UC Riverside

We present an open-source software package, VAN-DAMME (Versatile Approaches to Numerically Design, Accelerate, and Manipulate Magnetic Excitations), for massively-parallelized quantum optimal control (QOC) calculations of multi-qubit systems. To enable large QOC calculations, the VAN-DAMME software package utilizes symmetry-based techniques with custom GPU-enhanced algorithms. This combined approach allows for the simultaneous computation of hundreds of matrix exponential propagators that efficiently leverage the intra-GPU parallelism found in high-performance GPUs. In addition, to maximize the computational efficiency of the VAN-DAMME code, we carried out several extensive tests on data layout, computational complexity, memory requirements, and performance. These extensive analyses allowed us to develop computationally efficient approaches for evaluating complex-valued matrix exponential propagators based on Padé approximants. To assess the computational performance of our GPU-accelerated VAN-DAMME code, we carried out QOC calculations of systems containing 10 - 15 qubits, which showed that our GPU implementation is 18.4× faster than the corresponding CPU implementation. Our GPU-accelerated enhancements allow efficient calculations of multi-qubit systems, which can be used for the efficient implementation of QOC applications across multiple domains. Program summary: Program Title: VAN-DAMME CPC Library link to program files:: https://doi.org/10.17632/zcgw2n5bjf.1 Licensing provisions: GNU General Public License 3 Programming language: C++ and CUDA Nature of problem: The VAN-DAMME software package utilizes GPU-accelerated routines and new algorithmic improvements to compute optimized time-dependent magnetic fields that can drive a system from a known initial qubit configuration to a specified target state with a large (≈1) transition probability. Solution method: Quantum control, GPU acceleration, analytic gradients, matrix exponential, and gradient ascent optimization.

Uptake of COVID-19 vaccine booster doses is an important public health topic of study to prevent morbidity and mortality in underserved U.S. populations. However, limited research exists on COVID-19 vaccine booster use and willingness - including its associated factors - among Asian Americans (AA): the fastest growing racial group in the U.S. This study collected survey data from 447 AA adults from three large AA subgroups: Chinese, Korean, and Filipino. Data were collected as part of a community-driven county-wide needs assessment conducted in collaboration with AA community organizations in Riverside County, California. Data indicated that nearly 24% of AA participants received at least four doses of the COVID-19 vaccine, with 36% expressing definite willingness to receive future booster doses. Participants reported experiencing an average of 1.6 instances of racial discrimination across their lifetime. Ordered logistic regression and marginal effects analysis revealed ethnicity, education, racial discrimination, preexisting health conditions, and the number of prior COVID-19 vaccine doses received significantly predicted willingness to receive future vaccine doses. The study suggests that key social factors such as racial discrimination may play an important role in influencing public health efforts to promote vaccine uptake in diverse Asian American populations.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is an effective and safe option to prevent HIV acquisition and vertical HIV transmission in pregnant and breastfeeding women. Understanding health system factors influencing the integration of PrEP into care for pregnant and breastfeeding women is key to increasing access. We explored managers and health care workers (HCWs) experiences with integrating PrEP into antenatal care and postnatal care services in primary health care clinics in Cape Town, South Africa. METHODS: This exploratory qualitative study used codebook thematic analysis, where HCWs were purposively, heterogeneously sampled from an implementation science study. Semistructured individual interviews were conducted with 9 managerial-level staff, and 3 focus group discussions were conducted with HCWs (nurses, midwives, and HIV counselors) providing PrEP (6-7 HCWs per group) between November 2022 and January 2023 (N=28). Interview guides covered health system facilitators, barriers, and recommendations. The Health Systems Dynamics framework guided data analysis and presentation of results. RESULTS: PrEP integration into antenatal care services was described as acceptable and feasible; however, changes to HIV testing policy and indicators in breastfeeding women are needed to integrate PrEP into postnatal clinics, together with identification of mother and baby as a dyad in visits. Results showed that supportive policies facilitated wider, simplified PrEP provision. The availability and accessibility of prescribing nurses and lay HIV counselors, PrEP (both within facilities and in communities), and information about PrEP for implementers and pregnant and breastfeeding women will be pivotal to facilitating integration. CONCLUSION: Facilitators for PrEP integration include task-shifting PrEP education and identification of women for PrEP initiation to HIV counselors, changes to national guidelines defining who can prescribe PrEP, revision and integration of PrEP training for HCWs, community-level interventions for PrEP demand creation and stigma reduction, and provision of differentiated PrEP delivery options.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most N6-methyladenosine (m6A) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for m6A can promote oncogenesis. A gain-of-function missense mutation from patients with cancer, METTL14R298P, increases malignant cell growth in culture and transgenic mice without increasing global m6A levels in mRNAs. The mutant methyltransferase preferentially modifies noncanonical sites containing a GGAU motif, in vitro and in vivo. The m6A in GGAU context is detected by the YTH family of readers similarly to the canonical sites but is demethylated less efficiently by an eraser, ALKBH5. Combining the biochemical and structural data, we provide a model for how the cognate RNA sequences are selected for methylation by METTL3-METTL14. Our work highlights that sequence-specific m6A deposition is important and that increased GGAU methylation can promote oncogenesis.

UNLABELLED: Heterotrimeric G protein signaling pathways control growth and development in eukaryotes. In the multicellular fungus Neurospora crassa, the guanine nucleotide exchange factor RIC8 regulates heterotrimeric Gα subunits. In this study, we used RNAseq and liquid chromatography-mass spectrometry (LC-MS) to profile the transcriptomes and metabolomes of N. crassa wild type, the Gα subunit mutants Δgna-1 and Δgna-3, and Δric8 strains. These strains exhibit defects in growth and asexual development (conidiation), with wild-type and Δgna-1 mutants producing hyphae in submerged cultures, while Δgna-3 and Δric8 mutants develop conidiophores, particularly in the Δric8 mutant. RNAseq analysis showed that the Δgna-1 mutant possesses 159 mis-regulated genes, while Δgna-3 and Δric8 strains have more than 1,000 each. Many of the mis-regulated genes are involved in energy homeostasis, conidiation, or metabolism. LC-MS revealed changes in levels of primary metabolites in the mutants, with several arginine metabolic intermediates impacted in Δric8 strains. The differences in metabolite levels could not be fully explained by the expression or activity of pathway enzymes. However, transcript levels for two predicted vacuolar arginine transporters were affected in Δric8 mutants. Analysis of arginine and ornithine levels in transporter mutants yielded support for altered compartmentation of arginine and ornithine between the cytosol and vacuole in Δric8 strains. Furthermore, we validated previous reports that arginine and ornithine levels are low in wild-type conidia. Our results suggest that RIC8 regulates asexual sporulation in N. crassa at least in part through altered expression of vacuolar transporter genes and the resultant mis-compartmentation of arginine and ornithine. IMPORTANCE: Resistance to inhibitors of cholinesterase-8 (RIC8) is an important regulator of heterotrimeric Gα proteins in eukaryotes. In the filamentous fungus Neurospora crassa, mutants lacking ric8 undergo inappropriate asexual development (macroconidiation) during submerged growth. Our work identifies a role for RIC8 in regulating expression of transporter genes that retain arginine and ornithine in the vacuole (equivalent of the animal lysosome) and relates this function to the developmental defect. Arginine is a critical cellular metabolite, both as an amino acid for protein synthesis and as a precursor for an array of compounds, including proline, ornithine, citrulline, polyamines, creatine phosphate, and nitric oxide. These results have broad relevance to human physiology and disease, as arginine modulates immune, vascular, hormonal, and other functions in humans.

Thermal treatment of perfluoroalkyl and polyfluoroalkyl substances (PFASs) presents a promising opportunity to halt the PFAS cycle. However, how co-occurring materials such as granular activated carbon (GAC) influence thermal decomposition products of PFASs, and underlying mechanisms remain unclear. We studied the pyrolysis of two potassium salts of perfluoroalkanesulfonates (PFSAs, C_nF_2n+1SO₃K), perfluorobutanesulfonate (PFBS-K), and perfluorooctanesulfonate (PFOS-K), with or without GAC. PFBS-K is more stable than PFOS-K for pure standards, but when it is adsorbed onto GAC, its thermal stabilities and decomposition behaviors are similar. Temperatures and heating rates can significantly influence the decomposition mechanisms and products for pure standards, while these effects are less pronounced when PFSAs are adsorbed onto GAC. We further studied the underlying decomposition mechanisms. Pure standards of C_nF_2n+1SO₃K can decompose directly in their condense phase by reactions: F(CF₂)_nSO₃K → F(CF₂)_n-2CF═CF₂ + KFSO₃ or F(CF₂)_nSO₃K → F(CF₂)_n^- + K⁺ + SO₃. GAC appears to facilitate breakage of the C-S bond to release SO₂ at temperatures as low as 280 °C. GAC promotes fluorine mineralization through functional reactive sites. SiO₂ is particularly important for the surface-mediated mineralization of PFASs into SiF₄. These findings offer valuable insights into optimizing thermal treatment strategies for PFAS-contaminated waste.

Manta rays use wing-like pectoral fins for intriguing oscillatory swimming. It provides rich inspiration for designing potentially fast, efficient, and maneuverable soft swimming robots, which, however, have yet to be realized. It remains a grand challenge to combine fast speed, high efficiency, and high maneuverability in a single soft swimmer while using simple actuation and control. Here, we report leveraging spontaneous snapping stroke in the monostable flapping wing of a manta-like soft swimmer to address the challenge. The monostable wing is pneumatically actuated to instantaneously snap through to stroke down, and upon deflation, it will spontaneously stroke up by snapping back to its initial state, driven by elastic restoring force, without consuming additional energy. This largely simplifies designs, actuation, and control for achieving a record-high speed of 6.8 body length per second, high energy efficiency, and high maneuverability and collision resilience in navigating through underwater unstructured environments with obstacles by simply tuning single-input actuation frequencies.

The environmental challenges the human malaria parasite, Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light on the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using the CRISPR/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate that PfMORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggests that PfMORC binds to not only sub-telomeric regions and genes involved in antigenic variation but may also play a role in modulating stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation of PfMORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that PfMORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies.