134 research outputs found
ANALISIS KINERJA PEMASARAN DIGITAL MENGGUNAKAN METODE RETURN ON AD SPEND (ROAS) DI PT. RENER INTI INTERNASIONAL STOCKIS JEMBER
No full textIn recent years, there has been a significant shift in consumer behavior. More and more individuals are shopping online, as well as interacting with brands through social media. These changes have prompted businesses to shift from conventional marketing to digital marketing as a more effective method to reach target markets, including PT Rener Inti Internasional Stockis Jember (Stockis), seeking to maximize marketing through digital platforms. This study aims to analyze Stockis' marketing strategy using the 7P marketing mix approach and evaluate digital advertising performance through Return on Ad Spend (ROAS) analysis. Advertising data was obtained from the Meta Ads platform, with key indicators including turnover, advertising spend, frequency, and impressions. The results show that Stockis has implemented the 7P marketing mix elements, with a focus on promotion and process. The ROAS value of 3.36 in May and 3.15 in June exceeded the break-even point of 2.0 ROAS value, making advertising a worthy investment. In May, it earned a turnover of Rp259,492,500.00 with advertising spending of Rp77,134,091.00, while in June the turnover reached Rp314,160,000.00 with advertising spending of Rp99,677,344.00. In-depth analysis shows that the frequency of ad impressions above 2.1 contributes to better ad performance. This study concludes that Stockis' digital marketing strategy is effective in increasing sales. Evaluation of ad performance using the ROAS method with the help of ad performance metrics allows the identification of optimal patterns for strategic decision making. The findings of this pattern can be a reference for companies in designing efficient digital marketing campaigns
Effect of brivaracetam (400 mg/day) on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive in healthy women
No full textBrivaracetam is a high-affinity synaptic vesicle protein 2A ligand, in Phase III clinical development for epilepsy. This study assessed the effect of brivaracetam 400 mg/day on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive (OC) containing 30 µg ethinylestradiol and 150 µg levonorgestrel, in healthy pre-menopausal women. This open-label, single-center, randomized, two-way crossover, multiple oral dose study (N01080) included two consecutive 28-day cycles without (control) or with brivaracetam (test), and a 28-day follow-up. OC was taken on Days 1–21 of every cycle and brivaracetam 200 mg twice daily was administered on Days 1–20 of the test cycle. Ethinylestradiol and levonorgestrel pharmacokinetics were determined on Day 20 and endogenous hormones were measured frequently during both control and test cycles. Overall, 23/24 participants (age: 19–39 years) completed the study. AUC ratio (90% confidence interval) for brivaracetam versus control was 0.73 (0.69, 0.78) for ethinylestradiol and 0.78 (0.72, 0.83) for levonorgestrel, outside pre-defined bioequivalence limits (0.80–1.25). Levels of endogenous hormones were similar and normal during brivaracetam and control cycles. Brivaracetam in combination with OC was well tolerated. Brivaracetam 400 mg/day co-administered with a combination OC in healthy women reduced ethinylestradiol and levonorgestrel plasma levels but did not result in ovulation.Armel Stockis and Paul Rola
Crosstalk between ILC2 and Gata3<sup>high</sup> T<sub>reg</sub> locally constrains adaptive type-2 immunity
No full textRegulatory T cells (Tregs) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident Tregs and group 2 innate lymphoid cells (ILC2s); however, how Tregs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of Treg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and Tregs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3high Tregs, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-Treg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3high Tregs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-Treg interactions represent a critical feedback mechanism to control adaptive type 2 immunity
Competencies: A new currency for continuing professional development
No full text“No research without trained researchers” has become the mantra of the EU-funded Innovative Medicines Initiative (IMI) education and training projects. However, it is often hard to determine the type of training required at different stages of a scientist’s career. The situation is further complicated by the constantly changing environment, e.g. the growth of disruptive technologies, societal expectations of biomedical sciences, the greater need for multi-disciplinary collaborations, and conservative or changing regulatory requirements. This article summarises the experience from a series of five EMTRAIN Public Private Partnership PhD workshops that included both scientific and transferrable skill training. This is followed by an example of a recently developed training programme, including a competency profile, for translational research and medicines development; the C-COMEND teaching programme. The emphasis is on competencies as a new currency for continuing professional development. Finally, this paper describes what we consider to be the next steps required by the scientific community to address solutions to the current training challenges so that society can benefit from the innovations that only science can provide
Length frequency data from monthly catches of Pickhandle barracuda, Sphyraena jello, were studied during one year in coastal waters of Bushehr Province (Persian Gulf)
No full textA total of 311 specimens were collected from November 2006 to October 2007. We estimated Population parameters from length frequency data. These cases consist of the von Bertalanffy growth parameters and mortality, as well as exploitation rate. The result indicated that pickhandle barracuda had L_∞ =109.21 cm total length, K=0.37 and theoretical age at zero length, = -0.5 The total mortality rate (Z) was estimated to be 1.91, the fishing mortality rate (F) and the natural mortality(M) were 1.30 and 0.61, respectively. The exploitation rate (E) was 0.68. The exploitation rate indicated that the stockis in high pressure of catch and overexploited
On the statistical inference of a machine-generated autoregressive AR(1) model
No full textWe have obtained the asymptotic bias and the limiting distribution for the Yule-Walker estimator of the autoregressive parameter under a considerably weaker assumption than that of independence in the noise sequence. Among other things, these suggest robustness of the classical results and throw some light on the use of simulations based on pseudorandom numbers in verifying these results
Activation of the latent form of Transforming Growth Factor-beta occurs at the surface of human regulatory T cells
No full textRegulatory T cells (Tregs) are a subset of CD4+ T cells specialized in the inhibition of immune responses. Tregs are required for the maintenance of self-tolerance, but an excess of Treg function may inhibit anti-tumor immunity. Human Tregs are difficult to study due to the lack of a specific marker. To circumvent that issue, we derived stable human Treg clones from cancerous and non-cancerous patients. Treg clones were defined on the basis of in vitro suppressive function and were characterized by a stable epigenetic mark not found in other types of T cells. To gain insight into the suppression mechanisms by which Tregs inhibit immune responses, we performed gene expression profiling. We compared transcriptomes of Treg and T helper (Th) clones after stimulation through the T cell receptor (TCR). The only feature we found to distinguish stimulated Treg clones from Th clones was a signature suggestive of autocrine Transforming Growth Factor-beta (TGF-b) signaling. We showed that although both Treg and Th clones produce the latent, inactive form of TGF-b, only Treg clones produce active TGF-b after TCR stimulation. Furthermore, we provided evidence that Treg-derived TGF-b has paracrine actions on neighboring T cells, and that this effect requires cell-cell contact. Finally, we demonstrated that the in vitro suppressive function of Tregs relies at least in part on the production of active TGF-b.
TGF-b is initially produced as a latent, inactive form, in which the mature cytokine is associated to the so-called Latency-Associated Peptide (LAP), preventing binding of the cytokine to its receptor. A subsequent step of activation is required to release active TGF-b from the LAP. How Tregs activate latent TGF-b is presently unknown. We showed that stimulated Treg clones, but not Th clones, bear LAP at their surface. Searching for a LAP receptor on Tregs, we observed that transmembrane protein GARP is expressed in stimulated Treg clones, but not in Th clones. We also found that GARP binds LAP and mature TGF-b, i.e. latent TGF-b. Forced GARP expression induced by lentiviral transduction in Th cells is sufficient to induce the binding of latent TGF-b at the cell surface, confirming that GARP is a receptor for latent TGF-b. However, GARP-transduced Th cells do not produce active TGFb, indicating that GARP expression is not sufficient to induce the transformation of latent TGF-b into the active cytokine.
In summary, our results show that human Tregs, like other types of T cells, produce latent TGF-b. Latent TGF-b localizes at the Treg surface through binding to GARP, a receptor that is expressed upon TCR stimulation in Tregs, but not in other T cells. Stimulated Tregs transform latent TGF-b into the active cytokine, which exerts paracrine actions that require cell-cell contact. We propose therefore that a unique functional feature of human Tregs, by comparison to other T cells, consists in the ability to activate latent TGF-b, and this occurs close to the cell surface. GARP may be implicated in the activation of latent TGF-b by Tregs, but it is not sufficient. Altogether, our findings open the way for the discovery of the mechanism by which Tregs activate latent TGF-b.(SBIM 3) -- UCL, 201
Length frequency data from monthly catches of Pickhandle barracuda, Sphyraena jello, were studied during one year in coastal waters of Bushehr Province (Persian Gulf)
No full textA total of 311 specimens were collected from November 2006 to October 2007 . We estimated Population parameters from length frequency data. These cases consist of the von Bertalanffy growth parameters and mortality, as well as exploitation rate. The result indicated that pickhandle barracuda had L∞ =109.21 cm total length, K=0.37 and theoretical age at zero length, = -0.5 The total mortality rate (Z) was estimated to be 1.91, the fishing mortality rate (F) and the natural mortality(M) were 1.30 and 0.61, respectively. The exploitation rate (E) was 0.68. The exploitation rate indicated that the stockis in high pressure of catch and overexploited.Publishe
A modelling approach to reduce the simulation time of building stock models
No full textModelling of heating and cooling demandof the building stockis valuable for estimating thesizing of HVAC technologies. However,designer faces oversizing problemsas they rely on their experiencesor the use of single zone simulations. Multizone building stock models that take into consideration the interaction between the different zones’profiles, and building envelope propertiesto obtain reliable estimations is needed.Simulations of large amount of building stock models require extensive computationand simulationtime.Therefore, we developed multi-zone generic modelling approach that allows modelling and simulationof large population of building stock casesin shorter time.The approach relies on splitting the building into modules that are modelled separately and of which the simulation results are aggregated afterwards.This paper investigates the strengths and limitations of the proposed approach on a selected case-study building by comparing it to classical modelling approaches.Areduction of 80% in simulation time was achieved. The hourlyheating and cooling demands for the proposedand classical approachesreached alowest deviation of1.4% for buildings with higherU-values, and one set temperature
ChemInform Abstract: MOLECULAR ORBITAL ANALYSIS OF THE BONDING CAPABILITIES OF CARBON DISULFIDE AND CARBON DIOXIDE TOWARD TRANSITION METAL FRAGMENTS
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