The impact of balancing on problem hardness in a highly structured domain

Random problem distributions have played a key role in the study and design of algorithms for constraint satisfaction and Boolean satisfiability, as well as in ourunderstanding of problem hardness, beyond standard worst-case complexity. We consider random problem distributions from a highly structured problem domain that generalizes the Quasigroup Completion problem (QCP) and Quasigroup with Holes (QWH), a widely used domain that captures the structure underlying a range of real-world applications. Our problem domain is also a generalization of the well-known Sudoku puz- zle: we consider Sudoku instances of arbitrary order, with the additional generalization that the block regions can have rectangular shape, in addition to the standard square shape. We evaluate the computational hardness of Generalized Sudoku instances, for different parameter settings. Our experimental hardness results show that we can generate instances that are considerably harder than QCP/QWH instances of the same size. More interestingly, we show the impact of different balancing strategies on problem hardness. We also provide insights into backbone variables in Generalized Sudoku instances and how they correlate to problem hardness.

Investigation of business models of free zones and possible implications in South East Finland

Tutkielma tarkastelee vapaa alue konseptia osana yritysten kansainvälistä toimitusketjua. Tarkoituksena on löytää keinoja, millä tavoin vapaa alueen houkuttelevuutta voidaan lisätä yritysten näkökulmasta ja millaista liiketoimintaa yritysten on vapaa alueella mahdollista harjoittaa. Tutkielmassa etsitään tekijöitä, jotka vaikuttavat vapaa alueen menestykseen ja jotka voisivat olla sovellettavissa Kaakkois-Suomen ja Venäjän raja-alueelle ottaen huomioon vallitsevat olosuhteet ja lainsäädäntö rajoittavina tekijöinä. Menestystekijöitä ja liiketoimintamalleja haetaan tutkimalla ja analysoimalla lyhyesti muutamia olemassa olevia ja toimivia vapaa alueita. EU tullilain harmonisointi ja kansainvälisen kaupan vapautuminen vähentää vapaa alueen perinteistä merkitystä tullivapaana alueena. Sen sijaan vapaa alueet toimivat yhä enenevissä määrin logistisina keskuksina kansainvälisessä kaupassa ja tarjoavat palveluita, joiden avulla yritykset voivat parantaa logistista kilpailukykyään. Verkostoituminen, satelliitti-ratkaisut ja yhteistoiminta ovat keinoja, millä Kaakkois-Suomen alueen eri logistiikkapalvelujen tarjoajat voivat parantaa suorituskykyään ja joustavuutta kansainvälisessä toimitusketjussa.

Development of rotating drum under mechanical and thermal load

A variable temperature field sets exacting demands to the structure under mechanical load. Most of all the lifetime of the rotating drum structure depends on temperature differences between parts inside the drum. The temperature difference was known because of the measurements made before. The list of demands was created based on customers’ needs. The limits of this paper were set to the inner structure of the drum. Creation of ideas for the inner structure was started open minded. The main principle in the creation process was to create new ideas for the function of the product with the help of sub-functions. The sub-functions were created as independent as possible. The best sub-functions were combined together and the new working principles were created based on them. Every working principle was calculated separately and criticized at the end of the calculation process. The main objective was to create the new kind of structure, which is not based too much to the old, inoperative structure. The affect of own weight of the inner structure to the stress values was quite small but it was also taken into consideration when calculating the maximum stress value of the structure. Because of very complex structures all of the calculations were made with the help of the ProE – Mechanica software. The fatigue analyze was made also for the best structure solution.

TLR3-Mediated CD8+ Dendritic Cell Activation Is Coupled with Establishment of a Cell-Intrinsic Antiviral State.

Because of their unique capacity to cross-present Ags to CD8(+) T cells, mouse lymphoid tissue-resident CD8(+) dendritic cells (DCs) and their migratory counterparts are critical for priming antiviral T cell responses. High expression of the dsRNA sensor TLR3 is a distinctive feature of these cross-presenting DC subsets. TLR3 engagement in CD8(+) DCs promotes cross-presentation and the acquisition of effector functions required for driving antiviral T cell responses. In this study, we performed a comprehensive analysis of the TLR3-induced antiviral program and cell-autonomous immunity in CD8(+) DC lines and primary CD8(+) DCs. We found that TLR3-ligand polyinosinic-polycytidylic acid and human rhinovirus infection induced a potent antiviral protection against Sendai and vesicular stomatitis virus in a TLR3 and type I IFN receptor-dependent manner. Polyinosinic-polycytidylic acid-induced antiviral genes were identified by mass spectrometry-based proteomics and transcriptomics in the CD8(+) DC line. Nanostring nCounter experiments confirmed that these antiviral genes were induced by TLR3 engagement in primary CD8(+) DCs, and indicated that many are secondary TLR3-response genes requiring autocrine IFN-β stimulation. TLR3-activation thus establishes a type I IFN-dependent antiviral program in a DC subtype playing crucial roles in priming adaptive antiviral immune responses. This mechanism is likely to shield the priming of antiviral responses against inhibition or abrogation by the viral infection. It could be particularly relevant for viruses detected mainly by TLR3, which may not trigger type I IFN production by DCs that lack TLR3, such as plasmacytoid DCs or CD8(-) DCs.

Pointwise estimates for the Bergman kernel of the weighted Fock space

We prove upper pointwise estimates for the Bergman kernel of the weighted Fock space of entire functions in $L^{2}(e^{-2\phi}) $ where $\phi$ is a subharmonic function with $\Delta\phi$ a doubling measure. We derive estimates for the canonical solution operator to the inhomogeneous Cauchy-Riemann equation and we characterize the compactness of this operator in terms of $\Delta\phi$.

The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.

In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

Intrahemispheric cortico-cortical connections of the human auditory cortex.

The human auditory cortex comprises the supratemporal plane and large parts of the temporal and parietal convexities. We have investigated the relevant intrahemispheric cortico-cortical connections using in vivo DSI tractography combined with landmark-based registration, automatic cortical parcellation and whole-brain structural connection matrices in 20 right-handed male subjects. On the supratemporal plane, the pattern of connectivity was related to the architectonically defined early-stage auditory areas. It revealed a three-tier architecture characterized by a cascade of connections from the primary auditory cortex to six adjacent non-primary areas and from there to the superior temporal gyrus. Graph theory-driven analysis confirmed the cascade-like connectivity pattern and demonstrated a strong degree of segregation and hierarchy within early-stage auditory areas. Putative higher-order areas on the temporal and parietal convexities had more widely spread local connectivity and long-range connections with the prefrontal cortex; analysis of optimal community structure revealed five distinct modules in each hemisphere. The pattern of temporo-parieto-frontal connectivity was partially asymmetrical. In conclusion, the human early-stage auditory cortical connectivity, as revealed by in vivo DSI tractography, has strong similarities with that of non-human primates. The modular architecture and hemispheric asymmetry in higher-order regions is compatible with segregated processing streams and lateralization of cognitive functions.

Characterization of an antennal carboxylesterase from the pest moth Spodoptera littoralis degrading a host plant odorant.

Background: Carboxyl/cholinesterases (CCEs) are highly diversified in insects. These enzymes have a broad range of proposed functions, in neuro/developmental processes, dietary detoxification, insecticide resistance or hormone/pheromone degradation. As few functional data are available on purified or recombinant CCEs, the physiological role of most of these enzymes is unknown. Concerning their role in olfaction, only two CCEs able to metabolize sex pheromones have been functionally characterized in insects. These enzymes are only expressed in the male antennae, and secreted into the lumen of the pheromone-sensitive sensilla. CCEs able to hydrolyze other odorants than sex pheromones, such as plant volatiles, have not been identified. Methodology: In Spodoptera littoralis, a major crop pest, a diversity of antennal CCEs has been previously identified. We have employed here a combination of molecular biology, biochemistry and electrophysiology approaches to functionally characterize an intracellular CCE, SlCXE10, whose predominant expression in the olfactory sensilla suggested a role in olfaction. A recombinant protein was produced using the baculovirus system and we tested its catabolic properties towards a plant volatile and the sex pheromone components. Conclusion: We showed that SlCXE10 could efficiently hydrolyze a green leaf volatile and to a lesser extent the sex pheromone components. The transcript level in male antennae was also strongly induced by exposure to this plant odorant. In antennae, SlCXE10 expression was associated with sensilla responding to the sex pheromones and to plant odours. These results suggest that a CCE-based intracellular metabolism of odorants could occur in insect antennae, in addition to the extracellular metabolism occurring within the sensillar lumen. This is the first functional characterization of an Odorant- Degrading Enzyme active towards a host plant volatile.

Integrated regulation of the type III secretion system and other virulence determinants in Ralstonia solanacearum

In many plant and animal bacterial pathogens, the Type III secretion system (TTSS) that directly translocates effector proteins into the eukaryotic host cells is essential for the development of disease. In all species studied, the transcription of the TTSS and most of its effector substrates is tightly regulated by a succession of consecutively activated regulators. However, the whole genetic programme driven by these regulatory cascades is still unknown, especially in bacterial plant pathogens. Here, we have characterised the programme triggered by HrpG, a host-responsive regulator of the TTSS activation cascade in the plant pathogen Ralstonia solanacearum. We show through genome-wide expression analysis that, in addition to the TTSS, HrpG controls the expression of a previously undescribed TTSS-independent pathway that includes a number of other virulence determinants and genes likely involved in adaptation to life in the host. Functional studies revealed that this second pathway co-ordinates the bacterial production of plant cell wall-degrading enzymes, exopolysaccharide, and the phytohormones ethylene and auxin. We provide experimental evidence that these activities contribute to pathogenicity. We also show that the ethylene produced by R. solanacearum is able to modulate the expression of host genes and can therefore interfere with the signalling of plant defence responses. These results provide a new, integrated view of plant bacterial pathogenicity, where a common regulator activates synchronously upon infection the TTSS, other virulence determinants and a number of adaptive functions, which act co-operatively to cause disease.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes

Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

Impact of strong psychologically stressful events on the development of Alzheimer disease: a possible role of epigenetic?

Alzheimer disease (AD) is the most common neurodegenerative dementia. It leads to a progressive loss of cognitive functions, especially memory. Most of AD cases are sporadic, resulting from the interplay of genetic and environmental factors which get involved in the regulation of expression of thousands of genes, a mechanism called epigenetic. Epigenetic modifications, by modifying genes transcription, help to orchestrate the phenotypical changes linked to development, aging or even diseases and cancer. In AD, recent studies showed rapid, dynamic and persistent epigenetic mutations that are believed to have consequences on brain functions. One of the earliest biomarker of AD is amylo ̈ıd-beta (Aβ) deposition in the brain. According to current studies, deposition of amylo ̈ıd-beta begins approximately 20 years before the first symptoms linked to the disease which questions us about what could have happened around or before that time. In this exploratory study, we searched if there could be any correlation between the experience of a strong psychologically stressful event in life, which could have lead to several epigenetic changes and therefore the occurrence of Mild Cognitive Impairment (MCI) or AD approximately 30 years later, and to see if there is a difference in the delay between amnestic MCI and AD patients.

Music-supported training is more efficient than functional motor training for recovery of fine motor skills in stroke patients

MOTOR IMPAIRMENTS ARE COMMON AFTER STROKE but efficacious therapies for these dysfunctions are scarce. Extending an earlier study on the effects of music-supported training (MST), behavioral indices of motor function were obtained before and after a series of training sessions to assess whether this new treatment leads to improved motor functions. Furthermore, music-supported training was contrasted to functional motor training according to the principles of constraint-induced therapy (CIT). In addition to conventional physiotherapy, 32 stroke patients with moderately impaired motor function and no previous musical experience received 15 sessions of MST over a period of three weeks, using a manualized, step-bystep approach. A control group consisting of 15 patients received 15 sessions of CIT in addition to conventional physiotherapy. A third group of 30 patients received exclusively conventional physiotherapy and served as a control group for the other three groups. Fine as well as gross motor skills were trained by using either a MIDI-piano or electronic drum pads programmed to emit piano tones. Motor functions were assessed by an extensive test battery. MST yielded significant improvement in fine as well as gross motor skills with respect to speed, precision, and smoothness of movements. These improvements were greater than after CIT or conventional physiotherapy. In conclusion, with equal treatment intensity, MST leads to more pronounced improvements of motor functions after stroke than CIT.

Neurocognition in schizophrenia: a study of the productivity and visibility of spanish authors

This paper provides a map of the scientific productivity of authors affiliated to a Spanish institution and who have addressed one of the most important current topics in schizophrenia: The study of cognitive performance. A search of the Web of Science yielded 125 articles that met the inclusion criteria. In order to provide a comprehensive overview of scientific productivity, we examine several bibliometric indicators, concerning both productivity and impact or visibility. The analysis also focuses on qualitative aspects of key theoretical importance, such as the kinds of cognitive functions that are most often assessed and the tests most widely used to evaluate them in clinical practice. The study shows that interest in the subject of cognitive function in schizophrenia has increased considerably in Spain since the beginning of this century. The results also highlight the need to standardize the type of tests to be used in the cognitive assessment of patients with schizophrenia.

A Practical Micro Mechanical Model Based Local Approach Methodology for the Analysis of Ductile Fracture of Welded T-Joints

This thesis concentrates on developing a practical local approach methodology based on micro mechanical models for the analysis of ductile fracture of welded joints. Two major problems involved in the local approach, namely the dilational constitutive relation reflecting the softening behaviour of material, and the failure criterion associated with the constitutive equation, have been studied in detail. Firstly, considerable efforts were made on the numerical integration and computer implementation for the non trivial dilational Gurson Tvergaard model. Considering the weaknesses of the widely used Euler forward integration algorithms, a family of generalized mid point algorithms is proposed for the Gurson Tvergaard model. Correspondingly, based on the decomposition of stresses into hydrostatic and deviatoric parts, an explicit seven parameter expression for the consistent tangent moduli of the algorithms is presented. This explicit formula avoids any matrix inversion during numerical iteration and thus greatly facilitates the computer implementation of the algorithms and increase the efficiency of the code. The accuracy of the proposed algorithms and other conventional algorithms has been assessed in a systematic manner in order to highlight the best algorithm for this study. The accurate and efficient performance of present finite element implementation of the proposed algorithms has been demonstrated by various numerical examples. It has been found that the true mid point algorithm (a = 0.5) is the most accurate one when the deviatoric strain increment is radial to the yield surface and it is very important to use the consistent tangent moduli in the Newton iteration procedure. Secondly, an assessment of the consistency of current local failure criteria for ductile fracture, the critical void growth criterion, the constant critical void volume fraction criterion and Thomason's plastic limit load failure criterion, has been made. Significant differences in the predictions of ductility by the three criteria were found. By assuming the void grows spherically and using the void volume fraction from the Gurson Tvergaard model to calculate the current void matrix geometry, Thomason's failure criterion has been modified and a new failure criterion for the Gurson Tvergaard model is presented. Comparison with Koplik and Needleman's finite element results shows that the new failure criterion is fairly accurate indeed. A novel feature of the new failure criterion is that a mechanism for void coalescence is incorporated into the constitutive model. Hence the material failure is a natural result of the development of macroscopic plastic flow and the microscopic internal necking mechanism. By the new failure criterion, the critical void volume fraction is not a material constant and the initial void volume fraction and/or void nucleation parameters essentially control the material failure. This feature is very desirable and makes the numerical calibration of void nucleation parameters(s) possible and physically sound. Thirdly, a local approach methodology based on the above two major contributions has been built up in ABAQUS via the user material subroutine UMAT and applied to welded T joints. By using the void nucleation parameters calibrated from simple smooth and notched specimens, it was found that the fracture behaviour of the welded T joints can be well predicted using present methodology. This application has shown how the damage parameters of both base material and heat affected zone (HAZ) material can be obtained in a step by step manner and how useful and capable the local approach methodology is in the analysis of fracture behaviour and crack development as well as structural integrity assessment of practical problems where non homogeneous materials are involved. Finally, a procedure for the possible engineering application of the present methodology is suggested and discussed.