Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. METHODS: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. RESULTS: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. CONCLUSION: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.

Optical coherence tomography angiography suggests different retinal pathologies in multiple sclerosis and Sjögren's syndrome.

BACKGROUND: While retinal vessel changes are evident in the eyes of patients with relapsing-remitting multiple sclerosis (RRMS), changes in the vasculature of possible MS mimics such as primary Sjögren's syndrome (pSS) remain to be determined. We investigated the potential of retinal optical coherence tomography (OCT) angiography (OCTA) as diagnostic tool to differentiate between patients with RRMS and pSS. METHODS: This cross-sectional study included patients with RRMS (n = 36), pSS (n = 36) and healthy controls (n = 30). Participants underwent clinical examination, assessment of visual acuity, retinal OCT, OCTA, and serum markers of glial and neuronal damage. We investigated the associations between OCTA parameters, visual functions, and serum markers. Eyes with a history of optic neuritis (ON) were excluded from analysis. RESULTS: We observed a significant thinning of the combined ganglion cell and inner plexiform layer in the eyes of patients with RRMS but not with pSS, when compared to healthy controls. Retinal vessel densities of the superficial vascular complex (SVC) were reduced in both patients with RRMS and pSS. However, retinal vessel rarefication of the deep vascular complex (DVC) was only evident in patients with pSS but not RRMS. Using multivariate regression analysis, we found that DVC vessel loss in pSS patients was associated with worse visual acuity. CONCLUSIONS: Compared to patients with RRMS, rarefication of deep retinal vessels is a unique characteristic of pSS and associated with worse visual function. Assuming a disease-specific retinal vessel pathology, these data are indicative of a differential affliction of the gliovascular complex in the retina of RRMS and pSS patients.

B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4.

Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which the water-channel protein AQP4 is the target antigen1. The immunopathology in neuromyelitis optica is largely driven by autoantibodies to AQP42. However, the T cell response that is required for the generation of these anti-AQP4 antibodies is not well understood. Here we show that B cells endogenously express AQP4 in response to activation with anti-CD40 and IL-21 and are able to present their endogenous AQP4 to T cells with an AQP4-specific T cell receptor (TCR). A population of thymic B cells emulates a CD40-stimulated B cell transcriptome, including AQP4 (in mice and humans), and efficiently purges the thymic TCR repertoire of AQP4-reactive clones. Genetic ablation of Aqp4 in B cells rescues AQP4-specific TCRs despite sufficient expression of AQP4 in medullary thymic epithelial cells, and B-cell-conditional AQP4-deficient mice are fully competent to raise AQP4-specific antibodies in productive germinal-centre responses. Thus, the negative selection of AQP4-specific thymocytes is dependent on the expression and presentation of AQP4 by thymic B cells. As AQP4 is expressed in B cells in a CD40-dependent (but not AIRE-dependent) manner, we propose that thymic B cells might tolerize against a group of germinal-centre-associated antigens, including disease-relevant autoantigens such as AQP4.

CNS demyelinating events in primary Sjögren's syndrome: A single-center case series on the clinical phenotype.

Objective: The study aimed to assess the prevalence, clinical characteristics, and therapeutic outcomes of the central nervous system (CNS) demyelinating disease in a large cohort of primary Sjögren's syndrome (pSS). Methods: This is an explorative cross-sectional study of patients with pSS seen in the departments of rheumatology, otorhinolaryngology, or neurology of a tertiary university center between January 2015 and September 2021. Results: In a cohort of 194 pSS patients, 22 patients had a CNS manifestation. In this CNS group, 19 patients had a lesion pattern suggestive of demyelination. While there were no obvious differences in the patients' epidemiological disposition or rate of other extraglandular manifestations, the CNS group differed from the remaining patients with pSS by having less glandular manifestations but a higher seroprevalence for anti-SSA/Ro antibodies. Notably, patients with CNS manifestations were often diagnosed with multiple sclerosis (MS) and treated as such, although age and disease course were atypical of MS. Many first-line MS agents were ineffective in these "MS look-alikes"; however, the disease course was benign with B-cell-depleting agents. Conclusion: Neurological symptoms of pSS are common and clinically manifest mainly as myelitis or optic neuritis. Notably, in the CNS, the pSS phenotype can overlap with MS. The prevailing disease is crucial since it has a major impact on the long-term clinical outcome and the choice of disease-modifying agents. Although our observations neither confirm pSS as a more appropriate diagnosis nor rule out simple comorbidity, physicians should consider pSS in the extended diagnostic workup of CNS autoimmune diseases.

Association of the retinal vasculature, intrathecal immunity, and disability in multiple sclerosis.

Background: Optical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course. Material and methods: This study includes two different patient cohorts recruited at a tertiary German academic multiple sclerosis center between 2018 and 2020 and a cohort of 40 healthy controls. A total of 90 patients with RRMS undergoing lumbar puncture and OCT-A analysis were enrolled into a cross-sectional cohort study to search for associations between the retinal vasculature and the intrathecal immune compartment. We recruited another 86 RRMS patients into a prospective observational cohort study who underwent clinical examination, OCT-A and cerebral magnetic resonance imaging at baseline and during annual follow-up visits to clarify whether alterations of the retinal vessels are linked to RRMS disease activity. Eyes with a history of optic neuritis were excluded from the analysis. Results: Rarefication of the superficial vascular complex occured during RRMS and was linked to higher frequencies of activated B cells and higher levels of the pro-inflammatory cytokines interferon-γ, tumor necrosis factor α and interleukin-17 in the cerebrospinal fluid. During a median follow-up of 23 (interquartile range 14 - 25) months, vessel loss within the superficial (hazard ratio [HR] 1.6 for a 1%-point decrease in vessel density, p=0.01) and deep vascular complex (HR 1.6 for a 1%-point decrease, p=0.05) was associated with future disability worsening. Discussion: Optic neuritis independent rarefication of the retinal vasculature might be linked to neuroinflammatory processes during RRMS and might predict a worse disease course. Thus, OCT-A might be a novel biomarker to monitor disease activity and predict future disability.

Aquaporin-4 prevents exaggerated astrocytosis and structural damage in retinal inflammation.

Aquaporin-4 (AQP4) is the molecular target of the immune response in neuromyelitis optica (NMO) that leads to severe structural damage in the central nervous system (CNS) and in the retina. Conversely, AQP4 might be upregulated in astrocytes as a compensatory event in multiple sclerosis. Thus, the functional relevance of AQP4 in neuroinflammation needs to be defined. Here, we tested the role of AQP4 in the retina in MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE) using optical coherence tomography (OCT), OCT angiography, immunohistology, flow cytometry, and gene expression analysis in wild-type and Aqp4-/- mice. No direct infiltrates of inflammatory cells were detected in the retina. Yet, early retinal expression of TNF and Iba1 suggested that the retina participated in the inflammatory response during EAE in a similar way in wild-type and Aqp4-/- mice. While wild-type mice rapidly cleared retinal swelling, Aqp4-/- animals exhibited a sustainedly increased retinal thickness associated with retinal hyperperfusion, albumin extravasation, and upregulation of GFAP as a hallmark of retinal scarring at later stages of EAE. Eventually, the loss of retinal ganglion cells was higher in Aqp4-/- mice than in wild-type mice. Therefore, AQP4 expression might be critical for retinal Müller cells to clear the interstitial space from excess vasogenic edema and prevent maladaptive scarring in the retina during remote inflammatory processes of the CNS. KEY MESSAGES : Genetic ablation of AQP4 leads to a functional derangement of the retinal gliovascular unit with retinal hyperperfusion during autoimmune CNS inflammation. Genetic ablation of AQP4 results in a structural impairment of the blood retina barrier with extravasation of albumin during autoimmune CNS inflammation. Eventually, the lack of AQP4 in the retina during an inflammatory event prompts the exaggerated upregulation of GFAP as a hallmark of scarring as well as loss of retinal ganglion cells.

Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.

Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6+, and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.

2D Statistical Lung Shape Analysis Using Chest Radiographs: Modelling and Segmentation.

Accurate information of the lung shape analysis and its anatomical variations is very noticeable in medical imaging. The normal variations of the lung shape can be interpreted as a normal lung. In contrast, abnormal variations of the lung shape can be a result of one of the pulmonary diseases. The goal of this study is twofold: (1) represent two lung shape models which are different at the reference points in registration process considering to show their impact on estimating the inter-patient 2D lung shape variations and (2) using the obtained models in lung field segmentation by utilizing active shape model (ASM) technique. The represented models which showed the inter-patient 2D lung shape variations in two different forms are fully compared and evaluated. The results show that the models along with standard principal component analysis (PCA) can be able to explain more than 95% of total variations in all cases using only first 7 principal component (PC) modes for both lungs. Both models are used in ASM-based segmentation technique for lung field segmentation. The segmentation results are evaluated using leave-one-out cross validation technique. According to the experimental results, the proposed method has average dice similarity coefficient of 97.1% and 96.1% for the right and the left lung, respectively. The results show that the proposed segmentation method is more stable and accurate than other model-based techniques to inter-patient lung field segmentation.

Contour-based lung shape analysis in order to tuberculosis detection: modeling and feature description.

Statistical shape analysis of lung is a reliable alternative method for diagnosing pulmonary diseases such as tuberculosis (TB). The 2D contour-based lung shape analysis is investigated and developed using Fourier descriptors (FDs). The proposed 2D lung shape analysis is carried out in threefold: (1) represent the normal and the abnormal (i.e. pulmonary tuberculosis (PTB)) lung shape models using Fourier descriptors modeling (FDM) framework from chest X-ray (CXR) images, (2) estimate and compare the 2D inter-patient lung shape variations for the normal and abnormal lungs by applying principal component analysis (PCA) techniques, and (3) describe the optimal type of contour-based feature vectors to train a classifier in order to detect TB using one publicly available dataset-namely the Montgomery dataset. Since almost all of the previous works in lung shape analysis are content-based analysis, we proposed contour-based lung shape analysis for statistical modeling and feature description of PTB cases. The results show that the proposed approach is able to explain more than 95% of total variations in both of the normal and PTB cases using only 6 and 7 principal component modes for the right and the left lungs, respectively. In case of PTB detection, using 138 lung cases (80 normal and 58 PTB cases), we achieved the accuracy (ACC) and the area under the curve (AUC) of 82.03% and 88.75%, respectively. In comparison with existing state-of-art studies in the same dataset, the proposed approach is a very promising supplement for diagnosis of PTB disease. The method is robust and valuable for application in 2D automatic segmentation, classification, and atlas registration. Moreover, the approach could be used for any kind of pulmonary diseases. Graphical abstract Contour-based lung shape analysis in order to detect tuberculosis: modeling and feature description.

Inter-Patient Modelling of 2D Lung Variations from Chest X-Ray Imaging via Fourier Descriptors.

Detailed knowledge of anatomical lung variation is very important in medical image processing. Normal variations of lung consistent with the maintenance of pulmonary health and abnormal lung variations can be as a result of a pulmonary disease. Inter-patient lung variations can be due to the several factors such as sex, age, height, weight and type of disease. This study tries to show the inter-patient lung variations by using one of the shape-based descriptions techniques which is called Fourier descriptors. Shape-based description is an important approach to construct an object according to its parametric values. A different types of techniques are reported in the literature that aim to represent objects based on their shapes; each of these techniques has its cons and pros. Fourier descriptors, a simple yet powerful technique, has interesting properties such as rotational, scale, and translational invariance and these are powerful features for the recognition of two-dimensional connected shapes. In this paper, we use 380 CXR (Chest X-ray) images as a training set to construct the statistical mean model of lung contour. For modelling, the first step is evaluation of lung contour approximation and characterization to get the good spatial and frequency resolution. In the second step, all of the lung contours registered to show the variation and make a mean shape (i.e. lungs). And the final step is calculating the dispersion (i.e. covariance matrix) and analyzing by principle components. The proposed technique used to create the inter-patient statistical model and provide statistical parameters for application in segmentation, classification, 2D atlas based registration, etc. In this paper, we presented an approach for creating 2D modelling of human lungs from CXR image archives and reported some interesting statistical parameters to analysis the left and the right lung shape.

Skeletal muscle cells actively shape (auto)immune responses.

Histopathological analyses of muscle specimens from myositis patients indicate that skeletal muscle cells play an active role in the interaction with immune cells. Research over the last few decades has shown that skeletal muscle cells exhibit immunobiological properties that perfectly define them as non-professional antigen presenting cells. They are able to present antigens via major histocompatibility complex molecules, exhibit costimulatory molecules and secrete soluble molecules that actively shape the immune response in an either pro- or anti-inflammatory manner. Skeletal muscle cells regulate both innate and adaptive immune responses and are essentially involved in the pathophysiological processes of idiopathic inflammatory myopathies. Understanding the role of skeletal muscle cells might help to identify new therapeutic targets for these devastating diseases. This review summarizes the immunobiological features of skeletal muscle cells, especially in the context of idiopathic inflammatory myopathies, and discusses shortcomings and limitations in skeletal muscle related research providing potential perspectives to overcome them in the future.

Spatially Selective, High-Density Placement of Polyfluorene-Sorted Semiconducting Carbon Nanotubes in Organic Solvents.

High-performance logic based on carbon nanotubes (CNTs) requires high-density arrays of selectively placed semiconducting CNTs. Although polymer-wrapping methods can allow CNTs to be sorted to a >99.9% semiconducting purity, patterning these polymer-wrapped CNTs is an outstanding problem. We report the directed self-assembly of polymer-coated semiconducting CNTs using self-assembled monolayers that bind CNTs into arrays of patterned trenches. We demonstrate that CNTs can be placed into 100 nm wide HfO2 trenches with an electrical connection yield as high as 90% and into 50 nm wide trenches with a yield as high as 70%. Our directed self-assembly method is an important step forward in pitch scaling.

High-speed logic integrated circuits with solution-processed self-assembled carbon nanotubes.

As conventional monolithic silicon technology struggles to meet the requirements for the 7-nm technology node, there has been tremendous progress in demonstrating the scalability of carbon nanotube field-effect transistors down to the size that satisfies the 3-nm node and beyond. However, to date, circuits built with carbon nanotubes have overlooked key aspects of a practical logic technology and have stalled at simple functionality demonstrations. Here, we report high-performance complementary carbon nanotube ring oscillators using fully manufacturable processes, with a stage switching frequency of 2.82 GHz. The circuit was built on solution-processed, self-assembled carbon nanotube arrays with over 99.9% semiconducting purity, and the complementary feature was achieved by employing two different work function electrodes.

Animal models in idiopathic inflammatory myopathies: How to overcome a translational roadblock?

Idiopathic inflammatory myopathies (IIMs) encompass a heterogenic group of rare muscle diseases with common symptoms including muscle weakness and the presence of certain histological features. Since the pathogenesis remains unclear, therapeutic approaches in general comprise unspecific immunosuppression strategies that have been met with limited success. Therefore, a deeper understanding of the underlying pathophysiological mechanisms is critically required to assist in development of targeted therapies. Animal models have proven to be tremendously helpful in mechanistic studies and allow researchers to overcome the inevitable restrictions of human research. Although the number of different IIM models has drastically increased over the last few decades, a model that exhibits the phenotypical and histopathological hallmarks of IIM is still missing. Recent publications have shown promising results addressing different pathophysiological issues like mechanisms of onset, chronification or relapse in IIM. However, a standardization of the methodology is critically required in order to improve comparability and transferability among different groups. Here we provide an overview of the currently available IIM models including our own C-peptide based small-peptide model, critically discuss their advantages and disadvantages and give perspectives to their future use.

The potassium channels TASK2 and TREK1 regulate functional differentiation of murine skeletal muscle cells.

Two-pore domain potassium (K2P) channels influence basic cellular parameters such as resting membrane potential, cellular excitability, or intracellular Ca2+-concentration [Ca2+]i While the physiological importance of K2P channels in different organ systems (e.g., heart, central nervous system, or immune system) has become increasingly clear over the last decade, their expression profile and functional role in skeletal muscle cells (SkMC) remain largely unknown. The mouse SkMC cell line C2C12, wild-type mouse muscle tissue, and primary mouse muscle cells (PMMs) were analyzed using quantitative PCR, Western blotting, and immunohistochemical stainings as well as functional analysis including patch-clamp measurements and Ca2+ imaging. Mouse SkMC express TWIK-related acid-sensitive K+ channel (TASK) 2, TWIK-related K+ channel (TREK) 1, TREK2, and TWIK-related arachidonic acid stimulated K+ channel (TRAAK). Except TASK2 all mentioned channels were upregulated in vitro during differentiation from myoblasts to myotubes. TASK2 and TREK1 were also functionally expressed and upregulated in PMMs isolated from mouse muscle tissue. Inhibition of TASK2 and TREK1 during differentiation revealed a morphological impairment of myoblast fusion accompanied by a downregulation of maturation markers. TASK2 and TREK1 blockade led to a decreased K+ outward current and a decrease of ACh-dependent Ca2+ influx in C2C12 cells as potential underlying mechanisms. K2P-channel expression was also detected in human muscle tissue by immunohistochemistry pointing towards possible relevance for human muscle cell maturation and function. In conclusion, our findings for the first time demonstrate the functional expression of TASK2 and TREK1 in muscle cells with implications for differentiation processes warranting further investigations in physiologic and pathophysiologic scenarios.

ALAIN01--Alemtuzumab in autoimmune inflammatory neurodegeneration: mechanisms of action and neuroprotective potential.

BACKGROUND: Alemtuzumab (Lemtrada®) is a newly approved therapeutic agent for relapsing-remitting multiple sclerosis (RRMS). In previous phase II and III clinical trials, alemtuzumab has proven superior efficacy to subcutaneous interferon beta-1a concerning relapse rate and disability progression with unprecedented durability and long-lasting freedom of disease activity. The humanized monoclonal antibody targets CD52, leading to a rapid and long-lasting depletion, especially of B and T cells. Arising from hematopoietic precursor cells a fundamental reprogramming of the immune system restores tolerogenic networks effectively suppressing autoimmune inflammatory responses in the central nervous system (CNS). Despite its favourable effects alemtuzumab holds a severe risk of side effects with secondary autoimmunity being the most considerable. Markers for risk stratification and treatment response improving patient selection and therapy guidance are a big unmet need for MS patients and health care providers. METHODS/DESIGN: This is a mono center, single arm, explorative phase IV study including 15 patients with highly active RRMS designed for 3 years. Patients will be studied by a high-resolution analysis comprising a repertoire of various immunological assays for the detection of immune cells and their function in peripheral blood as well as the cerebrospinal fluid (CSF). These assays encompass a number of experiments investigating immune cell subset composition, activation status, cytokine secretion, migratory capacity, potential neuroprotective properties and cytolytic activity complemented by instrument-based diagnostics like MRI scans, evoked potentials and optical coherence tomography (OCT). DISCUSSION: Our study represents the first in-depth and longitudinal functional analysis of key immunological parameters in the periphery and the CNS compartment underlying the fundamental effects of alemtuzumab in MS patients. By combining clinical, experimental and MRI data our study will provide a deeper understanding of alemtuzumab's mechanisms of action (MOA) potentially identifying immune signatures associated with treatment response or the development of secondary autoimmunity. After validation in larger cohorts this might help to improve efficacy and safety of alemtuzumab therapy in RRMS patients. TRIAL REGISTRATION: NCT02419378 (clinicaltrials.gov), registered 31 March 2015.

Physically unclonable cryptographic primitives using self-assembled carbon nanotubes.

Information security underpins many aspects of modern society. However, silicon chips are vulnerable to hazards such as counterfeiting, tampering and information leakage through side-channel attacks (for example, by measuring power consumption, timing or electromagnetic radiation). Single-walled carbon nanotubes are a potential replacement for silicon as the channel material of transistors due to their superb electrical properties and intrinsic ultrathin body, but problems such as limited semiconducting purity and non-ideal assembly still need to be addressed before they can deliver high-performance electronics. Here, we show that by using these inherent imperfections, an unclonable electronic random structure can be constructed at low cost from carbon nanotubes. The nanotubes are self-assembled into patterned HfO2 trenches using ion-exchange chemistry, and the width of the trench is optimized to maximize the randomness of the nanotube placement. With this approach, two-dimensional (2D) random bit arrays are created that can offer ternary-bit architecture by determining the connection yield and switching type of the nanotube devices. As a result, our cryptographic keys provide a significantly higher level of security than conventional binary-bit architecture with the same key size.

The NKG2D-IL-15 signaling pathway contributes to T-cell mediated pathology in inflammatory myopathies.

NKG2D is an activating receptor on T cells, which has been implicated in the pathogenesis of autoimmune diseases. T cells are critically involved in idiopathic inflammatory myopathies (IIM) and have been proposed as specific therapeutic targets. However, the mechanisms underlying T cell-mediated progressive muscle destruction in IIM remain to be elucidated. We here determined the involvement of the NKG2D - IL-15 signaling pathway. Primary human myoblasts expressed NKG2D ligands, which were further upregulated upon inflammatory stimuli. In parallel, shedding of the soluble NKG2D ligand MICA (sMICA) decreased upon inflammation potentially diminishing inhibition of NKG2D signaling. Membrane-related expression of IL-15 by myoblasts induced differentiation of naïve CD8+ T cells into highly activated, cytotoxic CD8+NKG2Dhigh T cells demonstrating NKG2D-dependent lysis of myoblasts in vitro. CD8+NKG2Dhigh T cell frequencies were increased in the peripheral blood of polymyositis (PM) patients and correlated with serum creatinine kinase concentrations, while serum sMICA levels were not significantly changed. In muscle biopsy specimens from PM patients expression of the NKG2D ligand MICA/B was upregulated, IL-15 was expressed by muscle cells, CD68+ macrophages as well as CD4+ T cells, and CD8+NKG2D+ cells were frequently detected within inflammatory infiltrates arguing for a local signaling circuit in the inflammatory muscle milieu. In conclusion, the NKG2D - IL-15 signaling pathway contributes to progressive muscle destruction in IIM potentially opening new therapeutic avenues.

Toward high-performance digital logic technology with carbon nanotubes.

The slow-down in traditional silicon complementary metal-oxide-semiconductor (CMOS) scaling (Moore's law) has created an opportunity for a disruptive innovation to bring the semiconductor industry into a postsilicon era. Due to their ultrathin body and ballistic transport, carbon nanotubes (CNTs) have the intrinsic transport and scaling properties to usher in this new era. The remaining challenges are largely materials-related and include obtaining purity levels suitable for logic technology, placement of CNTs at very tight (∼5 nm) pitch to allow for density scaling and source/drain contact scaling. This review examines the potential performance advantages of a CNT-based computing technology, outlines the remaining challenges, and describes the recent progress on these fronts. Although overcoming these issues will be challenging and will require a large, sustained effort from both industry and academia, the recent progress in the field is a cause for optimism that these materials can have an impact on future technologies.