Embedding of ultrathin chips in highly flexible, photosensitive solder mask resist

This work presents an embedding process for ultrathin silicon chips in mechanically flexible solder mask resist and their electrical contacting by inkjet printing. Photosensitive solder mask resist is applied by conformal spray coating onto epoxy bonded ultrathin chips with daisy chain layout. The contact pads are opened by photolithography using UV direct light exposure. Circular and rectangular openings of 90 µm and 130 µm diameter respectively edge length are realized. Commercial inks containing nanoparticular silver and gold are inkjet printed to form conductive tracks between daisy chain structures. Different numbers of ink layers are applied. The track resistances are characterized by needle probing. Silver ink shows low resistances only for multiple layers and 90 µm openings, while gold ink exhibit low resistances in the single-digit Ω-range for minimum two printed layers

Profound Re-Organization of Cell Surface Proteome in Equine Retinal Pigment Epithelial Cells in Response to In Vitro Culturing

The purpose of this study was to characterize the cell surface proteome of native compared to cultured equine retinal pigment epithelium (RPE) cells. The RPE plays an essential role in visual function and represents the outer blood-retinal barrier. We are investigating immunopathomechanisms of equine recurrent uveitis, an autoimmune inflammatory disease in horses leading to breakdown of the outer blood-retinal barrier and influx of autoreactive T-cells into affected horses' vitrei. Cell surface proteins of native and cultured RPE cells from eye-healthy horses were captured by biotinylation, analyzed by high resolution mass spectrometry coupled to liquid chromatography (LC MS/MS), and the most interesting candidates were validated by PCR, immunoblotting and immunocytochemistry. A total of 112 proteins were identified, of which 84% were cell surface membrane proteins. Twenty-three of these proteins were concurrently expressed by both cell states, 28 proteins exclusively by native RPE cells. Among the latter were two RPE markers with highly specialized RPE functions: cellular retinaldehyde-binding protein (CRALBP) and retinal pigment epithelium-specific protein 65kDa (RPE65). Furthermore, 61 proteins were only expressed by cultured RPE cells and absent in native cells. As we believe that initiating events, leading to the breakdown of the outer blood-retinal barrier, take place at the cell surface of RPE cells as a particularly exposed barrier structure, this differential characterization of cell surface proteomes of native and cultured equine RPE cells is a prerequisite for future studies

Aerosol jet printing and interconnection technologies on additive manufactured substrates

Nowadays, digital printing technologies such as inkjet and aerosol jet printing are gaining more importance since they have proven to be suitable for the assembly of complex microsystems. This also applies to medical technology applications like hearing aids where patient-specific solutions are required. However, assembly is more challenging than with conventional printed circuit boards in terms of material compatibility between substrate, interconnect material and printed ink. This paper describes how aerosol jet printing of nano metal inks and subsequent assembly processes are utilized to connect electrical components on 3D substrates fabricated by Digital Light Processing (DLP). Conventional assembly technologies such as soldering and conductive adhesive bonding were investigated and characterized. For this purpose, curing methods and substrate pretreatments for different inks were optimized. Furthermore, the usage of electroless plating on printed metal tracks for improved solderability was investigated. Finally, a 3D ear mold substrate was used to build up a technology demonstrator by means of conductive adhesives.Federal Ministry of Education and Research (BMBF

Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy

Dendritic cells (DCs) are professional antigen-presenting cells that induce and regulate adaptive immunity by presenting antigens to T cells. Due to their coordinative role in adaptive immune responses, DCs have been used as cell-based therapeutic vaccination against cancer. The capacity of DCs to induce a therapeutic immune response can be enhanced by re-wiring of cellular signalling pathways with microRNAs (miRNAs). Methods: Since the activation and maturation of DCs is controlled by an interconnected signalling network, we deploy an approach that combines RNA sequencing data and systems biology methods to delineate miRNA-based strategies that enhance DC-elicited immune responses. Results: Through RNA sequencing of IKKβ-matured DCs that are currently being tested in a clinical trial on therapeutic anti-cancer vaccination, we identified 44 differentially expressed miRNAs. According to a network analysis, most of these miRNAs regulate targets that are linked to immune pathways, such as cytokine and interleukin signalling. We employed a network topology-oriented scoring model to rank the miRNAs, analysed their impact on immunogenic potency of DCs, and identified dozens of promising miRNA candidates, with miR-15a and miR-16 as the top ones. The results of our analysis are presented in a database that constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (https://www.synmirapy.net/dc-optimization). Conclusions: Our approach enables the systematic analysis and identification of functional miRNA-gene interactions that can be experimentally tested for improving DC immunogenic potency

Early changes in bone mineral density measured by digital X-ray radiogrammetry predict up to 20 years radiological outcome in rheumatoid arthritis

ABSTRACT: INTRODUCTION: Change in bone mineral density (BMD) in the hand, as evaluated by digital X-ray radiogrammetry (DXR) of the II-IV metacarpal bones, has been suggested to predict future joint damage in rheumatoid arthritis (RA). This study's objective was to investigate if DXR-BMD loss early in the disease predicts development of joint damage in RA patients followed for up to 20 years. METHODS: 183 patients (115 women and 68 men) with early RA (mean disease duration 11 months) included from 1985 to 1989 were followed prospectively (the Lund early RA cohort). Clinical and functional measures were assessed yearly. Joint damage was evaluated according to the Larsen score on radiographs of hands and feet taken in years 0 to 5, 10, 15 and 20. These radiographs were digitized and BMD of the II-IV metacarpal bones was evaluated by DXR (Sectra, Linkoping. Sweden). Early DXR-BMD change rate (bone loss) per year calculated from the first 2 radiographs taken on average 9 months apart (SD 4.8) were available for 135 patients. Mean values of right and left hand were used. RESULTS: Mean early DXR-BMD loss during the first year calculated was -0.023 g/cm2 (SD 0.025). Patients with marked bone loss, i.e. early DXR-BMD loss above the median for the group, had significantly worse progression of joint damage at all examinations during the 20-year period. CONCLUSIONS: Early DXR-BMD progression rate predicted development of joint damage evaluated according to Larsen at year one and further onwards up to 20 years in this cohort of early RA patients

Konsekvenser av reumatoid artrit i tidigt skede

The consequences of early rheumatoid arthritis were studied in a series of patients treated at University Hospital, Lund, during the period 1985-1989. Mean disease duration at enrollment was 12 months. Most of the patients have now been followed prospectively for five years, during which time disease activity and pain have increased markedly. Ability to perform the activities of daily living (ADL) was well maintained, and the level of psychological distress fairly low. Radiographic changes in the hands and feet increased markedly, hand deformity being a common sign of severe disease; and only about ten per cent of the patients remained non-erosive. Another subgroup of ten per cent of the patients manifested rapidly progressive disease, resulting in destruction of larger joints, particularly hip joints, necessitating joint replacement in one or both hips. Eighteen per cent of the patients were in remission at 5-year follow-up. At 2-year follow-up, there was a high (37 per cent) prevalence of work disability, most patients who had had to stop work having done so in the first year. Physically demanding work and difficulties in performing ADL at presentation were the best predictors of subsequent work disability. The disease had a pronounced effect on life style, ability to cope with shopping, housework, leisure activities and social activities being adversely affected in more than half the patients