As the data rates supported by the physical layer increase, overheads increasingly dominate the throughput of wireless networks. A promising approach for reducing overheads is to group a number of frames together into one transmission. This can reduce the impact of overheads by sharing headers and the time spent waiting to gain access to the transmission floor. Traditional aggregation schemes require that frames that are aggregated all be destined to the same receiver. These approaches neglect the fact that transmissions are broadcast and a single transmission will potentially be received by many receivers. Thus, by taking advantage of the broadcast nature of wireless transmissions, overheads can be amortized over more data and achieve more performance gain. To show this, we design a series of MAC-based aggregation protocols that take advantage of rate adaptation and the broadcast nature of wireless transmissions. We first show the design of a system that can aggregate both unicast and broadcast frames. Further, the system can classify TCP ACK segments so that they can be aggregated with TCP data flowing in the opposite direction. Second, we develop a rate-adaptive frame aggregation scheme that allows us to find the best aggregation size by tracking the size based on received data frames and the data rate chosen by rate adaptation. Third, we develop a multi-destination frame aggregation scheme to aggregate broadcast frames and unicast frames that are destined for different receivers using delayed ACKs. Using a delayed ACK scheme allows multiple receivers to control transmission time of the ACKs. Finally, we extend multi-destination rate-adaptive frame aggregation to allow piggybacking of various types of metadata with user packets. This promises to lower the impact of metadata-based control protocols on data transport. A novel aspect of our work is that we implement and validate the designs not through simulation, but rather using our wireless node prototype, Hydra, which supports a high performance PHY based on 802.11n. To validate our designs, we conduct extensive experiments both on real and emulator-based channels and measure system performance. / text

In quiescent yeast, the widespread reorganization of cytosolic proteins into punctate has been observed (Narayanaswamy et al. 2009). We seek to better understand and describe this reorganization, which we hypothesize to be a protein aggregation phenomenon. To test this hypothesis, we examined mutant proteins (Ade4p protein variants) in yeast with predicted non-native aggregation propensities and measured their punctate formation kinetics. Monitoring punctate formation kinetics involved the validation of an automated quantification technique using an Amnis ImageStream imaging flow cytometer. The automated punctate counts were strongly correlated with the manual punctate counts, with usual R² values of 0.99 or better, but evaluated 50-fold more cells per run. Fitness evaluations of the mutant yeast in the form of growth curves and batch competition experiments revealed the slowed growth of the Ade4-1286 strain and the functional inequality to the wild type strain of the Ade4-mtoin2034, Ade4-mtoin2105, and Ade4-2800 strains in competition experiments, especially when the mutants were forced to generate their own adenine. Subsequent structural analysis of the mutant proteins revealed destabilizing mutations for 4 of the 6 mutant proteins with 2 of the mutations classified as significantly destabilizing ([delta][delta]G >2 kcal/mol). We concluded that the reduction in protein fitness was likely due to the destabilizing effects of the mutations. Evaluation of the punctate formation kinetics revealed little difference between strains in the rate of punctate formation. Further examination revealed the wild type Ade4p and all of the mutants (with the exception of the Ade4-1286 mutant) were predicted to have similar aggregation propensities according to a secondary aggregation predicting algorithm (Zyggregator, Pawar et al. 2005). Additionally, solvent accessibility calculations estimate ~3-19% of the side chain surface area to be solvent accessible, which indicates proximity of mutations to the protein surface. However, mutating buried amino acids likely would have generated a greater disturbance (Matthews 1993, Tokuriki et al. 2007). We concluded that the mutations, although destabilizing, altered the aggregation propensity very little. Deletion of chaperone proteins (Hsp82p, Hsc82p, and Ssa1p) revealed no difference in the Ade4-GFP punctate formation kinetics, although a slight kinetic difference was detected in the chaperone (Hsp82p) knockout, Gln1-GFP strain and the wild type strain. While further workup is necessary in the chaperone knockout, Gln1-GFP work, the initial results are promising and suggest the involvement of protein folding machinery in punctate formation. / text

Online aggregation is a new trend in today’s world. It is developed from an IT concept to a much broader idea that applies to a variety of areas such as information, human capital, social power, and so on. The power of online aggregation has not only changed the way of business, but also affected the process of social development. The current study identified three models of online aggregation and provided examples of each. Some future implications and downsides of online aggregation are also discussed in this paper. / text

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant inherited neurodegenerative disease for which there is no cure. SCA7 belongs to the group of polyglutamine disorders, which are all caused by the expansion of a polyglutamine tract in different disease proteins. Common toxic mechanisms have been proposed for polyglutamine diseases; however the exact pathological mechanism(s) are still unclear. The aim of this thesis was to identify and characterize the molecular mechanisms by which polyglutamine expansion in the ATXN7 protein cause SCA7 and how this can be counteracted. We found that mutant ATXN7 can be degraded by the ubiquitin proteasome system (UPS) and autophagy, the two main cellular degradation pathways. However aggregation stabilized the protein against degradation. Moreover, we found that mutant ATXN7 blocked the induction of autophagy by interfering with p53 and the ULK1-ATG13-FIP200 complex. Pharmacological stimulation of autophagy ameliorated aggregation, as well as toxicity. We also found that oxidative stress plays an important role in mutant ATXN7 toxicity and that the oxidative stress is generated by activation of NADPH oxidase 1 (NOX1) complexes. Furthermore, we showed that the increased NOX1 activity, together with polyQ expanded ATXN7 mediated disruption of the transcription factor p53, results in metabolic alterations in SCA7 cells. The expression of key p53 regulated metabolic proteins like AIF, TIGAR and GLUT1 was altered in SCA7 cells and resulted in reduced mitochondrial respiration, a higher dependence on glycolysis and reduced ATP levels. In summary, our data indicate that mutant ATXN7 mediated dysregulation of p53, resulting in autophagic and metabolic alterations, could play a key role in SCA7 and possibly other polyglutamine diseases.

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Peripherin is a type III intermediate filament protein that is predominately expressed in the peripheral nervous system and in subsets of efferent projections in the central nervous systems. While the exact role of peripherin remains unclear, it is found upregulated after traumatic neuronal injury and in the devastating neurodegenerative disease amyotrophic lateral sclerosis (ALS). Interestingly, peripherin overexpressing transgenic mice succumb to motor neuron disease with pathological hallmarks reminiscent of those found in ALS. Pathological peripherin abnormalities occur with high frequency in both familial and sporadic forms of ALS, with peripherin found associated with the majority intracellular inclusions present within degenerating motor neuron populations. The findings of peripherin mutations in sporadic ALS have reinforced the importance of peripherin as a prospective etiological or propagative factor of disease pathogenesis. Surprisingly, inherited peripherin gene mutations have not been identified; as such, understanding the post-transcriptional mechanism at which peripherin imparts its effect(s) is considered a key goal and represents a pathological point-of-convergence for an otherwise complex, multifaceted disease. Prior to the commencement of this work, our group identified the presence of an abnormal peripherin alternative splice variant upregulated in ALS. In doing so, we consistently observed the presence of a second peripherin species of ~45 kDa on immunoblots of cell lysates derived from full-length peripherin transfections. Here, we identified this protein as a constitutively expressed isoform, termed Per-45, that arises from alternative translation and that is required for normal filament assembly: changes to the normal isoform expression pattern are associated with malformed filaments and intracellular inclusions. In lieu of the possibility of distinct peripherin intra-isoform associations, we identified isoform-specific expression and ratio changes in traumatic neuronal injury, in mouse models of motor neuron disease, and in ALS. Finally, we explored the interrelationships between peripherin isoform expression, protein aggregation, and neuritic outgrowth by linking these phenotypes with major pathogenic features associated with ALS, including in vitro models of oxidation, glutamate excitotoxicity, and neuroinflammation. Overall, this thesis provides exciting new insight into our knowledge of basic IF biology and the role of peripherin isoforms in injury and in motor neuron disease.

Šiame darbe aš apibendrinau informaciją apie pasirinkimo tarp tiesinio prognozavimo mikro ir makro-modelių problemą. Agregavimas suprantamas kaip sektorinis agregavomas, o modeliai yra iš vienmatės tiesinės regresijos klasės. Aš išvedžiau kriterijų pasirinkimui tarp makro ir mikro-modelių ir idealaus agregavimo testą tiesinio agregavimo su fiksuotais ir atsitiktiniais svoriais atvejais. Paskutiniu atveju idealų agregavimą rekomenduoju tikrinti permutaciniu testu. Rezultatai iliustruoju ekonominiu pavyzdžiu. Modeliuoju Lietuvos vidutinį darbo užmokestį agreguotu modeliu ir atskirose ekonominės veiklos sektoriuose. Analizės rezultatas parodo, kad modeliai yra ekvivalentūs. / This paper focuses on the choice between macro and micro models. I suggest a hypothesis testing procedure for in-sample model selection for such variables as average wage. Empirical results show that Lithuanian average wage should be predict by using aggregate model.

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