Lepto-hadronic interpretation of 2021 RS Ophiuchi nova outburst

Very high energy (VHE; 100 GeV $<$ E $\leq$ 100 TeV) and high energy (HE; 100 MeV $<$ E $\leq$ 100 GeV) gamma-rays were observed from the symbiotic recurrent nova RS Ophiuchi (RS Oph) during its outburst in August 2021, by various observatories such as High Energy Stereoscopic System (H.E.S.S.), Major Atmospheric Gamma Imaging Cherenkov (MAGIC), and {\it Fermi}-Large Area Telescope (LAT). The models explored so far tend to favor a hadronic scenario of particle acceleration over an alternative leptonic scenario. This paper explores a time-dependent lepto-hadronic scenario to explain the emission from the RS Oph source region. We have used simultaneous low frequency radio data observed by various observatories, along with the data provided by H.E.S.S., MAGIC, and \textit{Fermi}-LAT, to explain the multi-wavelength (MWL) spectral energy distributions (SEDs) corresponding to 4 days after the outburst. Our results show that a lepto-hadronic interpretation of the source not only explains the observed HE-VHE gamma-ray data but the corresponding model synchrotron component is also consistent with the first 4 days of low radio frequency data, indicating the presence of non-thermal radio emission at the initial stage of nova outburst. We have also calculated the expected neutrino flux from the source region and discussed the possibility of detecting neutrinos.Comment: 18 pages, 5 figures, 2 tables; accepted for publication in The Astrophysical Journal (ApJ

A comparative study of neonatal and maternal outcome between forceps delivery and vacuum extraction

Background: Aims and objectives of the study were to compare maternal and neonatal outcomes of forceps versus vacuum application in assisted vaginal delivery. Methods: This prospective study was conducted in a tertiary care hospital of West Bengal over one year. Women in labor with vertex presentation were delivered by vacuum and forceps. A total of 100 cases were included of which 50 patients selected for forceps delivery and 50 patients for vacuum extraction. The instruments were either silastic cup vacuum extractor or Wrigley`s outlet forceps. Maternal morbidity was studied in terms of cervical tears, vaginal lacerations, episiotomy extension, perineal tears, PPH, and retention of urine. Neonatal morbidity was studied in terms of Apgar score, instrumental injuries, cephalhematoma, NICU admission and the outcome was compared. Chi square test was used to analyze the data. Results: Observations maternal morbidity viz. episiotomy extension, traumatic PPH were significant in the forceps group (p=0.01). With regards to neonatal morbidity, SNCU admission were significantly higher in forceps delivery (p=0.02) and incidence of cephalohematomas were more in ventouse delivery (p=0.02). Conclusions: Vacuum and forceps should remain appropriate tools in the armamentarium of the modern obstetrician. However, ventouse may be chosen first (if there is no fetal distress) as it is significantly less likely to injure the mother.

Effect of dark matter halo substructures on galaxy rotation curves

The effect of halo substructures on galaxy rotation curves is investigated in this paper using a simple model of dark matter clustering. A dark matter halo density profile is developed based only on the scale free nature of clustering that leads to a statistically self-similar distribution of the substructures at galactic scale. Semi-analytical method is used to derive rotation curves for such a clumpy dark matter density profile. It is found that the halo substructures significantly affect the galaxy velocity field. Based on the fractal geometry of the halo, this self-consistent model predicts an NFW-like rotation curve and a scale free power spectrum of the rotation velocity fluctuations.Comment: 6 pages, 3 figures. Accepted for publication in ApJ. The definitive version will be available at http://iopscience.iop.org

The curious case of J113924.74+164144.0: a possible new group of galaxies at z = 0.0693

J113924.74+164144.0 is an interesting galaxy at z = 0.0693, i.e. D_L ~ 305 Mpc, with tidal-tail-like extended optical features on both sides. There are two neighbouring galaxies, a spiral galaxy J113922.85+164136.3 which has a strikingly similar 'tidal' morphology, and a faint galaxy J113923.58+164129.9. We report HI 21 cm observations of this field to search for signatures of possible interaction. Narrow HI emission is detected from J113924.74+164144.0, but J113922.85+164136.3 shows no detectable emission. The total HI mass detected in J113924.74+164144.0 is 7.7 x 10^9 M_solar. The HI emission from the galaxy is found to be extended and significantly offset from the optical position of the galaxy. We interpret this as signature of possible interaction with the neighbouring spiral galaxy. There is also a possible detection of HI emission from another nearby galaxy J113952.31+164531.8 at z = 0.0680 at a projected distance of 600 kpc, and with a total HI mass of 5.3 x 10^9 M_solar, suggesting that all these galaxies form a loose group at z ~ 0.069.Comment: 5 pages, 1 table, 6 figures. Accepted for publication in MNRAS Letters. The definitive version will be available at http://www.blackwell-synergy.com

Constraining the MOdified Newtonian Dynamics from spherically symmetrical hydrodynamic accretion

The MOdified Newtonian Dynamics (MOND) is an alternative to the dark matter assumption that can explain the observed flat rotation curve of galaxies. Here hydrodynamic accretion is considered to critically check the consistency and to constrain the physical interpretation of this theory. It is found that, in case of spherically symmetrical hydrodynamic accretion, the modified Euler's equation has real solution if the interpretation is assumed to be a modification of the law of dynamics. There is no real solution if it is assumed to be an acceleration scale dependent modification of the gravitational law. With the modified Euler's equation, the steady state mass accretion rate is found to change up to ~ 15%. The astrophysical and cosmological implications of these results are also discussed.Comment: 4 pages, 3 figures. Accepted for publication in MNRAS. The definitive version will be available at http://www.blackwell-synergy.com

Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4

The emergence of resistance against current antimalarial treatments has necessitated the need for the development of novel antimalarial chemotypes. Toward this goal, we recently optimised the antimalarial activity of the dihydroquinazolinone scaffold and showed it targeted PfATP4. Here, we deconstruct the lactam moiety of the tricyclic dihydroquinazolinone scaffold and investigate the structure-activity relationship of the truncated scaffold. It was shown that SAR between scaffolds was largely transferrable and generated analogues with potent asexual stage activity. Evaluation of the truncated analogues against PfATP4 mutant drug resistant parasite strains and in assays measuring PfATP4-associated ATPase activity demonstrated retention of PfATP4 as the molecular target. Analogues exhibited activity against both male and female gametes and multidrug resistant parasites. Limited efficacy of analogues in a P. berghei asexual stage mouse model was attributed to their moderate metabolic stability and low aqueous stability. Further development is required to address these attributes toward the potential use of the dihydroquinazolinone class in a curative and transmission blocking combination antimalarial therapy

Exploration and characterization of the antimalarial activity of cyclopropyl carboxamides that target the mitochondrial protein, cytochrome b.

Drug resistance against antimalarials is rendering them increasingly ineffective and so there is a need for the development of new antimalarials. To discover new antimalarial chemotypes a phenotypic screen of the Janssen Jumpstarter library against the P. falciparum asexual stage was undertaken, uncovering the cyclopropyl carboxamide structural hit class. Structure-activity analysis revealed that each structural moiety was largely resistant to change, although small changes led to the frontrunner compound, WJM280, which has potent asexual stage activity (EC50 40 nM) and no human cell cytotoxicity. Forward genetics uncovered that cyclopropyl carboxamide resistant parasites have mutations and an amplification in the cytochrome b gene. Cytochrome b was then verified as the target with profiling against cytochrome b drug-resistant parasites and a mitochondrial oxygen consumption assay. Accordingly, the cyclopropyl carboxamide class was shown to have slow-acting asexual stage activity and activity against male gametes and exoerythrocytic forms. Enhancing metabolic stability to attain efficacy in malaria mouse models remains a challenge in the future development of this antimalarial chemotype

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials

Background Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. Methods STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)–European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). Findings Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47–2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). Interpretation In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response

Cu(I)-Catalyzed Enantioselective [5+1] Cycloaddition of N-Aromatic Compounds and Alkynes via Chelating-Assisted 1,2-Dearomative Addition

© 2020 American Chemical Society. Copper-catalyzed [5 + 1] cycloadditions of N-aromatic zwitterions have been accomplished by chelation-assisted 1,2-dearomative addition of electron-deficient terminal alkynes. The unique modular skeleton of pyrazino[1,2-a]quinoline could be obtained from the regio- and stereoselective cascade annulation process, which was supported by computational studies. Further, an asymmetric variant of the developed strategy has been successfully extended for enabling access to optically enriched six-member cyclic systems11Nsciescopu

Cu(I)-Catalyzed Enantioselective [5 + 1] Cycloaddition of NAromatic Compounds and Alkynes via Chelating-Assisted 1,2-Dearomative Addition

© 2020 American Chemical Society. Copper-catalyzed [5 + 1] cycloadditions of N-aromatic zwitterions have been accomplished by chelation-assisted 1,2-dearomative addition of electron-deficient terminal alkynes. The unique modular skeleton of pyrazino[1,2-a]quinoline could be obtained from the regio- and stereoselective cascade annulation process, which was supported by computational studies. Further, an asymmetric variant of the developed strategy has been successfully extended for enabling access to optically enriched six-member cyclic systems11Nsciescopu