REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF EURYCOMA LONGIFOLIA AQUEOUS EXTRACT (PHYSTA®) IN WISTAR RATS

Objective: Reproductive and developmental toxicities of Eurycoma longifolia aqueous extract (PHYSTA®) in male and female wistar rats were examined concerning its effect on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition.Methods: Eurycoma longifolia aqueous extract at a dose of 250, 500 and 1000 mg/kg b. w. was administered daily by oral gavage during 14 day premating and 14 days mating period in both male and female, during gestation period and up to post natal day 3 in females. Animals were observed for clinical signs, morbidity, mortality, body weight development, food consumption and pub observation (number of live pups/litter, live birth index, implant sites, fetal resorption etc.). Male and females were sacrificed on day 29 and post natal day (PND) 4 respectively; then subjected to necropsy.Results: The result indicated non-significant predominant clinical signs, no mortality, and no toxicological relevance effect on body weight. In addition increased food consumption with no treatment related effect on litters, precoital interval and duration of gestation was observed. Pre and post natal data (Corpora lutea, implant sites, live pups, pre and post percent pre-implantation loss) remain unaffected. All pregnancies resulted in normal birth and delivery index remain unaffected. Survival of pups from PND 0 to PND 4 remained unaffected along with no treatment related gross external findings. No gross pathology findings and no statistically significant absolute and relative organ weight was observed. The histopathological evaluation does not revealed any lesions considered to be treatment related.Conclusion: In conclusion, the repeated dose administration of Eurycoma longifolia aqueous extract (PHYSTA®) to male Wistar rats for 28-29 days and female Wistar rats up to 54 days at dosages of 250, 500 and 1000 mg/kg b.w. revealed no major toxicological findings. As per the present investigation the non-observed-adverse event level (NOAEL) for Eurycoma longifolia aqueous extract (PHYSTA®) is believed to be 1000 mg/kg body weight for reproductive and developmental toxicity.Â

Mind the Gap: A Study in Global Development through Persistent Homology

The Gapminder project set out to use statistics to dispel simplistic notions about global development. In the same spirit, we use persistent homology, a technique from computational algebraic topology, to explore the relationship between country development and geography. For each country, four indicators, gross domestic product per capita; average life expectancy; infant mortality; and gross national income per capita, were used to quantify the development. Two analyses were performed. The first considers clusters of the countries based on these indicators, and the second uncovers cycles in the data when combined with geographic border structure. Our analysis is a multi-scale approach that reveals similarities and connections among countries at a variety of levels. We discover localized development patterns that are invisible in standard statistical methods

Synthesized grain size distribution in the interstellar medium

We examine a synthetic way of constructing the grain size distribution in the interstellar medium (ISM). First we formulate a synthetic grain size distribution composed of three grain size distributions processed with the following mechanisms that govern the grain size distribution in the Milky Way: (i) grain growth by accretion and coagulation in dense clouds, (ii) supernova shock destruction by sputtering in diffuse ISM, and (iii) shattering driven by turbulence in diffuse ISM. Then, we examine if the observational grain size distribution in the Milky Way (called MRN) is successfully synthesized or not. We find that the three components actually synthesize the MRN grain size distribution in the sense that the deficiency of small grains by (i) and (ii) is compensated by the production of small grains by (iii). The fraction of each {contribution} to the total grain processing of (i), (ii), and (iii) (i.e., the relative importance of the three {contributions} to all grain processing mechanisms) is 30-50%, 20-40%, and 10-40%, respectively. We also show that the Milky Way extinction curve is reproduced with the synthetic grain size distributions.Comment: 10 pages, 6 figures, accepted for publication in Earth, Planets, and Spac

Biomechanical comparison of nitinol compression staples versus fully threaded lag screws for talonavicular fusion

"Arthrodesis of the talonavicular joint is indicated for injury- and arthritis-related pain and is associated with consistently favorable outcomes. Current techniques for talonavicular arthrodesis vary, however, lag screw fixation is considered the reference standard. While nitinol compression staples have purported advantages for talonavicular arthrodesis, there is a relative paucity of data regarding their biomechanical performance compared to screw fixation. This study was designed to compare nitinol compression staples to fully threaded lag screws for use in talonavicular arthrodesis with respect to their biomechanical properties during functional testing."--Introduction

Dr. Martin Hillenbrand to Receive University of Dayton Distinguished Alumnus Award

News release announcing the University of Dayton will Award Assistant Secretary of State for European Affairs, Dr. Martin Hillenbrand, with the Distinguished Alumnus Award

Multi-year satellite observations of sulfur dioxide gas emissions and lava extrusion at bagana volcano, papua new guinea

Bagana, arguably the most active volcano in Papua New Guinea, has been in a state of near-continuous eruption for over 150 years, with activity dominated by sluggish extrusion of thick blocky lava flows. If current extrusion rates are representative, the entire edifice may have been constructed in only 300–500 years. Bagana exhibits a remarkably high gas flux to the atmosphere, with persistent sulfur dioxide (SO2) emissions of several thousand tons per day. This combination of apparent youth and high outgassing fluxes is considered unusual among persistently active volcanoes worldwide. We have used satellite observations of SO2 emissions and thermal infrared radiant flux to explore the coupling of lava extrusion and gas emission at Bagana. The highest gas emissions (up to 10 kt/day) occur during co-extrusive intervals, suggesting a degree of coupling between lava and gas, but gas emissions remain relatively high (~2,500 t/d) during inter-eruptive pauses. These passive emissions, which clearly persist for decades if not centuries, require a large volume of degassing but non-erupting magma beneath the volcano with a substantial exsolved volatile phase to feed the remarkable SO2 outgassing: an additional ~1.7–2 km3 basaltic andesite would be required to supply the excess SO2 emissions we observe in our study interval (2005 to present). That this volatile phase can ascend freely to the surface under most conditions is likely to be key to Bagana's largely effusive style of activity, in contrast with other persistently active silicic volcanoes where explosive and effusive eruptive styles alternate

Quantitative analysis of the CD4+ T cell response to therapeutic antibodies in healthy donors using a novel T cell:PBMC assay

Many biopharmaceuticals (BPs) are known to be immunogenic in the clinic, which can result in modified pharmacokinetics, reduced efficacy, allergic reactions and anaphylaxis. During recent years, several technologies to predict immunogenicity have been introduced, but the predictive value is still considered low. Thus, there is an unmet medical need for optimization of such technologies. The generation of T cell dependent high affinity anti-drug antibodies plays a key role in clinical immunogenicity. This study aimed at developing and evaluating a novel in vitro T cell:PBMC assay for prediction of the immunogenicity potential of BPs. To this end, we assessed the ability of infliximab (anti-TNF-α), rituximab (anti-CD20), adalimumab (anti-TNF-α) and natalizumab (anti-α4-integrin), all showing immunogenicity in the clinic, to induce a CD4+ T cells response. Keyhole limpet hemocyanin (KLH) and cytomegalovirus pp65 protein (CMV) were included as neo-antigen and recall antigen positive controls, respectively. By analyzing 26 healthy donors having HLA-DRB1 alleles matching the European population, we calculated the frequency of responding donors, the magnitude of the response, and the frequency of BP-specific T cells, as measured by 3[H]-thymidine incorporation and ELISpot IL-2 secretion. KLH and CMV demonstrated a strong T cell response in all the donors analyzed. The frequency of responding donors to the BPs was 4% for infliximab, 8% for adalimumab, 19% for rituximab and 27% for natalizumab, which is compared to and discussed with their respective observed clinical immunogenicity. This study further complements predictive immunogenicity testing by quantifying the in vitro CD4+ T cell responses to different BPs. Even though the data generated using this modified method does not directly translate to the clinical situation, a high sensitivity and immunogenic potential of most BPs is demonstrated

Photoluminescence from NV− centres in 5 nm detonation nanodiamonds: Identification and high sensitivity to magnetic field

This is the final version. Available from the publisher via the DOI in this record.The content of nitrogen-vacancy (NV−) colour centres in the nanodiamonds (DNDs) produced during the detonation of nitrogen-containing explosives was found to be 1.1 ± 0.3 ppm. This value is impressive for nanodiamonds of size < 10 nm with intentionally created NV− centres. The concentration was estimated from the electron paramagnetic resonance as determined from the integrated intensity of the g = 4.27 line. This line is related with “forbidden” ∆ms = 2 transitions between the Zeeman levels of a NV− centre’s ground triplet state. Confocal fluorescence microscopy enables detection of the red photoluminescence (PL) of the NV− colour centres in nanoscale DND aggregates formed from the 5-nm nanoparticles. Subwavelength emitters consisting of NV− with sizes a few times smaller than the diffraction-limited spot are clearly distinguished. We have further observed an abrupt drop in the PL intensity when mixing and anti-crossing of the ground and excited states spin levels in NV− occurs under an applied external magnetic field. This effect is a unique quantum feature of NV− centres, which cannot be observed for other visible domain light-emitting colour centres in a diamond lattice.Engineering and Physical Sciences Research Council (EPSRC