Investigations of aerosol impacts on hurricanes: virtual seeding flights

This paper examines the feasibility of mitigating the intensity of hurricanes by enhancing the CCN concentrations in the outer rainband region. Increasing CCN concentrations would cause a reduced collision and coalescence, resulting in more supercooled liquid water to be transported aloft which then freezes and enhances convection via enhanced latent heat of freezing. The intensified convection would condense more water ultimately enhancing precipitation in the outer rainbands. Enhanced evaporative cooling from the increased precipitation in the outer rainbands would produce stronger and more widespread areal cold pools which block the flow of energy into the storm core, ultimately inhibiting the intensification of the tropical cyclone. <br></br> We designed a series of multi-grid for which the time of the "virtual flights" as well as the aerosol release rates are varied. A code that simulates the flight of a plane is used to increase the CCN concentrations as an aircraft flies. Results show a significant sensitivity to both the seeding time and the aerosol release rates and support the aforementioned hypothesis

Estimations of free fatty acids (FFA) as a reliable proxy for larval performance in Mediterranean octocoral species

The survival, behavior, and competence period of lecithotrophic larvae depends not only on the energy allocation transferred by maternal colonies, but also on the amount of energy consumed to sustain embryonic, larval, and post-larval development. The objective of the present work is to understand the effect of energy consumption on the performance of lecithotrophic larvae. To this aim, we analysed free fatty acid (FFA) content and composition of the larvae of three Mediterranean octocorals (Corallium rubrum, Eunicella singularis, and Paramuricea clavata) as a proxy for energy consumption. Results showed that C. rubrum larvae consume more FFA than P. clavata, whereas the energy consumed by E. singularis larvae is high but highly variable. These results are in accordance with the larval behavior of these three species, since C. rubrum larvae are characterized by their high swimming activity frequency, P. clavata larvae are almost inactive, and the swimming activity frequency of E. singularis larvae is high, although variable. The differences in FFA composition of the larvae suggest contrasting energetic strategies that could explain the differences in survival and recruitment rates. In fact, high dispersal and recruitment capacities for E. singularis larvae can be inferred from the FFA composition, whereas the high spatial and temporal variability of recruitment observed in C. rubrum may be related to the non-selective transfer of fatty acid (FA) from maternal colonies. Finally, the high recovery rates after mass mortality events observed in P. clavata could be favored by the presence of a specific FA [22:6(n-3)] related to adaptation mechanisms under environmental stresses during the first developmental stages

A numerical modelling investigation of the role of diabatic heating and cooling in the development of a mid-level vortex prior to tropical cyclogenesis – Part 1: The response to stratiform components of diabatic forcing

Mid-tropospheric mesoscale convective vortices have been often observed to precede tropical cyclogenesis. Moreover, recent cloud-resolving numerical modelling studies that are initialized with a weak cyclonic mid-tropospheric vortex sometimes show a considerable intensification of the mid-level circulation prior to the development of the strong cyclonic surface winds that characterize tropical cyclogenesis. The objective of this two-part study is to determine the processes that lead to the development of a prominent mid-level vortex during a simulation of the transformation of a tropical disturbance into a tropical depression, in particular the role of diabatic heating and cooling. For simplicity simulations are initialized from a quiescent environment. In this first part, results of the numerical simulation are described and the response to stratiform components of the diabatic forcing is investigated. In the second part, the contribution of diabatic heating in convective cells to the development of the mid-level vortex is examined.Results show that after a period of intense convective activity, merging of anvils from numerous cells creates an expansive stratiform ice region in the upper troposphere, and at its base a mid-level inflow starts to develop. Subsequently conservation of angular momentum leads to strengthening of the mid-level circulation. A 12&thinsp;h period of mid-level vortex intensification is examined during which the mid-level tangential winds become stronger than those at the surface. The main method employed to determine the role of diabatic forcing in causing the mid-level inflow is to diagnose it from the full physics simulation and then impose it in a simulation with hydrometeors removed and the microphysics scheme turned off. Removal of hydrometeors is achieved primarily through artificially increasing their fall speeds 3&thinsp;h prior to the 12&thinsp;h period. This results in a state that is in approximate gradient wind balance, with only a weak secondary circulation. Then, estimates of various components of the diabatic forcing are imposed as source terms in the thermodynamic equation in order to examine the circulations that they independently induce. Sublimation cooling at the base of the stratiform ice region is shown to be the main factor responsible for causing the strong mid-level vortex to develop, with smaller contributions from stratiform heating aloft and low-level melting and evaporation. This contrasts with the findings of previous studies of mid-latitude vortices that indicate sublimation plays a relatively minor role. An unanticipated result is that the central cool region that develops near the melting level is to a large degree due to compensating adiabatic ascent in response to descent driven by diabatic cooling adjacent to the central region, rather than in situ diabatic cooling. The mid-level inflow estimated from stratiform processes is notably weaker than for the full physics simulation, suggesting a moderate contribution from diabatic forcing in convective cells.</p

A variant of green fluorescent protein exclusively deposited to active intracellular inclusion bodies

Background: Inclusion bodies (IBs) were generally considered to be inactive protein deposits and did not hold any attractive values in biotechnological applications. Recently, some IBs of recombinant proteins were confirmed to show their functional properties such as enzyme activities, fluorescence, etc. Such biologically active IBs are not commonly formed, but they have great potentials in the fields of biocatalysis, material science and nanotechnology. Results: In this study, we characterized the IBs of DL4, a deletion variant of green fluorescent protein which forms active intracellular aggregates. The DL4 proteins expressed in Escherichia coli were exclusively deposited to IBs, and the IBs were estimated to be mostly composed of active proteins. The spectral properties and quantum yield of the DL4 variant in the active IBs were almost same with those of its native protein. Refolding and stability studies revealed that the deletion mutation in DL4 didn&apos;t affect the folding efficiency of the protein, but destabilized its structure. Analyses specific for amyloid-like structures informed that the inner architecture of DL4 IBs might be amorphous rather than well-organized. The diameter of fluorescent DL4 IBs could be decreased up to 100-200 nm by reducing the expression time of the protein in vivo. Conclusions: To our knowledge, DL4 is the first GFP variant that folds correctly but aggregates exclusively in vivo without any self-aggregating/assembling tags. The fluorescent DL4 IBs have potentials to be used as fluorescent biomaterials. This study also suggests that biologically active IBs can be achieved through engineering a target protein itself.open0

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

OBJECTIVES: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. METHODS: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. RESULTS: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19

EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19

Practice Inquiry: Clinical Uncertainty as a Focus for Small-Group Learning and Practice Improvement

PROBLEM: Many primary care physicians in nonacademic settings lack a collegial forum for engaging the clinical uncertainties inherent in their work. PROGRAM DESCRIPTION: “Practice Inquiry” is proposed as a set of small-group, practice-based learning and improvement (PBLI) methods designed to help clinicians better manage case-based clinical uncertainty. Clinicians meet regularly at their offices/clinics to present dilemma cases, share clinical experience, review evidence for blending with experience, and draw implications for practice improvement. From 2001 through 2005, Practice Inquiry was introduced to sites in the San Francisco Bay Area as a demonstration effort. Meeting rosters, case logs, a feedback survey, and meeting field notes documented implementation and provided data for a formative, qualitative evaluation. PROGRAM EVALUATION: Of the 30 sites approached, 14 held introductory meetings. As of summer 2006, 98 clinicians in 11 sites continue to hold regularly scheduled group meetings. Of the 118 patient cases presented in the seven oldest groups, clinician–patient relationship and treatment dilemmas were most common. Clinician feedback and meeting transcript data provided insights into how busy practitioners shared cases, developed trust, and learned new knowledge/skills for moving forward with patients. DISCUSSION: Ongoing clinician involvement suggests that Practice Inquiry is a feasible, acceptable, and potentially useful set of PBLI methods. Two of the Practice Inquiry’s group learning tasks received comparatively less focus: integrating research evidence with clinical experience and tracking dilemma case outcomes. Future work should focus on reducing the methodological limitations of a demonstration effort and examining factors affecting clinician participation. Set-aside work time for clinicians, or other equally potent incentives, will be necessary for the further elaboration of these PBLI methods aimed at managing uncertainty

Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis

Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Buildup of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates of Escherichiacoli and Acinetobacterbaumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Objectives: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. Methods: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. Results: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy Conclusions: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19