Electron Beam Irradiation Dose Dependently Damages the Bacillus Spore Coat and Spore Membrane

Effective control of spore-forming bacilli begs suitable physical or chemical methods. While many spore inactivation techniques have been proven effective, electron beam (EB) irradiation has been frequently chosen to eradicate Bacillus spores. Despite its widespread use, there are limited data evaluating the effects of EB irradiation on Bacillus spores. To study this, B. atrophaeus spores were purified, suspended in sterile, distilled water, and irradiated with EB (up to 20 kGy). Irradiated spores were found (1) to contain structural damage as observed by electron microscopy, (2) to have spilled cytoplasmic contents as measured by spectroscopy, (3) to have reduced membrane integrity as determined by fluorescence cytometry, and (4) to have fragmented genomic DNA as measured by gel electrophoresis, all in a dose-dependent manner. Additionally, cytometry data reveal decreased spore size, increased surface alterations, and increased uptake of propidium iodide, with increasing EB dose, suggesting spore coat alterations with membrane damage, prior to loss of spore viability. The present study suggests that EB irradiation of spores in water results in substantial structural damage of the spore coat and inner membrane, and that, along with DNA fragmentation, results in dose-dependent spore inactivation

Evidence for Habitual and Goal-Directed Behavior Following Devaluation of Cocaine: A Multifaceted Interpretation of Relapse

BACKGROUND:Cocaine addiction is characterized as a chronically relapsing disorder. It is believed that cues present during self-administration become learned and increase the probability that relapse will occur when they are confronted during abstinence. However, the way in which relapse-inducing cues are interpreted by the user has remained elusive. Recent theories of addiction posit that relapse-inducing cues cause relapse habitually or automatically, bypassing processing information related to the consequences of relapse. Alternatively, other theories hypothesize that relapse-inducing cues produce an expectation of the drug's consequences, designated as goal-directed relapse. Discrete discriminative stimuli signaling the availability of cocaine produce robust cue-induced responding after thirty days of abstinence. However, it is not known whether cue-induced responding is a goal-directed action or habit. METHODOLOGY/PRINCIPAL FINDINGS:We tested whether cue-induced responding is a goal-directed action or habit by explicitly pairing or unpairing cocaine with LiCl-induced sickness (n = 7/group), thereby decreasing or not altering the value of cocaine, respectively. Following thirty days of abstinence, no difference in responding between groups was found when animals were reintroduced to the self-administration environment alone, indicating habitual behavior. However, upon discriminative stimulus presentations, cocaine-sickness paired animals exhibited decreased cue-induced responding relative to unpaired controls, indicating goal-directed behavior. In spite of the difference between groups revealed during abstinent testing, no differences were found between groups when animals were under the influence of cocaine. CONCLUSIONS/SIGNIFICANCE:Unexpectedly, both habitual and goal-directed responding occurred during abstinent testing. Furthermore, habitual or goal-directed responding may have been induced by cues that differed in their correlation with the cocaine infusion. Non-discriminative stimulus cues were weak correlates of the infusion, which failed to evoke a representation of the value of cocaine and led to habitual behavior. However, the discriminative stimulus-nearly perfectly correlated with the infusion-likely evoked a representation of the value of the infusion and led to goal-directed behavior. These data indicate that abstinent cue-induced responding is multifaceted, dynamically engendering habitual or goal-directed behavior. Moreover, since goal-directed behavior terminated habitual behavior during testing, therapeutic approaches aimed at reducing the perceived value of cocaine in addicted individuals may reduce the capacity of cues to induce relapse

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

Final Measurement of the U235 Antineutrino Energy Spectrum with the PROSPECT-I Detector at HFIR

This Letter reports one of the most precise measurements to date of the antineutrino spectrum from a purely U235-fueled reactor, made with the final dataset from the PROSPECT-I detector at the High Flux Isotope Reactor. By extracting information from previously unused detector segments, this analysis effectively doubles the statistics of the previous PROSPECT measurement. The reconstructed energy spectrum is unfolded into antineutrino energy and compared with both the Huber-Mueller model and a spectrum from a commercial reactor burning multiple fuel isotopes. A local excess over the model is observed in the 5MeV to 7MeV energy region. Comparison of the PROSPECT results with those from commercial reactors provides new constraints on the origin of this excess, disfavoring at 2.2 and 3.2 standard deviations the hypotheses that antineutrinos from U235 are solely responsible and non-contributors to the excess observed at commercial reactors respectively.Comment: The paper has been updated with an improved parametrization of the observed antineutrino spectrum excess and extended discussion on its potential isotopic origi

Calibration strategy of the PROSPECT-II detector with external and intrinsic sources

This paper presents an energy calibration scheme for an upgraded reactor antineutrino detector for the Precision Reactor Oscillation and Spectrum Experiment (PROSPECT). The PROSPECT collaboration is preparing an upgraded detector, PROSPECT-II (P-II), to advance capabilities for the investigation of fundamental neutrino physics, fission processes and associated reactor neutrino flux, and nuclear security applications. P-II will expand the statistical power of the original PROSPECT (P-I) dataset by at least an order of magnitude. The new design builds upon previous P-I design and focuses on improving the detector robustness and long-term stability to enable multi-year operation at one or more sites. The new design optimizes the fiducial volume by elimination of dead space previously occupied by internal calibration channels, which in turn necessitates the external deployment. In this paper, we describe a calibration strategy for P-II. The expected performance of externally deployed calibration sources is evaluated using P-I data and a well-benchmarked simulation package by varying detector segmentation configurations in the analysis. The proposed external calibration scheme delivers a compatible energy scale model and achieves comparable performance with the inclusion of an additional AmBe neutron source, in comparison to the previous internal arrangement. Most importantly, the estimated uncertainty contribution from the external energy scale calibration model meets the precision requirements of the P-II experiment.Comment: 19 pages, 10 figure

PROSPECT-II Physics Opportunities

The Precision Reactor Oscillation and Spectrum Experiment, PROSPECT, has made world-leading measurements of reactor antineutrinos at short baselines. In its first phase, conducted at the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory, PROSPECT produced some of the strongest limits on eV-scale sterile neutrinos, made a precision measurement of the reactor antineutrino spectrum from $^{235}$U, and demonstrated the observation of reactor antineutrinos in an aboveground detector with good energy resolution and well-controlled backgrounds. The PROSPECT collaboration is now preparing an upgraded detector, PROSPECT-II, to probe yet unexplored parameter space for sterile neutrinos and contribute to a full resolution of the Reactor Antineutrino Anomaly, a longstanding puzzle in neutrino physics. By pressing forward on the world's most precise measurement of the $^{235}$U antineutrino spectrum and measuring the absolute flux of antineutrinos from $^{235}$U, PROSPECT-II will sharpen a tool with potential value for basic neutrino science, nuclear data validation, and nuclear security applications. Following a two-year deployment at HFIR, an additional PROSPECT-II deployment at a low enriched uranium reactor could make complementary measurements of the neutrino yield from other fission isotopes. PROSPECT-II provides a unique opportunity to continue the study of reactor antineutrinos at short baselines, taking advantage of demonstrated elements of the original PROSPECT design and close access to a highly enriched uranium reactor core

Note on arXiv:2005.05301, 'Preparation of the Neutrino-4 experiment on search for sterile neutrino and the obtained results of measurements'

We comment on the claimed observation [arXiv:arXiv:2005.05301] of sterileneutrino oscillations by the Neutrino-4 collaboration. Such a claim, whichrequires the existence of a new fundamental particle, demands a level of rigorcommensurate with its impact. The burden lies with the Neutrino-4 collaborationto provide the information necessary to prove the validity of their claim tothe community. In this note, we describe aspects of both the data and analysismethod that might lead to an oscillation signature arising from a nullexperiment and describe additional information needed from the Neutrino-4collaboration to support the oscillation claim. Additionally, as opposed to theassertion made by the Neutrino-4 collaboration, we also show that the method of'coherent summation' using the $L/E$ parameter produces similar results to themethods used by the PROSPECT and the STEREO collaborations.<br