Enantioselective Total Synthesis of (—)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine

The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (−)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (−)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family

Education and Training of BS Analytical Chemists for Entry-Level Positions in Industry: A Survey

Surveys, in 1993 and 2003, of industrial employers of BS analytical chemists show that respondents consider employees’ abilities to work as a team member, solve problems, write and communicate orally, work safely with a positive ethic, perform calculations, and apply basic chemical principles to be the most important. There is dissatisfaction with the preparation of graduates with regard to communications skills, safety training, and problem-solving abilities. Respondents also indicated that graduates should have had hands-on experience with a variety of chromatographic and spectroscopic techniques as well as some techniques not commonly encountered in the teaching laboratory, such as auto-titration, microwave digestion, and optical microscopy. Examination of recent surveys of the content of analytical chemistry courses shows a decline in the extent to which electrochemical techniques feature in the curriculum, with the possible exception of cyclic voltammetry and potentiometry, and an increase in the prominence of spectroscopy and separations, in line with the expectations of industrial employers

Orthostatic Tremor: An Update on a Rare Entity

Background: Orthostatic tremor (OT) remains among the most intriguing and poorly understood of movement disorders. Compared to Parkinson’s disease or even essential tremor, there are very few articles addressing more basic science issues. In this review, we will discuss the findings of main case series on OT, including data on etiology, pathophysiology, diagnostic approach, treatment strategies, and outcome. Methods: Data for this review were identified by searching PUBMED (January 1966 to August 2016) for the terms “orthostatic tremor” or “shaky leg syndrome,” which yielded 219 entries. We did not exclude papers on the basis of language, country, or publication date. The electronic database searches were supplemented by articles in the authors’ files that pertained to this topic. Results: Owing to its rarity, the current understanding of OT is limited and is mostly based on small case series or case reports. Despite this, a growing body of evidence indicates that OT might be a progressive condition that is clinically heterogeneous (primary vs. secondary cases) with a broader spectrum of clinical features, mainly cerebellar signs, and possible cognitive impairment and personality disturbances. Along with this, advanced neuroimaging techniques are now demonstrating distinct anatomical and functional changes, some of which are consistent with neuronal loss. Discussion: OT might be a family of diseases, unified by the presence of leg tremor, but further characterized by etiological and clinical heterogeneity. More work is needed to understand the pathogenesis of this condition

Make the adder count: population trends from a citizen science survey of UK adders

Concern has been growing about the status of UK adder populations, with expert opinion reporting widespread declines. Assessing the true scale of these declines, however, has been hampered by a lack of quantitative data. Make the Adder Count began in 2005 as a national surveillance programme collecting standardised counts of adders lying-out after emerging from hibernation. 260 sites have contributed data, confirming a significant decline, on average, across sites with small populations, while the few with large populations (<10 % of sites) are weakly increasing. If these trends continue, within 15‒20 years, adders will be restricted to a few large population sites, significantly increasing the extinction risk for this priority species in the UK. Public pressure/disturbance was reported as the most frequent negative factor affecting sites, followed by habitat management and habitat fragmentation. Negative impacts from habitat management were reported almost as frequently as positive impacts, suggesting many management plans do not adequately consider the requirements of adders. The dataset also demonstrated earlier emergence among males, in warmer springs and at more northerly sites

Evaluation of a Recommender System for Assisting Novice Game Designers

Game development is a complex task involving multiple disciplines and technologies. Developers and researchers alike have suggested that AI-driven game design assistants may improve developer workflow. We present a recommender system for assisting humans in game design as well as a rigorous human subjects study to validate it. The AI-driven game design assistance system suggests game mechanics to designers based on characteristics of the game being developed. We believe this method can bring creative insights and increase users' productivity. We conducted quantitative studies that showed the recommender system increases users' levels of accuracy and computational affect, and decreases their levels of workload.Comment: The 15th AAAI Conference on Artificial Intelligence and Interactive Digital Entertainment (AIIDE 19

Assessment of myelination in infants and young children by T1 relaxation time measurements using the magnetization-prepared 2 rapid acquisition gradient echoes sequence

Background: Axonal myelination is an important maturation process in the developing brain. Increasing myelin content correlates with the longitudinal relaxation rate (R1=1/T1) in magnetic resonance imaging (MRI). Objective: By using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) on a 3-T MRI system, we provide R1 values and myelination rates for infants and young children. Materials and methods: Average R1 values in white and grey matter regions in 94 children without pathological MRI findings (age range: 3 months to 6 years) were measured and fitted by a saturating-exponential growth model. For comparison, R1 values of 36 children with different brain pathologies are presented. The findings were related to a qualitative evaluation using T2, magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and MP2RAGE. Results: R1 changes rapidly in the first 16 months of life, then much slower thereafter. R1 is highest in pre-myelinated structures in the youngest subjects, such as the posterior limb of the internal capsule (0.74-0.76 +/- 0.04 s(-1)) and lowest for the corpus callosum (0.37-0.44 +/- 0.03 s(-1)). The myelination rate is fastest in the corpus callosum and slowest in the deep grey matter. R1 is decreased in hypo- and dysmyelination disorders. Myelin maturation is clearly visible on MP2RAGE, especially in the first year of life. Conclusion: MP2RAGE permits a quantitative R1 mapping method with an examination time of approximately 6 min. The age-dependent R1 values for children without MRI-identified brain pathologies are well described by a saturating-exponential function with time constants depending on the investigated brain region. This model can serve as a reference for this age group and to search for indications of subtle pathologies. Moreover, the MP2RAGE sequence can also be used for the qualitative assessment of myelinated structures

Fish Species Introductions Provide Novel Insights into the Patterns and Drivers of Phylogenetic Structure in Freshwaters

Despite long-standing interest of terrestrial ecologists, freshwater ecosystems are a fertile, yet unappreciated, testing ground for applying community phylogenetics to uncover mechanisms of species assembly. We quantify phylogenetic clustering and overdispersion of native and non-native fishes of a large river basin in the American Southwest to test for the mechanisms (environmental filtering versus competitive exclusion) and spatial scales influencing community structure. Contrary to expectations, non-native species were phylogenetically clustered and related to natural environmental conditions, whereas native species were not phylogenetically structured, likely reflecting human-related changes to the basin. The species that are most invasive (in terms of ecological impacts) tended to be the most phylogenetically divergent from natives across watersheds, but not within watersheds, supporting the hypothesis that Darwin\u27s naturalization conundrum is driven by the spatial scale. Phylogenetic distinctiveness may facilitate non-native establishment at regional scales, but environmental filtering restricts local membership to closely related species with physiological tolerances for current environments. By contrast, native species may have been phylogenetically clustered in historical times, but species loss from contemporary populations by anthropogenic activities has likely shaped the phylogenetic signal. Our study implies that fundamental mechanisms of community assembly have changed, with fundamental consequences for the biogeography of both native and non-native species

Epileptogenic effects of NMDAR antibodies in a passive transfer mouse model

Most patients with N-methyl D-aspartate-receptor antibody encephalitis develop seizures but the epileptogenicity of the antibodies has not been investigated in vivo. Wireless electroencephalogram transmitters were implanted into 23 C57BL/6 mice before left lateral ventricle injection of antibody-positive (test) or healthy (control) immunoglobulin G. Mice were challenged 48 h later with a subthreshold dose (40 mg/kg) of the chemo-convulsant pentylenetetrazol and events recorded over 1 h. Seizures were assessed by video observation of each animal and the electroencephalogram by an automated seizure detection programme. No spontaneous seizures were seen with the antibody injections. However, after the pro-convulsant, the test mice (n = 9) had increased numbers of observed convulsive seizures (P = 0.004), a higher total seizure score (P = 0.003), and a higher number of epileptic 'spike' events (P = 0.023) than the control mice (n = 6). At post-mortem, surprisingly, the total number of N-methyl D-aspartate receptors did not differ between test and control mice, but in test mice the levels of immunoglobulin G bound to the left hippocampus were higher (P < 0.0001) and the level of bound immunoglobulin G correlated with the seizure scores (R2 = 0.8, P = 0.04, n = 5). Our findings demonstrate the epileptogenicity of N-methyl D-aspartate receptor antibodies in vivo, and suggest that binding of immunoglobulin G either reduced synaptic localization of N-methyl D-aspartate receptors, or had a direct effect on receptor function, which could be responsible for seizure susceptibility in this acute short-term model