Necroptosis is a caspase-independent form of regulated cell death executed by the receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Recently, ...necroptosis-based cancer therapy has been proposed to be a novel strategy for antitumor treatment. However, a big controversy exists on whether this type of therapy is feasible or just a conceptual model. Proponents believe that because necroptosis and apoptosis use distinct molecular pathways, triggering necroptosis could be an alternative way to eradicate apoptosis-resistant cancer cells. This hypothesis has been preliminarily validated by recent studies. However, some skeptics doubt this strategy because of the intrinsic or acquired defects of necroptotic machinery observed in many cancer cells. Moreover, two other concerns are whether or not necroptosis inducers are selective in killing cancer cells without disturbing the normal cells and whether it will lead to inflammatory diseases. In this review, we summarize current studies surrounding this controversy on necroptosis-based antitumor research and discuss the advantages, potential issues, and countermeasures of this novel therapy.
A fundamental question in evolutionary biology asks whether organisms experiencing similar selective pressures will evolve similar solutions or whether historical contingencies dominate the ...evolutionary process and yield disparate evolutionary outcomes. It is perhaps most likely that both shared selective forces as well as unique histories play key roles in the course of evolution. Consequently, when multiple species face a common environmental gradient, their patterns of divergence might exhibit both shared and unique elements. Here we describe a general framework for investigating and evaluating the relative importance of these contrasting features of diversification. We examined morphological diversification in three species of livebearing fishes across a predation gradient. All species (Gambusia affinisfrom the United States of America,Brachyrhaphis rhabdophorafrom Costa Rica, andPoecilia reticulatafrom Trinidad) exhibited more elongate bodies, a larger caudal peduncle, and a relatively lower position of the eye in predator populations. This shared response suggests that common selective pressures generated parallel outcomes within three different species. However, each species also exhibited unique features of divergence, which might reflect phylogenetic tendencies, chance events, or localized environmental differences. In this system, we found that shared aspects of divergence were of larger magnitude than unique elements, suggesting common natural selective forces have played a greater role than unique histories in producing the observed patterns of morphological diversification. Assessing the nature and relative importance of shared and unique responses should aid in elucidating the relative generality or peculiarity in evolutionary divergence.
In standard models of perceptual decision-making, noisy sensory evidence is considered to be the primary source of choice errors and the accumulation of evidence needed to overcome this noise gives ...rise to speed-accuracy tradeoffs. Here, we investigated how the history of recent choices and their outcomes interact with these processes using a combination of theory and experiment. We found that the speed and accuracy of performance of rats on olfactory decision tasks could be best explained by a Bayesian model that combines reinforcement-based learning with accumulation of uncertain sensory evidence. This model predicted the specific pattern of trial history effects that were found in the data. The results suggest that learning is a critical factor contributing to speed-accuracy tradeoffs in decision-making, and that task history effects are not simply biases but rather the signatures of an optimal learning strategy.
Contamination of drinking water by per- and polyfluoroalkyl substances (PFASs) emitted from manufacturing plants, fire-fighting foams, and urban waste streams has received considerable attention due ...to concerns over toxicity and environmental persistence; however, PFASs in ambient air remain poorly understood, especially in the United States (US). We measured PFAS concentrations in ambient fine particulate matter (PM
2.5
) at 5 locations across North Carolina over a 1 year period in 2019. Thirty-four PFASs, including perfluoroalkyl carboxylic, perfluoroalkane sulfonic, perfluoroalkyl ether carboxylic and sulfonic acids were analyzed by UHPLC/ESI-MS/MS. Quarterly averaged concentrations ranged from <0.004-14.1 pg m
−3
. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) ranged from <0.18 to 14.1 pg m
−3
, comparable to previous PM
2.5
measurements from Canada and Europe (<0.02-3.5 pg m
−3
). Concentrations above 1 pg m
−3
were observed in July-September at Charlotte (14.1 pg m
−3
, PFOA), Wilmington (4.75 pg m
−3
, PFOS), and Research Triangle Park (1.37 pg m
−3
, PFOS). Notably, PM
2.5
has a short atmospheric lifetime (<2 weeks), and thus, the presence of PFOS in these samples raises questions about their sources, since PFOS production was phased out in the US ∼20 years ago. This is the first US study to provide insights into ambient PFAS concentrations in PM
2.5
.
Quarterly PFOS concentrations (pg m
−3
) in ambient PM
2.5
in North Carolina, US. Highest concentrations were measured during July-September.
The synthesis and functionalization of porous organic cages (POCs) for separation have attracted growing interest over the past decade. However, the potential of solid-phase POCs for practical, ...large-scale separations will require incorporation into appropriate gas–solid or liquid–solid contactors. Contactors with more effective mass transfer properties and lower pressure drops than pelletized systems are preferred. Here, we prepared and characterized fiber sorbents with POCs throughout a cellulose acetate (CA) polymer matrix, which were then deployed in model separations. The POC CC3 was shown to be stable after exposure to spinning solvents, as confirmed by NMR, powder X-ray diffraction, and gas sorption experiments. CC3-CA fibers were spun using the dry-jet wet-quench spinning method. Spun fibers retained the adsorptive properties of CC3 powders, as confirmed by CO2 and N2 physisorption and TGA, reaching upward of 60 wt % adsorbent loading, whereas the pelletized CC3 counterparts suffered significant losses in textural properties. The separation capabilities of the CC3-CA fibers are tested with both simulated postcombustion flue gas and with Xe/Kr mixtures. Fixed bed breakthrough experiments performed on fibers samples show that CC3 embedded in polymeric fibers can effectively perform these proof-of-concept gas separations. The development of fiber sorbents embedded with POCs provides an alternative to traditional pelletization for the incorporation of these materials into adsorptive separation systems.
The risk to space crew health and safety posed by exposure to space radiation is regarded as a significant obstacle to future human exploration missions to the Moon, Mars, and beyond. Engineers ...developing future spacecraft or planetary surface habitats can benefit from detailed knowledge of a broad range of possible materials that could provide improved protection to space crews from the deleterious effects of prolonged exposure to the space radiation environment. As one step towards providing this knowledge base, we have developed an empirical weighted figure of merit, referred to as shielding effectiveness, that quantifies the ability of a candidate material to shield space crews from the space radiation environment. The shielding effectiveness, as formulated in this study, accounts for the competing physical aspects of target and projectile fragmentation to provide a comprehensive assessment of radiation protection with regard to passive shielding for space applications. The empirical data used in determining shielding effectiveness was obtained from proton and heavy ion accelerator-based experiments wherein Al2O3:C optically stimulated luminescence dosimeter and CR-39 plastic nuclear track detector were irradiated behind candidate space radiation shielding materials of varying composition and depth. As a test case, the experimental setup was exposed to nominal beams of 1 GeV protons, and 1 GeV/n 28Si and 56Fe heavy ions, the latter serving as a sample of the high linear energy transfer portion of the galactic cosmic ray spectrum. Established radiation dosimetry techniques were used to obtain linear energy transfer spectra, absorbed dose, and dose equivalent as a function of depth. Based on the measurement results, a shielding effectiveness value was computed, quantifying the efficacy of the candidate material as a function of depth, with cumulative weighting factors accounting for the measured percent composition of baryonic matter in the galactic cosmic ray spectrum, and the measured percent contribution to absorbed dose and dose equivalent. The methodology for shielding effectiveness was tested using the common materials of aluminum, copper, graphite, and water, with polyethylene serving as the standard reference. The preliminary shielding effectiveness values for these materials confirm the low Z principle for effective space radiation shielding, and, furthermore, these values tend to be lower when the effectiveness calculation is based on dose equivalent. Of the common materials studied here, at a bulkhead depth of 5 g/cm2, all materials provide a similar level of radiation protection to within standard error. In addition, this method can be used to supplement and/or verify similar findings obtained from transport models.
•A weighted figure of merit that quantifies the efficacy of space radiation shielding.•Test case used Al, Cu, graphite, and water, with polyethylene serving as reference.•This metric confirms the low Z principle for effective space radiation shielding.•Shielding effectiveness tends to be lower when based on dose equivalent.•Water performs just as well as polyethylene at 20 g/cm2 to within standard error.
Psychiatric problems among college students on USA campuses are common. Little is known about similar problems in developing countries, particularly the Arab region. The goal of this study was to ...assess the frequency of selected psychiatric problems among college students in two Arab countries: Qatar and Lebanon, and to compare them to the USA.
The Healthy Minds Study, an online confidential survey of common psychiatric symptoms designed for college campuses was used. We used the Patient Health Questionnaire-9 (PHQ-9) to screen for major depression, the Generalized Anxiety Disorder-7 (GAD-7) to screen for generalized anxiety and the SCOFF questionnaire to screen for eating disorders. Comparisons were made using ANOVA, Chi-Square tests and logistic regressions.
A total of 1841 students participated in the study. The rates of depression (PHQ-9 ≥ 12), generalized anxiety (GAD-7 ≥ 10) and eating disorders (SCOFF≥3) at the combined Arab universities were 34.6, 36.1 and 20.4% respectively. The corresponding rates in the USA were: 12.8, 15.9 and 6.8% (p < 0.001 for all measures). The impact of psychiatric problems on functioning in general and academic performance in particular was more severe in the Arab countries compared to the USA (p < 0.001). Independent predictors of psychiatric problems in general included location, female gender, financial difficulties and poor grades. Being religious had a protective association with mental health.
The rates of depression, anxiety and eating disorders were significantly higher among college students in Qatar and Lebanon compared to the USA. Additional research is needed to determine whether these results reflect methodological limitations or true differences in psychopathology across these populations. If replicated, the results indicate that the psychiatric problems on college campuses in the USA are a microcosm of a global problem that needs global solutions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Variation in terrestrial mammalian skull morphology is known to constrain feeding performance, which in turn influences dietary habits and ultimately fitness. Among mustelids, otters have evolved two ...feeding specializations: underwater raptorial capture of prey (mouth-oriented) and capture of prey by hand (hand-oriented), both of which have likely associations with morphology and bite performance. However, feeding biomechanics and performance data for otters are sparse. The first goal of this study was to investigate the relationships between feeding morphology and bite performance among two mouth-oriented piscivores (Pteronura brasiliensis and Lontra canadensis) and two hand-oriented invertebrate specialists (Enhydra lutris and Aonyx cinerea). Since other vertebrate taxa that are mouth-oriented piscivores tend to possess longer skulls and mandibles, with jaws designed for increased velocity at the expense of biting capability, we hypothesized that mouth-oriented otters would also possess long, narrow skulls indicative of high velocity jaws. Conversely, hand-oriented otters were expected to possess short, blunt skulls with adaptations to increase bite force and crushing capability. Concomitant with these skull shapes we hypothesized that sea otters would possess a greater mandibular bluntness index, providing for a greater mechanical advantage compared to other otter species investigated. A second goal was to examine morphological variation at a finer scale by assessing variation in cranial morphology among three sea otter subspecies. Since diet varies among these subspecies, and their populations are isolated, we hypothesized that the magnitude of mandibular bluntness and concomitant mechanical advantage, as well as occlusal surface area would also vary within species according to their primary food source (fish versus hard invertebrates). Functional expectations were met for comparisons among and within species. Among species the phylogeny suggests a deeply rooted transition to alternative foraging types. Yet within foraging types alternative species were also strongly variable, suggesting either selective differences in the extent or nature of realized foraging mode, or an accumulation of non-adaptive changes during the long independent evolutionary history. At the finest scale, variation among subspecies indicates that trophic adaptation occurred rapidly, making it interesting that we happened to find both deeply and shallowly-rooted transformations associated with diet type in otter species and subspecies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The risk posed by prolonged exposure to space radiation represents a significant obstacle to long-duration human space exploration. Of the ion species present in the galactic cosmic ray spectrum, ...relativistic protons are the most abundant and as such are a relevant point of interest with regard to the radiation protection of space crews involved in future long-term missions to the Moon, Mars, and beyond. This work compared the shielding effectiveness of a number of standard and composite materials relevant to the design and development of future spacecraft or planetary surface habitats. Absorbed dose was measured using Al2O3:C optically stimulated luminescence dosimeters behind shielding targets of varying composition and depth using the 1 GeV nominal energy proton beam available at the NASA Space Radiation Laboratory at the Brookhaven National Laboratory in New York. Absorbed dose scored from computer simulations performed using the multi-purpose Monte Carlo radiation transport code FLUKA agrees well with measurements obtained via the shielding experiments. All shielding materials tested and modeled in this study were unable to reduce absorbed dose below that measured by the (unshielded) front detector, even after depths as large as 30 g/cm2. These results could be noteworthy given the broad range of proton energies present in the galactic cosmic ray spectrum, and the potential health and safety hazard such space radiation could represent to future human space exploration.
Microencapsulated phase change materials (μPCM) are combined with the metal–organic framework (MOF) UiO-66 and a cellulose acetate fiber support to introduce thermal modulation into CO2 capture ...devices operating in subambient conditions. μPCM particles are incorporated into sorbent fibers during the fiber spin dope preparation step and are observed to withstand the spinning and subsequent solvent exchange steps with little to no loss of thermal modulating properties as determined by differential scanning calorimetry (DSC). The spinning of this novel sorbent-μPCM fiber sorbent is the first instance of single step spinning of sorbents with a thermal modulator. It was found that μPCM weight loading as high as 75 wt % was attainable while maintaining spinable fibers. Breakthrough adsorption experiments and subsequent temperature profile analysis were collected to compare CO2 breakthrough capacity and heat release for sorbent systems with and without phase change materials incorporated. In adsorption modules with a diameter of 0.455 cm, where heat dissipation through the module wall dominates the global thermal response of the system, modulated fibers showed a 20–25% increase in breakthrough capacity at short times (CO2 concentration C/C 0 = 0.05) as compared to their unmodulated counterparts. Higher breakthrough capacity indicates the phase change material would help manage the heat effects due to the local contact between the μPCM and the MOF. In larger diameter modules (0.7 cm) where wall heat dissipation effects are less dominant than the 0.455 cm diameter modules, fibers with “inactive” μPCM (i.e., 50 °C below their melting point) show larger sorption-induced thermal excursions and as much as 4× lower capacities at low adsorbate leakage as compared to fibers where the phase change material was active. Through the incorporation of phase change material, the sorbent in the system acts more efficiently, thus potentially driving down adsorption system cost.
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