Subspace-Search Quantum Imaginary Time Evolution for Excited State Computations.

Quantum systems in excited states are attracting significant interest with the advent of noisy intermediate-scale quantum (NISQ) devices. While ground states of small molecular systems are typically explored using hybrid variational algorithms like the variational quantum eigensolver (VQE), the study of excited states has received much less attention, partly due to the absence of efficient algorithms. In this work, we introduce the subspace search quantum imaginary time evolution (SSQITE) method, which calculates excited states using quantum devices by integrating key elements of the subspace search variational quantum eigensolver (SSVQE) and the variational quantum imaginary time evolution (VarQITE) method. The effectiveness of SSQITE is demonstrated through calculations of low-lying excited states of benchmark model systems including H2 and LiH molecules. A toy Hamiltonian is also employed to demonstrate that the robustness of VarQITE in avoiding local minima extends to its use in excited state algorithms. With this robustness in avoiding local minima, SSQITE shows promise for advancing quantum computations of excited states across a wide range of applications.

Effects of different pre-exercise strategies on jumping performance in female volleyball players.

BACKGROUND: The present study aimed to compare different pre-exercise strategies on jumping performance in female volleyball players. METHODS: Fifteen healthy female volleyball players (age=18±0.6 years; training experience = 7.3±1.4 years; height = 164.8±5.4 cm; body mass = 57.2±8.1 kg) volunteered to participate in the study. Three different pre-exercise conditions (5 repetition maximum knee extension, electromyostimulation [EMS] and ischemic preconditioning [IPC]) were applied to the subjects and compared to a control condition performing a standardized warmup. Subjects performed the squat jump and 15 sec repeated countermovement jumps following a rest period. Measures associated with jumping performance were collected and compared between conditions. Rating of perceived exertion was also collected after each performance test. RESULTS: No pre-exercise condition outperformed a standardized warm-up on inducing improvements in jumping performance and in fact, EMS and IPC conditions resulted in performance decrements compared to control (P<0.05). CONCLUSIONS: We conclude that a standardized warm-up is enough to induce improvements in jumping performance in female volleyball players. Future research should examine alternative strategies alongside standardized warm-up to determine how best to prepare for jumping and related sport-specific tasks in female volleyball players.

Rapid Quantification of Protein Secondary Structure Composition from a Single Unassigned 1D 13C Nuclear Magnetic Resonance Spectrum.

The function of a protein is predicated upon its three-dimensional fold. Representing its complex structure as a series of repeating secondary structural elements is one of the most useful ways by which we study, characterize, and visualize a protein. Consequently, experimental methods that quantify the secondary structure content allow us to connect a protein's structure to its function. Here, we introduce an automated gradient descent-based method we refer to as secondary-structure distribution by NMR that allows for rapid quantification of the protein secondary structure composition of a protein from a single, 1D 13C NMR spectrum without chemical shift assignments. The analysis of nearly 900 proteins with known structure and chemical shifts demonstrates the capabilities of our approach. We show that these results rival alternative techniques such as FT-IR and circular dichroism that are commonly used to estimate secondary structure compositions. The resulting method requires only the primary sequence of the protein and its referenced 13C NMR spectrum. Each residue is modeled in an ensemble of secondary structures with percentage contributions from random coil, α-helix, and ß-sheet secondary structures obtained by minimizing the difference between a simulated and experimental 1D 13C NMR spectrum. The capabilities of the method are demonstrated as applied to samples at natural abundance or enriched in 13C, acquired by either solution or solid-state NMR, and even on low magnetic field benchtop NMR spectrometers. This approach allows for rapid characterization of protein secondary structure across traditionally challenging to characterize states including liquid-liquid phase-separated, membrane-bound, or aggregated states.

Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase.

Dual-specificity mitogen-activated protein kinase (MAPK) phosphatases (MKPs) directly dephosphorylate and inactivate the MAPKs. Although the catalytic mechanism of dephosphorylation of the MAPKs by the MKPs is established, a complete molecular picture of the regulatory interplay between the MAPKs and MKPs still remains to be fully explored. Here, we sought to define the molecular mechanism of MKP5 regulation through an allosteric site within its catalytic domain. We demonstrate using crystallographic and NMR spectroscopy approaches that residue Y435 is required to maintain the structural integrity of the allosteric pocket. Along with molecular dynamics simulations, these data provide insight into how changes in the allosteric pocket propagate conformational flexibility in the surrounding loops to reorganize catalytically crucial residues in the active site. Furthermore, Y435 contributes to the interaction with p38 MAPK and JNK, thereby promoting dephosphorylation. Collectively, these results highlight the role of Y435 in the allosteric site as a novel mode of MKP5 regulation by p38 MAPK and JNK.

Which side of the coin are you on regarding possible postnatal oogenesis?

It is well known that oocytes are produced during fetal development and that the total number of primary follicles is determined at birth. In humans, there is a constant loss of follicles after birth until about two years of age. The number of follicles is preserved until the resumption of meiosis at puberty and there is no renewal of the oocytes; this dogma was maintained in the last century because there were no suitable techniques to detect and obtain stem cells. However, following stem cell markers, several scientists have detected them in developing and adult human ovarian tissues, especially in the ovarian surface epithelial cells. Furthermore, many authors using different methodological strategies have indicated this possibility. This evidence has led many scientists to explore this hypothesis; there is no definitive consensus to accept this idea. Interestingly, oocyte retrieval from mature ovaries and other tissue sources of stem cells has contributed to the development of strategies for the retrieval of mature oocytes, useful for assisted reproductive technology. Here, we review the evidence and controversies on oocyte neooogenesis in adult women; in addition, we agree with the idea that this process may occur in adulthood and that its alteration may be related to various pathologies in women, such as polycystic ovary syndrome, premature ovarian insufficiency, diminished ovarian reserve and several infertility and genetic disorders.

Mechano-responses of quadriceps muscles evoked by transcranial magnetic stimulation.

Mechanomyography (MMG) may be used to quantify very small motor responses resulting from muscle activation, voluntary or involuntary. The purpose of this study was to investigate the MMG mean peak amplitude (MPA) and area under the curve (AUC) and the corresponding mechanical responses following delivery of transcranial magnetic stimulation (TMS) to the knee extensors. Fourteen adults (23 ± 1 years) received single TMS pulses at intensities from 30-80 % maximum stimulator output to elicit muscle responses in the relaxed knee extensors while seated. An accelerometer-based sensor was placed on the rectus femoris (RF) and vastus lateralis (VL) muscle bellies to measure the MMG signal. Pearson correlation revealed a positive linear relationship between MMG MPA and TMS intensity for RF (r=0.569; p<0.001) and VL (r=0.618; p<0.001). TMS intensity of ≥60 % maximum stimulator output produced significantly higher MPA than at 30 % TMS intensity and evoked measurable movement at the knee joint. MMG MPA was positively correlated to AUC (r=0.957 for RF and r=0.603 for VL; both p<0.001) and knee extension angle (r=0.596 for RF and r=0.675 for VL; both p<0.001). In conclusion, MMG captured knee extensor mechanical responses at all TMS intensities with the response increasing with increasing TMS intensity. These findings suggest that MMG can be an additional tool for assessing muscle activation.

Catecholamine-Induced Cardiomyopathy Secondary to Pheochromocytoma Rescued With Percutaneous Left Ventricular Assist Device: Novel Application of the Impella CP in a Pediatric Patient.

Background: Catecholamine-induced cardiomyopathy is an uncommon complication of pheochromocytoma. Pheochromocytoma is a rare tumor that predominantly occurs in adults, making catecholamine-induced cardiomyopathy secondary to pheochromocytoma in children an exceedingly rare presentation. Treatment typically consists of medical management followed by surgical resection. Mechanical support, typically salvage therapy with extracorporeal membrane oxygenation, has been used in adult patients with cardiogenic shock and after cardiac arrest, but to our knowledge, the use of mechanical support has not been described in pediatric patients. Case Report: A 16-year-old female presented with cardiogenic shock resulting from catecholamine-induced cardiomyopathy secondary to pheochromocytoma. She was treated with a percutaneous left ventricular assist device to allow myocardial recovery while medical therapy was optimized. Given the early initiation, the patient's myocardial recovery was prompt, and only 3 days of device support were required. She was discharged in good condition and subsequently underwent uncomplicated laparoscopic resection of the tumor a few weeks later. Conclusion: In pediatric patients with catecholamine-induced cardiomyopathy secondary to pheochromocytoma, aggressive measures of support-including mechanical support and infrequently used options such as percutaneous left ventricular assist devices-should be considered early in treatment to maintain adequate cardiac output, avoid cardiac arrest, and allow for prompt myocardial recovery.

How Aligned are Human Chart Takeaways and LLM Predictions? A Case Study on Bar Charts with Varying Layouts.

Large Language Models (LLMs) have been adopted for a variety of visualizations tasks, but how far are we from perceptually aware LLMs that can predict human takeaways? Graphical perception literature has shown that human chart takeaways are sensitive to visualization design choices, such as spatial layouts. In this work, we examine the extent to which LLMs exhibit such sensitivity when generating takeaways, using bar charts with varying spatial layouts as a case study. We conducted three experiments and tested four common bar chart layouts: vertically juxtaposed, horizontally juxtaposed, overlaid, and stacked. In Experiment 1, we identified the optimal configurations to generate meaningful chart takeaways by testing four LLMs, two temperature settings, nine chart specifications, and two prompting strategies. We found that even state-of-the-art LLMs struggled to generate semantically diverse and factually accurate takeaways. In Experiment 2, we used the optimal configurations to generate 30 chart takeaways each for eight visualizations across four layouts and two datasets in both zero-shot and one-shot settings. Compared to human takeaways, we found that the takeaways LLMs generated often did not match the types of comparisons made by humans. In Experiment 3, we examined the effect of chart context and data on LLM takeaways. We found that LLMs, unlike humans, exhibited variation in takeaway comparison types for different bar charts using the same bar layout. Overall, our case study evaluates the ability of LLMs to emulate human interpretations of data and points to challenges and opportunities in using LLMs to predict human chart takeaways.

Simulating Cavity-Modified Electron Transfer Dynamics on NISQ Computers.

We present an algorithm based on the quantum-mechanically exact tensor-train thermo-field dynamics (TT-TFD) method for simulating cavity-modified electron transfer dynamics on noisy intermediate-scale quantum (NISQ) computers. The utility and accuracy of the proposed methodology is demonstrated on a model for the photoinduced intramolecular electron transfer reaction within the carotenoid-porphyrin-C60 molecular triad in tetrahydrofuran (THF) solution. The electron transfer rate is found to increase significantly with increasing coupling strength between the molecular system and the cavity. The rate process is also seen to shift from overdamped monotonic decay to under-damped oscillatory dynamics. The electron transfer rate is seen to be highly sensitive to the cavity frequency, with the emergence of a resonance cavity frequency for which the effect of coupling to the cavity is maximal. Finally, an implementation of the algorithm on the IBM Osaka quantum computer is used to demonstrate how TT-TFD-based electron transfer dynamics can be simulated accurately on NISQ computers.

Site-specific template generative approach for retrosynthetic planning.

Retrosynthesis, the strategy of devising laboratory pathways by working backwards from the target compound, is crucial yet challenging. Enhancing retrosynthetic efficiency requires overcoming the vast complexity of chemical space, the limited known interconversions between molecules, and the challenges posed by limited experimental datasets. This study introduces generative machine learning methods for retrosynthetic planning. The approach features three innovations: generating reaction templates instead of reactants or synthons to create novel chemical transformations, allowing user selection of specific bonds to change for human-influenced synthesis, and employing a conditional kernel-elastic autoencoder (CKAE) to measure the similarity between generated and known reactions for chemical viability insights. These features form a coherent retrosynthetic framework, validated experimentally by designing a 3-step synthetic pathway for a challenging small molecule, demonstrating a significant improvement over previous 5-9 step approaches. This work highlights the utility and robustness of generative machine learning in addressing complex challenges in chemical synthesis.

Beyond the "spine of hydration": Chiral SFG spectroscopy detects DNA first hydration shell and base pair structures.

Experimental methods capable of selectively probing water at the DNA minor groove, major groove, and phosphate backbone are crucial for understanding how hydration influences DNA structure and function. Chiral-selective sum frequency generation spectroscopy (chiral SFG) is unique among vibrational spectroscopies because it can selectively probe water molecules that form chiral hydration structures around biomolecules. However, interpreting chiral SFG spectra is challenging since both water and the biomolecule can produce chiral SFG signals. Here, we combine experiment and computation to establish a theoretical framework for the rigorous interpretation of chiral SFG spectra of DNA. We demonstrate that chiral SFG detects the N-H stretch of DNA base pairs and the O-H stretch of water, exclusively probing water molecules in the DNA first hydration shell. Our analysis reveals that DNA transfers chirality to water molecules only within the first hydration shell, so they can be probed by chiral SFG spectroscopy. Beyond the first hydration shell, the electric field-induced water structure is symmetric and, therefore, precludes chiral SFG response. Furthermore, we find that chiral SFG can differentiate chiral subpopulations of first hydration shell water molecules at the minor groove, major groove, and phosphate backbone. Our findings challenge the scientific perspective dominant for more than 40 years that the minor groove "spine of hydration" is the only chiral water structure surrounding the DNA double helix. By identifying the molecular origins of the DNA chiral SFG spectrum, we lay a robust experimental and theoretical foundation for applying chiral SFG to explore the chemical and biological physics of DNA hydration.

Exercise Habits in People with Parkinson's: A Multinational Survey.

BACKGROUND: Exercise has been demonstrated to result in improvements in physical function, cognition, and quality of life in People with Parkinson's (PwP) but its adoption is variable. OBJECTIVES: To investigate exercise preferences, levels, influencing factors among a diverse Parkinson's disease (PD) population, to understand exercise adoption patterns and plan informed interventions. METHODS: A cross-sectional survey collected data through online platforms and paper-based methods. The Exercise Index (ExI) calculated exercise level based on frequency and duration. RESULTS: Of 2976 PwP, 40.6% exercised regularly, 38.3% occasionally, and 21.2% did not exercise. The overall mean ExI was 18.99 ± 12.37. Factors associated with high exercise levels included exercising in groups (ExI 24-26), weightlifting (ExI 27 (highest)), using muscle-building equipment (ExI 25-26), and exercising at home following an app (ExI 26). A positive trend between ExI and varied exercise groups, locations, types, and equipment was observed. No expected benefit from exercise achieved the lowest ExI (8). Having at least two exercise-promoting factors, a bachelor's degree or higher, receiving exercise advice at initial visits, and aged ≤40 years at PD onset were strong predictors of exercise (adjust OR = 7.814; 6.981; 4.170; 3.565). Falls and "other" most troublesome PD symptoms were negative predictors (aOR = 0.359; 0.466). Barriers to exercise did not predict the odds of exercise. CONCLUSIONS: The study shows that PwP's exercise behavior is influenced by their exercise belief, age at PD onset, doctor's advice at initial visits, education level, symptoms, and exercise-promoting factors. High exercise levels were associated with certain types of exercises and exercising in groups.

Mucosal immune responses in peri-parturient dairy cattle.

The objectives of this study were to evaluate mucosal immune responses in peripartum Holstein cows, to assess the impact of intranasal modified live viral (MLV) vaccination on mucosal immunity, and to explore the relationship between genotype and peripartum immune responses. Eighty multiparous Holstein cows were randomized to receive either: 1) intranasal MLV tri-valent viral vaccine 18-24 days prior to expected calving (DC); 2) the same vaccine within twelve hours after parturition (F); 3) vaccine at both time points (DCF), or 4) no vaccine (CON). Nasal secretions and sera were collected from all cattle pre-vaccination and on multiple days before and after calving to determine concentrations of interferon beta (IFN-beta) and IFN-gamma and bovine herpesvirus-1 (BHV-1-) and bovine respiratory syncytial virus (BRSV-) specific IgA in nasal secretions, and BHV-1 and BRSV serum neutralizing (SN) titers. Cows were genotyped by bead-based microarray, genotypes were used to categorize previously established health traits, and relationships between immune responses and genotype were evaluated. There was no significant effect of vaccination on immune responses, although all vaccinated groups demonstrated numerically increased IFN-gamma within four days post vaccination. There was a significant (P <0.0001) time effect on nasal IgA in CON, F, and DCF groups, with the highest nasal IgA titers measured post calving. There was a significant (P <0.0001) time effect on nasal IFN-beta in all groups. Significant relationships between genotype and immune response were not detected. Contrary to previous reports of systemic immunosuppression, bovine mucosal responses appear to be intact in the peripartum period.

Evolution of Proton Radiation Therapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry.

PURPOSE: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR). MATERIAL AND METHODS: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint guidelines by treatment era, histology, and extent of surgical resection. RESULTS: A total of 467 patients with evaluable proton radiation therapy plans were reviewed. Median age was 7.1 years (range: <1-21.9), 63.0% (n = 296) were men, 76.0% (n = 357) were White, and predominant histology was medulloblastoma (55.0%, n = 256), followed by ependymoma (27.0%, n = 125). Extent of resection was mainly gross total resection (GTR) (67.0%, n = 312), followed by subtotal resection (STR) or biopsy (20.0%, n = 92), and near total resection (NTR) (9.2%, n = 43). The UF brainstem constraint metrics most often exceeded were the goal D50% of 52.4 gray relative biological equivalents (43.3%, n = 202) and maximal D50% of 54 gray relative biological equivalents (12.6%, n = 59). The compliance rate increased after the new guidelines (2002-2014: 64.0% vs 2015-2019: 74.6%, P = .02), except for ependymoma (46.3% pre- vs 50.0% post-guidelines, P = .86), presenting lower compliance (48.8%) in comparison to medulloblastoma/ primitive neuroectodermal tumors/pineoblastoma (77.7%), glioma (89.1%), and atypical teratoid/rhabdoid tumors (90.9%) (P < .001). Degree of surgical resection did not affect compliance rates (GTR/NTR 71.0% vs STR/biopsy 72.8%, P = .45), even within the ependymoma subset (GTR/NTR 50.5% vs STR/biopsy 38.1%, P = .82). CONCLUSION: Since the publication of the UF guidelines, the pediatric proton community has implemented more conservative brainstem constraints in all patients except those with ependymoma, irrespective of residual disease after surgery. Future work will evaluate if this change in practice is associated with decreased rates of brainstem toxicity.

Similarity Metrics for Subcellular Analysis of FRET Microscopy Videos.

Understanding the heterogeneity of molecular environments within cells is an outstanding challenge of great fundamental and technological interest. Cells are organized into specialized compartments, each with distinct functions. These compartments exhibit dynamic heterogeneity under high-resolution microscopy, which reflects fluctuations in molecular populations, concentrations, and spatial distributions. To enhance our comprehension of the spatial relationships among molecules within cells, it is crucial to analyze images of high-resolution microscopy by clustering individual pixels according to their visible spatial properties and their temporal evolution. Here, we evaluate the effectiveness of similarity metrics based on their ability to facilitate fast and accurate data analysis in time and space. We discuss the capability of these metrics to differentiate subcellular localization, kinetics, and structures of protein-RNA interactions in Forster resonance energy transfer (FRET) microscopy videos, illustrated by a practical example from recent literature. Our results suggest that using the correlation similarity metric to cluster pixels of high-resolution microscopy data should improve the analysis of high-dimensional microscopy data in a wide range of applications.

The Case for Bisphosphonate Use in Astronauts Flying Long-Duration Missions.

Changes in the structure of bone can occur in space as an adaptive response to microgravity and on Earth due to the adaptive effects to exercise, to the aging of bone cells, or to prolonged disuse. Knowledge of cell-mediated bone remodeling on Earth informs our understanding of bone tissue changes in space and whether these skeletal changes might increase the risk for fractures or premature osteoporosis in astronauts. Comparisons of skeletal health between astronauts and aging humans, however, may be both informative and misleading. Astronauts are screened for a high level of physical fitness and health, are launched with high bone mineral densities, and perform exercise daily in space to combat skeletal atrophy as an adaptive response to reduced weight-bearing function, while the elderly display cellular and tissue pathology as a response to senescence and disuse. Current clinical testing for age-related bone change, applied to astronauts, may not be sufficient for fully understanding risks associated with rare and uniquely induced bone changes. This review aims to (i) highlight cellular analogies between spaceflight-induced and age-related bone loss, which could aid in predicting fractures, (ii) discuss why overreliance on terrestrial clinical approaches may miss potentially irreversible disruptions in trabecular bone microarchitecture induced by spaceflight, and (iii) detail how the cellular effects of the bisphosphonate class of drugs offer a prophylactic countermeasure for suppressing the elevated bone resorption characteristically observed during long-duration spaceflights. Thus the use of the bisphosphonate will help protect the bone from structural changes while in microgravity either along with exercise or alone when exercise is not performed, e.g. after an injury or illness.

A synergetic cocatalyst for conversion of carbon dioxide, sunlight, and water into methanol.

The conversion of CO2 into liquid fuels, using only sunlight and water, offers a promising path to carbon neutrality. An outstanding challenge is to achieve high efficiency and product selectivity. Here, we introduce a wireless photocatalytic architecture for conversion of CO2 and water into methanol and oxygen. The catalytic material consists of semiconducting nanowires decorated with core-shell nanoparticles, with a copper-rhodium core and a chromium oxide shell. The Rh/CrOOH interface provides a unidirectional channel for proton reduction, enabling hydrogen spillover at the core-shell interface. The vectorial transfer of protons, electrons, and hydrogen atoms allows for switching the mechanism of CO2 reduction from a proton-coupled electron transfer pathway in aqueous solution to hydrogenation of CO2 with a solar-to-methanol efficiency of 0.22%. The reported findings demonstrate a highly efficient, stable, and scalable wireless system for synthesis of methanol from CO2 that could provide a viable path toward carbon neutrality and environmental sustainability.

Genomic data reveal a north-south split and introgression history of blood fluke (Schistosoma haematobium) populations from across Africa.

The human parasitic fluke, Schistosoma haematobium hybridizes with the livestock parasite S. bovis in the laboratory, but the extent of hybridization in nature is unclear. We analyzed 34.6 million single nucleotide variants in 162 samples from 18 African countries, revealing a sharp genetic discontinuity between northern and southern S. haematobium. We found no evidence for recent hybridization. Instead the data reveal admixture events that occurred 257-879 generations ago in northern S. haematobium populations. Fifteen introgressed S. bovis genes are approaching fixation in northern S. haematobium with four genes potentially driving adaptation. We identified 19 regions that were resistant to introgression; these were enriched on the sex chromosomes. These results (i) demonstrate strong barriers to gene flow between these species, (ii) indicate that hybridization may be less common than currently envisaged, but (iii) reveal profound genomic consequences of interspecific hybridization between schistosomes of medical and veterinary importance.