Addressing microarchitectural implications of serverless functions

Serverless computing has emerged as a widely-used paradigm for running services in the cloud. In this model, developers organize applications as a set of functions invoked on-demand in response to events, such as HTTP requests. Developers are charged for CPU time and memory footprint during function execution, incentivising them to reduce runtime and memory consumption. Furthermore, to avoid long start-up delays, cloud providers keep recently-triggered instances idle (or warm) for some time, anticipating future invocations. Consequently, a server may host thousands of warm instances of various functions, their executions interleaved based on incoming invocations. This thesis investigates the workload characteristics of serverless and observes that: (1) there is high interleaving among warm instances on a given server; (2) individual warm functions are invoked relatively infrequently, often at intervals of seconds or minutes; and (3) many function invocations complete within milliseconds. This interleaved execution of rarely invoked functions leads to thrashing of each function's microarchitectural state between invocations. Meanwhile, the short execution time of functions impedes the amortization of warming up on-chip microarchitectural state. As a result, when a given memory-resident function is re-invoked, it commonly finds its on-chip microarchitectural state completely cold due to thrashing by other functions---a phenomenon we term lukewarm execution. Our analysis reveals that the cold microarchitectural state severely affects CPU performance, with the main source of degradation being the core front-end, comprising instruction delivery, branch identification via the BTB, and conditional branch prediction. Based on our analysis, we propose two mechanisms to address performance degradation due to lukewarm invocations. The first technique is Jukebox, a record-and-replay instruction prefetcher specifically designed to mitigate the high cost of off-chip instruction misses. We demonstrate that Jukebox's simplistic design effectively eliminates more than 95% of long-latency off-chip instruction misses. The second technique is Ignite, which builds on Jukebox to offer a comprehensive solution for restoring front-end microarchitectural state, including instructions, BTB, and branch predictor state, via unified metadata. Ignite records an invocation's control flow graph in compressed format and uses that to restore the state of the front-end structures the next time the function is invoked. Ignite significantly reduces instruction misses, BTB misses, and branch mispredictions, resulting in an average performance improvement of 43%. In summary, this thesis demonstrates that serverless systems present distinct workload characteristics that fail to match traditional CPU designs, severely impacting performance. Two simple techniques can overcome these bottlenecks by preserving the microarchitectural state across function invocations

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment

Connecting structure, dynamics and viscosity in sheared soft colloidal liquids: a medley of anisotropic fluctuations

Structural distortion and relaxation are central to any liquid flow. Their full understanding requires simultaneous probing of the mechanical as well as structural and dynamical response. We provide the first full dynamical measurement of the transient structure using combined coherent X-ray scattering and rheology on electrostatically interacting colloidal fluids. We find a stress overshoot during the start-up of shear which is due to the strong anisotropic overstretching and compression of nearest-neighbor distances. The rheological response is reflected in uncorrelated entropy-driven intensity fluctuations. While the structural distortion under steady shear is well described by Smoluchowski theory, we find an increase of the particle dynamics beyond the trivial contribution of flow. After the cessation of shear, the full fluid microstructure and dynamics are restored, both on the structural relaxation timescale. We thus find unique structure-dynamics relations in liquid flow, responsible for the macroscopic rheological behavior of the system.crosscheck: This document is CrossCheck deposited related_data: Supplementary Information copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: The accepted version of this article will be made freely available after a 12 month embargo period history: Received 10 July 2015; Accepted 26 September 2015; Advance Article published 9 October 2015; Version of Record published 16 December 2015status: publishe

Connecting structure, dynamics and viscosity in sheared soft colloidal liquids: a medley of anisotropic fluctuations

Structural distortion and relaxation are central to any liquid flow. Their full understanding requiressimultaneous probing of the mechanical as well as structural and dynamical response. We provide thefirst full dynamical measurement of the transient structure using combined coherent X-ray scatteringand rheology on electrostatically interacting colloidal fluids. We find a stress overshoot during the start-upof shear which is due to the strong anisotropic overstretching and compression of nearest-neighbordistances. The rheological response is reflected in uncorrelated entropy-driven intensity fluctuations.While the structural distortion under steady shear is well described by Smoluchowski theory, we find anincrease of the particle dynamics beyond the trivial contribution of flow. After the cessation of shear, thefull fluid microstructure and dynamics are restored, both on the structural relaxation timescale. We thusfind unique structure-dynamics relations in liquid flow, responsible for the macroscopic rheologicalbehavior of the system

Genome-wide association study of over 40,000 bipolar disorder cases provides novel biological insights

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies

Genomics yields biological and phenotypic insights into bipolar disorder

Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60–80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder