the selective multiplication of Pb1-compatible blast strains. This epidemiological mechanism prevents ‘resistance collapse’. Interdisciplinary research and breeding are required to sustainably use genes that induce high field resistance.

Progesterone receptor (PGR) expression level determines biological characteristics of the serous ovarian carcinoma, and low PGR expression appears to be associated with chemoresistance and worse outcome. In this study, we aimed to find relationships between tumor progesterone receptor level and RNA-profile (miRNAs, piwiRNAs, and mRNAs), determining its biological characteristics and behavior. For this purpose, we applied next generation sequencing of small noncoding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze FFPE and frozen tumor samples as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumour (SBT), low-grade and high-grade serous ovarian carcinoma (LGSOC and HGSOC, respectively). We found significant upregulation of MMP7 and MUC16 and downregulation of PGR in LGSOC and HGSOC in comparison with BSC. The tissue content of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, miR-125b-5p significantly inversely correlated with the expression level of MUC16 and blood serum CA125 concentration, and significantly directly correlated with the PGR expression level in tumor tissue. On the contrary, the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, miR-93-5p, responsible for epithelial-mesenchymal transition (EMT) of the cell, significantly directly correlated with the blood serum CA125 concentration and significantly inversely correlated with the PGR expression level in the tumor tissue. Levels of the EMT-associated miRNAs significantly directly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, hsa_piR_019914 in tumor tissues. Among them, expression level of hsa_piR_004307 significantly inversly correlated with the PGR expression level in the tumor. Two optimal logistic regression models were developed based on the quantitation of hsa_piR_020813, miR-16-5p, hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, miR-93-5p in the tumor tissue, both of which significantly diagnose PGR-negative tumor phenotype with 93% sensitivity. According to FunRich3.1.3 functional enrichment analysis tool, 72 gene-targets of miRNA and piRNA identified here as markers of PGR-negative ovarian tumor phenotype were proven to be mutated in different cancers such as ovarian, breast, colorectal, liver, stomach, lung, endometrial, thyroid cancer. Among them, the blood plasma levels of miR-16-5p and hsa_piR_022437 can be used to diagnose PGR-negative tumor phenotype with 86% sensitivity before surgery and chemotherapy to choose the treatment strategy for this most aggressive type of ovarian cancer (for instance, neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy) to increase the effectiveness of treatment and longevity of the patient.

Fusarium wilt of banana is a devastating disease that has decimated banana production worldwide. Host resistance to Fusarium oxysporum f. sp. cubense (Foc), the causal agent of this disease, is genetically dissected in this study using two Musa acuminata ssp. malaccensis segregating populations segregating for Foc Tropical (TR4) and Subtropical (STR4) race 4 resistance. Marker loci and trait association using 11 SNP-based PCR markers allowed the candidate region to be delimited to a 12.9 cM genetic interval corresponding to a 959 kb region on Chromosome 3 of ‘DH-Pahang’ reference assembly v4. Within this region, there is a cluster of pattern recognition receptors, namely leucine rich repeat ectodomain containing receptor-like protein kinases, cysteine-rich cell wall associated protein kinases, and leaf rust 10 disease-resistance locus receptor-like proteins positioned in an interspersed arrangement. Their transcript levels were rapidly upregulated in the resistant but not in susceptible F2 progenies at the onset of infection. This suggests that one or several of these genes may control resistance at this locus. To confirm the segregation of single-gene resistance, we generated an inter-cross between the resistant parent ‘Ma850’ and a susceptible line ‘Ma848’, to show that the STR4 resistance co-segregated with marker ‘28820’ at this locus. Finally, an informative SNP marker 29730 allowed the locus specific resistance to be assessed in a collection of diploid and polyploid banana plants. Out of the 60 lines screened, 22 lines were predicted to carry resistance at this locus, including lines known to be TR4 resistant, such as ‘Pahang’, ‘SH-3362’, ‘SH-3217’, ‘Ma-ITC0250’, and ‘DH-Pahang/CIRAD 930’. Additional screening in the International Institute for Tropical Agriculture’s collection suggests that the dominant allele is common among in the elite ‘Matooke’ NARITA hybrids, as well as in other triploid or tetraploid hybrids derived from East African highland bananas. Fine-mapping and candidate gene identification will allow characterization of molecular mechanisms underlying TR4 resistance. The markers developed in this study can now aid the marker-assisted selection of TR4 resistance in breeding programs around the world.