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Microscale thermophoresis (MST) is a versatile technique to measure binding affinities of binder–ligand systems, based on the directional movement of molecules in a temperature gradient. We extended MST to measure binding kinetics as well as binding affinity in a single experiment by increasing the thermal dissipation of the sample. The kinetic relaxation fingerprints were derived from the fluorescence changes during thermodynamic re‐equilibration of the sample after local heating. Using this method, we measured DNA hybridization on‐rates and off‐rates in the range 104–106 m −1 s−1 and 10−4–10−1 s−1, respectively. We observed the expected exponential dependence of the DNA hybridization off‐rates on salt concentration, strand length and inverse temperature. The measured on‐rates showed a linear dependence on salt concentration and weak dependence on strand length and temperature. For biomolecular interactions with large enthalpic contributions, the kinetic MST technique offers a robust, cost‐effective and immobilization‐free determination of kinetic rates and binding affinity simultaneously, even in crowded solutions., The extension of microscale thermophoresis (MST) to perform temperature jumps by increasing the heat dissipation of the sample allows for quantification of binding affinities together with the kinetic rates. Relaxation kinetics for DNA hybridization were measured with high fidelity at different temperatures and various experimental conditions. The results shed light on the hybridization mechanism of DNA and confirmed determinants of DNA binding.

Objective: This study was undertaken to evaluate the efficacy of vagus nerve stimulation (VNS) over time, and to determine which patient groups derive the most benefit. Methods: Long-term outcomes are reported in 436 epilepsy patients from a VNS quality registry (52.8% adults, 47.2% children), with a median follow-up of 75 months. Patients were stratified according to evolution of response into constant responders, fluctuating responders, and nonresponders. The effect was evaluated at 6, 12, 24, 36, and 60 months. Multivariate regression analysis was used to identify predictors of response. Results: The cumulative probability of ≥50% seizure reduction was 60%; however, 15% of patients showed a fluctuating course. Of those becoming responders, 89.5% (230/257) did so within 2 years. A steady increase in effect was observed among constant responders, with 48.7% (19/39) of those becoming seizure-free and 29.3% (39/133) with ≥75% seizure reduction achieving these effects within 2–5 years. Some effect (25%–

Key requirements for the first cells on Earth include the ability to compartmentalize and evolve. Compartmentalization spatially localizes biomolecules from a dilute pool and an evolving cell which grows and divides permits mixing and propagation of information to daughter cells. Complex coacervate microdroplets are excellent candidates as primordial cells with the ability to partition and concentrate molecules into their core and support primitive and complex biochemical reactions. However, the evolution of coacervate protocells by fusion, growth and fission has not yet been demonstrated. In this work, a primordial environment initiated the evolution of coacervate-based protocells. Gas bubbles inside heated rock pores perturb the coacervate protocell distribution and drive the growth, fusion, division and selection of coacervate microdroplets. This setting provides a primordial non-equilibrium environment. Our findings describe how common gas bubbles within heated rock pores induce the early evolution processes of coacervate-based protocells, providing a compelling scenario for the evolution of membrane-free coacervate microdroplets on the early Earth.

Financial crises appear throughout human history. In particular, the financial crisis of 2008 highlighted the role of uncontrolled creation of money through lending as a source of financial instability. The creation of money is also problematic due to the implicit non-local transfers of wealth (Cantillon effect) and a leak of the economic memory of past transactions. Motivated by an analogy to particle physics, time-homogeneity can be imposed on monetary systems to approach and even possibly solve the associated problems. This implies a full reserve banking with a two-currency system which discriminates with an exchange rate between non-bank assets (money) and bank assets (antimoney). The associated liabilities are in the hands of banks and non-banks, respectively. Payments are either made by passing on money or receiving antimoney at respective price levels. Liquidity is provided by the simultaneous transfer of money and antimoney at a negotiated exchange rate between money and antimoney, also termed the liquidity price. In this system, interest rates and credit creation are replaced by a varying price for liquidity. We started to study the economic stability of such a system with an agent-based random economy model, in which households and firms are urged by random boundary conditions to apply stochastic exchanges of goods via a limit order book mechanism, implementing the trading scheme of stock markets. We compared the market simulations under the prevailing monetary system with the money–antimoney system and found that a symmetric price equilibrium was obtained by imposing a limit on the agents’ antimoney holdings. This is the equivalent of controlling lending in a money system. For both money and antimoney, quantity theory is satisfied. Production and credit shocks showed a quantitative and qualitative similar behavior for the different monetary systems, indicating the overall functionality of the proposed money–antimoney system.

Background: Vagus nerve stimulation (VNS) is used for patients with drug-resistant epilepsy not amenable to epilepsy surgery. However, the efficacy of VNS treatment over time, and which patients with which etiologies derive most benefit from VNS, is uncertain. Methods: We report long-term outcomes of VNS in 436 epilepsy patients (52·8% adults, 47·2% children), with median follow-up of 75 months (six to 254). Patients were stratified into constant responders, fluctuating responders, and non-responders. We used regression analysis to identify predictors of response. Findings: The cumulative probability of ≥50% seizure reduction was 60%, however 15% of patients showed a fluctuating course. Of those becoming responders, 89·5% (230/257) did so within two years. A steady increase in effect was observed among constant responders, with 48·7% (19/39) of those becoming seizure-free, and 29·3% (39/133) with ≥75% seizure reduction achieving these effects within between two and five years. Some effect (

Purpose to simultaneously evaluate interreader agreement and diagnostic accuracy in the of PI-RADS v2 and compare it to v1. Methods A total of 67 patients (median age 65.3 y, range 51.2–78.2 y; PSA 6.8 μg/L, 0.2–33 μg/L) undergoing MRI of the prostate and subsequent transperineal template biopsy within ≤6 months from MRI were included. Four readers from two institutions evaluated the likelihood of prostate cancer using PI-RADS v1 and v2 in two separate reading sessions ≥3 months apart. Interreader agreement was assessed for each pulse-sequence and for total PI-RADS scores using the intraclass correlation coefficient (ICC). Differences were considered significant for non-overlapping 95%-confidence intervals. Diagnostic accuracy was assessed with the area under the receiver operating characteristic curve (A Z ). A p-value Results Interreader agreement for DCE-scores was good in v2 (ICC 2 = 0.70; 95% CI: 0.66–0.74) and slightly lower in v1 (ICC 1 = 0.64, 0.59–0.69). Agreement for DWI scores (ICC 1 = 0.77, ICC 2 = 0.76) as well as final PI-RADS scores per quadrant were nearly identical (ICC 1 = ICC 2 = 0.71). Diagnostic accuracy showed no significant differences (p = 0.09–0.93) between v1 and v2 in any of the readers (range: A Z = 0.78–0.88). Conclusion PI-RADS scores show similar interreader agreement in v2 and v1 at comparable diagnostic performance. The simplification of the DCE interpretation in v2 might slightly improve agreement while not negatively affecting diagnostic performance.

An Yb:thin-disk laser delivering 615 fs pulses with 17 mJ energy at 3 kHz is harnessed towards generation of single-cycle multi-THz transients with few hundred MV/cm field strength via chirped-pulse difference frequency mixing in large-aperture GaSe crystals.

The fundamental interband absorption in gallium arsenide shows a strong blue shift when biased by mid-infrared transients exceeding 10 MV/cm. This subcycle feature is induced by the localization of electronic wavefunctions from 3D to 2D.

INTRODUCTION: The purpose of this study was to compare diagnostic accuracy of a prostate multiparametric magnetic resonance imaging (mpMRI) protocol for detection of prostate cancer between images acquired with and without en-dorectal coil (ERC). MATERIALS: This study was approved by the regional ethics committee. Between 2014 and 2015, 33 patients (median age 51.3 years; range 42.1-77.3 years) who underwent prostate-MRI at 3T scanners at 2 different institutions, acquired with (mpMRI(ERC)) and without (mpMRI(PPA)) ERC and who received radical prostatectomy, were included in this retrospective study. Two expert readers (R1, R2) attributed a PI-RADS version 2 score for the most suspect (i. e. index) lesion for mpMRI(PPA) and mpMRI(ERC). Sensitivity and positive predictive value for detection of index lesions were assessed using 2 × 2 contingency tables. Differences between groups were tested using the McNemar test. Whole-mount histopathology served as reference standard. RESULTS: On a quadrant-basis cumulative sensitivity ranged between 0.61-0.67 and 0.76-0.88 for mpMRI(PPA) and mpMRI(ERC) protocols, respectively (p > 0.05). Cumulative positive predictive value ranged between 0.80-0.81 and 0.89-0.91 for mpMRI(PPA) and mpMRI(ERC) protocols, respectively. The differences were not statistically significant for R1 (p = 0.267) or R2 (p = 0.508). CONCLUSION: Our results suggest that there may be no significant differences for detection of prostate cancer between images acquired with and without an ERC.

To compare image quality and geometric distortion between readout-segmented diffusion-weighted imaging (rs-DWI) and selective-excitation accelerated reduced-field of view (FOV) DWI (sTX-DWI) of the prostate.Sixty-five patients underwent 3-T MRI of the prostate including rs-DWI and sTX-DWI (b values, 0, 50, and 1000 seconds/mm²; FOV, 150 × 150 mm² and 77 ×150 mm for rs-DWI and sTX-DWI; slice thickness, 3 mm; acquisition time, 8:18 min and 1:37 min for rs-DWI and sTX-DWI). Two readers evaluated aspects of image quality and geometric distortion on a 5-point Likert scale. Quantitative analysis of geometric distortion was assessed by measurements of anteroposterior and left-right diameters and compared to T2-weighted turbo-spin echo sequence using intraclass correlation coefficient (ICC).There was no significant difference in resolution, capsule demarcation, and zonal anatomy (P = 0.111-0.866). Overall image quality was rated "above average" by reader 1 (4.09 ± 0.66 and 4.03 ± 0.79; P = 0.433) and reader 2 (3.86 ± 0.66 and 3.80 ± 0.74; P = 0.465) for rs-DWI and sTX-DWI. Reader 1 (0.74 ± 0.67 and 1.17 ± 0.84; P0.001) and reader 2 (0.55 ± 0.64 and 1.09 ± 0.95; P0.001) rated the level of geometric distortion significantly lower for rs-DWI than sTX-DWI. Readout-segmented DWI (0.9 ± 2.2 mm) and sTX-DWI (2.1 ± 3.8 mm) overestimated the anteroposterior diameter of the prostate compared to T2-weighted turbo-spin echo sequence (P0.001), the difference being more pronounced for sTX-DWI [ICC, 0.89 (95% confidence interval, 0.83-0.93)] compared to rs-DWI [ICC, 0.96 (95% confidence interval, 0.94-0.96)].Selective-excitation accelerated reduced-FOV DW images (sTX-DWI) of the prostate can be acquired more than 5 times faster than rs-DWI with comparable image quality, at the expense of significantly increased geometric distortion.

Sub-cycle transmission measurements of bulk gallium arsenide biased by intense mid-infrared transients reveal a strong blue-shift of the optical absorption when the peak electric field reaches 10 MV/cm, indicating 2D-localization of electronic wave functions.

615fs pulses with 17mJ energy at 3kHz repetition rate are generated by an Yb:thin-disk laser to pump a mJ-class near-IR OPA delivering 25fs pulses. This system targets the generation of intense THz radiation.

Generation of ultrashort and intense laser pulses is the primary motive in ultrafast and nonlinear science. Unfortunately, only a limited number of active media allows for scaling ultrashort pulses to energies greater than a few mJ at kHz repetition rate. For this reason, the available wavelengths are extremely restricted. To drive ultrafast processes in novel frequency domains, the ideal approach is to harness a source of intense pulses suitable for nonlinear frequency conversion at high power and ultrabroad bandwidth. Here we present generation of 615 fs pulses at 1030 nm with 17 mJ energy at 3 kHz repetition rate by a combination of Er/Yb:fiber and Yb:thin-disk technology. This system pumps an optical parametric amplifier (OPA) tunable in the near-IR wavelength range and capable of generating few-ten fs pulses with up to 500 μJ energy.

Purpose To compare the diagnostic performance of a short dual-pulse sequence magnetic resonance (MR) imaging protocol versus a standard six-pulse sequence multiparametric MR imaging protocol for detection of clinically significant prostate cancer. Materials and Methods This HIPAA-compliant study was approved by the regional ethics committee. Between July 2013 and March 2015, 63 patients from a prospectively accrued study population who underwent MR imaging of the prostate including transverse T1-weighted; transverse, coronal, and sagittal T2-weighted; diffusion-weighted; and dynamic contrast material-enhanced MR imaging with a 3-T imager at a single institution were included in this retrospective study. The short MR imaging protocol image set consisted of transverse T2-weighted and diffusion-weighted images only. The standard MR imaging protocol image set contained images from all six pulse sequences. Three expert readers from different institutions assessed the likelihood of prostate cancer on a five-point scale. Diagnostic performance on a quadrant basis was assessed by using areas under the receiver operating characteristic curves, and differences were evaluated by using 83.8% confidence intervals. Intra- and interreader agreement was assessed by using the intraclass correlation coefficient. Transperineal template saturation biopsy served as the standard of reference. Results At histopathologic evaluation, 84 of 252 (33%) quadrants were positive for cancer in 38 of 63 (60%) men. There was no significant difference in detection of tumors larger than or equal to 0.5 mL for any of the readers of the short MR imaging protocol, with areas under the curve in the range of 0.74-0.81 (83.8% confidence interval [CI]: 0.64, 0.89), and for readers of the standard MR imaging protocol, areas under the curve were 0.71-0.77 (83.8% CI: 0.62, 0.86). Ranges for sensitivity were 0.76-0.95 (95% CI: 0.53, 0.99) and 0.76-0.86 (95% CI: 0.53, 0.97) and those for specificity were 0.84-0.90 (95% CI: 0.79, 0.94) and 0.82-0.90 (95% CI: 0.77, 0.94) for the short and standard MR protocols, respectively. Ranges for interreader agreement were 0.48-0.60 (83.8% CI: 0.41, 0.66) and 0.49-0.63 (83.8% CI: 0.42, 0.68) for the short and standard MR imaging protocols. Conclusion For the detection of clinically significant prostate cancer, no difference was found in the diagnostic performance of the short MR imaging protocol consisting of only transverse T2-weighted and diffusion-weighted imaging pulse sequences compared with that of a standard multiparametric MR imaging protocol. © RSNA, 2017 Online supplemental material is available for this article.

To compare image quality (IQ) and patient discomfort during prostate MRI using a pelvic phased array (PPA) coil and an endorectal (ER) coil. Ninety-eight patients (median age, 65.7; range 42.1–78.1) underwent prostate MRI on a 3T scanner including T2w and DWI acquired with PPA and an ER coil within the same exam. Acquisition time was kept similar for both acquisitions. Two radiologists evaluated aspects of IQ on a 5-point Likert scale and classified image artifacts. All patients completed a questionnaire on discomfort/pain regarding the ER coil using a visual analogue scale from 1 to 10. There was no significant difference in overall IQ for T2w images for both readers (reader 1, 3.27 ± 0.91 and 3.07 ± 0.84, p = 0.057; reader 2, 3.70 ± 0.75 and 3.77 ± 0.81, p = 0.555) for PPA and ER coils, respectively. Overall IQ for DWI acquired with PPA and ER coils was rated similar by reader 1 (3.03 ± 1.10 and 3.08 ± 0.80, respectively, (p = 0.67)), while reader 2 preferred ER coil images (3.27 ± 0.81 and 3.66 ± 0.85 (p

Combined Er/Yb:fiber and Yb:thin-disk technology produces 615 fs pulses at 1030 nm with an energy of 17 mJ at 3 kHz repetition rate. The sub-ps duration allows efficient white-light generation and optical parametric amplification.

A combination of Er/Yb:fiber and Yb:thin-disk technology produces 615 fs pulses at 1030 nm with an average output power of 72 W. The regenerative amplifier allows variation of the repetition rate between 3 and 5 kHz with pulse energies from 13 to 17 mJ. A broadband and intense seed provided by the compact and versatile fiber front-end minimizes gain narrowing. The resulting sub-ps performance is ideal for nonlinear frequency conversion and pulse compression. Operating in the upper branch of a bifurcated pulse train, the system exhibits exceptional noise performance and stability. published

La validite du dosage du PSA a surtout ete remise en cause par le biais du Prostate Cancer Prevention Trial. D’autres donnees montrent cependant que la hauteur du taux de PSA initial pourrait etre un parametre pronostique optimal de l’evolution au long cours d’un carcinome cliniquement pertinent et soulignent ainsi le role du PSA comme outil de stratification de risque a long terme.

Die Validitat des PSA-Screenings wurde insbesondere durch den Prostate Cancer Prevention Trial angezweifelt. Andere Daten dokumentieren jedoch die Hohe des initialen PSA-Wertes als idealen Parameter fur die Langzeitentwicklung eines klinisch relevanten Karzinoms und unterstreichen damit die Rolle des PSA als Risiko­stratifizierer.

Noncollinear parametric amplification based on type-II phase matching for the generation of ultrabroadband and tunable spectra in the near infrared is investigated. In a noncollinear geometry the group velocity matching condition between signal and idler can be obtained in frequently used crystals such as β-barium borate (BBO) even for wavelengths fully located in the anomalous dispersion region. The extremely broadband operation, peculiar tuning possibilities and straightforward experimental implementation with the standard BBO crystal pave the way for a versatile NIR source in ultrafast spectroscopy.