Initial Experiments Research Articles

Memory-Augmenting Decoder-Only Language Models through Encoders (Student Abstract)

The Transformer architecture has seen a lot of attention in recent years also thanks to its ability to scale well and allow massive parallelism during training. This has made possible the development of Language Models (LMs) of increasing size and the discovery of latent abilities that completely outclass traditional methods e.g. rule-based systems. However, they also introduced new issues, like their inability to retain the history of previous interactions due to their stateless nature or the difficulty in controlling their generation. Different attempts have been made to address these issues, e.g. a `brute force' approach to solving the memory issue is to include the full conversation history in the context window, a solution that is limited by the quadratic scalability of Transformers. In this work, we explore computationally practical solutions to the memory problem. We propose to augment the decoder-only architecture of (most) Large LMs with a (relatively small) memory encoder. Its output is prepended to the decoder's input in a similar fashion to recent works in Adapters and the original Transformer architecture. Initial experiments show promising results, however future work is needed to compare with State-of-the-Art methods.

Abstract 5614: Mechanical regulation of cisplatin-DNA adduct repair in mesenchymal stem cells

Abstract This study examined whether loss of mechanotransduction in pluripotent mesenchymal stem cells (MSCs) disrupted repair of bulky DNA adducts, such as those induced by ultraviolet light or cisplatin. MSCs are important for the maintenance and responsiveness of skeletal tissues to environmental mechanical challenges. Beyond regulating proliferative and differentiative capacity of MSCs, emerging evidence suggests that physical activity is associated with improved recovery from DNA damage caused by environmental genotoxic stressors associated with stress and aging. Highlighting the possible crosstalk between DNA repair and bone health, defects in nucleotide excision repair (NER), which removes bulky DNA adducts, are associated with myelosuppression and progeroid aging phenotypes that result in bone defects and lipidodystrophies in mice. Cancer, early aging syndromes, and certain musculoskeletal diseases are associated with disruption of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that transduces environmental mechanical signals from the extracellular matrix into the nucleus of a cell. Loss of LINC complex elements is associated with breast cancer progression and poorer prognosis. We hypothesize that LINC-mediated mechanical stimulation into the nucleus is critical for repair of bulky DNA adducts. Our pilot project showed that mechanical stimulation applied in the form of low intensity vibration (LIV) improved NER of cisplatin-induced DNA adducts in cultured MSCs. Our findings show a 20% increase in repair of cisplatin-induced DNA adducts in LIV treated samples compared to non-vibrated samples at 24 hours (P<0.005). We also quantified the effect of LINC complex disruption on cisplatin-induced DNA damage removal. Intact MSCs showed significant adduct removal after 24 hours, while LINC disruption significantly reduced DNA repair (P<0.001). Furthermore, initial experiments suggest that LINC disrupted cells do not arrest at DNA repair checkpoints, therefore, loss of LINC complex may reduce entry into senescence increasing DNA mutagenesis. In conclusion, these findings suggest a novel interaction between mechanical stimulation, the DNA damage response, and LINC complex in DNA repair in multipotent mesenchymal stem cells. Furthermore, we suggest that LINC-mediated mechanical changes associated with LIV treatment may lead to novel therapeutic approaches to combat deleterious musculoskeletal conditions associated with anti-cancer treatments. Citation Format: Anamaria Gabriella Zavala, Nina Nikitina, Crystal Cantu, Dalia DeLaCruz, Gunes Uzer. Mechanical regulation of cisplatin-DNA adduct repair in mesenchymal stem cells [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 5614.

A prognostic model for Schistosoma japonicum infection-associated liver hepatocellular carcinoma: strengthening the connection through initial biological experiments

BackgroundNumerous studies have shown that Schistosoma japonicum infection correlates with an increased risk of liver hepatocellular carcinoma (LIHC). However, data regarding the role of this infection in LIHC oncogenesis are scarce. This study aimed to investigate the potential mechanisms of hepatocarcinogenesis associated with Schistosoma japonicum infection.MethodsBy examining chronic liver disease as a mediator, we identified the genes contributing to Schistosoma japonicum infection and LIHC. We selected 15 key differentially expressed genes (DEGs) using weighted gene co-expression network analysis (WGCNA) and random survival forest models. Consensus clustering revealed two subgroups with distinct prognoses. Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression identified six prognostic DEGs, forming an Schistosoma japonicum infection-associated signature for strong prognosis prediction. This signature, which is an independent LIHC risk factor, was significantly correlated with clinical variables. Four DEGs, including BMI1, were selected based on their protein expression levels in cancerous and normal tissues. We confirmed BMI1's role in LIHC using Schistosoma japonicum-infected mouse models and molecular experiments.ResultsWe identified a series of DEGs that mediate schistosomiasis, the parasitic disease caused by Schistosoma japonicum infection, and hepatocarcinogenesis, and constructed a suitable prognostic model. We analyzed the mechanisms by which these DEGs regulate disease and present the differences in prognosis between the different genotypes. Finally, we verified our findings using molecular biology experiments.ConclusionBioinformatics and molecular biology analyses confirmed a relationship between schistosomiasis and liver hepatocellular cancer. Furthermore, we validated the role of a potential oncoprotein factor that may be associated with infection and carcinogenesis. These findings enhance our understanding of Schistosoma japonicum infection's role in LIHC carcinogenesis.

L-carnitine enhances the kinematics and protects the sperm membranes of chilled and frozen-thawed Peruvian Paso horse spermatozoa

l-carnitine (LC) transports fatty acids to the mitochondria for energy production, reducing lipid availability for peroxidation through β-oxidation. This research examines the effect of LC supplementation to two skimmed milk-based extenders on the cryosurvival of chilled (5°C) and frozen-thawed Peruvian Paso horse spermatozoa .An initial experiment determined the optimal LC concentration (0, 1, 5, 10, 25, and 50 mM) when added to INRA-96® and UHT (skimmed milk + 6% egg yolk) extenders, using nine ejaculates from three stallions chilled for up to 96 h. Subsequently, the effect of 25 mM LC supplementation (the optimal concentration) on chilling (INRA-96) and freezing (INRA-Freeze®) extenders was evaluated using eight pooled samples from sixteen ejaculates (2 ejaculates/pool) from four stallions. Results indicated that all LC concentrations produced significantly higher values (P<0.05) for kinematic variables (total [TM] and progressive motilities, curvilinear [VCL] and straight-line [VSL] velocity, and beat-cross frequency [BCF]), and the integrity of plasma/acrosome membranes (IPIA) compared to non-supplemented chilled sperm samples for up to 96 h with both extenders. Moreover, the use of 25 mM LC was more efficient (P<0.05) in preserving the post-chilled values of velocity, BCF, and IPIA for the long term than lower LC concentrations (1–10 mM). Post-thaw values of total motility, the amplitude of lateral head displacement (ALH), and IPIA were significantly improved (P<0.05) when INRA-Freeze extender was supplemented with 25 mM LC. In conclusion, supplementation of l-carnitine to skimmed milk-based extenders enhanced kinematic variables and protected the membrane integrity in chilled and frozen-thawed Peruvian Paso horse spermatozoa.

The hybrid CL-SP-D molecule has the potential to regulate xenogeneic rejection by human neutrophils more efficiently than CD47

ObjectiveInnate immunity plays a vital role in xenotransplantation. A CD47 molecule, binding to the SIRPα expressed on monocyte/macrophage cells, can suppress cytotoxicity. Particularly, the SIRPα contains ITIM, which delivers a negative signal. Our previous study demonstrated that the binding between CL-P1 and surfactant protein-D hybrid (CL-SP-D) with SIRPα regulates macrophages' phagocytic activity. In this study, we examined the effects of human CD47 and CL-SP-D expression on the inhibition of xenograft rejection by neutrophils in swine endothelial cells (SECs). MethodsWe first examined SIRPα expression on HL-60 cells, a neutrophil-like cell line, and neutrophils isolated from peripheral blood. CD47-expressing SECs or CL-SP-D-expressing SECs were generated through plasmid transfection. Subsequently, these SECs were co-cultured with HL-60 cells or neutrophils. After co-culture, the degree of cytotoxicity was calculated using the WST-8 assay. The suppressive function of CL-SP-D on neutrophils was subsequently examined, and the results were compared with those of CD47 using naïve SECs as controls. Additionally, we assessed ROS production and neutrophil NETosis. ResultsIn initial experiments, the expression of SIRPα on HL-60 and neutrophils was confirmed. Exposure to CL-SP-D significantly suppressed the cytotoxicity in HL-60 (p = 0.0038) and neutrophils (p = 0.00003). Furthermore, engagement with CD47 showed a suppressive effect on neutrophils obtained from peripheral blood (p = 0.0236) but not on HL-60 (p = 0.4244). The results of the ROS assays also indicated a significant downregulation of SEC by CD47 (p = 0.0077) or CL-SP-D (p = 0.0018). Additionally, the suppression of NETosis was confirmed (p = 0.0125) in neutrophils co-cultured with S/CL-SP-D. ConclusionThese results indicate that CL-SP-D is highly effective on neutrophils in xenogeneic rejection. Furthermore, CL-SP-D was more effective than CD47 at inhibiting neutrophil-mediated xenograft rejection.

PDX proteins from Arabidopsis thaliana as novel substrates of cathepsin B: implications for vitamin B6 biosynthesis regulation.

Vitamin B6 is a critical molecule for metabolism, development, and stress sensitivity in plants. It is a cofactor for numerous biochemical reactions, can serve as an antioxidant, and has the potential to increase tolerance against both biotic and abiotic stressors. Due to the importance of vitamin B6, its biosynthesis is likely tightly regulated. Plants can synthesize vitamin B6 de novo via the concerted activity of Pyridoxine Biosynthesis Protein 1 (PDX1) and PDX2. Previously, PDX proteins have been identified as targets for ubiquitination, indicating they could be marked for degradation by two highly conserved pathways: the Ubiquitin Proteasome Pathway (UPP) and the autophagy pathway. Initial experiments show that PDXs are in fact degraded, but surprisingly, in a ubiquitin-independent manner. Inhibitor studies pointed toward cathepsin B, a conserved lysosomal cysteine protease, which is implicated in both programed cell death and autophagy in humans and plants. In plants, cathepsin Bs are poorly described, and no confirmed substrates have been identified. Here, we present PDX proteins from Arabidopsis thaliana as interactors and substrates of a plant Cathepsin B. These findings not only describe a novel cathepsin B substrate in plants, but also provide new insights into how plants regulate de novo biosynthesis of vitamin B6.

Retina images classification based on 2D empirical mode decomposition and multifractal analysis

Diabetic retinopathy is an ocular disease caused by long-term damage to the retina due to high blood sugar levels. Elevated blood sugar can impair the microvasculature in the retina, leading to vascular abnormalities and the formation of abnormal new blood vessels. These changes can manifest in the retina as hemorrhages, leaks, vessel dilation, retinal edema, and retinal detachment. The retinas of individuals with diabetes exhibit different morphologies compared to those without the condition. Most histological images cannot be accurately described using traditional geometric shapes or methods. Therefore, this study aims to evaluate and classify the morphology of retinas with varying degrees of severity using multifractal geometry. In the initial experiments, two-dimensional empirical mode decomposition was employed to extract high-frequency detailed features, and the classification process was based on the most relevant features in the multifractal spectrum associated with disease factors. To eliminate less significant features, the random forest algorithm was utilized. The proposed method achieved an accuracy of 96%, sensitivity of 96%, and specificity of 95%.

Effect of Chemical Modifications on the Adsorptive Ability of Palm Kernel Fiber for Indigo Blue Dye

This research work investigated the potentials of unmodified Palm Kernel Fibers and its modified forms for the adsorption of Indigo blue dye from aqueous solutions using batch adsorption procedures. Characterization of the fibers were done with the scanning electron microscopy (SEM) and FTIR. Adsorption result showed that maximum uptake of 38.3, 31.0, 33.5 and 14.5 mg/g were respectively obtained for Bleached (BPKF), Acetylated (APKF), Mercerized (MPKF) and Unmodified Palm Kernel Fibers (UPKF) adsorbents at an optimum time of 3 hours. The sorption kinetic obeyed pseudo second order with the bleached adsorbent (BPKF) having the best fit, and at a certain time limit, intra-particle diffusion controlled the process. Data collected from effect of initial concentration experiments were better fit to the Freundlich isotherm. The result from the thermodynamics of the process showed an endothermic process. Increasing adsorbent dosages led to corresponding increase in the quantity of the indigo dye adsorbed by the different adsorbents. This work revealed the potentials of modified palm kernel fibers over the unmodified fiber for effective removal of Indigo blue dye from wastewater.

Doubled haploidy methodology for three forage grasses [crested wheatgrass (Agropyron cristatum (L.) Gaertn.), hybrid bromegrass (Bromus riparius x B. inermis), and meadow bromegrass (Bromus riparius Rehm.)

Doubled haploidy (DH) methodology is used in many plant species to accelerate crop improvement and cultivar development; however not all species are amenable to the tissue culture technique. Experiments were undertaken to develop DH protocols for three perennial grasses [crested wheatgrass (Agropyron cristatum (L.) Gaertn.), hybrid bromegrass (Bromus riparius x B. inermis), and meadow bromegrass (Bromus riparius Rehm.)]. The initial experiment screened these forage grass species to established wheat (Triticum aestivum L.) microspore culture protocols. Following the initial screen, several factors influencing microspore embryogenesis were evaluated. These included genotype, donor plant conditions, developmental stage of the microspore, pretreatments, media composition, and culture conditions. For regeneration of the embryos to plants, media composition and culture conditions were assessed. Microspore-derived embryos/calli as well as green haploid/doubled haploid plants were regenerated from all three forage grasses. Differences were observed between species and genotypes within species in terms of embryogenic response. Modifications to the initial wheat DH protocol included the donor plant conditions, developmental stage of the microspore to late uninucleate to early binucleate and media composition. Regenerated plants were grown in the greenhouse.

FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation.

Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown. This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism. We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells. The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

Robust T2 estimation with balanced steady state free precession.

To develop a novel signal representation for balanced steady state free precession (bSSFP) displaying its T2 independence on B1 and on magnetization transfer (MT) effects. A signal model for bSSFP is developed that shows only an explicit dependence (up to a scaling factor) on E2 (and, therefore, T2) and a novel parameter c (with implicit dependence on the flip angle and E1). Moreover, it is shown that MT effects, entering the bSSFP signal via a binary spin bath model, can be captured by a redefinition of T1 and, therefore, leading to modification of E1, resulting in the same signal model. Various sets of phase-cycled bSSFP brain scans (different flip angles, different TR, different RF pulse durations, and different number of phase cycles) were recorded at 3 T. The parameters T2 (E2) and c were estimated using a variable projection (VARPRO) method and Monte-Carlo simulations were performed to assess T2 estimation precision. Initial experiments confirmed the expected independence of T2 on various protocol settings, such as TR, the flip angle, B1 field inhomogeneity, and the RF pulse duration. Any variation (within the explored range) appears to directly affect the estimation of the parameter c only-in agreement with theory. BSSFP theory predicts an extraordinary feature that all MT and B1-related variational aspects do not enter T2 estimation, making it a potentially robust methodology for T2 quantification, pending validation against existing standards.

Listening Preference for Child-Directed Speech Versus Time-Reversed Speech in Moderate-Preterm Infants Compared to Full-Term Infants.

The purpose of the present study was to examine whether there is a listening preference for child-directed speech (CDS) over backward speech in moderate-preterm infants (MPIs). Eighteen MPIs of gestational age of 32.0 weeks (range: 32-34.06 weeks), chronological age of 8.09 months, and maturation age of 6.48 months served as the experimental group. The two control groups consisted of a total of 36 infants-20 full-term infants matched for chronological age and 16 full-term infants matched for maturation age. The infants were tested using the central fixation procedure and were presented with 16 trials of CDS and backward speech. A follow-up was conducted 5 years after the initial experiment using a developmental and a five-item parent questionnaire. MPIs did not demonstrate a preference for CDS over backward speech, whereas both control groups demonstrated a listening preference for CDS over backward speech. MPIs showed a delayed use of first words and word combinations and lower scores on the five-item questionnaire compared to term infants. Twelve MPIs (67%) did not demonstrate a preference for CDS over backward speech. Four of them (33%) were later diagnosed with neurodevelopmental disorders. The lack of preference for CDS over backward speech in the MPIs group suggests delayed developmental pattern of speech processing compared to full-term peers. Delays in neurological maturation as well as listening experience in an unregulated environment outside the uterus during a sensitive period of brain development may affect the recognition of phonological and prosodic patterns that support listening preference for speech over backward speech.

Optimising 3D printing parameters through experimental techniques and ANOVA‐Based statistical analysis

AbstractAdditive manufacturing (AM) has revolutionized the manufacturing industry by enabling the fabrication of complex geometries and designs with ease. 3D printing—fused deposition modeling (FDM) has emerged as a prevalent technique, owing to its versatility and cost‐effectiveness. However, the FDM process is complex and depends on multiple parameters, which makes it challenging to obtain high‐quality and consistent 3D printed components. The purpose of this study is to simplify the printing process for users and potentially improve the overall quality and consistency of printed objects. This research delved into optimising 3D printing parameters, specifically raster orientation and in‐fill speed, for PLA material through three experimental studies. The mean effect of these parameters and the effects of their interaction through analysis of variance (ANOVA) on tensile properties were also discussed. Initial experiments identified the most suitable parameters and its optimal values for PLA, which were then applied to five different materials: PETG, PLA tough, Recycle PLA, Plain PLA, and ABS. Tensile tests assessed the printed parts, and scanning electron microscopy (SEM) was employed to analyze fracture interfaces and material failure causes. This study identified a raster of 45°/−45° and 30 mm/s infill speed as optimal for diverse 3D printing materials. Notably, ABS, PETG, and tough PLA exhibited better tensile strengths, surpassing manufacturer benchmarks. However, Plain PLA and Recycled PLA, despite lower tensile strengths, proved valuable for specific applications. Interestingly, all tested materials showed greater flexibility than manufacturer recommendations, suggesting their suitability in scenarios needing both strength and flexibility. This study's results offer promising avenues for refining 3D printing practices, to the advantage of all users. The findings from this study offer significant insights for future research to investigate the effect of other process parameters on the quality of 3D printed parts, leading to further advancements of AM.Highlights Optimised 3D printing parameters. Applicability of optimised settings extended across various materials. ABS, PETG, and tough PLA exceeded manufacturer benchmarks in tensile strength. Experimental and ANOVA findings are in good agreement, revealing significant process parameters.

Viewpoints/Points of View: Building a Transdisciplinary Data Theatre Collaboration in Six Scenes

Data now plays a central role in civic life and community practices. This has created a pressing need for new forms of translation and sense-making that can engage diverse publics. Research-based Theatre (RbT) has proven to be an effective approach to delivering qualitative data to community stakeholders. We extend this tradition by proposing “community-engaged data theatre”. This approach translates quantitative data into theatrical language to engage communities in deliberative conversations on relevant issues. Community-engaged data theatre requires bridging multiple disciplines and involves creating new definitions and shared vocabularies in discourses that formerly have had little overlap in meaning. In this article, we share key insights from our initial experiments in which we adapted quantitative and qualitative data to devise a pilot piece in collaboration with a local community partner. In this essay, we communicate our collaborative process in polyvocal, artistic form. We edit and adapt materials from our conversations and creative practices into scenes illustrating how we taught and learned from each other about data science, participatory modeling, material deliberation and Composition to pilot our lab’s first community-engaged data theatre prototype.

The Development of E-Module of Hydrocarbon Material Using Lectora Inspire

Hydrocarbon material is one of the materials in chemistry which is a problem for chemisty education students. In order to develop learning media that makes it easier for students to understand hydrocarbon, research to the development of e-modules is carried out. The goal of this research is to create an e-module of hydrocarbon material that is useful and receives positive feedback. ADDIE model consisted of analysis, design, and development was used as research and development model in this study. In total 12 students from the Chemistry Education Study Program FKIP Untan, and 32 students from the main test served as respondents. Measurement and indirect communication techniques are employed in the investigation. Feasibility evaluation sheets and response questionnaires are the instruments utilized for data collection. The results show that the e-module is highly viable, with a percentage of material feasibility 88%, linguistic feasibility 91%, technical feasibility 92%, and 95% graphic viability. In the initial experiment, the proportion of student questionnaire responses was calculated at 83%, and in the main test, it was calculated at 84%, which was deemed to be very good. E-module of hydrocarbon material using Lectora Inspire was pronouneed to be extremely feasible and received a very good reaction based on the research findings, that it can be used as a learning resource in learning hydrocarbon material to improve students’ understanding.

Should Decisions in QCDCL Follow Prefix Order?

Quantified conflict-driven clause learning (QCDCL) is one of the main solving approaches for quantified Boolean formulas (QBF). One of the differences between QCDCL and propositional CDCL is that QCDCL typically follows the prefix order of the QBF for making decisions. We investigate an alternative model for QCDCL solving where decisions can be made in arbitrary order. The resulting system QCDCLANY\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extsf{QCDCL}^\ extsf {{A\ iny {\\MakeUppercase {ny}}}}$$\\end{document} is still sound and terminating, but does not necessarily allow to always learn asserting clauses or cubes. To address this potential drawback, we additionally introduce two subsystems that guarantee to always learn asserting clauses (QCDCLUNI-ANY\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extsf{QCDCL}^\ extsf {{U\ iny {\\MakeUppercase {ni}}-A\ iny {\\MakeUppercase {ny}}}}$$\\end{document}) and asserting cubes (QCDCLEXI-ANY\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extsf{QCDCL}^\ extsf {{E\ iny {\\MakeUppercase {xi}}-A\ iny {\\MakeUppercase {ny}}}}$$\\end{document}), respectively. We model all four approaches by formal proof systems and show that QCDCLUNI-ANY\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extsf{QCDCL}^\ extsf {{U\ iny {\\MakeUppercase {ni}}-A\ iny {\\MakeUppercase {ny}}}}$$\\end{document} is exponentially better than QCDCL\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathsf{{QCDCL}} $$\\end{document} on false formulas, whereas QCDCLEXI-ANY\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extsf{QCDCL}^\ extsf {{E\ iny {\\MakeUppercase {xi}}-A\ iny {\\MakeUppercase {ny}}}}$$\\end{document} is exponentially better than QCDCL\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathsf{{QCDCL}} $$\\end{document} on true QBFs. Technically, this involves constructing specific QBF families and showing lower and upper bounds in the respective proof systems. We complement our theoretical study with some initial experiments that confirm our theoretical findings.

Implementation of mDoE‐methods to a microcarrier‐based expansion processes for mesenchymal stem cells

AbstractThe need for advanced therapy medicinal products (ATMPs) has gained increased attention in recent years. In this respect, a well‐designed cell expansion process is needed to efficiently manufacture the required number of cells with the desired product quality. This step is challenging due to the biological complexity of the respective primary cell (e.g., mesenchymal stem cells (MSC)) and the usage of microcarrier‐based expansion systems. One accelerating approach for process design is model‐assisted Design of Experiments (mDoE) combining mathematical process models and statistical tools. In this study, the mDoE workflow was used for the development of an expansion processes with human immortalized mesenchymal stem cells (hMSC‐TERT) and the aim of maximizing cell yield assuming only a limited amount of prior knowledge at a very early stage of development. First, suitable microcarriers for expansion in shake flasks were screened and the differentiation of the cells was proven. Second, initial experiments were performed to generate prior knowledge, which was then used to set up the mathematical model and to estimate the model parameters. Finally, the mDoE was used to determine and evaluate the design space to be performed experimentally. Overall, a cell expansion process using microcarriers in a shake flask culture was successfully implemented and a significant increase in cell yield (up to 6,2‐fold) was achieved compared to literature.

Difluoromethylated Difunctionalization of Alkenes under Visible Light.

Difluoromethylated compounds usually act as bioisosteres for alcohol functional groups and show unique physicochemical and biological properties. The cyano-difluoromethylation of alkenes using 5-((difluoromethyl)sulfonyl)-1-phenyl-1H-tetrazole as a CF2H radical difluoromethyl precursor was developed to afford nitriles including a CF2H group. A low-cost, stable, easily handled 5-((difluoromethyl)sulfonyl)-1-methyl-1H-tetrazole (DFSMT) was synthesized and applied as the radical CF2H reagent. Using DFSMT as the radical CF2H precursor, the oxyl-difluoromethylation of alkenes was developed to obtain difluoromethylated ether products. All of the reactions showed good functional group tolerability. Initial mechanistic experiments indicated that the CF2H radical was involved as the key active intermediate.

A balancing act: radicality and capture in institutionalising reflexive governance for urban sustainability transitions

Over the past two decades, urban actors have sought to foster long-lasting change towards sustainability through reflexive governance. Related activities, including transition labs, arenas, experiments, and roadmaps, have been problematised for disparities between using a discourse of transformation and radicality while failing to materialise radical action and succumbing to ‘projectification’ – meaning that the impact of an intervention tends to evaporate after the initial experiment impulse. Enabling a transformative legacy of such interventions requires institutionalising reflexive governance arrangements, i.e. a process of integrating these arrangements as part of the existing institutional set-ups while maintaining ‘radical’ elements. Particularly as the focus in certain urban transitions shifts from emerging and supporting niche practices towards institutionalising new ways of working and breaking down regime structures, it becomes paramount to better understand such processes. Based on a comparative empirical analysis of six European cities, we explore how these cities attempt to institutionalise reflexive governance and take stock of the tensions encountered, particularly to what extent cities manage to safeguard their radical ambitions, or whether these become ‘captured’ in the process. Other highlighted tensions are a focus on internal dynamics, a struggle around voluntary structures and accountability, and a challenge of keeping momentum with new actor constellations while trying to address complexity and uncertainty. We conclude by putting forward three recommendations for how reflexive governance processes may increase their impact: through prioritising institutional embeddedness in and outside of the local authority; creating transparency around how governance arrangements are adjusted and modified throughout the process for accountability; and renewing commitment periodically to ensure continuity and commitment from actors involved.

Molecular characterization of Fusarium venenatum-based microbial protein in animal models of obesity using multi-omics analysis

Microbial protein, produced by fermentation of Fusarium venenatum is a promising candidate alternative protein source. Previous study has demonstrated its ability to improve hyperlipidemia in rats, yet the related mechanism remains unclear. In this study, we aimed to evaluate the potential of F. venenatum as an alternative protein source and its impact on lipid metabolism using multi-omics analysis. Initial experiments with Caenorhabditis elegans revealed that F. venenatum enhanced longevity, improved immune responses, and reduced lipid metabolism by downregulating fat synthesis-related genes. Subsequently, we conducted experiments with mice on a high-fat diet to confirm the anti-obesity effects of F. venenatum. The groups fed F. venenatum showed improved lipid profiles and reduced hepatic fat accumulation. Furthermore, fecal metabolomic analysis showed higher excretion of primary bile acid and cholesterol in the groups fed F. venenatum which might lead to a decrease in lipid digestion and hepatic fat accumulation. Collectively, this series of experiments revealed the potential of F. venenatum as a sustainable alternative protein and its application as an anti-obesity supplement.