735 research outputs found

    Extreme Covariant Quantum Observables in the Case of an Abelian Symmetry Group and a Transitive Value Space

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    We represent quantum observables as POVMs (normalized positive operator valued measures) and consider convex sets of observables which are covariant with respect to a unitary representation of a locally compact Abelian symmetry group GG. The value space of such observables is a transitive GG-space. We characterize the extreme points of covariant observables and also determine the covariant extreme points of the larger set of all quantum observables. The results are applied to position, position difference and time observables.Comment: 23 page

    Biochem Soc Trans

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    Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of Abeta (amyloid beta-peptide) in the brain. Evidence shows that the AD-associated PS (presenilin) also forms aggregates under certain conditions and that another AD-associated protein, ubiquilin-1, controls protein aggregation and deposition of aggregated proteins. Here, we review the current knowledge of ubiquilin-1 and PS in protein aggregation and related events that potentially influence neurodegeneration

    Dictionary Matching with One Gap

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    The dictionary matching with gaps problem is to preprocess a dictionary DD of dd gapped patterns P1,,PdP_1,\ldots,P_d over alphabet Σ\Sigma, where each gapped pattern PiP_i is a sequence of subpatterns separated by bounded sequences of don't cares. Then, given a query text TT of length nn over alphabet Σ\Sigma, the goal is to output all locations in TT in which a pattern PiDP_i\in D, 1id1\leq i\leq d, ends. There is a renewed current interest in the gapped matching problem stemming from cyber security. In this paper we solve the problem where all patterns in the dictionary have one gap with at least α\alpha and at most β\beta don't cares, where α\alpha and β\beta are given parameters. Specifically, we show that the dictionary matching with a single gap problem can be solved in either O(dlogd+D)O(d\log d + |D|) time and O(dlogεd+D)O(d\log^{\varepsilon} d + |D|) space, and query time O(n(βα)loglogdlog2min{d,logD}+occ)O(n(\beta -\alpha )\log\log d \log ^2 \min \{ d, \log |D| \} + occ), where occocc is the number of patterns found, or preprocessing time and space: O(d2+D)O(d^2 + |D|), and query time O(n(βα)+occ)O(n(\beta -\alpha ) + occ), where occocc is the number of patterns found. As far as we know, this is the best solution for this setting of the problem, where many overlaps may exist in the dictionary.Comment: A preliminary version was published at CPM 201

    ”Kun maalaisjärki loppuu, niin otetaan lakikirja käsiin”:kokeneiden opettajien ajatuksia työrauhasta ja sen muutoksesta

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    Tiivistelmä. Tutkimuksessa selvitettiin kokeneiden luokanopettajien käsityksiä työrauhasta, työrauhahäiriöistä, työrauhalainsäädännöstä, sekä kokemuksia näiden muutoksesta työuran aikana. Työrauhaa on tutkittu suomalaisittain aktiivisesti erityisesti 70-luvun lopussa ja 80-luvun alussa. Aikaisempien tutkimusten perusteella työrauha on käsitteenä vaikea, sillä opettajat kokevat eri asioita häiriöiksi. Työrauhan määrittely on subjektiivista. Muutos työrauhan suhteen on nähtävissä jo käytetyssä termistössä. Entisinä aikoina on puhuttu kurinpito-ongelmista ja opettaja on ollut tiedonjakaja. Nykyään kuri ymmärretään negatiiviseksi asiaksi, joka ei edistä oppilaan oppimista. Opettajan rooli on vaihtunut tiedonjakajasta oma-aloitteisesti toimivan oppilaan ohjaajaksi. Lainsäädäntöä työrauhaan liittyen on tarkennettu viimeksi vuonna 2014. Työrauhalainsäädäntöä on viime vuosina tarkennettu ottamaan entistä enemmän huomioon oppilaiden ja opettajien perusoikeuksia. Opettajan autoritääriset yksinvaltiaan keinot ylläpitää työrauhaa ovat poistuneet ja laki ottaa huomioon entistä enemmän yksilöiden oikeuksia. Suuntaus on sama opettajan ja oppilaiden välisissä suhteissa koululuokissa. Työrauhan rakentamiseen käytetään entistä enemmän oppilaslähtöisiä keinoja ja oppilaita otetaan mukaan luokan päätöksentekoon ja yhteisten sääntöjen sopimiseen. Tutkimus toteutettiin fenomenografisena tapaustutkimuksena. Tutkimuksen aineisto kerättiin haastattelemalla vähintään 10 vuotta luokanopettajana toimineita opettajia. Yhteensä tutkimukseen osallistui kuusi opettajaa, joista kolme oli miehiä ja kolme oli naisia. Tulosten kannalta sukupuolilla ei ollut oleellista merkitystä. Opettajat kokevat työrauhan tilaksi, jossa oppilaat voivat työskennellä vailla pelkoa ja häiriötekijöitä. Hyvän työrauhan edellytyksenä ei ole luokassa vallitseva hiljaisuus. Useat työskentelytavat korostivat keskustelua. Opettajien mielestä työrauha häiriintyy silloin, kun oppimista ei tapahdu. Työrauhahäiriöiden syyt olivat ensin opettajassa ja vasta sitten oppilaassa. Opettajat tarkastivat häiriötilanteessa ensin omaa käyttäytymistään tai tehtävänantoaan ennen kuin käänsivät katseen oppilaasta johtuviin seikkoihin. Työrauhaa ylläpitäessään lainsäädäntö oli opettajilla taustalla vaikuttavana tekijänä, ei ensimmäisenä mielessä työrauhaan liittyviä ratkaisuja tehdessä. Opettajat pitävät oppilaita nykyään avoimempina ja reippaampina. Opettajat myös tuovat enemmän omaa persoonaansa mukaan ja ovat helpommin lähestyttävissä. Opettajien työtavat ovat yhteisöllisempiä ja opettamistapa ohjaavampi kuin ennen. Rangaistusmenetelmät ovat oppilaslähtöisempiä. Esimerkiksi jälki-istuntoa ei enää juuri käytetä, vaan tilalla ovat kasvatuskeskustelut. Työrauhaan liittyvän lainsäädännön muutos koettiin hyväksi. Laki ottaa entistä enemmän huomioon yksilöiden oikeuksia

    Ownership and governance of Finnish infrastructure networks

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    This research report investigates and analyzes the pros and cons of different ownership and governance models of infrastructure networks. The report covers most infrastructure networks: transportation networks (roads, streets, railways, airports, harbors) and utility networks (water and sewage, energy and electricity). There is no unifying solution that would fit all sectors in terms of the most efficient ownership model. However, in many sectors reforms are needed towards more elaborated client-supplier frameworks to ensure greater efficiency and cost transparency. Surprisingly, traditional organizational structures do not seem to impact on financial returns of those networks that provide user-financed services. In Finland technical infrastructure networks are typically owned, administered and managed by the public sector as they are considered public goods and critical assets for the wellbeing of citizens. In many ways the sectors have remained passive and with little interaction towards more innovative service provision solutions or organizational models. In terms of developing the networks’ services and their profitability, the greatest business opportunity would result from allowing open entry to market and competition in contracting. This would mean abandonment of negotiated contracts and proactive evolution of functional markets. The scope of business opportunities will increase in all aspect of service delivery; from management to engineering and economic studies, asset management systems, construction and maintenance works, and the labor to do all that

    Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood

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    The most frequent form of hemolytic-uremic syndrome (HUS) is associated with infections caused by Shiga-like toxin-producing Enterohaemorrhagic Escherichia coli (STEC). In rarer cases HUS can be triggered by Streptococcus pneumoniae. While production of Shiga-like toxins explains STEC-HUS, the mechanisms of pneumococcal HUS are less well known. S. pneumoniae produces neuraminidases with activity against cell surface sialic acids that are critical for factor H-mediated complement regulation on cells and platelets. The aim of this study was to find out whether S. pneumoniae neuraminidase NanA could trigger complement activation and hemolysis in whole blood. We studied clinical S. pneumoniae isolates and two laboratory strains, a wild-type strain expressing NanA, and a NanA deletion mutant for their ability to remove sialic acids from various human cells and platelets. Red blood cell lysis and activation of complement was measured ex vivo by incubating whole blood with bacterial culture supernatants. We show here that NanA expressing S. pneumoniae strains and isolates are able to remove sialic acids from cells, and platelets. Removal of sialic acids by NanA increased complement activity in whole blood, while absence of NanA blocked complement triggering and hemolytic activity indicating that removal of sialic acids by NanA could potentially trigger pHUS.Peer reviewe

    Survival of Enterococcus faecalis in root canals ex vivo

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72532/1/j.1365-2591.2005.01009.x.pd

    Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration

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    Staphylococcus aureus Panton-Valentine leukocidin is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored. Here, we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and present indirect evidence for receptor recycling that allows multiple toxin pores to be formed close together. With the use of live cell single-molecule super-resolution imaging, Forster resonance energy transfer and nanoscale total internal reflection fluorescence colocalization microscopy, we visualized toxin pore formation in the presence of its natural docking ligand. We demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyperinflammatory reactions in early stages of microbial infections and have implications for several other similar bicomponent toxins and the design of new antibiotics.Haapasalo, K., Wollman, A. J. M., de Haas, C. J. C., van Kessel, K. P. M., van Strijp, J. A. G., Leake, M. C. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration.Peer reviewe

    Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons

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    Neurofilament light (NFL) is one of the proteins forming multimeric neuron-specific intermediate filaments, neurofilaments, which fill the axonal cytoplasm, establish caliber growth, and provide structural support. Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene (NEFL) are among the causes of Charcot–Marie–Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons. We previously demonstrated that a neuropathy-causing homozygous nonsense mutation in NEFL led to the absence of NFL in patient-specific neurons. To understand the disease-causing mechanisms, we investigate here the functional effects of NFL loss in human motor neurons differentiated from induced pluripotent stem cells (iPSC). We used genome editing to generate NEFL knockouts and compared them to patient-specific nonsense mutants and isogenic controls. iPSC lacking NFL differentiated efficiently into motor neurons with normal axon growth and regrowth after mechanical axotomy and contained neurofilaments. Electrophysiological analysis revealed that motor neurons without NFL fired spontaneous and evoked action potentials with similar characteristics as controls. However, we found that, in the absence of NFL, human motor neurons 1) had reduced axonal caliber, 2) the amplitude of miniature excitatory postsynaptic currents (mEPSC) was decreased, 3) neurofilament heavy (NFH) levels were reduced and no compensatory increases in other filament subunits were observed, and 4) the movement of mitochondria and to a lesser extent lysosomes was increased. Our findings elaborate the functional roles of NFL in human motor neurons. NFL is not only a structural protein forming neurofilaments and filling the axonal cytoplasm, but our study supports the role of NFL in the regulation of synaptic transmission and organelle trafficking. To rescue the NFL deficiency in the patient-specific nonsense mutant motor neurons, we used three drugs, amlexanox, ataluren (PTC-124), and gentamicin to induce translational read-through or inhibit nonsense-mediated decay. However, the drugs failed to increase the amount of NFL protein to detectable levels and were toxic to iPSC-derived motor neurons
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