The use of NHCs for generating homoenolate species has gained widespread popularity in recent years. A number of highly stereoselective processes of NHC-homoenolates have emerged. Homoenolate ...reactions have also been employed as key steps in the total synthesis of a number of natural products. The use of compatible co-catalysts, improved NHC-catalyst design and the use of novel precursors for homoenolate generation are among the major developments in this area that were disclosed recently. This tutorial review organises and presents the advancements in this rapidly growing area of catalysis and in the process updates a previous account published in 2011 in this journal.
One objective of this paper is to investigate bifurcation of solutions of Ornstein–Zernike equation in liquid state theory for the gas–liquid coexistence region of simple fluids. The analysis uses a ...discrete form of the Ornstein–Zernike equation in real space, together with a closure relation which provides nearly self consistent thermodynamic properties of fluids governed by interaction potentials like the Lennard-Jones potential. Accurate asymptotic forms of correlation functions are incorporated in the real space algorithm so as to mitigate the influence of cutoff length used in the discrete approximations. The global error reduction of this algorithm is similar to that of Simpson’s rule. It is found that there is no spinodal on the vapor side on a sub-critical isotherm. However, there is a density at which compressibility vanishes, but this lies on a nonphysical branch. There are fold bifurcation points on the vapor and liquid sides together with a ‘no-real-solution-region’ in between. This is followed by a region of negative compressibility extending up to the spinodal on the liquid side. Importantly, it is found that in regions where compressibility is non-positive, there are infinite number of solutions to OZE which violate an integral constraint that is needed for applications to thermodynamics. The emerging picture is somewhat similar to that in the case of the hypernetted-chain-closure. It is also found that complex solutions connect the physical solutions that exist outside the ‘no-real-solution-region’ as well as in region of negative compressibility. The second objective of the paper, in the light of bifurcation scenario, is to evolve an interpretation of the coupling-parameter expansion of correlation functions pertaining to the region of negative compressibility. It is shown that the expansion provides an accurate description of results of the restricted ensembles, implied in mean field theories and simulation methods. Bifurcation of singlet density to an in-homogeneous distribution at a spinodal is also established using a simple equation, which uses the direct correlation function. Thus the paper re-establishes the fact that restriction to a homogeneous singlet density is the root cause of all inconsistencies found in the gas–liquid coexistence region.
•Ornstein–Zernike equation & Martynov–Sarkisov closure.•No spinodal on the vapour side on sub-critical isotherm, but spinodal on the liquid side.•Fold bifurcation points on both sides; complex solutions connect physical solution-branches.•Infinite solutions when compressibility is non-positive; inhomogeneous singlet-density between spinodals.•Coupling parameter expansion results related to restricted ensembles.
Functional magnetic resonance imaging has revealed correlated activities in brain regions even in the absence of a task. Initial studies assumed this resting-state functional connectivity (FC) to be ...stationary in nature, but recent studies have modeled these activities as a dynamic network. Dynamic spatiotemporal models better model the brain activities, but are computationally more involved. A comparison of static and dynamic FCs was made to quantitatively study their efficacies in identifying intrinsic individual connectivity patterns using data from the Human Connectome Project. Results show that the intrinsic individual brain connectivity pattern can be used as a 'fingerprint' to distinguish among and identify subjects and is more accurately captured with partial correlation and assuming static FC. It was also seen that the intrinsic individual brain connectivity patterns were invariant over a few months. Additionally, biological sex identification was successfully performed using the intrinsic individual connectivity patterns, and group averages of male and female FC matrices. Edge consistency, edge variability and differential power measures were used to identify the major resting-state networks involved in identifying subjects and their sex.
In Kerala, a coastal land in India, Ginger is cultivated as a rainfed annual. The current study on morphological characters of seed rhizomes stored in Zero Energy Cool Chambers recorded a weight loss ...of 28% at three months after storage. The number of sprouting buds was maximum (12.25) in the seed rhizomes stored for three months. The dimensions of the bud measured at the varied periods of storage interval showed variation. The length of the bud increased from 0.847μm to 2.19 μm and the breadth reduced from 1.19 μm to 0.703μm in three months of storage. The current study provides the anatomical morphology of ginger seed rhizomes. Histochemical studies of seed rhizome for three months storage showed that the number of cork layers varied from 5-15, size of starch grain decreased on storage from 40 μm to 20 μm and the oil globules found inside the parenchymatous cells increased from 20 μm to 40 μm. These results will be helpful to understand the bud development of ginger seed rhizome during storage.
The mammalian target of rapamycin (mTOR) is responsive to numerous extracellular and intracellular cues and, through the formation of two physically and functionally distinct complexes, has a central ...role in the homeostatic control of cell growth, proliferation and survival. Through the aberrant activation of mTOR signaling, the perception of cellular growth signals becomes disconnected from the processes promoting cell growth, and this underlies the pathophysiology of a number of genetic tumor syndromes and cancers. Here, we review the oncogenes and tumor suppressors comprising the regulatory network upstream of mTOR, highlight the human cancers in which mTOR is activated and discuss how dysregulated mTOR signaling provides tumors a selective growth advantage. In addition, we discuss why activation of mTOR, as a consequence of distinct oncogenic events, results in diverse clinical outcomes, and how the complexity of the mTOR signaling network might dictate therapeutic approaches.
Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously ...had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3.
ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score change was -0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial.
The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).
N-Heterocyclic carbenes (NHCs) have emerged as a powerful class of organocatalysts that mediate a variety of organic transformations. The Benzoin reaction constitutes one of the earliest known ...carbon-carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented.
Abstract
The emission from shock breakouts (SBOs) represents the earliest electromagnetic (EM) signal emitted by cataclysmic events involving the formation or the merger of neutron stars (NSs). As ...such, SBOs carry unique information on the structure of their progenitors and on the explosion energy. The characteristic SBO emission is expected in the UV range, and its detection is one of the key targets of the ULTRASAT satellite. Among SBO sources, we focus on a specific class involving the formation of fast-spinning magnetars in the core-collapse of massive stars. Fast-spinning magnetars are expected to produce a specific signature in the early UV supernova light curve, powered by the extra spin energy quickly released by the NS. Moreover, they are considered as optimal candidates for the emission of long-transient gravitational wave (GW) signals, the detection of which requires early EM triggers to boost the sensitivity of dedicated GW search pipelines. We calculate early supernova UV light curves in the presence of a magnetar central engine, as a function of the explosion energy, ejecta mass, and magnetar parameters. We then estimate the ULTRASAT detection horizon (
z
< 0.15) as a function of the same physical parameters, and the overall expected detection rate, finding that magnetar-powered SBOs may represent up to 1/5 of the total events detected by ULTRASAT. Moreover, at the expected sensitivity of the LIGO/Virgo/Kagra O5 science run, one such event occurring within 5 Mpc will provide an ideal trigger for a GW long-transient search. Future GW detectors like the Einstein Telescope will push the horizon for joint EM-GW detections to 35–40 Mpc.
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