While a number of assays for soluble analytes have been developed using paper-based microfluidic devices, the detection and analysis of blood cells has remained an outstanding challenge. In this ...Feature, we discuss how the properties of paper determine the performance of paper-based microfluidic devices and permit the design of cellular assays, which can ultimately impact disparities in healthcare that exist in limited-resource settings.
Traumatic Brain Injury (TBI) is defined by changes in brain function resulting from external forces acting on the brain and is typically characterized by a host of physiological and functional ...changes such as cognitive deficits including attention problems. In the present study, we focused on the effect of TBI on the ability to allocate attention in vision (i.e., the use of endogenous and exogenous visual cues) by systematically reviewing previous literature on the topic. We conducted quantitative synthesis of 16 selected studies of visual attention following TBI, calculating 80 effect size estimates. The combined effect size was large (g = 0.79,
p
< 0.0001) with medium heterogeneity (I
2
= 68.39%). Subgroup analyses revealed an increase in deficit with moderate-to-severe and severe TBI as compared to mild TBI
F
(2, 76)
= 24.14,
p
< 0.0001. Task type was another key source of variability and subgroup analyses indicated that higher order attention processes were severely affected by TBI
F
(2, 77)
= 5.66,
p
= 0.0051). Meta-regression analyses revealed significant improvement in visual attention deficit with time p(mild) = 0.031, p(moderate-to-severe) = 0.002, p(severe) < 0.0001. Taken together, these results demonstrate that visual attention is affected by TBI and that regular assessment of visual attention, using a systematic attention allocation task, may provide a useful clinical measure of cognitive impairment and change after TBI.
•Long term hand motor training and changes in performance and fMRI representation in healthy volunteers.•Differential transfer of unilateral training performance gain for the non-trained ...hand.•Differential increase in cerebellar-cortical and striatal-cortical loops during training of different tasks.
We were interested in motor performance gain after unilateral hand motor training and associated changes of cerebral and cerebellar movement representation tested with functional magnetic resonance imaging (fMRI) before and after training. Therefore, we trained the left hand of strongly right-handed healthy participants with a comprehensive training (arm ability training, AAT) over two weeks. Motor performance was tested for the trained and non-trained hand before and after the training period. Functional imaging was performed for the trained and the non-trained hand separately and comprised force modulation with the fist, sequential finger movements and a fast writing task. After the training period the performance gain of tapping movements was comparable for both hand sides, whereas the motor performance for writing showed a higher training effect for the trained hand. fMRI showed a reduction of activation in supplementary motor, dorsolateral prefrontal cortex, parietal cortical areas and lateral cerebellar areas during sequential finger movements over time. During left hand writing lateral cerebellar hemisphere also showed reduced activation, while activation of the anterior cerebellar hemisphere was increased. An initially high anterior cerebellar activation magnitude was a predictive value for high training outcome of finger tapping and visual guided movements. During the force modulation task we found increased activation in the striate.
Overall, a comprehensive long-term training of the less skillful hand in healthy participants resulted in relevant motor performance improvements, as well as an intermanual learning transfer differently pronounced for the type of movement tested. Whereas cortical motor area activation decreased over time, cerebellar anterior hemisphere and striatum activity seem to represent increasing resources after long-term motor training.
Anticancer agents often have a narrow therapeutic index (TI), requiring precise dosing to ensure sufficient exposure for clinical activity while minimizing toxicity. These agents frequently have ...complex pharmacology, and combination therapy may cause schedule‐specific effects and interactions. We review anticancer drug development, showing how integration of modeling and simulation throughout development can inform anticancer dose selection, potentially improving the late‐phase success rate. This article has a companion article in Clinical Pharmacology & Therapeutics with practical examples.
CPT Pharmacometrics Syst. Pharmacol. (2015) 4, 12–27; doi:10.1002/psp4.16; published online 21 January 2015
Hydroxymethylfurfural (HMF) is an interesting renewable platform molecule due to the number of products that can be obtained from it. Various catalytic systems have been used to produce HMF from ...glucose; however, challenges, such as the lack of recovery and reutilization and/or low catalytic activity, have been encountered. This article reports a series of novel polystyrene sulfonic acid (PSSA)-based catalysts with both Brønsted and Lewis acid sites for the one-pot synthesis of HMF from glucose. These catalysts combine the advantages of both homogeneous and heterogeneous catalysts, as they are soluble in water (highly active) and recoverable by ultrafiltration for further use. Due to the presence of Brønsted and Lewis acid sites, these catalysts have the ability to perform both the isomerization of glucose to fructose and the dehydration of fructose to HMF. The interplay between Brønsted and Lewis acid sites was investigated by synthesizing a series of PSSA-AlCl
3
catalysts with different Brønsted : Lewis acid ratios. A maximum HMF yield of ∼55 mol% was obtained with the PSSA-AlCl
3
catalyst with H
+
/Al mole ratio = 4 after 4 h of reaction, and this was recycled and reused up to five times without significant loss of activity. Remarkably, this catalyst was effective in the valorization of highly concentrated solutions of glucose in water (up to 16.7 wt%). A techno-economic analysis estimated that the minimum fuel selling price (MFSP) of this HMF would be $1.94 per kg at a feed price of $0.30 per kg glucose. This MFSP could be further reduced by improving the HMF yield, minimizing the volume of solvent used, or using a lower-cost feedstock.
One-pot synthesis of hydroxymethylfurfural from glucose using polymer-based catalysts with Brønsted and Lewis acidity.
The purpose of this study is to understand atmospheric factors, which cause mudflow variability on interannual and longer timescales, from local to synoptic scales. In a first step, historical data ...of mudflow occurrences in Uzbekistan provided by the Centre of Hydrometeorological Service of the Republic of Uzbekistan (Uzhydromet) for more than 140 years were analysed. During the investigation period a total of about 3000 mudflow events were observed with about 21 events per year on average. The majority of mudflows occur during the advection of westerly airflow when moist air from central and southern Europe reaches Uzbekistan. This synoptic weather type (SWT) can be related to one of the 15 primary synoptic circulation types over central Asia (CA) and Uzbekistan, which were subjectively derived by Bugayev and Giorgio in the 1930s and 1940s. To understand the main atmospheric regimes steering the variability in mudflow occurrences, we additionally applied an objective classification following the circulation weather type (CWT) approach. By means of the CWT approach, we found that on mudflow days the frequencies of cyclonic (C), westerly (W), south-westerly (SW) and north-westerly (NW) stream flows are increased in comparison to the climatological frequency of the occurrence of these circulation weather patterns. Results confirm that CWT westerly airflow initiates relatively more mudflow events comparing to other CWTs in the study area. An integrated approach of the CWT classification and an antecedent daily rainfall model are combined together in logistic regression analysis to construct a mudflow-triggering precipitation threshold for every CWT class. In general W, SW and C weather types require less antecedent rainfall to trigger mudflow occurrences in the study area. This technique is thus shown to be applicable to coarse-resolution climate model diagnostics.
Effects of climate change are particularly strong in high-mountain regions. Most visibly, glaciers are shrinking at a rapid pace, and as a consequence, glacier lakes are forming or growing. At the ...same time the stability of mountain slopes is reduced by glacier retreat, permafrost thaw and other factors, resulting in an increasing landslide hazard which can potentially impact lakes and therewith trigger far-reaching and devastating outburst floods. To manage risks from existing or future lakes, strategies need to be developed to plan in time for adequate risk reduction measures at a local level. However, methods to assess risks from future lake outbursts are not available and need to be developed to evaluate both future hazard and future damage potential. Here a method is presented to estimate future risks related to glacier lake outbursts for a local site in southern Switzerland (Naters, Valais). To generate two hazard scenarios, glacier shrinkage and lake formation modelling was applied, combined with simple flood modelling and field work. Furthermore, a land-use model was developed to quantify and allocate land-use changes based on local-to-regional storylines and three scenarios of land-use driving forces. Results are conceptualized in a matrix of three land-use and two hazard scenarios for the year 2045, and show the distribution of risk in the community of Naters, including high and very high risk areas. The study underlines the importance of combined risk management strategies focusing on land-use planning, on vulnerability reduction, as well as on structural measures (where necessary) to effectively reduce future risks related to lake outburst floods.
Display omitted
Recycling of receptors from the endosomal recycling compartment to the plasma membrane is a critical cellular process, and recycling is particularly important for maintaining ...invasiveness in solid tumors. In this work, we continue our efforts to inhibit EHD1, a critical adaptor protein involved in receptor recycling. We applied a diversity-oriented macrocyclization approach to produce cyclic peptides with varied conformations, but that each contain a motif that binds to the EH domain of EHD1. Screening these uncovered several new inhibitors for EHD1’s EH domain, the most potent of which bound with a Kd of 3.1μM. Several of the most potent inhibitors were tested in a cellular assay that measures extent of vesicle recycling. Inhibiting EHD1 could potentially slow cancer invasiveness and metastasis, and these cyclic peptides represent the most potent inhibitors of EHD1 to date.
Purpose: Signal lag is an inherent property of the digital detectors used for radiography. The extent and impact of signal lag can vary. In this exhibit we aim to:'¢ provide context for detector lag ...testing as a matter of acceptance testing for detectors used in digital radiography (DR)'¢ provide example lag data from various DR systems. Lag measurement and analysis techniques have been published but without the expected results that are useful for benchmarking.'¢bring greater awareness and understanding to the impact of detector lag for the performance of digital detectors and the appearance of image ghosting in clinical images. Methods: A standardized method was used for the quantification of lag similar to that described in the IPEM report 32 part vii 1. Six different vended detector options were measured and compared. Results: Lag images were visually compared and lag measurement values were normalized using the measured signal transfer properties of each system. The results are shown as normalized with exposure. The results show a wide variety of lag responses, even for the same physical detector hardware but different vendor implementations. Conclusions: The ultimate test for detector lag performance is whether residual ‘ghost’ images appear in clinical images. Some vendor systems are more prone to the appearance of lag than others. We attempt to quantify system properties at acceptance testing that can enable discriminationbetween systems which have poor or superior lag properties. A suggested easurement analysis technique which normalizes data to be linear with exposure does not appear to adequately assess the likelihood for the clinical appearance of lag. 1 Mackenzie A et al. Measurement of the Performance Characteristics of Diagnostic X‐Ray Systems: Digital Imaging Systems. Institute of Physics in Medicine 2009 (IPEM Report 32, part vii). 2010
We have previously shown that members of the ELR(+) CXC chemokine family, including IL-8; growth-related oncogenes alpha, beta, and gamma; granulocyte chemotactic protein 2; and epithelial ...neutrophil-activating protein-78, can mediate angiogenesis in the absence of preceding inflammation. To date, the receptor on endothelial cells responsible for chemotaxis and neovascularization mediated by these ELR(+) CXC chemokines has not been determined. Because all ELR(+) CXC chemokines bind to CXC chemokine receptor 2 (CXCR2), we hypothesized that CXCR2 is the putative receptor for ELR(+) CXC chemokine-mediated angiogenesis. To test this postulate, we first determined whether cultured human microvascular endothelial cells expressed CXCR2. CXCR2 was detected in human microvascular endothelial cells at the protein level by both Western blot analysis and immunohistochemistry using polyclonal Abs specific for human CXCR2. To determine whether CXCR2 played a functional role in angiogenesis, we determined whether this receptor was involved in endothelial cell chemotaxis. We found that microvascular endothelial cell chemotaxis in response to ELR(+) CXC chemokines was inhibited by anti-CXCR2 Abs. In addition, endothelial cell chemotaxis in response to ELR(+) CXC chemokines was sensitive to pertussis toxin, suggesting a role for G protein-linked receptor mechanisms in this biological response. The importance of CXCR2 in mediating ELR(+) CXC chemokine-induced angiogenesis in vivo was also demonstrated by the lack of angiogenic activity induced by ELR(+) CXC chemokines in the presence of neutralizing Abs to CXCR2 in the rat corneal micropocket assay, or in the corneas of CXCR2(-/-) mice. We thus conclude that CXCR2 is the receptor responsible for ELR(+) CXC chemokine-mediated angiogenesis.
PDF
