Identifying serological markers of recent P. falciparum exposure for precision malaria surveillance

Surveillance plays a key role in malaria control and elimination efforts by allowing for informed and effective allocation of often limited resources. Current methods for estimating malaria exposure are limited either by cost or accuracy. Serological data offers the potential to provide inexpensive and accurate estimates of exposure, but to date there is no consensus on which antibody responses are informative and how they can be interpreted. Previous studies have been limited to single age groups, transmission intensities, and geographic locations that are not generalizable across populations. This dissertation describes an investigation into serologic biomarkers of recent exposure to Plasmodium falciparum, the most deadly species causing malaria, using samples from 8 cohort studies representing diverse populations. Using an innovative approach that combined detailed individual-level exposure data, high-throughput screening of hundreds of antibody responses, and robust statistical methods, we were unable to identify a set of antibody responses predictive of recent exposure that was generalizable across settings. Although universal seromarkers may not exist, we found that accurate prediction of recent exposure was possible in a cohort of return travelers, suggesting the potential for seromarkers to be developed for specific settings, particularly those with limited cumulative exposure

Towards Scalable Sub-THz Massive MIMO: Beamforming ASICs and 3D Die-to-Die Interconnects

The incessant growth of wireless communication demand is driving the desire for massive antenna arrays operating at mm-Wave to sub-THz carrier frequencies, where many GHz of bandwidth are readily available. However, this opportunity comes with an integration dilemma as antenna pitch falls below 1mm and digitized baseband data rates surpass a terabit per second. To address these and other design challenges, heterogeneous integration (HI) of radio, mixed-signal, baseband, and power delivery chiplets is a solution. Towards this goal, this dissertation presents a multi-part exploration into the technologies and design methodologies required for future sub-THz massive MIMO systems.First, a pair of baseband ASICs for scalable linear massive MIMO arrays with digital beamforming is presented. The learnings from the design process of these chips is directly applied to the improvement of Hammer, a physical design flow generator, that has since accelerated the implementation of over ten research chips and is now used in multiple courses. Extrapolating from the integration limitations of the presented and other state-of-the-art chips, the scaling challenges and HI opportunities of sub-THz two-dimensional massive MIMO arrays is subsequently reviewed. The findings culminate in a case for 3D chiplet integration into ”radio cubes”, which are consequently tiled horizontally into a scalable array. To enable 3D integration, a comprehensive study of technology constraints for standardizing 3D die-to-die interconnects is performed, demonstrating how scaling roadmaps for process and packaging technologies converge towards a very different circuit architecture compared to existing die-to-die interconnects. Given the opportunities afforded by this architecture, a Chisel generator framework is presented that performs rapid design space exploration for a novel defect repair mechanism and validates a new standard (UCIe-3D) in the Intel 16 process technology. Most importantly, this generator demonstrates a significant design effort reduction for exploring and implementing die-to-die interconnects–a key enabler for a future chiplet ecosystem. Finally, with solutions proposed for key technologies needed for the envisioned heterogeneously-integrated system, a set of integration concepts is presented, detailing remaining technological feasibility tradeoffs

Empowering Large Language Models with Efficient and Automated Systems

Large Language Models (LLMs) have shown remarkable capabilities in a variety of tasks, including chatting, programming, and searching. However, the high costs of LLMs are preventing these models from being deployed for the vast majority of applications. In this dissertation, we focus on building efficient and automated systems to reduce costs and democratize access to large language models. We first introduce systems to optimize computational efficiency and reduce the engineering overhead for distributed LLM training. We develop TeraPipe, which proposes a new dimension to perform pipeline parallel training for LLMs, and also Alpa, the world’s first compiler capable of automatically distributing arbitrary neural networks with all existing parallelization methods. While training is typically a one-time cost, deploying and serving an LLM requires running LLM inference continuously, which is the top blocker for the real-world deployment of LLMs. We improve the serving scalability with AlpaServe through model parallelism, and increase the memory utilization and the LLM inference throughput with a new attention algorithm, PagedAttention, and an end-to-end serving system, vLLM.Overall, these systems provide comprehensive solutions that significantly improve both training and inference efficiency for large language models. Together, these systems lower the high costs associated with large language models, democratizing their deployment across various real-world applications

Virology—the path forward

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US

High-throughput protein characterization by complementation using DNA barcoded fragment libraries

Our ability to predict, control, or design biological function is fundamentally limited by poorly annotated gene function. This can be particularly challenging in non-model systems. Accordingly, there is motivation for new high-throughput methods for accurate functional annotation. Here, we used complementation of auxotrophs and DNA barcode sequencing (Coaux-Seq) to enable high-throughput characterization of protein function. Fragment libraries from eleven genetically diverse bacteria were tested in twenty different auxotrophic strains of Escherichia coli to identify genes that complement missing biochemical activity. We recovered 41% of expected hits, with effectiveness ranging per source genome, and observed success even with distant E. coli relatives like Bacillus subtilis and Bacteroides thetaiotaomicron. Coaux-Seq provided the first experimental validation for 53 proteins, of which 11 are less than 40% identical to an experimentally characterized protein. Among the unexpected function identified was a sulfate uptake transporter, an O-succinylhomoserine sulfhydrylase for methionine synthesis, and an aminotransferase. We also identified instances of cross-feeding wherein protein overexpression and nearby non-auxotrophic strains enabled growth. Altogether, Coaux-Seq's utility is demonstrated, with future applications in ecology, health, and engineering

Consequences of Social Policy on Creating a Homeless Population in the Oakland Area and Resulting Health Disparities for Older Adults

California has the largest homeless population in the nation, with a significant gap between the demand and supply of affordable housing. This disparity not only undermines the quality of life and educational opportunities for residents but also poses grave health risks. This study investigates the nexus between social policies and homelessness in California. By analyzing systemic factors such as exorbitant housing costs and inadequate social safety nets, we uncover the root causes of housing instability. Our examination extends to exploring the multifaceted health disparities experienced by homeless individuals, particularly older adults, and elucidating the complex interplay of mental health struggles within this demographic. Findings reveal that prevailing social policies significantly contribute to homelessness, exacerbating health inequities among vulnerable populations. Our analysis stresses the urgent need for evidence-based policy reforms and holistic, community-based approaches to address homelessness effectively and promote health equity

How Socio-Ecological Factors Contribute to Climate Anxiety in Young People

Several studies indicate the lack of a comprehensive understanding of climate change among the youth populations. However, perspectives regarding the socio-ecological factors influencing climate anxiety in young people have yet to be accomplished. We were able to report this in terms of a survey that collected data regarding participants’ levels of climate anxiety, demographic information, and perceptions of various socio-ecological factors. Although the sample size was limited, with this method, we gathered insight and opinions regarding effective strategies to address and alleviate anxiety surrounding the global climate change issue, specifically regarding the students in the University of California, Berkeley from varying demographic backgrounds. Such exposure to a range of perspectives contributed to varying levels of concern and engagement with climate change issues. The importance of individual and collective action to address climate change and its psychological impacts were highlighted. Gauging that none of the participants have seen support for climate-related anxiety or distress indicates potential gaps in support systems for climate-related mental distress, leading individuals to internally manage their anxiety rather than seek external support

Affordable Housing and Transportation Cost Burdens in San Diego County

The State of California has increasingly urged construction of affordable housing development in transit-rich areas (California Department of Housing and Community Development 2024) but so far transit-oriented development has generally not reduced vehicle miles traveled for low-income renters (Chatman et al. 2019; Lund, Cervero, and Willson 2004). This report quantifies the cost of daily travel needs for affordable housing residents in San Diego, California, especially seniors aged 62 and older, in two ways. First, it analyzes their trip travel time for the entire San Diego region using activity-based model (ABM) data. Second, it summarizes results from surveys of residents in six affordable housing buildings, three of which provide supportive housing to seniors. Overall, it finds that affordable housing residents use public transit more often than those who have access to a car. But traveling by public transit takes much longer on public transit than traveling by personal vehicle. Survey respondents under age 62 expressed greater dissatisfaction with the costs of public transit ridership, compared to seniors, and were also more likely to express dissatisfaction if they were working. Seniors were more likely to express dissatisfaction with the conditions of public transit stops

Idiopathic Spontaneous Rupture of a Subcostal Artery in a Patient Undergoing Hemodialysis: A Case Report.

The spontaneous rupture of a subcostal (12th intercostal) artery is exceptionally rare and could be fatal, requiring early diagnosis and treatment. Only one case of intercostal artery (ICA) bleeding in a patient undergoing hemodialysis (HD) has been reported. We additionally describe a 41-year-old man undergoing HD who presented with a spontaneous hemoperitoneum and shock resulting from a subcostal artery rupture. He initially complained of diffuse abdominal pain and dizziness at the emergency room. His abdomen was bloated, and there was tenderness in the right upper quadrant area. Enhanced computed tomography and arteriography revealed a rupture of the right subcostal artery. After the super-selection of the bleeding artery by a microcatheter, embolization was performed using a detachable coil and gelfoam. In a subsequent arteriogram, additional contrast leakage was no longer detected, and his blood pressure was restored to normal. The patient was discharged without any sequelae. He was followed up at our HD center without recurrence of ICA bleeding. To the best of our knowledge, this is the second case in the English literature documenting a spontaneous ICA rupture in a patient undergoing HD. This case indicates that injury to ICA should be suspected when patients undergoing HD complain of abdominal or chest pain and dizziness, although it is very rare

A Single Compartment Relaxed Eddy Accumulation Method

The relaxed eddy accumulation (REA) method is a widely-known technique that measures turbulent fluxes of scalar quantities. The REA technique has been used to measure turbulent fluxes of various compounds, such as methane, ethene, propene, butene, isoprene, nitrous oxides, ozone, and others. The REA method requires the accumulation of scalar concentrations in two separate compartments that conditionally sample updrafts and downdraft events. It is demonstrated here that the assumptions behind the conventional or two-compartment REA approach allow for one-compartment sampling, therefore called a one compartment or 1-C-REA approach, thereby expanding its operational utility. The one-compartment sampling method is tested across various land cover types and atmospheric stability conditions, and it is found that the one-compartment REA can provide results comparable to those determined from conventional two-compartment REA. This finding enables rapid expansion and practical utility of REA in studies of surface-atmosphere exchanges, interactions, and feedbacks