Criticality Aware Soft Error Mitigation in the Configuration Memory of SRAM based FPGA

Efficient low complexity error correcting code(ECC) is considered as an effective technique for mitigation of multi-bit upset (MBU) in the configuration memory(CM)of static random access memory (SRAM) based Field Programmable Gate Array (FPGA) devices. Traditional multi-bit ECCs have large overhead and complex decoding circuit to correct adjacent multibit error. In this work, we propose a simple multi-bit ECC which uses Secure Hash Algorithm for error detection and parity based two dimensional Erasure Product Code for error correction. Present error mitigation techniques perform error correction in the CM without considering the criticality or the execution period of the tasks allocated in different portion of CM. In most of the cases, error correction is not done in the right instant, which sometimes either suspends normal system operation or wastes hardware resources for less critical tasks. In this paper,we advocate for a dynamic priority-based hardware scheduling algorithm which chooses the tasks for error correction based on their area, execution period and criticality. The proposed method has been validated in terms of overhead due to redundant bits, error correction time and system reliabilityComment: 6 pages, 8 figures, conferenc

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a substantial and longstanding problem, so a proposed agenda for future research is offered

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

A geochemical and Nd, Sr and stable Ca isotopic study of carbonatites and associated silicate rocks from the similar to 65 Ma old Ambadongar carbonatite complex and the Phenai Mata igneous complex, Gujarat, India: Implications for crustal contamination, carbonate recycling, hydrothermal alteration and source-mantle mineralogy

Major, trace element concentrations and Nd, Sr and Ca stable isotopic compositions (delta Ca-44/40 and delta Ca-44/42 w.r.t. NIST SRM915a) of carbonatites and associated igneous silicate rocks from the -65 Ma old Ambadongar carbonatite complex and the surrounding Phenai Mata igneous complex of western India are reported. Samples of fluorspar from Ambadongar and the Bagh Limestone and Sandstone, which are part of the country rocks at Ambadongar, have also been analysed. The Ambadongar carbonatites are primarily calcio- and ferro-carbonatites while the silicate rocks from these two complexes are alkaline and tholeiitic in composition. The delta Ca-44/40 values of the carbonatites (0.58-1.1 parts per thousand, n = 7) and the associated igneous silicate rocks (0.50-0.92 parts per thousand, n = 14) show a broad range. The low K/Ca values of the carbonatites (<0.2) and silicate rocks (<2) along with their young eruption age (similar to 65 Ma) rule out any effect of radiogenic Ca-40 ingrowth due to decay of K-40 on the delta Ca-44/40 values. The lack of correlations between delta Ca-44/40 and Mg# as well as La/Yb-(N) values suggest that the variability in delta Ca-44/40 is not controlled by the degree of partial melting. The delta Ca-44/40 values of the carbonatites (0.58-1.1%0) overlap with that of the upper mantle/Bulk Silicate Earth and is mostly higher than the delta Ca-44/40 value of the Bagh Limestone (0.66 parts per thousand) suggesting that assimilation of these crustal limestones by the magma is unlikely to have caused the variability in delta Ca-44/40 of the carbonatites. In plots of delta Ca-44/40 versus epsilon Nd-(t) and Sr-87/Sr-86((t)), the igneous silicate rocks from the Ambadongar and Phenai Mata complexes plot on a mixing trend between a primitive (plume) mantle source and the continental crustal basement suggesting the role of continental crustal contamination during eruption of the Reunion plume. While simple binary mixing calculations yield unrealistically high amounts of crustal contamination (40%), assimilation and fractional crystallization (AFC) models suggest up to 20% contribution from a heterogeneous basement for these igneous silicate rocks. The role of continental crustal contamination in the genesis of the igneous silicate rocks is further supported by their unradiogenic epsilon Nd-(t), radiogenic Sr-87/Sr-86((t)) and low Ce/Pb values. In contrast, carbonatites plot away from the mixing trend between a primitive mantle (plume) source and continental crust in Ca-Sr-Nd isotopic diagrams suggesting that the Ca isotopic variability of carbonatites is not caused by continental crustal contamination. In contrast, the isotopic composition of the carbonatites can be explained by mixing of the plume end-member with up to 20% of similar to 160 Ma-old recycled carbonates suggesting their derivation from a highly heterogeneous, recycled carbonate-bearing plume mantle source. The composition of one carbonatite sample showing unusually high delta Ca-44/40 and highly radiogenic Sr-87/Sr-86((t)) is explained by hydrothermal alteration which is also invoked for the formation of massive fluorspar deposits with high delta Ca-44/40 (1.44 parts per thousand) at Ambadongar. In a plot of delta Ca-44/40 versus K/Rb, the carbonatites plot towards the phlogopite end-member (delta Ca-44/40 = 1 parts per thousand, K/Rb = 40-450) while the igneous silicate rocks plot towards the amphibole end-member (delta Ca-44/40 = 0.44 parts per thousand, K/Rb >1000). Phlogopite, especially if F-rich, is stable at greater depths in the mantle compared to amphibole. Hence, the correlated delta Ca-44/40 and K/Rb values of the carbonatites and associated igneous silicate rocks suggest the derivation of these carbonatites from a relatively deeper mantle source compared to the silicate rocks, both within the Reunion mantle plume. The origin of the carbonatites from the F-rich phlogopite-bearing mantle is also consistent with the occurrence of large fluorspar deposits within the Ambadongar carbonatite complex. (C) 2019 Elsevier B.V. All rights reserved

Large Ca stable isotopic (delta Ca-44/40) variation in a hand-specimen sized spheroidally weathered diabase due to selective weathering of clinopyroxene and plagioclase

Calcium stable isotopic compositions (delta Ca-44/40(SRM 915a)) as well as selected major and trace element concentrations are reported for micro-drilled samples of a hand-specimen sized spheroidally weathered diabase (synonymously used as dolerite or microgabbro) from southern India. A sample of the similar to 2.37 Ga old unweathered diabase (UW) dike was also analyzed. X-ray micro-CT imaging of a representative portion of the weathered sample shows the presence of two dominant mineral phases, plagioclase and clinopyroxene, with minor proportions of an iron-bearing phase (possibly haematite or ilmenite). Two different generations of crosscutting micro-fractures are identified from the micro-CT image. The older fracture is sealed with secondary mineral deposits. The delta Ca-44/40 values of the weathered samples range from 0.42 parts per thousand to 0.84 parts per thousand with samples showing both higher and lower values than that of the un-weathered diabase dike which shows a delta Ca-44/40 value of 0.65 parts per thousand. The variation in delta Ca-44/40 in the weathered samples is significantly higher than the external reproducibility of our measurements (< 0.1 parts per thousand) based on multiple measurements of Ca isotopic standards SRM 915a, SRM 915b and seawater (NASS-6). Mass balance calculations based on Sr/Ca and delta Ca-44/40 values rule out the contributions of secondary silicate as well as carbonate minerals in causing the variability of delta Ca-44/40 in the weathered samples. The positive correlations between delta Ca-44/40 and Mg/Al, Mg/Na in the weathered samples further negate the possible contribution of secondary carbonates in causing the variability in delta Ca-44/40, as Al and Na are unlikely to be present in carbonates. The samples with lower delta Ca-44/40 show higher CIA (Chemical Index of Alteration) values and Al/Ca than the UW diabase while samples having higher delta Ca-44/40 show lower CIA and Al/Ca than the UW diabase. The weathered sample having the lowest delta Ca-44/40 (close to the delta Ca-44/40 of plagioclase) exhibits the highest value of europium anomaly (Eu/Eu*). These observations are explained by the presence of variable relative proportions of residual clinopyroxene and plagioclase in the weathered diabase, due to selective weathering of these minerals. Since plagioclase and clinopyroxene could not be separated from the diabase, we measured the Ca isotopic compositions of a clinopyroxene (delta Ca-44/40= 1.06 parts per thousand) from the San Carlos mantle peridotite and plagioclase from the Chilka anorthosite complex (delta Ca-44/40= 0.40 parts per thousand) from the Eastern Ghats and used these isotopic values as representative of the compositions of these minerals in the diabase. Based on mixing models, using delta Ca-44/40, Al/Ca and Sr/Ca of the plagioclase and clinopyroxene end-members, we estimate that the delta Ca-44/40 of the UW diabase can be explained by 31 parts per thousand clinopyroxene and 69 parts per thousand plagioclase, which is consistent with the modal proportion of these minerals in an average unweathered diabase. Based on mixing calculations, the delta Ca-44/40, Sr/Ca and Al/Ca variability of the micro-drilled samples of the weathered diabase are explained by the presence of varying proportions of residual clinopyroxene (20-65 parts per thousand) and plagioclase (80-35 parts per thousand) in the weathered rock. This study demonstrates that selective weathering of major rock-forming minerals in nature can result in significant variation in delta Ca-44/40 in weathered rocks and that selective weathering of rock-forming minerals should be considered as an additional mechanism to explain the delta Ca-44/40 variability in rivers