Trustworthy Experimentation Under Telemetry Loss

Failure to accurately measure the outcomes of an experiment can lead to bias and incorrect conclusions. Online controlled experiments (aka AB tests) are increasingly being used to make decisions to improve websites as well as mobile and desktop applications. We argue that loss of telemetry data (during upload or post-processing) can skew the results of experiments, leading to loss of statistical power and inaccurate or erroneous conclusions. By systematically investigating the causes of telemetry loss, we argue that it is not practical to entirely eliminate it. Consequently, experimentation systems need to be robust to its effects. Furthermore, we note that it is nontrivial to measure the absolute level of telemetry loss in an experimentation system. In this paper, we take a top-down approach towards solving this problem. We motivate the impact of loss qualitatively using experiments in real applications deployed at scale, and formalize the problem by presenting a theoretical breakdown of the bias introduced by loss. Based on this foundation, we present a general framework for quantitatively evaluating the impact of telemetry loss, and present two solutions to measure the absolute levels of loss. This framework is used by well-known applications at Microsoft, with millions of users and billions of sessions. These general principles can be adopted by any application to improve the overall trustworthiness of experimentation and data-driven decision making.Comment: Proceedings of the 27th ACM International Conference on Information and Knowledge Management, October 201

HIGH RIGIDITY AND VIBRATION ENDURANCE BAR FOR DEEP HOLES

Different constructions of bars are analyzed in the article, all of which are based on the idea of creating prestressed state in material. Improved construction of bar is proposed for equable spreading of elasticity zone along axis of boring bar

Bifurcation structure of a swept source laser

We numerically analyze a delay differential equation model of a short-cavity semiconductor laser with an intracavity frequency swept filter and reveal a complex bifurcation structure responsible for the asymmetry of the output characteristics of this laser. We show that depending on the direction of the frequency sweep of a narrowband filter, there exist two bursting cycles determined by different parts of a continuous-wave solutions branch

ABOUT METHODS OF SEISMIC ANALYSIS OF UNDERGROUND STRUCTURES

As is known, underground facilities are an integral part of the infrastructure of modern society. These objects have some specific characteristics such as complex construction, high cost, long life cycle, etc. Once it is destroyed, the direct and indirect losses are more seriousness than the general structure in the ground. Under-ground facilities built in areas subject to earthquake activity must withstand both seismic and static loading. Therefore, it is very important to carry on the seismic design of the underground structure in a safe and economi-cal way. The distinctive paper presents a summary of the current state of seismic analysis for underground struc-tures. Classification and brief overview of methods of seismic analysis of underground structures (force-based methods, displacement-based methods, numerical methods of seismic analysis of coupled system “soil – under-ground structure”) are presented, problems of soil-structure interaction are under consideration as well. So-called static finite element method with substructure technique for seismic analysis of underground structures is de-scribed

Insights into the mechanisms of eukaryotic translation gained with ribosome profiling

The development of Ribosome Profiling (RiboSeq) has revolutionized functional genomics. RiboSeq is based on capturing and sequencing of the mRNA fragments enclosed within the translating ribosome and it thereby provides a â snapshotâ of ribosome positions at the transcriptome wide level. Although the method is predominantly used for analysis of differential gene expression and discovery of novel translated ORFs, the RiboSeq data can also be a rich source of information about molecular mechanisms of polypeptide synthesis and translational control. This review will focus on how recent findings made with RiboSeq have revealed important details of the molecular mechanisms of translation in eukaryotes. These include mRNA translation sensitivity to drugs affecting translation initiation and elongation, the roles of upstream ORFs in response to stress, the dynamics of elongation and termination as well as details of intrinsic ribosome behavior on the mRNA after translation termination. As the RiboSeq method is still at a relatively early stage we will also discuss the implications of RiboSeq artifacts on data interpretation

Systematic analysis of the PTEN 5 ' leader identifies a major AUU initiated proteoform

Abundant evidence for translation within the 5' leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5' leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5' leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5' leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5' leader that control the ratio of PTEN proteoforms

Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes

Background: Oxygen and glucose metabolism play pivotal roles in many (patho) physiological conditions. In particular, oxygen and glucose deprivation (OGD) during ischemia and stroke results in extensive tissue injury and cell death. Results: Using time-resolved ribosome profiling, we assess gene expression levels in a neural cell line, PC12, during the first hour of OGD. The most substantial alterations are seen to occur within the first 20 minutes of OGD. While transcription of only 100 genes is significantly altered during one hour of OGD, the translation response affects approximately 3,000 genes. This response involves reprogramming of initiation and elongation rates, as well as the stringency of start codon recognition. Genes involved in oxidative phosphorylation are most affected. Detailed analysis of ribosome profiles reveals salient alterations of ribosome densities on individual mRNAs. The mRNA-specific alterations include increased translation of upstream open reading frames, site-specific ribosome pauses, and production of alternative protein isoforms with amino-terminal extensions. Detailed analysis of ribosomal profiles also reveals six mRNAs with translated ORFs occurring downstream of annotated coding regions and two examples of dual coding mRNAs, where two protein products are translated from the same long segment of mRNA, but in two different frames. Conclusions: These findings uncover novel regulatory mechanisms of translational response to OGD in mammalian cells that are different from the classical pathways such as hypoxia inducible factor (HIF) signaling, while also revealing sophisticated organization of protein coding information in certain genes