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The aims of this study were to: (1) compare actigraphy (ACTICAL) and a commercially available sleep wearable (i.e., WHOOP) under two functionalities (i.e., sleep auto-detection (WHOOP-AUTO) and manual adjustment of sleep (WHOOP-MANUAL)) for two-stage categorisation of sleep (sleep or wake) against polysomnography, and; (2) compare WHOOP-AUTO and WHOOP-MANUAL for four-stage categorisation of sleep (wake, light sleep, slow wave sleep (SWS), or rapid eye movement sleep (REM)) against polysomnography. Six healthy adults (male: n = 3; female: n = 3; age: 23.0 ± 2.2 yr) participated in the nine-night protocol. Fifty-four sleeps assessed by ACTICAL, WHOOP-AUTO and WHOOP-MANUAL were compared to polysomnography using difference testing, Bland–Altman comparisons, and 30-s epoch-by-epoch comparisons. Compared to polysomnography, ACTICAL overestimated total sleep time (37.6 min) and underestimated wake (−37.6 min); WHOOP-AUTO underestimated SWS (−15.5 min); and WHOOP-MANUAL underestimated wake (−16.7 min). For ACTICAL, sensitivity for sleep, specificity for wake and overall agreement were 98%, 60% and 89%, respectively. For WHOOP-AUTO, sensitivity for sleep, wake, and agreement for two-stage and four-stage categorisation of sleep were 90%, 60%, 86% and 63%, respectively. For WHOOP-MANUAL, sensitivity for sleep, wake, and agreement for two-stage and four-stage categorisation of sleep were 97%, 45%, 90% and 62%, respectively. WHOOP-AUTO and WHOOP-MANUAL have a similar sensitivity and specificity to actigraphy for two-stage categorisation of sleep and can be used as a practical alternative to polysomnography for two-stage categorisation of sleep and four-stage categorisation of sleep.

Diamond’s properties are dictated by its crystalline, fully tetrahedrally bonded structure. Here authors synthesize a bulk sp 3-bonded amorphous form of carbon under high pressure and temperature, show that it has bulk modulus comparable to crystalline diamond and that it can be recovered under ambient conditions.

Probabilistic reasoning biases have been widely associated with levels of delusional belief ideation (Galbraith, Manktelow, & Morris, 2010; Lincoln, Ziegler, Mehl, & Rief, 2010; Speechley, Whitman, & Woodward, 2010; White & Mansell, 2009), however, little research has focused on biases occurring during every day reasoning (Galbraith, Manktelow, & Morris, 2011), and moral and crime based reasoning (Wilkinson, Caulfield, & Jones, 2014; Wilkinson, Jones, & Caulfield, 2011). 235 participants were recruited across four experiments exploring crime based reasoning through different modalities and dual processing tasks. Study one explored delusional ideation when completing a visually presented crime based reasoning task. Study two explored the same task in an auditory presentation. Study three utilised a dual task paradigm to explore modality and executive functioning. Study four extended this paradigm to the auditory modality. The results indicated that modality and delusional ideation have a significant effect on individuals reasoning about violent and non-violent crime (p < .05), which could have implication for the presentation of evidence in applied setting such as the courtroom.

Abstract Very high multiplicity, spherically-symmetric distributions of soft particles, with p T ∼ few×100 MeV, may be a signature of strongly-coupled hidden valleys that exhibit long, efficient showering windows. With traditional triggers, such ‘soft bomb’ events closely resemble pile-up and are therefore only recorded with minimum bias triggers at a very low efficiency. We demonstrate a proof-of-concept for a high-level triggering strategy that efficiently separates soft bombs from pile-up by searching for a ‘belt of fire’: a high density band of hits on the innermost layer of the tracker. Seeding our proposed high-level trigger with existing jet, missing transverse energy or lepton hardware-level triggers, we show that net trigger efficiencies of order 10% are possible for bombs of mass several × 100 GeV. We also consider the special case that soft bombs are the result of an exotic decay of the 125 GeV Higgs. The fiducial rate for ‘Higgs bombs’ triggered in this manner is marginally higher than the rate achievable by triggering directly on a hard muon from associated Higgs production.

James Dean,1 Umme Kolsum,1,2 Paul Hitchen,1 Vandana Gupta,1 Dave Singh1,2 1Medicines Evaluation Unit, Manchester, 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK Abstract: We have used impulse oscillometry to identify COPD patients with tidal expiratory flow limitation (EFL), which is a measurement related to small airway disease. We report that 37.4% of COPD patients had EFL; these patients had multiple clinical characteristics of more severe disease including lower forced expiratory volume in 1 second values, greater hyperinflation, reduced exercise performance, and increased small airway impairment. We highlight that EFL can be used to identify a subgroup of COPD patients with distinct characteristics associated with small airway disease. Keywords: COPD, expiratory flow limitation, IOS, small airway, reactance

The increasing ageing prison population is becoming a pressing issue throughout the criminal justice system. Alongside the rising population, are a host of health and wellbeing issues that contribute to older offenders needs whilst in prison. It has been recommended that meaningful activities can have positive effects on this population and therefore this paper uniquely reviews older offenders accounts of taking part in an arts based project, Good Vibrations, whilst imprisoned. The Good Vibrations project engages individuals in Gamelan music making with an end of project performance. This study used independent in-depth interviews to capture the voices of older offenders who took part in an art based prison project. The interview data was analysed using thematic analysis, which highlighted themes that were consistent with other populations who have taken part in a Good Vibrations project, along with specific age relating issues of mobility, motivation, identity and wellbeing.

With the recent surge of affordable, high-performance virtual reality (VR) headsets, there is unlimited potential for applications ranging from education, to training, to entertainment, to fitness and beyond. As these interfaces continue to evolve, passive user-state monitoring can play a key role in expanding the immersive VR experience, and tracking activity for user well-being. By recording physiological signals such as the electroencephalogram (EEG) during use of a VR device, the user's interactions in the virtual environment could be adapted in real-time based on the user's cognitive state. Current VR headsets provide a logical, convenient, and unobtrusive framework for mounting EEG sensors. The present study evaluates the feasibility of passively monitoring cognitive workload via EEG while performing a classical n-back task in an interactive VR environment. Data were collected from 15 participants and the spatio-spectral EEG features were analyzed with respect to task performance. The results indicate that scalp measurements of electrical activity can effectively discriminate three workload levels, even after suppression of a co-varying high-frequency activity.

Neural interfaces that directly produce intelligible speech from brain activity would allow people with severe impairment from neurological disorders to communicate more naturally. Here, we record neural population activity in motor, premotor and inferior frontal cortices during speech production using electrocorticography (ECoG) and show that ECoG signals alone can be used to generate intelligible speech output that can preserve conversational cues. To produce speech directly from neural data, we adapted a method from the field of speech synthesis called unit selection, in which units of speech are concatenated to form audible output. In our approach, which we call Brain-To-Speech, we chose subsequent units of speech based on the measured ECoG activity to generate audio waveforms directly from the neural recordings. Brain-To-Speech employed the user's own voice to generate speech that sounded very natural and included features such as prosody and accentuation. By investigating the brain areas involved in speech production separately, we found that speech motor cortex provided more information for the reconstruction process than the other cortical areas.

Background As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long‐term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve. Methods and Results A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in REPRISE III (The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System—Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre‐specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent. Conclusions Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier NCT02202434.

The chemoselective reduction of diaryl imines in the presence of competitively reducible groups is uniquely accessed through precise control of reaction and irradiation time by continuous flow visible light photoredox catalysis. The method enables the mild and efficient transfer hydrogenation of diaryl imines in the presence of sensitive functionality including halides, ester, ketone, and cyano groups. The flow protocol is efficient, rapid (>98% conversion within 9 min) and readily scaled to deliver multigram quantities of amine products in high purity.

Heart rate (HR) and HR variability (HRV) infer readiness to perform exercise in athletic populations. Technological advancements have facilitated HR and HRV quantification via photoplethysmography (PPG). This study evaluated the validity of WHOOP’s PPG-derived HR and HRV against electrocardiogram-derived (ECG) measures. HR and HRV were assessed via WHOOP 2.0 and ECG over 15 opportunities during October–December 2018. WHOOP-derived pulse-to-pulse (PP) intervals were edited with WHOOP’s proprietary filter, in addition to various filter strengths via Kubios HRV software. HR and HRV (Ln RMSSD) were quantified for each filter strength. Agreement was assessed via bias and limits of agreement (LOA), and contextualised using smallest worthwhile change (SWC) and coefficient of variation (CV). Regardless of filter strength, bias (≤0.39 ± 0.38%) and LOA (≤1.56%) in HR were lower than the CV (10–11%) and SWC (5–5.5%) for this parameter. For Ln RMSSD, bias (1.66 ± 1.80%) and LOA (±5.93%) were lowest for a 200 ms filter and WHOOP’s proprietary filter, which approached or exceeded the CV (3–13%) and SWC (1.5–6.5%) for this parameter. Acceptable agreement was found between WHOOP- and ECG-derived HR. Bias and LOA in Ln RMSSD approached or exceeded the SWC/CV for this variable and should be interpreted against its own level of bias precision.

This review describes unexpected dynamical behaviors of rearranging carbocations and the modern computational methods used to elucidate these aspects of reaction mechanisms. Unique potential energy surface topologies associated with these rearrangements have been discovered in recent years that are not only of fundamental interest, but also provide insight into the way Nature manipulates chemical space to accomplish specific chemical transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout.

Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein’s poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations.

Background: Disturbed sleep may negatively influence physical health, cognitive performance, metabolism, and general wellbeing. Nutritional interventions represent a potential non-pharmacological means to increase sleep quality and quantity. Objective: (1) Identify an optimal suite of nutritional ingredients and (2) validate the effects of this suite utilising polysomnography, and cognitive and balance tests. Methods: The optimal and least optimal combinations of six ingredients were identified utilising 55 male participants and a Box–Behnken predictive model. To validate the model, 18 healthy, male, normal sleepers underwent three trials in a randomised, counterbalanced design: (1) optimal drink, (2) least optimal drink, or (3) placebo were provided before bed in a double-blinded manner. Polysomnography was utilised to measure sleep architecture. Cognitive performance, postural sway, and subjective sleep quality, were assessed 30 min after waking. Results: The optimal drink resulted in a significantly shorter sleep onset latency (9.9 ± 12.3 min) when compared to both the least optimal drink (26.1 ± 37.4 min) and the placebo drink (19.6 ± 32.0 min). No other measures of sleep, cognitive performance, postural sway, and subjective sleep quality were different between trials. Conclusion: A combination of ingredients, optimised to enhance sleep, significantly reduced sleep onset latency. No detrimental effects on sleep architecture, subjective sleep quality or next day performance were observed.

The recreational bait trade is a potential pathway for pathogen introduction and spread when anglers dump bait shop sourced water into aquatic systems. Despite this possibility, and previous recognition of the importance of the bait trade in the spread of aquatic invasive species (AIS), to date there has been no region wide survey documenting pathogens in retail bait shops. In this study, we analyzed 96 environmental DNA samples from retail bait shops around the Great Lakes region to identify pathogens, targeting the V4 hypervariable region of the 16S rRNA gene. Additionally, we used samples from one site in Lake Michigan as a comparison to pathogen diversity and abundance in natural aquatic systems. Our results identified nine different groups of pathogens in the bait shop samples, including those that pose risks to both humans and fish species. Compared to wild sourced samples, the bait shops had higher relative abundance and greater taxonomic diversity. These findings suggest that the bait trade represents a potentially important pathway that could introduce and spread pathogens throughout the Great Lakes region. Improving pathogen screening and angler outreach should be used in combination to aid in preventing the future spread of high risk pathogens.

Cardiopulmonary exercise testing (CPET) using a spectrum of different approaches demonstrates usefulness for objectively assessing patient disease severity in clinical and research settings. Still, an absence of trained specialists and/or improper data interpretation techniques can pose major limitations to the effective use of CPET for the clinical classification of patients. This study aimed to test an automated disease likelihood scoring algorithm system based on cardiopulmonary responses during a simplified step-test protocol. For patients with heart failure (HF), pulmonary hypertension (PAH), obstructive lung disease (OLD), or restrictive lung disease (RLD), we compared patient scores stratified into one of four “silos” generated from our novel algorithm system against patient evaluations provided by expert clinicians. Patients with HF (n = 12), PAH (n = 9), OLD (n = 16), or RLD (n = 10) performed baseline pulmonary function testing followed by submaximal step-testing. Breath-by-breath measures of ventilation and gas exchange, in addition to oxygen saturation and heart rate were collected continuously throughout testing. The algorithm demonstrated close alignment with patient assessments provided by clinical specialists: HF (r = 0.89, P

Inattentional blindness is a failure to notice an unexpected event when attention is directed elsewhere. The current study examined participants’ awareness of an unexpected object that maintained luminance contrast, switched the luminance once, or repetitively flashed. One hundred twenty participants performed a dynamic tracking task on a computer monitor for which they were instructed to count the number of movement deflections of an attended set of objects while ignoring other objects. On the critical trial, an unexpected cross that did not change its luminance (control condition), switched its luminance once (switch condition), or repetitively flashed (flash condition) traveled across the stimulus display. Participants noticed the unexpected cross more frequently when the luminance feature matched their attention set than when it did not match. Unexpectedly, however, a proportion of the participants who noticed the cross in the switch and flash conditions were statistically comparable. The results suggest that an unexpected object with even a single luminance change can break inattentional blindness in a multi-object tracking task.

Computational chemistry approaches for studying the formation of terpenes/terpenoids in wines are presented, using five particular terpenes/terpenoids (1,8-cineole, α-ylangene, botrydial, rotundone, and the wine lactone), volatile compounds (or their precursors) found in wine and/or wine grapes, as representative examples. Through these examples, we show how modern computational quantum chemistry can be employed as an effective tool for assessing the validity of proposed mechanisms for terpene/terpenoid formation.

INTRODUCTION: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge. METHODS: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled in the ICU-RESUScitation trial (NCT02837497). The lowest documented systolic BP (SBP) and diastolic BP (DBP) were percentile-adjusted for age, height and sex. Receiver operator characteristic curves and cubic spline analyses controlling for illness category and presence of pre-arrest hypotension were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Optimal cutoffs for post-arrest BP thresholds were based on analysis of receiver operator characteristic curves and spline curves. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes. RESULTS: Among 693 index events with 0-6 h post-arrest BP data, identified thresholds were: SBP > 10th percentile and DBP > 50th percentile for age, sex and height. Fifty-one percent (n = 352) of subjects had lowest SBP above threshold and 50% (n = 346) had lowest DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP: aRR 1.21 [95% CI 1.10, 1.33]; DBP: aRR 1.23 [1.12, 1.34]) and survival to hospital discharge with favorable neurologic outcome (SBP: aRR 1.22 [1.10, 1.35]; DBP: aRR 1.27 [1.15, 1.40]) (all p  10th percentile for age and DBP > 50th percentile for age during the first 6 h post-arrest.

BACKGROUND: Previous studies have identified pulmonary hypertension (PH) as a relatively common diagnosis in children with in-hospital cardiac arrest (IHCA), and preclinical laboratory studies have found poor outcomes and low systemic blood pressures during CPR for PH-associated cardiac arrest. The objective of this study was to determine the prevalence of PH among children with IHCA and the association between PH diagnosis and intra-arrest physiology and survival outcomes. METHODS: This was a prospectively designed secondary analysis of patients enrolled in the ICU-RESUS clinical trial (NCT02837497). The primary exposure was a pre-arrest diagnosis of PH. The primary survival outcome was survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline). The primary physiologic outcome was event-level average diastolic blood pressure (DBP) during CPR. RESULTS: Of 1276 patients with IHCAs during the study period, 1129 index IHCAs were enrolled; 184 (16.3%) had PH and 101/184 (54.9%) were receiving inhaled nitric oxide at the time of IHCA. Survival with favorable neurologic outcome was similar between patients with and without PH on univariate (48.9% vs. 54.4%; p = 0.17) and multivariate analyses (aOR 0.82 [95%CI: 0.56, 1.20]; p = 0.32). There were no significant differences in CPR event outcome or survival to hospital discharge. Average DBP, systolic BP, and end-tidal carbon dioxide during CPR were similar between groups. CONCLUSIONS: In this prospective study of pediatric IHCA, pre-existing PH was present in 16% of children. Pre-arrest PH diagnosis was not associated with statistically significant differences in survival outcomes or intra-arrest physiologic measures.

Extensive hypertrophic scarring of the halluces secondary to chronic onychocryptosis is a rare condition, which causes significant physical and psychosocial effects. In this case, a 31-year-old male developed large lesions on both great toes after he delayed treatment of chronic hallucal onychocryptosis for over a decade. Current treatment options for hypertrophic and keloid lesions in the foot and ankle vary considerably and differentiation is critical for appropriate treatment planning. In this case, surgical excision with total matrixectomy (modified Zadik–Syme) was considered optimal management. Histopathology testing confirmed the diagnosis of irritated hypertrophic scar secondary to onychocryptosis. The patient was monitored closely and at 3 months post-operatively, the incisional scars exhibited progressive maturation, and there was no recurrence of the lesions and no nail regrowth. Furthermore, the halluces were only marginally shorter providing good function and cosmesis. At the long-term follow-up consultation (5.5 years), the patient indicated complete satisfaction and had returned to regular footwear and social activities. Chronic onychocryptosis can trigger and facilitate proliferation of large benign keloid-like fibrous lesions; excision with total matrixectomy can provide an excellent long-term outcome.

Lakes are dynamic and complex ecosystems that can be influenced by physical, chemical, and biological processes. Additionally, individual lakes are often chemically and physically distinct, even within the same geographic region. Here we show that differences in physicochemical conditions among freshwater lakes located on (and around) the same island, as well as within the water column of each lake, are significantly related to aquatic microbial community diversity. Water samples were collected over time from the surface and bottom-water within four freshwater lakes located around Beaver Island, MI within the Laurentian Great Lakes region. Three of the sampled lakes experienced seasonal lake mixing events, impacting either O2, pH, temperature, or a combination of the three. Microbial community alpha and beta diversity were assessed and individual microbial taxa were identified via high-throughput sequencing of the 16S rRNA gene. Results demonstrated that physical and chemical variability (temperature, dissolved oxygen, and pH) were significantly related to divergence in the beta diversity of surface and bottom-water microbial communities. Despite its correlation to microbial community structure in unconstrained analyses, constrained analyses demonstrated that dissolved organic carbon (DOC) concentration was not strongly related to microbial community structure among or within lakes. Additionally, several taxa were correlated (either positively or negatively) to environmental variables, which could be related to aerobic and anaerobic metabolisms. This study highlights the measurable relationships between environmental conditions and microbial communities within freshwater temperate lakes around the same island.

We developed a simplified automated algorithm to interpret noninvasive gas exchange in healthy subjects and patients with heart failure (HF, n = 12), pulmonary arterial hypertension (PAH, n = 11), chronic obstructive lung disease (OLD, n = 16), and restrictive lung disease (RLD, n = 12). They underwent spirometry and thereafter an incremental 3-minute step test where heart rate and Sp O 2 respiratory gas exchange were obtained. A custom-developed algorithm for each disease pathology was used to interpret outcomes. Each algorithm for HF, PAH, OLD, and RLD was capable of differentiating disease groups ( P

An efficient periodic operation to obtain the maximum work from a nonequilibrium initial state in an N–level quantum system is shown. Each cycle consists of a stabilization process followed by an isentropic restoration process. The instantaneous time limit can be taken in the stabilization process from the nonequilibrium initial state to a stable passive state. In the restoration process that preserves the passive state a minimum period is needed to satisfy the uncertainty relation between energy and time. An efficient quantum feedback control in a symmetric two–level quantum system connected to an energy source is proposed.

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known, with a human LD50 of ~1 ng/kg. Equine antitoxin has a half-life in circulation of less than 1 day and is limited to a treatment rather than a prevention indication. The development of monoclonal antibodies (mAbs) may represent an alternative therapeutic option that can be produced at high quantities and of high quality and with half-lives of >10 days. Two different three mAb combinations are being developed that specifically neutralize BoNT serotypes A (BoNT/A) and B (BoNT/B). We investigated the pharmacokinetics of the anti-BoNT/A and anti-BoNT/B antibodies in guinea pigs (Cavia porcellus) and their ability to protect guinea pigs against an aerosol challenge of BoNT/A1 or BoNT/B1. Each antibody exhibited dose-dependent exposure and reached maximum circulating concentrations within 48 h post intraperitoneal or intramuscular injection. A single intramuscular dose of the three mAb combination protected guinea pigs against an aerosol challenge dose of 93 LD50 of BoNT/A1 and 116 LD50 of BoNT/B1 at 48 h post antibody administration. These mAbs are effective in preventing botulism after an aerosol challenge of BoNT/A1 and BoNT/B1 and may represent an alternative to vaccination to prevent type A or B botulism in those at risk of BoNT exposure.

Biomass could be a key source of renewable energy. Agricultural waste products, such as corn stover, provide a convenient means to replace fossil fuels, such as coal, and a large amount of feedstock is currently available for energy consumption in the U.S. This study has two main objectives: (1) to understand the impact of corn stover moisture content and grinder speed on grind physical properties; and (2) develop response surface models and optimize these models using a hybrid genetic algorithm. The response surface models developed were used to draw surface plots to understand the interaction effects of the corn stover grind moisture content and grinder speed on the grind physical properties and specific energy consumption. The surface plots indicated that a higher corn stover grind moisture content and grinder speed had a positive effect on the bulk and tapped density. The final grind moisture content was highly influenced by the initial moisture content of the corn stover grind. Optimization of the response surface models using the hybrid genetic algorithm indicated that moisture content in the range of 17 to 19% (w.b.) and a grinder speed of 47 to 49 Hz maximized the bulk and tapped density and minimized the geomantic mean particle length. The specific energy consumption was minimized when the grinder speed was about 20 Hz and the corn stover grind moisture content was about 10% (w.b.).

Substrates engineered to undergo a 1,4-C-H insertion to yield benzocyclobutenes resulted in a novel elimination reaction to yield ortho-quinone dimethide (o-QDM) intermediates that undergo Diels-Alder or hetero-Diels-Alder cycloadditions. The analogous benzylic acetals or ethers avoid the C-H insertion pathway completely and, after hydride transfer, undergo a de-aromatizing elimination reaction to o-QDM at ambient temperature. The resulting dienes undergo a variety of cycloaddition reactions with high diastereo- and regio-selectivity. This is one of the few examples of catalytic generation of o-QDM without the intermediacy of a benzocyclobutene and represents one of the mildest, ambient temperature processes to access these useful intermediates. This proposed mechanism is supported by DFT calculations. Moreover, the methodology was applied to the synthesis of (±)-isolariciresinol in 41% overall yield.

SUMMARY Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease for which there is no cure and limited treatment options. Prednisone is currently the first line treatment option for DMD and studies have demonstrated that it improves muscle strength. Although prednisone has been used for the treatment of DMD for decades, the mechanism of action of this drug remains unclear. Recent studies have shown that the α7β1 integrin is a major modifier of disease progression in mouse models of DMD and is therefore a target for drug-based therapies. In this study we examined whether prednisone increased α7β1 integrin levels in mdx mouse and GRMD dog models and myogenic cells from humans with DMD. Our results show that prednisone promotes an increase in α7 integrin protein in cultured myogenic cells and in the muscle of mdx and GRMD animal models of DMD. The prednisone-mediated increase in α7 integrin was associated with increased laminin-α2 in prednisone-treated dystrophin-deficient muscle. Together, our results suggest that prednisone acts in part through increased merosin in the muscle basal lamina and through sarcolemmal stabilization of α7β1 integrin in dystrophin-deficient muscle. These results indicate that therapies that target an increase in muscle α7β1 integrin, its signaling pathways and/or laminin could be therapeutic in DMD.

Density functional theory calculations on mechanisms of the formation of caryolene, a putative biosynthetic precursor to caryol-1(11)-en-10-ol, reveal two mechanisms for caryolene formation: one involves a base-catalyzed deprotonation/reprotonation sequence and tertiary carbocation minimum, whereas the other (with a higher energy barrier) involves intramolecular proton transfer and the generation of a secondary carbocation minimum and a hydrogen-bridged minimum. Both mechanisms are predicted to involve concerted suprafacial/suprafacial [2 + 2] cycloadditions, whose asynchronicity allows them to avoid the constraints of orbital symmetry.