Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptive evolution in the Saccharomyces kudriavzevii Aro4p promoted a reduced production of higher alcohols

The use of unconventional yeast species in human‐driven fermentations has attracted a lot of attention in the last few years. This tool allows the alcoholic beverage industries to solve problems related to climate change or the consumer demand for newer high‐quality products. In this sense, one of the most attractive species is Saccharomyces kudriavzevii, which shows interesting fermentative traits such as the increased and diverse aroma compound production in wines. Specifically, it has been observed that different isolates of this species can produce higher amounts of higher alcohols such as phenylethanol compared with Saccharomyces cerevisiae. In this work, we have shed light on this feature relating it to the S. kudriavzevii aromatic amino acid anabolic pathway in which the enzyme Aro4p plays an essential role. Unexpectedly, we observed that the presence of the S. kudriavzevii ARO4 variant reduces phenylethanol production compared with the S. cerevisiae ARO4 allele. Our experiments suggest that this can be explained by increased feedback inhibition, which might be a consequence of the changes detected in the Aro4p amino end such as L26Q24 that have been under positive selection in the S. kudriavzevii specie.
Association of Perfusion Lesion Variables With Functional Outcome in Patients With Mild Stroke and Large Vessel Occlusion Managed Medically

Background and Objectives The best management of patients with mild stroke and large vessel occlusion (LVO) remains unclear. This study aimed to identify perfusion imaging predictors of poor functional outcome in such patients. Methods This cohort study retrospectively selected patients enrolled in the International Stroke Perfusion Imaging Registry between August 2011 and April 2022. The registry enrolled patients with acute ischemic stroke and with baseline CT perfusion scanned within 24 hours of stroke onset. This study identified patients with mild symptoms, defined by an NIH Stroke Scale score of ≤5. Patients with LVO of anterior circulation were selected. This study further selected patients who received medical management and excluded patients who received endovascular treatment. The primary outcome was poor functional outcome defined as a modified Rankin Scale of 3–6 at 3 months. Perfusion lesion was defined by delay time > 3 seconds on CTP. Regression analyses were used to identify clinical and imaging variables that predicted poor functional outcome. Results A total of 139 patients with mild stroke were included, of whom 27 (19%) had poor functional outcome. Patients with poor outcome, compared with those with good outcome, had much larger perfusion lesion volume (median 80 mL vs 41 mL, p < 0.001). Perfusion lesion was a significant predictor of poor outcome in either univariable regression (crude OR = 1.02, 95% CI = [1.01–1.03]) or multivariable regression model (adjusted OR = 1.01, 95% CI = [1.01–1.02]), adjusting for occlusion site, good collaterals, baseline stroke severity, age, IV thrombolysis (IVT), and onset to scan time. A perfusion lesion of 65 mL was the optimal cutpoint to identify poor functional outcome (sensitivity = 59%, specificity = 77%). Patients with perfusion lesion ≥65 mL, compared with patients with perfusion lesion <65 mL, showed a much higher rate of poor functional outcome (38% vs 11%, p < 0.001). Of the 139 patients in this study, 95 received IVT. Patients treated with or without IVT did not influence their outcomes (crude OR = 0.74, 95% CI = [0.31–1.78]). Discussion A perfusion lesion of ≥65 mL predicted poor functional outcome in mild stroke patients with LVO.
Role of regional anesthesia in patients with acute sickle cell pain: A scoping review

Sickle cell disease is the most prevalent inherited blood disorder in the world, with significant morbidity and mortality. Patients often have recurrent painful vaso‐occlusive episodes, and the American Society of Hematology gives a conditional recommendation for the use of regional anesthesia for acute sickle cell pain management. This scoping review summarizes the current evidence and identifies gaps for future research. Our screening process is outlined, and articles that mentioned the use of regional anesthesia for acute sickle cell crises were included. We present and interpret our results and highlight opportunities for future investigation.
Taming the Selection of Optimal Substitution Models in Phylogenomics by Site Subsampling and Upsampling

Abstract The selection of the optimal substitution model of molecular evolution imposes a high computational burden for long sequence alignments in phylogenomics. We discovered that the analysis of multiple tiny subsamples of site patterns from a full sequence alignment recovers the correct optimal substitution model when sites in the subsample are upsampled to match the total number of sites in the full alignment. The computational costs of maximum-likelihood analyses are reduced by orders of magnitude in the subsample–upsample (SU) approach because the upsampled alignment contains only a small fraction of all site patterns. We present an adaptive protocol, ModelTamer, that implements the new SU approach and automatically selects subsamples to estimate optimal models reliably. ModelTamer selects models hundreds to thousands of times faster than the full data analysis while needing megabytes rather than gigabytes of computer memory.
Peptide-DNA origami as a cryoprotectant for cell preservation

Cryopreservation of cells is essential for the conservation and cold chain of bioproducts and cell-based medicines. Here, we demonstrate that self-assembled DNA origami nanostructures have a substantial ability to protect cells undergoing freeze-thaw cycles; thereby, they can be used as cryoprotectant agents, because their nanoscale morphology and ice-philicity are tailored. In particular, a single-layered DNA origami nanopatch functionalized with antifreezing threonine peptides enabled the viability of HSC-3 cells to reach 56% after 1 month of cryopreservation, surpassing dimethyl sulfoxide, which produced 38% viability. It also exhibited minimal dependence on the cryopreservation period and freezing conditions. We attribute this outcome to the fact that the peptide-functionalized DNA nanopatches exert multisite actions for the retardation of ice growth in both intra- and extracellular regions and the protection of cell membranes during cryopreservation. This discovery is expected to deepen our fundamental understanding of cell survival under freezing environment and affect current cryopreservation technologies.
Nuclear magnetic resonance implementation of a quantum clock synchronization algorithm

The quantum clock synchronization (QCS) algorithm proposed by Chuang [Phys. Rev. Lett. 85, 2006 (2000)] has been implemented in a three qubit nuclear magnetic resonance quantum system. The time difference between two separated clocks can be determined by measuring the output states. The experimental realization of the QCS algorithm also demonstrates an application of the quantum phase estimation.
Bell Measurement and Local Measurement in the Modified Lo-Chau Quantum Key Distribution Protocol

We clarify the argument on the how (nonlocal) degenerate Bell measurement can be replaced by local measurements in the modified Lo-Chau quantum key distribution protocol. Discussing security criterion for users, we describe how eavesdropper’s refined information on the final state is not helpful. We argue that current discussions on the equivalence of the Bell and the local measurements are not clear. We show how the problem of equivalence can be resolved using the fact that eavesdropper’s refined information is not helpful for her.
Creating a common language for the subanatomy of the ovary

Creating a common language for the subanatomy of the ovary Elizabeth L. Tsui1,2, Kathleen E. O’Neill3, Richard D. LeDuc4, Ariella Shikanov5, Veronica Gomez-Lobo6 and Monica M. Laronda1,2,* 1Department of Endocrinology and Department of Pediatric Surgery, Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA 2Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 3Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 4Proteomics Center of Excellence, Northwestern University, Evanston, IL, USA 5Department of Biomedical Engineering, Department of Obstetrics and Gynecology, Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI, USA 6Pediatric and Adolescent Gynecology Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA *Correspondence: 225 E Chicago Ave, Box 205, Chicago, IL 60611, USA. E-mail: m-laronda@northwestern.edu
A non-mathemtaical introduction to statistics of extremes

This short introduction aims at describing extreme value theory and its applications. However, the language is statistics and the grammar is mathematics but this will be tried to be held at a minimum. The introduction is by no means complete and the interested reader is referred to Coles (2001) and Embrechts et al. (1997). The book by Coles (2001) is from a statistical point of view while the book by Embrechts et al. (1997) is more theoretical but still focusing on applications such as insurance and finance. A common problem in many areas of science is to answer the question how likely it is that a certain event occurs. Also, one is often more interested in events that has a low probability to occur, so called extreme events, as these events tends to influence an environErik Brodin ebrodin@math.chalmers. se
Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma

YAP/TAZ have been identified as master regulators in malignant phenotypes of glioblastoma (GBM); however, YAP/TAZ transcriptional disruptor in GBM treatment remains ineffective. Whether post‐transcriptional dysregulation of YAP/TAZ improves GBM outcome is currently unknown. Here, we report that insulin‐like growth factor 2 (IGF2) mRNA‐binding protein 1 (IGF2BP1 or IMP1) is upregulated in mesenchymal GBM compared with proneural GBM and correlates with worse patient outcome. Overexpression of IMP1 in proneural glioma stem‐like cells (GSCs) promotes while IMP1 knockdown in mesenchymal GSCs attenuates tumorigenesis and mesenchymal signatures. IMP1 binds to and stabilizes m6A‐YAP mRNA, leading to activation of YAP/TAZ signaling, depending on its m6A recognition and binding domain. On the other hand, TAZ functions as enhancer for IMP1 expression. Collectively, our data reveal a feedforward loop between IMP1 and YAP/TAZ maintaining GBM/GSC tumorigenesis and malignant progression and a promising molecular target in GBM.
An objective evaluation of simulated surgical outcomes among surgical trainees using manual small-incision cataract surgery virtual reality simulator

Purpose: The purpose of this study was to evaluate trainee performance across six modules of a virtual reality (VR) simulator. Methods: A retrospective observational study was conducted on 10 manual small-incision cataract surgery (MSICS) trainees who practiced cataract surgery on an MSICS VR simulator for one month. They were assessed in six major steps which included scleral groove, tunnel dissection, keratome entry, capsulorhexis, nucleus delivery, and intraocular lens (IOL) insertion under a trainer's supervision. The information included in their score metrics was collected, and their overall performance was evaluated. Results: Thirty attempts were evaluated for scleral groove, tunnel dissection, and capsulorhexis and 15 attempts for keratome entry. Candidates had varied results in the dimensional aspects and their rates of complications with a mean satisfactory score of 3.1 ± 4.17, 6.8 ± 5.75, 5.8 ± 7.74, and 1.8 ± 2.57, respectively. Nucleus delivery (n = 5) had more of iris pull and IOL insertion (n = 5) had more of lost IOL as complications but both had a higher satisfactory outcome. Conclusion: A VR simulator is a useful tool for training surgeons before their entry into live surgery. It is an effective method for evaluating objectively the structural characteristics of each phase in MSICS and their associated complications, helping them anticipate it earlier during live surgery by giving them a near real world experience.
Accurate cosmology with galaxy and quasar surveys

Observations of the cosmic microwave background have led to a golden age of cosmology, where precise measurements can be confronted with predictions from cosmological models. Ongoing and future surveys of the distribution of galaxies will continue this revolution: they will enable us to test the laws of gravity, uncover the properties of dark energy and dark matter, and reinforce the connection to high-energy physics. However, current galaxy survey analyses are already limited by our ability to identify and treat observational systematics, and this problem will be even more pronounced in future experiments. Therefore, it is essential to develop novel methods to deal with these complications when testing cosmological models and searching for new physics. This is the focus of this thesis. Firstly, I will present measurements of primordial non-Gaussianity obtained from the clustering of quasars from the Sloan Digital Sky Survey. Primordial non-Gaussianity is a powerful probe of inflation, the leading theory of the initial conditions of the universe, but its effects on the distribution of quasars are mimicked by observational systematics. I will describe a framework to deal with these systematics and robustly measure primordial non-Gaussianity from the clustering of quasars. Secondly, I will present a new set of wavelet transforms on the sphere and the ball. These approaches are highly promising for analysing cosmological and geophysical data and dealing with their systematics in novel ways. Finally, I will examine the recent claims that extra massive neutrinos can resolve the tensions between cosmic microwave background, galaxy survey and supernova observations. I will demon- strate that this conclusion is premature since it is driven by the least robust data sets. Given the growing number of cosmological observables and their varied levels of robustness, combining data sets and dealing with such tensions will become critical in the near future.
T-cell lymphoma in a Himalayan black bear in China

A 12-y-old Himalayan black bear suddenly developed depression, anorexia, cough, and dyspnea and died at the Ordos Zoo, China. At autopsy, the mesenteric and cranial mediastinal lymph nodes (LNs) were enlarged; the largest cranial mediastinal LN was ~13 cm in diameter. Scattered-to-diffuse, rounded-or-oval, gray, firm 1–6-mm nodules were observed on the surfaces of the spleen, liver, lungs, and small intestine. Histologically, the enlarged cranial mediastinal and mesenteric LNs, spleen, small intestine, lungs, and liver contained dense populations of neoplastic lymphoid cells (NLCs). The NLCs were round-or-oval with small amounts of mildly eosinophilic cytoplasm and round-or-oval hyperchromatic nuclei with indistinct nucleoli; the mitotic count was 55 in 2.37 mm2. Immunohistochemically, cell membranes and the cytoplasm of NLCs were CD3+, CD79a−, CD20−, CD15−, CD30−, and CD45RA−; hence, the NLCs were derived from T lymphocytes. To our knowledge, T-cell lymphoma has not been reported previously in a Himalayan black bear.
Spiral-arm instability: giant clump formation via fragmentation of a galactic spiral arm

Fragmentation of a spiral arm is thought to drive the formation of giant clumps in galaxies. Using linear perturbation analysis for self-gravitating spiral arms, we derive an instability parameter and define the conditions for clump formation. We extend our analysis to multi-component systems that consist of gas and stars in an external potential. We then perform numerical simulations of isolated disc galaxies with isothermal gas, and compare the results with the prediction of our analytic model. Our model describes accurately the evolution of the spiral arms in our simulations, even when spiral arms dynamically interact with one another. We show that most of the giant clumps formed in the simulated disc galaxies satisfy the instability condition. The clump masses predicted by our model are in agreement with the simulation results, but the growth time-scale of unstable perturbations is overestimated by a factor of a few. We also apply our instability analysis to derive scaling relations of clump properties. The expected scaling relation between the clump size, velocity dispersion, and circular velocity is slightly different from that given by the Toomre instability analysis, but neither is inconsistent with currently available observations. We argue that the spiral-arm instability is a viable formation mechanism of giant clumps in gas-rich disc galaxies.
The tapetal tissue is essential for the maintenance of redox homeostasis during microgametogenesis in tomato

SUMMARY The tapetum is a specialized layer of cells within the anther, adjacent to the sporogenous tissue. During its short life, it provides nutrients, molecules and materials to the pollen mother cells and microsporocytes, being essential during callose degradation and pollen wall formation. The interaction between the tapetum and sporogenous cells in Solanum lycopersicum (tomato) plants, despite its importance for breeding purposes, is poorly understood. To investigate this process, gene editing was used to generate loss‐of‐function mutants that showed the complete and specific absence of tapetal cells. These plants were obtained targeting the previously uncharacterized Solyc03g097530 (SlTPD1) gene, essential for tapetum specification in tomato plants. In the absence of tapetum, sporogenous cells developed and callose deposition was observed. However, sporocytes failed to undergo the process of meiosis and finally degenerated, leading to male sterility. Transcriptomic analysis conducted in mutant anthers lacking tapetum revealed the downregulation of a set of genes related to redox homeostasis. Indeed, mutant anthers showed a reduction in the accumulation of reactive oxygen species (ROS) at early stages and altered activity of ROS‐scavenging enzymes. The results obtained highlight the importance of the tapetal tissue in maintaining redox homeostasis during male gametogenesis in tomato plants.
A Quantum Logic Gate Representation of Quantum Measurement: Reversing and Unifying the Two Steps of von Neumann's Model

In former work, quantum computation has been shown to be a problem solving process essentially affected by both the reversible dynamics leading to the state before measurement, and the logical-mathematical constraints introduced by quantum measurement (in particular, the constraint that there is only one measurement outcome). This dual influence, originated by independent initial and final conditions, justifies the quantum computation speed-up and is not representable inside dynamics, namely as a one-way propagation. In this work, we reformulate von Neumann's model of quantum measurement at the light of above findings. We embed it in a broader representation based on the quantum logic gate formalism and capable of describing the interplay between dynamical and non-dynamical constraints. The two steps of the original model, namely (1) dynamically reaching a complete entanglement between pointer and quantum object and (2) enforcing the one-outcome-constraint, are unified and reversed. By representing step (2) right from the start, the same dynamics of step (1) yields a probability distribution of mutually exclusive measurement outcomes. This appears to be a more accurate and complete representation of quantum measurement. PACS: 03.67. -a, 03.67. Lx, 03.65. Bz
A study of scaling and geometry effects on the forces between cuboidal and cylindrical magnets using analytical force solutions

Kelvin's formula is used to calculate forces acting on a permanent magnet in the presence of an external magnetic field from a second permanent magnet. This approach is used to derive explicit analytical solutions for the axial and lateral forces between cuboidal and cylindrical permanent magnets as functions of magnet dimensions and separation. While exact solutions can be found for cuboidal magnets, a hypergeometric expansion is used to approximate the elliptic integrals in solving for the fields and forces for the cylindrical magnets. The resulting equations are applied over a range of magnet sizes and geometries to explore scaling laws and other geometrical effects. It is shown that cuboidal magnets provide larger forces than equivalently sized cylindrical magnets. Also, the aspect ratio of the magnets significantly affects the forces. These results are intended to benefit the design and optimization of sensors, actuators and systems that rely on magnetic forces, particularly at the microscale.
KDM6A Loss Recruits Tumor-Associated Neutrophils and Promotes Neutrophil Extracellular Trap Formation in Pancreatic Cancer.

Lysine (K)-specific demethylase 6A (KDM6A) is a frequently mutated tumor suppressor gene in pancreatic ductal adenocarcinoma (PDAC). However, the impact of KDM6A loss on the PDAC tumor immune microenvironment is not known. This study used a genetically engineered, pancreas-specific Kdm6a knockout (KO) PDAC mouse model and human PDAC tissue samples to demonstrate that KDM6A loss correlates with increased tumor-associated neutrophils and neutrophil extracellular traps (NET) formation, which are known to contribute to PDAC progression. Genome-wide bromouridine sequencing analysis to evaluate nascent RNA synthesis showed that the expression of many chemotactic cytokines, especially CXC motif chemokine ligand 1 (CXCL1), was upregulated in KDM6A KO PDAC cells. KDM6A-deficient PDAC cells secreted higher levels of CXCL1 protein, which in turn recruited neutrophils. Furthermore, in a syngeneic orthotopic mouse model, treatment with a CXCL1 neutralizing antibody blocked the chemotactic and NET-promoting properties of KDM6A-deficient PDAC cells and suppressed tumor growth, confirming CXCL1 as a key mediator of chemotaxis and PDAC growth driven by KDM6A loss. These findings shed light on how KDM6A regulates the tumor immune microenvironment and PDAC progression and suggests that the CXCL1-CXCR2 axis may be a candidate target in PDAC with KDM6A loss. SIGNIFICANCE KDM6A loss in pancreatic cancer cells alters the immune microenvironment by increasing CXCL1 secretion and neutrophil recruitment, providing a rationale for targeting the CXCL1-CXCR2 signaling axis in tumors with low KDM6A.