Journal articles on the topic 'Robinson, D. W. B'

BackgroundGliomas represent the most common brain tumors within the central nervous system, with glioblastoma being the most aggressive type.1 Conventional treatment combines several approaches including surgery, chemotherapy, and radiation.2 However, the prognosis for glioblastoma remains unfavorable, with only 5% of patients surviving more than 5 years post-diagnosis.3 Thus, new treatment approaches are urgently needed. Natural killer (NK) cells directly lyse malignantly transformed or virally infected cells and secrete inflammatory cytokines that polarize cytotoxic immunity. Allogeneic NK cell adoptive transfer has shown clinical benefit in patients with advanced cancer.4–7 However, limitations of this approach include relatively low numbers of donor NK cells that can be isolated during an apheresis and variability in the quality of NK cells between donors. To overcome these limitations, we have developed a GMP manufacturing strategy to mass produce NK cells from induced pluripotent stem cells (iPSCs) as an approach to off-the-shelf cancer immunotherapy. We refer to these cells as ‘iNK’ (iPSC-derived NK) cells. Here, we provide preclinical data demonstrating the efficacy of iNK cells for immunotherapy against glioblastoma.Abstract 155 Figure 1Engineered iNK cells exhibit highly effective antitumor function in a xenogeneic model of glioblastoma. (A) Schematic of the experimental design to test iNK cell function against glioblastoma in vivo. (B) Kaplan Meier plots showing survival for groups of mice that received either vehicle alone or iNK cells after tumor engraftment (n=5 mice/group)MethodsWe generated iNK cells using previously published methods.8–10 iNK cells were used as effectors against an array of patient-derived glioblastoma lines in 2-dimensional live imaging IncuCyte assays where iNK cell-mediated killing was observed over the course of 48 hours. To investigate iNK cell infiltration and cytotoxicity in a more physiological context that accounts for the 3-dimensional architecture of the tumor, we also performed live imaging IncuCyte assays using iNK cells as effectors against glioblastoma spheroids. To test the anti-tumor function of iNK cells in vivo, we implanted patient-derived glioblastoma cells into mice via intracranial injection. Seven days later, 5 mice received intratumoral injections of iNK cells, and 5 mice received vehicle alone (as a control; figure 1A). All mice were monitored for weight and survival over 100 days.Results iNK cells exhibited strong and sustained cytotoxicity against 6 primary patient-derived mesenchymal glioblastoma lines in 2-dimensional IncuCyte assays and complete infiltration and destruction of glioblastoma spheroids in 3-dimensional IncuCyte assays. In xenogeneic adoptive transfer experiments, all mice receiving intratumoral injections of iNK cells survived out to day 100, while all mice in the vehicle group became moribund and had to be sacrificed by day 60 (figure 1B).ConclusionsiNK cells are highly cytotoxic against glioblastoma cells, and our preclinical in vivo data provides proof-of-concept for future clinical trials.Ethics ApprovalThis project has been approved by the University of Minnesota IACUC. Approval ID: 1812-36595AReferencesLouis D N, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee W K, Ohgaki H, Wiestler O D, Kleihues P, Ellison D W. The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016;131:803–820.Stupp R, Mason W P, van den Bent M J, Weller M, Fisher B, Taphoorn M J B, Belanger K, Brandes A A, Marosi C, Bogdahn U, Curschmann J, Janzer R C, Ludwin S K, Gorlia T, Allgeier A, Lacombe D, Cairncross J G, Eisenhauer E, Mirimanoff R O, European Organization for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholz-Sloan JS, Villano JL. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 2017;23:1985–1996.Miller J S, Soignier Y, Panoskaltsis-Mortari A, McNearney S A, Yun G H, Fautsch S K, McKenna D, Le C, Defor T E, Burns L J, Orchard P J, Blazar B R, Wagner J E, Slungaard A, Weisdorf D J, Okazaki J, McGlave P B. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105:3051–3057.Bachanova V, Cooley S, Defor T E, Verneris M R, Zhang B, McKenna D H, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf D J, Blazar B R, Miller J S. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 2014;123:3855.Ciurea S O, Schafer J R, Bassett R, Denman C J, Cao K, Willis D, Rondon G, Chen J, Soebbing D, Kaur I, Gulbis A, Ahmed S, Rezvani K, Scpall E J, Lee D A, Champlin R E. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplant. Blood 2017;130:1857–1868.Romee R, Rosario M, Berrien-Elliott M M, Wagner J A, Jewell B A, Schappe T, Leong J W, Abdel-Latif S, Schneider S E, Willey S, Neal C C, Yu L, Oh T, Lee S, Mulder A, Cooper M A, Fehniger T A. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukiemia. Sci Transl Med 2016:8;375ra123.Valamehr B, Abujarour R, Robinson M, Le T, Robbins D, Shoemaker D, Flynn P. A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs. Sci Rep 2012:2;213.Valamehr B, Robinson M, Abujarour R, Rezner B, Vranceanu F, Le T, Medcalf A, Lee T T, Fitch M, Robbins D, Flynn P. Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells. Stem Cell Reports 2014;2:366–381.Zhu H, Blum R H, Bjordahl R, Gaidarova S, Rogers P, Lee T T, Abujarour R, Bonello G B, Wu J, Tsai P-F, Miller J S, Walcheck B, Valamehr B, Kaufman D S. Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor immunity. Blood 2020;135:399–410.

The safety of concerns of lithium-ion batteries continues to be a prevalent obstacle toward their widespread application from vehicle electrification to space exploration. Aside from the highly oxidising and reducing electrode materials, their safety is compounded by an inherent drawback of poor heat dissipation [1]. High-speed imaging with in-situ/operando X-ray CT has been used extensively to study various lithium-ion battery safety features and failure mechanisms [2][3], including thermal failure [4]. However, these are exclusively using synchrotron X-ray sources which are limited in terms of both access and data recording capabilities: high frame rates require the data collection window to be restricted to a few seconds. During lithium-ion battery failure, there are several changes to a cell structure leading up to thermal runaway (TR) which can take minutes, and as a result are often missed. Here, we present an instrument that simulates thermal failure for lab-based radiography at slower imaging speeds and longer recording lengths, which has been validated by correlative synchrotron measurements. The failure mechanisms within a fully charged (100 % SOC, 4.2 V) commercially available LiCoO2 cathode and graphite anode pouch cell (651628-2C, AA Portable Power Corp) rated at 210 mAh are investigated. Three samples are studied using lab-based radiography at a frame rate of 3.75 fps with a 16.1 µm pixel resolution and, for comparison, an additional three samples are studied using synchrotron X-ray sources at a higher speed of 20,000 fps with a 13.3 µm pixel resolution. For the six samples investigated, the total time taken from a start temperature of 80 °C to TR is approximately 20 minutes and the onset temperatures for TR are recorded within the range of 196 °C to 210 °C. The beginning of the TR event (defined as a sample temperature increase greater than 15 °C s-1), where the effects to the electrode structure are the most catastrophic, lasts for approximately 1 s. Operando radiographic images during this event reveal that the structural displacement of electrode layers begins at the centre of the cell and propagates outwards in a wave-like motion. The electrode displacement, as a result, is quantified by cross-correlating Gabor signals and spatiotemporal mapping [5] in both types of datasets. For the lab-based radiography, data is recorded from the start temperature to TR (lasting approximately 20 minutes), and reactions such as the electrolyte decomposition, ca. 105 °C, and separator melting, ca.130 °C are characterised in the context of electrode deformation and gas evolution. Investigations of pre- and post-failure 3D X-ray CT images further verify the uniformity of the pristine (or pre-failure) cell assembly as well as the estimated post-failure behaviour between samples. Finally, by comparison with correlative synchrotron measurements, the instrument for inducing thermal failure for lab-based X-ray CT is proven to be a viable and more accessible method to investigate thermal failure within a 210 mAh pouch cell. While synchrotron data has a higher-speed imaging advantage, it is limited to only recording the short TR event at a high temporal resolution. Whereas continuous imaging in lab-based radiography has the benefit of measuring the slower architectural changes taking place up to TR, albeit at a marginally lower spatial resolution. References [1] D. H. Doughty and E. P. Roth, Interface Mag., 21, 37–44 (2012). [2] D. P. Finegan, M. Scheel, J. B. Robinson, B. Tjaden, M. Di Michiel, G. Hinds, D. J. L. Brett, and P. R. Shearing, Phys. Chem. Chem. Phys., 18, 30912–30919 (2016). [3] D. P. Finegan, M. Scheel, J. B. Robinson, B. Tjaden, I. Hunt, T. J. Mason, J. Millichamp, M. Di Michiel, G. J. Offer, G. Hinds, D. J. L. Brett, and P. R. Shearing, Nat. Commun., 6, 6924 (2015). [4] M. T. M. Pham, J. J. Darst, D. P. Finegan, J. B. Robinson, T. M. M. Heenan, M. D. R. Kok, F. Iacoviello, R. Owen, W. Q. Walker, O. V. Magdysyuk, T. Connolley, E. Darcy, G. Hinds, D. J. L. Brett, and P. R. Shearing, J. Power Sources, 470, 228039 (2020). [5] A. N. P. Radhakrishnan, M. Buckwell, M. Pham, D. P. Finegan, A. Rack, G. Hinds, D. J. L. Brett, and P. R. Shearing, ChemRxiv (2021).

The phenomenon of economic growth is studied by economists and statisticians in various aspects for a long time. Economic theory is devoted to assessing factors of growth in the tradition of R. Solow, R. Barrow, W. Easterly and others. During the last quarter of the century, however, the institutionalists, namely D. North, D. Wallis, B. Weingast as well as D. Acemoglu and J. Robinson, have shown the complexity of the problem of development on the part of socioeconomic and political institutions. As a result, solving the problem of how economic growth affects inequality between countries has proved extremely difficult. The modern world is very diverse in terms of development level, and the article offers a new approach to the formation of the idea of stylized facts using cluster analysis. The existing statistics allows to estimate on a unified basis the level of GDP production by 174 countries of the world for 1992—2016. The article presents a structured picture of the world: the distribution of countries in seven clusters, different in levels of development. During the period under review, there was a strong per capita GDP growth in PPP in the middle of the distribution, poverty in various countries declined markedly. At the same time, in 1992—2016, the difference increased not only between rich and poor groups of countries, but also between clusters.

In editing Plato's Sophist for the new OCT vol. I, ed. E. A. Duke, W. F. Hicken, W. S. M. Nicoll, D. B. Robinson, and J. C. G. Strachan (Oxford, 1995), there was less chance of giving novel information about W = Vind. Supp. Gr. 7 for this dialogue than for others in the volume, since Apelt's edition of 1897 was used by Burnet in 1900 and was based on Apelt's own collation of W. The result was better than the somewhat confused information printed by Burnet, even in his 1905 reprint, for W for the other dialogues in vol. I. (This seems perhaps to have arisen from some misinterpretation by Burnet of Kral's method of reporting W.) But in the Sophist as elsewhere in vol. I collations largely due to Dr W. S. M. Nicoll added new facts about all of BDTWP and their correctors, and the search for testimonia largely carried out by Dr E. A. Duke added new facts in that area. A reviewer counts 66 changes in our text of the Sophist, which may perhaps be a slight over-estimate. Classification of changes as substantive or as falling into different groups is sometimes difficult, but I think plausible figures are as follows. We (myself aided in the earlier sections by Nicoll) have in 25 places made a different choice of readings from the primary mss. and testimonia. We have printed conjectures where Burnet kept a ms. reading in 17 places, but conversely we have reverted to a ms. reading where Burnet had a conjecture in 8 places. We have printed alternative conjectures to conjectures adopted by Burnet in 6 places. So we have actually departed from the primary sources on at most 9 more occasions overall than Burnet. What must be noted is that Burnet had already printed conjectures (including readings from secondary mss.) on something like 87 occasions (12 from secondary mss., 75 from modern conjectures from Stephanus onwards), so our percentage addition to Burnet's departures from the primary sources is modest. Moreover Burnet printed about 25 readings from testimonia; we have followed him in 20 or so of these cases, and this in turn implies that the primary mss. are in error at these further 20 places. It needs to be underlined that though Burnet undoubtedly deserved to be regarded as a safe and cautious editor, nevertheless he departed from the primary mss. on average about twice per Stephanus page in this dialogue. Sometimes, of course, testimonia showed him right to do this, but testimonia cover only a quite small part of this dialogue. Otherwise Burnet accepted almost 90 conjectures. For the Politicus the figures are fairly similar; Burnet accepted 22 Byzantine conjectures and 35–40 more modern ones. The new OCT there adds 15 or so more (not all new) conjectures. (On the Politicus in the new OCT see Robinson [1995].)

MacWhinney, Bates, and colleagues developed the Competition Model in the 1980s as an alternate to Chomskyan models that encapsulate syntax as a special-purpose module. The Competition Model adopted the functional perspective that language serves communicative goals and functions. In contrast to the premise that knowledge of language is innate, the Competition model asserts that language is learned and processed through general cognitive mechanisms that identify and weight phonological, morphological, syntactic, and semantic cues in the language experiences of the learner. These weighted cues guide the language user in the comprehension and production of language forms. The present article provides background on the Competition Model, describes machine simulations of linguistic competition, and extends the principles of the Competition Model to new machine models and applications through deep learning networks. References Bates, E. & MacWhinney, B. (1982). A functionalist approach to grammar. In E. Wanner & L. Gleitman (Eds.), Language acquisition: the state of the art. New York: Cambridge University Press. Bates, E., & MacWhinney, B. (1989). Functionalism and the competition model. In: The Crosslinguistic Study of Sentence Processing, (pp 3-76). B. MacWhinney and E. Bates (Eds.), New York: Cambridge University Press. Devescovi, A., D’Amico, S., Smith, S., Mimica, I., & Bates, E. (1998). The development of sentence comprehension in Italian and Serbo-Croatian: Local versus distributed cues. In: Syntax and Semantics: Vol. 31. Sentence Pocessing: A Cross-Linguistic Perspective, (pp. 345-377). D. Hillert (Ed.), San Diego: Academic Press. Hauser, M. D., Chomsky, N., & Fitch, W. T. (2002). The faculty of language: What it is, who has it, and how did it evolve? Science, 298, 1569-1579. Just, M. A., & Carpenter, P. A. (1980). A theory of reading: From eye fixations to comprehension. Psychological Review, 87, 329-354. Langacker, R. (1989). Foundations of cognitive grammar. Vol. 2: Applications. Stanford: Stanford University Press. Li, P., & MacWhinney, B. (2013). Competition model. In: The Encyclopedia of Applied Linguistics. C. A. Chapelle (Ed.), Malden, MA: Wiley. MacWhinney, B. (1987). The competition model. In: Mechanisms of Language Acquisition, (pp.249-308). B. MacWhinney (Ed.).Hillsdale, NJ: Lawrence Erlbaum. MacWhinney, B. (2001). The competition model: The input, the context, and the brain. In: Cognition and Second Language Instruction, (pp. 69–90). P. Robinson (Ed.), New York: Cambridge University Press. MacWhinney, B. (2008). A Unified Model. In: Handbook of Cognitive Linguistics and Second Language Acquisition, (pp. 341-371). P. Robinson & N. Ellis (Eds.). Mahwah, NJ: Lawrence Erlbaum Associates. MacWhinney B. (2012). The logic of the Unified Model. In: The Routledge Handbook of Second Language Acquisition, (pp. 211–227). S. Gass and A. Mackey (Eds.). New York: Routledge. MacWhinney, B. (2015). Multidimensional SLA. In: Usage-Based Perspectives on Second Language Learning, (pp. 22-45). S. Eskilde and T. Cadierno (Eds.). New York: Oxford University Press. MacWhinney, B., Bates, E. & Kliegl, R. (1984). Cue validity and sentence interpretation in English, German, and Italian. Journal of Verbal Learning and Verbal Behavior, 23, 127-150. MacWhinney, B., Leinbach, J., Taraban, R., & McDonald, J. (1989). Language learning: Cues or rules? Journal of Memory and Language, 28, 255-277. McClelland, J. L., & Rumelhart, D. E. (1986). Parallel Distributed Processing. Explorations in the Microstructure of Cognition. Volume 2: Psychological and Biological Models. Cambridge, MA: MIT Press. Presson, N. & MacWhinney, B. (2011). The Competition Model and language disorders. In: Handbook of Psycholinguistic and Cognitive Processes, (pp. 31-48). J. Guendozi, F. Loncke, and M. Williams (Eds.). New York: Psychology Press. Sokolov, J. L. (1988). Cue validity in Hebrew sentence comprehension. Journal of Child Language, 15, 129-156. Taraban, R. (2004). Drawing learners’ attention to syntactic context aids gender-like category induction. Journal of Memory and Language, 51(2), 202-216. Taraban, R. (2017). Hate, white supremacy, PTSD, and metacognition. In: Improve With Metacognition [online]. L. Scharff, A. Richmond, & J. Draeger (Eds.). Retrieved from: www.improvewithmetacognition.com. Taraban, R., & Kempe, V. (1999). Gender processing in native and non-native Russian speakers. Applied Psycholinguistics, 20, 119-148. Taraban, R., McDonald, J., & MacWhinney, B. (1989). Category learning in a connectionist model: Learning to decline the German definite article. In R. Corrigan, F. Eckman, & M. Noonan (Eds.), Linguistic categorization (pp. 163-193). Philadelphia: Benjamins. Taraban, R., & Roark, B. (1996). Competition in learning language-based categories. Applied Psycholinguistics, 17, 125-148.

Organic and metalorganic reactants have become promising for long-lifetime flow batteries. Synthetic chemistry unlocks a wide design space to tailor reactant redox potential, solubility, chemical and electrochemical stability, redox kinetics, and transport properties. Minimizing the crossover of reactants through the membrane or separator is one crucial design goal. To that end, this work contributes a systematic evaluation of size- and charge-based effects on small molecule permeability through Nafion. These results inform the design of flow battery electrolytes that improve the transport selectivity of ion exchange membranes. Some recent flow battery designs have included crossover suppression strategies based on size and charge of reactants. One option is to leverage size-exclusion, for example by tethering redox-active moieties to polymer backbones,1,2 or by oligomerizing redox-active monomers.3-5 A charge-based strategy has been employed to decrease viologen crossover: sulfonate6 or phosphonate7 solubilizing groups were attached to the redox active core and paired with a cation exchange membrane, reducing crossover compared to previous iterations of this chemistry. Crossover rates of some organic-based flow battery molecules have been estimated to be very low, but other considerations must be balanced for designing viable battery technology. For example, electrolyte cost and solubility may be in direct tension with a crossover suppression strategy based on increasing redox mediator size.8 Untangling the effects of different membrane-molecule selectivity mechanisms is a valuable step on the path to advancing redox active molecule design. This work evaluates a set of quinones in which size is varied by the number of aromatic rings (e.g. hydroquinone, anthraquinone) and charge number is varied almost independently through sulfonation. Each sulfonate moiety contributes a -1 charge, increasing the magnitude of the molecule charge number with the same sign as the fixed charges in Nafion. Effective size of solvated species is accessed through rotating disk electrode voltammetry: Stokes radii are calculated from measured diffusion coefficients. We found over an order of magnitude permeability reduction per sulfonate, emphasizing the importance of charge-based exclusion for ion exchange membranes. In comparison, size-exclusion effects are less impactful. For example, the Stokes radius of anthraquinone 2,6-disulfonate (AQDS) is twice that of hydroquinone 2,5-disulfonate but their permeabilities fall within the same order of magnitude. 1. T. Hagemann, J. Winsberg, M. Grube, I. Nischang, T. Janoschka, N. Martin, M. D. Hager, and U. S. Schubert, Journal of Power Sources, 378, 546 (2018). 2. T. Janoschka, N. Martin, U. Martin, C. Friebe, S. Morgenstern, H. Hiller, M. D. Hager, and U. S. Schubert, Nature, 527, 78 (2015). 3. M. J. Baran, M. N. Braten, E. C. Montoto, Z. T. Gossage, L. Ma, E. Chenard, J. S. Moore, J. Rodrıguez-Lopez, and B. A. Helms, Chemistry of Materials, 30, 3861 (2018). 4. K. H. Hendriks, S. G. Robinson, M. N. Braten, C. S. Sevov, B. A. Helms, M. S. Sigman, S. D. Minteer, and M. S. Sanford, ACS Central Science, 4, 189 (2018). 5. S. E. Doris, A. L. Ward, A. Baskin, P. D. Frischmann, N. Gavvalapalli, E. Chenard, C. S. Sevov, D. Prendergast, J. S. Moore, and B. A. Helms, Angewandte Chemie, 129, 1617 (2017). 6. C. Debruler, B. Hu, J. Moss, J. Luo, and T. L. Liu, ACS Energy Letters, 3, 663, (2018). 7. S. Jin, E. M. Fell, L. Vina-Lopez, Y. Jing, P. W. Michalak, R. G. Gordon, and M. J. Aziz, Advanced Energy Materials, 10, (2020). 8. M. L. Perry, J. D. Saraidaridis, and R. M. Darling, Current Opinion in Electrochemistry, 21, 311 (2020).

Spatial and temporal gradients in reactant concentration, influenced by local microstructure and surface properties, govern the performance and durability of various advanced electrochemical systems. The cell and stack performance is typically assessed using traditional electrochemical diagnostics (e.g. polarization curves, electrochemical impedance spectroscopy) and the influence of materials is macroscopically evaluated based on empirical comparison of novel materials with the current state-of-the-art. While this is a valid approach to identify promising candidates, valuable information is lost due to the difficulty of identifying performance-limiting factors. Operando imaging of electrochemical systems, in tandem with complementary electrochemical diagnostics, has been instrumental in the development of advanced polymer electrolyte fuel cells1,2 and, more recently, lithium-ion batteries3,4. Over the past few years, several groups have developed novel imaging and spectroscopic techniques for operando characterization of redox flow batteries, which is the focus of this work. Wong et al. employed fluorescence microscopy and particle velocimetry to image concentration and velocity distributions near the electrode-flow field interface5. Tanaka et al. visualized flow distribution in redox flow batteries with infrared thermography6. Zhao et al. employed in-situ nuclear magnetic resonance to track reaction mechanisms occurring within the electrolyte7. Finally, several groups recently employed X-ray tomographic microscopy to visualize gas pockets within the liquid electrolyte imbibed porous electrode8–10. While these methods have provided important insights, an approach that enables quantitative mapping of species concentrations, in a non-invasive fashion and within an operating cell, has remained elusive. In this presentation, I will discuss our recent efforts to develop neutron radiography as an operando characterization method for non-aqueous redox flow batteries. We leverage the high attenuation of organic materials (i.e., high hydrogen content) in solution and, combined with isotopic labelling, we perform subtractive neutron imaging to quantify the concentration of active species and supporting electrolytes. To demonstrate the potential of this diagnostic tool, we characterize active species concentration distribution within a redox flow cell in a single electrolyte configuration with a non-aqueous electrolyte containing a TEMPO/TEMPO+ redox couple and study the influence of electrode microstructure, membrane type (e.g. porous or dense), and flow field design. To resolve the concentration profiles across the different layers, we employ the in-plane imaging configuration11 and correlate these concentration profiles to cell performance via polarization measurements under different operating conditions. In the final part of the talk, I will discuss our latest experimental campaign in which we investigated the use of energy-selective neutron radiography to deconvolute concentrations of active species and supporting electrodes during operation. References 1 P. Boillat, E. H. Lehmann, P. Trtik and M. Cochet, Curr. Opin. Electrochem., , DOI:https://doi.org/10.1016/j.coelec.2017.07.012. 2 J. Eller, T. Rosén, F. Marone, M. Stampanoni, A. Wokaun and F. N. Büchi, J. Electrochem. Soc., 2011, 158, B963. 3 B. Michalak, H. Sommer, D. Mannes, A. Kaestner, T. Brezesinski and J. Janek, Sci. Rep., 2015, 5, 15627. 4 D. P. Finegan, M. Scheel, J. B. Robinson, B. Tjaden, I. Hunt, T. J. Mason, J. Millichamp, M. Di Michiel, G. J. Offer, G. Hinds, D. J. L. Brett and P. R. Shearing, Nat. Commun., 2015, 6, 6924. 5 A. A. Wong, M. J. Aziz and S. Rubinstein, ECS Trans. , 2017, 77, 153–161. 6 H. Tanaka, Y. Miyafuji, J. Fukushima, T. Tayama, T. Sugita, M. Takezawa and T. Muta, J. Energy Storage, 2018, 19, 67–72. 7 E. W. Zhao, T. Liu, E. Jónsson, J. Lee, I. Temprano, R. B. Jethwa, A. Wang, H. Smith, J. Carretero-González, Q. Song and C. P. Grey, Nature, 2020, 579, 224–228. 8 R. Jervis, L. D. Brown, T. P. Neville, J. Millichamp, D. P. Finegan, T. M. M. Heenan, D. J. L. Brett and P. R. Shearing, J. Phys. D. Appl. Phys., , DOI:10.1088/0022-3727/49/43/434002. 9 F. Tariq, J. Rubio-Garcia, V. Yufit, A. Bertei, B. K. Chakrabarti, A. Kucernak and N. Brandon, Sustain. Energy Fuels, 2018, 2, 2068–2080. 10 K. Köble, L. Eifert, N. Bevilacqua, K. F. Fahy, A. Bazylak and R. Zeis, J. Power Sources, , DOI:10.1016/j.jpowsour.2021.229660. 11 P. Boillat, D. Kramer, B. C. Seyfang, G. Frei, E. Lehmann, G. G. Scherer, A. Wokaun, Y. Ichikawa, Y. Tasaki and K. Shinohara, Electrochem. commun., 2008, 10, 546–550.

Lithium-ion batteries (LIBs) find use in a wide range of applications, each of which has its own design specifications and practical requirements. With regards to the role of LIBs in mitigating carbon emissions, and therefore climate change, it is desirable to support the rapidly growing adoption of electric vehicles and renewable grid-storage systems via development of higher energy density, lower cost, and improved rate capability. However, the design of energy-dense, low-cobalt, and/or high-rate cell chemistries is impeded by inherent trade-offs with cycling and calendar lifetimes. A key goal for the automotive and utilities industries is therefore to predict battery lifetime for new cell designs and chemistries at a very high level of confidence, for example through improved understanding of the physical and chemical processes that determine the state of health of battery systems. As part of the Faraday Institution, the UK’s independent institute for electrochemical energy storage technology, the Battery Degradation Project has built new understanding of the underlying physical and chemical processes that can lead to degradation in energy-dense NMC811/graphite lithium-ion cells as a model system. Led by the University of Cambridge (Clare Grey PI) in collaboration with eight UK universities, the research consortium is working closely with industry partners to create a new hub for lithium-ion battery research and to address key challenges and opportunities in the field. This presentation will give an overview of the research consortium’s diverse membership, key milestones, and technical progress. To date, the consortium has been applying a variety of analytical techniques to study degradation processes in NMC811/graphite cells. For example, electrochemical testing and operando solid-state 7Li nuclear magnetic resonance spectroscopy (NMR) were combined to monitor processes in both electrodes individually, including Li-ion mobility and its changes with temperature.1 The method is now being applied to understand how the dynamics are affected by long-term structural damage to the NMC811 material. A series of differential voltage analysis experiments have been paired with operando X-ray diffraction measurements to propose the mechanism behind a critical ‘turning point’ in NMC811/graphite cells, following which degradation accelerates significantly.2 New operando cell designs have been developed to measure changes in cell pressure,3 which are being paired with solution NMR spectroscopy,4 and differential electrochemical mass spectrometry to quantify electrolyte oxidation. The role and rate of transition-metal dissolution in cells under stressed cycling conditions, namely cycling at high temperature (60 °C) and high upper cut-off voltages (4.4, 4.6 V), has been investigated.5 Scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX) measurements were coupled with time-of-flight secondary-ion mass spectrometry (Tof-SIMS) to observe the Al-containing phases at NMC811 surfaces and grain boundaries.7 New spectroscopic methods are also being developed, including Kerr-gated Raman, which allows sensitive measurements of electrode materials and electrolytes with lower background signal than conventional Raman spectroscopy.6 Finally, X-ray computed tomography methods have been developed that enable operando imaging and spectroscopic mapping of heterogeneities at a sub-particle length scale and across large areas of electrodes, which are being applied to study the origins of microstructural defects, cracking, and redox activity during charging, cycling, or storage.8,9 Reference s: K. Märker, C. Xu, and C. P. Grey, J. Am. Chem. Soc., 142, 17447–17456 (2020). W. M. Dose, C. Xu, C. P. Grey, and M. F. L. De Volder, Cell Rep. Phys. Sci., 1, 100253 (2020). N. Ryall and N. Garcia-Araez, J. Electrochem. Soc., 167, 110511 (2020). B. L. D. Rinkel, D. S. Hall, I. Temprano, and C. P. Grey, J. Am. Chem. Soc., 142, 15058–15074 (2020). Z. Ruff, C. Xu, and C. P. Grey, J. Electrochem. Soc., 168, 060518 (2021). L. Cabo-Fernandez, A. R. Neale, F. Braga, I. V. Sazanovich, R. Kostecki, and L. J. Hardwick, Phys. Chem. Chem. Phys., 21, 23833–23842 (2019). J. Lee, H. Amari, M. Bahri, Z. Shen, C. Xu, Z. Ruff, C. P. Grey, O. Ersen, A. Aguadero, N. D. Browning, and B. L. Mehdi, Batter. Supercaps, 4, 1813–1820 (2021). T. M. M. Heenan, A. Wade, C. Tan, J. E. Parker, D. Matras, A. S. Leach, J. B. Robinson, A. Llewellyn, A. Dimitrijevic, R. Jervis, P. D. Quinn, D. J. L. Brett, and P. R. Shearing, Adv. Energy Mater., 10, 2002655 (2020). C. Tan, A. S. Leach, T. M. M. Heenan, H. Parks, R. Jervis, J. N. Weker, D. J. L. Brett, and P. R. Shearing, Cell Rep. Phys. Sci., 100647 (2021).

To improve online learning pedagogy within the field of paralegal education, this study investigated how paralegal students and paralegal instructors perceived the effectiveness of synchronous and asynchronous online paralegal courses. This study intended to inform paralegal instructors and course developers how to better design, deliver, and evaluate effective online course instruction in the field of paralegal studies.Survey results were analyzed using independent samples t-test and correlational analysis, and indicated that overall, paralegal students and paralegal instructors positively perceived synchronous and asynchronous online paralegal courses. Paralegal instructors reported statistically significant higher perceptions than paralegal students: (1) of instructional design and course content in synchronous online paralegal courses; and (2) of technical assistance, communication, and course content in asynchronous online paralegal courses. Instructors also reported higher perceptions of the effectiveness of universal design, online instructional design, and course content in synchronous online paralegal courses than in asynchronous online paralegal courses. Paralegal students reported higher perceptions of asynchronous online paralegal course effectiveness regarding universal design than paralegal instructors. No statistically significant differences existed between paralegal students’ perceptions of the effectiveness of synchronous and asynchronous online paralegal courses. A strong, negative relationship existed between paralegal students’ age and their perceptions of effective synchronous paralegal courses, which were statistically and practically significant. Lastly, this study provided practical applicability and opportunities for future research. Akyol, Z., & Garrison, D. R. (2008). The development of a community of inquiry over time in an online course: Understanding the progression and integration of social, cognitive and teaching presence. Journal of Asynchronous Learning Networks, 12, 3-22. Retrieved from https://files.eric.ed.gov/fulltext/EJ837483.pdf Akyol, Z., Garrison, D. R., & Ozden, M. Y. (2009). Online and blended communities of inquiry: Exploring the developmental and perceptional differences. The International Review of Research in Open and Distributed Learning, 10(6), 65-83. Retrieved from http://www.irrodl.org/index.php/irrodl/article/view/765/1436 Allen, I. E., & Seaman, J. (2014). Grade change: Tracking online education in the United States. Babson Park, MA: Babson Survey Research Group and Quahog Research Group, LLC. Retrieved from https://www.utc.edu/learn/pdfs/online/sloanc-report-2014.pdf Alreck, P. L., & Settle, R. B. (2004). The Survey Research Handbook (3rd ed.) New York, NY: McGraw-Hill Irwin. American Association for Paralegal Education (2013, Oct.). AAfPE core competencies for paralegal programs. Retrieved from https://cdn.ymaws.com/www.aafpe.org/resource/resmgr/Docs/AAfPECoreCompetencies.pdf American Bar Association, Standing Committee on Paralegals. (2017). https://www.americanbar.org/groups/paralegals.html American Bar Association, Standing Committee on Paralegals (2013, September). Guidelines for the approval of paralegal education programs. Retrieved from https://www.americanbar.org/content/dam/aba/administrative/paralegals/ls_prlgs_2013_paralegal_guidelines.authcheckdam.pdf Astani, M., Ready, K. J., & Duplaga, E. A. (2010). Online course experience matters: Investigating students’ perceptions of online learning. Issues in Information Systems, 11(2), 14-21. Retrieved from http://iacis.org/iis/2010/14-21_LV2010_1526.pdf Bailey, C. J., & Card, K. A. (2009). Effective pedagogical practices for online teaching: Perception of experienced instructors. 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У статті досліджується актоіллокутивний потенціал англійського побутового дискурсу виправдання шляхом зіставлення іллокутивних характеристик частотних у дискурсі виправдання мовленнєвих актів. Спираючись на змодельовані конструкти змісту виправдання, дифенсивну інтенцію мовця визначено передумовою породження дискурсу виправдання. У результаті вивчення наявних у науковій літературі класифікацій мовленнєвих актів визначено, що домінантна іллокутивна сила дискурсу виправдання включає складові інформування та переконування, що типово представлено констативом та асертивом. Власне мовленнєвий акт виправдання визначено як кредитив з включеною перлокуцією винесення виправдального вердикту, яким регулюється міжсуб’єктна взаємодія. Література References Вендлер З. Причинные отношения // Новое в зарубежной лингвистике. – Вып. 18:Логический анализ естественного языка. – М.: Прогресс, 1986. – С. 264–277.Vendler, Z. (1986). Prichinnije otnoshenija [Causal Relations]. 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Слово как действие // Новое в зарубежной лингвистике. – Вып. 17: ТРА. – М. :Прогресс, 1986. – С. 22–129.Austin, J. (1986). Slovo kak deistvije [Word as Action] In: New in World Linguistics, (pp. 22–129), Issue 17: Speech Acts Theory. M.: Progress. Хилпинен Р. Семантика императивов и деонтическая логика // Новое в зарубежнойлингвистике. – Вып. 18: Логический анализ естественного языка. – М. : Прогресс, 1986. –С. 300–318.Hilpinen, R. (1986). Semantica imperativov i deonticheskaja logica [Semantics of Imperativesand Deontic Logic]. In: New in World Linguistics, (pp. 300–318), Issue 18: Study in Logic ofNatural Language. Moscow: Progress. Шевченко І. С. Дискурс як мисленнєво-комунікативна діяльність / І. С. Шевченко,О. І. Морозова // Дискурс як когнітивно-комунікативний феномен: [кол. монографія] / [зазаг. ред. І. С. Шевченко]. – Х. : Константа, 2005. – С. 21–28.Shevchenko, I. (2005). Dyskurs jak myslenevo-komunikatyvna diyalnist [Discourse as Mentaland Communicative Activity]. 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Continuous, pinhole-free thin films of transparent conductive materials (TCMs) with p- and n-type conductivity are critical components of optoelectronic devices including photovoltaics (PV), transparent electronics, and LEDs [1]. TCMs with n-type conductivity are widely available in the form of semiconducting oxides [2]; however, p-type TCMs (hole transport materials, HTMs) with suitable conductivity are comparatively rare [1]. Particularly in the rapidly growing field of thin film perovskite PV, device-quality thin films of HTMs with high stability and conductivity are urgently needed to replace the organic HTMs typically employed in perovskite PV research [3]. As such, techniques to deposit inorganic HTM thin films are desired. With a focus on applying HTMs in optoelectronic devices at the commercial scale, these materials must be deposited by a scalable technique yielding thin, continuous, pinhole-free films. Chemical vapor deposition (CVD) is a highly scalable thin film deposition technique widely used in industry, with a proven ability to yield high-quality thin films on large-area substrates [4]. A variety of n-type TCMs are accessible by CVD techniques, but few CVD methods exist for p-type TCMs; examples include atomic layer deposition of NiOx and VOx [5]. The cuprous halides (CuX, X = Cl, Br, I), which are optically transparent p-type semiconductors with bandgaps ~3 eV, are promising inorganic HTM candidates. Cuprous iodide is of particular interest due to its low resistivity (~10-2 Ohm·cm), high hole concentration and mobility (~1019 cm-3 and ~1-10 cm2V-1s-1, respectively), and its valence band maximum position (ionization potential: 5.0-5.4 eV), which is well-aligned with common perovskite absorber materials [6]. While CuI crystallite arrays have been obtained by metal-organic CVD [7], CVD of continuous CuI thin films has only been achieved by a two-step vapor conversion process, requiring initial deposition of a copper chalcogen followed by vapor-phase conversion to the halide [6]. Our group has recently published a CVD technique enabling direct deposition of continuous CuBr thin films via CVD reaction between hydrogen bromide and vinyltrimethylsilane(hexafluoroacetylacetonato)copper(I) [Cu(hfac)(vtms)] [8], and this technique has been extended to deposition of CuI. X-ray photoelectron spectroscopy indicates pure CuI films with an atomic ratio of approximately 1:1 Cu:I, and x-ray diffraction confirms deposition of γ-CuI. Similar to our observations for CuBr films, substrate identity has significant effects on CuI film continuity. Progress towards CVD of continuous CuI films on substrates of interest for practical application in optoelectronic devices will be discussed, with a particular focus on perovskite PV. [1] A. N. Fioretti and M. Morales-Masis, "Bridging the p-type transparent conductive materials gap: synthesis approaches for disperse valence band materials," J. Photon. Energy, 10, 042002 (2020). [2] M. Morales-Masis, S. De Wolf, R. Woods-Robinson, J. W. Ager, and C. Ballif, "Transparent Electrodes for Efficient Optoelectronics," Adv. Electron. Mater., 3, 1600529 (2017). [3] B. Gil, A. J. Yun, Y. Lee, J. Kim, B. Lee, and B. Park, "Recent Progress in Inorganic Hole Transport Materials for Efficient and Stable Perovskite Solar Cells," Electron. Mater. Lett., 15, 505 (2019). [4] R. Gordon, "Chemical Vapor Deposition of Coatings on Glass," J. Non-Cryst. Solids, 218, 81 (1997). [5] J. A. Raiford, S. T. Oyakhire, and S. F. Bent, "Applications of atomic layer deposition and chemical vapor deposition for perovskite solar cells," Energy Environ. Sci., 13, 1997 (2020). [6] R. Heasley, L. M. Davis, D. Chua, C. M. Chang, and R. G. Gordon, "Vapor Deposition of Transparent, p-Type Cuprous Iodide Via a Two-Step Conversion Process," ACS Appl. Energy Mater., 1, 6953 (2018). [7] V. Gottschalch, S. Blaurock, G. Benndorf, J. Lenzner, M. Grundmann, and H. Krautscheid, "Copper iodide synthesized by iodization of Cu-films and deposited using MOCVD," J. Cryst. Growth, 471, 21 (2017). [8] C. M. Chang, L. M. Davis, E. K. Spear, and R. G. Gordon, "Chemical Vapor Deposition of Transparent, p-Type Cuprous Bromide Thin Films," Chem. Mater., 33, 1426 (2021).

We have previously used a series of insertion-deletion mutants of the mutationally activated v-rasH gene to identify several regions of the encoded protein that are dispensable for cellular transformation (B. M. Willumsen, A. G. Papageorge, H.-F. Kung, E. Bekesi, T. Robins, M. Johnsen, W. C. Vass, and D. R. Lowy, Mol. Cell. Biol. 6:2646-2654, 1986). To determine if some of these amino acids are more important for the biological activity of c-rasH, we have now tested many of the same insertion-deletion mutants in the c-rasH form for their ability to transform NIH 3T3 cells. Since the transforming activity of c-rasH is low, we have used cotransfection with the bovine papillomavirus (BPV) genome to develop a more sensitive transformation assay for c-rasH mutants. The increased sensitivity of the assay, which is seen both in focal transformation and in anchorage-independent growth, is mediated by cooperation between the BPV E5 gene and ras. E5-dependent cooperation was seen for v-rasH as well as for c-rasH, which suggests that the major effect of E5 was to increase the susceptibility of the cell to transformation to a given level of ras activity. The cooperation assay was used to test the potential importance, in c-rasH, of codons 93 to 108, 123 to 130, and 166 to 183, which were nonessential for v-rasH transformation. Relative to the respective transforming activity of wild-type c-rasH and v-rasH, mutants with lesions in codons 102 and 103 were significantly less active in their c-rasH forms than in their v-rasH forms. We conclude that a region including amino acids 102 and 103 encodes a function that is more critical to c-rasH than to v-rasH. Guanine nucleotide exchange is one function that is compatible with such a phenotype.

We have previously used a series of insertion-deletion mutants of the mutationally activated v-rasH gene to identify several regions of the encoded protein that are dispensable for cellular transformation (B. M. Willumsen, A. G. Papageorge, H.-F. Kung, E. Bekesi, T. Robins, M. Johnsen, W. C. Vass, and D. R. Lowy, Mol. Cell. Biol. 6:2646-2654, 1986). To determine if some of these amino acids are more important for the biological activity of c-rasH, we have now tested many of the same insertion-deletion mutants in the c-rasH form for their ability to transform NIH 3T3 cells. Since the transforming activity of c-rasH is low, we have used cotransfection with the bovine papillomavirus (BPV) genome to develop a more sensitive transformation assay for c-rasH mutants. The increased sensitivity of the assay, which is seen both in focal transformation and in anchorage-independent growth, is mediated by cooperation between the BPV E5 gene and ras. E5-dependent cooperation was seen for v-rasH as well as for c-rasH, which suggests that the major effect of E5 was to increase the susceptibility of the cell to transformation to a given level of ras activity. The cooperation assay was used to test the potential importance, in c-rasH, of codons 93 to 108, 123 to 130, and 166 to 183, which were nonessential for v-rasH transformation. Relative to the respective transforming activity of wild-type c-rasH and v-rasH, mutants with lesions in codons 102 and 103 were significantly less active in their c-rasH forms than in their v-rasH forms. We conclude that a region including amino acids 102 and 103 encodes a function that is more critical to c-rasH than to v-rasH. Guanine nucleotide exchange is one function that is compatible with such a phenotype.

Sharenting is a habit of using social media to share content that disseminates pictures, videos, information, and parenting styles for their children. The purpose of this article is to describe the sharenting phenomenon that occurs among young parents, and the importance of parenting programs, rather than protecting children's privacy. Writing articles use a qualitative approach as a literature review method that utilizes various scientific articles describing the sharenting phenomenon in various countries. The findings show that sharenting behaviour can create the spread of children's identity openly on social media and tends not to protect children's privacy and even seems to exploit children. Apart from that, sharenting can also create pressure on the children themselves and can even have an impact on online crime. 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The present article involves a qualitative study of the framing of dementia in ‘Alzheimer’s and Dementia’, the Journal of the Alzheimer’s Association, published in 2016. The aim of this study is to elucidate how dementia is framed qualitatively in the corpus consisting of scientific articles involving dementia published in ‘Alzheimer’s and Dementia’. The results of the qualitative analysis indicate that dementia is represented in ‘Alzheimer’s and Dementia’ in 2016 as the frames associated with gender, age, costs, caregiver and care-recipients, disability and death, health policy, spatial orientation, medical condition, and ethnic groups. These findings are further discussed in the article. References Andrews, J. (2011). We need to talk about dementia. Journal of Research in Nursing, 16(5),397–399. Aronowitz, R. (2008). Framing Disease: An Underappreciated Mechanism for the SocialPatterning Health. Social Science & Medicine, 67, 1–9. Bayles, K. A. (1982). 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Abstract Background Changing climate and demographic trends have led to recent increases in the incidence of tick-borne illnesses. Early diagnosis of Lyme disease (LD) is critical for initiation of antibiotics to mitigate symptoms and prevent late manifestations. In patients not presenting with a typical erythema migrans rash, 2-tiered serologic testing is recommended to support a diagnosis of LD. However, 2-tiered testing is limited by ambiguity in interpretation and low sensitivity in early disease, highlighting an unmet clinical need for alternative diagnostic approaches. We identified a clinical signal for early LD based on evaluation of the T-cell response to B. burgdorferi infection. Methods We immunosequenced T-cell receptor (TCR) repertoires in blood samples from 3 independent cohorts of patients with laboratory-confirmed or clinically diagnosed early LD and endemic/non-endemic controls to identify 251 public, LD-associated TCRs. These TCRs were used to train a classifier that identified early LD with 99% specificity. Classifier sensitivity was evaluated in 211 LD cases and 2631 endemic controls and compared to that of standard 2-tiered testing (STTT). Biologic specificity was assessed by correlating TCR assay scores with clinical measures and by mapping the antigen specificity of Lyme-associated TCRs to B. burgdorferi antigens. Figure 1. LD-associated TCRs distinguish cases (orange) from controls (blue) in training cohorts. (A) Logistic-growth curve used to define a scoring function. (B) Positive-call threshold (99th percentile in endemic controls). Results In early LD, TCR testing demonstrated a 1.9-fold increase in sensitivity compared to STTT (56% vs 30%), with a 3.1-fold increase ≤4 days from the onset of symptoms (44% vs 14%). TCR positivity predicted subsequent seroconversion in 37% of initially STTT-negative patients, suggesting the T-cell response is detectable before the humoral response. While positivity for both tests declined following treatment, greater declines in posttreatment sensitivity were observed for STTT compared to TCR testing. Higher TCR scores were associated with measures of disease severity, including abnormal liver function tests, disseminated rash, and number of symptoms. A subset of LD-associated TCRs mapped to B. burgdorferi antigens, demonstrating the high specificity of a TCR immunosequencing approach. Figure 2. Validation of the TCR classifier in the JHU cohort and other holdout endemic controls. Distribution of model scores (A) and assay sensitivity (B). Model scores (C) and ROC (D) curves by serostatus. Figure 3. Clinical correlates of TCR scoring. (A) Liver function test; (B) lymphocyte count, (C) rash presentation, (D) number of symptoms. Conclusion T-cell-based testing has potential clinical utility as a sensitive and specific diagnostic for early LD, particularly in the initial days of illness. Disclosures Sudeb C. Dalai, MD, PhD, Adaptive Biotechnologies (Employee, Shareholder) Julia Greissl, PhD, Microsoft (Employee, Shareholder) Mitch Pesesky, PhD, Adaptive Biotechnologies (Employee, Shareholder) Allison W. Rebman, MPH, Global Lyme Alliance (Research Grant or Support)Steven and Alexandra Cohen Foundation (Research Grant or Support) Mark J. Soloski, PhD, NIH grant P30 AR070254 (Grant/Research Support)Steven and Alexandra Cohen Foundation (Research Grant or Support) Elizabeth J. Horn, PhD, Adaptive Biotechnologies (Research Grant or Support)Bay Area Lyme Foundation (Research Grant or Support)Lyme Disease Biobank (Employee)Steven and Alexandra Cohen Foundation (Research Grant or Support) Jennifer N. Dines, MD, Adaptive Biotechnologies (Employee, Shareholder) Rachel M. Gittelman, PhD, Adaptive Biotechnologies (Employee, Shareholder) Thomas M. Snyder, PhD, Adaptive Biotechnologies (Employee, Shareholder) Ryan O. Emerson, PhD, Adaptive Biotechnologies (Other Financial or Material Support, Employment with Adaptive Biotechnologies during the time of this study) Edward Meeds, PhD, Microsoft (Employee, Shareholder) Thomas Manley, MD, Adaptive Biotechnologies (Other Financial or Material Support, Declares employment with Adaptive Biotechnologies during the time of this study) Ian M. Kaplan, PhD, Adaptive Biotechnologies (Employee, Shareholder) Lance Baldo, MD, Adaptive Biotechnologies (Employee, Shareholder, Leadership Interest) Jonathan M. Carlson, PhD, Microsoft (Employee, Shareholder) Harlan S. Robins, PhD, Adaptive Biotechnologies (Board Member, Employee, Shareholder) John Aucott, MD, Adaptive Biotechnologies (Advisor or Review Panel member)Bay Area Lyme Foundation (Other Financial or Material Support, Scientific Advisory Board member)Department of Health and Human Services (Other Financial or Material Support, Past Chair, 2018, HHS Tick-borne Disease Working Group, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary of Health)Expert testimony (Other Financial or Material Support, Expert testimony)Global Lyme Alliance (Research Grant or Support)Pfizer (Consultant)Steven and Alexandra Cohen Foundation (Research Grant or Support)Tarsus Pharmaceuticals (Consultant)

La ermoza istorya de Robinzon o la mizerya: Sephardi Versions of Robinson CrusoeIn the second half of the 19th century the Haskalah, an intellectual movement whose objective was to educate and westernize Eastern European Jews, also reached the Sephardic communities in the Ottoman Empire. As a result, there emerged Sephardic modern secular literature, represented mainly by narrative fiction, theatre plays and press. It should be added that modern Sephardic literature is primarily based on translations or adaptations of Western novels. Among these texts we find Sephardic editions of classics of European literature, such as Romeo and Juliet by William Shakespeare, Robinson Crusoe by Daniel Defoe and Gulliver’s Travels by Jonathan Swift.I have found four different versions of Robinson Crusoe that were written in Judeo-Spanish and edited in aljamía. Two of them were published serially in Sephardi press, one in Salonica in 1881 and the other in Constantinople in 1900. The other two editions were prepared by Ben Tsiyon Taragan and published as complete versions, the first one in Jerusalem in 1897 and the second one in Constantinople in 1924. The aim of this paper is to provide a brief analysis of the Sephardic adaptations of Robinson Crusoe by Taragan. La ermoza istorya de Robinzon o la mizerya: sefardyjska wersja Robinsona CrusoeHaskala, zwana także Żydowskim Oświeceniem, to ruch intelektualny, którego celem było odrodzenie kulturowe i społeczne Żydów z EuropyWschodniej oraz ich integracja ze środowiskiem lokalnym. W drugiej połowie XIX wieku Haskala objęła także społeczność Żydów sefardyjskich zamieszkujących tereny należące do Imperium Osmańskiego, w wyniku czego powstała współczesna, świecka literatura sefardyjska reprezentowana głównie przez prozę, sztuki teatralne oraz prasę. Warto dodać, że współczesna literatura sefardyjska oparta jest przede wszystkim na przekładach lub adaptacjach powieści uważanych za klasykę literatury europejskiej, takich jak Romeo i Julia Williama Szekspira, Robinson Crusoe Daniela Defoe czy Podróże Guliwera Jonathana Swifta.W trakcie prowadzonych przeze mnie badań natrafiłam na cztery różne judeo-hiszpańskie wersje Robinsona Crusoe, które zapisane zostały alfabetem hebrajskim, tzw. pismem Rasziego. Dwie z nich ukazały się w prasie sefardyjskiej, jako powieść w odcinkach, pierwsza w Salonikach w 1881 r., a druga w Konstantynopolu w 1900 r. Pozostałe dwie, autorstwa Ben Tsiyona Taragana, zostały wydane w całości, pierwsza w Jerozolimie w 1897 r., druga zaś w Konstantynopolu w 1924 r. Celem tego artykułu jest prezentacja oraz krótka analiza sefardyjskich adaptacji Robinsona Crusoe autorstwa B. T. Taragana.

On the example of four micro-plots, the key theses of the economic views of the Nobel laureate S. Kuznets have been revealed. The main papers of Kuznets and his supervisor – W. K. Mitchell have been analysed, the reception of methods used by S. Kuznets in the prospect of economic theory has been traced. The reception of the mechanics of S. Kuznets’ research in modern political economy theory, referring to the research of D. Acemoglu and J. Robinson has been considered. In Appendix to this paper, a brief analysis of the political interpretation of the S. Kuznets cycle theory, proposed by D. Acemoglu and J. Robinson has presented. The research presented in the article summarizes the experience of research on economic views of S. Kuznets and emphasizes the prospect of using the author’s experiential optics.

For a continuous and positive function w (λ), λ > 0 and µ a positive measure on (0, ∞) we consider the following integral transform D (w, µ) (T ) := ∫0∞w (λ) (λ + T ) −1 dµ (λ) , where the integral is assumed to exist for T a positive operator on a complex Hilbert space H. We show among others that, if A ≥ m 1 > 0, B ≥ m 2 > 0, then ||D (w, µ) (B) − D (w, µ) (A) − D (D (w, µ)) (A) (B − A)|| ≤|B − A|2×[D(w,µ)(m2)−D(w,µ)(m1)−(m2- m1)D’(w,µ)(m1)]/(m2−m1)2 if m1≠m2, ≤ D’’(w, µ)(m)/2 if m1=m2=m, where D (D (w, µ)) is the Fréchet derivative of D (w, µ) as a function of operator and D’’(w, µ) is the second derivative of D (w, µ) as a real function. We also prove the norm integral inequalities for power r ∈ (0, 1] and A, B ≥ m > 0, ||∫01((1−t)A+tB)r−1dt−((A+B)/2)r−1|| ≤ (1−r) (2−r) mr−3||B−A||2/24 and ||((Ar−1+Br−1 )/2) − ∫01((1−t) A+tB)r−1dt|| ≤ (1−r) (2−r) mr−3||B − A||2/12.

W artykule przedstawiono imiona i nazwiska postaci literackich, które pojawiają siępóźniej w utworach innych autorów. Są dwa cele takiego zabiegu: 1) obdarzenie nowychbohaterów imionami i/lub nazwiskami bohaterów innych dzieł; 2) przekazanie sensówmetaforycznych, które niosą nomina propria znane z wybitnych, najpopularniejszychdzieł literackich. Ad 1: Pokazano wtórne zastosowanie nazwisk z dzieł S. Żeromskiegow powieści kryminalnej; przejęcie imienia i nazwiska z powieści A. Szklarskiego przezM. M. Kuźmińskich; odwołania do imion tożsamych u postaci z dawniejszych i nowszychutworów literackich. Ad 2: Pokazano powieściowe użycia antroponimów, które nabrałyznaczenia przenośnego: Kopciuszek, Don Kiszot, Robinson, Faust, Frankenstein, Romeoi Julia, Werter, Alicja (z krainy czarów), Sherlock Holmes, Ania (z Zielonego Wzgórza),Zagłoba, Wołodyjowski, Borejko. Konteksty powieściowe zostały skonfrontowane ze słownikami:Słownik eponimów czyli wyrazów odimiennych, Słownik mitów i tradycji kultury,Skrzydlate słowa i Alfabetycznym wykazem onimów bazowych i ich derywatów B. Dereń.

Analogies between gravitation and electromagnetism have been known since the 1950s. Here, we examine a fairly general type D solution — the exact seven parameter solution of Plebański–Demiański (PD) — to demonstrate these analogies for a physically meaningful spacetime. The two quadratic curvature invariants B2 - E2 and E⋅B are evaluated analytically. In the asymptotically flat case, the leading terms of E and B can be interpreted as gravitoelectric mass and gravitoelectric current of the PD solution, respectively, if there are no gravitomagnetic monopoles present. Furthermore, the square of the Bel–Robinson tensor reads (B2 + E2)2 for the PD solution, reminiscent of the square of the energy density in electrodynamics. By analogy to the energy–momentum 3-form of the electromagnetic field, we provide an alternative way to derive the recently introduced Bel–Robinson 3-form, from which the Bel–Robinson tensor can be calculated. We also determine the Kummer tensor, a tensor cubic in curvature, for a general type D solution for the first time, and calculate the pieces of its irreducible decomposition. The calculations are carried out in two coordinate systems: In the original polynomial PD coordinates and in a modified Boyer–Lindquist-like version introduced by Griffiths and Podolský (GP) allowing for a more straightforward physical interpretation of the free parameters.

The first compound with a quadruple bond was described by Al Cotton et al on August of 1964 (Cotton, F. A.; Curtis, N. F.; Harris, C. B.; Johnson, B. F. G.; Lippard, S. J.; Mague, J. T.; Robinson, W. R.; Wood, J. S. Science 1964, 145, 1305.). Since that time X-ray crystallography along other techniques such as EPR, electrochemistry, NMR, PES, electronic spectra, circular dichroism, magnetism, theoretical calculation have played an important role understanding of the delta bond. Here we will discuss some of the latest advances in the field.

Abstract The crystal structures of C6H5NClCOCH2Cl (1), C6H5NClCOCHCl2 (2), C6H5NClCOCCl3 (3),and C6H5NHCOCCl3 (4) have been determined at room temperature (lattice constants, d in pm).(1): P21 /c, Z = 4, a = 738, b = 645, c = 1891, β = 90.41°, d (N -C l) = 171, d (C = O ) = 121; (2): P21 /c, Z = 4, a = 820, b = 1495, c = 905, β = 114.78°, d (N -Cl) = 171, d (C = O ) = 120; (3): P 21/c, Z = 4,a = 819, b = 1853, c = 718, β = 103.64°, d (N -Cl) = 172, d (C = O ) = 120; (4): P21/c, Z = 4, a = 551, b = 1704, c = 1035, β = 93.08°, d (C = O) = 121.For (2), (3), and (4) the 35Cl NQR frequencies have been determined in the range 77 ≤ T /K ≤ 300. At 77 K (γ in MHz): (2): γ(w,1) = 37.600, γ(w,2) = 38.188, γ(N) = 51.858; (3): γ(w,1) = 39.944, γ(w,2) = 40.512, γ(w,3) = 40.739, γ(N) = 52.791; (4): γ(w,1) = 39.428, γ(w,2) = 39.452, γ(w,3) = 39.986. For the compound C6H5NHCOCHCl2 (5) the 35Cl NQ R measured at 77 K is: γ(w,1) = 37.195 MHz, γ(w,2) = 37.596 MHz. The relation, γ(35Cl) = d (N -Cl) is discussed.

Following Soare [11] we say a recursively enumerable (r.e.) degree a has the anticupping (a.c.) property if there is a nonzero r.e. degree b < a such that for no r.e. c < a does a = b ∪ c.Cooper [2] and Yates showed that 0′ has the a.c. property, while Harrington (see Miller [6]) proved that every high r.e. degree a has the a.c. property.The recent paper by Ambos-Spies, Jockusch, Shore and Soare [1] describes a general theoretical framework for cupping and capping below 0′ which seems likely to be useful in a wider context.Definition. (1) We say b is strongly noncuppable belowa if 0 < b < a and, for each d < a, b ∪ d ≠ a.(2) We say an r.e. a has the strong anticupping property if there is an r.e. b which is strongly noncuppable below a.The main results on cupping in (≤ 0′) are due to Epstein, Posner and Robinson. For instance it is known (Posner and Robinson [8]) that the s.a.c. property fails for 0′.We prove below that r.e. degrees with the s.a.c. property do exist, hence obtaining a nonzero r.e. degree a such that (≤ a) ≢e(≤h) for any high r.e. degree h. This result, obtained by means of an infinite injury construction in (≤ 0′), extends Theorem 2 of [3], proved using a finite injury construction in (≤ 0′).Our main source of notation and terminology is [3].

T h e q u e stio n show ed in a T itle of th is m o n o g rap h re g a rd th eC h a p te r c o n stitu te d in C hełm in v irtu e of F o u n d a tio n A ct of th eK in g W ład y sław Jag iełło fro m 1429, a n d tram sfered in 1490 to K ra ­sn y staw . F o r th e en d o v em e n t of thfe C h a p ter com posed in itia l fro m2 p re la te s a n d 10 canons d em an d e d th e K ing, th a t a ll m em b ers oft-he C h ap te r sh o u ld resid e by th e C a th e d ra l to k eep a sp len d o r ofG od’s C u lt a n d in o rd e r th a t th ey should say p re y e rs fo r th e fo u n d er,h is fam ily, th e deceased w ifes a n d fo r a p ro sp e rity of K ingdom .S im ila r resid en ce d em an d e d also T re n t’s C ouncil a n d C h a p te r’s C h a rte rs a p p ro v ed b y B ishop W ojciech Sobi-ejuski fro m S taro izrzeb iec in 1572. C ause a pooor endow m ent of th e C haiptar th e p ré la ts a n d th ecanons alm o st since a b eg in n in g assu m ed o th e r P a s to ra l’s b eneficesin a D iocese, it w as la ck of th e fu n d s a d e q u a te fo r all m em b ers ofa C h a p ter (in itial 12, a n d la te r 19) fo r su b sisten ce b esid e th e C ath e d ra l, chiefly th a t in som e y e ars th e e states of C h a p te r w e re dev a sta te d b y T a ta r’s invasions.G oing th ro u g h th e y ro u n d of d u ties th e B ishops w e re w a tc h in gab o u t th e fu lfilm e n t th e ir o b lig atio n of R esidence by p ré la ts an dcanons, a n d th ey w a tc h in g also th a t G od’s cu lt sh o u ld be rig h tlyp erfo rm ed , a t le a s t successively b y a p a rt of th e m em b ers of a C h ap ­te r. I t w as se ttle d a cu sto m co n cern in g th e p e rfo rm a n ce o f a C ulta n d th e fu lfilm e n t of d u ties re la te d to, in a fa rm of ro ta tio n design a te d by a C h ap ter.I t w e re w eek ly ro ta tio n , a n d o ften m o n th ly, com posed by tw o p ré ­la ts or canons. S om etim e o n ly th e y w e re re p la ce d b y h o n o ra ry canons. A lso th is m a n n e r of resid en ce w aist ev e ry tim e co n serv e v erye x actly , w h a t w as show ed in th e reco rd s of C h a p te r’s sessions a n din R e fo rm atio n al D ecrees issu ed b y B ishops a fte r th e acco m p lish m ­en ts of C a th e d ra l v isitatio n s.I t w as in a p rin c ip le d u rin g a ll tim e of th is C h a p te r ex istatio n ,w h ich w as ab ro g a te d to g e th e r w ith th e ab ro g a tio n o f C helm ’s diocese by a P o p e P iu s V II w ith a B u lla Q u em a d m o d u m R o m a n o ru mP o n tific u m fro m O ct. 9, 1805, p u t in to effect in 18C7, sim u ltan eo u slyto a c rea tio n of L u b lin ’s diocese a n d it C a th e d ra l C h ap ter.

AbstractLet D be a bounded pseudoconvex domain in ℂn and ζ ∈ D. By KD and BD we denote the Bergman kernel and metric of D, respectively. Given a ball B = B(ζ, R), we study the behavior of the ratio KD/KD∩B(w) when w ∈ D ∩ B tends towards ζ. It is well-known, that it remains bounded from above and below by a positive constant. We show, that the ratio tends to 1, as w tends to ζ, under an additional assumption on the pluricomplex Green function D(·, w) of D with pole at w, namely that the diameter of the sublevel sets Aw :={z ∈ D | D(z, w) < −1} tends to zero, as w → ζ. A similar result is obtained also for the Bergman metric. In this case we also show that the extremal function associated to the Bergman kernel has the concentration of mass property introduced in [DiOh1], where the question was discussed how to recognize a weight function from the associated Bergman space. The hypothesis concerning the set Aw is satisfied for example, if the domain is regular in the sense of Diederich-Fornæss, ([DiFo2]).

V. Rama Subbaraoa* aNatural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Habsiguda, Hyderabad 500007, India. Study and optimization of Diels-Alder reaction of piperine in aqueous ionic solutions using Gn.HCl as a catalyst. The semi-synthesis of these products using intermolecular [4+2] cycloaddition reaction has been described. Obtained products were characterized using IR, HNMR, CNMR and Mass Spectroscopy. Introduction An outsized number of phenomena concern to and are conducted in liquid phase involving ionic species (Millions of years ago, Mother Nature discovered the secrets of water molecule) in different biological and other natural processes. Salt present in the oceans, a striking example from Nature, is a multi component salt solution reflecting the distant marine origin of life on earth together with the composition of physiological fluids. In general the ionic solutions play roles in several industrial and geological processes in addition to their deep impact on the biological molecules. This enormous power of ionic solutions is based on the interactions of ion with solvent. In this work, we present some interesting results with comprehensive implications on the application of ion-solvent (i-s) interactions on organic reactions. Ion-Solvent interactions Cohesion among molecules in the liquid phase results from intermolecular forces. These forces include hydrogen-bonding, dipole-dipole, multi polar, dispersion interactions and also interactions emerging from the repulsion between two molecules. The cohesion due to intermolecular forces gives rise to a 'pressure' which is experienced by the solvent molecules. A liquid undergoing a small, isothermal volume expansion does work against the cohesive forces which causes a change in the internal energy, U. The function (∂U/∂V)T, is called as internal pressure (Pi) of a liquid and is supported by the equation of state. Internal pressure increases upon the addition of some solutes like NaCl, KCI, etc. and decreases by salts like of guanidinium salts. Diels-Alder Reaction in aqueous medium For long time water was not a popular solvent for the Diels-Alder reaction. Before 1980 its use had been reported only incidentally. Diels and Alder themselves performed the reaction between furan and maleic acid in an aqueous medium in 1931,27 an experiment which was repeated by Woodward and Baer in 1948. 28 They noticed a change in endo-exo selectivity when comparing the reaction in water with ether. The extreme influence of water can exert on the Diels-Alder reaction was rediscovered by Breslow in 1980, much by coincidence 29,30 while studying the effect of β-cyclodextrin on the rate of a Diels-Alder reaction in water, accidentally. Schem 1. Alternatively, Grieco et al., have repeatedly invoked the internal pressure of water as an explanation of the rate enhancement of Diels-Alder reactions in these solvents. 31 They probably inspired by the well known large effects of the external pressure on rates of cycloadditions. However the internal pressure of water is very low and offers no valid explanation for its effects on the Diels-Alder reaction. The internal pressure is defined as the energy required bringing about an infinitesimal change in the volume of the solvent at constant temperature. Due to the open and relatively flexible hydrogen-bond network of water, a small change in volume of these solvents does not require much energy. A related, but much more applicable solvent parameter is the cohesive energy density. This quantity is a measure of energy required for evaporation of the solvent per unit volume. The reactions in water were less accelerated by pressure than those in organic solvents, which is in line with notion that pressure diminishes hydrophobic interactions. The effect of water on the selectivity of Diels-Alder reactions Three years after the Breslow report on the large effects of water on the rate of the Diels-Alder reaction, he also demonstrated that the endo-exo selectivity of this reaction benefits markedly from employing aqueous media. Based on the influence of salting-in and salting-out agents, Breslow pinpoints hydrophobic effects as the most important contributor to the enhanced endo-exo selectivity. Hydrophobic effects are assured to stabilize the more compact endo transition state more than the extended exo transition state. In Breslow option the polarity of water significantly enhances the endo-exo selectivity. In conclusion, the special influence of water on the endo-exo selectivity seems to be a result of the fact that this solvent combines in it three characteristics that all favors formation of the endo/exo adduct. 1. water is strong hydrogen bond donor 2. water is polar and water induces hydrophobic interactions. Study of salting-out and salting-in reagents towards the Diels-Alder reaction of piperine (1): The special effects of water as solvent for valuable Diels-Alder reaction (Scheme 1) of piperine (1), greatly altered by the addition of ionic solutes (Table 1) such as LiCl, LiBr, LiClO4,- NaCl, NaBr, KF, KCl, KBr, MgCl2, CaCl2, guanidinium chloride, guanidinium carbonate, guanidinium nitrate. Aqueous salts solutions accelerated cycloaddition reactions (Scheme 1) of piperine (1) to give resultant cycloadducts 2, 3 and 4 among them 2 is major ortho-exo cyclohexene type dimeric amide alkaloid and also known as chabamide, which is previously isolated from this plant, isomer 3 is also known adduct and previously isolated from Piper nigrum. 21 Cycloadduct 4 was synthesized from piperine by Diels-Alder reaction by Wei. et al. its physical and spectroscopic data were identical with reported data22 (1H-NMR & Mass spectra). Table 1: Study of different salts towards the Diels-Alder reaction of piperine (1). aOverall yield of adducts after HPLC, un-reacted piperine was recovered in all reactions. Reaction showed good overall yield and more exo selectivity. This reaction showed completely regioselectivity (yield of 2+3>4) due to maximum involvement of α-double bond rather than γ-double bond of 1 during Diels-Alder reaction. Table 2: Comparision of salting-out and salting-in reagents towards the Diels-Alder reaction of piperine (1). Study of Salting-out reagents Increased rate in Diels-Alder reaction (over all yield up to 79 %) of piperine (1) has been attributed to the hydrophobic effect. Owing to the difference in polarity between water and the reactants, water molecules tend to associate amongst themselves, excluding the organic reagents and forcing them to associate together forming small drops surrounded by water. A further method of increasing the rate of Diels-Alder reaction in water is so called ‘salting-out’ effect. Among the salting-out reagents used (Table 1) in this methodology CaCl2 is the best reagent and gave 79 % over all yield. If anion size increases, reaction yield decreases, where as cation size increases, reaction yield increases. Here a salt such as calcium chloride is added to the aqueous solution. In this case water molecules attracted to the polar ions, increasing the internal pressure and reducing the volume. This has the effect of further excluding the organic reagents. For reactions such as Diels-Alder, which have negative activation volumes, the rates are enhanced by this increase in internal pressure in much the same way as expected for an increase in external pressure. This salting-out reagent showed good exo selectivity, due to formation of cycloadduct 2 (ortho-exo) is major up to 69 % (cycloadduct ratio) compare to cycloadducts 3 (21 %, meta-exo) and 4 (10%, meta-exo) are poor in yield. Schem 2. Plausible mechanism of Diels-Alder reaction catalyzed by Gn.HCl. Study of Salting-in reagents Among the tested salting-in reagents used in this methodology (Table 1) guanidinium chloride (Gn.HCL) is the best reagent and gave 81 % overall yield, where as LiClO4 end up with only 15 % overall yield. Gn.HCL reagent exhibited well selectivity towards the Diels-Alder reaction of piperine in given conditions (scheme 1). Formation of cycloadduct 2 in 80 %, 3 in 15 % and 4 in 5 % ratio is clearly indicates this methodology received good attention towards the exo selectivity in Diels-Alder reaction of piperine. Overall yield is also high with salting-in reagents when compare to salting-out reagents. Procedure for aqueous ionic salts catalyzed Diels–Alder reactions of piperine (1): To a stirred mixture of piperine (1) (50.0 mg, 0.175 mmol), 6M aqueous guanidinium. Hydrochloride (2 mL) in a round bottom flask fitted with condenser and refluxed for 70 h in an oil bath. After completion of the reaction, monitored by TLC (dipped in 5% solution of phosphomolybdic acid in methanol and heating), the reaction mixture was cooled to room temperature and diluted with water (3 mL). Then extracted with EtOAc (2x5 mL), the combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue obtained was then purified by reversed-phase (RP) HPLC (column: Phenomenex Luna C18, 250 x 10 mm, 10µ), solvent system: 80% acetonitrile in water, flow rate: 1.5 mL/min, to give pure compounds of adducts (2) 0.065 g, (3) 0.012 g and (4) 0.004 g. Cycloaddition reaction between piperine (1a) and pellitorine (1b): Our aim of this cycloaddition reaction is to explain to study different cycloadducts and selectivity of diene among piperine and pellitorine (Scheme 4). This biomimetic synthesis will explain the probability of diene, which participated in Diels-Alder reaction between piperine (1a) and pellitorine (1b) both were isolated from same plant (P. chaba). Nigramide N, which is formed biosynthetically via cycloaddition reaction between piperine and pellitorine, this adduct previously isolated from roots of P. nigrum 21 by Wei. et. al. Lewis acid catalyzed cycloaddition reactions of piperine (1a) and pellitorine (1b) under organic and aqueous solvent conditions to give resultant cycloadducts 2c, 3c, 4c, 2a and 3b. Cycloadduct 2c and 3c is new cycloadducts and their structures were illustrated by 1D and 2D spectral data. Structure elucidation of compound 2c: Compound 2c was obtained as pale yellow liquid. The molecular formula of 2c was established as C31H44N2O4 by HRESIMS (Fig-18), which provided a molecular ion peak at m/z 509.3381 [M++H], in conjunction with its 13C NMR spectrum (Fig-12). The IR spectrum displayed absorption bands diagnostic of carbonyl (1640 cm-1) (Fig-10). The 300 MHz 1H NMR spectrum (in CDCl3) indicated the presence of two signals at δ 5.86 (dd, J = 15.6, 10.1 Hz) and 6.27 (d, J = 15.6 Hz), which were assigned to trans-olefinic protons by the coupling constant of 15.6 Hz. It also displayed aromatic protons due to two 1, 3, 4-trisubstituted aromatic rings at δ 6.82 (1H, br s), 6.76 (1H, dd, J = 7.8, 1.4 Hz), 6.75 (1H, d, J = 7.8 Hz) (Fig-11), (Table 4). In addition to the above-mentioned moieties, combined inspection of 1H NMR and 1H–1H COSY revealed the presence of cyclohexene ring, one isobutylamide and one pyrrolidine ring. The 13C NMR spectrum (Fig-12) displayed the presence of 31 carbon atoms and were further confirmed by DEPT experiments (Fig-13) into categories of 11 methylenes, 12 methines and 5 quaternary carbons including two carbonyls (δ 173.01 and 172.50). On the basis of these characteristic features, database and literature search led the skeleton of compound 2c as a dimeric alkaloidal framework. A comprehensive analysis of the 2D NMR data of compound 2c facilitated the proton and carbon assignments. 1H–1H COSY spectrum (Fig-16) suggested the sequential correlations of δ 3.51 (dq, J = 5.0, 2.6 Hz)/5.62 (dt, J = 9.8, 2.6 Hz)/6.10 (ddd, J = 9.8, 1.5 Hz)/2.20 (m)/2.72 (ddd, J = 11.1, 10.1, 5.2 Hz)/3.35 (dd, J = 11.1, 9.8 Hz) assignable to H-2-H-3-H-4-H-5-H-3"-H-2" of the cyclohexene ring. Concerning the connections of the n-amyl and 3, 4-methylenedioxy styryl groups, HMBC spectrum (Fig-15) showed correlations of H-4, H-6, H-7/C-5; H-5", H-4"/C-3", which implies that these units were bonded to the cyclohexene ring at C-5 and C-3". Further, HMBC correlations of two methylene protons at δ 5.95 with 147.91 (C-8"), 146.87 (C-9"), confirmed the location of methylenedioxy group at C-8", and C-9". Remaining units, isobutylamine and pyrrolidine (rings) were connected through carbonyl groups at C-2 and C-2", which was confirmed by HMBC correlations of H-2 and H-1' to C-1 (δ 173.01) and H-2" and H-1''' to C-1" (δ 172.50). The assignment of the relative configuration of compound 2c, and confirmation of overall structure were achieved by the interpretation of the NOESY spectral data and by analysis of 1H NMR coupling constants. The large vicinal coupling constants of H-2"/H-2 (11.1 Hz) and H-2"/H-3" (11.1 Hz) indicated anti-relations of H-2"/H-2 and H-2"/H-3" and the axial orientations for these protons. In the NOESY spectrum (Fig-17), the occurrence of the correlations between H-2/H-3" and the absence of NOE effects between H-2/H-2" and H-2"/H-3" supported the above result. This data indicated β-orientation for H-2" and α-orientation for H-2 and H-3". The α-orientation of H-5 was suggested by the coupling constant of H-5/H-3" (5.2 Hz) and the absence of the NOESY correlations between H-3" and H-2". On the basis of these spectral data, the structure of compound 2c was unambiguously established and trivially named as chabamide M. Compound 3a: IR (KBr) nmax: 2923, 2855,1628, 1489, 1242, 1128, 1035 cm-1 d ppm 0.69 & 1.25 (2H, m, H-2'"), 1.15 & 1.23 (2H, m, H-4'"), 1.31 & 1.40 (2H, m, H-3'"), 1.52 (2H, m, H-2'), 1.56 (2H, m, 4'), 1.61 (2H, m, H-3'), 2.94 (1H, td, J = 10.1, 10.1, 5.5 Hz, H-3"), 3.02 & 3.60 (2H, m, H-5'"), 3.09 & 3.32 (2H, m, H-1'"), 3.51 (2H, m, H-1'), 3.61 (1H, m, H-2), 3.61 (2H, m, H-5'), 3.78 (1H, dq, J = 10.0, 2.3 Hz, H-5), 4.07 (1H, t, J = 10.1, H-2"), 5.72 (1H, ddd, J = 9.8, 5.0, 2.7 Hz, H-3), 5.88 (2H, s, H-12), 5.89 (1H, dt, 10.3, 1.8 Hz, H-4), 5.90 (1H, J =15.8, 9.8 Hz, H-4"), 5.92 (1H, s, H-12"), 6.37 (1H, d, J = 15.8 Hz, H-5"), 6.68 (1H, brs, H-7), 6.69 (1H, d, J = 8.0 Hz, H-10"), 6.70 (1H, dd, J = 8.0, 1.4 Hz, H-11), 6.69 (1H, d, J = 8.0 Hz, H-10), 6.74 (1H, dd, J = 8.0, 1.6 Hz, H-11"), 6.79 (1H, brs, H-7"). ESIMS (m/z): 571 [M+ +H] Table 4: 1H & 13C NMR data of cycloadduct 2c in CDCl3 (300 MHz, δ in ppm, mult, J in Hz) Compound 4a: IR (KBr) nmax: 2926, 2857,1627, 1484, 1440, 1240, 1034 cm-1 1H NMR (300 MHz, CDCl3): d ppm 0.81 & 1.35 (2H, m, H-2'), 1.29 & 1.47 (2H, m, H-4'), 1.35 (2H, m, H-2"'), 1.36 & 1.51 (1H, m, H-3'), 1.47 (2H, m, H-4"'), 1.51 (2H, m, H-3"'), 2.92 (2H, m, H-1"'), 2.99 (1H, ddd, J = 12.5, 9.7, 5.5 Hz, H-4"), 3.22 (2H, m, H-1'), 3.29 & 3.71 (2H, m, H-5'), 3.38 (1H, m, H-4"'), 3.44 (1H, dd, J = 12.1, 10.1 Hz, H-5"), 3.59 (1H, t, J = 5.3 Hz, H-5), 3.70 (1H, dq, J = 12.1, 2.1, H-2), 5.65 (1H, dd, J = 15.6, 9.5 Hz, H-3"), 5.70 (1H, dt, J = 9.9, 1.6, H-3), 5.81 (1H, d, J = 15.6 Hz, H-2"), 5.84 (1H, s, H-12"), 5.90-5.92 (2H, brs, H-12), 5.96 (1H, ddd, J = 9.2, 5.8, 2.6 Hz, H-4), 6.55 (1H, dd, J =7.9, 1.5 Hz, H-11"), 6.61 (1H, d, J = 8.2 Hz, H-10"), 6.62 (1H, d, J = 1.4 Hz, H-7"), 6.79 (1H, d, J = 7.9 Hz, H-10), 6.92 (1H, dd, J = 8.0, 1.5 Hz, H-11), 7.01 (1H, d, J = 1.5 Hz, H-7). ESIMS (m/z): 571 [M+ +H] Acknowledgements The authors are thankful to Director IICT for his constant encouragement and CSIR New Delhi for providing the fellowship References Braun, M. Synth. Highlights 1991, 232 Robinson, R. Chem. Soc. 1917, 762. Stork, G.; Burgstahler, A. W. Am. Chem. Soc. 1955, 38, 1890. Johnson, W. S.; Gravestock, M. B.; McCarry, B. E. Am. Chem. Soc. 1971, 93, 4332. Chapman, O. L.; Engel, M. R.; Springer, J. P.; Clardy, J. C. Am. Chem. Soc. 1971, 93, 6696. Bandaranayake, W. M.; Banfield, J. E.; Black, D. St. C. Chem. Soc., Chem Commun. 1980, 902. Nicolaou, K. C.; Zipkin, R. E.; Petasis, N. A. Am. Chem. Soc. 1982, 104, 5558. O.; Alder, K. Ann. 1928, 460, 98. Woodward, R. B.; Hoffmann, R. Chem. 1969, 81, 797. Fakui, K. Chem. Res. 1971, 4, 57. Houk, K. N. Chem.. Res. 1975, 8, 361. Houk, K. N.; Li, Y.; Evanseck, D. Angew Chem., Ed. Engl. 1992, 31, 682. Alder, K.; Stein, G. Chem. 1937, 50, 510. Fotiadu, F.; Michel, F.; Buono, G. Tetraheron Lett. 1990, 34, 4863. 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Spherically symmetric classical model of an elementary particle or a black hole spacetime without central singularity had been constructed by O. B. Zaslavskii, Classical model of an elementary particle with a Bertotti–Robinson core and extremal black holes, Phys. Rev. D 70 (2004) 104017. In this model, an extremal Reissner–Nordström (RN) black hole and a Bertotti–Robinson (BR) spacetime are glued at the horizon such that the inner/core spacetime is the regular BR while outside is the extremal RN. The fact that near horizon geometry of the extremal RN coincides with BR spacetime becomes helpful in the construction. We investigate the stability of such a particle/regular black hole against linear radial perturbations. The model turns out to be stable against such perturbations with a linear equation of state for a perfect fluid after the perturbation. To complete our study, we give a generic particle model whose inner and outer metrics must satisfy more general conditions.

In this paper, we study the existence of solutions for the following differential equations by using a fixed point theorems \[ \begin{cases} D^{\mu}_{c}w(\varsigma)\pm D^{\nu}_{c}w(\varsigma)=h(\varsigma,w(\varsigma)),& \varsigma\in J,\ \ 0<\nu<\mu<1,\\ w(0)=w_0,& \ \end{cases} \] where $D^{\mu}$, $D^{\nu}$ is the Caputo derivative of order $\mu$, $\nu$, respectively and $h:J\times \mathbb{R}\rightarrow \mathbb{R}$ is continuous. The results are well demonstrated with the aid of exciting examples.