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Systems and methods for matrix-vector multiplication
Full text linkA patent filed on multiples techniques to implement efficient and scalable optical matrix-vector multiplication.Othe
Regulation of vascular smooth muscle: calponin 3 contributes to phorbol ester-induced cell contraction and is critical for cell proliferation and migration
No full text2025Under physiological conditions, vascular smooth muscle cells (VSMCs) exhibit a contractile phenotype, which maintains vascular tone through contraction. In response to vascular injury, VSMCs switch to a synthetic phenotype, contributing to tissue repair through proliferation and migration. While the Ca2+-calmodulin-myosin light chain kinase pathway is the best-studied mechanism regulating vascular smooth muscle (VSM) contraction, the regulation of actin filaments (F-actin) in this process is not fully understood. Apart from cross-bridge cycling, cytoskeletal actin remodeling is also essential for VSM contraction, yet the underlying mechanisms remain unclear. Calponin 3 (CNN3), an actin-binding protein, is expressed in both non-muscle and smooth muscle tissues, whereas its function has been minimally investigated in smooth muscle. The known functions of CNN3 in other cell types are closely associated with its regulation of F-actin. This study elucidates the roles of CNN3 in regulating VSMC contraction, proliferation, and migration, processes that are contingent upon F-actin.
This study reveals that CNN3, though containing binding sites for ERK and PKC, does not interact with either protein in contractile VSMCs and has no significant effect on ERK phosphorylation, suggesting it does not function as an adaptor protein in phospho-ERK-mediated VSM contraction. During DPBA-induced VSM contraction, the binding of CNN3 to F-actin increases after 5 minutes but subsequently decreases after 10 minutes, suggesting its biphasic role in regulating the availability of F-actin. The interactions of CNN3 with three actin isoforms—alpha-smooth muscle actin (α-SMA), beta-cytoplasmic actin (β-actin), and gamma-cytoplasmic actin (γ-actin)—are characterized here. In resting VSM, CNN3 binds to all three actin isoforms. Following DPBA-induced VSM contraction, the interactions of CNN3 with all three actin isoforms undergo significant changes, with isoform-specific changes observed across different cell compartments. These findings suggest that CNN3 acts as a stabilizer of contractile actin filaments and as a regulator of cytoskeletal actin, facilitating actin cytoskeleton remodeling during VSM contraction. Furthermore, this study shows that CNN3 knockdown disrupts VSMC proliferation and migration, highlighting its role in vascular injury repair.
Characterizing CNN3’s biological functions in contractile and synthetic VSMCs broadens our knowledge of its functions in these cells and provides insights into the mechanisms underlying VSMC contraction, proliferation, and migration, thereby advancing therapeutic strategies by identifying potential targets for vascular diseases associated with impaired or abnormal VSMC functions.2027-05-16T00:00:00
Power, politics, and finance: how multilateral development banks shape ASEAN’s energy transition - insights from Viet Nam and Indonesia
Full text linkThis thesis examines the effectiveness of multilateral development banks (MDBs) in shaping ASEAN’s energy transition through climate finance, focusing on Viet Nam and Indonesia between 2016 and 2023. Using a mixed-methods approach that integrates project-level data analysis with qualitative policy review, the study evaluates how the Asian Development Bank (ADB), Asian Infrastructure Investment Bank (AIIB), and the World Bank Group (WBG) mobilize financial and technical resources in two of ASEAN’s largest economies. The study finds that although Indonesia received more funding, MDB financial commitments contributed a greater share to Viet Nam’s climate finance needs, GDP, and renewable energy (RE) targets.Indonesia had a higher share of technical assistance projects, reflecting the country’s complex regulatory environment. The findings highlight the
importance of institutional capacity, and streamlined regulatory and policy frameworks in shaping MDB effectiveness. Regional initiatives such as the ASEAN Catalytic Green Finance Facility (ACGF) illustrate MDBs’ potential to catalyze coordinated efforts in ASEAN’s energy transition. The study concludes that MDB success depends not only on the scale of financial contributions, but also on how well MDBs navigate national and regional policy environments to accelerate the energy transition
Investigating the components of heterotypic immunity associated with protection against coronavirus related disease
Full text link2025A few highly pathogenic coronaviruses (CoVs) have emerged in the human population in the past twenty-five years and have impacted the world on a global scale. Several demographic and clinical factors are associated with protection against severe disease from these pathogenic human CoV infections. In the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recent infection with a “common cold” causing human endemic CoV (eCoV) is associated with protection against severe coronavirus disease 2019 (COVID-19). Yet, the cross-reactive immune components providing this heterotypic immunity between heterologous coronaviruses have not been fully elucidated. We hypothesize that heterotypic immune protection is not mediated by neutralizing antibodies (nAbs) because of the diversity in spike protein receptor binding domains within the CoV family, but by alternative adaptive immune factors that target more conserved CoV regions. To test this hypothesis, we identified individuals from Boston Medical Center (BMC) with prior infections or vaccinations to SARS-CoV-2 or the eCoVs (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) and measured both homologous and heterologous CoV directed immune responses. First, in a study of risk factors of SARS-CoV-2 reinfection, SARS-CoV-2 antibody responses were similar between those with or without a SARS-CoV-2 reinfection and nAbs were not associated with long-term homotypic CoV protection. To explore heterotypic immunity, we classified individuals with or without a presumed or documented recent eCoV infection in a cohort of SARS-CoV-2 naïve individuals. Cross-reactive T cell and nAb responses against SARS-CoV-2 were similar between individuals regardless of recent eCoV infection history. Meanwhile, individuals with a presumed or documented recent eCoV infection had higher and correlative levels of Fc receptor (FcR) binding antibodies against eCoV spikes (S) and SARS-CoV-2 S2 subunit. Lastly to investigate the extent of coronavirus heterotypic immunity, we investigated immune components associated with SARS-CoV-2 mediated protection against subsequent symptomatic eCoV infections. Cross-reactive replication and transcription complex (RTC)-specific CD8+ T cells were associated with protection against symptomatic eCoV infections in individuals with a previous SARS-CoV-2 infection, while other eCoV-responsive T cells and nAbs were not predictive of heterotypic immune protection. In aggregate, nAbs were not associated with long-term protection against homologous or heterologous CoV infections and associated disease, but instead, antibody Fc effector functions and CD8+ T cells were associated with protective roles. These findings indicate that eliciting diverse immune functions along with nAbs in a future pan-CoV vaccine will be important to protect against disease from current and novel human CoVs
SMAD signaling in early foregut development and the basal cell program: mechanisms driving lung competence and airway maintenance
No full text2025During foregut development, several domains are rapidly specified into organs that are diverse in terms of cellular composition and function, including the trachea and lungs. These respiratory airways and alveolar regions are lined with an epithelium that conducts the critical functions of gas exchange, host defense, filtration and hydration. While the respiratory epithelium is essential to human health, airway and alveolar disfunction contribute to a multitude of chronic diseases that are major contributors to death and disability worldwide. Though animal models continue to progress our understanding of respiratory epithelial development, mature cell function and disease, in-vitro culture of human cell and tissue types can broaden our investigative abilities, enabling precise chemical and physical environmental modulation. In these studies, I utilized cutting edge in-vitro technology to investigate both the early stages of human respiratory epithelial development as well as mature airway stem cell function. First, I leveraged the induced pluripotent stem cell (iPSC) directed differentiation platform to enhance our understanding of the molecular mechanisms that control early embryonic development of the gut tube endoderm, with a particular emphasis on the signals that define the presumptive lung domain. Using multifactorial design of experiment (DOE), I observed a sensitive concentration dependent role of bone morphogenic protein (BMP) on priming the foregut to a respiratory fate. RNA sequencing of iPSC derived foregut patterned with decreasing levels of BMP signaling revealed dose dependent patterning of the foregut in an anterior to posterior manner from pharynx to lung to liver. Using in-vivo and ex-vivo animal models of early development, I validated the specific anterior-posterior priming of liver, lung and pharyngeal pouch fates within iPSCs and confirmed the central role of BMP in driving this process. Second, I sought to gain insight into the molecular program of the airway basal cell (BC), the primary stem cell of the airway epithelium, with a focus on BC heterogeneity. I employed lentiviral barcoding technology on primary human BCs to understand how the transcriptional profile of BC subpopulations informs stem cell function. Barcoding uncovered significant heterogeneity in both proliferation and differentiation ability of uniquely labeled BC clones that did not correlate with their starting gene expression profile. Analysis revealed a subset of BC clones generated a large pool of daughter cells, including basal and differentiated cells. This multipotent group of clones was used to identify the most stem BCs which were enriched for key regulators of TGF-β, Notch, and Wnt signaling pathways, including Follistatin (FST), delta-like noncanonical notch ligand 2 (DLK2) and Dickkopf Wnt Signaling Pathway Inhibitor 3 (DKK3), as well as downstream targets of the Salvador-Warts-Hippo (SWH) signaling pathway, connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61). Modulation of Hippo pathway kinases large tumor suppressor kinase (LATS1/2) resulted in augmented stem cell ability ex vivo and increased expression of BC stemness markers. In summary, these studies reveal important insights into respiratory development and stem cell function that can help generate more effective iPSC derived respiratory cell types and lead to a better understanding of pathological airway remodeling in the context of disease.2027-11-24T00:00:00
Journal of African Christian Biography: v. 8, no. 2: Separate cover file (PDF), print-ready
No full textThe full issue of Journal of African Christian Biography: v. 8, no. 2 is available at: https://hdl.handle.net/2144/4608
Sequence learning and experience-driven modifications create sparse predictive representations of visual information in mouse primary visual cortex
No full text2024Vision is a widely studied aspect of brain function, and a great deal of research has uncovered the principles by which the cortical hierarchy converts spatiotemporal light patterns into unique neural representations that are the basis of our ability to perceive objects in the visual scene. More recently, primary visual areas have been used to study common principles of cortical function that are shared with other brain regions. Predictive coding is an influential theory of cortical function that might explain some properties of extra classical receptive fields in the visual system but has not been experimentally verified in a general sense. Particularly absent is an understanding of how evoked neural activity modifies cortical circuits to form predictive representations. The visual cortex is highly plastic and can encode spatiotemporal relationships, making it a useful model system to test how experience modifies cortical circuits to encode memories that include temporal information, and how these modification affect the processing of subsequent sensory inputs and are used to make predictions. We begin with a review of visual neuroscience with a particular focus on what is known about the architecture and function of the mouse visual system. We discuss the anatomical circuits that convert light into neural activity and how it this filtered, processed, and refined in the early visual system. This includes a discussion of the coding strategies employed by the retina, properties of thalamic relay cells, and an overview of neocortical circuitry. This section concludes with a review of visual cortical plasticity. Next, we review the theoretical and conceptual framework that underlies predictive processing theories of cortical function. We compare several predictive coding models and discuss implementation details proposed by these theories with respect to the neocortical circuit. We then conduct a review of previous experimental work aimed at testing the extent to which cortical dynamics can be understood as predictive processing. This includes computational studies of visual cortical responses, mismatch negativity, sensorimotor mismatch signals, and recent discoveries of prediction error cells in the visual and auditory systems. We then present our original research investigating predictive and temporal processing in the mouse primary visual cortex (V1). We conducted two-photon calcium imaging in layer 2/3 of the mouse V1 while animals were exposed to visual sequences over several days. We analyzed thousands of cells in search of prediction error responses and characterized how visual experience and expectation change temporally coordinated activity in visually responsive cells. Consistent with predictive coding models, we find that neural activity during following the omission of a predicted element is elevated at the time of expected visual transitions in a trained but not naïve animals. Substituting an unexpected stimulus, however, did not generate significant prediction error responses. Using linear decoders, we show that training has little effect on the ability to accurately decode stimulus identity or time within an experiment despite finding that evoked response dynamics are significantly modified over training. We also show that individual cells’ peak firing times span the temporal duration of both active visual stimulation and interstimulus gray periods. Finally, we show that low-dimensional representations of neural activity become more selective for individual elements of the trained sequence while population level responses become sparser and decorrelated, consistent with the efficient coding hypothesis
Characterization of tuberculosis-affiliated immune correlates of protection in an immunocompetent susceptible mouse model
No full text2024Roughly 25% of the global population is estimated to harbor a latent tuberculosis infection at any given time. For reasons currently largely unknown, 10% of primary lesions caused by this infection reactivate and progress to the contagious form of post-primary pulmonary tuberculosis (pppTB). pppTB causes 1.5 million deaths annually, making it second to COVID-19 for most-lethal by volume disease in recent years. Humans are the only known reservoir of infection, making complete eradication a possibility. The BCG tuberculosis vaccine is administered to 100 million children annually, but does not confer lifelong immunity, rather it prevents progression from primary infection to pppTB. We aimed to investigate lesional immune cell population differences in BCG–vaccinated Kramnik mice, which faithfully recapitulate human-like pppTB pathogenesis. We found that low-titer vaccination is more similar to not being vaccinated at all than it is to adequately high-dosage vaccination via multiplex fluorescent immunohistochemistry to characterize myeloid and lymphocyte subpopulations within pulmonary lesions
Journal of African Christian Biography: v. 1, no. 6: Booklet, no cover (A4 format), print-ready
No full textThe full issue of Journal of African Christian Biography: v. 1, no. 6 is available at: https://hdl.handle.net/2144/3566