From George Eliot to Her \u27Rabbi\u27: An Epistolary Find

I cannot be easy without writing a word or two this morning for I am conscious that I made myself more disagreeable than nature obliges me to be by my hard quips to you. They were not warrantable by anything but a strong personal and impersonal interest in that sensitive being of yours, which holds what may be very precious things in its keeping. And even with that warrant it will be a proof of your fondness if you quite forgive me. You look wretched - and I have now so much of that subtle misery which can be explained to nobody, that I cannot help thinking of you as a sharer in that sort of suffering since you tell me there is nothing more severaly [sic] comprehensible as a moment (?) of melancholy. We hungry, quick-wincing creatures who are always seeking our food with wounded tentacles, must simply accept life as a misfortune to our primary and direct self, and make up our minds that all our joy must come of working ourselves powerfully into the lives of other beings, or else giving ourselves up to be possessed by them. We may grumble and say that rosy and comfortable dejection is better than those sublime heights - but then we never shall be rosy and comfortable, some good is to be got by weary struggle, and by that alone. That is not to tell you what you don\u27t know already, 0 Rabbi, but it is simply the discourse of a fellow Houywhynm (spelling improved) who is bearing the yoke with you. We tell each other that the day is fine, & that the north east wind is biting. You need not answer if you have nothing to say, which is a rare privilege in this world

Encoding points on hyperelliptic curves over finite fields in deterministic polynomial time

We present families of (hyper)elliptic curve which admit an efficient deterministic encoding function

Identifying Threshold Values of Accelerometer-Determined Moderate-to-Vigorous Physical Activity that Correspond to Self-Reported Compliance to the 2008 Physical Activity Guidelines for Americans : National Health and Nutrition Examination Survey 2003-2006

Current public health guidelines for physical activity (PA) were primarily formulated using evidence collected from a series of prospective cohort epidemiological investigations that measured self-reported PA. In light of this observation, and the known discordance between self-reported and objectively-monitored PA, it remains common for researchers to assess compliance to current PA guidelines (≥ 150 minutes/week of an equivalent combination of moderate- and vigorous-intensity PA [MV2PA]) using objective-monitoring methods such as accelerometer-determined PA. However, investigations seeking to calibrate accelerometer-determined PA against self-reported compliance to current PA guidelines are scant within the extant literature. Calibration of objective-monitoring methods, such as accelerometer-determined PA, may prove fruitful in mitigating the discordance between self-reported and accelerometer-determined PA, while also providing compliance estimates for PA that better reflect a population’s associated health risks. Therefore, the purpose of this study was to identify optimal accelerometer-determined thresholds of MV2PA that correspond to 150 minutes/week of self-reported MV2PA outlined in the current 2008 Physical Activity Guidelines for Americans (PAGA). This study was a secondary analysis of 4,784 adults (18-64 years) from the 2003-2006 NHANES who provided ≥ 4 valid days of accelerometer data. Receiver operating characteristic (ROC) curves were used to identify accelerometer-determined thresholds of weekly MV2PA corresponding to self-reported compliance to the 2008 PAGA. MV2PA in modified 10-minute bouts and total MV2PA were significant predictors of self-reported compliance to the 2008 PAGA (both p < 0.001). Optimal thresholds of accelerometer-determined MV2PA predicting self-reported compliance to the 2008 PAGA were 13.00 ± 1.69 minutes/week in modified 10-minute bouts and 122.30 ± 4.62 minutes/week in total (no bout requirement). However, levels of sensitivity and specificity associated with ROC curve analyses were low (all < 70%). Construct validity analyses revealed that self-reported compliance to the 2008 PAGA was only favorably associated with one cardiometabolic biomarker (glycated hemoglobin, p = 0.003). Conversely, compliance to the 2008 PAGA assessed using the newly identified accelerometer-determined MV2PA threshold in modified 10-minute bouts (≥ 13.0 minutes/week of MV2PA) was favorably associated with 5 biomarkers (glycated hemoglobin, high-density lipoprotein [HDL], systolic blood pressure [SBP], waist circumference, and body mass index [BMI]; all p < 0.05) and 2 chronic diseases (hypertension and obesity; all p < 0.01). Similarly, compliance to the 2008 PAGA assessed via total accelerometer-determined MV2PA (≥ 122.3 minutes/week of MV2PA; no bout requirement) was favorably associated with 6 biomarkers (glycated hemoglobin, fasting plasma glucose, triglycerides, SBP, waist circumference, and BMI; all p < 0.05) and 4 chronic diseases (hypertension, obesity, impaired fasting glucose, and diabetes mellitus; all p < 0.05). However, follow-up analyses using different activity counts/minute cut-points produced a wide range of optimal thresholds for MV2PA in 10-minute bouts (0.03 to 58.8 minutes/week) and in total (22.5 to 166.7 minutes/week). Although accelerometer-determined MV2PA was significantly related to self-reported compliance to the 2008 PAGA, the strength of this relationship was weak. Absolute estimates of weekly accelerometer-determined MV2PA corresponding to self-reported compliance to the 2008 PAGA were significantly less than the 150 minutes/week minimum criteria. Construct validity analyses indicated that compliance to the 2008 PAGA, as assessed using the newly identified accelerometer-determined MV2PA thresholds, was more strongly related to various anthropometric and cardiometabolic constructs than self-reported compliance. Future epidemiological and clinical research is needed to aid the development of PA guidelines informed by accelerometer-determined estimates of PA

Adjusting Laser Injections for Fully Controlled Faults

Hardware characterizations of integrated circuits have been evolving rapidly with the advent of more precise, sophisticated and cost-efficient tools. In this paper we describe how the fine tuning of a laser source has been used to characterize, set and reset the state of registers in a 90 nm chip. By adjusting the incident laser beam’s location, it is possible to choose to switch any register value from ‘ 0 ’ to ‘ 1 ’ or vice-versa by targeting the PMOS side or the NMOS side. Plus, we show how to clear a register by selecting a laser beam’s power. With the help of imaging techniques, we are able to explain the underlying phenomenon and provide a direct link between the laser mapping and the physical gate structure. Thus, we correlate the localization of laser fault injections with implementations of the PMOS and NMOS areas in the silicon substrate. This illustrates to what extent laser beams can be used to monitor the bits stored within registers, with adverse consequences in terms of security evaluation of integrated circuits

Dynamics of chromosome organization in a minimal bacterial cell

Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculate in silico chromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM. </p

Increasing the proportion of healthier foods available with and without reducing portion sizes and energy purchased in worksite cafeterias:protocol for a stepped-wedge randomised controlled trial

BACKGROUND: Overconsumption of energy from food contributes to high rates of overweight and obesity in many populations. A promising set of interventions tested in pilot studies in worksite cafeterias, suggests energy intake may be reduced by increasing the proportion of healthier - i.e. lower energy - food options available, and decreasing portion sizes. The current study aims to assess the impact on energy purchased of i. increasing the proportion of lower energy options available; ii. combining this with reducing portion sizes, in a full trial. METHODS: A stepped-wedge randomised controlled trial in 19 worksite cafeterias, where the proportion of lower energy options available in targeted food categories (including main meals, snacks, and cold drinks) will be increased; and combined with reduced portion sizes. The primary outcome is total energy (kcal) purchased from targeted food categories using a pooled estimate across all sites. Follow-up analyses will test whether the impact on energy purchased varies according to the extent of intervention implementation. DISCUSSION: This study will provide the most reliable estimate to date of the effect sizes of two promising interventions for reducing energy purchased in worksite cafeterias. TRIAL REGISTRATION: The study was prospectively registered on ISRCTN (date: 24.05.19; TRN: ISRCTN87225572; doi: https://doi.org/10.1186/ISRCTN87225572)

Divide-and-Rule: Self-Supervised Learning for Survival Analysis in Colorectal Cancer

With the long-term rapid increase in incidences of colorectal cancer (CRC), there is an urgent clinical need to improve risk stratification. The conventional pathology report is usually limited to only a few histopathological features. However, most of the tumor microenvironments used to describe patterns of aggressive tumor behavior are ignored. In this work, we aim to learn histopathological patterns within cancerous tissue regions that can be used to improve prognostic stratification for colorectal cancer. To do so, we propose a self-supervised learning method that jointly learns a representation of tissue regions as well as a metric of the clustering to obtain their underlying patterns. These histopathological patterns are then used to represent the interaction between complex tissues and predict clinical outcomes directly. We furthermore show that the proposed approach can benefit from linear predictors to avoid overfitting in patient outcomes predictions. To this end, we introduce a new well-characterized clinicopathological dataset, including a retrospective collective of 374 patients, with their survival time and treatment information. Histomorphological clusters obtained by our method are evaluated by training survival models. The experimental results demonstrate statistically significant patient stratification, and our approach outperformed the state-of-the-art deep clustering methods