Control of unstable steady states by time-delayed feedback methods

We show that time-delayed feedback methods, which have successfully been used to control unstable periodic ortbits, provide a tool to stabilize unstable steady states. We present an analytical investigation of the feedback scheme using the Lambert function and discuss effects of both a low-pass filter included in the control loop and non-zero latency times associated with the generation and injection of the feedback signal.Comment: 8 pages, 11 figure

Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14-CD15(high) and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16(hi) LDGs. Clinical data on disease course, medication, and antibody status were obtained. Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group. Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD

Synthesis of high-T_g hole-transporting polymers with different redox potentials and their performance in organic two-layer LEDs

Organic hole transport materials are used in organic LEDs, where they substantially improve device performance if placed as a hole transport layer (HTL) between the anode and the electroluminescent layer (EL). Soluble polymeric hole transport materials with high glass transition temperatures are of particular interest, because they allow for efficient device fabrication through spin casting of the HTL, and high glass transition temperatures have been found to improve thermal and long-term stability of the device. The redox potential of the hole transport material determines the facility of charge injection at the anode/HTL and the HTL/EL interfaces, thus affecting the overall device efficiency. We have synthesized a series of soluble hole-transporting polymers with glass transition temperatures in the range of 130 degrees C to 150 degrees C. The synthetic method allows facile substitution of the hole transport functionality with electron-withdrawing and electron-donating groups, which permits tuning of the redox potential of the polymer. These polymers have been used as HTL in tow-layer devices ITO/HTL/Alq/Mg. The maximum external quantum efficiency increase, if the redox potential is changed to facilitate reduction of the hole transport material at the HTL/EL interface. Electron-deficient derivatives show higher external quantum efficiencies. The device stability, however, follows the opposite trend

Radiative damping: a case study

We are interested in the motion of a classical charge coupled to the Maxwell self-field and subject to a uniform external magnetic field, B. This is a physically relevant, but difficult dynamical problem, to which contributions range over more than one hundred years. Specifically, we will study the Sommerfeld-Page approximation which assumes an extended charge distribution at small velocities. The memory equation is then linear and many details become available. We discuss how the friction equation arises in the limit of "small" B and contrast this result with the standard Taylor expansion resulting in a second order equation for the velocity of the charge.Comment: 4 figure

Capgras syndrome as a psychiatric manifestation in Parkinson’s disease: a case report and literature review

We present the case of a 58-year-old male patient who had symptoms of anxiety after witnessing a case of social violence in his community in 2005. After that, he presented symptoms of Parkinson Disease and in 2006 we established this as the main diagnosis. In 2009 he presented neuropsychiatric symptoms such as apathy, anhedonia, social isolation, blunted affect, visual and auditory hallucinations, paranoid delusions, soliloquies, and the false belief that his wife and daughter had been replaced by identical impostors. We established the diagnosis of Capgras Syndrome. This case is clinically relevant because of the presentation of its symptoms, its evolution and its presenting comorbidity

Uncovering convolutional neural network decisions for diagnosing multiple sclerosis on conventional MRI using layer-wise relevance propagation

Machine learning-based imaging diagnostics has recently reached or even surpassed the level of clinical experts in several clinical domains. However, classification decisions of a trained machine learning system are typically non-transparent, a major hindrance for clinical integration, error tracking or knowledge discovery. In this study, we present a transparent deep learning framework relying on 3D convolutional neural networks (CNNs) and layer-wise relevance propagation (LRP) for diagnosing multiple sclerosis (MS), the most widespread autoimmune neuroinflammatory disease. MS is commonly diagnosed utilizing a combination of clinical presentation and conventional magnetic resonance imaging (MRI), specifically the occurrence and presentation of white matter lesions in T2-weighted images. We hypothesized that using LRP in a naive predictive model would enable us to uncover relevant image features that a trained CNN uses for decision-making. Since imaging markers in MS are well-established this would enable us to validate the respective CNN model. First, we pre-trained a CNN on MRI data from the Alzheimer's Disease Neuroimaging Initiative (n = 921), afterwards specializing the CNN to discriminate between MS patients (n = 76) and healthy controls (n = 71). Using LRP, we then produced a heatmap for each subject in the holdout set depicting the voxel-wise relevance for a particular classification decision. The resulting CNN model resulted in a balanced accuracy of 87.04% and an area under the curve of 96.08% in a receiver operating characteristic curve. The subsequent LRP visualization revealed that the CNN model focuses indeed on individual lesions, but also incorporates additional information such as lesion location, non-lesional white matter or gray matter areas such as the thalamus, which are established conventional and advanced MRI markers in MS. We conclude that LRP and the proposed framework have the capability to make diagnostic decisions of CNN models transparent, which could serve to justify classification decisions for clinical review, verify diagnosis-relevant features and potentially gather new disease knowledge

SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1(+) myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1(+) myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases. We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. In our cohort, SIGLEC1 expression on monocytes was-apart from those patients receiving interferon treatment-not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. SIGLEC1(+) myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions. The presence of SIGLEC1(+) myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion

Epstein-Barr virus antibodies in serum and DNA load in saliva are not associated with radiological or clinical disease activity in patients with early multiple sclerosis

OBJECTIVE: To investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS). METHODS: EBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls. EBV DNA load was measured in saliva of 48 patients and 50 controls. Patients underwent clinical assessment with the Expanded Disability Status Scale (EDSS) and 3 Tesla magnetic resonance imaging at baseline and after a median of 20 months of follow-up (n = 63 for MRI, n = 71 for EDSS). The association of EBV parameters with occurrence of a second relapse, indicating conversion to clinically definite MS (CDMS), was evaluated over a median of 35 months of follow-up after the first clinical event (n = 89). RESULTS: BNA-1 IgG antibody frequency (p = 0.00005) and EBNA-1 and VCA IgG antibody levels (p<0.0001 for both) were higher in patients than in controls. EBV DNA load in saliva did not differ between groups. Neither EBV antibody levels nor DNA load in saliva were associated with baseline or follow-up number or volume of T2-weighted (T2w) or contrast enhancing lesions, number of Barkhof criteria or the EDSS, or with the number of new T2w lesions, T2w lesion volume change or EDSS change on follow-up. Likewise, levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to CDMS. CONCLUSIONS: While these findings confirm the association of EBV infection with early MS, neither EBNA-1 nor VCA IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with CIS/early RRMS. These data are compatible with the concept that EBV may be a trigger for MS acting very early during the development of the disease

Synthesis of high-T_g hole-transporting polymers with different redox potentials and their performance in organic two-layer LEDs

Organic hole transport materials are used in organic LEDs, where they substantially improve device performance if placed as a hole transport layer (HTL) between the anode and the electroluminescent layer (EL). Soluble polymeric hole transport materials with high glass transition temperatures are of particular interest, because they allow for efficient device fabrication through spin casting of the HTL, and high glass transition temperatures have been found to improve thermal and long-term stability of the device. The redox potential of the hole transport material determines the facility of charge injection at the anode/HTL and the HTL/EL interfaces, thus affecting the overall device efficiency. We have synthesized a series of soluble hole-transporting polymers with glass transition temperatures in the range of 130 degrees C to 150 degrees C. The synthetic method allows facile substitution of the hole transport functionality with electron-withdrawing and electron-donating groups, which permits tuning of the redox potential of the polymer. These polymers have been used as HTL in tow-layer devices ITO/HTL/Alq/Mg. The maximum external quantum efficiency increase, if the redox potential is changed to facilitate reduction of the hole transport material at the HTL/EL interface. Electron-deficient derivatives show higher external quantum efficiencies. The device stability, however, follows the opposite trend