46 research outputs found

    Machine learning suggests sleep as a core factor in chronic pain

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    Patients with chronic pain have complex pain profiles and associated problems. Subgroup analysis can help identify key problems. We used a data-based approach to define pain phenotypes and their most relevant associated problems in 320 patients undergoing tertiary pain management. Unsupervised machine learning analysis of parameters "pain intensity," "number of pain areas," "pain duration," "activity pain interference," and "affective pain interference," implemented as emergent self-organizing maps, identified 3 patient phenotype clusters. Supervised analyses, implemented as different types of decision rules, identified "affective pain interference" and the "number of pain areas" as most relevant for cluster assignment. These appeared 698 and 637 times, respectively, in 1000 cross-validation runs among the most relevant characteristics in an item categorization approach in a computed ABC analysis. Cluster assignment was achieved with a median balanced accuracy of 79.9%, a sensitivity of 74.1%, and a specificity of 87.7%. In addition, among 59 demographic, pain etiology, comorbidity, lifestyle, psychological, and treatment-related variables, sleep problems appeared 638 and 439 times among the most important characteristics in 1000 cross-validation runs where patients were assigned to the 2 extreme pain phenotype clusters. Also important were the parameters "fear of pain," "self-rated poor health," and "systolic blood pressure." Decision trees trained with this information assigned patients to the extreme pain phenotype with an accuracy of 67%. Machine learning suggested sleep problems as key factors in the most difficult pain presentations, therefore deserving priority in the treatment of chronic pain.Peer reviewe

    Spectral hole burning: examples from photosynthesis

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    The optical spectra of photosynthetic pigment–protein complexes usually show broad absorption bands, often consisting of a number of overlapping, ‘hidden’ bands belonging to different species. Spectral hole burning is an ideal technique to unravel the optical and dynamic properties of such hidden species. Here, the principles of spectral hole burning (HB) and the experimental set-up used in its continuous wave (CW) and time-resolved versions are described. Examples from photosynthesis studied with hole burning, obtained in our laboratory, are then presented. These examples have been classified into three groups according to the parameters that were measured: (1) hole widths as a function of temperature, (2) hole widths as a function of delay time and (3) hole depths as a function of wavelength. Two examples from light-harvesting (LH) 2 complexes of purple bacteria are given within the first group: (a) the determination of energy-transfer times from the chromophores in the B800 ring to the B850 ring, and (b) optical dephasing in the B850 absorption band. One example from photosystem II (PSII) sub-core complexes of higher plants is given within the second group: it shows that the size of the complex determines the amount of spectral diffusion measured. Within the third group, two examples from (green) plants and purple bacteria have been chosen for: (a) the identification of ‘traps’ for energy transfer in PSII sub-core complexes of green plants, and (b) the uncovering of the lowest k = 0 exciton-state distribution within the B850 band of LH2 complexes of purple bacteria. The results prove the potential of spectral hole burning measurements for getting quantitative insight into dynamic processes in photosynthetic systems at low temperature, in particular, when individual bands are hidden within broad absorption bands. Because of its high-resolution wavelength selectivity, HB is a technique that is complementary to ultrafast pump–probe methods. In this review, we have provided an extensive bibliography for the benefit of scientists who plan to make use of this valuable technique in their future research

    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

    Impact of temperature on conduction mechanisms and switching parameters in HfO2-based 1T-1R resistive random access memories devices

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    In this work, the impact of temperature in the range from -40 to +150 °C on the leakage mechanism and resistive switching voltages of 1T-1R HfO2-based devices is investigated. By using incremental step pulses with an additional read and verify algorithm, the devices are switched from the high resistive state (HRS) to the low resistive state (LRS) and vice versa. In the HRS, the leakage current values are not affected by the temperature, suggesting a tunnel-like conduction mechanism through the filament constriction. By applying the quantum-point contact model, this temperature independence is attributed to compensation between the width and the height variations of the tunnel barrier. In contrast to the HRS, the leakage currents values of the LRS are decreasing linearly with raising temperature, suggesting a metal-like conduction mechanism. Therefore, the on/off ratio is slightly decreasing with increasing temperature. Regarding the switching voltages, no impact of temperature was found, ensuring stable switching cycles of the devices in the relevant temperature range for applications

    The effect of excipient particle size on the reduction of compactibility after roller compaction

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    Developing a robust roller compaction process can be challenging, due to the diversity in process parameters and material properties of the components in a formulation. A major challenge in dry granulation is the reduction of tablet strength as a result of re-compaction of the materials. The aim of this study is to investigate the impact of excipient type and particle size distribution on tablet tensile strength after roller compaction. Lactose monohydrate, anhydrous lactose and microcrystalline cellulose with different particle sizes are roller compacted at varying specific compaction forces. Granules obtained are compressed into tablets to evaluate the reduction in tablet strength upon increasing the specific compaction force. The impact of particle size of the starting material is shown to be vastly different for the three types of excipients investigated, due to the differences in mechanical deformation mechanisms. The presence of rough surfaces and a high degree of fragmentation for anhydrous lactose appears to be beneficial for compaction and re-compaction process. Additionally, the particle size of anhydrous lactose hardly affects the tensile strength of tablets, which can be beneficial for the robustness of a roller compaction process

    Stellar variability on time-scales of minutes: results from the first 5 yr of the Rapid Temporal Survey

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    The definitive version can be found at: http://onlinelibrary.wiley.com/ Copyright Royal Astronomical SocietyThe Rapid Temporal Survey (RATS) explores the faint, variable sky. Our observations search a parameter space which, until now, has never been exploited from the ground. Our strategy involves observing the sky close to the Galactic plane with wide-field CCD cameras. An exposure is obtained approximately every minute with the total observation of each field lasting around 2 h. In this paper, we present the first six epochs of observations which were taken over 5 yr from 2003-08 and cover over 31 deg2 of which 16.2 is within 10 degrees of the Galactic plane. The number of stars contained in these data is over 3.0 x 106. We have developed a method of combining the output of two variability tests in order to detect variability on time-scales ranging from a few minutes to a few hours. Using this technique, we find 1.2 x 105 variables - equal to 4.1 per cent of stars in our data. Follow-up spectroscopic observations have allowed us to identify the nature of a fraction of these sources. These include a pulsating white dwarf which appears to have a hot companion, a number of stars with A-type spectra that vary on a period in the range 20-35 min. Our primary goal is the discovery of new AM CVn systems: we find 66 sources which appear to show periodic modulation on a time-scales less than 40 min and a colour consistent with the known AM CVn systems. Of those sources for which we have spectra of, none appears to be an AM CVn system, although we have 11 candidate AM CVn systems with periods less than 25 min for which spectra are still required. Although our numbers are not strongly constraining, they are consistent with the predictions of Nelemans et al.Peer reviewedFinal Accepted Versio
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