Particle Acceleration by Fast Modes in Solar Flares

We address the problem of particle acceleration in solar flares by fast modes which may be excited during the reconnection and undergo cascade and are subjected to damping. We extend the calculations beyond quasilinear approximation and compare the acceleration and scattering by transit time damping and gyroresonance interactions. We find that the acceleration is dominated by the so called transit time damping mechanism. We estimate the total energy transferred into particles, and show that our approach provides sufficiently accurate results We compare this rate with energy loss rate. Scattering by fast modes appears to be sufficient to prevent the protons from escaping the system during the acceleration. Confinement of electrons, on the other hand, requires the existence of plasma waves. Electrons can be accelerated to GeV energies through the process described here for solar flare conditions.Comment: 7 pages, 4 figures, accepted to Ap

Scattering of Cosmic Rays by Magnetohydrodynamic Interstellar Turbulence

Recent advances in understanding of magnetohydrodynamic (MHD) turbulence call for substantial revisions in our understanding of cosmic ray transport. In this paper we use gyroresonance recently obtained scaling laws for MHD modes to calculate the scattering frequency for cosmic rays in the ISM. We consider gyroresonance with MHD modes (Alfvenic, slow and fast) and transit-time damping (TTD) by fast modes. We conclude that the gyroresonance with fast modes is the dominant contribution to cosmic ray scattering for the typical interstellar conditions. In contrast to earlier studies, we find that Alfvenic and slow modes are inefficient because they are far from isotropy usually assumed.Comment: 4 pages, 2 figures, Phys. Rev. Lett. in press, minor change

Exploring Entrepreneurial Roles and Identity in the United Kingdom and China

This paper examines entrepreneurial identity in both the United Kingdom and China through the lenses of identity theory and social identity theory to develop a deeper and more holistic understanding of the concept of entrepreneurial identity. By examining the entrepreneur as both a role and an identity this paper explores how an entrepreneur views the role of the entrepreneur, the counter-roles to the entrepreneur, the ‘self-as-entrepreneur’ understand how entrepreneurs construct their identity as entrepreneur. By looking at the role identity in different social constructs, a more nuanced view of entrepreneurial identity can be uncovered for entrepreneurs in both the UK and China. The study argues that entrepreneurs in the UK use counter-roles to bridge the disconnect between their understanding of the entrepreneur-as-role and the self-as-entrepreneur whereas entrepreneurs in China have less conflict reconciling the two, and use the counter-role as a way to paint entrepreneurship as a ‘calling’, justifying their abandonment of other identities

Novel paradigms for the gut–brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder

Introduction: Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Methods: Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23–63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). Results: CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1β and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). Discussion: The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut–brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut–brain axis response to heavy drinking. Trial registration: ClinicalTrials.gov, identifier: NCT# 00106106

Novel paradigms for the gut–brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder

IntroductionPatients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms.MethodsForty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23–63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS).ResultsCS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1β and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5).DiscussionThe interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut–brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut–brain axis response to heavy drinking.Trial registrationClinicalTrials.gov, identifier: NCT# 00106106

Loss of Cannabinoid Receptor CB1 Induces Preterm Birth

Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in aberrant corticotrophin-releasing hormone and corticosterone activities prior to parturition, suggesting that CB1 regulates labor by interacting with the corticotrophin-releasing hormone-driven endocrine axis

Mouse models of GNAO1-associated movement disorder: Allele- and sex-specific differences in phenotypes.

BackgroundInfants and children with dominant de novo mutations in GNAO1 exhibit movement disorders, epilepsy, or both. Children with loss-of-function (LOF) mutations exhibit Epileptiform Encephalopathy 17 (EIEE17). Gain-of-function (GOF) mutations or those with normal function are found in patients with Neurodevelopmental Disorder with Involuntary Movements (NEDIM). There is no animal model with a human mutant GNAO1 allele.ObjectivesHere we develop a mouse model carrying a human GNAO1 mutation (G203R) and determine whether the clinical features of patients with this GNAO1 mutation, which includes both epilepsy and movement disorder, would be evident in the mouse model.MethodsA mouse Gnao1 knock-in GOF mutation (G203R) was created by CRISPR/Cas9 methods. The resulting offspring and littermate controls were subjected to a battery of behavioral tests. A previously reported GOF mutant mouse knock-in (Gnao1+/G184S), which has not been found in patients, was also studied for comparison.ResultsGnao1+/G203R mutant mice are viable and gain weight comparably to controls. Homozygotes are non-viable. Grip strength was decreased in both males and females. Male Gnao1+/G203R mice were strongly affected in movement assays (RotaRod and DigiGait) while females were not. Male Gnao1+/G203R mice also showed enhanced seizure propensity in the pentylenetetrazole kindling test. Mice with a G184S GOF knock-in also showed movement-related behavioral phenotypes but females were more strongly affected than males.ConclusionsGnao1+/G203R mice phenocopy children with heterozygous GNAO1 G203R mutations, showing both movement disorder and a relatively mild epilepsy pattern. This mouse model should be useful in mechanistic and preclinical studies of GNAO1-related movement disorders