Publications

The Stanford Smart Memories polymorphic chip-multipro-cessor architecture was conceived as a unified multipurpose hardware architecture base, capable of supporting a vari-ety of programming models and per-application optimiza-tions [17]. Backing the architectural claims, our team of PhD students set out to implement this challenging design in silicon, targeting 90nm technology. Now, with 55M tran-sistors covering 61mm2, this is one of the most complex chips ever fabricated in academia.

Scientific journals may counter the misuse, misreporting, and misinterpretation of statistics by providing guidance to authors. We described the nature and prevalence of statistical guidance at 15 journals (top-ranked by Impact Factor) in each of 22 scientific disciplines across five high-level domains (N = 330 journals). The frequency of statistical guidance varied across domains (Health & Life Sciences: 122/165 journals, 74%; Multidisciplinary: 9/15 journals, 60%; Social Sciences: 8/30 journals, 27%; Physical Sciences: 21/90 journals, 23%; Formal Sciences: 0/30 journals, 0%). In one discipline (Clinical Medicine), statistical guidance was provided by all examined journals and in two disciplines (Mathematics and Computer Science) no examined journals provided statistical guidance. Of the 160 journals providing statistical guidance, 93 had a dedicated statistics section in their author instructions. The most frequently mentioned topics were confidence intervals (90 journals) and p-values (88 journals). For six “hotly debated” topics (statistical significance, p-values, Bayesian statistics, effect sizes, confidence intervals, and sample size planning/justification) journals typically offered implicit or explicit endorsement and rarely provided opposition. The heterogeneity of statistical guidance provided by top-ranked journals within and between disciplines highlights a need for further research and debate about the role journals can play in improving statistical practice.

State-of-the-art deep learning models for computer vision tasks are based on the transformer architecture and often deployed in real-time applications. In this

Markov Random Field Based Automatic Image Alignment for Electron Tomography Farshid Moussavi ∗ Department of Electrical Engineering Stanford University Stanford, CA 94305 farshid1@stanford.edu Luis R. Comolli Life Sciences Division Lawrence Berkeley National Laboratory Berkeley, CA 94704 lrcomolli@lbl.gov Kenneth H. Downing Life Sciences Division Lawrence Berkeley National Laboratory Berkeley, CA 94704 khdowning@lbl.gov Fernando Amat ∗ Department of Electrical Engineering Stanford University Stanford, CA 94305 famat@stanford.edu Gal Elidan Department of Computer Science Stanford University Stanford, CA 94305 galel@cs.stanford.edu Mark Horowitz Department of Electrical Engineering Stanford University Stanford, CA 94305 horowitz@stanford.edu Introduction Cryo electron tomography (cryo-ET) is the primary method for obtaining 3D reconstructions of intact bacteria, viruses, and complex molecular machines ([7],[2]). It first flash freezes a specimen in a thin layer of ice, and then rotates the ice sheet in a transmission electron microscope (TEM) recording images of different projections through the sample. The resulting images are aligned and then back projected to form the desired 3-D model. The typical resolution of biological electron microscope is on the order of 1 nm per pixel which means that small imprecision in the microscope’s stage or lenses can cause large alignment errors. To enable a high precision alignment, biologists add a small number of spherical gold beads to the sample before it is frozen. These beads generate high contrast dots in the image that can be tracked across projections. Each gold bead can be seen as a marker with a fixed location in 3D, which provides the reference points to bring all the images to a common frame as in the classical structure from motion problem. A high accuracy alignment is critical to obtain a high resolution tomogram (usually on the order of 5-15nm resolution). While some methods try to automate the task of tracking markers and aligning the images ([8],[4]), they require user intervention if the SNR of the image becomes too low. Unfortunately, cryogenic electron tomography (or cryo-ET) often has poor SNR, since the samples are relatively thick (for TEM) and the restricted electron dose usually results in projections with SNR under 0 dB. This paper shows that formulating this problem as a most-likely estimation task yields an approach that is able to automatically align with high precision cryo-ET datasets using inference in graphical models. This approach has been packaged into a publicly available software called RAPTOR-Robust Alignment and Projection estimation for Tomographic Reconstruction. 1 These authors contributed equally to this work. [1] presents an extended version of the results reported in this abstract.

In this chapter, we'll examine image processing in more depth, showing why it is particularly amenable to hardware acceleration, and describing the architectural patterns that we will leverage in the remainder of the book.

Simulation is the primary method for evaluating computer systems during all phases of the design process. One significant problem with simulation is that it rarely models the system exactly, and quantifying the resulting simulator error can be difficult. More importantly, architects often assume without proof that although their simulator may make inaccurate absolute performance predictions, it will still accurately predict architectural trends.This paper studies the source and magnitude of error in a range of architectural simulators by comparing the simulated execution time of several applications and microbenchmarks to their execution time on the actual hardware being modeled. The existence of a hardware gold standard allows us to find, quantify, and fix simulator inaccuracies. We then use the simulators to predict architectural trends and analyze the sensitivity of the results to the simulator configuration. We find that most of our simulators predict trends accurately, as long as they model all of the important performance effects for the application in question. Unfortunately, it is difficult to know what these effects are without having a hardware reference, as they can be quite subtle. This calls into question the value, for architectural studies, of highly detailed simulators whose characteristics are not carefully validated against a real hardware design.

A small number of reanalyses of RCTs have been published to date. Only a few were conducted by entirely independent authors. Thirty-five percent of published reanalyses led to changes in findings that implied conclusions different from those of the original article about the types and number of patients who should be treated.

Significance Statement Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events. Less than 5% of the studies performed an external validation. The authors also showed the poor transparency reporting and identified a data beautification phenomenon. These findings suggest that there is much wasted research effort in transplant biomarker medical research and highlight the need to produce more rigorous studies so that more biomarkers may be validated and successfully implemented in clinical practice. Background Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology, and reporting might contribute to this phenomenon. Methods We formed a consortium of experts in systematic reviews, nephrologists, methodologists, and epidemiologists. A systematic literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library between January 1, 2005, and November 12, 2022 (PROSPERO ID: CRD42020154747). All English language, original studies investigating the association between a biomarker and kidney allograft outcome were included. The final set of publications was assessed by expert reviewers. After data collection, two independent reviewers randomly evaluated the inconsistencies for 30% of the references for each reviewer. If more than 5% of inconsistencies were observed for one given reviewer, a re-evaluation was conducted for all the references of the reviewer. The biomarkers were categorized according to their type and the biological milieu from which they were measured. The study characteristics related to the design, methods, results, and their interpretation were assessed, as well as reproducible research practices and transparency indicators. Results A total of 7372 publications were screened and 804 studies met the inclusion criteria. A total of 1143 biomarkers were assessed among the included studies from blood ( n =821, 71.8%), intragraft ( n =169, 14.8%), or urine ( n =81, 7.1%) compartments. The number of studies significantly increased, with a median, yearly number of 31.5 studies (interquartile range [IQR], 23.8–35.5) between 2005 and 2012 and 57.5 (IQR, 53.3–59.8) between 2013 and 2022 ( P < 0.001). A total of 655 studies (81.5%) were retrospective, while 595 (74.0%) used data from a single center. The median number of patients included was 232 (IQR, 96–629) with a median follow-up post-transplant of 4.8 years (IQR, 3.0–6.2). Only 4.7% of studies were externally validated. A total of 346 studies (43.0%) did not adjust their biomarker for key prognostic factors, while only 3.1% of studies adjusted the biomarker for standard-of-care patient monitoring factors. Data sharing, code sharing, and registration occurred in 8.8%, 1.1%, and 4.6% of studies, respectively. A total of 158 studies (20.0%) emphasized the clinical relevance of the biomarker, despite the reported nonsignificant association of the biomarker with the outcome measure. A total of 288 studies assessed rejection as an outcome. We showed that these rejection studies shared the same characteristics as other studies. Conclusions Biomarker studies in kidney transplantation lack validation, rigorous design and methodology, accurate interpretation, and transparency. Higher standards are needed in biomarker research to prove the clinical utility and support clinical use.