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Astrophysical jets are relativistic outflows that remain collimated for remarkably many orders of magnitude. Despite decades of research, the origin of cosmic rays (CRs) remains unclear, but jets launched by both supermassive black holes in the centre of galaxies and stellar-mass black holes harboured in X-ray binaries (BHXBs) are among the candidate sources for CR acceleration. When CRs accelerate in astrophysical jets, they initiate particle cascades that form {\gamma}-rays and neutrinos. In the so-called hadronic scenario, the population of accelerated CRs requires a significant amount of energy to properly explain the spectral constraints similarly to a purely leptonic scenario. The amount of energy required often exceeds the Eddington limit, or even the total energy available within the jets. The exact energy source for the accelerated protons is unclear, but due to energy conservation along the jets, it is believed to come from the jet itself via transfer of energy from the magnetic fields, or kinetic energy from the outflow. To address this hadronic energy issue and to self-consistently evolve the energy flux along the flows, we explore a novel treatment for including hadronic content, in which instabilities along the jet/wind border play a critical role. We discuss the impact of the different jet composition on the jet dynamics for a pair dominated and an electron-proton jet, and consequently the emitted spectrum, accounting for both leptonic and hadronic processes. Finally, we discuss the implications of this mass-loading scenario to address the proton energy issue., Comment: 17+6 pages, 10+9 figures

Non-ionic surfactants, poly oxyethylene sorbitan adipose acid esters (polysorbate), were used in this work to explore the consequence of temperature on CMC throughout a wide temperature range. The phase separation model is used to analyze the enthalpy and entropy of micelle conformation. The Du Nöuys ring was used to determine the results' face pressure. The CMC standards were derived after the strong break down in surfactant attention plots of face pressure vs. logarithms. The CMC at continuous temperature decreases as the chain length of the surfactants rises, which is completely connected to the reduction in hydrophilicity of the motes. Because of the lower possibility of hydrogen bond conformation on high temperatures, the CMC of each surfactant initially declines and then increases as the system temperature rises. As the temperature rises, the commencement of micellization tends to happen at a faster rate. The focus of this research is on the characterization of solubilization of drugs that aren't sufficiently responsive. Face pressure measurements for nonionic surfactant TritonX-100 were also taken in order to assess the solubilization features. In the presence of colourful organic detergent, the medium's opposition and the likely positions of SMX and TMP were also discussed. TritonX-100, a nonionic surfactant, was also tested. In the presence of colourful organic detergents, the medium's opposition and the likely position of SMX and TMP were also discussed.

Indian travelers in Victorian London began engaging with questions of nationhood, modernity, family, home, and gender roles within the ambit of reproducing the city’s imperial geography on increasingly gendered and sexist lines. The rise of Indian feminists like Sarojini Naidu, Cornelia Sorabji, Rukhmabai, and Princess Sophia notwithstanding, Indian men redrew London’s patriarchal contours. Drawing on a legacy of accounts by nineteenth-century Indian men, like T. N. Mukharji, Behramji Malabari, M. K. Gandhi, Lala Baijnath, T. B. Pandian, and G. P. Pillai, this article examines the maps of the geography of Victorian womanhood that they sought to reproduce. I argue that—while colonial travelers helped India derive administrative, bureaucratic, and architectural models—the geopolitical roots of postcolonial Indian patriarchy date back to ways in which an emotionally vulnerable Indian male gaze perceived Victorian Englishwomen. There is much to be troubled by the gendered relations that made imperial London and had an ominous afterlife in India, normalizing patriarchal expectations and codes of womanhood—a social malignancy whose etiology stems from structures of India’s colonial conflicts.

Beginning as a symptomatic reading of Arthur Conan Doyle’s use of a fictional African root poison, the Radix pedis diaboli, in “The Adventure of the Devil’s Foot” (1907), and Indian poisoned darts in The Sign of the Four (1890), this article makes some general comments on the history of colonial tropical toxicology, focusing on the Indian aconite ( Aconitum ferox) and its roots ( Radix aconiti indica). Arguably, Doyle had aconite in his mind while creating the fictional African root poison. Victorian toxicologists, who were deeply interested in Indian poisons, created stereotypes of India as congeries of melancholy and culturally backward, industrially primitive, and morally corrupt societies. Doyle’s fictional poisons were influenced by a normative cultural bias that saw tropical pharmakons like aconite with an Orientalizing gaze. By shifting the geographical focus from Doyle’s “Ubangi country” to nineteenth-century India, I draw attention to a larger spectrum of tropical toxicology. The colonial zeal to taxonomize the properties and utility of tropical pharmakons obsessively revolved around their toxic uses as criminal weapons or accidental killers, while marginalizing the medicinal uses that the plant had been historically put to by ancient Indian physicians.

This paper proposes an unsigned approximate multiplier architecture segmented into three portions; the least significant portion that contributes least to the partial product is replaced with a new constant compensation term to improve hardware savings without sacrificing accuracy. The partial products in the middle portion are simplified using a new 4:2 approximate compressor, and the error due to approximation is compensated using a simple yet efficient error correction module. The most significant portion of the multiplier is implemented using exact logic as approximating it will results in a large error. Experimental results of 8-bit multiplier show that power and power-delay products are reduced up to 47.7% and 55.2% respectively in comparison with the exact design and 36.9% and 39.5% respectively in comparison with the existing designs without significant compromise on accuracy.

BackgroundOver 65% of American women are overweight or obese. Obesity and the closely related metabolic syndrome increase the probability for developing several diseases, including cardiovascular disease (CVD). Chronic low-grade inflammation has been recognized as an underlying event linking obesity to CVD. However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we performed a pilot study to determine the levels of key circulating biomarkers of endotoxemia and inflammation in overweight vs. lean women with high cholesterol and/or high blood pressure - two important conventional risk factors for CVD.MethodsPlasma samples from adult female subjects who were lean (n=20, BMI=22.4±1.6 kg/m2) or overweight (n=20, BMI=27.0±1.5 kg/m2) with similar ages (55.65±9.1 years and 59.7±6.1 years), and race/ethnicity, and self-reported high cholesterol and/or high blood pressure were analyzed and compared. Samples were obtained through the Northwell Health “Genotype and Phenotype, GaP” registry. Plasma levels of lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin were analyzed using commercially available assay kits.ResultsPlasma levels of LBP (a recognized marker of metabolic endotoxemia in obesity) were significantly higher in the overweight group compared with the lean group (p=0.005). The levels of CRP, a general marker of inflammation, were also significantly higher in overweight subjects (p=0.01), as were those of the cytokine IL-6 (p=0.02) and the adipokine leptin (p=0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti-atherogenic functions, were significantly lower in the overweight group (p=0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (p=0.02). Alterations in LBP, CRP, leptin, and adiponectin significantly correlated with BMI, but not with age. The absolute levels of these analytes were within the ranges reported for healthy subjects evaluated in larger clinical trials and thus can be classified as consistent with subclinical endotoxemia.ConclusionThese results document the presence of a pro-inflammatory state in overweight compared with lean women and are of interest for further evaluation of evidence of inflammation in overweight individuals as an additional risk factor for cardiometabolic disease.

KEAP1 (Kelch-like ECH-associated protein), a cytoplasmic repressor of the oxidative stress responsive transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), senses the presence of electrophilic agents by modification of its sensor cysteine residues. In addition to xenobiotics, several reactive metabolites have been shown to covalently modify key cysteines on KEAP1, although the full repertoire of these molecules and their respective modifications remain undefined. Here, we report the discovery of sAKZ692, a small molecule identified by high-throughput screening that stimulates NRF2 transcriptional activity in cells by inhibiting the glycolytic enzyme pyruvate kinase. sAKZ692 treatment promotes the buildup of glyceraldehyde 3-phosphate, a metabolite which leads to S-lactate modification of cysteine sensor residues of KEAP1, resulting in NRF2-dependent transcription. This work identifies a posttranslational modification of cysteine derived from a reactive central carbon metabolite and helps further define the complex relationship between metabolism and the oxidative stress-sensing machinery of the cell.

In the case of solubility limited absorption, creating supersaturation in the GI fluid is very critical as supersaturation may provide great improvement of oral absorption. The techniques to create the so-called supersaturation in the GI fluid include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles. Ciprofloxacin was chosen because it is practically insoluble in water; hence its salt form is used commercially, which is soluble in water. The objective of the present investigation was to enhance the solubility of ciprofloxacin by formulating solid dispersions techniques in water soluble carriers have attracted considerable interests as a mean of improving the dissolution rate & hence possibly bioavailability range of hydrophobic drugs. The poor solubility of ciprofloxacin leads to poor dissolution & hence variation in bioavailability. The purpose of present investigation was formulation & evaluation of controlled release floating capsule of ciprofloxacin with improved solubility & dissolution rate. In the present study solid dispersions using various carriers like mannitol & lactose in different ratios were prepared by solvent evaporation method. The prepared solid dispersions were characterized for drug content, solubility & dissolution rate. The dissolution rate substantially improved for ciprofloxacin from its solid dispersions compared with the pure drug. Dissolution rate increased with increasing carrier content.

The radiative counterpart of the supermassive black hole at the Galactic Centre, Sagittarius A*, displays flaring emission in the X-ray band atop a steady, quiescent level. Flares are also observed in the near-infrared band. The physical process producing the flares is not fully understood and it is unclear if the flaring rate varies, although some recent works suggest it has reached unprecedented variability in recent years. Using over a decade of regular X-ray monitoring of Neil Gehrels Swift Observatory, we studied the variations in count rate of Sgr A* on time scales of years. We decomposed the X-ray emission into quiescent and flaring emission, modelled as a constant and power law process, respectively. We found that the complete, multi-year dataset cannot be described by a stationary distribution of flare fluxes, while individual years follow this model better. In three of the ten studied years, the data is consistent with a purely Poissonian quiescent distribution, while for five years only an upper limit of the flare flux distribution parameter could be determined. We find that these possible changes cannot be explained fully by the different number of observations per year. Combined, these results are instead consistent with a changing flaring rate of Sgr A*, appearing more active between 2006-2007 and 2017-2019, than between 2008-2012. Finally, we discuss this result in the context of flare models and the passing of gaseous objects, and discuss the extra statistical steps taken, for instance to deal with the background in the Swift observations., 14 pages, 10 figures, Accepted for publication in MNRAS

Radical cure ofPlasmodium vivaxmalaria must include elimination of quiescent ‘hypnozoite’ forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets, we screened the Repurposing, Focused Rescue, and Accelerated Medchem library againstP. vivaxliver stages and identified the DNA methyltransferase inhibitors hydralazine and cadralazine as active against hypnozoites. We then used bisulfite sequencing and immunostaining to identify cytosine modifications in the infectious stage (sporozoites) and liver stages, respectively. A subsequent screen of epigenetic inhibitors revealed hypnozoites are broadly sensitive to histone acetyltransferase and methyltransferase inhibitors, indicating that several epigenetic mechanisms are likely modulating hypnozoite persistence. Our data present an avenue for the discovery and development of improved radical cure antimalarials.One-Sentence SummaryA drug repurposing screen reveals antihypertension drugs are active againstP. vivaxhypnozoites and epigenetic mechanisms play a role in hypnozoite quiescence.

Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H2O2exposure induced efficient VE-cadherin proteolysis by MMPs and γ-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by γ-secretase, VE-Cad/CTF2 - a fragment that has eluded identification so far - could readily be detected after H2O2treatment. VE-Cad/CTF2, released into the cytosol, was tightly regulated by proteasomal degradation and was sequentially produced from an ADAM10/17-generated C-terminal fragment, VE-Cad/CTF1. Interestingly, BMP9 and BMP10, two circulating ligands critically involved in vascular maintenance, significantly reduced VE-Cad/CTF2 levels during H2O2challenge, as well as mitigated H2O2-mediated actin cytoskeleton disassembly during VE-cadherin processing. Notably, BMP9/10 pretreatments efficiently reduced apoptosis induced by H2O2, favoring endothelial cell recovery. Thus, oxidative stress is a trigger of MMP- and γ-secretase-mediated endoproteolysis of VE-cadherin and AJ disassembly from the cytoskeleton in ECs, a mechanism that is negatively controlled by the EC quiescence factors, BMP9 and BMP10.

Sherlock Holmes is often oversimplified as a secular modern professional, with a remorselessly scientific outlook. This hypothesis overlooks late-nineteenth-century English society’s pursuit of new social possibilities for spiritualism, following challenges from Darwinist biological determinism to orthodox biblical mythology and morality. If we see Holmes in a default empirical scientism affiliated to imperial ideologies, we will remain blind to the effects of multiple countercultural and spiritual tones that also underpin the “science of deduction.” Holmes’ methods were subliminally informed by theosophy, as Doyle gleaned much of his spiritual knowledge from first- or second-hand readings on Blavatsky. Thus, Vedantic and Buddhist philosophy find inadvertent—but not coincidental—traces in Holmes through theosophy. An intellectual offspring of the trinity of Darwin, Huxley, and Tyndall, Holmes was also a child of Blavatsky’s occult philosophy. Adopting a decolonial praxis, this paper argues that comparisons between the materialistic principles of Darwin, Huxley, and Tyndall, on the one hand, and Holmes on the other, are as useful as comparing the detective’s work to Blavatsky’s theosophy.

In this work, a comprehensive and systematic study on synergistic effect and kinetics of three coal ranks (anthracite coal, bituminous coal, and waste coal), and three biomass materials (wheat straw, sawdust, groundnut) were performed under different blending ratios. The kinetic parameters of coal and biomass devolatilization were estimated by means of thermogravimetric analysis (TGA) at 10, 20, 30 and 40 Kmin−1. These kinetic parameters were subsequently validated using Artificial Neural Network (ANN) Model. Further, for fitting the experimental data, a numerical approach to distributed activation energy model (DAEM) has been evaluated and the experimental findings were compared with simulated data. Subsequently, the kinetic and thermodynamic parameters were estimated and compared with three model-free methods viz., KAS, OFW, and Friedman. The results from TG study indicate that the interactions between the waste coal with higher rank coal and biomass samples present an inhibitive effect during the devolatilization process. Furthermore, the values of activation energy were found in the range of 270, 250, 149 kJmol−1 by using OFW, KAS and Friedman model, respectively. Additionally, the thermodynamic parameters viz., enthalpy (ΔH), Gibbs free energy (ΔG) and entropy (ΔS) were estimated as 275.2 kJ mol−1, 184.5 kJmol−1, and 59.7 Jmol−1, respectively.

Sagittarius A* exhibits regular variability in its multiwavelength emission, including daily X-ray flares and roughly continuous near-infrared (NIR) flickering. The origin of this variability is still ambiguous since both inverse Compton and synchrotron emission are possible radiative mechanisms. The underlying particle distributions are also not well constrained, particularly the non-thermal contribution. In this work, we employ the GPU-accelerated general relativistic magnetohydrodynamics (GRMHD) code H-AMR perform a study of flare flux distributions, including the effect of particle acceleration for the first time in high-resolution 3D simulations of Sgr A*. For the particle acceleration, we use the general relativistic ray-tracing (GRRT) code BHOSS to perform the radiative transfer, assuming a hybrid thermal+non-thermal electron energy distribution. We extract ~60 h lightcurves in the sub-millimetre, NIR and X-ray wavebands, and compare the power spectra and the cumulative flux distributions of the lightcurves to statistical descriptions for Sgr A* flares. Our results indicate that non-thermal populations of electrons arising from turbulence-driven reconnection in weakly magnetised accretion flows lead to moderate NIR and X-ray flares and reasonably describe the X-ray flux distribution while fulfilling multiwavelength flux constraints. These models exhibit high rms% amplitudes, >~150% both in the NIR and the X-rays, with changes in the accretion rate driving the 230~GHz flux variability, in agreement with Sgr A* observations., Accepted by MNRAS

Objectives Oxytocin (OXT) is widely used to facilitate labor. However, little is known about the effects of perinatal OXT exposure on the developing brain. We investigated the effects of maternal OXT administration on gene expression in perinatal mouse brains. Methods Pregnant C57BL/6 mice were treated with saline or OXT at term (n=6–7/group). Dams and pups were euthanized on gestational day (GD) 18.5 after delivery by C-section. Another set of dams was treated with saline or OXT (n=6–7/group) and allowed to deliver naturally; pups were euthanized on postnatal day 9 (PND9). Perinatal/neonatal brain gene expression was determined using Illumina BeadChip Arrays and real time quantitative PCR. Differential gene expression analyses were performed. In addition, the effect of OXT on neurite outgrowth was assessed using PC12 cells. Results Distinct and sex-specific gene expression patterns were identified in offspring brains following maternal OXT administration at term. The microarray data showed that female GD18.5 brains exhibited more differential changes in gene expression compared to male GD18.5 brains. Specifically, Cnot4 and Frmd4a were significantly reduced by OXT exposure in male and female GD18.5 brains, whereas Mtap1b, Srsf11, and Syn2 were significantly reduced only in female GD18.5 brains. No significant microarray differences were observed in PND9 brains. By quantitative PCR, OXT exposure reduced Oxtr expression in female and male brains on GD18.5 and PND9, respectively. PC12 cell differentiation assays revealed that OXT induced neurite outgrowth. Conclusions Prenatal OXT exposure induces sex-specific differential regulation of several nervous system-related genes and pathways with important neural functions in perinatal brains.

Vortex chamber fluidized bed (VCFB) is a novel type of fluidized bed which has many advantages compare to conventional fluidized beds due to its high-G operation. Hence, the VCFB can replace the conventional fluidized bed for process intensification. However, particle loss at the initial stage of particle injection from VCFB is an important issue which may prevent the particle bed formation inside the VCFB. Therefore, the quality of the fluidized bed will largely depends upon it. The present work aims to study the particle loss from a VCFB at the beginning of particle injection by varying different conditions such as particle feeding location, number of feeding points and particle diameter. A three-dimensional computational fluid dynamics (CFD) model of the VCFB is developed and the particle loss is studied numerically. It is observed that particle loss is minimal when particles are injected from the rear wall of the vortex chamber. Particle loss increases with increasing the number of particle injection points and particle diameter.

Water is the preferred cooling media in numerous industrial applications. Recirculating cooling water system with cooling tower is a common setup in thermal power plants, iron & steel plant, petroleum refinery and other industries. Cooling Tower working in the principle of evaporative cooling allows a small fraction of circulating water to pass into the vapour phase dissipating the thermal load from water as latent heat. As water molecule evaporates, concentration of dissolved species in circulating water build-up with consequence of deposition of scales like CaCO3, CaSO4 inside heat-exchanging equipment. Scaling is the biggest danger for heat transfer process. The preventive mechanism is to discharge a portion of cooling water termed as “blow-down” along with dosing of scale inhibiting chemical in the circulating water. The blow-down constitutes a major portion of the total makeup water demand of the cooling water circuit. The current article demonstrates an innovative scheme of ion-exchange based side-stream softening treatment (3ST) for a small fraction (~ 1%) of circulating water is capable of reducing blow-down quantity significantly with simultaneous reduction of scale-formation possibility. While reduction in blow-down helps conservation of water, additional benefits are lower scale problems and better equipment (Heat exchangers, pipes) health, and a possible reduction in dosing of scale inhibiting chemical. From theoretical viewpoint with 3ST technique, a close approach to “zero blow-down” is possible with negligible quantity of forced blow-down in the form of drift loss.

Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT.TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890).From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64).In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT.Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.

A new motion estimation method and its hardware implementation are presented in this paper. In this method, all the frames are firstly gray coded. After that, the two most significant bits from the...

Reprogramming known medicines for a novel target with activity and selectivity over the canonical target is challenging. By studying the binding interactions between RNA folds and known small-molecule medicines and mining the resultant dataset across human RNAs, we identified that Dovitinib, a receptor tyrosine kinase (RTK) inhibitor, binds the precursor to microRNA-21 (pre-miR-21). Dovitinib was rationally reprogrammed for pre-miR-21 by using it as an RNA recognition element in a chimeric compound that also recruits RNase L to induce the RNA's catalytic degradation. By enhancing the inherent RNA-targeting activity and decreasing potency against canonical RTK protein targets in cells, the chimera shifted selectivity for pre-miR-21 by 2500-fold, alleviating disease progression in mouse models of triple-negative breast cancer and Alport Syndrome, both caused by miR-21 overexpression. Thus, targeted degradation can dramatically improve selectivity even across different biomolecules, i.e., protein versus RNA.

This paper uncovers new complexity for Shakespearean studies in examining three anecdotes overlooked in related historiography—the first Indian baptism in Britain, that of Peter Pope, in 1616, and its extrapolation in Victorian history as Calibanesque; the tale of Catherine Bengall, an Indian servant baptised in 1745 in London and left to bear an illegitimate child, before vanishing from Company records (like Virginia Woolf’s invention Judith Shakespeare vanishing in Shakespeare’s London); and the forgotten John Talbot Shakespear, a Company official in early nineteenth-century Bengal and descendant of William Shakespeare. I argue that the anecdotal links between Peter, Caliban, Catherine, Judith, Shakespear and Shakespeare should be seen as Jungian effects of non-causal “synchronic” reality or on lines of Benoit Mandelbrot’s conception of fractals (rough and self-regulating geometries of natural microforms). Although anecdotes and historemes get incorporated into historical establishmentarianism, seeing history in a framework of fractals fundamentally resists such appropriations. This poses new challenges for Shakespearean historiography, while underscoring distinctions between Shakespeareanism (sociological epiphenomena) and Shakespeare (the man himself).