Upper bounds for the eigenvalues of Hessian equations

We prove some upper bounds for the Dirichlet eigenvalues of a class of fully nonlinear elliptic equations, namely the Hessian equationsComment: 15 pages, 1 figur

Resolving MISS conceptions and misconceptions: A geological approach to sedimentary surface textures generated by microbial and abiotic processes

The rock record contains a rich variety of sedimentary surface textures on siliciclastic sandstone, siltstone and mudstone bedding planes. In recent years, an increasing number of these textures have been attributed to surficial microbial mats at the time of deposition, resulting in their classification as microbially induced sedimentary structures, or MISS. Research into MISS has developed at a rapid rate, resulting in a number of misconceptions in the literature. Here, we attempt to rectify these MISS misunderstandings. The first part of this paper surveys the stratigraphic and environmental range of reported MISS, revealing that contrary to popular belief there are more reported MISS-bearing rock units of Phanerozoic than Precambrian age. Furthermore, MISS exhibit a pan-environmental and almost continuous record since the Archean. Claims for the stratigraphic restriction of MISS to intervals prior to the evolution of grazing organisms or after mass extinction events, as well as claims for the environmental restriction of MISS, appear to result from sampling bias. In the second part of the paper we suggest that raised awareness of MISS has come at the cost of a decreasing appreciation of abiotic processes that may create morphologically similar features. By introducing the umbrella term ‘sedimentary surface textures’, of which MISS are one subset, we suggest a practical methodology for classifying such structures in the geological record. We illustrate how elucidating the formative mechanisms of ancient sedimentary surface textures usually requires consideration of a suite of sedimentological evidence from surrounding strata. Resultant interpretations, microbial or non-microbial, should be couched within a reasonable degree of uncertainty. This approach recognizes that morphological similarity alone does not constitute scientific proof of a common origin, and reinstates a passive descriptive terminology for sedimentary surface textures that cannot be achieved with the current MISS lexicon. It is hoped that this new terminology will reduce the number of overly sensational and misleading claims of MISS occurrence, and permit the means to practically separate initial observation from interpretation. Furthermore, this methodology offers a scientific approach that appreciates the low likelihood of conclusively identifying microbial structures from visual appearance alone, informing the search for true MISS in Earth's geological record and potentially on other planetary bodies such as Mars.Instances of sedimentary surface textures in the field were identified coincidentally during multiple seasons of varied field investigations primarily funded for NSD by a variety of organisations including a George Frederic Matthew Research Grant from the New Brunswick Museum for 2012, and a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to MRG. AGL is supported by the Natural Environment Research Council [grant number NE/L011409/1].This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.earscirev.2016.01.00

Major and trace-element zoning in metamorphic garnets and their metamorphic process implications

This article introduces some of the modern techniques for analyzing compositional zonings/profiles in metamorphic garnet, emphasizing the significance of two-dimensional composition X-ray mapping for such investigations. The compositional zonings/profiles in garnet can be divided into uniform-changed type and abrupt-changed type. The uniform-changed type is formed in equilibrium-controlled growth; the abrupt-changed type may be subdivided into step-changed subtype and spike-changed subtype, the forming mechanism of each is relatively complex. The step-changed subtype may be related to the processes such as poly-metamorphism, p-T changes with large magnitudes, and changes in metamorphic reactions or disturbance of crustal melting. As an example, the petrography, the major-and trace-element zoning and distribution patterns of REEs in the garnet from the Xiaomiao Group in the East Kunlun Mountains suggest two episodes of regional metamorphism.published_or_final_versio

Evolutionary synchrony of Earth's biosphere and sedimentary-stratigraphic record

The landscapes and seascapes of Earth’s surface provide the theatre for life, but to what extent did the actors build the stage? The role of life in the long-term shaping of the planetary surface needs to be understood to ascertain whether Earth is singular among known rocky planets, and to frame predictions of future changes to the biosphere. Modern geomorphic observations and modelling have made strides in this respect, but an under-utilized lens through which to interrogate these questions resides in the most complete tangible record of our planetary history: the sedimentary-stratigraphic record (SSR). The characteristics of the SSR have been frequently explained with reference to changes in boundary conditions such as relative sea level, climate, and tectonics. Yet despite the fact that the long-term accrual of the SSR was contemporaneous with the evolution of almost all domains of life on Earth, causal explanations related to biological activity have often been overlooked, particularly within siliciclastic strata. This paper explores evidence for the ways in which organisms have influenced the SSR throughout Earth history and emphasizes that further investigation can help lead us towards a mechanistic understanding of how the planetary surface has co-evolved with life. The practicality of discerning life signatures in the SSR is discussed by: 1) distinguishing biologically-dependent versus biologically-influenced sedimentary signatures; 2) emphasizing the importance of determining relative time-length scales of processes and demonstrating how different focal lengths of observation (individual geological outcrops and the complete SSR) can reveal different insights; and 3) promoting an awareness of issues of equifinality and underdetermination that may hinder the recognition of life signatures. Multiple instances of life signatures and their historic range within the SSR are reviewed, with examples covering siliciclastic, biogenic and chemogenic strata, and trigger organisms from across the spectrum of Earth’s extant and ancient life. With this novel perspective, the SSR is recognised as a dynamic archive that expands and complements the fossil and geochemical records that it hosts, rather than simply being a passive repository for them. The SSR is shown to be both the record and the result of long-term evolutionary synchrony between life and planetary surface processes

Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

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Extreme Risk Mitigation in Reinforcement Learning using Extreme Value Theory

Risk-sensitive reinforcement learning (RL) has garnered significant attention in recent years due to the growing interest in deploying RL agents in real-world scenarios. A critical aspect of risk awareness involves modeling highly rare risk events (rewards) that could potentially lead to catastrophic outcomes. These infrequent occurrences present a formidable challenge for data-driven methods aiming to capture such risky events accurately. While risk-aware RL techniques do exist, their level of risk aversion heavily relies on the precision of the state-action value function estimation when modeling these rare occurrences. Our work proposes to enhance the resilience of RL agents when faced with very rare and risky events by focusing on refining the predictions of the extreme values predicted by the state-action value function distribution. To achieve this, we formulate the extreme values of the state-action value function distribution as parameterized distributions, drawing inspiration from the principles of extreme value theory (EVT). This approach effectively addresses the issue of infrequent occurrence by leveraging EVT-based parameterization. Importantly, we theoretically demonstrate the advantages of employing these parameterized distributions in contrast to other risk-averse algorithms. Our evaluations show that the proposed method outperforms other risk averse RL algorithms on a diverse range of benchmark tasks, each encompassing distinct risk scenarios

Synergistic and compensatory effects of two point mutations conferring target-site resistance to fipronil in the insect GABA receptor RDL

Insecticide resistance can arise from a variety of mechanisms, including changes to the target site, but is often associated with substantial fitness costs to insects. Here we describe two resistance-associated target-site mutations that have synergistic and compensatory effects that combine to produce high and persistent levels of resistance to fipronil, an insecticide targeting on γ-aminobytyric acid (GABA) receptors. In Nilaparvata lugens, a major pest of rice crops in many parts of Asia, we have identified a single point mutation (A302S) in the GABA receptor RDL that has been identified previously in other species and which confers low levels of resistance to fipronil (23-fold) in N. lugans. In addition, we have identified a second resistance-associated RDL mutation (R300Q) that, in combination with A302S, is associated with much higher levels of resistance (237-fold). The R300Q mutation has not been detected in the absence of A302S in either laboratory-selected or field populations, presumably due to the high fitness cost associated with this mutation. Significantly, it appears that the A302S mutation is able to compensate for deleterious effects of R300Q mutation on fitness cost. These findings identify a novel resistance mechanism and may have important implications for the spread of insecticide resistance

EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate JNK and cell death pathways in human cervical cancer cells

Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction. Mechanistic studies indicated that EM23-induced apoptosis was mediated by reactive oxygen species (ROS) and the knockdown of thioredoxin (Trx) or thioredoxin reductase (TrxR) resulted in a reduction in apoptosis. EM23 attenuated TrxR activity by alkylation of C-terminal redox-active site Sec498 of TrxR and inhibited the expression levels of Trx/TrxR to facilitate ROS accumulation. Furthermore, inhibition of Trx/TrxR system resulted in the dissociation of ASK1 from Trx and the downstream activation of JNK. Pretreatment with ASK1/JNK inhibitors partially rescued cells from EM23-induced apoptosis. Additionally, EM23 inhibited Akt/mTOR pathway and induced autophagy, which was observed to be proapoptotic and mediated by ROS. Together, these results reveal a potential molecular mechanism for the apoptotic induction observed with SL compound EM23, and emphasize its putative role as a therapeutic agent for human cervical cancer.published_or_final_versio

Experiments on Multidimensional Solitons

This article presents an overview of experimental efforts in recent years related to multidimensional solitons in Bose-Einstein condensates. We discuss the techniques used to generate and observe multidimensional nonlinear waves in Bose-Einstein condensates with repulsive interactions. We further summarize observations of planar soliton fronts undergoing the snake instability, the formation of vortex rings, and the emergence of hybrid structures.Comment: review paper, to appear as Chapter 5b in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

Territory-Wide Chinese Cohort of Long QT Syndrome: Random Survival Forest and Cox Analyses

Introduction: Congenital long QT syndrome (LQTS) is a cardiac ion channelopathy that predisposes affected individuals to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD). The main aims of the study were to: (1) provide a description of the local epidemiology of LQTS, (2) identify significant risk factors of ventricular arrhythmias in this cohort, and (3) compare the performance of traditional Cox regression with that of random survival forests. / Methods: This was a territory-wide retrospective cohort study of patients diagnosed with congenital LQTS between 1997 and 2019. The primary outcome was spontaneous VT/VF. / Results: This study included 121 patients [median age of initial presentation: 20 (interquartile range: 8–44) years, 62% female] with a median follow-up of 88 (51–143) months. Genetic analysis identified novel mutations in KCNQ1, KCNH2, SCN5A, ANK2, CACNA1C, CAV3, and AKAP9. During follow-up, 23 patients developed VT/VF. Univariate Cox regression analysis revealed that age [hazard ratio (HR): 1.02 (1.01–1.04), P = 0.007; optimum cut-off: 19 years], presentation with syncope [HR: 3.86 (1.43–10.42), P = 0.008] or VT/VF [HR: 3.68 (1.62–8.37), P = 0.002] and the presence of PVCs [HR: 2.89 (1.22–6.83), P = 0.015] were significant predictors of spontaneous VT/VF. Only initial presentation with syncope remained significant after multivariate adjustment [HR: 3.58 (1.32–9.71), P = 0.011]. Random survival forest (RSF) model provided significant improvement in prediction performance over Cox regression (precision: 0.80 vs. 0.69; recall: 0.79 vs. 0.68; AUC: 0.77 vs. 0.68; c-statistic: 0.79 vs. 0.67). Decision rules were generated by RSF model to predict VT/VF post-diagnosis. / Conclusions: Effective risk stratification in congenital LQTS can be achieved by clinical history, electrocardiographic indices, and different investigation results, irrespective of underlying genetic defects. A machine learning approach using RSF can improve risk prediction over traditional Cox regression models