Anna Goldie, Azalia Mirhoseini, Mustafa Yazgan, Joe Wenjie Jiang, Ebrahim Songhori, Shen Wang, Young-Joon Lee, Eric Johnson, Omkar Pathak, Azade Nova, Jiwoo Pak, Andy Tong, Kavya Srinivasa, William Hang, Emre Tuncer, Quoc V. Le, James Laudon, Richard Ho, Roger Carpenter, Jeff Dean <<<

Nga Yan Tse, Aswin Ratheesh, Ye Ella Tian, Colm G. Connolly, Christopher G. Davey, Saampras Ganesan, Ian H. Gotlib, Ben J. Harrison, Laura K. M. Han, Tiffany C. Ho, Alec J. Jamieson, Jaclyn S. Kirshenbaum, Yong Liu, Xiaohong Ma, Amar Ojha, Jiang Qiu, Matthew D. Sacchet, Lianne Schmaal, Alan N. Simmons, John Suckling, Dongtao Wei, Xiao Yang, Tony T. Yang, Robin F. H. Cash, Andrew Zalesky <<<

AbstractExtracting the underlying temporal structure of experience is a fundamental aspect of learning and memory that allows us to predict what is likely to happen next. Current knowledge about the neural underpinnings of this cognitive process in humans stems from functional neuroimaging research1–5. As these methods lack direct access to the neuronal level, it remains unknown how this process is computed by neurons in the human brain. Here we record from single neurons in individuals who have been implanted with intracranial electrodes for clinical reasons, and show that human hippocampal and entorhinal neurons gradually modify their activity to encode the temporal structure of a complex image presentation sequence. This representation was formed rapidly, without providing specific instructions to the participants, and persisted when the prescribed experience was no longer present. Furthermore, the structure recovered from the population activity of hippocampal–entorhinal neurons closely resembled the structural graph defining the sequence, but at the same time, also reflected the probability of upcoming stimuli. Finally, learning of the sequence graph was related to spontaneous, time-compressed replay of individual neurons’ activity corresponding to previously experienced graph trajectories. These findings demonstrate that neurons in the hippocampus and entorhinal cortex integrate the ‘what’ and ‘when’ information to extract durable and predictive representations of the temporal structure of human experience. <<<

AbstractSeveral computational methods have recently been developed for characterizing molecular tissue regions in spatially resolved transcriptomics (SRT) data. However, each method fundamentally relies on spatially smoothing transcriptomic features across neighboring cells. Here, we demonstrate that smoothing increases autocorrelation between neighboring cells, causing latent space to encode physical adjacency rather than spatial transcriptomic patterns. We find that randomly sub-sampling neighbors before smoothing mitigates autocorrelation, improving the performance of existing methods and further enabling a simpler, more efficient approach that we callspatialintegration (SPIN). SPIN leverages the conventional single-cell toolkit, yielding spatial analogies to each tool: clustering identifies molecular tissue regions; differentially expressed gene analysis calculates region marker genes; trajectory inference reveals continuous, molecularly defined ana tomical axes; and integration allows joint analysis across multiple SRT datasets, regardless of tissue morphology, spatial resolution, or experimental technology. We apply SPIN to SRT datasets from mouse and marmoset brains to calculate shared and species-specific region marker genes as well as a molecularly defined neocortical depth axis along which several genes and cell types differ across species. <<<

Recent advancements in quantum computing have opened new avenues for tacklinglong-standing complex combinatorial optimization problems that are intractablefor classical computers. Predicting secondary structure of mRNA is one suchnotoriously difficult problem that can benefit from the ever-increasingmaturity of quantum computing technology. Accurate prediction of mRNA secondarystructure is critical in designing RNA-based therapeutics as it dictatesvarious steps of an mRNA life cycle, including transcription, translation, anddecay. The current generation of quantum computers have reached utility-scale,allowing us to explore relatively large problem sizes. In this paper, weexamine the feasibility of solving mRNA secondary structures on a quantumcomputer with sequence length up to 60 nucleotides representing problems in thequbit range of 10 to 80. We use Conditional Value at Risk (CVaR)-based VQEalgorithm to solve the optimization problems, originating from the mRNAstructure prediction problem, on the IBM Eagle and Heron quantum processors. Toour encouragement, even with ``minimal'' error mitigation and fixed-depthcircuits, our hardware runs yield accurate predictions of minimum free energy(MFE) structures that match the results of the classical solver CPLEX. Ourresults provide sufficient evidence for the viability of solving mRNA structureprediction problems on a quantum computer and motivate continued research inthis direction. <<<

AbstractBackgroundNeurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL.MethodsSerum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained.ResultsBaseline samples were available from 110 controls, 90 premanifest HD (pre‐HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre‐HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre‐HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset.ConclusionsAlthough sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society. <<<

This paper presents a prototype of a low-cost two-phase axial-gap transverse flux generator, in which the magnetic and electric circuits have been made of reused materials, and the stator housing has been manufactured by 3D printing of plastic. Therefore, this work presents as a novelty the combination of the novel transverse flux topology and two challenging trends in electrical machines manufacturing, such as reusing of components and additive manufacturing. Axial-gap transverse flux machines potentially enable the combination of two of the main advantages of axial flux machines and transverse flux machines, i.e., short axial length and a high number of poles. The two-phase arrangement with shared air gap is of great interest in order to reduce further the axial length while avoiding the use of magnetic materials in the rotor, such as iron or soft magnetic composites. However, the equivalent air gap might be large, with significant leakage and fringing effects as the magnetic flux closes through the air. Therefore, in this paper the accuracy of the analytical equations and the magnetic equivalent circuit is firstly investigated. The two-phase axial-gap transverse flux machine is prone to misalignment between phases and rotor imbalances that alter the air gap length, so these effects have been included in the simulations with the finite element method. Experimental tests have been conducted throughout the investigation, from the prototype characterization to the steady-state operation, both with no load and with resistive loads. <<<

Qiang Ning, Yinan Jian, Yanfang Du, Yunfu Li, Xiaomeng Shen, Haitao Jia, Ran Zhao, Jimin Zhan, Fang Yang, David Jackson, Lei Liu, Zuxin Zhang <<<

AbstractMaize ear size and kernel number differ among lines, however, little is known about the molecular basis of ear length and its impact on kernel number. Here, we characterize a quantitative trait locus, qEL7, to identify a maize gene controlling ear length, flower number and fertility. qEL7 encodes 1-aminocyclopropane-1- carboxylate oxidase2 (ACO2), a gene that functions in the final step of ethylene biosynthesis and is expressed in specific domains in developing inflorescences. Confirmation of qEL7 by gene editing of ZmACO2 leads to a reduction in ethylene production in developing ears, and promotes meristem and flower development, resulting in a ~13.4% increase in grain yield per ear in hybrids lines. Our findings suggest that ethylene serves as a key signal in inflorescence development, affecting spikelet number, floral fertility, ear length and kernel number, and also provide a tool to improve grain productivity by optimizing ethylene levels in maize or in other cereals. <<<

Fine-tuning large pre-trained models is an effective transfer mechanism inNLP. However, in the presence of many downstream tasks, fine-tuning isparameter inefficient: an entire new model is required for every task. As analternative, we propose transfer with adapter modules. Adapter modules yield acompact and extensible model; they add only a few trainable parameters pertask, and new tasks can be added without revisiting previous ones. Theparameters of the original network remain fixed, yielding a high degree ofparameter sharing. To demonstrate adapter's effectiveness, we transfer therecently proposed BERT Transformer model to 26 diverse text classificationtasks, including the GLUE benchmark. Adapters attain near state-of-the-artperformance, whilst adding only a few parameters per task. On GLUE, we attainwithin 0.4% of the performance of full fine-tuning, adding only 3.6% parametersper task. By contrast, fine-tuning trains 100% of the parameters per task. <<<

Abstract Background A feature common to all DNA sequencing technologies is the presence of base-call errors in the sequenced reads. The implications of such errors are application specific, ranging from minor informatics nuisances to major problems affecting biological inferences. Recently developed "next-gen" sequencing technologies have greatly reduced the cost of sequencing, but have been shown to be more error prone than previous technologies. Both position specific (depending on the location in the read) and sequence specific (depending on the sequence in the read) errors have been identified in Illumina and Life Technology sequencing platforms. We describe a new type of systematic error that manifests as statistically unlikely accumulations of errors at specific genome (or transcriptome) locations. Results We characterize and describe systematic errors using overlapping paired reads from high-coverage data. We show that such errors occur in approximately 1 in 1000 base pairs, and that they are highly replicable across experiments. We identify motifs that are frequent at systematic error sites, and describe a classifier that distinguishes heterozygous sites from systematic error. Our classifier is designed to accommodate data from experiments in which the allele frequencies at heterozygous sites are not necessarily 0.5 (such as in the case of RNA-Seq), and can be used with single-end datasets. Conclusions Systematic errors can easily be mistaken for heterozygous sites in individuals, or for SNPs in population analyses. Systematic errors are particularly problematic in low coverage experiments, or in estimates of allele-specific expression from RNA-Seq data. Our characterization of systematic error has allowed us to develop a program, called SysCall, for identifying and correcting such errors. We conclude that correction of systematic errors is important to consider in the design and interpretation of high-throughput sequencing experiments. <<<

Rachael B. Chanin, Patrick T. West, Jakob Wirbel, Matthew O. Gill, Gabriella Z. M. Green, Ryan M. Park, Nora Enright, Arjun M. Miklos, Angela S. Hickey, Erin F. Brooks, Krystal K. Lum, Ileana M. Cristea, Ami S. Bhatt <<<

We present a practical example for the phenomenon of color assimilation. We describe the advances in research on color assimilation from von Bezold, to Albers and Munker, and provide a compelling example of the recently described “Confetti-illusion” by Novick. Our research introduces a novel aspect by showing how unripe and greenish looking oranges can be perceived as ripe and vibrantly colored when viewed through an orange net. These findings highlight the significant implications of color assimilation in everyday consumer environments, offering a fresh perspective on how visual perception can be manipulated. <<<

Jonas Richiardi, Andre Altmann, Anna-Clare Milazzo, Catie Chang, M. Mallar Chakravarty, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Patricia Conrod, Mira Fauth-Bühler, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Penny Gowland, Andreas Heinz, Hervé Lemaître, Karl F. Mann, Jean-Luc Martinot, Frauke Nees, Tomáš Paus, Zdenka Pausova, Marcella Rietschel, Trevor W. Robbins, Michael N. Smolka, Rainer Spanagel, Andreas Ströhle, Gunter Schumann, Mike Hawrylycz, Jean-Baptiste Poline, Michael D. Greicius, , Lisa Albrecht, Chris Andrew, Mercedes Arroyo, Eric Artiges, Semiha Aydin, Christine Bach, Tobias Banaschewski, Alexis Barbot, Gareth Barker, Nathalie Boddaert, Arun Bokde, Zuleima Bricaud, Uli Bromberg, Ruediger Bruehl, Christian Büchel, Arnaud Cachia, Anna Cattrell, Patricia Conrod, Patrick Constant, Jeffrey Dalley, Benjamin Decideur, Sylvane Desrivieres, Tahmine Fadai, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Fanny Gollier Briand, Penny Gowland, Bert Heinrichs, Andreas Heinz, Nadja Heym, Thomas Hübner, James Ireland, Bernd Ittermann, Tianye Jia, Mark Lathrop, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Katharina Lüdemann, Christine Macare, Catherine Mallik, Jean-François Mangin, Karl Mann, Jean- Luc Martinot, Eva Mennigen, Fabiana Mesquita de Carvahlo, Xavier Mignon, Ruben Miranda, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Marie-Laure Paillere, Tomas Paus, Zdenka Pausova, Jean-Baptiste Poline, Luise Poustka, Michael Rapp, Gabriel Robert, Jan Reuter, Marcella Rietschel, Stephan Ripke, Trevor Robbins, Sarah Rodehacke, John Rogers, Alexander Romanowski, Barbara Ruggeri, Christine Schmäl, Dirk Schmidt, Sophia Schneider, MarkGunter Schumann, Florian Schubert, Yannick Schwartz, Michael Smolka, Wolfgang Sommer, Rainer Spanagel, Claudia Speiser, Tade Spranger, Alicia Stedman, Sabina Steiner, Dai Stephens, Nicole Strache, Andreas Ströhle, Maren Struve, Naresh Subramaniam, Lauren Topper, Robert Whelan, Steve Williams, Juliana Yacubian, Monica Zilbovicius, C Peng Wong, Steven Lubbe, Lourdes Martinez-Medina, Alinda Fernandes, Amir Tahmasebi <<<

Cooperating brain regions express similar genesWhen the brain is at rest, a number of distinct areas are functionally connected. They tend to be organized in networks. Richiardiet al.compared brain imaging and gene expression data to build computational models of these networks. These functional networks are underpinned by the correlated expression of a core set of 161 genes. In this set, genes coding for ion channels and other synaptic functions such as neurotransmitter release dominate.Science, this issue p.1241 <<<

Huilin Wang, Zirui Dong, Rui Zhang, Matthew Hoi Kin Chau, Zhenjun Yang, Kathy Yin Ching Tsang, Hoi Kin Wong, Baoheng Gui, Zhuo Meng, Kelin Xiao, Xiaofan Zhu, Yanfang Wang, Shaoyun Chen, Tak Yeung Leung, Sau Wai Cheung, Yvonne K. Kwok, Cynthia C. Morton, Yuanfang Zhu, Kwong Wai Choy <<<

Breast cancer, the most prevalent malignancy in women, is also the leading cause of cancer-related deaths in women worldwide. The activation of the Wnt pathway plays a pivotal role in the metastatic abilities of breast cancer. In this study, IL1F6, MRGPRX1, and SEC14L3 were significantly correlated to breast cancer patients'overall survival based on TCGA-BRCA dataset. Although IL1F6, MRGPRX1 and SEC14L3 high expression were associated with better survival in breast cancer patients, SEC14L3 had the biggest survival benefit for breast cancer; therefore, SEC14L3 was selected for the subsequent investigation. SEC14L3 mRNA expression and protein levels within breast cancer cell lines decreased compared with normal human breast epithelial cells. Overexpressing SEC14L3 in breast cancer cells inhibited the malignant phenotypes of cancer cells, including the capacity of cells to migrate and invade. SEC14L3 overexpression decreased the levels of mesenchymal markers, whereas SEC14L3 knockdown facilitated the malignant behaviors of breast cancer cells. SEC14L3 overexpression also inhibited Wnt/β-catenin activation. The Wnt agonist strengthened the malignant phenotypes of breast cancer cells; moreover, the anti-tumor effects of SEC14L3 overexpression were partially attenuated by the Wnt agonist. Conclusively, SEC14L3, which is underexpressed in breast cancer cells and tissues, could play a tumor-suppressive role in a Wnt/β-catenin-related way. <<<

The hippocampus and entorhinal cortex have been linked to both memory functions and to spatial cognition, but it has been unclear how these ideas relate to each other. An important part of spatial cognition is the ability to keep track of a reference location using self-motion cues (sometimes referred to as path integration), and it has been suggested that the hippocampus or entorhinal cortex is essential for this ability. Patients with hippocampal lesions or larger lesions that also included entorhinal cortex were led on paths while blindfolded (up to 15 m in length) and were asked to actively maintain the path in mind. Patients pointed to and estimated their distance from the start location as accurately as controls. A rotation condition confirmed that performance was based on self-motion cues. When demands on long-term memory were increased, patients were impaired. Thus, in humans, the hippocampus and entorhinal cortex are not essential for path integration. <<<

Adolescence is a period of substantial social-emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain. <<<