Violation of a Leggett-Garg inequality with ideal non-invasive measurements

The quantum superposition principle states that an entity can exist in two different states simultaneously, counter to our 'classical' intuition. Is it possible to understand a given system's behaviour without such a concept? A test designed by Leggett and Garg can rule out this possibility. The test, originally intended for macroscopic objects, has been implemented in various systems. However to-date no experiment has employed the 'ideal negative result' measurements that are required for the most robust test. Here we introduce a general protocol for these special measurements using an ancillary system which acts as a local measuring device but which need not be perfectly prepared. We report an experimental realisation using spin-bearing phosphorus impurities in silicon. The results demonstrate the necessity of a non-classical picture for this class of microscopic system. Our procedure can be applied to systems of any size, whether individually controlled or in a spatial ensemble.Comment: 6+4 pages. Supplementary Methods section include

HSP27 induced glaucomatous damage in mice of young and advanced age

IntroductionAge-related diseases such as glaucoma, a leading cause of blindness, are having an upward trend due to an aging society. In glaucoma, some patients display altered antibody profiles and increased antibody titers, for example against heat shock protein 27 (HSP27). An intravitreal injection of HSP27 leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones.MethodsWe intravitreally injected HSP27 into young (1–2 months) and aged (7–8 months) mice to compare glaucomatous damage. Respective age-matched controls received PBS. Not injected eyes served as naive controls.ResultsOptical coherence tomography 4 weeks after injection showed no changes in retinal thickness in all groups at both ages. Cell counts and RT-qPCR revealed a significant reduction in RGC numbers in HSP27 mice at both ages. Comparing aged and young HSP27 mice, no differences in Rbpms and Pou4f1 (RGCs) expression was detected, while the Tubb3 expression (neuronal cells) was significantly upregulated in aged HSP27 animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in HSP27 mice at both ages. Nevertheless, increased relative Iba1 and Tmem119 expression was detected in young and aged HSP27 mice. Aged HSP27 mice displayed a significantly lower Iba1 expression than young ones, whereas Cd68 levels were upregulated. A larger GFAP+ area and an upregulation of GFAP expression in HSP27 animals of both ages indicated a macrogliosis. Also, elevated Il1b and Nos2 expression levels were observed in young and aged HSP27 mice. However, only Il1b levels were upregulated when comparing 7–8 months to 1–2 months old animals. A larger HSP25+ area was seen in aged HSP27 animals, while Hspb2 expression levels were downregulated in both HSP27 groups. The aged HSP27 group displayed an upregulated Hspb2 expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged HSP27 groups.DiscussionThese findings indicate that an intravitreal injection of HSP27 led to RGC loss accompanied by inflammation. Age-dependent effects (7–8 months vs. 1–2 months) were not very prominent. The results suggest a potential role of extracellular HSP27 in the development of glaucoma

Intravitreal S100B Injection Leads to Progressive Glaucoma Like Damage in Retina and Optic Nerve

The glial protein S100B, which belongs to a calcium binding protein family, is up-regulated in neurological diseases, like multiple sclerosis or glaucoma. In previous studies, S100B immunization led to retinal ganglion cell (RGC) loss in an experimental autoimmune glaucoma (EAG) model. Now, the direct degenerative impact of S100B on the retina and optic nerve was evaluated. Therefore, 2 μl of S100B was intravitreally injected in two concentrations (0.2 and 0.5 μg/μl). At day 3, 14 and 21, retinal neurons, such as RGCs, amacrine and bipolar cells, as well as apoptotic mechanisms were analyzed. Furthermore, neurofilaments, myelin fibers and axons of optic nerves were evaluated. In addition, retinal function and immunoglobulin G (IgG) level in the serum were measured. At day 3, RGCs were unaffected in the S100B groups, when compared to the PBS group. Later, at days 14 and 21, the RGC number as well as the β-III tubulin protein level was reduced in the S100B groups. Only at day 14, active apoptotic mechanisms were noted. The number of amacrine cells was first affected at day 21, while the bipolar cell amount remained comparable to the PBS group. Also, the optic nerve neurofilament structure was damaged from day 3 on. At day 14, numerous swollen axons were observed. The intraocular injection of S100B is a new model for a glaucoma like degeneration. Although the application site was the eye, the optic nerve degenerated first, already at day 3. From day 14 on, retinal damage and loss of function was noted. The RGCs in the middle part of the retina were first affected. At day 21, the damage expanded and RGCs had degenerated in all areas of the retina as well as amacrine cells. Furthermore, elevated IgG levels in the serum were measured at day 21, which could be a sign of a late and S100B independet immune response. In summary, S100B had a direct destroying impact on the axons of the optic nerve. The damage of the retinal cell bodies seems to be a consequence of this axon loss

Разработка информационной системы учета и анализа проектной деятельности студента

В статье показан процесс проектирования информационной системы учета и анализа проектной деятельности студента. Проектная деятельность является на сегодняшний день актуальным методом ведения учебной деятельности, который активно внедряется в университеты, в том числе и в ТПУ

Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?

BACKGROUND To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON). METHODS All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome. CONCLUSION Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes

Entanglement in a Solid State Spin Ensemble

Entanglement is the quintessential quantum phenomenon and a necessary ingredient in most emerging quantum technologies, including quantum repeaters, quantum information processing (QIP) and the strongest forms of quantum cryptography. Spin ensembles, such as those in liquid state nuclear magnetic resonance, have been powerful in the development of quantum control methods, however, these demonstrations contained no entanglement and ultimately constitute classical simulations of quantum algorithms. Here we report the on-demand generation of entanglement between an ensemble of electron and nuclear spins in isotopically engineered phosphorus-doped silicon. We combined high field/low temperature electron spin resonance (3.4 T, 2.9 K) with hyperpolarisation of the 31P nuclear spin to obtain an initial state of sufficient purity to create a non-classical, inseparable state. The state was verified using density matrix tomography based on geometric phase gates, and had a fidelity of 98% compared with the ideal state at this field and temperature. The entanglement operation was performed simultaneously, with high fidelity, to 10^10 spin pairs, and represents an essential requirement of a silicon-based quantum information processor.Comment: 4 pages, 3 figures plus supporting information of 4 pages, 1 figure v2: Updated reference

From Ganglion Cell to Photoreceptor Layer: Timeline of Deterioration in a Rat Ischemia/Reperfusion Model

Neuronal damage and impaired vision in different retinal disorders are induced, among other factors, by ischemia/reperfusion (I/R). Since the mechanisms and the progression of ischemic injury are still not completely clarified, a timeline of this retinal degeneration is needed. In this study, we investigated protein and mRNA alterations at 2, 6, 12, and 24 h as well as 3 and 7 days after ischemia to determine the course of an ischemic insult through the whole retina. Moreover, functional analyses were performed at later stages. We detected a significant functional loss of cells in the inner nuclear layer and photoreceptors at 3 and 7 days. Additionally, the thickness of the whole retina was decreased at these points in time, indicating a severe degradation of all retinal layers. Immunohistological and qRT-PCR analyses of retinal ganglion cells (RGCs), glial cells, AII amacrine, cone and rod bipolar as well as cone and rod photoreceptor cells confirmed this first assumption. Our results show that all investigated cell types were damaged by ischemia induction. Especially RGCs, cone bipolar cells, and photoreceptor cones are very sensitive to I/R. These cells were lost shortly after ischemia induction with a progressive course up to 7 days. In addition, Müller cell gliosis was observed over the entire period of time. These results provide evidence, that I/R induces damage of the whole retina at early stages and increases over time. In conclusion, our study could demonstrate the intense impact of an ischemic injury. The ischemic defect spreads across the whole retina right up to the outer layers in the long-term and thus seems to impair the visual perception already during the stimulus processing. In addition, our findings indicate that the cone pathway seems to be particularly affected by this damage

Enhanced glaucomatous damage accompanied by glial response in a new multifactorial mouse model

IntroductionGlaucoma is a complex, multifactorial neurodegenerative disease, which can lead to blindness if left untreated. It seems that, among others, immune processes, elevated intraocular pressure (IOP), or a combination of these factors are responsible for glaucomatous damage. Here, we combined two glaucoma models to examine if a combination of risk factors (IOP and immune response) results in a more severe damage of retinal ganglion cells (RGCs) and the optic nerves as well as an additional glia activation.MethodsSix-week-old wildtype (WT+ONA) and βB1-Connective Tissue Growth Factor (CTGF) mice (CTGF+ONA) were immunized with 1 mg ONA (optic nerve antigen). A WT and a CTGF control group (CTGF) received sodium chloride instead. IOP was measured before and every two weeks after immunization. After six weeks, electroretinogram (ERG) measurements were performed. Then, retinae and optic nerves were processed for (immuno-) histology. Further, mRNA levels of corresponding genes in optic nerve and retina were analyzed via RT-qPCR.ResultsSix weeks after immunization, the IOP in CTGF and CTGF+ONA mice was increased. The optic nerve of CTGF+ONA animals displayed the most severe cell inflammation, demyelination, and macroglia activation. Fewer numbers of oligodendrocytes were only observed in WT+ONA optic nerves, while more apoptotic cells triggered by the extrinsic pathway could be revealed in all three glaucoma groups. The number of microglia/macrophages was not altered within the optic nerves of all groups. The loss of neuronal cells, especially RGCs was most pronounced in CTGF+ONA retinae in the central part and this was accompanied by an enhanced activation of microglia/macrophages. Also, Müller cell activation could be noted in CTGF and CTGF+ONA retinae.DiscussionIn this new model, an additive degeneration could be noted in optic nerves as well as in the number of RGCs. These results suggest a potential additive role of high IOP and immune factors in glaucoma development, which will aid for understanding this multifactorial disease more precisely in the future

Mutations in GDF5 Reveal a Key Residue Mediating BMP Inhibition by NOGGIN

Signaling output of bone morphogenetic proteins (BMPs) is determined by two sets of opposing interactions, one with heterotetrameric complexes of cell surface receptors, the other with secreted antagonists that act as ligand traps. We identified two mutations (N445K,T) in patients with multiple synostosis syndrome (SYM1) in the BMP–related ligand GDF5. Functional studies of both mutants in chicken micromass culture demonstrated a gain of function caused by a resistance to the BMP–inhibitor NOGGIN and an altered signaling effect. Residue N445, situated within overlapping receptor and antagonist interfaces, is highly conserved among the BMP family with the exception of BMP9 and BMP10, in which it is substituted with lysine. Like the mutant GDF5, both BMPs are insensitive to NOGGIN and show a high chondrogenic activity. Ectopic expression of BMP9 or the GDF5 mutants resulted in massive induction of cartilage in an in vivo chick model presumably by bypassing the feedback inhibition imposed by endogenous NOGGIN. Swapping residues at the mutation site alone was not sufficient to render Bmp9 NOG-sensitive; however, successive introduction of two additional substitutions imparted high to total sensitivity on customized variants of Bmp9. In conclusion, we show a new mechanism for abnormal joint development that interferes with a naturally occurring regulatory mechanism of BMP signaling