Molecules for security measures: From keypad locks to advanced communication protocols

The idea of using molecules in the context of information security has sparked the interest of researchers from many scientific disciplines. This is clearly manifested in the diversity of the molecular platforms and the analytical techniques used for this purpose, some of which we highlight in this Tutorial Review. Moreover, those molecular systems can be used to emulate a broad spectrum of security measures. For a long time, molecular keypad locks enjoyed a clear preference and the review starts off with a description of how these devices developed. In the last few years, however, the field has evolved into something larger. Examples include more complex authentication protocols (multi-factor authentication and one-time passwords), the recognition of erroneous procedures in data transmission (parity devices), as well as steganographic and cryptographic protection

Vortex Waves and Channel Capacity: Hopes and Reality

Several recent contributions have envisioned the possibility of increasing currently exploitable maximum channel capacity of a free space link, both at optical and radio frequencies, by using vortex waves, i.e. carrying Orbital Angular Momentum (OAM). Our objective is to disprove these claims by showing that they are in contradiction with very fundamental properties of Maxwellian fields. We demonstrate that the Degrees of Freedom (DoF) of the field cannot be increased by the helical phase structure of electromagnetic vortex waves beyond what can be done without invoking this property. We also show that the often-advocated over-quadratic power decay of OAM beams with distance does not play any fundamental role in the determination of the channel DoF.Comment: 8 pages, 7 figure

Proinflammatory Protein Signatures in Cryptogenic and Large Artery Atherosclerosis Stroke

Objectives: The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle‐aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke. Materials & Methods: Blood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18–69 years and once from age‐matched controls (n = 235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C‐statistics. Results: We identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs ≥ 0.85). For both subtypes, RANTES, IL‐4, and IFN‐γ contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs ≥ 0.76), and here eotaxin and MCP‐1 contributed the most. Conclusions: The protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL‐4, and IFN‐γ in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP‐1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause

Lumbar and ventricular CSF concentrations of extracellular matrix proteins before and after shunt surgery in idiopathic normal pressure hydrocephalus

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible CNS disease characterized by disturbed cerebrospinal fluid (CSF) dynamics. Changes in the extracellular matrix (ECM) composition might be involved in the pathophysiology of iNPH. The aim of this study was to explore possible differences between lumbar and ventricular CSF concentrations of the ECM markers brevican and neurocan, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and their relation to clinical symptoms in iNPH patients before and after shunt surgery. Methods: Paired lumbar and ventricular CSF was collected from 31 iNPH patients, before and four months after shunt surgery. CSF was analysed for concentrations of tryptic peptides originating from brevican and neurocan using a mass spectrometry-based panel, and for MMP-1, -2, -9, -10 and TIMP-1 using fluorescent or electrochemiluminescent immunoassays. Results: Brevican and neurocan peptide levels were not influenced by CSF origin, but MMP-1, -2, -10 and TIMP-1 were increased (p ≤ 0.0005), and MMP-9 decreased (p ≤ 0.0003) in lumbar CSF compared with ventricular CSF. There was a general trend of ECM proteins to increase following shunt surgery. Ventricular TIMP-1 was inversely correlated with overall symptoms (rho = − 0.62, p < 0.0001). CSF concentrations of the majority of brevican and neurocan peptides were increased in iNPH patients with a history of cardiovascular disease (p ≤ 0.001, AUC = 0.84–0.94) compared with those without. Conclusion: Levels of the CNS-specific proteins brevican and neurocan did not differ between the lumbar and ventricular CSF, whereas the increase of several CNS-unspecific MMPs and TIMP-1 in lumbar CSF suggests contribution from peripheral tissues. The increase of ECM proteins in CSF following shunt surgery could indicate disturbed ECM dynamics in iNPH that are restored by restitution of CSF dynamics

Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology

INTRODUCTION: Pyroglutamate‐modified amyloid β (Aβ_{pE3}) could be a biomarker for Aβ plaque pathology in the brain. An ultra‐high‐sensitive assay is needed for detecting Aβ_{pE3-40}. METHODS: mmunomagnetic reduction was used for quantification of Aβ_{pE3-40} in plasma from 46 participants. The concentrations of Aβ_{pE3-40} of these subjects were compared with 18F‐florbetapir positron emission tomography (PET) images. RESULTS: Aβ_{pE3-40} concentration was 44.1 ± 28.2 fg/mL in PET‐ (n = 28) and 91.6 ± 54.6 fg/mL in PET+ (n = 18; P < .05). The cutoff value of Aβ_{pE3-40} for discriminating PET‐ from PET+ was 55.5 fg/mL, resulting in a sensitivity of 83.3%, a specificity of 71.4%. The concentration of Aβ_{pE3-40} showed a moderate correlation (r = 0.437) with PET standardized uptake value ratio. DISCUSSION: We did not enroll pre‐clinical AD subject with normal cognition but Aβ PET+. It would be an important issue to explore the feasibility of using Aβ_{pE3-40} for screening pre‐clinical subjects. CONCLUSION: These results reveal the feasibility of detecting Aβ pathology using quantification of a plaque‐derived Aβ molecule in plasma

Circulating levels of vascular endothelial growth factor and post-stroke long-term functional outcome

OBJECTIVES: Vascular endothelial growth factor (VEGF) acts in angiogenesis and neuroprotection, although the beneficial effects on experimental ischemic stroke (IS) have not been replicated in clinical studies. We investigated serum VEGF (s-VEGF) in the acute stage (baseline) and 3 months post-stroke in relation to stroke severity and functional outcome. METHODS: The s-VEGF and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in patients enrolled in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) at the acute time-point (median 4 days, N=492, 36% female; mean age, 57 years) and at 3 months post-stroke (N=469). Baseline stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS) and functional outcomes (3 months and 2 years) were evaluated using the modified Rankin Scale (mRS), dichotomized into good (mRS 0-2) and poor (mRS 3-6) outcomes. Multivariable logistic regression analyses were adjusted for covariates. RESULTS: The baseline s-VEGF did not correlate with stroke severity but correlated moderately with hs-CRP (r=0.17, p<0.001). The baseline s-VEGF was 39.8% higher in total anterior cerebral infarctions than in lacunar cerebral infarctions. In binary logistic regression analysis, associations with 3-month functional outcome were non-significant. However, an association between the 3-month s-VEGF and poor 2-year outcome withstood adjustments for age, sex, cardiovascular covariates, and stroke severity (per ten-fold increase in s-VEGF, odds ratio [OR], 2.56, 95% confidence interval [CI] 1.12-5.82) or hs-CRP (OR 2.53, CI 1.15-5.55). CONCLUSIONS: High 3-month s-VEGF is independently associated with poor 2-year functional outcome but not with 3-month outcome

Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias

Heterozygous mutations in the granulin (GRN) gene may result in haploinsufficiency of progranulin (PGRN), which might lead to frontotemporal dementia (FTD). In this study, we aimed to perform analytical and clinical validation of a commercial progranulin kit for clinical use. Analytical validation parameters including assay precision, selectivity, measurement range, dilution linearity, interferences and sample stability were tested according to previously described procedures. For clinical validation, PGRN levels were measured in plasma from 32 cognitively healthy individuals, 52 confirmed GRN mutation carriers, 25 C9orf72 mutation carriers and 216 patients with different neurodegenerative diseases of which 70 were confirmed as non-mutation carriers. Among the analytical validation parameters, assay precision and repeatability were very stable (coefficients of variation <7 %). Spike recovery was 96 %, the measurement range was 6.25-400 μg/L and dilution linearity ranged from 1:50-1:200. Hemolysis did not interfere with progranulin levels, and these were resistant to freeze/thaw cycles and storage at different temperatures. For the clinical validation, the assay was capable of distinguishing GRN mutation carriers from controls and non-GRN mutation carriers with very good sensitivity and specificity at a cut-off of 57 μg/L (97 %, 100 %, respectively). In this study, we demonstrate robust analytical and diagnostic performance of this commercial progranulin kit for implementation in clinical laboratory practice. This easy-to-use test allows identification of potential GRN mutation carriers, which may guide further evaluation of the patient. This assay might also be used to evaluate the effect of novel PGRN-targeting drugs and therapies

Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample

Background: Neurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer’s disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system. Methods: The sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student’s T-test and ANCOVA. Results: CSF NfL concentration was higher in the A−T−N+ group (p=0.001) and the A−T+N+ group (p=0.006) compared with A−T−N−. CSF Ng concentration was higher in the A−T−N+, A−T+N+, A+T−N+, and A+T+N+ groups (p<0.0001) compared with A−T−N−. We found no difference in NfL or Ng concentration in A+ compared with A− (disregarding T− and N− status), whereas those with N+ had higher concentrations of NfL and Ng compared with N− (p<0.0001) (disregarding A− and T− status). Conclusions: CSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration

Circulating granulocyte colony-stimulating factor and functional outcome after ischemic stroke: an observational study

Objectives: While granulocyte colony-stimulating factor (G-CSF) has shown beneficial effects in experimental ischemic stroke (IS), these effects have not been reproduced clinically. Small-to-medium-sized observational studies have reported varying associations for G-CSF with stroke severity and post-stroke functional outcome, prompting their investigation in a larger study. Methods: Endogenous serum G-CSF (S-GCSF) was measured in the acute phase and after 3 months in patients with IS (N = 435; 36% females; mean age, 57 years) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was scored according to the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) assessed functional outcomes at 3-month and 2-year post-stroke. Correlation and logistic regression analyses with confounder adjustments assessed the relationships. Results: The acute S-GCSF level was 23% higher than at 3-month post-stroke (p < 0.001). Acute G-CSF correlated weakly with stroke severity quintiles (r = 0.12, p = 0.013) and with high-sensitivity C-reactive protein (r = 0.29, p < 0.001). The association between S-GCSF (as quintiles, q) and poor functional outcome at 3 months (mRS 3–6; S-GCSF-q5 vs. S-GCSF-q1, age- and sex-adjusted odds ratio: 4.27, 95% confidence interval: 1.82–9.99; p = 0.001) withstood adjustment for cardiovascular risk factors and stroke subtype, but not additional correction for stroke severity. Post-stroke changes in S-GSCF and absolute 3-month S-GCSF were not associated with 3-month or 2-year functional outcomes. Discussion: Early post-stroke S-GCSF is increased in severe IS and associated with 3-month poor functional outcomes. The change in S-GCSF and the 3-month S-GCSF appear to be less-important, and S-GCSF likely reflects inflammation in large infarctions