Early Generation Research Articles

Abstract 4609: Plixorafenib (plixo) synergizes with MEK inhibitors (MEKi) in MAPK pathway inhibition in BRAF V600 and non V600 alterations, with higher potency compared to early generation BRAFi and pan-RAFi

Abstract The efficacy of BRAFi in V600 mutated tumors is established and requires effective inhibition of the MAPK pathway. However, the use approved BRAFi leads to paradoxical MAPK pathway activation associated with toxicities and to acquired resistance. Therefore, these inhibitors were combined with MEKi to mitigate toxicities, which has been shown to be more effective than monotherapy in some settings. Although effective, these combinations result in bothersome side effects, a high discontinuation rate, and risk of secondary malignancies, indicating a continued unmet need. Also, ~35% of all BRAF mutations occur outside the V600 codon, composed of a wide array of missense mutations, fusions, and in-frame deletions, which are not targeted by the earlier generation BRAFi. By design, plixo (FORE8394; PLX8394), a clinical stage BRAFi, binds the monomeric form of BRAF and inhibits its dimerization, while sparing the WT form, avoiding paradoxical MAPK pathway activation. We hypothesized that the combination of plixo with a MEKi will improve its efficacy and potency through maximal suppression of the MAPK pathway. Using ForeSight assay, a unique platform for testing MAPK signaling, we tested the efficacy of plixo and 4 MEKi (trametinib, cobimetinib, binimetinib and mirdametinib) across a cohort 18 BRAF alterations (V600E, 2 class II and 15 fusions) as single agents and in combinations. The combinations of plixo with the different MEKi were synergistic across all BRAF alterations tested. Furthermore, we compared the potency of a combination of plixo with binimetinib (bini) to that of another BRAFi (vemurafenib) or pan-RAFi’s (tovorafenib and lifirafenib) with bini in 2 class I, 3 class II and 7 BRAF fusions using the foresight assay. The IC:50 of BRAF V600E expressing cells treated with plixo + bini was 6nM compared with 57nM, 103nM and 190nM for the tovorafenib, vemurafenib, and lifirafenib combinations with bini respectively. A similar trend was shown in 9 of 11 additional alterations tested, indicating the potency of the combination of plixo + bini. Results were validated using western blot analysis and cell viability assays of both melanoma and CRC V600E mutated cell lines. Western blot correlated with ForeSight results both in single agents and combination treatment. Cells treated with plixo + bini showed complete growth inhibition while the same drug concentrations of vemurafenib + bini and tovorafenib + binimetinib showed no growth inhibition beyond the effect of bini single agent. These results indicate the improved efficacy of plixo + bini combination in inhibiting MAPK signaling and cancer cell proliferation. Overall results support that maximal suppression of the MAPK pathway with plixo is more potent in combination with a MEK inhibitor in BRAF V600 and non-V600 nonclinical models compared to BRAF or pan-RAF combinations. Citation Format: Gabi Tarcic, Limor Cohen, Stacie Peacock Shepherd, Natalie Filippov Levy, Hana Billauer, Lea Birnbaum, Sara Gasasa, Roey Maor, Reham Abu-Liel, Eden Goldfarb. Plixorafenib (plixo) synergizes with MEK inhibitors (MEKi) in MAPK pathway inhibition in BRAF V600 and non V600 alterations, with higher potency compared to early generation BRAFi and pan-RAFi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4609.

The Evolution of Mobile Communication: A Comprehensive Survey on 5G Technology

This comprehensive survey meticulously navigates the evolution of mobile communication, focusing on the revolutionary strides introduced by 5G technology. The study elucidates primary objectives, research methodology, pivotal findings, and implications inherent in the trajectory of mobile communication. It aims for a detailed examination of the technological landscape, outlining features that distinguish 5G from its predecessors. The research methodology involves an exhaustive literature review, culminating in a comprehensive overview of 5G technology. Key findings highlight 5G's transformative capacities, spanning unparalleled data transfer speeds, low-latency communication, and applications like IoT, augmented reality, and autonomous vehicles. The study underscores 5G's far-reaching impact across various sectors. Serving as both a retrospective analysis and a valuable resource, the survey guides researchers, industry professionals, and policymakers through the intricate landscape of 5G technology. Addressing the imperative of accommodating increasing mobile data traffic, the 5G network strives for improved spectrum utilization, energy efficiency, and QoS parameters. Notable innovations include Massive MIMO, promising high spectral efficiency. The focus on efficacy, accuracy, and channel estimation techniques is evident. The article explores specific requirements of 5G wireless communication systems, addressing challenges faced by earlier mobile generations. The advent of 5G emerges as a pivotal solution, aiming for a 1000-fold capacity gain and assuring quality-of-service, higher spectral efficiency, ultra-reliable communication, and facilitating massive machinetype communication. Challenges in traffic load and resource consumption necessitate innovative approaches. The research reviews emerging wireless technologies, including an analysis of Massive MIMO as an efficient solution. The paper promises to be a valuable resource, contributing to the seamless development of state-of-the-art 5G and B5G networks, recognizing the importance of continued research and innovation in the dynamic landscape of mobile communication technologies.

Real-World Outcomes for the Fifth-Generation Balloon Expandable Transcatheter Heart Valve in the United States

BackgroundThe fifth-generation SAPIEN 3 Ultra Resilia valve (S3UR) incorporates several design changes as compared with its predecessors, the SAPIEN 3 (S3) and SAPIEN 3 Ultra (S3U) valves, including bovine leaflets treated with a novel process intended to reduce structural valve deterioration via calcification, as well as a taller external skirt on the 29-mm valve size to reduce paravalvular leak (PVL). The clinical performance of S3UR compared with S3 and S3U in a large patient population has not been previously reported. ObjectivesThe aim of this study was to compare S3UR to S3/S3U for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR). MethodsPatients enrolled in the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between January 1, 2021, and June 30, 2023, who underwent TAVR with S3UR or S3U/S3 valve platforms were propensity-matched and evaluated for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes. Results10,314 S3UR patients were propensity matched with 10,314 patients among 150,539 S3U/S3 patients. At 30 days, there were no statistically significant differences in death, stroke, or bleeding, but a numerically higher hospital readmission rate in the S3UR cohort (8.5% vs 7.7%; P = 0.04). At discharge, S3UR patients exhibited significantly lower mean gradients (9.2 ± 4.6 mm Hg vs 12.0 ± 5.7 mm Hg; P < 0.0001) and larger aortic valve area (2.1 ± 0.7 cm2 vs 1.9 ± 0.6 cm2; P < 0.0001) than patients treated with S3/S3U. The 29-mm valve size exhibited significant reduction in mild PVL (5.3% vs 9.4%; P < 0.0001). ConclusionsS3UR TAVR is associated with lower mean gradients and lower rates of PVL than earlier generations of balloon expandable transcatheter heart valve platforms.

User generated content and its influence on relationship marketing among Generation Z

The post-millennial Generation Z, which was born into a technologically advanced society, is one of the most recent subjects in marketing. There are numerous companies with a wide range of products, and you are bombarded with advertisements from every direction. How then do you market to the most technologically advanced generation, whose focus is hard to get and who has higher expectations of you as a marketer than earlier generations? User generated material is one of the options you might consider (UGC).

Structural and Geochemistry of Air Piau Gold Mineralisation in Kelantan, North-East Peninsular Malaysia

The formation of the Air Piau Gold Deposit in North-East Peninsular Malaysia due to Permo–Triassic subduction and collision between Sibumasu and East Malaya blocks and resulted in several phases of deformation, contraction, and metamorphism. Kinematic and petrography study of quartz veins in Air Piau area observed whether following the foliation of metamorphic rock or crosscut the foliation. Early generation of veining system in Air Piau follow the host rock foliation (V1). Meanwhile the later formation of the hydrothermal vein has a cross-cutting relationship with foliation (V2). Some veins observed were sheared and brecciated (V3). Positive correlation between Au and As concentration that can be characterized these deposit formed at mesozonal zone. V3 vein type showed the brecciated texture of vein indicates the brittle structure deformation. The conceptual model of orogenic gold, this type of V3 vein can be classified as epizonal zone. Regionally, the Air Piau gold deposit shares geologically similarities (in term of tectonic setting, geological structures controlled, host rock, ore gechemistry) with many other sediment/metasediment- hosted, orogenic gold deposits in Peninsular Malaysia such as Tersang, Selinsing and Penjom. Furthermore, Air Piau gold deposit characteristics as discussed before supported the theory related with orogenic/mesothermal gold from various researchers However, a number of inferences on classified Air Piau gold deposit model as orogenic gold deposit remains speculative in the absence importance data like ore geochemistry data (Hg, Sb and Te element concentrations) and fluid inclusion data.

Timing and Mechanism of Ore Precipitation in Porphyry Cu Systems: Insight from LA-ICP-MS Analysis of Fluid Inclusions and In Situ Oxygen Isotope Analysis of Hydrothermal Quartz at Zhunuo Porphyry Cu Deposit, China

Abstract The timing and mechanism of ore precipitation in porphyry copper systems are hot topics and remain controversial. The large Miocene collision-related Zhunuo porphyry Cu deposit in the Gangdese belt of southern Tibet, China, was produced by multistage quartz veining and hydrothermal alteration, accompanied by Cu sulfide precipitation. In this study, we have combined cathodoluminescence (CL) petrography with in situ oxygen isotope analysis and fluid inclusion microthermometry and laser ablation-inductively coupled plasma-mass spectrometer microanalysis to constrain the growth history of individual quartz veins, the source and evolution of the hydrothermal fluids, and the timing and mechanism of ore precipitation at Zhunuo. Early quartz A veins associated with potassic alteration are composed of quartz, K-feldspar, biotite, Cu-Fe sulfides, and pyrite. Quartz B veins are composed of quartz, Cu-Fe sulfides, molybdenite, and pyrite. CL imaging shows that quartz grains in the A and B veins consist of abundant early generation of bright-luminescent quartz (QA and QB) with volumetrically minor later generation of dull-luminescent quartz (QA-crack and QB-crack) occurring in the voids or at the margins of the QA and QB veins with embayed contacts. Cu-Fe sulfides are generally in contact with the dull-luminescent quartz and locally in contact with the bright-luminescent quartz and K-feldspar in the A and B veins or occur as disseminations in the potassic-altered porphyries that have been overprinted by chlorite ± muscovite alteration. QA and QB contain single-phase intermediate-density inclusions and abundant brine and vapor-rich inclusions. A boiling assemblage in QA has a homogenization temperature of ~560°C and trapping pressure of ~530 bar. Two boiling assemblages in QB have homogenization temperatures of ~440°C with trapping pressures of ~230 and ~250 bar, indicating a transition from lithostatic to hydrostatic conditions at a paleodepth of ~2.0 to 2.5 km. QA-crack and QB-crack contain aqueous inclusions with lower homogenization temperatures of 340° to 400°C and salinities of 6 to 12 wt % NaCl equiv. In situ oxygen isotopes indicate that QA and QB have δ18O values of 7.6 to 11.4‰, whereas QA-crack and QB-crack have δ18O values of –7.2 to 6.7‰. Combined with fluid inclusion compositions, we propose that condensation of vapors into brines and mixing with 25 to 60% meteoric water can produce the salinity and oxygen isotopes of fluids that caused the dissolution of the early bright-luminescent quartz and the precipitation of the later dull-luminescent quartz. Zhunuo Cu-Fe sulfides are in contact with the bright-luminescent quartz and cut the growth bands. The dull-luminescent quartz in contact with the Cu-Fe sulfides has oscillatory growth banding. In addition, Cu-Fe sulfides in the A and B veins or in the potassic-altered rocks coexist with chlorite ± muscovite alteration minerals. These geologic observations, together with evidence that there is an abrupt drop in the Cu/(Na + K) ratio by more than one order of magnitude in the aqueous fluids within the dull-luminescent quartz compared to the brines within the bright-luminescent quartz, indicate that precipitation of Cu-Fe sulfides occurred after the potassic alteration stage and during the chlorite ± muscovite alteration stage. Ore precipitation was associated with mixing of magmatic fluids (brines + vapors) with meteoric water, accompanied by fluid cooling, salinity decrease, and retrograde quartz solubility as the rocks transitioned from lithostatic to hydrostatic conditions. During continued cooling in the latest stage, the hydrothermal fluids precipitated D veins that contain abundant pyrite with minor quartz. Quartz in the D veins (QD) contains aqueous inclusions with much lower temperatures and Cu/(Na + K) ratios, indicating that most of the Cu-Fe sulfides have been precipitated during this stage.

Blended BA.5 infection within 8 days after a boosted bivalent mRNA vaccination strengthens and lengthens the host immunity.

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.

Effects of Seed Rate on Seed Multiplication Ratio, Seed Quality And Yield of Malt Barley Seed Classes Under Irrigated Conditions in Northwest Amhara

Field experiments were conducted to identify seed rate enhancing seed multiplication ratio, seed quality and yield on Ibone (174/03) malt barely variety performance in Koga district during 2019 and 2020 irrigation seasons. Three seed classes (breeder, pre-basic and basic seeds) and seed rates (40, 60, 80 and 100 kg.ha-1) were compared. The experimental design randomized complete block in factorial arrangement with three replications. Analysis of variance was showed that the interaction effect of seed class and seed rate was not significant (P&gt;0.05) for the parameters of days to maturity, plant height, spike length, seed yield, seed multiplication ratio and thousand seed weight. The study result depicted that seed rate had brought significant effect on the seed yield and multiplication ratio of malt barely. Results indicated that lower seed rates gave better seed multiplication ratio in the districts. Increasing seed rate from 40 to 80 kg.ha-1 has increased seed yield from 3356.1 kg.ha-1 to 3696.8 kg ha-1 though seed yield difference between seed rates of 60 and 80 kg.ha-1 was statistically non-significant (p&gt;0.05). Increasing seed rate from 40 to 60 kg.ha-1 has continuously improved seed yield from 3356.1 to 3592.1 kg.ha-1 in all seed class in the districts, but the difference was statistically non-significant. In conclusion, seed rates as low as 60 kg.ha-1 can be used at all seed classes to accelerate early generation seed multiplication within the fast track variety release program in Western Amhara Region.

Hybridization and gene expression: Beyond differentially expressed genes.

Gene expression has a key role in reproductive isolation, and studies of hybrid gene expression have identified mechanisms causing hybrid sterility. Here, we review the evidence for altered gene expression following hybridization and outline the mechanisms shown to contribute to altered gene expression in hybrids. Transgressive gene expression, transcending that of both parental species, is pervasive in early generation sterile hybrids, but also frequently observed in viable, fertile hybrids. We highlight studies showing that hybridization can result in transgressive gene expression, also in established hybrid lineages or species. Such extreme patterns of gene expression in stabilized hybrid taxa suggest that altered hybrid gene expression may result in hybridization-derived evolutionary novelty. We also conclude that while patterns of misexpression in hybrids are well documented, the understanding of the mechanisms causing misexpression is lagging. We argue that jointly assessing differences in cell composition and cell-specific changes in gene expression in hybrids, in addition to assessing changes in chromatin and methylation, will significantly advance our understanding of the basis of altered gene expression. Moreover, uncovering to what extent evolution of gene expression results in altered expression for individual genes, or entire networks of genes, will advance our understanding of how selection moulds gene expression. Finally, we argue that jointly studying the dual roles of altered hybrid gene expression, serving both as a mechanism for reproductive isolation and as a substrate for hybrid ecological adaptation, will lead to significant advances in our understanding of the evolution of gene expression.

Assessment of Genetic Variability, Heritability and Genetic Advance in Maize Genotypes (Zea mays L.)

Aim: The aim of the present research work was to estimate the genetic variability, broad sense heritability and genetic advance for various yield and its contributing characters of 39 maize genotypes.&#x0D; Methodology: 39 maize genotypes were sown in randomized block design and replicated thrice to evaluate various genetic parameters. The data was recorded on twelve quantitative traits including days to fifty percent tasseling, days to fifty percent silking, days to maturity, plant height, ear height, ear length, ear diameter, number of kernel rows/ear, number of kernels/row, 100kernels weight, shelling % and grain yield/plant.&#x0D; Results: The mean sum of squares due to genotypes for each of the 12 traits under study indicated significant differences in analysis of variance. High to moderate genotypic and phenotypic coefficients of variation as well as genetic advance were observed in the traits yield per plant, plant height, ear height, number of kernels per row, and 100-kernel weight. These findings suggest that the heritability of these traits is most likely the result of additive gene effects and that selection in early generations may be effective for these traits. On the other hand, the remaining characters days to 50% tasseling, days to 50% silking, number of kernel rows per ear, and shelling percentage were recorded with high heritability with low genotypic and phenotypic coefficient of variation and genetic advance suggesting non-additive gene action for control of these traits which provides limited scope for improvement by selection.&#x0D; Conclusion: Among the characters studied, grain yield, plant height, and ear height had high heritability and high values of genetic advance indicating that these characters were controlled by additive gene action and so phenotypic selection is effective for improvement of these traits.

Synthesis and Preliminary Evaluation of an ASGPr-Targeted Polycationic β-Cyclodextrin Carrier for Nucleosides and Nucleotides.

Most antiviral and anticancer nucleosides are prodrugs that require stepwise phosphorylation to their triphosphate nucleotide form for biological activity. Monophosphorylation may be rate-limiting, and the nucleotides may be unstable and poorly internalized by target cells. Effective targeting and delivery systems for nucleoside drugs, including oligonucleotides used in molecular therapeutics, could augment their efficacy. The development of a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor (ASGPr) is now reported. In this work, the polycationic, polygalactosyl drug delivery carrier heptakis[6-amino-6-deoxy-2-O-(3-(1-thio-β-D-galactopyranosyl)-propyl)]-β-cyclodextrin hepta-acetate salt (GCyDAc), potentially a bifunctional carrier of (poly)nucleotides, was modeled by molecular docking in silico as an ASGPr-ligand, then synthesized for testing. The antivirals arabinosyl adenine (araA, vidarabine, an early generation antiviral nucleoside), arabinosyl adenine 5'-monophosphate (araAMP), and 12-mer-araAMP (p-araAMP) were selected for individual formulation with GCyDAc to develop this concept. Experimentally, beta cyclodextrin was decorated with seven protonated amino substituents on the primary face, and seven thiogalactose residues on its secondary face. AraA, araAMP, and p-araAMP were individually complexed with GCyDAc and complex formation for each drug was confirmed by differential scanning calorimetry (DSC). Finally, the free drugs and their GCyDAc complexes were evaluated for antiviral activity using ASGPr-expressing HepAD38 cells in cell culture. In this model, araA, araAMP, and p-araAMP showed relative antiviral potencies of 1.0, 1.1, and 1.2, respectively. In comparison, GCyDAc-complexes of araA, araAMP, and p-araAMP were 2.5, 1.3, and 1.2 times more effective than non-complexed araA in suppressing viral DNA production. The antiviral potencies of these complexes were minimally supportive of the hypothesis that ASGPr-targeted, CyD-based charge-association complexation of nucleosides and nucleotides could effectively enhance antiviral efficacy. GCyDAc was non-toxic to mammalian cells in cell culture, as determined using the MTS proliferation assay.

Artificial maturation of a Silurian hydrocarbon source rock: Effect of sample grain size and pyrolysis heating rate on oil generation and expulsion efficiency

Although artificial maturation of hydrocarbon source rocks by laboratory pyrolysis is far from representing natural maturation, it is a useful tool to investigate the process. In this study, we used routine open system pyrolysis for powder samples and Restricted System anhydrous Pyrolysis (RSP) for cm-sized Silurian shale source rock fragments to artificially mature the samples to different end-temperatures in the presence of a flowing carrier gas. Maturation experiments on rock fragments enable the simulation of physical barriers for the generated hydrocarbons that need to be overcome before expulsion from the source rock can occur. Based on the artificial maturation results in this study, oil expulsion efficiency from the Silurian shale source rock was 46% at the early oil generation stage and increased to 74% at approximately the peak oil generation stage.Furthermore, we have compared artificial maturation results from powder-form and fragment-form samples with natural-maturation series and found that artificial maturation of fragment-form samples sufficiently resembles natural maturation of the Silurian shales. It is therefore possible to simulate the early, middle and peak oil generation stages of natural maturation and expulsion efficiencies. This implies that, lab-based oil expulsion efficiencies from increasing maturity and hydrocarbon generation can be incorporated into the basin modeling.

Deciphering biomass contributing traits of interspecific and intergeneric hybrids derived from early generations hybrids of Saccharum and Erianthus Spp. as potential sources of biomass and bioenergy

Sugarcane (Saccharum spp., hybrids (2 n=100–130)) is one of the industrial crops cultivated mainly for sugar in the tropical and subtropical regions. It has earned the attention of many countries as a prominent energy crop owing to its exceptional biomass production potential. Energy cane is a hybrid of commercial and wild sugarcane, which was bred for high fiber content and low sucrose. Average energy cane biomass production potential is much higher, and brix levels are lower, compared with commercial sugarcane. A total of 138 Saccharum spp. hybrids representing 99 interspecific hybrids (ISH) and 39 intergeneric hybrids (IGH) derived from intercrossing of species clones of S. spontaneum, S. robustum and wild genus, Erianthus arundinaceus were evaluated along with the commercial hybrids for their cane growth and quality parameters, fibre and biomass traits. In general, the ISH and IGH clones recorded higher fibre per cent with maximum of 32% (ISH-562) and maximum biomass yield of 396.16 t/ha (ISH-571), lower values for quality characters such as juice brix 10.68% (ISH-571), sucrose 6.65% (ISH-579) and commercial cane sugar (CCS) 3.66% (ISH-579). Total biomass showed a significant positive correlation with the number of tillers (‘000/ha) at 120 days (r =0.176), number of shoots (‘000/ha) at 240 days (r = 0.129), number of stalks (‘000/ha) at 360 days (r = 0.249), cane height (r = 0.163) and single cane weight (SCW) (r = 0.508) and positive correlation with quality traits indicates the possibility of simultaneous improvement for biomass and quality traits. However, the fibre per cent has showed a significant negative correlation with quality traits viz., extraction % (r = −0.616), juice brix % (r = −0.419), sucrose % (r = −0.422), CCS % (r = −0.409), cane diameter (r = −0.600) and SCW (r = −0.475) suggests difficulty in combining both the traits. In the cluster analysis, the cluster III with 12 clones is more similar to commercial cultivars for juice quality (20.16% juice brix and 18.08% of sucrose) and cane traits, however the cluster V consist of 4 clones (ISH-557, ISH-563, ISH-571 and ISH-572) recorded highest total biomass yield of 368.72 t/ha and a mean fibre of 19.50% could be exploited for green energy purposeor as parental stocks in breeding programme.

One model to unite them all: Personalized federated learning of multi-contrast MRI synthesis

Curation of large, diverse MRI datasets via multi-institutional collaborations can help improve learning of generalizable synthesis models that reliably translate source- onto target-contrast images. To facilitate collaborations, federated learning (FL) adopts decentralized model training while mitigating privacy concerns by avoiding sharing of imaging data. However, conventional FL methods can be impaired by the inherent heterogeneity in the data distribution, with domain shifts evident within and across imaging sites. Here we introduce the first personalized FL method for MRI Synthesis (pFLSynth) that improves reliability against data heterogeneity via model specialization to individual sites and synthesis tasks (i.e., source-target contrasts). To do this, pFLSynth leverages an adversarial model equipped with novel personalization blocks that control the statistics of generated feature maps across the spatial/channel dimensions, given latent variables specific to sites and tasks. To further promote communication efficiency and site specialization, partial network aggregation is employed over later generator stages while earlier generator stages and the discriminator are trained locally. As such, pFLSynth enables multi-task training of multi-site synthesis models with high generalization performance across sites and tasks. Comprehensive experiments demonstrate the superior performance and reliability of pFLSynth in MRI synthesis against prior federated methods.

An Optimal Model to Improve Genomic Prediction for Protein Content and Test Weight in a Diverse Spring Wheat Panel

In recent years, genomic selection has been widely used in plant breeding to increase genetic gain. Selections are based on breeding values of each genotype estimated using genome-wide markers. The present study developed genomic prediction models for grain protein content (GPC) and test weight (TW) in a diverse panel of 170 spring wheat lines phenotyped in five environments. Five prediction models (GBLUP, RRBLUP, EGBLUP, RF, RKHS) were investigated. The population was genotyped for genome-wide markers with the Infinium iSelect 90 K SNP assay. Environmental variation was adjusted by calculating BLUPs across environments using the complete random effect GxE model. Both GPC and TW showed high heritability of 0.867 and 0.854, respectively. When using the five-fold cross-validation scheme in the five statistical models, we found that the EGBLUP model had the highest mean prediction accuracy (0.743) for GPC, while the RRBLUP model showed the highest mean prediction accuracy (0.650) for TW. Testing various proportions of the training population indicated that a minimum of 100 genotypes were required to train the model for optimum accuracy. Testing the prediction across environments showed that BLUPs outperformed 80% of the tested environments, even though at least one of the environments had higher prediction accuracies for each trait. Thus, the optimized GS model for GPC and TW has the potential to predict trait values accurately. Implementing GS would aid breeding through accurate early generation selection of superior lines, leading to higher genetic gain per breeding cycle.

Detection of six potato viruses using double antibody sandwich ELISA from in vitro, screen house and field grown potato crops in Ethiopia

Virus infection in seed potato reduces yield, and the problem is exacerbated when an early-generation seed is affected. The prevalence of six key potato viruses, PVY, PVX, PLRV, PVA, PVS, and PVM, was assessed among decentralized seed multipliers such as individuals, farmer seed group cooperatives, private companies, and agricultural research centers that produce early generation seed in six major potato growing districts in Ethiopia. A total of 262 leaf samples were randomly collected from potato plants and analyzed using a double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) for six major potato viruses. Potato virus prevalence was calculated as the proportion of samples that tested positive for the viruses against the total number of samples tested. The prevalence of infection with at least one of the six viruses was 98.2%. Among the samples analyzed, 17.2% had a single viral infection with one of the six viruses while the majority had multiple infections. The ELISA tests confirmed presence of latent virus infection in early generation seeds from the three EGS producers and in different seed classes. This result indicates that virus infection is widespread in the country, limiting potato production. To address this issue, it is critical to develop a robust system that prevents viral infection build-up and spread in the seed system through regular seed quality assurance and certification, particularly for early generation seed.

Unveiling the sweetness: evaluating yield and quality attributes of early generation sweet corn (Zea mays subsp. sachharata) inbred lines through morphological, biochemical and marker-based approaches.

Sweet corn is gaining tremendous demand worldwide due to urbanization and changing consumer preferences. However, genetic improvement in this crop is being limited by narrow genetic base and other undesirable agronomic traits that hinder the development of superior cultivars. The main requirement in this direction is the development of potentially promising parental lines. One of the most important strategies in this direction is to develop such lines from hybrid-oriented source germplasm which may provide diverse base material with desirable biochemical and agro-morphological attributes. The study was undertaken to carry out morphological and biochemical evaluation of 80 early generation inbred lines (S2) of sweet corn that were developed from a cross between two single cross sweet corn hybrids (Mithas and Sugar-75). Moreover, validation of favourable recessive alleles for sugar content was carried out using SSR markers. The 80 sweet corn inbreds evaluated for phenotypic characterization showed wide range of variability with respect to different traits studied. The highest content of total carotenoids was found in the inbred S27 (34μgg-1) followed by the inbred S65 (31.1μgg-1). The highest content for total sugars was found in S60 (8.54%) followed by S14 (8.34%). Molecular characterization of 80 inbred lines led to the identification of seven inbreds viz., S21, S28, S47, S48, S49, S53, and S54, carrying the alleles specific to the sugary gene (su1) with respect to the markers umc2061 and bnlg1937. Comparing the results of scatter plot for biochemical and morphological traits, it was revealed that inbreds S9, S23, S27 and S36 contain high levels of total sugars and total carotenoids along with moderate values for amylose and yield attributing traits. The inbred lines identified with desirable biochemical and agro-morphological attributes in the study could be utilized as source of favourable alleles in sweet corn breeding programmes after further validation for disease resistance and other agronomic traits. Consequently, the study will not only enhance the genetic base of sweet corn germplasm but also has the potential to develop high-yielding hybrids with improved quality. The inbreds possessing su1 gene on the basis of umc2061 and bnlg1937 markers were also found to possess high sugar content. This indicates the potential of these lines as desirable candidates for breeding programs aimed at improving sweet corn yield and quality. These findings also demonstrate the effectiveness of the molecular markers in facilitating marker-assisted selection for important traits in sweet corn breeding.

QTL-seq analysis identified the genomic regions of plant height and days to heading in high-latitude rice.

Introduction: Rice (Oryza sativa L.) is one of the most extensive crops in the world. China's Heilongjiang Province is the northernmost rice-growing region in the world. However, rice cultivars suitable for growth in low-latitude regions may not mature normally due to their distinct climate and short frost-free period. It is necessary to precisely determine the frost-free period for each region to make the best use of the rice growth stage so as to ensure the maturity and yield of different rice cultivars in Heilongjiang Province. The time span of the heading stage is a key parameter for evaluating the adaptability of a rice cultivar to a specific rice-growing region. Given the above facts, it is of high importance to study the associated genes and sites controlling days to heading (DH) and plant height (PH) of rice in Heilongjiang Province. Bulked segregant analysis (BSA) combined with high-throughput sequencing can effectively exclude interferences from background genomic differences, making it suitable for analyzing the associated sites of complex agronomic traits in early generations. Methods: In this study, an F3 segregating population was obtained by crossing two main cultivars that are grown under different temperatures and day-light conditions in Heilongjiang. Two pools of extreme phenotypes were built for the DH and PH of the population. For SNP and InDel variants obtained from whole-genome resequencing in the pools, an association analysis was performed using the Euclidean distance (ED) algorithm and the SNP/InDel index algorithm. Results: The intersection of SNP and InDel regions associated with the phenotypes was considered to obtain the final associated sites. After excluding interferences from the cloned genes on chromosomes 2 and 7, a total length of 6.34Mb on chromosomes 1, 3, and 10 and 3.16Mb on chromosomes 1 and 10 were left associated with PH and DH, respectively. Then, we performed a gene annotation analysis for candidate genes in the remaining regions using multiple genome annotation databases. Our research provides basic data for subsequent gene mapping and cloning. Discussion: By mining more genetic loci associated with the days to heading and plant height of rice, we may provide abundant genetic resources for refined molecular breeding in Heilongjiang Province.

Optimizing speed breeding and seed/pod chip based genotyping techniques in pigeonpea: A way forward for high throughput line development

BackgroundThe challenge of pigeonpea breeding lies in its photosensitivity and seasonal specificity. This poses a problem to the breeder, as it restricts to single generation advancement in a year. Currently, the cross to cultivar gap is twelve to thirteen years resulting in a limited number of varietal releases over the past six decades. Shortening the breeding cycle was need of the hour, unlikely achieved by conventional breeding. To overcome these hindrances speed breeding was a necessary leap. An experiment was planned to optimize the speed breeding coupled with single seed descent and seed or pod chip-based genotyping to shorten the breeding cycle in pigeonpea at ICRISAT, Hyderabad. Monitored photoperiod, light wavelength, temperature and crop management regime were the indicators attributing to the success of speed breeding.ResultA photoperiod of 13 h: 8 h: 13 h at vegetative: flowering and pod filling stages is ideal for shortening the breeding cycle. Broad spectrum light (5700 K LED) hastened early vegetative growth and pod formation. Whereas far-red (735 nm) light favoured early flowering. A significant difference between the photoperiods, genotypes as well as photoperiod x genotype interaction for both days to flowering and plant height was noted.ConclusionThe optimized protocol serves as a road map for rapid generation advancement in pigeonpea. Deploying this protocol, it is possible to advance 2–4 generations per year. The breeding cycle can be reduced to 2–4 years which otherwise takes 7 years under conventional breeding. Single Seed Descent and seed or pod chip-based genotyping for early generation marker assisted selection, strengthened the precision of this technique aiding in high throughput line development.

Stability of grain zinc concentrations across lowland rice environments favors zinc biofortification breeding.

One-third of the human population consumes insufficient zinc (Zn) to sustain a healthy life. Zn deficiency can be relieved by increasing the Zn concentration ([Zn]) in staple food crops through biofortification breeding. Rice is a poor source of Zn, and in countries predominantly relying on rice without sufficient dietary diversification, such as Madagascar, Zn biofortification is a priority. Multi-environmental trials were performed in Madagascar over two years, 2019 and 2020, to screen a total of 28 genotypes including local and imported germplasm. The trials were conducted in the highlands of Ankazomiriotra, Anjiro, and Behenji and in Morovoay, a location representative of the coastal ecosystem. Contributions of genotype (G), environment (E), and G by E interactions (GEIs) were investigated. The grain [Zn] of local Malagasy rice varieties was similar to the internationally established grain [Zn] baseline of 18-20 μg/g for brown rice. While several imported breeding lines reached 50% of our breeding target set at +12 μg/g, only few met farmers' appreciation criteria. Levels of grain [Zn] were stable across E. The G effects accounted for a main fraction of the variation, 76% to 83% of the variation for year 1 and year 2 trials, respectively, while GEI effects were comparatively small, contributing 23% to 9%. This contrasted with dominant E and GEI effects for grain yield. Our results indicate that local varieties tested contained insufficient Zn to alleviate Zn malnutrition, and developing new Zn-biofortified varieties should therefore be a priority. GGE analysis did not distinguish mega-environments for grain [Zn], whereas at least three mega-environments existed for grain yield, differentiated by the presence of limiting environmental conditions and responsiveness to improved soil fertility. Our main conclusion reveals that grain [Zn] seems to be under strong genetic control in the agro-climatic conditions of Madagascar. We could identify several interesting genotypes as potential donors for the breeding program, among those BF156, with a relatively stable grain [Zn] (AMMI stability value (ASV) = 0.89) reaching our target (>26 μg/g). While selection for grain yield, general adaptation, and farmers' appreciation would have to rely on multi-environment testing, selection for grain [Zn] could be centralized in earlier generations.