Highlights • Synaptic plasticity in juvenile mice is impaired 7 days after cardiac arrest. • Therapeutic hypothermia protects synaptic function when applied after cardiac arrest in juvenile mice. • ...There is a sexually dimorphic response to hypothermic functional protection in female juvenile mice compared to males. • The mechanism of synaptic impairment appears to be downstream of NMDA receptor functional changes after ischemia.
Abstract
Research on proximity effects in superconductor/ferromagnetic hybrids has most often focused on how superconducting properties are affected—and can be controlled—by the effects of the ...ferromagnet’s exchange or magnetic fringe fields. The opposite, namely the possibility to craft, tailor and stabilize the magnetic texture in a ferromagnet by exploiting superconducting effects, has been more seldom explored. Here we show that the magnetic flux trapped in high-temperature superconducting YBa
2
Cu
3
O
7-δ
microstructures can be used to modify the magnetic reversal of a hard ferromagnet—a cobalt/platinum multilayer with perpendicular magnetic anisotropy—and to imprint unusual magnetic domain distributions in a controlled manner via the magnetic field history. The domain distributions imprinted in the superconducting state remain stable, in absence of an external magnetic field, even after increasing the temperature well above the superconducting critical temperature, at variance to what has been observed for soft ferromagnets with in-plane magnetic anisotropy. This opens the possibility of having non-trivial magnetic configuration textures at room temperature after being tailored below the superconducting transition temperature. The observed effects are well explained by micromagnetic simulations that demonstrate the role played by the magnetic field from the superconductor on the nucleation, propagation, and stabilization of magnetic domains.
Global cerebral ischemia following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) causes injury to hippocampal CA1 pyramidal neurons and impairs cognition. Small conductance Ca2+‐activated ...potassium channels type 2 (SK2), expressed in CA1 pyramidal neurons, have been implicated as potential protective targets. Here we showed that, in mice, hippocampal long‐term potentiation (LTP) was impaired as early as 3 h after recovery from CA/CPR and LTP remained impaired for at least 30 days. Treatment with the SK2 channel agonist 1‐Ethyl‐2‐benzimidazolinone (1‐EBIO) at 30 min after CA provided sustained protection from plasticity deficits, with LTP being maintained at control levels at 30 days after recovery from CA/CPR. Minimal changes in glutamate release probability were observed at delayed times after CA/CPR, implicating post‐synaptic mechanisms. Real‐time quantitative reverse transcriptase‐polymerase chain reaction indicated that CA/CPR did not cause a loss of N‐methyl‐D‐aspartate (NMDA) receptor mRNA at 7 or 30 days after CA/CPR. Similarly, no change in synaptic NMDA receptor protein levels was observed at 7 or 30 days after CA/CPR. Further, patch‐clamp experiments demonstrated no change in functional synaptic NMDA receptors at 7 or 30 days after CA/CPR. Electrophysiology recordings showed that synaptic SK channel activity was reduced for the duration of experiments performed (up to 30 days) and that, surprisingly, treatment with 1‐EBIO did not prevent the CA/CPR‐induced loss of synaptic SK channel function. We concluded that CA/CPR caused alterations in post‐synaptic signaling that were prevented by treatment with the SK2 agonist 1‐EBIO, indicating that activators of SK2 channels may be useful therapeutic agents to prevent ischemic injury and cognitive impairments.
Sustained protection of hippocampal plasticity by 1‐EBIO.
Each year there are approximately 7000 out of hospital cardiac arrests in the pediatric population, with 30% resuscitation rate and a 6–10% rate of survival to hospital discharge. Survivors of ...cardiac arrest exhibit learning and memory deficits that are devastating during the school years. Delayed neuronal cell death occurs in the hippocampus following cardiac arrest and likely contributes to memory impairments. Circulating endogenous estrogen in young adult females has been shown to provide protection against ischemic cell death, as does chronic exogenous administration of 17β-estradiol (E2). Chronic estrogen benefit can have undesirable feminizing effects, particularly in pre-adolescents. Here, we tested if a single-dose of E2 is neuroprotective in our pediatric cardiac arrest mouse model performed in juvenile mice. We subjected P21P25 C57Blk6 male and female mice to 8 min of cardiac arrest followed by cardiopulmonary resuscitation (CA/CPR). This developmental stage preceded the hormonal onset and serum estradiol and testosterone levels were not different in males and females. A single dose of E2 (100μg/kg) or vehicle was administered 30 min after resuscitation. Neuronal cell death measured 3 days after CA/CPR showed reduced hippocampal cell death in E2-treated females, but not males. Benefit of E2 in females was blocked by the P38 MAPK inhibitor, SB203580. Hippocampal-dependent memory function was equally impaired in E2-and vehicle-treated females measured in the contextual fear conditioning task at 7 days. Our findings demonstrate female-specific transient neuroprotection with E2 that does not provide sustained functional benefit.
•Single dose estradiol provided neuroprotection only in females.•Estradiol neuroprotection was blocked by a P38 MAPK inhibitor.•Acute neuroprotection did not provide sustained histological or functional benefit.
Key-Recovery Attacks on KIDS, a Keyed Anomaly Detection System Tapiador, Juan E.; Orfila, Agustin; Ribagorda, Arturo ...
IEEE Transactions on Dependable and Secure Computing/IEEE transactions on dependable and secure computing,
2015-May-June, 2015-5-00, 20150501, Letnik:
12, Številka:
3
Journal Article
Odprti dostop
Most anomaly detection systems rely on machine learning algorithms to derive a model of normality that is later used to detect suspicious events. Some works conducted over the last years have pointed ...out that such algorithms are generally susceptible to deception, notably in the form of attacks carefully constructed to evade detection. Various learning schemes have been proposed to overcome this weakness. One such system is Keyed IDS (KIDS), introduced at DIMVA "10. KIDS" core idea is akin to the functioning of some cryptographic primitives, namely to introduce a secret element (the key) into the scheme so that some operations are infeasible without knowing it. In KIDS the learned model and the computation of the anomaly score are both key-dependent, a fact which presumably prevents an attacker from creating evasion attacks. In this work we show that recovering the key is extremely simple provided that the attacker can interact with KIDS and get feedback about probing requests. We present realistic attacks for two different adversarial settings and show that recovering the key requires only a small amount of queries, which indicates that KIDS does not meet the claimed security properties. We finally revisit KIDS' central idea and provide heuristic arguments about its suitability and limitations.
Septic patients frequently develop cognitive impairment that persists beyond hospital discharge. The impact of sepsis on electrophysiological and molecular determinants of learning is underexplored. ...We observed that mice that survived sepsis or endotoxemia experienced loss of hippocampal long-term potentiation (LTP), a brain-derived neurotrophic factor-mediated (BDNF-mediated) process responsible for spatial memory formation. Memory impairment occurred despite preserved hippocampal BDNF content and could be reversed by stimulation of BDNF signaling, suggesting the presence of a local BDNF inhibitor. Sepsis is associated with degradation of the endothelial glycocalyx, releasing heparan sulfate fragments (of sufficient size and sulfation to bind BDNF) into the circulation. Heparan sulfate fragments penetrated the hippocampal blood-brain barrier during sepsis and inhibited BDNF-mediated LTP. Glycoarray approaches demonstrated that the avidity of heparan sulfate for BDNF increased with sulfation at the 2-O position of iduronic acid and the N position of glucosamine. Circulating heparan sulfate in endotoxemic mice and septic humans was enriched in 2-O- and N-sulfated disaccharides; furthermore, the presence of these sulfation patterns in the plasma of septic patients at intensive care unit (ICU) admission predicted persistent cognitive impairment 14 days after ICU discharge or at hospital discharge. Our findings indicate that circulating 2-O- and N-sulfated heparan sulfate fragments contribute to septic cognitive impairment.
We demonstrate the utility of using the equivalent bottom roughness for calculating the friction factor and the drag coefficient of a seagrass meadow for conditions in which the meadow height is ...small compared to the water depth. Wave attenuation induced by the seagrassPosidonia oceanicais evaluated using field data from bottom-mounted acoustic doppler velocimeters (ADVs). Using the data from one storm event, the equivalent bottom roughness is calculated for the meadow ask
s~ 0.40 m. This equivalent roughness is used to predict the wave friction factorƒ
w, the drag coefficient on the plant,C
D, and ultimately the wave attenuation for other storms. Root mean squared wave height (H
rms) is reduced by around 50% for incident waves of 1.1 m propagating over ~ 1000 m of a meadow ofP. oceanicawith shoot density of ~600 shoots m−2.
Metabotropic glutamate receptors (mGluR) are implicated in long-term memory storage. mGluR-I and mGluR-II antagonists impede various forms of learning and long-term potentiation (LTP) in animals. ...Despite the evidence linking mGluR to learning mechanisms, their role in mossy fiber-CA3 long-term potentiation (LTP) is not yet clear. To explain the involvement of mGluR-I in memory mechanisms, we examined the function of the mGluR-I antagonist 1-aminoindan-1, 5-dicarboxylic acid (AIDA) on the induction of mossy fiber-CA3 LTP in vivo in male Sprague Dawley and Fischer 344 (F344) rats. Acute extracellular mossy fiber (MF) responses were evoked by stimulation of the MF bundle and recorded in the stratum lucidum of CA3. The excitatory postsynaptic potential (EPSP) magnitude was measured by using the initial slope of the field EPSP slope measured 2-3 ms after response onset. After collection of baseline MF-CA3 responses at 0.05 Hz, animals received either ((+/-))-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (N-methyl-D-aspartate-R antagonist, 10 mg/kg ip), naloxone (opioid-R antagonist, 10 mg/kg ip), or AIDA (mGluR antagonist, 1 mg/kg ip or 37.5 nmol ic). LTP was induced by two 100-Hz trains at the intensity sufficient to evoke 50% of the maximal response. Responses were collected for an additional 1 h. AIDA blocked induction of LTP in the mossy fiber pathway (P < 0.05) in both strains of rats after systemic and in Sprague Dawley rats after intrahippocampal injection.
Neurological symptoms following cerebellar stroke can range from motor to cognitive-affective impairments. Topographic imaging studies from patients with lesions confined to the cerebellum have shown ...evidence linking anterior cerebellar lobules with motor function and posterior lobules with cognitive function. Damage to the cerebellum can disrupt functional connectivity in cerebellar stroke patients, as it is highly interconnected with forebrain motor and cognitive areas. The hippocampus plays a key role in memory acquisition, a cognitive domain that is negatively impacted by posterior cerebellar stroke, and there is increasing evidence that the cerebellum can affect hippocampal function in health and disease. To study these topographical dissociations, we developed a mouse photo-thrombosis model to produce unilateral strokes in anterior (lobules III-V) or posterior (lobules VI-VIII) cerebellar cortex to examine hippocampal plasticity and behavior. Histological and MRI data demonstrate reproducible injury that is confined to the targeted lobules. We then measured hippocampal long-term potentiation (LTP) ex-vivo with extracellular field recording experiments in acute brain slices obtained from mice 7 days post-cerebellar stroke. Interestingly, we found that a unilateral posterior stroke resulted in a contralateral hippocampal impairment, matching the cerebellothalamic pathway trajectory, while LTP was intact in both hippocampi of mice with anterior strokes. We also assessed motor coordination and memory function at 7 days post-stroke using a balance beam, contextual and delay fear conditioning (CFC and DFC), and novel object recognition (NOR) tasks. Mice with anterior strokes showed lack of coordination evaluated as an increased number of missteps, while mice with posterior strokes did not. Mice with anterior or posterior cerebellar strokes demonstrated similar freezing behavior to shams in CFC and DFC, while only posterior stroke mice displayed a reduced discrimination index in the NOR task. These data suggest that a unilateral LTP impairment observed in mice with posterior strokes produces a mild memory impairment. Our results demonstrate that our model recapitulates aspects of clinical lesion-symptom mapping, with anterior cerebellar strokes producing impaired motor coordination and posterior cerebellar strokes producing an object-recognition memory impairment. Further studies are warranted to interrogate other motor and cognitive-affective behaviors and brain region specific alterations following focal cerebellar stroke. The novel model presented herein will allow for future preclinical translational studies to improve neurological deficits after cerebellar stroke.
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•We present a novel cerebellar stroke model to assess motor and cognitive-affective impairments•Hippocampal plasticity is impaired contralateral to a posterior cerebellar infarction•A dissociation of motor functions to anterior lobules mimics clinical lesion-symptom mapping after cerebellar stroke
The Josephson effect results from the coupling of two superconductors across a spacer such as an insulator, a normal metal or a ferromagnet to yield a phase coherent quantum state. However, in ...junctions with ferromagnetic spacers, very long-range Josephson effects have remained elusive. Here we demonstrate extremely long-range (micrometric) high-temperature (tens of kelvins) Josephson coupling across the half-metallic manganite La
Sr
MnO
combined with the superconducting cuprate YBa
Cu
O
. These planar junctions, in addition to large critical currents, display the hallmarks of Josephson physics, such as critical current oscillations driven by magnetic flux quantization and quantum phase locking effects under microwave excitation (Shapiro steps). The latter display an anomalous doubling of the Josephson frequency predicted by several theories. In addition to its fundamental interest, the marriage between high-temperature, dissipationless quantum coherent transport and full spin polarization brings opportunities for the practical realization of superconducting spintronics, and opens new perspectives for quantum computing.
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