Particle-in-cell experiments examine electron diffusion by whistler-mode waves: 1. Benchmarking with a cold plasma

Using a particle-in-cell code, we study the diffusive response of electrons due to wave particle interactions with whistler-mode waves. The relatively simple configuration of field-aligned waves in a cold plasma is used in order to benchmark our novel method, and to compare with previous works that used a different modelling technique. In this boundary-value problem, incoherent whistler-mode waves are excited at the domain boundary, and then propagate through the ambient plasma. Electron diffusion characteristics are directly extracted from particle data across all available energy and pitch-angle space. The ‘nature’ of the diffusive response is itself a function of energy and pitch-angle, such that the rate of diffusion is not always constant in time. However, after an initial transient phase, the rate of diffusion tends to a constant, in a manner that is consistent with the assumptions of quasilinear diffusion theory. This work establishes a framework for future investigations on the nature of diffusion due to whistler-mode wave-particle interactions, using particle-in-cell numerical codes with driven waves as boundary value problems

Myristica lowiana Phytochemicals as Inhibitor of Plasmid Conjugation in Escherichia coli

Hexane extract and methanol fraction from the stem bark of Myristica lowiana specifically and significantly inhibited the conjugal transfer of the IncW plasmid R7K, a plasmid which harbors ampicillin-, streptomycin-, and spectinomycin-resistant genes. The transfer of this plasmid via the conjugative pilli of Escherichia coli was reduced by 76.5 ± 2.0% and 79.0 ± 1.2% by hexane extract and methanol fraction of M. lowiana, respectively. The hexane extract exhibited significant anti-conjugant activity at a non-cytotoxic concentration of 100 mg/L as assessed against adult human dermal fibroblast cells. The hexane extract and methanol fraction were screened using phytochemical tests, NMR spectroscopy, IR spectroscopy, and high-resolution electrospray ionization mass spectrometry (HRESIMS) and were found to contain terpenoids, sterols, and fatty acids

MAP Kinase-Interacting Kinases—Emerging Targets against Cancer

Mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) regulate the initiation of translation through phosphorylation of eukaryotic initiation factor 4E (eIF4E). Mnk-mediated eIF4E activation promotes cancer development and progression. While the phosphorylation of eIF4E is necessary for oncogenic transformation, the kinase activity of Mnks seems dispensable for normal development. For this reason, pharmacological inhibition of Mnks could represent an ideal mechanism-based and nontoxic therapeutic strategy for cancer treatment. In this review, we discuss the current understanding of Mnk biological roles, structures, and functions, as well as clinical implications. Importantly, we propose different strategies for identification of highly selective small molecule inhibitors of Mnks, including exploring a structural feature of their kinase domain, DFD motif, which is unique within the human kinome. We also argue that a combined targeting of Mnks and other pathways should be considered given the complexity of cancer

On the design of sparse but efficient structures in operations

It is widely believed that a little flexibility added at the right place can reap significant benefits for operations. Unfortunately, despite the extensive literature on this topic, we are not aware of any general methodology that can be used to guide managers in designing sparse (i.e., slightly flexible) and yet efficient operations. We address this issue using a distributionally robust approach to model the performance of a stochastic system under different process structures. We use the dual prices obtained from a related conic program to guide managers in the design process. This leads to a general solution methodology for the construction of efficient sparse structures for several classes of operational problems. Our approach can be used to design simple yet efficient structures for workforce deployment and for any level of sparsity requirement, to respond to deviations and disruptions in the operational environment. Furthermore, in the case of the classical process flexibility problem, our methodology can recover the k-chain structures that are known to be extremely efficient for this type of problem when the system is balanced and symmetric. We can also obtain the analog of 2-chain for nonsymmetrical system using this methodology. This paper was accepted by Yinyu Ye, optimization. </jats:p

Disruption risk mitigation in supply chains: The risk exposure index revisited

A novel approach has been proposed in the literature using the time-to-recover (TTR) parameters to analyze the risk-exposure index (REI) of supply chains under disruption. This approach is able to capture the cascading effects of disruptions in the supply chains, albeit in simplified environments; TTRs are deterministic, and at most, one node in the supply chain can be disrupted. In this paper, we propose a new method to integrate probabilistic assessment of disruption risks into the REI approach and measure supply chain resiliency by analyzing the worst-case conditional value at risk of total lost sales under disruptions. We show that the optimal strategic inventory positioning strategy in this model can be fully characterized by a conic program. We identify appropriate cuts that can be added to the formulation to ensure zero duality gap in the conic program. In this way, the optimal primal and dual solutions to the conic program can be used to shed light on comparative statics in the supply chain risk mitigation problem. This information can help supply chain risk managers focus their mitigation efforts on critical suppliers and/or installations that will have a greater impact on the performance of the supply chain when disrupted.Accepted versio

Updated Parameters and a New Transmission Spectrum of HD 97658b

Recent years have seen increasing interest in the characterization of sub-Neptune-sized planets because of their prevalence in the Galaxy, contrasted with their absence in our solar system. HD 97658 is one of the brightest stars hosting a planet of this kind, and we present the transmission spectrum of this planet by combining four Hubble Space Telescope transits, 12 Spitzer/IRAC transits, and eight MOST transits of this system. Our transmission spectrum has a higher signal-to-noise ratio than those from previous works, and the result suggests that the slight increase in transit depth from wavelength 1.1–1.7 μm reported in previous works on the transmission spectrum of this planet is likely systematic. Nonetheless, our atmospheric modeling results are inconclusive, as no model provides an excellent match to our data. Nonetheless, we find that atmospheres with high C/O ratios (C/O ≳ 0.8) and metallicities of ≳100× solar metallicity are favored. We combine the mid-transit times from all of the new Spitzer and MOST observations and obtain an updated orbital period of P = 9.489295 ± 0.000005, with a best-fit transit time center at T₀ = 2456361.80690 ± 0.00038 (BJD). No transit timing variations are found in this system. We also present new measurements of the stellar rotation period (34 ± 2 days) and stellar activity cycle (9.6 yr) of the host star HD 97658. Finally, we calculate and rank the Transmission Spectroscopy Metric of all confirmed planets cooler than 1000 K and with sizes between 1 R⊕ and 4 R⊕. We find that at least a third of small planets cooler than 1000 K can be well characterized using James Webb Space Telescope, and of those, HD 97658b is ranked fifth, meaning that it remains a high-priority target for atmospheric characterization

Analysis of SMALP co-extracted phospholipids shows distinct membrane environments for three classes of bacterial membrane protein

Biological characterisation of membrane proteins lags behind that of soluble proteins. This reflects issues with the traditional use of detergents for extraction, as the surrounding lipids are generally lost, with adverse structural and functional consequences. In contrast, styrene maleic acid (SMA) copolymers offer a detergent-free method for biological membrane solubilisation to produce SMA-lipid particles (SMALPs) containing membrane proteins together with their surrounding lipid environment. We report the development of a reverse-phase LC-MS/MS method for bacterial phospholipids and the first comparison of the profiles of SMALP co-extracted phospholipids from three exemplar bacterial membrane proteins with different topographies: FtsA (associated membrane protein), ZipA (single transmembrane helix), and PgpB (integral membrane protein). The data showed that while SMA treatment per se did not preferentially extract specific phospholipids from the membrane, SMALP-extracted ZipA showed an enrichment in phosphatidylethanolamines and depletion in cardiolipins compared to the bulk membrane lipid. Comparison of the phospholipid profiles of the 3 SMALP-extracted proteins revealed distinct lipid compositions for each protein: ZipA and PgpB were similar, but in FtsA samples longer chain phosphatidylglycerols and phosphatidylethanolamines were more abundant. This method offers novel information on the phospholipid interactions of these membrane proteins

Cell-Penetrating Protein/Corrole Nanoparticles

Recent work has highlighted the potential of metallocorroles as versatile platforms for the development of drugs and imaging agents, since the bioavailability, physicochemical properties and therapeutic activity can be dramatically altered by metal ion substitution and/or functional group replacement. Significant advances in cancer treatment and imaging have been reported based on work with a water-soluble bis-sulfonated gallium corrole in both cellular and rodent-based models. We now show that cytotoxicities increase in the order Ga < Fe < Al < Mn < Sb < Au for bis-sulfonated corroles; and, importantly, that they correlate with metallocorrole affinities for very low density lipoprotein (VLDL), the main carrier of lipophilic drugs. As chemotherapeutic potential is predicted to be enhanced by increased lipophilicity, we have developed a novel method for the preparation of cell-penetrating lipophilic metallocorrole/serum-protein nanoparticles (NPs). Cryo-TEM revealed an average core metallocorrole particle size of 32 nm, with protein tendrils extending from the core (conjugate size is ~100 nm). Optical imaging of DU-145 prostate cancer cells treated with corrole NPs (≤100 nM) revealed fast cellular uptake, very slow release, and distribution into the endoplasmic reticulum (ER) and lysosomes. The physical properties of corrole NPs prepared in combination with transferrin and albumin were alike, but the former were internalized to a greater extent by the transferrin-receptor-rich DU-145 cells. Our method of preparation of corrole/protein NPs may be generalizable to many bioactive hydrophobic molecules to enhance their bioavailability and target affinity