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Water soluble thioglycosylated BODIPYs for mitochondria targeted cytotoxicity
No full textThe facile synthesis of water-soluble mitochondria targeting thioglycosylated BODIPYs is reported. Thioglycosylated BODIPYs were synthesized in 25-26% yields via thioglycosylated dipyrromethanes in four steps. The dipyrromethanes and thioglycosylated BODIPYs were characterized by various techniques including HRMS, NMR spectroscopy and X-ray crystallography. In-vitro cellular investigations in skin keratinocyte (HaCaT) and cervical (HeLa) cancer cells revealed significant cytotoxicities with IC50 values between 23.83 to 48.61 mu M. The flow cytometry experiments revealed significant cellular uptake of thioglycosylated BODIPYs into HaCaT cells and thioglucosyl substituted BODIPY (9) showed higher cellular uptake and ROS generation than the rest of the molecules. The highlight of this study is the mitochondrial targeting by the neutral BODIPYs, as judged by the colocalization experiments using confocal microscopy
Machine Learning in the Air
No full textThanks to the recent advances in processing speed, data acquisition and storage, machine learning (ML) is penetrating every facet of our lives, and transforming research in many areas in a fundamental manner. Wireless communications is another success story - ubiquitous in our lives, from handheld devices to wearables, smart homes, and automobiles. While recent years have seen a flurry of research activity in exploiting ML tools for various wireless communication problems, the impact of these techniques in practical communication systems and standards is yet to be seen. In this paper, we review some of the major promises and challenges of ML in wireless communication systems, focusing mainly on the physical layer. We present some of the most striking recent accomplishments that ML techniques have achieved with respect to classical approaches, and point to promising research directions where ML is likely to make the biggest impact in the near future. We also highlight the complementary problem of designing physical layer techniques to enable distributed ML at the wireless network edge, which further emphasizes the need to understand and connect ML with fundamental concepts in wireless communications
Carbonyl Sulfide (COS) Donor Induced Protein Persulfidation Protects against Oxidative Stress
No full textThe emergence of hydrogen sulfide (H2S) as an important signalling molecule in redox biology with therapeutic potential has triggered interest in generating this molecule within cells. One strategy that has been proposed is to use carbonyl sulfide (COS) as a surrogate for hydrogen sulfide. Small molecules that generate COS have been shown to produce hydrogen sulfide in the presence of carbonic anhydrase, a widely prevalent enzyme. However, other studies have indicated that COS may have biological effects which are distinct from H2S. Thus, it would be useful to develop tools to compare (and contrast) effects of COS and H2S. Here we report enzyme-activated COS donors that are capable of inducing protein persulfidation, which is symptomatic of generation of hydrogen sulfide. The COS donors are also capable of mitigating stress induced by elevated reactive oxygen species. Together, our data suggests that the effects of COS parallel that of hydrogen sulfide, laying the foundation for further development of these donors as possible therapeutic agents
Arginine methylation augments Sbp1 function in translation repression and decapping
No full textThe fate of messenger RNA in cytoplasm plays a crucial role in various cellular processes. However, the mechanisms that decide whether mRNA will be translated, degraded or stored remain unclear. Single stranded nucleic acid binding protein (Sbp1), an Arginine-Glycine-Glycine (RGG-motif) protein, is known to promote transition of mRNA into a repressed state by binding eukaryotic translation initiation factor 4G1 (eIF4G1) and to promote mRNA decapping, perhaps by modulation of Dcp1/2 activity. Sbp1 is known to be methylated on arginine residues in RGG-motif; however, the functional relevance of this modification in vivo remains unknown. Here, we report that Sbp1 is arginine-methylated in an hnRNP methyl transferase (Hmt1)-dependent manner and that methylation is enhanced upon glucose deprivation. Characterization of an arginine-methylation-defective (AMD) mutant provided evidence that methylation affects Sbp1 function in vivo. The AMD mutant is compromised in causing growth defect upon overexpression, and the mutant is defective in both localizing to and inducing granule formation. Importantly, the Sbp1-eIF4G1 interaction is compromised both for the AMD mutant and in the absence of Hmt1. Upon overexpression, wild-type Sbp1 increases localization of another RGG motif containing protein, Scd6 (suppressor of clathrin deficiency) to granules; however, this property of Sbp1 is compromised in the AMD mutant and in the absence of Hmt1, indicating that Sbp1 repression activity could involve other RGG-motif translation repressors. Additionally, the AMD mutant fails to increase localization of the decapping activator DEAD box helicase homolog to foci and fails to rescue the decapping defect of a dcp1-2 Delta ski8 strain, highlighting the role of Sbp1 methylation in decapping. Taken together, these results suggest that arginine methylation modulates Sbp1 role in mRNA fate determination
Thin Film PZT-Based PMUT Arrays for Deterministic Particle Manipulation
No full textLead zirconate titanate (PZT)-based piezoelectric micromachined ultrasonic transducers (PMUTs) for particle manipulation applications were designed, fabricated, characterized, and tested. The PMUTs had a diaphragm diameter of 60 mu m, a resonant frequency of similar to 8 MHz, and an operational bandwidth (BW) of 62.5%. Acoustic pressure output in water was 9.5 kPa at 7.5 mm distance from a PMUT element excited with a unipolar waveform at 5 V-pp. The element consisted of 20 diaphragms connected electrically in parallel. Particle trapping of 4 mu m silica beads was shown to be possible with 5 V-pp unipolar excitation. Trapping of multiple beads by a single element and deterministic control of particles via acoustophoresis without the assistance of microfluidic flow were demonstrated. It was found that the particles move toward diaphragm areas of highest pressure, in agreement with literature and simulations. Unique bead patterns were generated at different driving frequencies and were formed at frequencies up to 60 MHz, much higher than the operational BW. Levitation planes were generated above the 30 MHz driving frequency
Hormonal regulation and function of an RNA helicase, Ddx5 in corpus luteum of adult Wistar rats
No full textCorpus luteum (CL) is an endocrine tissue involved in regulation of reproductive cycle and early pregnancy establishment. In the present study DEAD-box helicase-5 (Ddx5), a member of the DEAD box family of RNA helicases was investigated for its expression, regulation and function in CL of Wistar rats. Ddx5 was expressed in adult rat CL. Primary cell culture from supra-ovulated ovaries were established for in vitro studies. Addition of luteinizing hormone (LH; 100 ng/ml), a luteotrophic factor in primary cell culture, decreased Ddx5 RNA expression (foldchange:0.6 +/- 0.075) while prostaglandin alpha (PGF(2 alpha); 1 mu M), a luteolytic factor caused an increase (foldchange:2.4 +/- 0.4) compared to control group. Under in vivo conditions, the administration of PGF(2 alpha) or gonadotropin-releasing hormone antagonist; cetrorelix (CET) caused luteolysis as well as an increase in the protein level of Ddx5 (foldchange:1.9 +/- 0.27 and 1.4 +/- 0.09 viz.; p < 0.05) in CL of adult rats. LH was administered post CET treatment which suppressed Ddx5 protein expression (foldchange:0.8 +/- 0.16; p < 0.05) compared to CET treated group. Further, it was observed that the expression of Ddx5 was upregulated (fold-change:1.5 +/- 0.23; p < 0.05) in CL during late pregnancy compared to mid pregnancy concomitant to luteolysis in adult rats. Overall, the results suggest for the first time that Ddx5 is expressed in rat CL and regulated by luteolytic and luteotrophic factors in an inverse fashion. Further, the data significantly correlates ddx5 expression to CL regression suggesting involvement of ddx5 in luteolysis. These results suggest a significant role of Ddx5 in female reproduction biology and warrant in depth examination of the function of Ddx5 in CL
Geminal Difunctionalization of Vinylarenes: Concise Synthesis of 1,3-Dioxolan-4-ones
No full textWe report a straightforward method for the synthesis of five-membered 1,3-dioxolan-4-ones by an unprecedented oxidative alkene geminal difunctionalization strategy using alpha-hydroxy carboxylic acids. Under the geminal oxidative addition conditions, various substituted alpha-hydroxy carboxylic acids and styrenes containing a variety of substituents, including beta-substituted styrenes, were effectively coupled regioselectively (anti-Markovnikov) with an isobutyl-substituted chiral alpha-hydroxy carboxylic acid, providing an annulation with excellent dia--stereoselectivity. An aryl migration in the semipinacol rearrangement leading to geminal oxidative addition of the alpha-hydroxy carboxylic acids was confirmed by deuterium-labelling and control studies
Noninvasive Subsurface Electrical Probe for Encapsulated Layers in van der Waals Heterostructures
No full textVan der Waals heterostructures formed by stacking different atomically thin layered materials have emerged as the sought-after device platform for electronic and optoelectronic applications. Determination of the spatial extent of all the encapsulated components in such vertical stacks is key to optimal fabrication methods and improved device performance. Here, we employ electrostatic force microscopy as a fast and noninvasive microscopic probe that provides compelling images of two-dimensional layers buried over 30 nm below the sample surface. We demonstrate the versatility of the technique by studying hetero-junctions comprising graphene, hexagonal boron nitride, and transition-metal dichalcogenides. The work function of each constituent layer acts as a unique fingerprint during imaging, thereby providing important insights into the charge environment, disorder, structural imperfections, and doping profile. The technique holds great potential for gaining a comprehensive understanding of the quality and flatness as well as local electrical properties of buried layers in a large class of nanoscale materials and vertical heterostructures
Study of energy deposition patterns in hadron calorimeter for prompt and displaced jets using convolutional neural network
No full textSophisticated machine learning techniques have promising potential in search for physics beyond Standard Model in Large Hadron Collider (LHC). Convolutional neural networks (CNN) can provide powerful tools for differentiating between patterns of calorimeter energy deposits by prompt particles of Standard Model and long-lived particles predicted in various models beyond the Standard Model. We demonstrate the usefulness of CNN by using a couple of physics examples from well motivated BSM scenarios predicting long-lived particles giving rise to displaced jets. Our work suggests that modern machine-learning techniques have potential to discriminate between energy deposition patterns of prompt and long-lived particles, and thus, they can be useful tools in such searches
Parametric analysis and comparative study of multimode waveguides on lithium niobate-on-insulator and silicon-on-insulator platforms
No full textMultimode waveguides on lithium niobate-on-insulator (LNOI) and silicon-on-insulator (SOI) platforms are numerically investigated in buried, rib, and strip configurations. Performance of waveguides is compared in terms of waveguide cross-sectional area, dispersion, mode hybridization, and power confinement for both quasi-transverse electric and quasi-transverse magnetic modes. Tall waveguides with single mode in the horizontal direction, supporting higher order modes in the vertical direction, are analyzed. Also, wide waveguides with single mode in the vertical direction, supporting higher order modes in the horizontal direction, are studied. Designs that overcome mode hybridization are proposed, which are well suited for applications such as optical interconnects. LNOI waveguides were found to exhibit lower dispersion in all the configurations, with power confinement and physical dimensions comparable to those of SOI waveguides. The results are instrumental in design optimization of multimode components for on-chip mode-division multiplexing schemes and multiparameter sensing applications. Electro-optic effect is also illustrated in a buried multimode LNOI waveguide that is largely useful in modulation and switching applications