The Parallel Persistent Memory Model

We consider a parallel computational model that consists of $P$ processors, each with a fast local ephemeral memory of limited size, and sharing a large persistent memory. The model allows for each processor to fault with bounded probability, and possibly restart. On faulting all processor state and local ephemeral memory are lost, but the persistent memory remains. This model is motivated by upcoming non-volatile memories that are as fast as existing random access memory, are accessible at the granularity of cache lines, and have the capability of surviving power outages. It is further motivated by the observation that in large parallel systems, failure of processors and their caches is not unusual. Within the model we develop a framework for developing locality efficient parallel algorithms that are resilient to failures. There are several challenges, including the need to recover from failures, the desire to do this in an asynchronous setting (i.e., not blocking other processors when one fails), and the need for synchronization primitives that are robust to failures. We describe approaches to solve these challenges based on breaking computations into what we call capsules, which have certain properties, and developing a work-stealing scheduler that functions properly within the context of failures. The scheduler guarantees a time bound of $O(W/P_A + D(P/P_A) \lceil\log_{1/f} W\rceil)$ in expectation, where $W$ and $D$ are the work and depth of the computation (in the absence of failures), $P_A$ is the average number of processors available during the computation, and $f \le 1/2$ is the probability that a capsule fails. Within the model and using the proposed methods, we develop efficient algorithms for parallel sorting and other primitives.Comment: This paper is the full version of a paper at SPAA 2018 with the same nam

Exponential Distribution of Locomotion Activity in Cell Cultures

In vitro velocities of several cell types have been measured using computer controlled video microscopy, which allowed to record the cells' trajectories over several days. On the basis of our large data sets we show that the locomotion activity displays a universal exponential distribution. Thus, motion resulting from complex cellular processes can be well described by an unexpected, but very simple distribution function. A simple phenomenological model based on the interaction of various cellular processes and finite ATP production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure

Electrical resistance tomography of unsaturated flow and transport in Yucca Mountain

Electrical Resistance Tomography (ERT), a new geophysical imaging technique, was used to study the movement of a tracer through the test block at the Unsaturated Zone Transport Test (UZTT) at Busted Butte, Nevada. Data were collected four times starting in July and ending in early September, 1998. ERT baseline images show a resistivity structure which is consistent with the known lithology in the rear part of the test block. There appears to be a low resistivity region in the front half of the block, particularly near the bottom. Difference images from August 19 and September 9 show clear and consistent resistivity decreases in the region near injection holes 18, 20, and 21 which can be associated with the injection of conductive water. The images show very little effect in the region around the other injection holes, 23, and 24 through 27 where far less water was injected. Difference images from August 19 and September 9 show resistivity decreases which could be interpreted as water moving down into the block. This is the same region which has an anomalously low resistivity in the baseline image. These results should be considered preliminary, and are subject to further interpretation

Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate.

An intricate link is becoming apparent between metabolism and cellular identities. Here, we explore the basis for such a link in an in vitro model for early mouse embryonic development: from naïve pluripotency to the specification of primordial germ cells (PGCs). Using single-cell RNA-seq with statistical modelling and modulation of energy metabolism, we demonstrate a functional role for oxidative mitochondrial metabolism in naïve pluripotency. We link mitochondrial tricarboxylic acid cycle activity to IDH2-mediated production of alpha-ketoglutarate and through it, the activity of key epigenetic regulators. Accordingly, this metabolite has a role in the maintenance of naïve pluripotency as well as in PGC differentiation, likely through preserving a particular histone methylation status underlying the transient state of developmental competence for the PGC fate. We reveal a link between energy metabolism and epigenetic control of cell state transitions during a developmental trajectory towards germ cell specification, and establish a paradigm for stabilizing fleeting cellular states through metabolic modulation.J.T. was supported by the Austrian Academy of Sciences, the Wellcome Trust, and the Swiss National Fund for Science, W.H.G. by EMBO and the Wellcome Trust, J.R. and L.W. by the UK Medical Research Council, and E.A. by the Wellcome Trust. M.A.S. is a Wellcome Senior Investigator. Work at the Gurdon Institute is supported by a core grant from the Wellcome Trust and Cancer Research UK

Humanin: A Novel Central Regulator of Peripheral Insulin Action

Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD). A novel mitochondria-associated peptide, Humanin (HN), has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity.Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice.We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM

Genome-Wide Mapping of DNA Methylation 5mC by Methylated DNA Immunoprecipitation (MeDIP)-Sequencing Methods and Protocols

Methylated DNA immunoprecipitation is a large scale purification technique. It enables the isolation of methylated DNA fragments for subsequent locus-specific or genome-wide analysis. Here we describe an immunoprecipitation protocol using a monoclonal mouse anti 5-methyl-cytidine antibody followed by next-generation sequencing (MeDIP-Seq)