Automated Machine Learning Strategies for Multi-Parameter Optimisation of a Caesium-Based Portable Zero-Field Magnetometer.

Machine learning (ML) is an effective tool to interrogate complex systems to find optimal parameters more efficiently than through manual methods. This efficiency is particularly important for systems with complex dynamics between multiple parameters and a subsequent high number of parameter configurations, where an exhaustive optimisation search would be impractical. Here we present a number of automated machine learning strategies utilised for optimisation of a single-beam caesium (Cs) spin exchange relaxation free (SERF) optically pumped magnetometer (OPM). The sensitivity of the OPM (T/Hz), is optimised through direct measurement of the noise floor, and indirectly through measurement of the on-resonance demodulated gradient (mV/nT) of the zero-field resonance. Both methods provide a viable strategy for the optimisation of sensitivity through effective control of the OPM's operational parameters. Ultimately, this machine learning approach increased the optimal sensitivity from 500 fT/Hz to <109fT/Hz. The flexibility and efficiency of the ML approaches can be utilised to benchmark SERF OPM sensor hardware improvements, such as cell geometry, alkali species and sensor topologies.

A transistor-based label-free immunosensor for rapid detection of tau protein.

Tau protein in cerebrospinal fluid (CSF) is a central and relevant biomarker of Alzheimer's disease (AD) that correlates with the severity of dementia. Unfortunately, so far, direct label-free detection of tau remains a challenge. Here, we present a transistor-based biosensor that detects the net charge of tau protein directly under physiological conditions. To achieve this, readily available whole anti-tau IgG antibodies are co-immobilized on the sensor surface with polyethylene glycol (PEG) molecules of different molecular weight. We show that by increasing the PEG size from 10 kDa to 20 kDa, the electrical response upon binding of tau improves significantly. These results support recent theoretical work that predicted larger PEGs to form a thicker surface layer with a higher detectable analyte charge. With 20 kDa PEG, we demonstrate label-free tau detection in a wide concentration range with detection limits <1 pM in 150 mM buffer and cell culture media, as well as < 10 pM in artificial CSF. This purely electrical method allows fast and simple tau detection within 30 min without sample processing, washing steps, or labeled detection antibodies. By exchanging the capture antibody, the platform is also amenable to different biomarkers and may enable future diagnostic tools for AD and other diseases.

Quantitative intrinsic auto-cathodoluminescence can resolve spectral signatures of tissue-isolated collagen extracellular matrix.

By analyzing isolated collagen gel samples, we demonstrated in situ detection of spectrally deconvoluted auto-cathodoluminescence signatures of specific molecular content with precise spatial localization over a maximum field of view of 300 µm. Correlation of the secondary electron and the hyperspectral images proved ~40 nm resolution in the optical channel, obtained due to a short carrier diffusion length, suppressed by fibril dimensions and poor electrical conductivity specific to their organic composition. By correlating spectrally analyzed auto-cathodoluminescence with mass spectroscopy data, we differentiated spectral signatures of two extracellular matrices, namely human fibrin complex and rat tail collagen isolate, and uncovered differences in protein distributions of isolated extracellular matrix networks of heterogeneous populations. Furthermore, we demonstrated that cathodoluminescence can monitor the progress of a human cell-mediated remodeling process, where human collagenous matrix was deposited within a rat collagenous matrix. The revealed change of the heterogeneous biological composition was confirmed by mass spectroscopy.

Direct, Label-Free, and Rapid Transistor-Based Immunodetection in Whole Serum.

Transistor-based biosensors fulfill many requirements posed upon transducers for future point-of-care diagnostic devices such as scalable fabrication and label-free and real-time quantification of chemical and biological species with high sensitivity. However, the short Debye screening length in physiological samples (<1 nm) has been a major drawback so far, preventing direct measurements in serum. In this work, we demonstrate how tailoring the sensing surface with short specific biological receptors and a polymer polyethylene glycol (PEG) can strongly enhance the sensor response. In addition, the sensor performance can be dramatically improved if the measurements are performed at elevated temperatures (37 °C instead of 21 °C). With this novel approach, highly sensitive and selective detection of a representative immunosensing parameter-human thyroid-stimulating hormone-is shown over a wide measuring range with subpicomolar detection limits in whole serum. To the best of our knowledge, this is the first demonstration of direct immunodetection in whole serum using transistor-based biosensors, without the need for sample pretreatment, labeling, or washing steps. The presented sensor is low-cost, can be easily integrated into portable diagnostics devices, and offers a competitive performance compared to state-of-the-art central laboratory analyzers.

Dislocations in AlGaN: Core Structure, Atom Segregation, and Optical Properties.

We conducted a comprehensive investigation of dislocations in Al0.46Ga0.54N. Using aberration-corrected scanning transmission electron microscopy and energy dispersive X-ray spectroscopy, the atomic structure and atom distribution at the dislocation core have been examined. We report that the core configuration of dislocations in AlGaN is consistent with that of other materials in the III-Nitride system. However, we observed that the dissociation of mixed-type dislocations is impeded by alloying GaN with AlN, which is confirmed by our experimental observation of Ga and Al atom segregation in the tensile and compressive parts of the dislocations, respectively. Investigation of the optical properties of the dislocations shows that the atom segregation at dislocations has no significant effect on the intensity recorded by cathodoluminescence in the vicinity of the dislocations. These results are in contrast with the case of dislocations in In0.09Ga0.91N where segregation of In and Ga atoms also occurs but results in carrier localization limiting non-radiative recombination at the dislocation. This study therefore sheds light on why InGaN-based devices are generally more resilient to dislocations than their AlGaN-based counterparts.

Chirped fiber Bragg grating written in highly birefringent fiber in simultaneous strain and temperature monitoring.

A new sensor configuration is proposed for simultaneous strain and temperature monitoring in a composite material that is based on a chirped fiber Bragg grating (CFBG) written in a highly birefringent (HB) polarization-maintaining fiber. The sensor is designed in the reflective configuration in which the CFBG acts both as a reflector and a sensing element. Since CFBG and HB fiber induce changes in the state of polarization (SOP), interference between polarization modes in the reflected spectrum is observed and analyzed. We used a simple readout setup to enable fast, linear operation of strain sensing as well simultaneous strain and temperature measurements in the composite.

Shear wave elastography of the spleen: evaluation of spleen stiffness in healthy volunteers.

PURPOSE: The aim of this study was to assess the mean value of spleen stiffness measured by Shear wave elastography in healthy patients and its dependence on age, sex, and spleen dimensions, and to evaluate the repeatability of this method. METHODS: The final study group included 59 healthy volunteers without any clinical evidence of liver disease, portal hypertension, hematological disorders, and without any pathological ultrasonographic spleen findings. Each patient underwent abdominal ultrasound examination and elastography of the liver and the spleen. RESULTS: The mean value of spleen stiffness was 16.6 ± 2.5 kPa. In the group of men (N = 25), it was 17.3 ± 2.7 kPa, and in the group of women (N = 34), it was 16.1 ± 2.2 kPa. The study confirmed no correlation between spleen stiffness and sex, age of patients, and spleen size. Coefficient of repeatability and correlation coefficient between the results of the first and the second measurement showed good but not ideal repeatability of the measurement results. CONCLUSION: Our outcomes may be a reference point for evaluating spleen stiffness in research on patients with various illnesses.

Hollow Mesoporous Plasmonic Nanoshells for Enhanced Solar Vapor Generation.

In the past decade, nanomaterials have made their way into a variety of technologies in solar energy, enhancing the performance by taking advantage of the phenomena inherent to the nanoscale. Recent examples exploit plasmonic core/shell nanoparticles to achieve efficient direct steam generation, showing great promise of such nanoparticles as a useful material for solar applications. In this paper, we demonstrate a novel technique for fabricating bimetallic hollow mesoporous plasmonic nanoshells that yield a higher solar vapor generation rate compared with their solid-core counterparts. On the basis of a combination of nanomasking and incomplete galvanic replacement, the hollow plasmonic nanoshells can be fabricated with tunable absorption and minimized scattering. When exposed to sun light, each hollow nanoshell generates vapor bubbles simultaneously from the interior and exterior. The vapor nucleating from the interior expands and diffuses through the pores and combines with the bubbles formed on the outer wall. The lack of a solid core significantly accelerates the initial vapor nucleation and the overall steam generation dynamics. More importantly, because the density of the hollow porous nanoshells is essentially equal to the surrounding host medium these particles are much less prone to sedimentation, a problem that greatly limits the performance and implementation of standard nanoparticle dispersions.

Ultrasound Elastography--Review of Techniques and Its Clinical Applications in Pediatrics--Part 1.

Sonoelastography is a novel technique that uses ultrasound waves to assess the elasticity of tissues noninvasively. It provides an ultrasound-based method to detect and display the relative stiffness of tissue. The main principle of sonoelastography is the measurement of tissue distortion in response to external compression. Changes in elasticity and tissue deformation elicited by compression are measured, processed and then shown in real time presentation with color-coded elastograms. One of the most important applications of sonoelastography is the evaluation of liver diseases, mainly liver fibrosis assessment and staging. Although in terms of definite diagnosis the liver biopsy still remains the golden standard, elastography seems to be a very inexpensive, repeatable and noninvasive method to evaluate most of liver conditions. The technique is also applicable in detection and differential diagnosis of focal lesions. It provides better imaging information and therefore more accurate evaluation of the lesions nature, e.g. in liver, lymphatic nodes or thyroid gland. Most of the applications mentioned above are well known and have been described in details in adults. Similarly, most of sonoelastographic studies are based on groups of adults. The purpose of this review article is to bring this technology closer to pediatric clinicians and to summarize some of its current clinical applications that are being pursued. In this part we focus on utility of elastography in liver assessment in pediatric patients.

An in vivo neovascularization assay for screening regulators of angiogenesis and assessing their effects on pre-existing vessels.

Therapeutic regulation of tissue vascularization has appeared as an attractive approach to treat a number of human diseases. In vivo neovascularization assays that reflect physiological and pathological formation of neovessels are important in this effort. In this report we present an assay where the effects of activators and inhibitors of angiogenesis can be quantitatively and qualitatively measured. A provisional matrix composed of collagen I and fibrin was formed in a plastic cylinder and implanted onto the chick chorioallantoic membrane. A nylon mesh separated the implanted matrix from the underlying tissue to distinguish new from pre-existing vessels. Vascularization of the matrix in response to fibroblast growth factor-2 or platelet-derived growth factor-BB was scored in a double-blinded manner, or vessel density was measured using a semi-automated image analysis procedure. Thalidomide, fumagillin, U0126 and TGFß inhibited neovessel growth while hydrocortisone exerted a negative and wortmannin a toxic effect on the pre-existing vasculature. This quantitative, inexpensive and rapid in vivo angiogenesis assay might be a valuable tool in screening and characterizing factors that influence wound or tumor induced vascularization and in assessing their effects on the normal vasculature.

Spheroids of granulosa cells provide an in vitro model for programmed cell death coupled to steroidogenesis.

UNLABELLED: We describe the use of rotary cultures (72 rpm) as an excellent method for generating spheroids from dispersed bovine granulosa cells (GC). The GC spheroids were symmetrical (diameter between 100 and 200 microm), easily accessible, and could be obtained at high yields. On day one, the spheroids showed a two-layered outer zone of cells that stained lighter than the inner zone in semi-thin sections. Bromodeoxyuridine (BrdU) uptake was frequent and randomly distributed. By day two, a striking decrease in BrdU uptake was noted. Apoptotic bodies appeared up to day four, as did TUNEL and propidium iodide labelled dead cells. At that time, the inner zone contained cells with large-sized vacuoles and the core was amorphous. The large-sized vacuoles were identified at the ultrastructural level and represented autophagosomes and autophagolysosomes that were in different stages of development. Surprisingly, conspicuous signs of cell death were accompanied by an increase in spontaneous luteinization compared to conventional stationary cultures. We detected high levels of progesterone (immunoassay) accompanied by high levels of the proteins and enzymes relevant for steroidogenesis (StAR, P450scc, 3beta-HSD by immunoblot and immunohistochemistry, respectively). CONCLUSIONS: Concomitant to cell death, GC spheroids augment progesterone synthesis. The GC spheroids provide an ideal model for studying steroidogenesis coupled to programmed cell death at the level of the mitochondria.

[The quality of life related to depressive symptoms in coronary artery disease patients after successful coronary angioplasty: one-year follow up]. / Jakosc zycia a objawy depresyjne u pacjentów z choroba niedokrwienna serca po zabiegach przezskórnej angioplastyki wiencowej w ciagu rocznej obserwacji.

AIM: The aim of the study was to assess how the comorbidity of depressive symptoms and cardiac ischemic disease (CAD) influences the quality of life (QoL) in patients after the successful coronary angioplasty (PCI). METHOD: 227 patients with CAD selected for PTCA were enrolled. 156 patients with full clinical and angiographic success and without restenosis within 4 weeks after the intervention were included in one year follow-up. Patients' status was assessed four times (one day before and at 1, 6 and 12 months after the intervention), with the Polish version of SF-36, Beck's Depression Inventory (BDI), Rosenberg's Self-Esteem Scale (RS), Beck's Hopelessness Scale (HS) and the Automatic Thoughts Questionnaire (ATQ). RESULTS: In the whole study group (n=156) the quality of life at 1 month after PTCA was significantly improved. This tendency persisted in further examinations. There was a significant correlation between the quality of life (SF-36), severity of depressive symptoms (BDI) and parameters describing depressive changes in thinking (HS, RS, ATQ). On each occasion during the one-year follow-up' the presence of depressive symptoms was associated with the poorer quality of life, both with respect to the total SF-36 points and individual components of QoL measured by 8 subscales of the SF-36. CONCLUSIONS: Present findings indicate that depressive disorders in patients with CAD--even after successful intervention--significantly affect the quality of life. Optimized comprehensive approach to CAD patients with concomitant depressive disorders may require the inclusion of psychological interventions, and in severe cases even psychiatric treatment.

[The role of zinc in the pathogenesis and treatment of affective disorders]. / Udzial cynku w patogenezie i terapii zaburzen afektywnych.

Zinc is an important modulator of glutaminergic transmission. Recent data indicate that pathology of amino-acidergic neurotransmission may contribute to mood disorders and may be involved in antidepressant-like actions in laboratory models. A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders. The zinc deficiency is related to a variety of psychological symptoms especially depression. There are many reports indicating significant changes in blood levels of zinc during a depressive episode. Moreover zinc exhibits antidepressant-like and anxiolytic-like effects in animal models of depression, in rodents. Recent data revealed that zinc enhances the antidepressant effect in laboratory animals. This article reviews the alterations in central and peripheral zinc homeostasis in relation to pathophysiology and treatment of depression.

Effects of quinidine on pharmacokinetics and pharmacodynamics of digitoxin achieving steady-state conditions.

Quinidine has been reported to increase digoxin plasma concentrations, which increases the risk of digoxin overdose. The effect of quinidine on digitoxin pharmacokinetics is still controversial because most studies were not performed with subjects achieving definite steady-state conditions. To determine whether quinidine affects digitoxin kinetics and cardiac efficacy, we measured glycoside plasma concentrations and renal excretion as well as ECG parameters and systolic time intervals before and during quinidine dosing in eight healthy subjects at steady state. Mean (+/- SD) digitoxin plasma concentrations and renal excretion increased from 13.6 +/- 2.2 ng/ml and 16.1 +/- 5.8 micrograms/24 hours before dosing to 19.7 +/- 3.1 ng/ml and 23.4 +/- 4.9 micrograms/24 hours, respectively, during quinidine dosing for 32 days. While renal digitoxin clearance was not noticeably changed by quinidine, total digitoxin clearance and extrarenal digitoxin clearance decreased by an average of 32% and 40.5%, respectively. The elimination t1/2 was prolonged from 150.3 +/- 20.6 to 202.6 +/- 37.5 hours. The increased digitoxin plasma level is pharmacodynamically active. We conclude that there is a clinically important interaction between digitoxin and quinidine, but it is to a lesser extent and is caused by different mechanism, in part, than the interaction between digoxin and quinidine.

Effects of verapamil on pharmacokinetics and pharmacodynamics of digitoxin in patients.

Investigations by various teams have shown that combined treatment with verapamil and digoxin may result in a marked increase in digoxin plasma concentrations, necessitating a reduction in the dose of digoxin. This is mainly due to an impairment of the renal digoxin excretion. Unlike digoxin, the excretion of digitoxin is independent of renal function. A prospective clinical study was therefore planned to investigate the influence of a daily dose of 240 mg of verapamil on pharmacokinetics and the cardiac effect of digitoxin after a single dose (n = 3) and under steady-state conditions (n = 10). While pretreatment with verapamil did not alter pharmacokinetics of digitoxin in the single-dose study, there was a slight rise of digitoxin plasma concentrations (an average of 35% in 8 out of 10 patients) following administration of verapamil for a period of 4 to 6 weeks. Renal excretion of digitoxin, however, was not changed significantly. Simultaneous with a rise of digitoxin plasma concentrations and until a new steady state was reached, PQ interval was prolonged and T wave flattening intensified. On the other hand, the antagonistic effect on contractility which was initially observed after verapamil administration was diminished. Based on these observations, it can be concluded that the risk of digitalis overdose after combined treatment with verapamil and digitoxin may be less pronounced than after digoxin, and that this glycoside can prove a valuable alternative.

[Pharmacokinetic and cardiac efficacy of beta-acetyldigoxin and digitoxin in combination therapy with diltiazem]. / Pharmakokinetik und kardiale Wirksamkeit von beta-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Diltiazem.

The effect of diltiazem (D) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 12) and digitoxin (DGT; n = 10) was studied in 22 patients with cardiac insufficiency stages II-III by the New York Heart Association. Glycoside plasma concentration and renal excretion as well as electrocardiogram [heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QTc), mean amplitude of T-waves in leads V2 to V6 (TV2-6)] and systole time intervals [total electromechanical systole index (QS21), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET ratio] were recorded repeatedly before and during co-administration of 180 mg/day D. In eight patients digoxin plasma levels increased continuously during additional D administration. After reaching a new steady state at 0.93 +/- 0.35 ng/ml digoxin concentrations were at an average 43% higher than before D administration (0.65 +/- 0.27 ng/ml) with a simultaneous increase in renal glycoside excretion. The other four patients showed neither changes in digoxin concentrations in plasma nor in renal glycoside excretion. Only half the patients treated with DGT and D revealed an increase in DGT plasma levels of 21.4%. Daily renal glycoside excretion was not altered by D administration. In accordance to the increasing AD plasma concentration, PQ-interval was prolonged and T-wave flattening was intensified, whereas the systolic time intervals after concomitant treatment of AD and D did not differ from those after AD alone.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacokinetics and cardiac effect of beta-acetyldigoxin and digitoxin in combination therapy with nifedipine]. / Pharmakokinetik und kardiale Wirksamkeit von beta-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Nifedipin.

The effect of nifedipine (N) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 11) and digitoxin (DGT; n = 10) was studied in 21 patients with cardiac insufficiency stage II-III NYHA. Glycoside plasma concentration and renal excretion as well as electrocardiogram heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QTc), mean amplitude of T waves in leads V2 to V6 (TV2-6) and systolic time intervals total electromechanical systole index (QS21), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET-ratio were recorded repeatedly before and during co-administrations of 40-60 mg/day N. Plasma AD concentrations were 0.64 +/- 0.22 ng/ml (mean +/- SD) before and 0.61 +/- 0.21 ng/ml during co-administration of N over 10-14 days, plasma DGT concentrations 13.9 +/- 4.1 ng/ml before and 13.7 +/- 4.5 ng/ml during co-administration of N over 4-6 weeks. Daily glycoside excretion was not affected by treatment with N. Heart rate and PQ-interval were not significantly changed during co-administration of N whereas T-wave flattening was intensified and QT-duration was lengthened. Concomitant treatment of AD and N led to an increase of PEPI and PEP/LVET compared to AD alone in ten patients whereas the systolic time intervals after concomitant treatment of DGT and N in most patients did not differ from those after DGT alone. From our findings we conclude that N had no clinically significant effect on pharmacokinetics and pharmacodynamics of AD or DGT.