386 research outputs found
Parity Problem With A Cellular Automaton Solution
The parity of a bit string of length is a global quantity that can be
efficiently compute using a global counter in time. But is it
possible to find the parity using cellular automata with a set of local rule
tables without using any global counter? Here, we report a way to solve this
problem using a number of binary, uniform, parallel and deterministic
cellular automata applied in succession for a total of time.Comment: Revtex, 4 pages, final version accepted by Phys.Rev.
Stortingets kontroll av forvaltningen Blir Riksrevisjonens forvaltningsrevisjoner fulgt opp?
Temaet for denne oppgaven er om Riksrevisjonens forvaltningsrevisjoner blir fulgt opp av reviderte virksomheter. Forvaltningsrevisjon er Riksrevisjonens arbeid med å sjekke om sentralforvaltningen gjør det Stortinget har vedtatt. Riksrevisjonen følger opp alle forvaltningsrevisjoner de har gjennomført etter tre år. Sentralforvaltningen har det overordene ansvaret for svært mange viktige områder, og det er essensielt at områdene fungerer på best mulig måte.
Oppgavens problemstilling er: Hvordan fører Riksrevisjonens forvaltningsrevisjon, deres råd og anbefalinger til en oppfølgning av virksomheter/organisasjoner? For å besvare problemstillingen har det benyttet seg av Riksrevisjonens forvaltningsundersøkelser fra perioden 2015 til 2019 og de påfølgende oppfølgingsdokumentene. Fire forventinger i form av variabler blir knyttet opp mot datamaterialet for å undersøke om det foreligger en sammenheng mellom disse og Riksrevisjonen vurdering om å følge opp undersøkelsene. Forventingene er en beskrivelse om forventende sammenhenger mellom to variabler, basert på søppelkasse-modellen. Oppgavens forventinger er: statsrådens holdning, grad av kritikk, omfanget av forvaltningsrevisjonen og det økonomiske omfanget. Metoden som er brukt for å analysere disse dokumentene, er en innholdsanalyse både i en kvantitativ form og en kvalitativ form. Innholdsanalysen ble benyttet til å gjennomgå alle dokumentene for den nevnte tidsperioden, og kode disse fra lav til høy. Dette ble gjort for å peke på potensielle sammenhenger. Teorien om strategiske svar til institusjonelt press ble benyttet seg for å forklare funnene i den kvalitative analysen og videre brukt i diskusjonen.
Analysen og den påfølgende diskusjonen av datamaterialet viser at det ikke sammenheng mellom forventningene og at Riksrevisjonen følger opp en undersøkelse. Funnene indikerer derimot at de politiske områdene kan ha en innvirkning på oppfølgingen av undersøkelsene.publishedVersio
Losing the Lust for Life: A New Role for an Old Feeding Peptide?
A recent paper in Nature (Lim et al., 2012) describes the effects of melanocortin receptors in the nucleus accumbens. The studies connect a hypothalamic peptide system with brain reward centers and show effects on specific neuronal populations and behavioral components of mood
Repeated Administration of Norbinaltorphimine Produces Cumulative Kappa Opioid Receptor Inactivation
Kappa receptor activation by dynorphins contributes to the anxiogenic, dysphoric, and cognitive disrupting effects of repeated stress, suggesting that kappa receptor antagonists might have therapeutic utility in the treatment of stress disorders. Three classes of kappa antagonists have been distinguished: non-selective, selective-competitive (readily reversible), and non-competitive (receptor-inactivating); however, which would be the most effective medication has not been established. To assess the utility of receptor inactivating antagonists, we tested the effects of a range of doses in both male and female mice. As previously established, the antinociceptive effects of the kappa agonist U50,488 were blocked by a single injection of the long-acting antagonist norbinatorphimine (norBNI) (10 mg/kg i.p.) in male mice. Ten to 20-fold lower doses of norBNI were ineffective after a single administration, but daily administration of 1.0 or 0.5 mg/kg for 5 days completely blocked U50,488 antinociceptive effects. Daily administration of 0.1 mg/kg norBNI produced slowly accumulating inhibition and completely blocked the antinociceptive effect of U50,488 after 20–30 days. Estrogen reduces female sensitivity to kappa opioid effects, but 30 days of 0.1 mg/kg norBNI completely blocked U50,488 analgesia in ovariectomized mice. Receptor inactivation in both male and female mice treated for 30 days with 0.1 mg/kg norBNI persisted for at least 1-week. These results suggest that receptor-inactivating kappa antagonists are effective in both males and females when given at 100-fold lower doses than typically administered in preclinical studies. The enhanced safety of this low-dosing protocol has important clinical implications if receptor inactivating kappa antagonists advance in medication development
Evaluating operational AVHRR sea surface temperature data at the coastline using surfers
Sea surface temperature (SST) is an essential climate variable that can be measured routinely from Earth Observation (EO) with high temporal and spatial coverage. To evaluate its suitability for an application, it is critical to know the accuracy and precision (performance) of the EO SST data. This requires comparisons with co-located and concomitant in situ data. Owing to a relatively large network of in situ platforms there is a good understanding of the performance of EO SST data in the open ocean. However, at the coastline this performance is not well known, impeded by a lack of in situ data. Here, we used in situ SST measurements collected by a group of surfers over a three year period in the coastal waters of the UK and Ireland, to improve our understanding of the performance of EO SST data at the coastline. At two beaches near the city of Plymouth, UK, the in situ SST measurements collected by the surfers were compared with in situ SST collected from two autonomous buoys located ∼7 km and ∼33 km from the coastline, and showed good agreement, with discrepancies consistent with the spatial separation of the sites. The in situ SST measurements collected by the surfers around the coastline, and those collected offshore by the two autonomous buoys, were used to evaluate the performance of operational Advanced Very High Resolution Radiometer (AVHRR) EO SST data. Results indicate: (i) a significant reduction in the performance of AVHRR at retrieving SST at the coastline, with root mean square errors in the range of 1.0 to 2.0 °C depending on the temporal difference between match-ups, significantly higher than those at the two offshore stations (0.4 to 0.6 °C); (ii) a systematic negative bias in the AVHRR retrievals of approximately 1 °C at the coastline, not observed at the two offshore stations; and (iii) an increase in the root mean square error at the coastline when the temporal difference between match-ups exceeded three hours. Harnessing new solutions to improve in situ sampling coverage at the coastline, such as tagging surfers with sensors, can improve our understanding of the performance of EO SST data in coastal regions, helping inform users interested in EO SST products for coastal applications. Yet, validating EO SST products using in situ SST data at the coastline is challenged by difficulties reconciling the two measurements, which are provided at different spatial scales in a dynamic and complex environment
CRF1-R Activation of the Dynorphin/Kappa Opioid System in the Mouse Basolateral Amygdala Mediates Anxiety-Like Behavior
Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF) were triggered by CRF1-R activation of the dynorphin/kappa opioid receptor (KOR) system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM). The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF1-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF2-R agonist urocortin III did not affect open arm time, and mice lacking CRF2-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF2-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF1-R activation may mediate anxiety and CRF2-R may encode aversion. Using a phosphoselective antibody (KORp) to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype, but not in mice pretreated with the selective CRF1-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was surprising, and these results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced anxiety behaviors and aversive behaviors via different mechanisms
Gene Sets Identified with Oncogene Cooperativity Analysis Regulate In Vivo Growth and Survival of Leukemia Stem Cells
SummaryLeukemia stem cells (LSCs) represent a biologically distinct subpopulation of myeloid leukemias, with reduced cell cycle activity and increased resistance to therapeutic challenge. To better characterize key properties of LSCs, we employed a strategy based on identification of genes synergistically dysregulated by cooperating oncogenes. We hypothesized that such genes, termed “cooperation response genes” (CRGs), would represent regulators of LSC growth and survival. Using both a primary mouse model and human leukemia specimens, we show that CRGs comprise genes previously undescribed in leukemia pathogenesis in which multiple pathways modulate the biology of LSCs. In addition, our findings demonstrate that the CRG expression profile can be used as a drug discovery tool for identification of compounds that selectively target the LSC population. We conclude that CRG-based analyses provide a powerful means to characterize the basic biology of LSCs as well as to identify improved methods for therapeutic targeting
Radiation and breast cancer: a review of current evidence
This paper summarizes current knowledge on ionizing radiation-associated breast cancer in the context of established breast cancer risk factors, the radiation dose–response relationship, and modifiers of dose response, taking into account epidemiological studies and animal experiments. Available epidemiological data support a linear dose–response relationship down to doses as low as about 100 mSv. However, the magnitude of risk per unit dose depends strongly on when radiation exposure occurs: exposure before the age of 20 years carries the greatest risk. Other characteristics that may influence the magnitude of dose-specific risk include attained age (that is, age at observation for risk), age at first full-term birth, parity, and possibly a history of benign breast disease, exposure to radiation while pregnant, and genetic factors
Functional Relationship between Protein Disulfide Isomerase Family Members during the Oxidative Folding of Human Secretory Proteins
We systematically depleted PDI family members and show that whereas ERp72 and P5 contributed minimally to oxidative protein folding, PDI and ERp57 were the predominant catalysts. Depletion of PDI or ERp57 alone modestly delayed folding, but depletion of both led to generalized protein misfolding and degradation
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