TNF is a pleiotropic cytokine with important functions in homeostasis and disease pathogenesis. Recent discoveries have provided insights into TNF biology that introduce new concepts for the ...development of therapeutics for TNF-mediated diseases. The model of TNF receptor signalling has been extended to include linear ubiquitination and the formation of distinct signalling complexes that are linked with different functional outcomes, such as inflammation, apoptosis and necroptosis. Our understanding of TNF-induced gene expression has been enriched by the discovery of epigenetic mechanisms and concepts related to cellular priming, tolerization and induction of 'short-term transcriptional memory'. Identification of distinct homeostatic or pathogenic TNF-induced signalling pathways has introduced the concept of selectively inhibiting the deleterious effects of TNF while preserving its homeostatic bioactivities for therapeutic purposes. In this Review, we present molecular mechanisms underlying the roles of TNF in homeostasis and inflammatory disease pathogenesis, and discuss novel strategies to advance therapeutic paradigms for the treatment of TNF-mediated diseases.
Contrast-Associated Acute Kidney Injury Mehran, Roxana; Dangas, George D; Weisbord, Steven D
The New England journal of medicine,
05/2019, Letnik:
380, Številka:
22
Journal Article
Environmental Toxicants Morton Lippmann, George D. Leikauf
2020, 2020-02-19, 2020-03-03
eBook
An Updated Reference on Human Exposure to Environmental Toxicants and A Study of Their Impact on Public Health With the 4th edition of Environmental Toxicants: Human Exposures and Their Health ...Effects, readers have access to up-to-date information on the study and science of environmental toxicology and public health worldwide. Practitioners and professionals can use this resource to understand newly discovered information on the adverse health effects of toxins and pollutants in air, water, and occupational and environmental environments on large human populations. The 4th edition of this book is updated to reflect new knowledge and research on: ? Performing risk assessments on exposed individuals ? Assessing the effects of toxicants and substances on large populations for health and medical professionals ? Patterns of human exposure to select chemical toxicants ? World Trade Center dust, agents for chemical terrorism, and nanoparticles For health professionals, including health authorities, public health officials, physicians, and industrial managers, who are seeking new research and techniques for managing environmental substances, this invaluable reference will guide you through in a thorough, easy- to-read manner.
This Perspective is intended to raise questions about the conventional interpretation of protein folding. According to the conventional interpretation, developed over many decades, a protein ...population can visit a vast number of conformations under unfolding conditions, but a single dominant native population emerges under folding conditions. Accordingly, folding comes with a substantial loss of conformational entropy. How is this price paid? The conventional answer is that favorable interactions between and among the side chains can compensate for entropy loss, and moreover, these interactions are responsible for the structural particulars of the native conformation. Challenging this interpretation, the Perspective introduces a proposal that high energy (i.e., unfavorable) excluding interactions winnow the accessible population substantially under physical–chemical conditions that favor folding. Both steric clash and unsatisfied hydrogen bond donors and acceptors are classified as excluding interactions, so called because conformers with such disfavored interactions will be largely excluded from the thermodynamic population. Both excluding interactions and solvent factors that induce compactness are somewhat nonspecific, yet together they promote substantial chain organization. Moreover, proteins are built on a backbone scaffold consisting of α‐helices and strands of β‐sheet, where the number of hydrogen bond donors and acceptors is exactly balanced. These repetitive secondary structural elements are the only two conformers that can be both completely hydrogen‐bond satisfied and extended indefinitely without encountering a steric clash. Consequently, the number of fundamental folds is limited to no more than ~10,000 for a protein domain. Once excluding interactions are taken into account, the issue of “frustration” is largely eliminated and the Levinthal paradox is resolved. Putting the “bottom line” at the top: it is likely that hydrogen‐bond satisfaction represents a largely under‐appreciated parameter in protein folding models.
We present new measurements of the intensity of the ionizing ultraviolet background and the global emissivity of ionizing photons over 2 < z < 5. Our results are based on a suite of updated ...measurements of physical properties of the high-redshift intergalactic medium (IGM), including gas temperatures and the opacity of the IGM to Lyα and ionizing photons. Consistent with previous works, we find a relatively flat hydrogen photoionization rate over 2 < z < 5, although our measurements are roughly a factor of 2 higher than the 2008 values of Faucher-Giguère et al., due primarily to our lower gas temperatures. The ionizing emissivity we derive is also generally higher than other recent estimates due to a combination of lower gas temperatures, higher ionizing opacity and an accounting of cosmological radiative transfer effects. We find evidence that the emissivity increases from z ∼ 3 to 5, reaching ∼5 ionizing photons per atom per Gyr at z = 4.75 for realistic galaxy spectra. We further find that galaxies must dominate the emissivity near 1 Ryd at z ≥ 4, and possibly at all redshifts z ≥ 2.4. Our results suggest that the globally averaged ionizing 'efficiency' of star-forming galaxies increases substantially with redshift over 3.2 ≤ z ≤ 4.75. This trend is consistent with the conclusion often drawn from reionization models that the ionizing efficiency of galaxies must be higher during reionization in order for galaxies to reionize the IGM by z = 6. Our emissivity values at z ∼ 5 suggest that ionizing photons may have been a factor of 2 more abundant during the final stages of reionization than previously indicated. The evolution of the ionizing emissivity over 2 < z < 5 suggests, moreover, that the steep decline in the photoionization rate from z ∼ 5 to 6 may indicate a rapid evolution in the mean free path at z > 5.
Preparation of natural hazards maps are vital and essential for urban development. The main scope of this study is to synthesize natural hazard maps in a single multi-hazard map and thus to identify ...suitable areas for the urban development. The study area is the drainage basin of Xerias stream (Northeastern Peloponnesus, Greece) that has frequently suffered damages from landslides, floods and earthquakes.
Landslide, flood and seismic hazard assessment maps were separately generated and further combined by applying the Analytical Hierarchy Process (AHP) and utilizing a Geographical Information System (GIS) to produce a multi-hazard map. This map represents the potential suitability map for urban development in the study area and was evaluated by means of uncertainty analysis.
The outcome revealed that the most suitable areas are distributed in the southern part of the study area, where the landslide, flood and seismic hazards are at low and very low level. The uncertainty analysis shows small differences on the spatial distribution of the suitability zones. The produced suitability map for urban development proves a satisfactory agreement between the suitability zones and the landslide and flood phenomena that have affected the study area. Finally, 40% of the existing urban pattern boundaries and 60% of the current road network are located within the limits of low and very low suitability zones.
Display omitted
•Individual landslide, flood and seismic hazard assessment maps are produced.•Natural hazard maps are created and correlated via multi-criteria analysis.•Suitable sites for urban development are selected using multi-hazard map.•Suitable area for urban development is located in the southern part of the study area.•Almost 40% of the urban area is located in the low to very low susceptibility zones.
The type of bacteria, bacterial cell concentration, initial urea concentration, reaction temperature, the initial Ca
2+ concentration, ionic strength, and the pH of the media are some factors that ...control the activity of the urease enzyme, and may have a significant impact on microbial carbonate precipitation (MCP). Factorial experiments were designed based on these factors to determine the optimum conditions that take into consideration economic advantage while at the same time giving quality results.
Sporosarcina pasteurii strain ATCC 11859 was used at constant temperature (25
°C) and ionic strength with varying amounts of urea, Ca
2+, and bacterial cell concentration. The results indicate that the rate of ureolysis (
k
urea) increases with bacterial cell concentration, and the bacterial cell concentration had a greater influence on
k
urea than initial urea concentration. At 25
mM Ca
2+ concentration, increasing bacterial cell concentration from 10
6 to 10
8
cells
mL
−1 increased the CaCO
3 precipitated and CO
2 sequestrated by over 30%. However, when the Ca
2+ concentration was increased 10-fold to 250
mM Ca
2+, the amount of CaCO
3 precipitated and CO
2 sequestrated increased by over 100% irrespective of initial urea concentration. Consequently, the optimum conditions for MCP under our experimental conditions were 666
mM urea and 250
mM Ca
2+ at 2.3
×
10
8
cells
mL
−1 bacterial cell concentration. However, a greater CaCO
3 deposition is achievable with higher concentrations of urea, Ca
2+, and bacterial cells so long as the respective quantities are within their economic advantage. X-ray Diffraction, Scanning Electron Microscopy and Energy Dispersive X-ray analyzes confirmed that the precipitate formed was CaCO
3 and composed of predominantly calcite crystals with little vaterite crystals.
Here, a single‐step, biomimetic approach for the realization of omnidirectional transparent antireflective glass is reported. In particular, it is shown that circularly polarized ultrashort laser ...pulses produce self‐organized nanopillar structures on fused silica (SiO2). The laser‐induced nanostructures are selectively textured on the glass surface in order to mimic the spatial randomness, pillar‐like morphology, as well as the remarkable antireflection properties found on the wings of the glasswing butterfly, Greta oto, and various Cicada species. The artificial structures exhibit impressive antireflective properties, both in the visible and infrared frequency ranges, which are remarkably stable over time. Accordingly, the laser‐processed glass surfaces show reflectivity smaller than 1% for various angles of incidence in the visible spectrum for s–p linearly polarized configurations. However, in the near‐infrared spectrum, the laser‐textured glass shows higher transmittance compared to the pristine. It is envisaged that the current results will revolutionize the technology of antireflective transparent surfaces and impact numerous applications from glass displays to optoelectronic devices.
A novel single‐step and chemical‐free process for the fabrication of broadband, omnidirectional, antireflective glass, using laser nanostructuring, is demonstrated. Nanostructures are selectively textured on glass to mimic the morphology and the remarkable antireflection properties found on the Greta oto butterfly and Cicada wings. Bioinspired glass could revolutionize the antireflection technology and impact numerous applications, ranging from displays to optoelectronic devices.
A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).
Two similarly designed, double-masked, randomized, ...phase 3 trials, VISTA(DME) and VIVID(DME).
We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.
Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.
The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.
Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.
At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.
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