Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).
The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.
ObjectivesTo compare health-related quality of life (HRQoL) before and after treatment with etanercept in patients with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis using spydergram representations. Methods Data from randomised, controlled trials of etanercept in patients with RA, PsA and psoriasis were analysed. HRQoL was assessed by the medical outcomes survey short form 36 (SF-36) physical (PCS) and mental (MCS) component summary and domain scores. Baseline comparisons with age and gender-matched norms and treatment-associated changes in domain scores were quantifi ed using spydergrams and the health utility SF-6D measure.
We discuss the unusual critical behavior of a generalized XY model containing both 2π-periodic and π-periodic couplings between sites, allowing for ordinary vortices and half-vortices. The phase diagram of this system includes both single-particle condensate and pair-condensate phases. Using a field theoretic formulation and worm algorithm Monte Carlo simulations, we show that in two dimensions it is possible for the system to pass directly from the disordered (high temperature) phase to the single particle (quasi)-condensate via an Ising transition, a situation reminiscent of the 'deconfined criticality' scenario.More than 25 years ago, Korshunov [1] and Lee and Grinstein [2] discussed the statistical mechanics of certain generalizations of the familiar XY model. XY models are the simplest systems capturing the rich physics of vortices, and these topological defects are well known to govern the critical behavior in two dimensions [3]. The generalizations discussed by the above authors give rise to half vortices, about which the XY order parameter winds by π, connected by strings with a finite tension. This in turn leads to a far richer phase diagram (see Fig. 1), whose essential elements were verified by numerical simulation [4].Over time there has been considerable interest in identifying systems where the physics of half vortices and strings plays a role, ranging from nematic liquid crystals [2,5] to the A-phase of 3 He [1,6], to spinor Bose condensates [7,8]. Indeed, half vortices have now been directly observed in exciton-polariton condensates [9]. In recent years a large amount of activity has focused on one particular candidate: a gas of attractive bosons. It can have two distinct superfluid phases: an atomic superfluid of bosons and a molecular superfluid of boson pairs, with the latter supporting half vortices [10,11]. Such a system is in general likely to be unstable to collapse, but a possible resolution of this difficulty is to harness threebody loss to project out triple occupancy of each site of an optical lattice [12]. This idea led to a resurgence of interest in the problem [13][14][15][16][17].We have looked anew at the phase diagram of this type of system. Previous studies found that one could either pass directly from the normal state to the atomic condensate at low temperatures, or first into a molecular condensate with no single-particle long-range order, and thence to the atomic condensate in an Ising transition. Remarkably, we find that in two dimensions there is a region of the finite temperature phase diagram where the normalto-atomic superfluid transition is of the Ising, rather than the Kosterlitz-Thouless type (see Fig. 1). Such unconventional behavior is reminiscent of the 'deconfined criticality' scenario [18]. The two have a common origin in that the expected proliferation of point-like defects is suppressed by critical fluctuations. Our prediction is further supported by Monte Carlo simulations using the We discuss the unusual critical behavior of a generalized XY model containi...
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