RESUMO
This paper uncovers and exploits a link between a central object in harmonic analysis, the so-called Schur functions, and the very hot topic of symmetry protected topological phases of quantum matter. This connection is found in the setting of quantum walks, i.e. quantum analogs of classical random walks. We prove that topological indices classifying symmetry protected topological phases of quantum walks are encoded by matrix Schur functions built out of the walk. This main result of the paper reduces the calculation of these topological indices to a linear algebra problem: calculating symmetry indices of finite-dimensional unitaries obtained by evaluating such matrix Schur functions at the symmetry protected points ± 1 . The Schur representation fully covers the complete set of symmetry indices for 1D quantum walks with a group of symmetries realizing any of the symmetry types of the tenfold way. The main advantage of the Schur approach is its validity in the absence of translation invariance, which allows us to go beyond standard Fourier methods, leading to the complete classification of non-translation invariant phases for typical examples.
RESUMO
OBJECTIVE: To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400 U or 200 U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment. The primary efficacy measure was the daily average numeric rating scale pain score for the study knee over 7 days at week 8. Secondary efficacy measures included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function scores, the patient global impression of change score and the 7-day average worst pain score. RESULTS: Of the 176 enrolled patients, 158 completed the study. The daily average pain score was reduced by approximately two points for all treatments (week 8); the reduction was sustained throughout follow-up, with no significant between-group difference between onabotulinumtoxinA and placebo (both doses: 0.22 [95% confidence interval (CI): -0.33, 0.76]; 400 U: 0.42 [95% CI: -0.26, 1.10]; 200 U: -0.03 [95% CI: -0.70, 0.64]). Similar results were found for all secondary efficacy measures. Treatment-related adverse events occurred in 3.4% of the pooled onabotulinumtoxinA group and placebo group; none were serious. CONCLUSIONS: There were no significant differences between onabotulinumtoxinA and placebo in reducing average pain score at week 8 compared with baseline in patients with knee OA. No safety concerns were identified. CLINICALTRIALS. GOV IDENTIFIER: NCT02230956.
Assuntos
Artralgia/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Artralgia/diagnóstico , Artralgia/etiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares/administração & dosagem , Osteoartrite do Joelho/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Human herpes virus-8 (HHV8) encodes a cytokine named viral interleukin-6 (vIL-6) that shares 25% amino-acid identity with its human homologue. Human IL-6 is known to be a growth and differentiation factor of lymphatic cells and plays a potential role in the pathophysiology of various lymphoproliferative diseases. vIL-6 is expressed in HHV8-associated-diseases including Kaposi's sarcoma, Body-cavity-based-lymphoma and Castleman's disease, suggesting a pathogenetic involvement in the malignant growth of B-cell associated diseases and other malignant tumours. We expressed vIL-6 in Escherichia coli as a fusion protein with recombinant periplasmic maltose binding protein. After cleavage from the maltose binding protein moiety and purification, vIL-6 was shown to be correctly folded using circular dichroism spectroscopy. A rabbit antiserum was raised against the recombinant vIL-6 protein. vIL-6 turned out to be active on cells that expressed gp130 but no IL-6 receptor (IL-6-R) suggesting that, in contrast to human IL-6, vIL-6 stimulated gp130 directly. Accordingly, vIL-6 activity could be inhibited by a soluble gp130 Fc Fusion protein. vIL-6 was shown to induce neuronal differentiation of rat pheochromocytoma cells and to stimulate colony formation of human hematopoietic progenitor cells. Thus, vIL-6 exhibits biologic activity that has only been observed for the IL-6/soluble IL-6-R complex but not for IL-6 alone. These properties are important for the evaluation of the pathophysiological potential of vIL-6.
Assuntos
Antígenos CD/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Herpesvirus Humano 8 , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Glicoproteínas de Membrana/metabolismo , Neurônios/metabolismo , Proteínas Virais/metabolismo , Proteínas Virais/farmacologia , Sequência de Aminoácidos , Animais , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Receptor gp130 de Citocina , Proteína GAP-43/efeitos dos fármacos , Proteína GAP-43/metabolismo , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Interleucina-6/genética , Dados de Sequência Molecular , Neurônios/efeitos dos fármacos , Células PC12/efeitos dos fármacos , Ratos , Receptores de Interleucina/metabolismo , Receptores de Interleucina-6/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas Virais/genéticaRESUMO
The genome of human herpes virus 8, which is associated with Kaposi's sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6. Although the function of these viral proteins is unclear, they might have the potential to modulate the immune system. For viral IL-6 (vIL-6), it has been demonstrated that it stimulates IL-6-dependent cells, indicating that the IL-6R system is used. IL-6 binds to IL-6R, and the IL-6/IL-6R complex associates with gp130 which dimerizes and initiates intracellular signaling. Cells that only express gp130 but no IL-6R cannot be stimulated by IL-6 unless a soluble form of the IL-6R is present. This type of signaling has been shown for hematopoietic progenitor cells, endothelial cells, and smooth muscle cells. In this paper we show that purified recombinant vIL-6 binds to gp130 and stimulates primary human smooth muscle cells. IL-6R fails to bind vIL-6 and is not involved in its signaling. A Fc fusion protein of gp130 turned out to be a potent inhibitor of vIL-6. Our data demonstrate that vIL-6 is the first cytokine which directly binds and activates gp130. This property points to a possible role of this viral cytokine in the pathophysiology of human herpes virus 8.
Assuntos
Antígenos CD/metabolismo , Interleucina-6/fisiologia , Glicoproteínas de Membrana/metabolismo , Receptores de Interleucina-6/fisiologia , Transdução de Sinais/imunologia , Proteínas Virais/fisiologia , Idoso , Animais , Antígenos CD/biossíntese , Células COS , Precipitação Química , Clonagem Molecular , Receptor gp130 de Citocina , Proteínas de Ligação a DNA/metabolismo , Vetores Genéticos , Inibidores do Crescimento/farmacologia , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Glicoproteínas de Membrana/biossíntese , Fosforilação , Ligação Proteica , Receptores de Interleucina-6/metabolismo , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT3 , Sarcoma de Kaposi/química , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/patologia , Transativadores/metabolismo , Células Tumorais Cultivadas , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
The threshold of binocular depth perception was measured in 11 healthy volunteers. A three-rod arrangement was employed in which both the luminance of the rods and that of the adapting field could be adjusted independently. This allowed fixing the contrast when the effect of luminance was studied or fixing the luminance when the effect of contrast was investigated. The observation distance was 400 mm. Thresholds were expressed as angular disparities and were based on 75% correct responses. Points of subjective equality were also determined. Lowest thresholds (2.85 +/- 0.67 s of arc) were found for a moderate contrast of 0.5 whereas low (0.05) and high (0.95) contrast both produced significantly higher thresholds (luminance 250 cd/m2). Altering the field luminance (50, 250, 1600 cd/m2) under constant contrast conditions (0.95) did not measurably influence stereoscopic acuity.