Escaping the accelerator; how, when and in what numbers do cosmic rays get out of supernova remnants?

The escape of charged particles accelerated by diffusive shock acceleration from supernova remnants is shown to be a more complex process than normally appreciated. Using a box model it is shown that the high-energy end of the spectrum can exhibit spectral breaks even with no formal escape as a result of geometrical dilution and changing time-scales. It is pointed out that the bulk of the cosmic ray particles at lower energies must be produced and released in the late stages of the remnant's evolution whereas the high energy particles are produced early on; this may explain recent observations of slight compositional variations with energy. Escape resulting from ion-neutral friction in dense and partially ionized media is discussed briefly and some comments made on the use of so-called "free escape boundary conditions". Finally estimates are made of the total production spectrum integrated over the life of the remnant.Comment: To appear in MNRA

Role of dorsomedial striatum neuronal ensembles in incubation of methamphetamine craving after voluntary abstinence

Abstract We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. SIGNIFICANCE STATEMENT: In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we used classical pharmacology, in situ hybridization, immunohistochemistry, and the Daun02 inactivation procedure to demonstrate a critical role of dorsomedial striatum neuronal ensembles in this new form of incubation of drug craving

Jellyfish bioprospecting in the mediterranean sea: Antioxidant and lysozyme-like activities from aurelia coerulea (cnidaria, scyphozoa) extracts

Marine invertebrates represent a vast, untapped source of bioactive compounds. Cnidarians are represented by nearly 10,000 species that contain a complex mixture of venoms, collagen, and other bioactive compounds, including enzymes, oligosaccharides, fatty acids, and lipophilic molecules. Due to their high abundance in coastal waters, several jellyfish taxa may be regarded as candidate targets for the discovery of novel lead molecules and biomaterials and as a potential source of food/feed ingredients. The moon jellyfish Aurelia coerulea is one of the most common jellyfish worldwide and is particularly abundant in sheltered coastal lagoons and marinas of the Mediterranean Sea, where it first appeared—as an alien species—in the last century, when Pacific oyster cultivation began. In the present study, the antioxidant and lysozyme antibacterial activities associated with extracts from different medusa compartments—namely the umbrella, oral arms, and secreted mucus—were investigated. Extracts from the oral arms of A. coerulea displayed significant antioxidant activity. Similarly, lysozyme-like activity was the highest in extracts from oral arms. These findings suggest that A. coerulea outbreaks may be used in the search for novel cytolytic and cytotoxic products against marine bacteria. The geographically wide occurrence and the seasonally high abundance of A. coerulea populations in coastal waters envisage and stimulate the search for biotechnological applications of jellyfish biomasses in the pharmaceutical, nutritional, and nutraceutical sectors

Magnetic Resonance Imaging of Optic Nerve Traction During Adduction in Primary Open-Angle Glaucoma With Normal Intraocular Pressure.

PurposeWe used magnetic resonance imaging (MRI) to ascertain effects of optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in primary open-angle glaucoma (POAG).MethodsSeventeen patients with POAG and maximal IOP ≤ 20 mm Hg, and 31 controls underwent MRI in central gaze and 20° to 30° abduction and adduction. Optic nerve and sheath area centroids permitted computation of midorbital lengths versus minimum paths.ResultsAverage mean deviation (±SEM) was -8.2 ± 1.2 dB in the 15 patients with POAG having interpretable perimetry. In central gaze, ON path length in POAG was significantly more redundant (104.5 ± 0.4% of geometric minimum) than in controls (102.9 ± 0.4%, P = 2.96 × 10-4). In both groups the ON became significantly straighter in adduction (28.6 ± 0.8° in POAG, 26.8 ± 1.1° in controls) than central gaze and abduction. In adduction, the ON in POAG straightened to 102.0% ± 0.2% of minimum path length versus 104.5% ± 0.4% in central gaze (P = 5.7 × 10-7), compared with controls who straightened to 101.6% ± 0.1% from 102.9% ± 0.3% in central gaze (P = 8.7 × 10-6); and globes retracted 0.73 ± 0.09 mm in POAG, but only 0.07 ± 0.08 mm in controls (P = 8.8 × 10-7). Both effects were confirmed in age-matched controls, and remained significant after correction for significant effects of age and axial globe length (P = 0.005).ConclusionsAlthough tethering and elongation of ON and sheath are normal in adduction, adduction is associated with abnormally great globe retraction in POAG without elevated IOP. Traction in adduction may cause mechanical overloading of the ON head and peripapillary sclera, thus contributing to or resulting from the optic neuropathy of glaucoma independent of IOP

AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies

Cosmic-ray acceleration in supernova remnants: non-linear theory revised

A rapidly growing amount of evidences, mostly coming from the recent gamma-ray observations of Galactic supernova remnants (SNRs), is seriously challenging our understanding of how particles are accelerated at fast shocks. The cosmic-ray (CR) spectra required to account for the observed phenomenology are in fact as steep as $E^{-2.2}--E^{-2.4}$, i.e., steeper than the test-particle prediction of first-order Fermi acceleration, and significantly steeper than what expected in a more refined non-linear theory of diffusive shock acceleration. By accounting for the dynamical back-reaction of the non-thermal particles, such a theory in fact predicts that the more efficient the particle acceleration, the flatter the CR spectrum. In this work we put forward a self-consistent scenario in which the account for the magnetic field amplification induced by CR streaming produces the conditions for reversing such a trend, allowing --- at the same time --- for rather steep spectra and CR acceleration efficiencies (about 20%) consistent with the hypothesis that SNRs are the sources of Galactic CRs. In particular, we quantitatively work out the details of instantaneous and cumulative CR spectra during the evolution of a typical SNR, also stressing the implications of the observed levels of magnetization on both the expected maximum energy and the predicted CR acceleration efficiency. The latter naturally turns out to saturate around 10-30%, almost independently of the fraction of particles injected into the acceleration process as long as this fraction is larger than about $10^{-4}$.Comment: 24 pages, 5 figures, accepted for publication in JCA

Comparison of Outcomes between Endoscopic and Transcleral Cyclophotocoagulation.

Importance: Traditionally cyclophotocoagulation has been reserved as a treatment of last resort for eyes with advanced stage glaucoma, but increasingly it is offered to eyes with less severe disease. Endoscopic approaches in particular are utilized in increasing numbers of patients despite only a small number of publications on its results. Objective: The purpose of this study was to compare the efficacy and safety of endoscopic and transcleral cyclophotocoagulation (ECP and TCP) procedures in eyes with refractory glaucomas. Design, Setting, and Participants: A chart review was performed on consecutive patients who underwent ECP and TCP at a tertiary ophthalmology care center between January 2000 and December 2010. Cases with fewer than 3 months of follow-up or that had concurrent pressure reducing procedures were excluded. The main outcome measures examined were intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), additional glaucoma procedure required, and complications. Main Outcomes and Measures: Forty-two eyes (42 patients) that underwent ECP and forty-four eyes (44 patients) that underwent TCP were identified. The TCP group had a statistically higher mean age (71.2 ± 16.7 vs. 58.1 ± 22.9 years, respectively), larger proportion of neovascular glaucoma (40.9% vs. 16.7%), worse initial BCVA (logMAR 2.86 vs. 1.81), and higher preoperative IOP (45.3 vs. 26.6 mmHg) than the ECP group. At 12 months follow-up, the mean IOP difference between groups was not statistically significant, although the change in IOP from baseline to 12 months was greater for the TCP group (p = 0.006). The rates of progression to no light perception (NLP) and phthisis bulbi were significantly higher amongst TCP eyes than ECP eyes (27.2% vs. 4.8%, p = 0.017, and 20.5% vs. 0%, p = 0.003, respectively). Of these eyes that progressed, a majority had neovascular glaucoma (NVG). Corneal decompensation was the most frequent complication following ECP (11.9%). Conclusions and Relevance: In patients with preoperative BCVA of 20/400 or better, overall complication rates (cystoid macular edema, exudative retinal detachment, inflammation, cornea decompensation) were higher after ECP than with TCP. In refractory glaucomas in a real world setting (not a trial), TCP was more frequently used in ischemic eyes. TCP was associated with a higher rate of progression to phthisis bulbi and loss of light perception than ECP. However, ECP was associated with a clinically significant rate of corneal decompensation. These outcomes likely were related to the severity of underlying ocular diseases found in these eyes

Identification of Dimethyldioctadecylammonium Ion (m/z 550.6) and Related Species (m/z 522.6, 494.6) as a Source of Contamination in Mass Spectrometry

Chemical contamination can be one of the more common problems encountered when performing trace-level analysis regardless of the analytical technique. Minimizing or eliminating background interferences can be a difficult task, so knowledge of the chemical composition of these contaminants can prove invaluable when it comes to identifying the source. Once the source is identified, proper steps may be taken to reduce or eliminate it. In this study, we report the identity of some commonly seen contaminants (m/z 550.6, 522.6, and 494.6) in electrospray ionization (ESI) mass spectrometry (MS). Through MS, tandem MS, accurate-mass, and high-resolution measurements we have identified these background contaminants as being quaternary ammonium species that contain long-chain hydrocarbon groups, where m/z 550.6 is a dimethyldioctadecylammonium ion (C18, C18) and m/z 522.6 and 494.6 are similar in nature but have shorter alkyl-chain groups. The lipophilic nature of these compounds and the fact that they have molecular weights similar to lysophospholipids make them a frequent contaminant in lipidomic studies. The likely sources of these compounds are commonly used personal and household products

Asymmetric phenotype of Axenfeld-Rieger anomaly and aniridia associated with a novel PITX2 mutation

PurposeTo evaluate the asymmetry of the anterior segment phenotype between the two eyes of a patient with Axenfeld-Rieger syndrome (ARS).MethodsThe entire database of a tertiary glaucoma practice was screened for patients with ARS. The medical records of patients with ARS were reviewed. The clinical characteristics of ocular examination of the two eyes of each patient were recorded and compared. Dental and medical information were also reviewed where available. The anterior segment phenotype was tabulated to assess asymmetry. Asymmetric anterior segment characteristics of patients with ARS were compared with reported cases in the literature.ResultsEight patients with ARS were identified from screening of more than 5,000 patients of a tertiary glaucoma practice. All patients had Axenfeld-Rieger anomaly in both eyes except one patient presented with an asymmetric phenotype of the anterior segment with features of Axenfeld-Rieger anomaly in one eye, but aniridia in the other eye. This patient had non-ocular findings including flat midface, hypodontia with lack of an upper incisor, and redundant periumbilical skin, typical for ARS. A heterozygous C>T nucleotide substitution was identified in exon 4 of the pituitary homeobox 2 (PITX2) gene, resulting in the replacement of a glutamine codon (CAG) with a stop codon (TAG) at amino acid position 67. This mutation is denoted c.199C>T at the cDNA level or p.Gln67Stop (or Q67X) at the protein level. Only three cases with asymmetric anterior segment phenotype between the two eyes of a patient with AGS have been reported in the literature.ConclusionsVariability in phenotype may occur between the two eyes of an individual affected by ARS. The current case undermines the advantage of genetic testing to correctly diagnose a rare disease

Distinct fos-expressing neuronal ensembles in the ventromedial prefrontal cortex mediate food reward and extinction memories

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration.Wefirst trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area