Interferon y Stimulation Modulates the Proteolytic Activity and Cleavage Site Preference of 20S Mouse Proteasomes

The proteasome is a 700-kD multisubunit enzyme complex with several proteolytically active sites. The enzyme complex is involved in both ubiquitin-dependent and -independent protein degradation and may contribute to the processing of antigens presented by major histocompatibility complex (MHC) class I molecules. Here we demonstrate that treatment of mouse fibroblast cells with 20 U interferon qr (IFN-y) for 3 d induces a change in the proteasome subunit composition and that the B-type subunit LMP2, which is encoded in the MHC class II region, is incorporated into the enzyme complex. This is paralleled by reduction of the homologous 6-subunit. IFN-3' stimulation results in a downregulation of the chymotrypsin-like Suc-LLVY-MCA peptide hydrolyzing activity of 20S proteasomes whereas the trypsin-like activity remains unaffected. When tested as a substrate a synthetic 25-mer polypeptide whose sequence covers the antigenic nonapeptide YPHFMPTNL of the MCMV pp89, 20S proteasomes of IFN-3'-induced cells exhibit altered chymotrypsin-like cleavage site preferences. In the absence of IFN-qr induction, the naturally processed nonamer peptide that is presented by MHC class.I molecules appears as a minor cleavage product. IFN-'y activation does not result in an increase of the final peptide but results in a different set of peptides. We hypothesize that these peptides represent precursor peptides that can be trimmed to final peptide size

Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration under Similar Systemic Exposures

Objective To test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by intravenous administration. Background Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous alcohol administration techniques, and any differences attributable to the route employed should be understood. Methods We conducted a 2‐session, within‐subject study in 44 young adult, healthy, non‐dependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an intravenous alcohol infusion rate profile, pre‐computed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals’ baseline‐corrected responses at peak BrAC and at half‐peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson‐product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response. Results No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations. Conclusion The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar

Variance of Relative Surprisal as Single-Shot Quantifier

The variance of (relative) surprisal, also known as varentropy, so far mostly plays a role in information theory as quantifying the leading-order corrections to asymptotic independent and identically distributed (IID) limits. Here, we comprehensively study the use of it to derive single-shot results in (quantum) information theory. We show that it gives genuine sufficient and necessary conditions for approximate state transitions between pairs of quantum states in the single-shot setting, without the need for further optimization. We also clarify its relation to smoothed min and max entropies, and construct a monotone for resource theories using only the standard (relative) entropy and variance of (relative) surprisal. This immediately gives rise to enhanced lower bounds for entropy production in random processes. We establish certain properties of the variance of relative surprisal, which will be useful for further investigations, such as uniform continuity and upper bounds on the violation of subadditivity. Motivated by our results, we further derive a simple and physically appealing axiomatic single-shot characterization of (relative) entropy, which we believe to be of independent interest. We illustrate our results with several applications, ranging from interconvertibility of ergodic states, over Landauer erasure to a bound on the necessary dimension of the catalyst for catalytic state transitions and Boltzmann’s H theorem

Breeding for genetic resistance to Salmonella in pigs

Previous experimental Salmonella infection studies in Denmark have shown that some pigs remain faecal culture negative and seronegative despite oral inoculation with 10 c.f.u. S. Typhimunum and housing in highly contaminated pens, suggesting that some pigs are genetically resistant to Salmonella. Our study tested the following hypothesis: The Salmonella-negative status in certain pigs is due to genetic resistance, related to a single gene The resistance gene was supposed to have a low frequency and to be recessive and that full resistance only would appear if both alleles were recessive

Risk-based surveillance for human health hazards: the example of Trichinella

Increasing demands for cost-effectiveness in surveillance for human health hazards can be met by introducmg risk-based principles. This implies targeting subpopulations w1th higher risk of infection compared to the whole population. We demonstrate how historical data from surveillance can be used to assess risk of infection. The model is called Discounting historical evidence and depends mainly on two variables: Annual risk of introduction Plntro and surveillance system sensitivity SSe (ability to detect infection if present). The model Implies simulations that reiterate for a number of years, and for each year the output is updated with the confidence on absence of infection. Trichinella spiralis infection in pigs is used as an example. In Denmark, pigs at slaughter are tested (currently 23 million per year), and despite of \u3e 70 years of sampling no pigs have been found positive. Hence, we concluded that Plntro is low. SSe can be estimated from the maximum number of infected carcasses expected under the specified design prevalence, and the sensitivity of the test applied. According to the assessment, the prevalence of Trichmella in Danish pigs is negligible (\u3c1 case/million). Based on this , a risk-based surveillance programme for Trichinella is designed that targets all out-door reared pigs as well as all sows and boars (currently 610,000 per year). Compared to confined pigs, outdoor-reared pigs have higher risk of getting Trichinella because of their exposure to wildlife, which might harbour Trichinella. Sows and boars are at increased risk, because they live longer than fimshers. Again, SSe and Plntro are estimated and the model is used to show how risk-based surveillance can be applied without jeopardizing human health. Finally, we incorporate wildlife surveys and test quality assurance in the programme. The model results are included in an application to the European Commission concern1ng Denmark\u27s status as a region with negligible risk of Trichinella

By-passing fluctuation theorems

Fluctuation theorems impose constraints on possible work extraction probabilities in thermodynamical processes. These constraints are stronger than the usual second law, which is concerned only with average values. Here, we show that such constraints, expressed in the form of the Jarzysnki equality, can be by-passed if one allows for the use of catalysts---additional degrees of freedom that may become correlated with the system from which work is extracted, but whose reduced state remains unchanged so that they can be re-used. This violation can be achieved both for small systems but also for macroscopic many-body systems, and leads to positive work extraction per particle with finite probability from macroscopic states in equilibrium. In addition to studying such violations for a single system, we also discuss the scenario in which many parties use the same catalyst to induce local transitions. We show that there exist catalytic processes that lead to highly correlated work distributions, expected to have implications for stochastic and quantum thermodynamics

Impulse waves at Kühtai reservoir generated by avalanches and lindslides

The Kühtai reservoir is planned as an addition to the existing Sellrain-Silz group of HPPs. Two natural hazards relevant in terms of potential impulse wave impact on the dam were identified: a snow avalanche near the dam axis and a possible landslide further upstream. A preliminary analytical evaluation of impulse wave heights and wave run-up based on empirical equations showed that dam overtopping could not be excluded. However, several limitations of this evaluation were not satisfied, resulting in a reduced validity of the prediction. Thus, impulse wave generation was investigated in a 1:130 hydraulic scale model. Beside tests related to the relevant events, an additional systematic parameter variation validated the quality of the results. However, as no overtopping occurred even for the parameter variation, no measures such as breakwater or increase of the freeboard were required. The model test results are compared to a further analytical evaluation based on the recently published VAW-manual on landslide generat-ed impulse waves

Lubricant study in ultrahigh vacuum and in various gas environments Final report, 26 Jan. 1965 - 15 Mar. 1966

Wear and friction of lubricated and unlubricated stainless steel bearings in sliding and rolling contact in ultrahigh vacuum and various gas environment