Identification of cancer/testis-antigen genes by massively parallel signature sequencing.

Massively parallel signature sequencing (MPSS) generates millions of short sequence tags corresponding to transcripts from a single RNA preparation. Most MPSS tags can be unambiguously assigned to genes, thereby generating a comprehensive expression profile of the tissue of origin. From the comparison of MPSS data from 32 normal human tissues, we identified 1,056 genes that are predominantly expressed in the testis. Further evaluation by using MPSS tags from cancer cell lines and EST data from a wide variety of tumors identified 202 of these genes as candidates for encoding cancer/testis (CT) antigens. Of these genes, the expression in normal tissues was assessed by RT-PCR in a subset of 166 intron-containing genes, and those with confirmed testis-predominant expression were further evaluated for their expression in 21 cancer cell lines. Thus, 20 CT or CT-like genes were identified, with several exhibiting expression in five or more of the cancer cell lines examined. One of these genes is a member of a CT gene family that we designated as CT45. The CT45 family comprises six highly similar (>98% cDNA identity) genes that are clustered in tandem within a 125-kb region on Xq26.3. CT45 was found to be frequently expressed in both cancer cell lines and lung cancer specimens. Thus, MPSS analysis has resulted in a significant extension of our knowledge of CT antigens, leading to the discovery of a distinctive X-linked CT-antigen gene family.

C4 Photosynthesis evolved in grasses via parallel adaptive genetic changes.

Phenotypic convergence is a widespread and well-recognized evolutionary phenomenon. However, the responsible molecular mechanisms remain often unknown mainly because the genes involved are not identified. A well-known example of physiological convergence is the C4 photosynthetic pathway, which evolved independently more than 45 times [1]. Here, we address the question of the molecular bases of the C4 convergent phenotypes in grasses (Poaceae) by reconstructing the evolutionary history of genes encoding a C4 key enzyme, the phosphoenolpyruvate carboxylase (PEPC). PEPC genes belong to a multigene family encoding distinct isoforms of which only one is involved in C4 photosynthesis [2]. By using phylogenetic analyses, we showed that grass C4 PEPCs appeared at least eight times independently from the same non-C4 PEPC. Twenty-one amino acids evolved under positive selection and converged to similar or identical amino acids in most of the grass C4 PEPC lineages. This is the first record of such a high level of molecular convergent evolution, illustrating the repeatability of evolution. These amino acids were responsible for a strong phylogenetic bias grouping all C4 PEPCs together. The C4-specific amino acids detected must be essential for C4 PEPC enzymatic characteristics, and their identification opens new avenues for the engineering of the C4 pathway in crops.

Data-parallel computation in parallel and distributed environments

The past few decades have seen a considerable increase in the number of parallel and distributed systems. With the development of more complex applications, the need for more powerful systems has emerged and various parallel and distributed environments have been designed and implemented. Each of the environments, including hardware and software, has unique strengths and weaknesses. There is no single parallel environment that can be identified as the best environment for all applications with respect to hardware and software properties. The main goal of this thesis is to provide a novel way of performing data-parallel computation in parallel and distributed environments by utilizing the best characteristics of difference aspects of parallel computing. For the purpose of this thesis, three aspects of parallel computing were identified and studied. First, three parallel environments (shared memory, distributed memory, and a network of workstations) are evaluated to quantify theirsuitability for different parallel applications. Due to the parallel and distributed nature of the environments, networks connecting the processors in these environments were investigated with respect to their performance characteristics. Second, scheduling algorithms are studied in order to make them more efficient and effective. A concept of application-specific information scheduling is introduced. The application- specific information is data about the workload extractedfrom an application, which is provided to a scheduling algorithm. Three scheduling algorithms are enhanced to utilize the application-specific information to further refine their scheduling properties. A more accurate description of the workload is especially important in cases where the workunits are heterogeneous and the parallel environment is heterogeneous and/or non-dedicated. The results obtained show that the additional information regarding the workload has a positive impact on the performance of applications. Third, a programming paradigm for networks of symmetric multiprocessor (SMP) workstations is introduced. The MPIT programming paradigm incorporates the Message Passing Interface (MPI) with threads to provide a methodology to write parallel applications that efficiently utilize the available resources and minimize the overhead. The MPIT allows for communication and computation to overlap by deploying a dedicated thread for communication. Furthermore, the programming paradigm implements an application-specific scheduling algorithm. The scheduling algorithm is executed by the communication thread. Thus, the scheduling does not affect the execution of the parallel application. Performance results achieved from the MPIT show that considerable improvements over conventional MPI applications are achieved.

Introducing massively parallel computers into operational weather forecasting

Numerical weather prediction and climate simulation have been among the computationally most demanding applications of high performance computing eversince they were started in the 1950's. Since the 1980's, the most powerful computers have featured an ever larger number of processors. By the early 2000's, this number is often several thousand. An operational weather model must use all these processors in a highly coordinated fashion. The critical resource in running such models is not computation, but the amount of necessary communication between the processors. The communication capacity of parallel computers often fallsfar short of their computational power. The articles in this thesis cover fourteen years of research into how to harness thousands of processors on a single weather forecast or climate simulation, so that the application can benefit as much as possible from the power of parallel high performance computers. The resultsattained in these articles have already been widely applied, so that currently most of the organizations that carry out global weather forecasting or climate simulation anywhere in the world use methods introduced in them. Some further studies extend parallelization opportunities into other parts of the weather forecasting environment, in particular to data assimilation of satellite observations.

Commentary on "The Cognitive-Emotional Brain: From Interactions to Integration" by Luiz Pessoa - "On theory integration: Toward developing affective components within cognitive architectures"

In The Cognitive-Emotional Brain, Pessoa (2013) suggests that cognition and emotion should not be considered separately. We agree with this and argue that cognitive architectures can provide steady ground for this kind of theory integration and for investigating interactions among underlying cognitive processes. We briefly explore how affective components can be implemented and how neuroimaging measures can help validate models and influence theory development.

Parallel feedback loops control the basal activity of the HOG MAPK signaling cascade.

Tight regulation of the MAP kinase Hog1 is crucial for survival under changing osmotic conditions. Interestingly, we found that Hog1 phosphorylates multiple upstream components, implying feedback regulation within the signaling cascade. Taking advantage of an unexpected link between glucose availability and Hog1 activity, we used quantitative single cell measurements and computational modeling to unravel feedback regulation operating in addition to the well-known adaptation feedback triggered by glycerol accumulation. Indeed, we found that Hog1 phosphorylates its activating kinase Ssk2 on several sites, and cells expressing a non-phosphorylatable Ssk2 mutant are partially defective for feedback regulation and proper control of basal Hog1 activity. Together, our data suggest that Hog1 activity is controlled by intertwined regulatory mechanisms operating with varying kinetics, which together tune the Hog1 response to balance basal Hog1 activity and its steady-state level after adaptation to high osmolarity.

Platform Architectures for Policy-Based Network Access Control

Tämä diplomityö käsittelee sääntöpohjaisen verkkoon pääsyn hallinnan (NAC) ratkaisuja arkkitehtonisesta näkökulmasta. Työssä käydään läpi Trusted Computing Groupin, Microsoft Corporationin, Juniper Networksin sekä Cisco Systemsin NAC-ratkaisuja. NAC koostuu joukosta uusia sekä jo olemassa olevia teknologioita, jotka auttavat ennalta määriteltyyn sääntökantaan perustuen hallitsemaan suojattuun verkkoon pyrkivien laitteiden tietoliikenneyhteyksiä. Käyttäjän tunnistamisen lisäksi NAC pystyy rajoittamaan verkkoon pääsyä laitekohtaisten ominaisuuksien perusteella, esimerkiksi virustunnisteisiin ja käyttöjärjestelmäpäivityksiin liittyen ja paikkaamaan tietyin rajoituksin näissä esiintyviä puutteita verkkoon pääsyn sallimiseksi. NAC on verraten uusi käsite, jolta puuttuu tarkka määritelmä. Tästä johtuen nykymarkkinoilla myydään ominaisuuksiltaan puutteellisia tuotteita NAC-nimikkeellä. Standardointi eri valmistajien NAC-komponenttien yhteentoimivuuden takaamiseksi on meneillään, minkä perusteella ratkaisut voidaan jakaa joko avoimia standardeja tai valmistajakohtaisia standardeja noudattaviksi. Esitellyt NAC-ratkaisut noudattavat standardeja joko rajoitetusti tai eivät lainkaan. Mikään läpikäydyistä ratkaisuista ei ole täydellinen NAC, mutta Juniper Networksin ratkaisu nousee niistä potentiaalisimmaksi jatkokehityksen ja -tutkimuksen kohteeksi TietoEnator Processing & Networks Oy:lle. Eräs keskeinen ongelma NAC-konseptissa on työaseman tietoverkolle toimittama mahdollisesti valheellinen tietoturvatarkistuksen tulos, minkä perusteella pääsyä osittain hallitaan. Muun muassa tähän ongelmaan ratkaisuna voisi olla jo nykytietokoneista löytyvä TPM-siru, mikä takaa tiedon oikeellisuuden ja koskemattomuuden.

Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study.

BACKGROUND: Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies. METHODS: Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC). RESULTS: Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients. CONCLUSIONS: Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.

On the computation of reducible invariant tori on a parallel computer

We present an algorithm for the computation of reducible invariant tori of discrete dynamical systems that is suitable for tori of dimensions larger than 1. It is based on a quadratically convergent scheme that approximates, at the same time, the Fourier series of the torus, its Floquet transformation, and its Floquet matrix. The Floquet matrix describes the linearization of the dynamics around the torus and, hence, its linear stability. The algorithm presents a high degree of parallelism, and the computational effort grows linearly with the number of Fourier modes needed to represent the solution. For these reasons it is a very good option to compute quasi-periodic solutions with several basic frequencies. The paper includes some examples (flows) to show the efficiency of the method in a parallel computer. In these flows we compute invariant tori of dimensions up to 5, by taking suitable sections.

Bernoulli correction to viscous losses: Radial flow between two parallel discs

For a massless fluid (density = 0), the steady flow along a duct is governed exclusively by viscous losses. In this paper, we show that the velocity profile obtained in this limit can be used to calculate the pressure drop up to the first order in density. This method has been applied to the particular case of a duct, defined by two plane-parallel discs. For this case, the first-order approximation results in a simple analytical solution which has been favorably checked against numerical simulations. Finally, an experiment has been carried out with water flowing between the discs. The experimental results show good agreement with the approximate solution

Developing of the Variable Speed Drive -control in simulated parallel pumping systems

This thesis presents briefly the basic operation and use of centrifugal pumps and parallel pumping applications. The characteristics of parallel pumping applications are compared to circuitry, in order to search analogy between these technical fields. The purpose of studying circuitry is to find out if common software tools for solving circuit performance could be used to observe parallel pumping applications. The empirical part of the thesis introduces a simulation environment for parallel pumping systems, which is based on circuit components of Matlab Simulink —software. The created simulation environment ensures the observation of variable speed controlled parallel pumping systems in case of different controlling methods. The introduced simulation environment was evaluated by building a simulation model for actual parallel pumping system at Lappeenranta University of Technology. The simulated performance of the parallel pumps was compared to measured values of the actual system. The gathered information shows, that if the initial data of the system and pump perfonnance is adequate, the circuitry based simulation environment can be exploited to observe parallel pumping systems. The introduced simulation environment can represent the actual operation of parallel pumps in reasonably accuracy. There by the circuitry based simulation can be used as a researching tool to develop new controlling ways for parallel pumps.