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

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 $G$. The value space of such observables is a transitive $G$-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

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

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

Biochem Soc Trans

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

Ownership and governance of Finnish infrastructure networks

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

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

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

Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood

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

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

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

Carbonic anhydrase IX in oligodendroglial brain tumors

Background Carbonic anhydrase IX is a hypoxia-induced enzyme that has many biologically important functions, including its role in cell adhesion and invasion. Methods This study was set out to investigate the role of CA IX in a series of 86 oligodendroglial brain tumors (71 primary and 15 recurrent; 48 pure oligodendrogliomas and 40 mixed oligoastrocytomas). Results 80% of the tumors showed CA IX expression by immunohistochemistry. Tumors with moderate or strong CA IX expression had decreased level of cell proliferation compared to weak or no CA IX expression (median 2.9 vs. 5.8, p = 0.015). CA IX correlated with two antioxidative enzymes, manganese superoxide dismutase (MnSOD) and regulatory gammaglutamylcysteine synthetase (GLCL-R): CA IX expression was significantly higher in MnSOD-positive tumors (p = 0.008) and decreased in GLCL-R-positive tumors (p = 0.044). In Cox multivariate analysis CA IX expression, patient age and histological component (pure oligodendroglioma vs. mixed oligoastrocytoma) showed independent prognostic values (p = 0.009, p = 0.003 and p = 0.022, respectively), CA IX positivity predicting poorer outcome. Conclusion CA IX was proved to be an independent prognostic indicator in oligodendroglial brain tumors, and it also correlates reversely with cell proliferation. It may have a role in the biology of oligodendrogliomas, and most interestingly, as it is mainly expressed in tumor tissue, CA IX could serve as a target molecule for anticancer treatments.BioMed Central Open acces

The Psoriasis Risk Allele HLA-C*06:02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis

Pharyngeal tonsillitis is one of the most common upper respiratory tract infections, and group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffers from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic forms of this disease are not yet fully understood, but genetic predisposition has been suggested. A genetic association study using Illumina's Immunochip single-nucleotide polymorphism (SNP) array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. More than 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (odds ratio [OR], 3.7 to 4.7; P = 4.9 x 10(-6) to 5.7 x 10(-6)). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (P = 4.8 x 10(-4); OR, 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*57:01, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis (P = 3.2 x 10(-4); OR, 6.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis

PP2A inhibitor PME-1 drives kinase inhibitor resistance in glioma cells

Glioblastoma multiforme (GBM) lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in GBM, glioma cells exhibit intrinsic resistance towards many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here we show that overexpression of the protein phosphatase 2A (PP2A) inhibitor protein PME-1 drives resistance of glioma cells to various multikinase inhibitors. The PME-1-elicited resistance was dependent on specific PP2A complexes and was mediated by a decrease in cytoplasmic HDAC4 activity. Importantly, both PME-1 and HDAC4 associated with human glioma progression, supporting clinical relevance of the identified mechanism. Synthetic lethality induced by both PME-1 and HDAC4 inhibition was dependent on the co-expression of pro-apoptotic protein BAD. Thus, PME-1-mediated PP2A inhibition is a novel mechanistic explanation for multikinase inhibitor resistance in glioma cells. Clinically, these results may inform patient stratification strategies for future clinical trials with selected kinase inhibitors in GBM