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

A three amino acid deletion in the transmembrane domain of the nicotinic acetylcholine receptor α6 subunit confers high-level resistance to spinosad in Plutella xylostella

Spinosad is a macrocyclic lactone insecticide that acts primarily at the nicotinic acetylcholine receptors (nAChRs) of target insects. Here we describe evidence that high levels of resistance to spinosad in the diamondback moth (Plutella xylostella) are associated with a three amino acid (3-aa) deletion in the fourth transmembrane domain (TM4) of the nAChR α6 subunit (Pxα6). Following laboratory selection with spinosad, the SZ-SpinR strain of P. xylostella exhibited 940-fold resistance to spinosad. In addition, the selected insect population had 1060-fold cross-resistance to spinetoram but, in contrast, no cross-resistance to abamectin was observed. Genetic analysis indicates that spinosad resistance in SZ-SpinR is inherited as a recessive and autosomal trait, and that the 3-aa deletion (IIA) in TM4 of Pxα6 is tightly linked to spinosad resistance. Because of well-established difficulties in functional expression of cloned insect nAChRs, the analogous resistance-associated deletion mutation was introduced into a prototype nAChR (the cloned human α7 subunit). Two-electrode voltage-clamp recording with wild-type and mutated nAChRs expressed in Xenopus laevis oocytes indicated that the mutation causes a complete loss of agonist activation. In addition, radioligand binding studies indicated that the 3-aa deletion resulted in significantly lower-affinity binding of the extracellular neurotransmitter-binding site. These findings are consistent with the 3-amino acid (IIA) deletion within the transmembrane domain of Pxα6 being responsible for target-site resistance to spinosad in the SZ-SpinR strain of P. xylostella

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

Research on E-Learning in the Workplace 2000-2012: A Bibliometric Analysis of the Literature

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ProteoMirExpress: inferring microRNA-centered regulatory networks from high-throughput proteomic and transcriptome data

MicroRNAs (miRNAs) regulate gene expression through translational repression and RNA degradation. Recently developed high-throughput proteomic methods measure gene expression changes at protein levels, and therefore can reveal the direct effects of miRNAs’ translational repression. Here, we present a web server, ProteoMirExpress that integrates proteomic and mRNA expression data together to infer miRNA-centered regulatory networks. With both high throughput data from the users, ProteoMirExpress is able to discover not only miRNA targets that have mRNA decreased, but also subgroups of targets whose proteins are suppressed but mRNAs are not significantly changed or whose mRNAs are decreased but proteins are not significantly changed, which were usually ignored by most current methods. Furthermore, both direct and indirect targets of miRNAs can be detected. Therefore ProteoMirExpress provides more comprehensive miRNA-centered regulatory networks. We use several published data to assess the quality of our inferred networks and prove the value of our server. ProteoMirExpress is available at http://jjwanglab.org/ProteoMirExpress, with free access to academic users.postprin

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

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Mutations on M3 helix of Plutella xylostella glutamate-gated chloride channel confer unequal resistance to abamectin by two different mechanisms

Abamectin is one of the most widely used avermectins for agricultural pests control, but the emergence of resistance around the world is proving a major threat to its sustained application. Abamectin acts by directly activating glutamate-gated chloride channels (GluCls) and modulating other Cys-loop ion channels. To date, three mutations occurring in the transmembrane domain of arthropod GluCls are associated with target-site resistance to abamectin: A309V in Plutella xylostella GluCl (PxGluCl), G323D in Tetranychus urticae GluCl1 (TuGluCl1) and G326E in TuGluCl3. To compare the effects of these mutations in a single system, A309V/I/G and G315E (corresponding to G323 in TuGluCl1 and G326 in TuGluCl3) substitutions were introduced individually into the PxGluCl channel. Functional analysis using Xenopus oocytes showed that the A309V and G315E mutations reduced the sensitivity to abamectin by 4.8- and 493-fold, respectively. In contrast, the substitutions A309I/G show no significant effects on the response to abamectin. Interestingly, the A309I substitution increased the channel sensitivity to glutamate by one order of magnitude (∼12-fold). Analysis of PxGluCl homology models indicates that the G315E mutation interferes with abamectin binding through a steric hindrance mechanism. In contrast, the structural consequences of the A309 mutations are not so clear and an allosteric modification of the binding site is the most likely mechanism. Overall the results show that both A309V and G315E mutations may contribute to target-site resistance to abamectin and may be important for the future prediction and monitoring of abamectin resistance in P. xylostella and other arthropod pests

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

Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: Implications for evasion of immune responses and design of vaccine immunogens

Several human monoclonal antibodies (hmAbs) including b12, 2G12, and 2F5 exhibit relatively potent and broad HIV-1-neutralizing activity. However, their elicitation in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. We have hypothesized that HIV-1 has evolved a strategy to reduce or eliminate the immunogenicity of the highly conserved epitopes of such antibodies by using "holes" (absence or very weak binding to these epitopes of germline antibodies that is not sufficient to initiate and/or maintain an efficient immune response) in the human germline B cell receptor (BCR) repertoire. To begin to test this hypothesis we have designed germline-like antibodies corresponding most closely to b12, 2G12, and 2F5 as well as to X5, m44, and m46 which are cross-reactive but with relatively modest neutralizing activity as natively occurring antibodies due to size and/or other effects. The germline-like X5, m44, and m46 bound with relatively high affinity to all tested Envs. In contrast, germline-like b12, 2G12, and 2F5 lacked measurable binding to Envs in an ELISA assay although the corresponding mature antibodies did. These results provide initial evidence that Env structures containing conserved vulnerable epitopes may not initiate humoral responses by binding to germline antibodies. Even if such responses are initiated by very weak binding undetectable in our assay it is likely that they will be outcompeted by responses to structures containing the epitopes of X5, m44, m46, and other antibodies that bind germline BCRs with much higher affinity/avidity. This hypothesis, if further supported by data, could contribute to our understanding of how HIV-1 evades immune responses and offer new concepts for design of effective vaccine immunogens.postprin