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846 result(s) for "Ding, Andrew"
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HyperSense: Hyperdimensional Intelligent Sensing for Energy‐Efficient Sparse Data Processing
Introducing HyperSense, the co‐designed hardware and software system efficiently controls analog‐to‐digital converter (ADC) modules’ data generation rate based on object presence predictions in sensor data. Addressing challenges posed by escalating sensor quantities and data rates, HyperSense reduces redundant digital data using energy‐efficient low‐precision ADC, diminishing machine learning system costs. Leveraging neurally inspired hyperdimensional computing, HyperSense analyzes real‐time raw low‐precision sensor data, offering advantages in handling noise, memory‐centricity, and real‐time learning. The proposed HyperSense model combines high‐performance software for object detection with real‐time hardware prediction, introducing the novel concept of intelligent sensor control. Comprehensive software and hardware evaluations demonstrate the solution's superior performance, evidenced by the highest area under the curve and sharpest receiver operating characteristic curve among lightweight models. Hardware‐wise, the field programmable gate array‐based domain‐specific accelerator tailored for HyperSense achieves a 5.6× speedup compared to YOLOv4 on NVIDIA Jetson Orin while showing up to 92.1% energy saving compared to the conventional system. These results underscore HyperSense's effectiveness and efficiency, positioning it as a promising solution for intelligent sensing and real‐time data processing across diverse applications. The article introduces HyperSense, a novel system that enhances sensor efficiency through hyperdimensional computing. This innovative approach significantly reduces unnecessary data processing by focusing solely on crucial information, saving energy, and improving both the speed and accuracy of data analysis. Ideal for real‐world applications, it holds promise for various industries.
Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
The salivary gland (SG) is vital for oral function and overall health through secretion of saliva. However salivary dysfunction due to aging, medications, autoimmune disorders, and cancer treatments poses significant challenges. We established the first diverse and clinically annotated salivary regenerative biobank at Mayo Clinic to study salivary gland stem/progenitor cells (SGSPCs). Optimization of cell isolation and progenitor assays revealed SGSPCs enriched within the CD24/EpCAM/CD49f+ and PSMA- phenotypes of both submandibular and parotid glands, with clonal differentiation assays highlighting heterogeneity. Induction of PSMA/FOLH1 expression was associated with SGSPC differentiation. Using mass spectrometry-based single cell proteomics, we identified 2461 proteins in SGSPC-enriched cells, including co-expressed cytokeratins, expressed in rare salivary ductal basal cells. Additionally, PRDX, a unique class of peroxiredoxin peroxidases enriched in SGSPCs, demonstrated H 2 O 2 -dependent growth, suggesting a role in salivary homeostasis. These findings provide a foundation for SGSPC research and potential regenerative therapies for salivary gland dysfunction.
Temporal and cell-type specific SPAK-NKCC1 disruption following severe TBI in the developing gyrencephalic brain
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in infants and toddlers, with limited treatment options and persistent neurological sequelae. We developed a multi-pathoanatomic lesion multi-insult (MuLMI) severe TBI model in piglets that replicates age-dependent damage patterns to the cortical ribbon observed in human patients with less injury in postnatal day (PND) 7 “infant” piglets and more extensive tissue damage in PND30 “toddler” piglets. Given that neuronal chloride homeostasis influences excitability, seizure susceptibility, and edema, we examined the developmental and injury-induced regulation of key cation-chloride cotransporters and modulators: NKCC1 (sodium-potassium-2-chloride cotransporter), KCC2 (potassium-chloride cotransporter), and the regulatory kinase SPAK, which are biomarkers of neuronal chloride concentrations. This study is the first to define the spatiotemporal expression and phosphorylation profiles of these proteins in the developing piglet brain. We found a perinatal shift in the ratio of KCC2:NKCC1 across the brain, driven primarily by protein abundance, rather than transcriptional levels. We hypothesized that toddler piglets would exhibit an increase in cortical NKCC1 and SPAK causing hyperexcitability and perhaps explaining their more severe, unilateral cortical damage. Severe TBI induced a transcriptional increase in Slc12a2 (Solute Carrier Family 12 Member 2) and Stk39 (Serine Threonine Kinase 39) , and a decrease in Slc12a5 (Solute Carrier Family 12 Member 5) in toddler piglets, but not infant piglets. We further found that infant piglets, not toddler piglets, upregulated SPAK and Tyrosine Receptor Kinase B (TRKB) protein in cortex after TBI, with minimal changes in NKCC1 and KCC2. However, phosphorylated NKCC1 (pNKCC1) was significantly upregulated in surviving cortical neurons after TBI in infant piglets and was unchanged in toddlers, despite more severe injury. These findings suggest that cortical neuronal NKCC1 activation may play a role in post-traumatic excitability or resilience in the immature brain and identify NKCC1 and/or SPAK as a potential therapeutic target. In human tissue, the KCC2:NKCC1 ratio also increased postnatally, and TBI caused region and cell-type specific dysregulation of pNKCC1. Our results establish piglets as a valuable model for investigating age-specific mechanisms of pediatric TBI and for testing targeted interventions, particularly for infant populations where seizure control remains a major clinical challenge.
Fibreoptic Orotracheal Intubation of Obese Patients Using Parker Flex-Tip vs. Standard Endotracheal Tube
Objective: Advancement of the endotracheal tube through a fibreoptic scope can sometimes prove to be challenging in obese patients. The Parker Flex-Tip endotracheal tube was developed with a curved and tapered distal tip to facilitate easier placement in the trachea. This study examined the use of the Parker Flex-Tip tube as compared to standard endotracheal tubes in patients with a body mass index of 30 or greater. Methods: Sixty patients undergoing surgery requiring general anaesthesia were randomised into two groups. Using the fibreoptic scope, one group was intubated with the Parker Flex-Tip tube and the other group with a standard polyvinyl Portex tube. The time for intubation and the number of attempts required to place the endotracheal tube were measured and recorded. Results: Using the Mann-Whitney U rank sum test, the median time needed for intubation with the two types of endotracheal tubes did not show a significant difference. The chi-square analyses were conducted for the number of attempts needed to place the endotracheal tubes, which also did not demonstrate any significant difference. Conclusion: Parker Flex-Tip endotracheal tube was not superior to the standard endotracheal tubes for fibreoptic intubation in obese patients.
The Mayo Clinic Salivary Tissue-Organoid Biobanking: A Resource for Salivary Regeneration Research
The salivary gland (SG) is an essential organ that secretes saliva, which supports versatile oral function throughout life, and is maintained by elusive epithelial stem and progenitor cells (SGSPC). Unfortunately, aging, drugs, autoimmune disorders, and cancer treatments can lead to salivary dysfunction and associated health consequences. Despite many ongoing therapeutic efforts to mediate those conditions, investigating human SGSPC is challenging due to lack of standardized tissue collection, limited tissue access, and inadequate purification methods. Herein, we established a diverse and clinically annotated salivary regenerative biobanking at the Mayo Clinic, optimizing viable salivary cell isolation and clonal assays in both 2D and 3D-matrigel growth environments. Our analysis identified ductal epithelial cells in vitro enriched with SGSPC expressing the CD24/EpCAM/CD49f+ and PSMA- phenotype. We identified PSMA expression as a reliable SGSPC differentiation marker. Moreover, we identified progenitor cell types with shared phenotypes exhibiting three distinct clonal patterns of salivary differentiation in a 2D environment. Leveraging innovative label-free unbiased LC-MS/MS-based single-cell proteomics, we identified 819 proteins across 71 single cell proteome datasets from purified progenitor-enriched parotid gland (PG) and sub-mandibular gland (SMG) cultures. We identified distinctive co-expression of proteins, such as KRT1/5/13/14/15/17/23/76 and 79, exclusively observed in rare, scattered salivary ductal basal cells, indicating the potential de novo source of SGSPC. We also identified an entire class of peroxiredoxin peroxidases, enriched in PG than SMG, and attendant H2O2-dependent cell proliferation in vitro suggesting a potential role for PRDX-dependent floodgate oxidative signaling in salivary homeostasis. The distinctive clinical resources and research insights presented here offer a foundation for exploring personalized regenerative medicine.Competing Interest StatementThe authors have declared no competing interest.
Linear Modeling of Biomarkers of Cardiac and Central Nervous System Histopathology in Macaques Infected With Simian Immunodeficiency Virus
Comorbidities of human immunodeficiency virus (HIV) infection are the leading cause of HIV-associated mortality in the United States. Some of the most prevalent comorbidities include cardiovascular disease and HIV-associated neurocognitive deficit. Common to both cardiovascular disease and HIV-associated neurocognitive deficit is chronic inflammation, elevated soluble markers produced by monocytes and macrophages, and the accumulation of monocytes and macrophages in tissue. Recently, galectin-3 and interleukin-18 have been identified as biomarkers of cardiovascular disease, and galectin-9 has been identified a biomarker of HIV-associated neurocognitive deficit. Galectin-3, interleukin-18, and galectin-9 play important roles in the innate immune response and can be produced by, or act on monocytes and macrophages. Galectin-3, interleukin-18, and galectin-9 are most often studied independent of one another and as specific biomarkers of either cardiovascular disease or neurocognitive deficit. We asked if these biomarkers increased in both cardiovascular disease and neurocognitive deficit, rather than being selective for either comorbidity. Using a model of simian immunodeficiency virus infection which results in AIDS with cardiac and/or central nervous system histopathology, we find that these biomarkers are not selective to either pathology. We show that galectin-3, interleukin-18, and galectin-9 correlate with the monocyte activation marker sCD163 and monocyte turnover by the percentage of BrdU+ monocytes in blood 24 hours post-pulse. Using linear mixed models, we identify interleukin-18 as a potential prognostic marker of co-developing cardiac and central nervous system histopathology. These findings suggest that cardiovascular disease and neurocognitive deficit in people living with HIV are linked manifestations of innate immune system activation, rather than independent phenomena.
Structural basis of the ultrasensitive calcium indicator GCaMP6
GCaMP is one of the most widely used calcium indicators in neuronal imaging and calcium cell biology. The newly developed GCaMP6 shows superior brightness and ultrasensitivity to calcium concentration change. In this study, we determined crystal structures of CaZ+-bound GCaMP6 monomer and dimer and presented detailed structural analyses in comparison with its par- ent version GCaMP5G. Our analyses reveal the structural basis for the outperformance of this newly developed Ca2+ indicator. Three substitution mutations and the resulting changes of local structure and interaction explain the ultrasensitivity and in- creased fluorescence intensity common to all three versions of GCaMP6. Each particular substitution in the three GCaMP6 is also structurally consistent with their differential sensitivity and intensity, maximizing the potential of using GCaMP6 in solving diverse problems in neuronal research and calcium signaling. Our studies shall also be beneficial to further structure-guided optimization of GCaMP and facilitate the design of novel calcium indicators.
The adenoviral E1A protein displaces corepressors and relieves gene repression by unliganded thyroid hormone receptors in vivo
The human adenovirus type 5 early region 1A (E1A) is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone (T3) receptors (TRs). However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.
MapSAM2: Adapting SAM2 for Automatic Segmentation of Historical Map Images and Time Series
Historical maps are unique and valuable archives that document geographic features across different time periods. However, automated analysis of historical map images remains a significant challenge due to their wide stylistic variability and the scarcity of annotated training data. Constructing linked spatio-temporal datasets from historical map time series is even more time-consuming and labor-intensive, as it requires synthesizing information from multiple maps. Such datasets are essential for applications such as dating buildings, analyzing the development of road networks and settlements, studying environmental changes etc. We present MapSAM2, a unified framework for automatically segmenting both historical map images and time series. Built on a visual foundation model, MapSAM2 adapts to diverse segmentation tasks with few-shot fine-tuning. Our key innovation is to treat both historical map images and time series as videos. For images, we process a set of tiles as a video, enabling the memory attention mechanism to incorporate contextual cues from similar tiles, leading to improved geometric accuracy, particularly for areal features. For time series, we introduce the annotated Siegfried Building Time Series Dataset and, to reduce annotation costs, propose generating pseudo time series from single-year maps by simulating common temporal transformations. Experimental results show that MapSAM2 learns temporal associations effectively and can accurately segment and link buildings in time series under limited supervision or using pseudo videos. We will release both our dataset and code to support future research.
T-SAR: A Full-Stack Co-design for CPU-Only Ternary LLM Inference via In-Place SIMD ALU Reorganization
Recent advances in LLMs have outpaced the computational and memory capacities of edge platforms that primarily employ CPUs, thereby challenging efficient and scalable deployment. While ternary quantization enables significant resource savings, existing CPU solutions rely heavily on memory-based lookup tables (LUTs) which limit scalability, and FPGA or GPU accelerators remain impractical for edge use. This paper presents T-SAR, the first framework to achieve scalable ternary LLM inference on CPUs by repurposing the SIMD register file for dynamic, in-register LUT generation with minimal hardware modifications. T-SAR eliminates memory bottlenecks and maximizes data-level parallelism, delivering 5.6-24.5x and 1.1-86.2x improvements in GEMM latency and GEMV throughput, respectively, with only 3.2% power and 1.4% area overheads in SIMD units. T-SAR achieves up to 2.5-4.9x the energy efficiency of an NVIDIA Jetson AGX Orin, establishing a practical approach for efficient LLM inference on edge platforms.