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Dielectric electrostatic capacitors1, because of their ultrafast charge–discharge, are desirable for high-power energy storage applications. Along with ultrafast operation, on-chip integration can enable miniaturized energy storage devices for emerging autonomous microelectronics and microsystems2–5. Moreover, state-of-the-art miniaturized electrochemical energy storage systems—microsupercapacitors and microbatteries—currently face safety, packaging, materials and microfabrication challenges preventing on-chip technological readiness2,3,6, leaving an opportunity for electrostatic microcapacitors. Here we report record-high electrostatic energy storage density (ESD) and power density, to our knowledge, in HfO2–ZrO2-based thin film microcapacitors integrated into silicon, through a three-pronged approach. First, to increase intrinsic energy storage, atomic-layer-deposited antiferroelectric HfO2–ZrO2 films are engineered near a field-driven ferroelectric phase transition to exhibit amplified charge storage by the negative capacitance effect7–12, which enhances volumetric ESD beyond the best-known back-end-of-the-line-compatible dielectrics (115 J cm−3) (ref. 13). Second, to increase total energy storage, antiferroelectric superlattice engineering14 scales the energy storage performance beyond the conventional thickness limitations of HfO2–ZrO2-based (anti)ferroelectricity15 (100-nm regime). Third, to increase the storage per footprint, the superlattices are conformally integrated into three-dimensional capacitors, which boosts the areal ESD nine times and the areal power density 170 times that of the best-known electrostatic capacitors: 80 mJ cm−2 and 300 kW cm−2, respectively. This simultaneous demonstration of ultrahigh energy density and power density overcomes the traditional capacity–speed trade-off across the electrostatic–electrochemical energy storage hierarchy1,16. Furthermore, the integration of ultrahigh-density and ultrafast-charging thin films within a back-end-of-the-line-compatible process enables monolithic integration of on-chip microcapacitors5, which can unlock substantial energy storage and power delivery performance for electronic microsystems17–19.Using a three-pronged approach — spanning field-driven negative capacitance stabilization to increase intrinsic energy storage, antiferroelectric superlattice engineering to increase total energy storage, and conformal three-dimensional deposition to increase areal energy storage density — very high electrostatic energy storage density and power density are reported in HfO2–ZrO2-based thin film microcapacitors integrated into silicon. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. Here we show that mice heterozygous for an Ikbkb gain-of-function mutation develop psoriasis. Doubling the gene dose (IkbkbGoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. IkbkbGoF mice exhibit a selective expansion of Foxp3 + CD25+ Tregs of which a subset express IL-17. These modified Tregs are enriched in both inflamed tissues, blood and spleen, and their transfer is sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs reveal expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-κB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation. [ABSTRACT FROM AUTHOR]

Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132P in biological membranes and MLKLS132P overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, MlklS131P homozygosity reduces the capacity to clear Salmonella from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the MLKL S132P polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease. MLKL is regarded as an executor of the necroptotic inflammatory cell death pathway. Here authors show, by introducing a mutation into mouse MLKL representing a frequently occurring human single nucleotide polymorphism, that MLKL mutations could critically alter the inflammatory response and the clearance of Salmonella from organs upon infection. [ABSTRACT FROM AUTHOR]

Landslides are widespread geomorphological features on the North Island of New Zealand, where they represent one of the primary landscape-forming processes. This study focuses on the steepland terrain surrounding Gisborne, a city located on the east coast of the North Island, at the Hikurangi subduction margin. This terrain consists of young, weak, sedimentary rocks and soils; the most common modes of slope failures are soil creep, slides and flows in shallow, clay-rich soil and regolith, triggered by heavy rainfall. Based on observational data from Sentinel-1 imagery, this study leverages results from interferometric synthetic aperture radar (InSAR) processing to reveal the distribution of deformation across Gisborne's steepland periphery from January 2016 to December 2021. Velocities in the line of sight were obtained from the stack of interferograms and projected along the direction of maximum slope, to extract the true displacement on the slopes. The ascending and descending data sets were combined to reveal the vertical and horizontal components of the deformation. The results were combined with a regional LiDAR data set, aerial imagery and field observations to delineate areas of slope deformation. Finally, slope deformation time series data was compared with rainfall records to identify seasonal changes, due to shrinking and swelling of expansive soils. Although the InSAR displacement data contains some noise, results could be used to identify 132 unstable slopes within the study area, caused by soil creep and earthflows. Also, the shrink-swell of expansive soils causes a seasonal pattern of displacements, which varied by 10–20 mm/year between Austral winter and summer, strongly correlated to rainfall. [ABSTRACT FROM AUTHOR]

The East Coast region of New Zealand has some of the highest erosion rates in the world, due to its proximity to an active plate boundary, susceptibility to high-intensity storms and steep terrain underlain by young soft sedimentary rock and soil. In the city of Gisborne, expansion of residential blocks into steeper terrain in peri-urban areas has required improved capacity for the characterisation and monitoring of slope stability. Landslides have affected several properties and have destroyed infrastructure. Slope failure commonly occurs during heavy rainfall events when slow-moving retrogressive slides transition into earthflows and mudflows. In this study, we used in situ sampling and testing methods combined with remote sensing techniques to provide an understanding of the pre-failure and post-failure behaviour of an urban landslide in Gisborne. High-resolution aerial imagery, unmanned aerial vehicle imagery and light detection and ranging data revealed slope morphology and contours of prehistoric failures in the area, and highlighted the more recent impacts of deforestation on slope stability. Furthermore, Sentinel-1 InSAR analysis determined that gradual deformation began in 2017, following two ex-tropical cyclone events. Deformation downslope continued until an initial failure in July 2020. Following that event, some parts of the slope proceeded to accelerate, leading to a further reactivation event in November 2021, following heavy rainfall. During this November 2021 event, average line of sight velocities ranged from −7.9 to −11.2 mm/year, and deformation rates in the vertical direction (related to rotational slumping) averaged −11.2 to −11.9 mm/year, consistent with field observations. [ABSTRACT FROM AUTHOR]

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants. Despite effective vaccines against SARS-CoV-2, therapeutic options such as anti-virals and neutralizing antibodies are critical in treating disease, especially given the breakthrough infections of emerging VOCs. Here, Peng et al. generate two potent monoclonal antibodies and a bispecific antibody with two antigenrecognition variable regions targeting SARS-CoV-2 spike, provide CryoEM structures and show in vitro and in vivo efficacy of a humanized antibody against wildtype virus and delta variant. [ABSTRACT FROM AUTHOR]

Social anxiety is associated with dissociative experiences, which are thought to occur when coping or avoidance is unavailable, and distress is experienced. Emotion regulation difficulties maintain social anxiety. The current study examined the moderating effect of emotion regulation on social anxiety and dissociation. It was hypothesized that social anxiety would be positively associated with dissociation and that emotion regulation difficulties would moderate the relationship between social anxiety and dissociation such that the relationship would be stronger at higher levels of emotion regulation difficulties. College students aged 18 or older (n = 572) were recruited from a large public university. All participants completed measures of social anxiety, emotion regulation, and dissociation as part of a larger online study. Results supported both hypotheses. Future studies should investigate dissociative symptoms during times of acute stress or anxiety in social anxiety, how emotion regulation difficulties are associated with the genesis of dissociative symptoms, and how these variables are related in more diverse community samples. [ABSTRACT FROM AUTHOR]

We have developed a novel and affordable way to texture virtual hands from individually taken photographs and integrated the virtual hands into a mixed reality neurorehabilitation system. This mixed reality system allows for serious game play with mirrored and non-mirrored hands, designed for patients with unilateral motor impairments. Before we can ethically have patients use the system, we must show that embodiment can be achieved for healthy users. We compare our approach's results to previous work in the field and present a study with 48 healthy (non-clinical) participants targeting visual fidelity and self-location. We show that embodiment can be achieved for mirrored and non-mirrored hand representations and that the higher realism of virtual hands achieved by our texturing approach alters perceived embodiment. We further evaluate whether using virtual hands resized to the individual's hand size affects embodiment. We present a 16-participant study where we could not find a significant difference with personal resized hands. In addition to rehabilitation contexts, our findings have implications for the design and development of applications where embodiment is of high importance, such as surgical training and remote collaboration. [ABSTRACT FROM AUTHOR]

Introduction: Few of the 5000–8000 snakebites reported to poison control centers annually in the USA are attributed to coral snakes. This study describes Texas coral snake envenomations reported to the North American Snakebite Registry. Methods: All Texas coral snake envenomation cases reported to the registry were identified for the period from January 1, 2015, through December 31, 2019. Data reviewed for this study included details regarding the snake encounter, patient demographics, signs and symptoms, treatment, and outcomes. Descriptive statistics were used to report results. Results: Ten men and four nonpregnant women reported coral snake bites. The median patient age was 15.5 (range 5–72 years). There were 12 upper extremity bites and two bites to the lower extremity. The most common symptoms reported were paresthesias and pain. All subjects had paresthesias, often described as an "electric" sensation. Seven patients described them as painful. The most common clinical findings were erythema and swelling. No patient developed tissue damage, hematotoxicity, rhabdomyolysis, hypotension, weakness, or respiratory symptoms. Thirteen subjects were treated with opioids. Six patients were treated with antiemetics: three prophylactically and two for opioid-induced nausea. One patient developed nausea and non-bloody, nonbilious emesis within 1 hour of the bite, prior to receiving opioids. No patients were treated with antivenom. Antibiotics were not administered to any patient, and no infections were reported. Conclusions: Envenomations from M. tener in Southeast Texas are characterized by painful paresthesias. Mild swelling and erythema are common. Neurotoxicity necessitating antivenom or mechanical ventilation did not occur. [ABSTRACT FROM AUTHOR]

Introduction: The Toxicology Investigators Consortium (ToxIC) database, created in 2010 by the American College of Medical Toxicology (ACMT), compiles data recorded by medical toxicologists. In January 2017, the data field for transgender (and if transgender, male-to-female or female-to-male) was added to the ToxIC form. Little is known regarding trends in poisonings among transgender patients. We sought to review consultations managed by a bedside toxicologist and provide descriptive data in trends among types of exposures within the transgender demographic. Methods: A retrospective ToxIC database evaluation of cases in which the patient identified as transgender were reviewed from January 2017–June 2019 and descriptive demographics reported. Results: The registry contained 113 cases that involved transgender patients. Of those with complete data, 41 (36.6%) were male-to-female, 68 (60.7%) were female-to-male, and 3 (2.7%) identified as gender non-conforming. Of those with complete data, the most common reason for encounter was intentional use of a pharmaceutical drug (N = 97, 85.8%), of which 85 (87.6%) were classified as intentional pharmaceutical use intended for self-harm. Analgesics were the most common class of drugs used out of those reported (N = 24, 22%). Forty-six (90.2%) patients aged 13–18 with complete data were identified as encounters due to self-harm. Attempt at self-harm was the most common reason for intentional pharmaceutical encounter among the sample of transgender patients with complete data (N = 85, 87.6%); with female-to-male patients having an N = 53 (77.9%). Conclusion: Among transgender patients in the ToxIC registry, the most common primary reason for the encounter was intentional use of a pharmaceutical drug intended for self-harm. In this small cohort, there were some age and transition differences in prevalence. These findings may inform poisoning prevention practices as well as sex- and gender-based management of patients in this vulnerable population. [ABSTRACT FROM AUTHOR]

Objective: To review pediatric poisonings evaluated at the bedside by medical toxicologists and reported in the ToxIC registry, by sex and age group. Methods: Pediatric poisoning cases age ≤18 years, reported between January 2010 and December 2016, were reviewed. Descriptive statistics were used to describe study variables by age group and sex. Results: A total of 12,699 cases were analyzed. There were 7517 females and 5182 males. Those < 2 years old represented 12.5% of the study group (n = 1584), 17.2% were 2–6 years old (n = 2178), 8.6% were 7–12 years old (n = 1097), and 61.7% were 13–18 years old (n = 7840). The most common primary reasons for encounter were intentional pharmaceutical with 4900 females and 1836 males; intentional non-pharmaceutical with 952 females and 1213 males; unintentional pharmaceutical with 539 females and 644 males; and unintentional non-pharmaceutical with 435 females and 593 males. Overall, pharmaceuticals were the most commonly involved agents, including analgesics (20.9% of cases) and antidepressants (11% of cases): 27.8% of females and 10.7% of males were reportedly exposed to an analgesic.13.7% of females and 7.0% of males were reportedly exposed to an antidepressant. Among 1584 cases under 2 years, there were 747 females and 837 males; among 2178 cases aged 2–6 years, there were 954 females and 1224 males; among 1097 cases aged 7–12 years, there were 555 females and 542 males; and among 7840 cases aged 13–18 years, there were 5261 females and 2579 males. Death was reported in 0.7% of the cases: 20 females and 18 males. 6.1% of cases were managed with intubation: 421 females and 351 males. Conclusions: Sex-based characteristics of poisonings varied by age group among pediatric poisoning presentations reported to the ToxIC registry and further research is needed to determine implications for education and prevention efforts. [ABSTRACT FROM AUTHOR]

Psychologists have made substantial progress at developing empirically validated formal expressions of how people perceive, learn, remember, think, and know. In this article, we present an academic search engine for cognitive psychology that leverages computational expressions of human cognition (vector-space models of semantics) to represent and find articles in the psychological record. The method shows how psychological theory can be used to inform and aid the design of psychologically intuitive computer interfaces. [ABSTRACT FROM AUTHOR]

Purpose: Magnesium supplementation modulates glucose metabolism and inflammation, which could influence exercise performance and recovery. This study investigated the effect of magnesium intake on physiological responses and performance during eccentric exercise and recovery.Methods: Nine male recreational runners completed a counterbalanced, double-blind, placebo-controlled, cross-over study, registered at ClinicalTrial.gov. Participants consumed low magnesium diets and were supplemented with 500 mg/day of magnesium (SUP) or placebo (CON) for 7 days prior to a 10 km downhill (- 10%) running time trial (TT), separated by a 2-week washout period. At baseline and 24 h post-TT, maximal muscle force was measured. Interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R) and creatine kinase (CK) were measured at rest, 0 h, 1 h and 24 h post-TT. Muscle soreness was measured at the previous times plus 48 h and 72 h post. Glucose and lactate were measured during the TT.Results: The main effect of condition was detected for IL-6 (SUP: 1.36 ± 0.66 vs CON: 2.06 ± 1.14 pg/ml) (P < 0.05, η2 = 0.54), sIL-6R (SUP: 27,615 ± 8446 vs CON: 24,368 ± 7806 pg/ml) (P < 0.05, η2 = 0.41) and muscle soreness (P < 0.01, η2 = 0.67). Recovery of blood glucose and muscle soreness were enhanced in SUP post-TT. There were no differences in glucose and lactate during the TT, or post measures of CK and maximal muscle force.Conclusion: Magnesium supplementation reduced the IL-6 response, enhanced recovery of blood glucose, and muscle soreness after strenuous exercise, but did not improve performance or functional measures of recovery. [ABSTRACT FROM AUTHOR]

Purpose: It has been previously shown that New Zealand blackcurrant (NZBC) extract increased fat oxidation during short duration cycling. The present study examined the effect of different doses of NZBC extract on substrate oxidation and physiological responses during prolonged cycling.Methods: Using a randomized counterbalanced Latin-square design, 15 endurance-trained male cyclists (age: 38 ± 12 years, height: 187 ± 5 cm, body mass: 76 ± 10 kg, [Formula: see text]: 56 ± 8 mL kg-1 min-1, and mean ± SD) completed four separate 120-min cycling bouts at 65% [Formula: see text] after ingesting no dose, or one of three doses (300, 600, or 900 mg day-1) of NZBC extract (CurraNZ™) for 7 days.Results: A dose effect (P < 0.05) was observed for average fat oxidation (0, 300, 600, and 900 mg day-1 values of 0.63 ± 0.21, 0.70 ± 0.17, 0.73 ± 0.19, and 0.73 ± 0.14 g min-1) and carbohydrate oxidation (0, 300, 600, and 900 mg day-1 values of 1.78 ± 0.51, 1.65 ± 0.48, 1.57 ± 0.44, and 1.56 ± 0.50 g min-1). The individual percentage change of mean fat oxidation was 21.5 and 24.1% for 600 and 900 mg day-1 NZBC extract, respectively, compared to no dose. Heart rate, [Formula: see text], [Formula: see text], plasma lactate, and glucose were not affected.Conclusion: Seven-day intake of New Zealand blackcurrant extract demonstrated a dose-dependent effect on increasing fat oxidation during 120-min cycling at 65% [Formula: see text] in endurance-trained male cyclists. [ABSTRACT FROM AUTHOR]

Purpose: Blackcurrant contains anthocyanins that could alter cardiovascular function and reduce cardiovascular disease risk. We examined dose responses of New Zealand blackcurrant (NZBC) extract on cardiovascular function during supine rest.Methods: Fifteen endurance-trained male cyclists (age: 38 ± 12 years, height: 178 ± 5 cm, body mass: 76 ± 10 kg, [Formula: see text]: 56 ± 8 mL kg-1 min-1, mean ± SD) were randomly assigned using a counterbalanced Latin square design to complete four conditions, a control of no NZBC, or one of three doses (300, 600 or 900 mg day-1) of NZBC extract (CurraNZ™) for 7-days with a 14-day washout. Cardiovascular function (i.e., blood pressure, heart rate, ejection time, cardiac output, stroke volume, and total peripheral resistance) during supine rest was examined (Portapres® Model 2).Results: Systolic and diastolic blood pressure, heart rate and ejection time were unchanged by NZBC. A dose effect (P < 0.05) was observed for cardiac output, stroke volume, and total peripheral resistance. A trend for a dose effect was observed for mean arterial blood pressure. Cardiac output increased by 0.6 ± 0.6 L min-1 (15%) and 1.0 ± 1.0 L min-1 (28%) and stroke volume by 5 ± 8 mL (7%) and 6 ± 17 mL (18%) between control and 600, and 900 mg day-1, respectively. Total peripheral resistance decreased by 4 ± 3 mmHg L-1 min-1 (20%) and 5 ± 9 mmHg L-1 min-1 (20%) for 600, and 900 mg day-1.Conclusion: Seven-days intake of New Zealand blackcurrant extract demonstrated dose-dependent changes on some cardiovascular parameters during supine rest in endurance-trained male cyclists. [ABSTRACT FROM AUTHOR]

Introduction: Adverse drug events/reactions (ADE/ADRs) cost more than $30 billion annually and are among the leading causes of death in the USA. Little is known about patients treated at the bedside for ADE/ADR by medical toxicologists. Methods: We conducted a retrospective study of ADE/ADR cases reported to the Toxicology Investigators Consortium (ToxIC) registry between January 1, 2010, and December 31, 2016. Clinical and demographic data were collected including age, sex, circumstances surrounding exposure, suspected offending substance, clinical manifestations, treatment, disposition, and outcome. Results: Among 51,440 ToxIC cases during this time period, 673 ADE/ADR cases were reported (337 females). By age, ADE/ADRs were seen most commonly among adults age 19–65 years (442/673, 65.7% of ADE/ADR) and older adults age 65–89 years (134/673, 19.9% of ADE/ADR). 222/673 (33%) of consults for ADE/ADR were seen in the emergency department (ED); 181/673 (26.9%) were seen in the hospital ward; and 160/673 (23.8%) were seen in the intensive care unit (ICU). The most commonly reported sign for ADE/ADR was tachycardia: 51/673 (7.6%), followed by bradycardia: 49/673 (7.3%). Most commonly reported agents associated with ADE/ADR were as follows: 97/673 (14.4%) due to cardiovascular medications; 76/673 (11.3%) due to antipsychotic medications; and 61/673 (9.1%) due to antidepressants. 429/673 (63.7%) of ADE/ADR were reported as due to a single agent, and 212/673 (31.5%) were reported as due to multiple agents. Conclusions: 4.2% of cases managed at the bedside by a consulting toxicologist and reported to the ToxIC registry between 2010 and 2016 had ADE/ADR as the reason for consultation. Agents most commonly involved in ADE/ADRs included cardiovascular medications, antipsychotic medications, and antidepressants. [ABSTRACT FROM AUTHOR]

Background: The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.Objectives: The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps.Methods: A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies.Results: The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups.Conclusions: There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching. [ABSTRACT FROM AUTHOR]

A method for producing realistic surrogate debris characteristic of those that would be expected to be found following a nuclear detonation in an urban environment is tested. The melt glass samples are benchmarked against synthetic trinitite via electron microscopy and X-ray diffractometry analysis. The surrogates produced proved to be similar to trinitite and synthetic nuclear melt glass, but showed differences indicative of the calculated precursor matrix for each city modeled. The synthetic debris produced may serve as a tool to advance and validate existing rapid nuclear forensic analysis methods. [ABSTRACT FROM AUTHOR]

Purpose: Blackcurrant intake increases peripheral blood flow in humans, potentially by anthocyanin-induced vasodilation which may affect substrate delivery and exercise performance. We examined the effects of New Zealand blackcurrant (NZBC) extract on substrate oxidation, cycling time-trial performance and plasma lactate responses following the time-trial in trained cyclists.Methods: Using a randomized, double-blind, crossover design, 14 healthy men (age: 38 ± 13 years, height: 178 ± 4 cm, body mass: 77 ± 9 kg, VO2max: 53 ± 6 mL kg(-1) min(-1), mean ± SD) ingested NZBC extract (300 mg day(-1) CurraNZ™ containing 105 mg anthocyanin) or placebo (PL, 300 mg microcrystalline cellulose M102) for 7 days (washout 14 days). On day 7, participants performed 30 min of cycling (3 × 10 min at 45, 55 and 65 % VO2max), followed by a 16.1 km time-trial with lactate sampling during a 20-min passive recovery.Results: NZBC extract increased fat oxidation at 65 % VO2max by 27 % (P < 0.05) and improved 16.1 km time-trial performance by 2.4 % (NZBC: 1678 ± 108 s, PL: 1722 ± 131 s, P < 0.05). Plasma lactate was higher with NZBC extract immediately following the time-trial (NZBC: 7.06 ± 1.73 mmol L(-1), PL: 5.92 ± 1.58 mmol L(-1), P < 0.01).Conclusions: Seven-day intake of New Zealand blackcurrant extract improves 16.1 km cycling time-trial performance and increases fat oxidation during moderate intensity cycling. [ABSTRACT FROM AUTHOR]

To simplify the problem of studying how people learn natural language, researchers use the artificial grammar learning (AGL) task. In this task, participants study letter strings constructed according to the rules of an artificial grammar and subsequently attempt to discriminate grammatical from ungrammatical test strings. Although the data from these experiments are usually analyzed by comparing the mean discrimination performance between experimental conditions, this practice discards information about the individual items and participants that could otherwise help uncover the particular features of strings associated with grammaticality judgments. However, feature analysis is tedious to compute, often complicated, and ill-defined in the literature. Moreover, the data violate the assumption of independence underlying standard linear regression models, leading to Type I error inflation. To solve these problems, we present AGSuite, a free Shiny application for researchers studyingAGL. The suite’s intuitive Web-based user interface allows researchers to generate strings from a database of published grammars, compute feature measures (e.g., Levenshtein distance) for each letter string, and conduct a feature analysis on the strings using linear mixed effects (LME) analyses. The LME analysis solves the inflation of Type I errors that afflicts more common methods of repeated measures regression analysis. Finally, the software can generate a number of graphical representations of the data to support an accurate interpretation of results.We hope the ease and availability of these tools will encourage researchers to take full advantage of item-level variance in their datasets in the study of AGL. We moreover discuss the broader applicability of the tools for researchers looking to conduct feature analysis in any field. [ABSTRACT FROM AUTHOR]

We show that the winning positions of a certain type of two-player game form interesting patterns which often defy analysis, yet can be computed by a cellular automaton. The game, known as Blocking Wythoff Nim, consists of moving a queen as in chess, but always towards (0, 0), and it may not be moved to any of $$k-1$$ temporarily 'blocked' positions specified on the previous turn by the other player. The game ends when a player wins by blocking all possible moves of the other player. The value of k is a parameter that defines the game, and the pattern of winning positions can be very sensitive to k. As k becomes large, parts of the pattern of winning positions converge to recurring chaotic patterns that are independent of k. The patterns for large k display an unprecedented amount of self-organization at many scales, and here we attempt to describe the self-organized structure that appears. This paper extends a previous study (Cook et al. in Cellular automata and discrete complex systems, AUTOMATA 2015, Lecture Notes in Computer Science, vol 9099, pp 71-84, 2015), containing further analysis and new insights into the long term behaviour and structures generated by our blocking queen cellular automaton. [ABSTRACT FROM AUTHOR]

High concentrations of dimethylsulfoniopropionate (DMSP), a chemical compound released by lysed phytoplankton, may indicate high rates of grazing by zooplankton and may thus be a foraging cue for planktivorous fishes. Previous studies have shown that some planktivorous fishes and birds aggregate or alter locomotory behavior in response to this chemical cue, which is likely adaptive because it helps them locate prey. These behavioral responses have been demonstrated in juveniles and adults, but no studies have tested for effects on larval fish. Larvae suffer from high mortality rates and are vulnerable to starvation. While larvae are generally thought to be visual predators, they actually have poor vision and cryptic prey. Thus, larval fish should benefit from a chemical cue that provides information on prey abundance. We reared larval sablefish, Anoplopoma fimbria, for one week and supplemented feedings with varying concentrations of DMSP to test the hypothesis that DMSP affects larval survival. Ecologically relevant DMSP concentrations increased larval survival by up to 70 %, which has implications for production in aquaculture and recruitment in nature. These results provide a new tool for increasing larval production in aquaculture and also suggest that larvae may use DMSP as an olfactory cue. The release of DMSP may be a previously unappreciated mechanism through which phytoplankton affect larval survival and recruitment. [ABSTRACT FROM AUTHOR]

The development of realistic nuclear melt glass surrogates is important to the nuclear forensics community in order to establish analytical protocols for post-detonation analysis. In addition to creating surrogates that are accurate with regard to physical morphology and chemical composition, it is important to develop surrogates that also have similar radiological characteristics. A synthetic melt glass sample was irradiated at the High-Flux Isotope Reactor at Oak Ridge National Laboratory. This sample was counted twice using a semiconductor radiation detector to capture both fission-product signatures as well as those from neutron activation. A qualitative and quantitative analysis was performed to make recommendations for the next irradiation campaign. [ABSTRACT FROM AUTHOR]

A method is developed for predicting and formulating realistic synthetic post-detonation debris relevant to a nuclear surface detonation in arbitrary urban settings. Using these methods guides the development of synthetic debris that serves as a tool for developing and validating novel rapid forensic analysis methods. In order to accurately fabricate realistic homogenous surrogate material, the method incorporates regional soil compositions, land use data, and vehicle contributions to the urban environment. [ABSTRACT FROM AUTHOR]

A method for producing synthetic debris similar to the melt glass produced by nuclear surface testing is demonstrated. Melt glass from the first nuclear weapon test (commonly referred to as trinitite) is used as the benchmark for this study. These surrogates can be used to simulate a variety of scenarios and will serve as a tool for developing and validating forensic analysis methods. [ABSTRACT FROM AUTHOR]

In most human breast cancers, tumor cell proliferation is estrogen dependent. Although hormone-responsive tumors initially respond to anti-estrogen therapies, most of them eventually develop resistance. Our goal was to identify alternative targets that might be regulated to control breast cancer progression. Sulforhodamine B assay was used to measure the viability of cultured human breast cancer cell lines exposed to various inhibitors. Protein expression in whole-cell extracts was determined by Western blotting. BT-474 tumor xenografts in nude mice were used for in vivo studies of tumor progression. RO 48-8071 ([4′-[6-(Allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate]; RO), a small-molecule inhibitor of oxidosqualene cyclase (OSC, a key enzyme in cholesterol biosynthesis), potently reduced breast cancer cell viability. In vitro exposure of estrogen receptor (ER)-positive human breast cancer cells to pharmacological levels of RO or a dose close to the IC for OSC (nM) reduced cell viability. Administration of RO to mice with BT-474 tumor xenografts prevented tumor growth, with no apparent toxicity. RO degraded ERα while concomitantly inducing the anti-proliferative protein ERβ. Two other cholesterol-lowering drugs, Fluvastatin and Simvastatin, were less effective in reducing breast cancer cell viability and were found not to induce ERβ. ERβ inhibition or knockdown prevented RO-dependent loss of cell viability. Importantly, RO had no effect on the viability of normal human mammary cells. RO is a potent inhibitor of hormone-dependent human breast cancer cell proliferation. The anti-tumor properties of RO appear to be in part due to an off-target effect that increases the ratio of ERβ/ERα in breast cancer cells. [ABSTRACT FROM AUTHOR]

In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents--B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages--or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Despite the sequencing of the human and mouse genomes, few genetic mechanisms for protecting against autoimmune disease are currently known. Here we systematically screen the mouse genome for autoimmune regulators to isolate a mouse strain, sanroque, with severe autoimmune disease resulting from a single recessive defect in a previously unknown mechanism for repressing antibody responses to self. The sanroque mutation acts within mature T cells to cause formation of excessive numbers of follicular helper T cells and germinal centres. The mutation disrupts a repressor of ICOS, an essential co-stimulatory receptor for follicular T cells, and results in excessive production of the cytokine interleukin-21. sanroque mice fail to repress diabetes-causing T cells, and develop high titres of autoantibodies and a pattern of pathology consistent with lupus. The causative mutation is in a gene of previously unknown function, roquin (Rc3h1), which encodes a highly conserved member of the RING-type ubiquitin ligase protein family. The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability. [ABSTRACT FROM AUTHOR]

We derive percolation results in the continuum plane that lead to what appears to be a general tendency of many stochastic network models. Namely, when the selection mechanism according to which nodes are connected to each other, is sufficiently spread out, then a lower density of nodes, or on average fewer connections per node, are sufficient to obtain an unbounded connected component. We look at two different transformations that spread-out connections and decrease the critical percolation density while preserving the average node degree. Our results indicate that real networks can exploit the presence of spread-out and unreliable connections to achieve connectivity more easily, provided they can maintain the average number offunctioningconnections per node. [ABSTRACT FROM AUTHOR]

The article reviews the book "The Powerful Ephemeral: Everyday Healing in an Ambiguously Islamic Place" by Carla Bellamy.

Highlights from the article: Cellular automata are discrete systems where dynamics are governed by simple local rules of interaction between discrete elements that are applied in parallel throughout the entire system. The paper "A Universal Non-Conservative Reversible Elementary Triangular Partitioned Cellular Automaton That Shows Complex Behavior" by Kenichi Morita gives an 8-state triangular partitioned cellular automaton with a very simple form of update rule that is both isotropic and reversible. The article "Cellular Automata and Finite Groups" by Alonso Castillo-Ramirez and Maximilien Gadouleau studies the algebraic properties of cellular automata over a finite group.