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We have a long-term vision to develop drug discovery research capacity within Ghana, to tackle unmet medical needs in Ghana and the wider West African region. However, there are several issues and challenges that need to be overcome to enable this vision, including training, human resource, equipment, infrastructure, procurement, and logistics. We discuss these challenges from the context of Ghana in this review. An important development is the universities and research centres within Ghana working together to address some of these challenges. Therefore, while there is a long way to go to fully accomplish our vision, there are encouraging signs.

We have a long-term vision to develop drug discovery research capacity within Ghana, to tackle unmet medical needs in Ghana and the wider West African region. However, there are several issues and challenges that need to be overcome to enable this vision, including training, human resource, equipment, infrastructure, procurement, and logistics. We discuss these challenges from the context of Ghana in this review. An important development is the universities and research centres within Ghana working together to address some of these challenges. Therefore, while there is a long way to go to fully accomplish our vision, there are encouraging signs.

Background Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5′-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported. Methods To investigate the role of PfdUTPase in cell survival different strategies to generate knockout mutants were used. For validation of PfdUTPase as the intracellular target of four inhibitors of the enzyme, mutants overexpressing PfdUTPase and HsdUTPase were created and the IC50 for each cell line with each compound was determined. The effect of these compounds on dUTP and dTTP levels from P. falciparum was measured using a DNA polymerase assay. Detailed localization studies by indirect immunofluorescence microscopy and live cell imaging were also performed using a cell line overexpressing a Pfdut -GFP fusion protein. Results Different attempts of disruption of the dut gene of P. falciparum were unsuccessful while a 3′ replacement construct could recombine correctly in the locus suggesting that the enzyme is essential. The four 5′-tritylated deoxyuridine analogues described are potent inhibitors of the P. falciparum dUTPase and exhibit antiplasmodial activity. Overexpression of the Plasmodium and human enzymes conferred resistance against selective compounds, providing chemical validation of the target and confirming that indeed dUTPase inhibition is involved in anti-malarial activity. In addition, incubation with these inhibitors was associated with a depletion of the dTTP pool corroborating the central role of dUTPase in dTTP synthesis. PfdUTPase is mainly localized in the cytosol. Conclusion These results strongly confirm the pivotal and essential role of dUTPase in pyrimidine biosynthesis of P. falciparum intraerythrocytic stages.

Abstract Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error ( p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections ( p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

As European business ties develop, how are they reflected in the way companies promote themselves? And as our sense of group identity is broken down by global communications technologies, how do adverts continue to target mass audiences? This volume stands alone as the first structured assessment of the impact of advertising, in terms of both culture and business across the national boundaries of Europe. It considers the successes and failures of several strategic marketing plans from across Europe, and describes stylistic and persuasive qualities of specific promotional texts. Advertisers have long been aware of the need to target specific groups of consumers and to appeal to them precisely in terms of their sense of membership to groups. Our post-industrial society is characterized by greatly altered work and leisure patterns as well as a weakening of national and communal frameworks for collective identity. Theories relating to identity not only reflect, but actively make use of such concerns. As a part of our everyday lives, the advertising considered looks at – but is not limited to – explicit inducements to buy products. Rather it considers all promotional texts designed to inform and persuade. With examples from Scandinavia to the Iberian Peninsula, the contributors also explore the different constructions of regional, national, social and sexual identities exploited by advertisers to render their messages effective. As a result, the book will be of relevance not only to those concerned with marketing but to all scholars of media studies, language, cultural and gender studies.

We present an upgraded version of TRICERATOPS, a software package designed to calculate false positive probabilities for planet candidates identified by the Transiting Exoplanet Survey Satellite (TESS). This enhanced framework now incorporates ground-based light curves in separate bandpasses, which are routinely obtained as part of the candidate vetting process. We apply this upgraded framework to explore the planetary nature of 14 TESS planet candidates, combining primarily J band light curves acquired with the 200-inch Hale Telescope at Palomar Observatory with complementary archival observations from the Las Cumbres Observatory Global Telescope (LCOGT), the Fred Lawrence Whipple Observatory (FLWO), and the Teide Observatory, along with existing TESS data and contrast curves from high-resolution imaging. As a result of this analysis we statistically validate (False Positive Probability < 1.5% and Nearby False Positive Probability < 0.1%) six new planets in five systems: TOI-1346 b, TOI-1346 c, TOI-2719 b, TOI-4155 b, TOI-6000 b, and TOI-6324 b. For these systems, we provide updated estimates of their stellar and planetary properties derived from the TESS and ground-based observations. These new systems contain planets with radii between 0.9-6 Re and orbital periods between 0.3-5.5 days. Finally, we use our upgraded version of TRICERATOPS to quantify the relative importance of multi-wavelength transit photometry and high-resolution imaging for exoplanet candidate validation, and discuss which kinds of candidates typically benefit the most from ground-based multi-color transit observations.

We report the detection of a Saturn-size exoplanet orbiting HD 332231 (TOI 1456) in light curves from the Transiting Exoplanet Survey Satellite (TESS). HD 332231, an F8 dwarf star with a V-band magnitude of 8.56, was observed by TESS in Sectors 14 and 15. We detect a single-transit event in the Sector 15 presearch data conditioning (PDC) light curve. We obtain spectroscopic follow-up observations of HD 332231 with the Automated Planet Finder, Keck I, and SONG telescopes. The orbital period we infer from the radial velocity (RV) observations leads to the discovery of another transit in Sector 14 that was masked by PDC due to scattered light contamination. A joint analysis of the transit and RV data confirms the planetary nature of HD 332231 b, a Saturn-size (\\(0.867^+0.027_-0.025 \\; R_ J\\)), sub-Saturn-mass (\\(0.2440.021 \\; M_ J\\)) exoplanet on a 18.71 day circular orbit. The low surface gravity of HD 332231 b and the relatively low stellar flux it receives make it a compelling target for transmission spectroscopy. Also, the stellar obliquity is likely measurable via the Rossiter-McLaughlin effect, an exciting prospect given the 0.14 au orbital separation of HD 332231 b. The spectroscopic observations do not provide substantial evidence for any additional planets in the HD 332231 system, but continued RV monitoring is needed to further characterize this system. We also predict that the frequency and duration of masked data in the PDC light curves for TESS Sectors 14-16 could hide transits of some exoplanets with orbital periods between 10.5 and 17.5 days.

We present the discovery of TOI-1420b, an exceptionally low-density (\\( = 0.080.02\\) g cm\\(^-3\\)) transiting planet in a \\(P = 6.96\\) day orbit around a late G dwarf star. Using transit observations from TESS, LCOGT, OPM, Whitin, Wendelstein, OAUV, Ca l'Ou, and KeplerCam along with radial velocity observations from HARPS-N and NEID, we find that the planet has a radius of \\(R_p\\) = 11.9 \\(\\) 0.3 \\(R_\\) and a mass of \\(M_p\\) = 25.1 \\(\\) 3.8 \\(M_\\). TOI-1420b is the largest-known planet with a mass less than \\(50M_\\), indicating that it contains a sizeable envelope of hydrogen and helium. We determine TOI-1420b's envelope mass fraction to be \\(f_env = 82^+7_-6\\%\\), suggesting that runaway gas accretion occurred when its core was at most \\(4-5\\) the mass of the Earth. TOI-1420b is similar to the planet WASP-107b in mass, radius, density, and orbital period, so a comparison of these two systems may help reveal the origins of close-in low-density planets. With an atmospheric scale height of 1950 km, a transmission spectroscopy metric of 580, and a predicted Rossiter-McLaughlin amplitude of about \\(17\\) m s\\(^-1\\), TOI-1420b is an excellent target for future atmospheric and dynamical characterization.