Study of springback of green bodies using micromechanical experiments and the discrete element method

The Discrete Element Method (DEM) is today a commonly used tool to simulate compaction of particulate media. The main issue when using DEM in compaction problems is the description of the contact between two powder particles. If the material properties are known, analytical and semi-analytical methods can be used [1,2] but for many industrial applications, for instance spray dried granules, the mechanical behaviour is unknown. The compaction behaviour and green properties of a cemented carbide powder is studied in this work and the issue of the contact description is solved by performing experiments on the powder granules. Firstly, compression tests are made on the single granules giving information of the mechanical properties at low strains. To get information at high strains, which are needed in powder compaction simulations, nanoindentation tests are performed. The measured material parameters are used in a FE model of two spheres in contact and the resulting contact law is exported to a DEM program. The DEM program is used to investigate the compaction properties of a powder compact and especially the springback during unloading which is important for predicting the final shape of the product. The results are compared with presently performed experiments and the applicability range of the discrete element simulations will be discussed

Differential cytokine regulation by NF-κB and AP-1 in Jurkat T-cells

BACKGROUND: Activator protein (AP)-1 and nuclear factor (NF)-kappaB largely control T-cell activation, following binding of foreign antigens to the T-cell receptor leading to cytokine secretion. Elevated levels of pro-inflammatory cytokines and chemokines such as TNF, IL-6 and CXCL8 are associated with several human diseases including cystic fibrosis, pulmonary fibrosis and AIDS. The aim of this study was to investigate the role of the transcription factors, AP-1 and NF-kappaB, in IL-6 and CXCL8 regulation in Jurkat T-cells. RESULTS: Phorbol myristate acetate (PMA) exposure resulted in an up-regulation of AP-1 and down-regulation of NF-kappaB activity, however, exposure to heat killed (HK) Escherichia. coli MG1655 resulted in a dose-dependent increase in NF-kappaB activity without affecting AP-1. The cytokine profile revealed an up-regulation of the chemokine CXCL8 and the pro-inflammatory cytokines TNF, IL-2 and IL-6 following treatment with both PMA and HK E. coli, while the levels of the anti-inflammatory cytokine IL-10 were not affected by PMA but were significantly down-regulated by HK E. coli. AP-1 activation was significantly increased 2 h after PMA exposure and continued to increase thereafter. In contrast, NF-kappaB responded to PMA exposure by a rapid up-regulation followed by a subsequent down-regulation. Increased intracellular Ca2+ concentrations countered the down-regulation of NF-kappaB by PMA, while similar treatment with calcium ionophore resulted in a reduced NF-kappaB activity following induction with HK E. coli. In order to further study NF-kappaB activation, we considered two up-stream signalling proteins, PKC and Bcl10. Phosphorylated-PKC levels increased in response to PMA and HK E. coli, while Bcl10 levels significantly decreased following PMA treatment. Using an NF-kappaB activation inhibitor, we observed complete inhibition of IL-6 expression while CXCL8 levels only decreased by 40% at the highest concentration. Treatment of Jurkat T-cells with PMA in the presence of JNK-inhibitor suppressed both CXCL8 and IL-6 while PKC-inhibitor primarily decreased CXCL8 expression. CONCLUSION: The present study shows that NF-kappaB regulated IL-6 but not CXCL8. This complex regulation of CXCL8 suggests that there is a need to further evaluate the signalling pathways in order to develop new treatment for diseases with elevated CXCL8 levels, such as AIDS and autoimmune diseases

17beta-estradiol induced vitellogenesis is inhibited by cortisol at the post-transcriptional level in Arctic char (Salvelinus alpinus)

This study was performed to investigate stress effects on the synthesis of egg yolk precursor, vitellogenin (Vtg) in Arctic char (Salvelinus alpinus). In particular the effect of cortisol (F) was determined since this stress hormone has been suggested to interfere with vitellogenesis and is upregulated during sexual maturation in teleosts. Arctic char Vtg was purified and polyclonal antibodies were produced in order to develop tools to study regulation of vitellogenesis. The Vtg antibodies were used to develop an enzyme-linked immunosorbent assay. The corresponding Vtg cDNA was cloned from a hepatic cDNA library in order to obtain DNA probes to measure Vtg mRNA expression. Analysis of plasma from juvenile Arctic char, of both sexes, exposed to different steroids showed that production of Vtg was induced in a dose dependent fashion by 17β-estradiol (E2), estrone and estriol. Apart from estrogens a high dose of F also upregulated Vtg. In addition, F, progesterone (P) and tamoxifen were tested to determine these compounds ability to modulate E2 induced Vtg synthesis at both the mRNA and protein level. Tamoxifen was found to inhibit E2 induced Vtg mRNA and protein upregulation. P did not alter the Vtg induction while F reduced the Vtg protein levels without affecting the Vtg mRNA levels. Furthermore the inhibition of Vtg protein was found to be dose dependent. Thus, the inhibitory effect of F on Vtg appears to be mediated at the post-transcriptional level

Androgen receptor-beta mRNA levels in different tissues in breeding and post-breeding male and female sticklebacks, Gasterosteus aculeatus

<p>Abstract</p> <p>Background</p> <p>Androgens induce male characters by activating androgen receptors (AR). Previous quantitative studies on AR in fishes have been limited to few tissues and/or a single season/reproductive state. The aim of this investigation was to study the possible role of AR-beta expression levels in the control of male traits in the three-spined stickleback. To that end, AR-beta expression levels in major tissues in breeding and post-breeding male and female sticklebacks were examined.</p> <p>Methods</p> <p>AR-beta mRNA levels were quantified in ten tissues; eye, liver, axial muscle, heart, brain, intestine, ovary, testis, kidney and pectoral muscle in six breeding and post-breeding males and females using reverse transcription quantitative PCR.</p> <p>Results</p> <p>Breeding in contrast to post-breeding males built nests and showed secondary sexual characters (e.g. kidney hypertrophy) and elevated androgen levels. Post-breeding females had lower ovarian weights and testosterone levels than breeding females. AR-beta was expressed in all studied tissues in both sexes and reproductive states with the highest expression in the gonads and in the kidneys. The kidney is an androgen target organ in sticklebacks, from which breeding males produce the protein spiggin, which is used in nest-building. There was also high AR-beta expression in the intestine, an organ that appears to take over hyperosmo-regulation in fresh water when the kidney hypertrophies in mature males and largely loses this function. The only tissue that showed effects of sex or reproductive state on AR-beta mRNA levels was the kidneys, where post-breeding males displayed higher AR-beta mRNA levels than breeding males.</p> <p>Conclusion</p> <p>The results indicate that changes in AR-beta mRNA levels play no or little role in changes in androgen dependent traits in the male stickleback.</p

Characterization of antibodies for quantitative determination of spiggin protein levels in male and female three-spined stickleback (Gasterosteus aculeatus)

Spiggin is an adhesive glycoprotein produced in the kidney of sticklebacks during the breeding season and is subsequently secreted into the urinary bladder from where it is employed for nest building. Since the production of the protein has been shown to be under androgenic control, spiggin has been suggested to be a useful biomarker for androgenic substances in the environment. In this study, two polyclonal spiggin antibodies based on synthetic peptides and one polyclonal antibody directed against native spiggin have been characterized. The antibodies ability to identify spiggin was investigated by quantitative immunoassay. For both peptide antibodies the quantification range was determined to be between 1 and 80 ng spiggin and determination of renal spiggin levels from immature and mature males displayed a 15-fold increase in total spiggin content of the kidney resulting in a 6-fold increase in male kidney weight due to hypertrophy. The kidney somatic index (KSI) was found to correlate well with the total renal spiggin content and therefore it appears that KSI in sticklebacks could be used as an initial method to identify substances displaying androgenic effects. Furthermore, western blot analysis revealed that the polyclonal antibodies recognize different spiggin isoforms and that spiggin can be detected in the urinary bladder and kidney of both males and female sticklebacks. In order to develop a quantitative detection method for native spiggin it is necessary to produce a standard that can be used in a bioassay. Due to the adhesive and polymerization characteristics of spiggin the protein is difficult to use as a standard in bioassays. So far spiggin has been shown to exist in at least 14 isoforms, all of which contain polymerization domains. To overcome the solubility problem we have produced recombinant spiggin gamma, with only one polymerization domain, that can be expressed in E. coli. Western blot analysis demonstrated that the polyclonal antibodies were able to detect recombinant spiggin gamma protein in bacterial cell lysate, suggesting that it may be developed into a useful source of standard spiggin to be used for quantitative determination of androgen induced spiggin production in sticklebacks

Biochemical characterization of the Arctic char (<it>Salvelinus alpinus</it>) ovarian progestin membrane receptor

<p>Abstract</p> <p>Membrane progestin receptors are involved in oocyte maturation in teleosts. However, the maturation-inducing steroid (MIS) does not appear to be conserved among species and several progestins may fulfill this function. So far, complete biochemical characterization has only been performed on a few species. In the present study we have characterized the membrane progestin receptor in Arctic char (Salvelinus alpinu<it>s</it>) and show that the 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) receptor also binds several xenobiotics, thus rendering oocyte maturation sensitive to environmental pollutants. We identified a single class of high affinity (K_d, 13.8 ± 1.1 nM), low capacity (B_max, 1.6 ± 0.6 pmol/g ovary) binding sites by saturation and Scatchard analyses. Receptor binding displayed rapid association and dissociation kinetics typical of steroid membrane receptors, with t_1/2s of less than 1 minute. The 17,20beta-P binding also displayed tissue specificity with high, saturable, and specific 17,20beta-P binding detected in ovaries, heart and gills while no specific binding was observed in muscle, brain or liver. Changes in 17,20beta-P binding during oocyte maturation were consistent with its identity as the oocyte MIS membrane receptor. Incubation of fully-grown ovarian follicles with gonadotropin induced oocyte maturation, which was accompanied by a five-fold increase in 17,20beta-P receptor binding. In addition, competition studies with a variety of steroids revealed that receptor binding is highly specific for 17,20beta-P, the likely maturation-inducing steroid (MIS) in Arctic char. The relative-binding affinities of all the other progestogens and steroids tested were less than 5% of that of 17,20beta-P for the receptor. Several ortho, para derivatives of DDT also showed weak binding affinity for the 17,20beta-P receptor supporting the hypothesis that xenobiotics may bind steroid receptors on the oocyte's surface and might thereby interfere with oocyte growth and maturation.</p

Feasibility Study of FPGA-Based Equalizer for 112-Gbit/s Optical Fiber Receivers

With ever increasing demands on spectral efficiency, complex modulation schemes are being introduced in fiber communication. However, these schemes are challenging to implement as they drastically increase the computational burden at the fiber receiver’s end. We perform a feasibility study of implementing a 16-QAM 112-Gbit/s decision directed equalizer on a state-of-the-art FPGA platform. An FPGA offers the reconfigurability needed to allow for modulation scheme updates, however, its clock rate is limited. For this purpose, we introduce a new phase correction technique to significantly relax the delay requirement on the critical phase-recovery feedback loop

Transforming innovation for sustainability

The urgency of charting pathways to sustainability that keep human societies within a "safe operating space" has now been clarified. Crises in climate, food, biodiversity, and energy are already playing out across local and global scales and are set to increase as we approach critical thresholds. Drawing together recent work from the Stockholm Resilience Centre, the Tellus Institute, and the STEPS Centre, this commentary article argues that ambitious Sustainable Development Goals are now required along with major transformation, not only in policies and technologies, but in modes of innovation themselves, to meet them. As examples of dryland agriculture in East Africa and rural energy in Latin America illustrate, such "transformative innovation" needs to give far greater recognition and power to grassroots innovation actors and processes, involving them within an inclusive, multi-scale innovation politics. The three dimensions of direction, diversity, and distribution along with new forms of "sustainability brokering" can help guide the kinds of analysis and decision making now needed to safeguard our planet for current and future generations

Effectiveness of a self-managed digital exercise programme to prevent falls in older community-dwelling adults -study protocol for the Safe Step randomized controlled trial

INTRODUCTION: Exercise interventions have a strong evidence base for falls prevention. However, exercise can be challenging to implement and often has limited reach and poor adherence. Digital technology provides opportunities for both increased access to the intervention and support over time. Further knowledge needs to be gained regarding the effectiveness of completely self-managed digital exercise interventions. The main objective of this study is to compare the effectiveness of a self-managed digital exercise programme, Safe Step, in combination with monthly educational videos with educational videos alone, on falls over 1 year in older community-dwelling adults.METHODS AND ANALYSIS: A two-arm parallel randomised controlled trial will be conducted with at least 1400 community-living older adults (70+ years) who experience impaired balance. Participants will be recruited throughout Sweden with enrolment through the project website. They will be randomly allocated to either the Safe Step exercise programme with additional monthly educational videos about healthy ageing and fall prevention, or the monthly education videos alone. Participants receiving the exercise intervention will be asked to exercise at home for at least 30 min, 3 times/week with support of the Safe Step application. The primary outcome will be rate of falls (fall per person year). Participants will keep a fall calendar and report falls at the end of each month through a digital questionnaire. Further assessments of secondary outcomes will be made through self-reported questionnaires and a self-test of 30 s chair stand test at baseline and 3, 6, 9 and 12 months after study start. Data will be analysed according to the intention-to-treat principle.ETHICS AND DISSEMINATION: Ethical approval was obtained by The Regional Ethical Review Board in Umeå (Dnr 2018/433-31). Findings will be disseminated through the project web-site, peer-reviewed journals, national and international conferences and through senior citizen organisations' newsletters.TRIAL REGISTRATION NUMBER: NCT03963570