Wireless ad-hoc networks on Android operating system

Brezžična ad hoc omrežja so omrežja brezžičnih naprav, ki za delovanje ne uporabljajo infrastrukture (dostopovne točke). Naprave, ki tvorijo ad hoc omrežje, so med seboj enakovredne in vse sodelujejo pri usmerjanju podatkov skozi omrežje. Brezžični tehnologiji Bluetooth in Wi-Fi Direct omogočata preprosto izmenjavo podatkov med napravami v dosegu. Zaradi neodvisnosti od infrastrukture lahko Bluetooth in Wi-Fi Direct naprave komunicirajo kjerkoli in kadarkoli. V magistrskem delu smo pregledali možnosti ad hoc povezovanja različnih mobilnih naprav s poudarkom na mobilnem operacijskem sistemu Android. V praktičnem delu naloge smo razvili aplikacijo Android, ki omogoča samodejno povezovanje bližnjih naprav. Za posredovanje podatkov med napravami smo razvili lasten usmerjevalni algoritem, ki v najhitrejšem možnem času poišče najkrajšo pot za prejeti paket podatkov. Vzpostavljeno ad hoc omrežje se prilagaja razmeram s samodejnim povezovanjem. Omenjene so tudi težave in omejitve, na katere smo naleteli pri izdelavi mobilne aplikacije. Te so nastale predvsem zaradi varnostnih zahtev in tehničnih omejitev samih mobilnih naprav in operacijskega sistema.Wireless ad hoc networks are decentralized types of wireless networks which do not rely on infrastructure (such as access points). Devices forming ad hoc networks are equivalent to each other and all participate in the routing process by forwarding data to the other devices. Wireless technologies such as Bluetooth and Wi-Fi Direct allow simple data sharing between devices in reach. Because Bluetooth and Wi-Fi Direct are independent of any infrastructure, devices may communicate anywhere, anytime. This master thesis covers ad hoc connecting possiblities using mobile devices on Android operating system. We developed an Android application that allows automatic ad hoc connecting between mobile devices. For data sharing between devices, we implemented our own routing algorithm that finds the shortest path in the fastest time possible. Established ad hoc network also automatically adapts to any changes. We also mentioned problems and limits that were encountered during the development. Most were a result of a security and technical limits of the mobile devices and operating system

Comparison and evaluation of different methodologies and tests for detection of anti-dsDNA antibodies on 889 Slovenian patients’ and blood donors’ sera

Aim To evaluate four different commercially available assays for anti-double stranded DNA (dsDNA) detection and compare them with the in-house radioimmunoassay according to Farr (FARR-RIA) in order to select the optimal primary method for use in combination with FARR-RIA. Methods Sera from 583 consecutive patients sent to our laboratory for routine diagnosis, 156 selected patients with autoimmune diseases (76 systemic lupus erythematosus [SLE] patients and 80 patients with other autoimmune diseases), and 150 blood donors were tested for anti-dsDNA antibodies with two enzyme-linked immunoassays (ELISA), two Crithidia luciliae immunoflourescence tests (CLIFT), and FARR-RIA. The specificities and sensitivities of the tests were calculated and compared. Results FARR-RIA and CLIFT 2 showed the highest specificity for SLE (100%), with CLIFT 2 showing higher sensitivity (33% vs 47%). Both ELISAs showed higher sensitivities (>53%) than FARR-RIA but lower specificities (<93%), whereas CLIFT 1 showed the lowest overall agreement with FARR-RIA. Conclusion CLIFT 2 was selected as the primary test for use in combination with FARR-RIA. The use of CLIFT 2 reduced the number of sera that needed to be tested by FARR-RIA, the time needed to report the results, and environmental toxicity, cancerogenicity, and radioactivity

Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL) that cause endothelial injury and thrombophilia. Extracellular vesicles are involved in endothelial and thrombotic pathologies and may therefore have an influence on the prothrombotic status of APS patients. Intercellular communication and connectivity are important mechanisms of interaction between healthy and pathologically altered cells. Despite well-characterized in vitro and in vivo models of APS pathology, the field of extracellular vesicles is still largely unexplored and could therefore provide an insight into the APS mechanism and possibly serve as a biomarker to identify patients at increased risk. The analysis of EVs poses a challenge due to the lack of standardized technology for their isolation and characterization. Recent findings in the field of EVs offer promising aspects that may explain their role in the pathogenesis of various diseases, including APS

Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis

In this study, we explored expression of microRNA (miR), miR-target genes and matrix remodelling molecules in temporal artery biopsies (TABs) from treatment-naïve patients with giant cell arteritis (GCA, n = 41) and integrated these analyses with clinical, laboratory, ultrasound and histological manifestations of GCA. NonGCA patients (n = 4) served as controls. GCA TABs exhibited deregulated expression of several miRs (miR-21-5p, -145-5p, -146a-5p, -146b-5p, -155-5p, 424-3p, -424-5p, -503-5p), putative miR-target genes (YAP1, PELI1, FGF2, VEGFA, KLF4) and matrix remodelling factors (MMP2, MMP9, TIMP1, TIPM2) with key roles in Toll-like receptor signaling, mechanotransduction and extracellular matrix biology. MiR-424-3p, -503-5p, KLF4, PELI1 and YAP1 were identified as new deregulated molecular factors in GCA TABs. Quantities of miR-146a-5p, YAP1, PELI1, FGF2, TIMP2 and MMP9 were particularly high in histologically positive GCA TABs with occluded temporal artery lumen. MiR-424-5p expression in TABs and the presence of facial or carotid arteritis on ultrasound were associated with vision disturbances in GCA patients. Correlative analysis of miR-mRNA quantities demonstrated a highly interrelated expression network of deregulated miRs and mRNAs in temporal arteries and identified KLF4 as a candidate target gene of deregulated miR-21-5p, -146a-5p and -155-5p network in GCA TABs. Meanwhile, arterial miR and mRNA expression did not correlate with constitutive symptoms and signs of GCA, elevated markers of systemic inflammation nor sonographic characteristics of GCA. Our study provides new insights into GCA pathophysiology and uncovers new candidate biomarkers of vision impairment in GCA

Laboratory Methodology Important in the Diagnosis and Prognosis of Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by thrombosis and pregnancy complications with persistently elevated levels of antiphospholipid antibodies (aPL). Recently, a unique mathematical calculation has been presented to assess the risk of thrombosis in patients with APS called antiphospholipid score or global antiphospholipid syndrome score (GAPSS). This new approach in the diagnosis of APS leads to the assessment of the risk of thrombosis considering the results of different aPL (lupus anticoagulants (LA), anticardiolipin antibodies (aCL), antibodies against β2GPI (anti-β2GPI), and phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) (isotypes IgG and IgM). This chapter provides an overview of the algorithm strategy for APS diagnosis with the aims of characterizing in detail the laboratory methodology of criteria aPL (LA, aCL, and anti-β2GPI) and noncriteria aPL, such as IgA aCL and IgA anti-β2GPI, anti-domain I β2GPI, and antiprothrombin antibodies. In order to improve APS diagnosis, several new approaches in aPL detection have recently been suggested, such as multiline immunodot assay, detection of aPL by flow cytometry using beads with particular surface properties, and the newly developed automated BioPlex system technology for parallel detection of aCL and anti-β2GPI antibodies of IgG, IgA, and IgM isotypes. A completely different and promising approach in future research lies in the potential of microRNAs as biomarkers for risk of thrombosis and/or obstetric complication

Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis

Introduction: Phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N‐terminal and mid‐region p‐tau181 and p‐tau217 fragments are available, but head‐to‐head comparison in clinical settings is lacking. / Methods: N‐terminal‐directed p‐tau217 (N‐p‐tau217), N‐terminal‐directed p‐tau181 (N‐p‐tau181), and standard mid‐region p‐tau181 (Mid‐p‐tau181) biomarkers in CSF were evaluated in three cohorts (n = 503) to assess diagnostic performance, concordance, and associations with amyloid beta (Aβ). / Results: CSF N‐p‐tau217 and N‐p‐tau181 had better concordance (88.2%) than either with Mid‐p‐tau181 (79.7%–82.7%). N‐p‐tau217 and N‐p‐tau181 were significantly increased in early mild cognitive impairment (MCI)‐AD (A+T–N–) without changes in Mid‐p‐tau181 until AD‐dementia. N‐p‐tau217 and N‐p‐tau181 identified Aβ pathophysiology (area under the curve [AUC] = 94.8%–97.1%) and distinguished MCI‐AD from non‐AD MCI (AUC = 82.6%–90.5%) signficantly better than Mid‐p‐tau181 (AUC = 91.2% and 70.6%, respectively). P‐tau biomarkers equally differentiated AD from non‐AD dementia (AUC = 99.1%–99.8%). / Discussion: N‐p‐tau217 and N‐p‐tau181 could improve diagnostic accuracy in prodromal‐AD and clinical trial recruitment as both identify Aβ pathophysiology and differentiate early MCI‐AD better than Mid‐p‐tau181

N-terminal and mid-region tau fragments as fluid biomarkers in neurological diseases

Brain-derived tau secreted into CSF and blood consists of different N-terminal and mid-domain fragments, which may have a differential temporal course and thus, biomarker potential across the Alzheimer's disease continuum or in other neurological diseases. While current clinically validated total-tau (t-tau) assays target mid-domain epitopes, comparison of these assays with new biomarkers targeting N-terminal epitopes using the same analytical platform may be important to increase the understanding of tau pathophysiology. We developed three t-tau immunoassays targeting specific N-terminal (NTA and NTB t-tau) or mid-region (MR t-tau) epitopes, using single molecule array technology. After analytical validation, the diagnostic performance of these biomarkers was evaluated in CSF and compared with the Innotest t-tau (and as proof of concept, with N-p-tau181 and N-p-tau217) in three clinical cohorts (n = 342 total). The cohorts included participants across the Alzheimer's disease continuum (n = 276), other dementia (n = 22), Creutzfeldt-Jakob disease (n = 24), acute neurological disorders (n = 18) and progressive supranuclear palsy (n = 22). Furthermore, we evaluated all three new t-tau biomarkers in plasma (n = 44) and replicated promising findings with NTA t-tau in another clinical cohort (n = 50). In CSF, all t-tau biomarkers were increased in Alzheimer's disease compared with controls (P < 0.0001) and correlated with each other (rs = 0.53-0.95). NTA and NTB t-tau, but not other t-tau assays, distinguished amyloid-positive and amyloid-negative mild cognitive impairment with high accuracies (AUCs 84% and 82%, P < 0.001) matching N-p-tau217 (AUC 83%; DeLong test P = 0.93 and 0.88). All t-tau assays were excellent in differentiating Alzheimer's disease from other dementias (P < 0.001, AUCs 89-100%). In Creutzfeldt-Jakob disease and acute neurological disorders, N-terminal t-tau biomarkers had significantly higher fold changes versus controls in CSF (45-133-fold increase) than Innotest or MR t-tau (11-42-fold increase, P < 0.0001 for all). In progressive supranuclear palsy, CSF concentrations of all t-tau biomarkers were similar to those in controls. Plasma NTA t-tau concentrations were increased in Alzheimer's disease compared with controls in two independent cohorts (P = 0.0056 and 0.0033) while Quanterix t-tau performed poorly (P = 0.55 and 0.44). Taken together, N-terminal-directed CSF t-tau biomarkers increase ahead of standard t-tau alternatives in the Alzheimer's disease continuum, increase to higher degrees in Creutzfeldt-Jakob disease and acute neurological diseases and show better potential than Quanterix t-tau as Alzheimer's disease blood biomarkers. For progressive supranuclear palsy, other tau biomarkers should still be investigated

Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells

Olive leaf extract (OLE) is used in traditional medicine as a food supplement and as an over-the-counter drug for a variety of its effects, including anti-inflammatory and anti-atherosclerotic ones. Mechanisms through which OLE could modulate these pathways in human vasculature remain largely unknown. Serum amyloid A (SAA) plays a causal role in atherosclerosis and cardiovascular diseases and induces pro-inflammatory and pro-adhesive responses in human coronary artery endothelial cells (HCAEC). Within this study we explored whether OLE can attenuate SAA-driven responses in HCAEC. HCAEC were treated with SAA (1,000 nM) and/or OLE (0.5 and 1 mg/ml). The expression of adhesion molecules VCAM-1 and E-selectin, matrix metalloproteinases (MMP2 and MMP9) and microRNA 146a, let-7e, and let-7g (involved in the regulation of inflammation) was determined by qPCR. The amount of secreted IL-6, IL-8, MIF, and GRO-α in cell culture supernatants was quantified by ELISA. Phosphorylation of NF-κB was assessed by Western blot and DNA damage was measured using the COMET assay. OLE decreased significantly released protein levels of IL-6 and IL-8, as well as mRNA expression of E-selectin in SAA-stimulated HCAEC and reduced MMP2 levels in unstimulated cells. Phosphorylation of NF-κB (p65) was upregulated in the presence of SAA, with OLE significantly attenuating this SAA-induced effect. OLE stabilized SAA-induced upregulation of microRNA-146a and let-7e in HCAEC, suggesting that OLE could fine-tune the SAA-driven activity of NF-κB by changing the microRNA networks in HCAEC. SAA induced DNA damage and worsened the oxidative DNA damage in HCAEC, whereas OLE protected HCAEC from SAA- and H2O2-driven DNA damage. OLE significantly attenuated certain pro-inflammatory and pro-adhesive responses and decreased DNA damage in HCAEC upon stimulation with SAA. The reversal of SAA-driven endothelial activation by OLE might contribute to its anti-inflammatory and anti-atherogenic effects in HCAEC