180 research outputs found
Minimizers with discontinuous velocities for the electromagnetic variational method
The electromagnetic two-body problem has \emph{neutral differential delay}
equations of motion that, for generic boundary data, can have solutions with
\emph{discontinuous} derivatives. If one wants to use these neutral
differential delay equations with \emph{arbitrary} boundary data, solutions
with discontinuous derivatives must be expected and allowed. Surprisingly,
Wheeler-Feynman electrodynamics has a boundary value variational method for
which minimizer trajectories with discontinuous derivatives are also expected,
as we show here. The variational method defines continuous trajectories with
piecewise defined velocities and accelerations, and electromagnetic fields
defined \emph{by} the Euler-Lagrange equations \emph{% on} trajectory points.
Here we use the piecewise defined minimizers with the Li{\'{e}}nard-Wierchert
formulas to define generalized electromagnetic fields almost everywhere (but on
sets of points of zero measure where the advanced/retarded velocities and/or
accelerations are discontinuous). Along with this generalization we formulate
the \emph{generalized absorber hypothesis} that the far fields vanish
asymptotically \emph{almost everywhere%} and show that localized orbits with
far fields vanishing almost everywhere \emph{must} have discontinuous
velocities on sewing chains of breaking points. We give the general solution
for localized orbits with vanishing far fields by solving a (linear) neutral
differential delay equation for these far fields. We discuss the physics of
orbits with discontinuous derivatives stressing the differences to the
variational methods of classical mechanics and the existence of a spinorial
four-current associated with the generalized variational electrodynamics.Comment: corrected minor typo: piecewise differentiable on closed instead of
open interval
Расчёт напряженно-деформированного состояния виброизоляторов сложной формы
Розглянуто пружно-деформований стан гумових віброізоляторів з урахуванням контактної взаємодії з деталями конструкції.Stress-strain state of rubber vibroinsulators is considered, taking into account contact interaction with construction parts
Plasma–wall interaction in laser inertial fusion reactors: novel proposals for radiation tests of first wall materials
Dry-wall laser inertial fusion (LIF) chambers will have to withstand strong bursts of fast charged particles which will deposit tens of kJ m−2 and implant more than 1018 particles m−2 in a few microseconds at a repetition rate of some Hz. Large chamber dimensions and resistant plasma-facing materials must be combined to guarantee the chamber performance as long as possible under the expected threats: heating, fatigue, cracking, formation of defects, retention of light species, swelling and erosion. Current and novel radiation resistant materials for the first wall need to be validated under realistic conditions. However, at present there is a lack of facilities which can reproduce such ion environments. This contribution proposes the use of ultra-intense lasers and high-intense pulsed ion beams (HIPIB) to recreate the plasma conditions in LIF reactors. By target normal sheath acceleration, ultra-intense lasers can generate very short and energetic ion pulses with a spectral distribution similar to that of the inertial fusion ion bursts, suitable to validate fusion materials and to investigate the barely known propagation of those bursts through background plasmas/gases present in the reactor chamber. HIPIB technologies, initially developed for inertial fusion driver systems, provide huge intensity pulses which meet the irradiation conditions expected in the first wall of LIF chambers and thus can be used for the validation of materials too
Sirtuin 6 Activation Rescues the Age-Related Decline in DNA Damage Repair in Primary Human Chondrocytes
While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from young (≤45 years old) as compared to middle-aged (50-65 years old) or older (\u3e70 years old) cadaveric donors. Activation of SIRT6 with MDL-800 improved the repair efficiency, while inhibition with EX-527 reduced the rate of repair and increased the percentage of cells that retain high levels of damage. In addition to affecting repair after acute damage, treating chondrocytes from older donors with MDL-800 for 48 hours significantly reduced the amount of baseline DNA damage. Chondrocytes isolated from the knees of mice between 4 months and 22 months of age revealed both an increase in DNA damage with aging, and a decrease in DNA damage following MDL-800 treatment. Lastly, treating murine cartilage explants with MDL-800 lowered the percentage of chondrocytes with high p16 promoter activity, which supports the concept that using SIRT6 activation to maintain low levels of DNA damage may prevent the initiation of senescence
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Open science, communal culture, and women’s participation in the movement to improve science
Science is undergoing rapid change with the movement to improve science focused largely on reproducibility/replicability and open science practices. This moment of change—in which science turns inward to examine its methods and practices—provides an opportunity to address its historic lack of diversity and noninclusive culture. Through network modeling and semantic analysis, we provide an initial exploration of the structure, cultural frames, and women’s participation in the open science and reproducibility literatures (n = 2,926 articles and conference proceedings). Network analyses suggest that the open science and reproducibility literatures are emerging relatively independently of each other, sharing few common papers or authors. We next examine whether the literatures differentially incorporate collaborative, prosocial ideals that are known to engage members of underrepresented groups more than independent, winner-takes-all approaches. We find that open science has a more connected, collaborative structure than does reproducibility. Semantic analyses of paper abstracts reveal that these literatures have adopted different cultural frames: open science includes more explicitly communal and prosocial language than does reproducibility. Finally, consistent with literature suggesting the diversity benefits of communal and prosocial purposes, we find that women publish more frequently in high-status author positions (first or last) within open science (vs. reproducibility). Furthermore, this finding is further patterned by team size and time. Women are more represented in larger teams within reproducibility, and women’s participation is increasing in open science over time and decreasing in reproducibility. We conclude with actionable suggestions for cultivating a more prosocial and diverse culture of science
Cartilage-specific <i>Sirt6</i> deficiency represses IGF-1 and enhances osteoarthritis severity in mice.
ObjectivesPrior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of Sirt6 deficiency on the development of post-traumatic and age-associated OA in mice.MethodsMale cartilage-specific Sirt6-deficient mice and Sirt6 intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting.ResultsSirt6-deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that SIRT6 depletion significantly repressed cartilage extracellular matrix (eg, COL2A1) and anabolic growth factor (eg, insulin-like growth factor-1 (IGF-1)) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced SIRT6 activation promoted IGF-1 signalling by increasing Aktser473 phosphorylation.ConclusionsSIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA
Suplementacija s antioksidansima i serumski lipidi kod bolesnika s Graves-ovom bolesti: Učinak na LDL-kolesterol
The effect of supplementation with a fixed combination of antioxidants (beta-carotene, selenium, vitamins C and E) on serum lipids was monitored in patients with newly detected Graves\u27 disease. Measurements were made prior to the commencement of therapy and after 30 and 60 days. Patients were randomized into two groups. Test group comprised patients who received antioxidant supplementation in addition to methimazole, while patients treated with methimazole only were in the control group. The concentration of total and HDL-cholesterol increased significantly in test and control groups (p < 0.05) but these groups did not differ significantly. Concentration of LDL-cholesterol increased significantly in the test group only (p < 0.005) and was significantly different from the control group 60 days after the commencing the therapy (p < 0.005). Significant increase in the LDL-cholesterol concentration in the test group requires further investigations.U ovom istraživanju promatran je učinak suplementacije fiksnom kombinacijom antioksidansa (beta-karoten, selen, vitamin C i E) na koncentracije serumskih lipida, u odnosu na brzinu postizanja eutiroze. Mjerenja su obavljena u bolesnika s novo otkrivenom Graves-ovom bolešću liječenih metimazolom (tiamazolom) prije početka terapije, te nakon 30 i 60 dana. Bolesnici su bili randomizirani u dvije skupine. Test skupinu sačinjavali su bolesnici koji su dodatno uzimali antioksidanse, a kontrolnu skupinu bolesnici koji su uzimali samo metimazol (tiamazol). Koncentracije ukupnog i HDL-kolesterola u serumu rasle su tijekom terapije kod bolesnika iz obje skupine (p < 0,05) no, nisu se međusobno značajno razlikovale 60 dana nakon početka terapije. Kod bolesnika test skupine, koncentracija LDL-kolesterola se značajno povećala (p < 0,005) i bila je značajno različita od one u kontrolnoj skupini (p < 0,005), 60 dana nakon početka liječenja.
Rezultati ovog istraživanja ukazuju da suplementacija s ovom kombinacijom antioksidansa nema značajnog utjecaja na promjene koncentracije serumskih lipida kod bolesnika s Graves-ovom bolešću 60 dana nakon početka terapije, s izuzetkom LDL-kolesterola. Zbog značajnog porasta koncentracije LDL-kolesterola kod bolesnika s Graves-ovom bolešću, koji su dodatno uzimali antioksidanse, potrebna su daljnja istraživanja u cilju pojašnjenja opisanih promjena
Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries
BACKGROUND: The mycotoxin zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), synthesized by genera Fusarium, often occur as contaminants in cereal grains and animal feeds. The importance of ZEA on reproductive disorders is well known in domestic animals species, particularly in swine and cattle. In the horse, limited data are available to date on the influence of dietary exposure to ZEA on reproductive health and on its in vitro effects on reproductive cells. The aim of this study was to evaluate the effects of ZEA and its derivatives, alpha and beta-ZOL, on granulosa cells (GCs) from the ovaries of cycling mares. METHODS: The cell proliferation was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test after 3 days exposure at different concentrations of ZEA and its derivatives (from 1 × 10-7 to 0.1 microM). The apoptosis induction was evaluated after 1 day exposure, by DNA analysis using flow cytometry. RESULTS: An increase in cell proliferation with respect to the control was observed in the presence of ZEA at 1 × 10-3 and 1 × 10-4 microM and apoptosis was induced by all mycotoxins at different concentrations. CONCLUSION: The simultaneous presence of apoptosis and proliferation in GC cultures treated with zearalenones could indicate that these mycotoxins could be effective in inducing follicular atresia. These effects of zearalenones may result from both direct interaction with oestrogen-receptors as well as interaction with the enzymes 3alpha (beta)-hydroxysteroid dehydrogenase (HSD), involved in the synthesis and metabolism of endogenous steroid hormones. These cellular disturbances, described for the first time in equine GCs cultured in vitro, could be hypothesized as referred to reproductive failures of unknown ethiology in the mare
Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis
Abstract Introduction Functional status is an integral component of health-related quality of life in patients with ankylosing spondylitis (AS). The purpose of this study was to investigate the role of psychological variables in self-reported functional limitation in patients with AS, while controlling for demographic and medical variables. Methods 294 AS patients meeting modified New York Criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality and helplessness at the baseline visit. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of correlation of psychological variables with functional limitation, as measured by the Bath AS Functional Index (BASFI). Results In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASFI scores, adding an additional 24% to the overall R-square beyond that accounted by demographic and medical variables (R-square 32%), resulting in a final R-square of 56%. Specifically, arthritis helplessness, depression and passive coping beside age, ESR and the Bath AS Radiograph Index accounted for a significant portion of the variance in BASFI scores in the final model. Conclusions Arthritis helplessness, depression, and passive coping accounted for significant variability in self-reported functional limitation beyond demographic and clinical variables in patients with AS. Psychological health should be examined and accounted for when assessing functional status in the AS patients
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