Lithium chloride modulates chondrocyte primary cilia and inhibits Hedgehog signaling

This work was supported in part by funding from the AO Foundation (project S-12-15K) and the Medical Research Council (Swindon, United Kingdom) (MR/L002876/1). C.A.P. was supported by the Royal Society of New Zealand through a James Cook Research Fellowshi

The influence of location, source, and emission type in estimates of the human health benefits of reducing a ton of air pollution

The benefit per ton ($/ton) of reducing PM2.5 varies by the location of the emission reduction, the type of source emitting the precursor, and the specific precursor controlled. This paper examines how each of these factors influences the magnitude of the$/ton estimate. We employ a reduced-form air quality model to predict changes in ambient PM2.5 resulting from an array of emission control scenarios affecting 12 different combinations of sources emitting carbonaceous particles, NOx, SOx, NH3, and volatile organic compounds. We perform this modeling for each of nine urban areas and one nationwide area. Upon modeling the air quality change, we then divide the total monetized health benefits by the PM2.5 precursor emission reductions to generate $/ton metrics. The resulting$/ton estimates exhibit the greatest variability across certain precursors and sources such as area source SOx, point source SOx, and mobile source NH3. Certain $/ton estimates, including mobile source NOx, exhibit significant variability across urban areas. Reductions in carbonaceous particles generate the largest$/ton across all locations

Cerenkov Radiator Driven by a Superconducting RF Electron Gun

Abstract The Naval Postgraduate School (NPS), Niowave, Inc., and Boeing have recently demonstrated operation of the first superconducting RF electron gun based on a quarter wave resonator structure. In preliminary tests, this gun has produced 10 ps long bunches with charge in excess of 78 pC, and with beam energy up to 396 keV. Initial testing occurred at Niowave's Lansing, MI facility, but the gun and diagnostic beam line are planned for installation in California in the near future. The design of the diagnostic beam line is conducive to the addition of a Cerenkov radiator without interfering with other beam line operations. Design and simulations of a Cerenkov radiator, consisting of a dielectric lined waveguide will be presented. The dispersion relation for the structure is determined and the beam interaction is studied using numerical simulations. The characteristics of the microwave radiation produced in both the short and long bunch regimes will be presented

Configurational Entropy and Diffusivity of Supercooled Water

We calculate the configurational entropy S_conf for the SPC/E model of water for state points covering a large region of the (T,rho) plane. We find that (i) the (T,rho) dependence of S_conf correlates with the diffusion constant and (ii) that the line of maxima in S_conf tracks the line of density maxima. Our simulation data indicate that the dynamics are strongly influenced by S_conf even above the mode-coupling temperature T_MCT(rho).Comment: Significant update of reference

Composition of the pericellular matrix modulates the deformation behaviour of chondrocytes in articular cartilage under static loading

The aim was to assess the role of the composition changes in the pericellular matrix (PCM) for the chondrocyte deformation. For that, a three-dimensional finite element model with depth-dependent collagen density, fluid fraction, fixed charge density and collagen architecture, including parallel planes representing the split-lines, was created to model the extracellular matrix (ECM). The PCM was constructed similarly as the ECM, but the collagen fibrils were oriented parallel to the chondrocyte surfaces. The chondrocytes were modelled as poroelastic with swelling properties. Deformation behaviour of the cells was studied under 15% static compression. Due to the depth-dependent structure and composition of cartilage, axial cell strains were highly depth-dependent. An increase in the collagen content and fluid fraction in the PCMs increased the lateral cell strains, while an increase in the fixed charge density induced an inverse behaviour. Axial cell strains were only slightly affected by the changes in PCM composition. We conclude that the PCM composition plays a significant role in the deformation behaviour of chondrocytes, possibly modulating cartilage development, adaptation and degeneration. The development of cartilage repair materials could benefit from this information

A mixed-methods evaluation of the acceptability and fidelity of the James’ Place model for men experiencing suicidal crisis

Background: Research supports development of informal, community-based suicide prevention interventions that can be tailored to suit men’s unmet needs. The James’ Place model (JPM) is a community-based, clinical suicide prevention intervention for men experiencing suicidal crisis. Evidence supports the efficacy of the JPM and there are plans to expand to additional sites across the UK. This study evaluates therapists perceived acceptability of the JPM, and if fidelity to the planned delivery of the model is maintained within therapeutic practice. Method: A mixed-methods design was used. Descriptive analyses of 30 completed intervention cases were examined to review fidelity of the model against the intervention delivery plan. Eight therapists took part in semi-structured interviews between November 2021 and March 2022 exploring the perceived acceptability, and barriers and facilitators to delivering the JPM. Results: Descriptive analyses of James’ Place audit notes revealed high levels of adherence to the JPM amongst therapists, but highlighted components of the model needed to be tailored according to individual men’s needs. Thematic analysis led to the development of five themes. The first theme, therapeutic environment highlighted importance of the therapy setting. The second theme identified was specialised suicide prevention training in the JPM that facilitated therapists understanding and expertise. The third theme identified was therapy engagement which discusses men’s engagement in therapy. The fourth theme, person-centred care related to adaptation of delivery of JPM components. The final theme, adapting the JPM to individual needs describes tailoring of the JPM by therapists to be responsive to individual men’s needs. Conclusion: The findings evidence therapist’s acceptability and their moderate adherence to the JPM. Flexibility in delivery of the JPM enables adaptation of the model and co-production of therapy to meet men’s needs. Implications for clinical practice are discussed

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

Isotope effect on the transition temperature TcT_c in Fe-based superconductors: the current status

The results of the Fe isotope effect (Fe-IE) on the transition temperature $T_c$ obtained up to date in various Fe-based high temperature superconductors are summarized and reanalyzed by following the approach developed in [Phys. Rev. B 82, 212505 (2010)]. It is demonstrated that the very controversial results for Fe-IE on $T_c$ are caused by small structural changes occurring simultaneously with the Fe isotope exchange. The Fe-IE exponent on $T_c$ [$\alpha_{\rm Fe}=-(\Delta T_c/T_c)/(\Delta M/M)$, $M$ is the isotope mass] needs to be decomposed into two components with the one related to the structural changes ($\alpha_{\rm Fe}^{\rm str}$) and the genuine (intrinsic) one ($\alpha_{\rm Fe}^{\rm int}$). The validity of such decomposition is further confirmed by the fact that $\alpha_{\rm Fe}^{\rm int}$ coincides with the Fe-IE exponent on the characteristic phonon frequencies $\alpha_{\rm Fe}^{\rm ph}$ as is reported in recent EXAFS and Raman experiments.Comment: 7 pages, 4 figures. The paper is partially based on the results published in [New J. Phys. 12, 073024 (2010) = arXiv:1002.2510] and [Phys. Rev. B 82, 212505 (2010) = arXiv:1008.4540

Liquid-liquid critical point in supercooled silicon

A novel liquid-liquid phase transition has been proposed and investigated in a wide variety of pure substances recently, including water, silica and silicon. From computer simulations using the Stillinger-Weber classical empirical potential, Sastry and Angell [1] demonstrated a first order liquid-liquid transition in supercooled silicon, subsequently supported by experimental and simulation studies. Here, we report evidence for a liquid-liquid critical end point at negative pressures, from computer simulations using the SW potential. Compressibilities exhibit a growing maximum upon lowering temperature below 1500 K and isotherms exhibit density discontinuities below 1120 K, at negative pressure. Below 1120 K, isotherms obtained from constant volume-temperature simulations exhibit non-monotonic, van der Waals-like behavior signaling a first order transition. We identify Tc ~ 1120 +/- 12 K, Pc -0.60 +/- 0.15 GPa as the critical temperature and pressure for the liquid-liquid critical point. The structure of the liquid changes dramatically upon decreasing the temperature and pressure. Diffusivities vary over 4 orders of magnitude, and exhibit anomalous pressure dependence near the critical point. A strong relationship between local geometry quantified by the coordination number, and diffusivity, is seen, suggesting that atomic mobility in both low and high density liquids can usefully be analyzed in terms of defects in the tetrahedral network structure. We have constructed the phase diagram of supercooled silicon. We identify the lines of compressibility, density extrema (maxima and minima) and the spinodal which reveal the interconnection between thermodynamic anomalies and the phase behaviour of the system as suggested in previous works [2-9]Comment: (to be published in revised form); small corrections to previous version; Nature Physics 201

The broad-spectrum antimicrobial potential of [Mn(CO)4(S2CNMe(CH2CO2H))], a water-soluble CO-releasing molecule (CORM-401): intracellular accumulation, transcriptomic and statistical analyses, and membrane Polarization

Aims: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. Results: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo, but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity. CORM-401 stimulates respiration, polarizes the cytoplasmic membrane in an uncoupler-like manner, and elicits loss of intracellular potassium and zinc. Transcriptomics and mathematical modeling of transcription factor activities reveal a multifaceted response characterized by elevated expression of genes encoding potassium uptake, efflux pumps, and envelope stress responses. Regulators implicated in stress responses (CpxR), respiration (Arc, Fnr), methionine biosynthesis (MetJ), and iron homeostasis (Fur) are significantly disturbed. Although CORM-401 reduces bacterial growth in combination with cefotaxime and trimethoprim, fractional inhibition studies reveal no interaction. Innovation: We present the most detailed microbiological analysis yet of a CORM that is not a ruthenium carbonyl. We demonstrate CO-independent striking effects on the bacterial membrane and global transcriptomic responses. Conclusions: CORM-401, contrary to our expectations of a CO delivery vehicle, does not inhibit respiration. It accumulates in the cytoplasm, acts like an uncoupler in disrupting cytoplasmic ion balance, and triggers multiple effects, including osmotic stress and futile respiration