Comparison of Different Mass Spectrometry Workflows for the Proteomic Analysis of Tear Fluid

The tear film is a multi-layer fluid that covers the corneal and conjunctival epithelia of the eye and provides lubrication, nutrients, and protection from the outside environment. Tear fluid contains a high concentration of proteins and has thus been recognized as a potential source of biomarkers for ocular disorders due to its proximity to disease sites on the ocular surface and the non-invasive nature of its collection. This is particularly true in the case of dry eye disease, which directly impacts the tear film and its components. Proteomic analysis of tear fluid is challenging mainly due to the wide dynamic range of proteins and the small sample volumes. However, recent advancements in mass spectrometry have revolutionized the field of proteomics enabling unprecedented depth, speed, and accuracy, even with small sample volumes. In this study using the Orbitrap Fusion Tribrid mass spectrometer, we compared four different mass spectrometry workflows for the proteomic analysis of tear fluid collected via Schirmer strips. We were able to establish a method of in-strip protein digestion that identified >3000 proteins in human tear samples from 11 healthy subjects. Our method offers a significant improvement in the number of proteins identified compared to previously reported methods without pooling samples.     

Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways

Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.     

Experimental validation of control rod related perturbations of moderator regions in an SCWR-like fuel lattice

Two different types of perturbations of an SCWR-like fuel lattice have been investigated experimentally in the central test zone of the PROTEUS zero-power research reactor at the Paul Scherrer Institute in Switzerland. In each case, a campaign of high-resolution gamma-ray spectroscopy measurements was carried out on 34 fuel pins of the test lattice. In the first case, the test lattice was perturbed by inserting aluminum rods into the four central moderator regions, while in the second case, the perturbation was affected using steel absorber rods (instead of aluminum). The derived reaction rates are the capture rate in ²³⁸U (C₈) and the total fission rate (F_tot), as also the reaction rate ratio C₈/F_tot. Each of these has been mapped on the lattice and compared to calculated results from whole-reactor Monte Carlo simulations with MCNPX. Excellent agreement has been obtained, for both perturbed lattices, between the calculated and experimental distributions of C₈, F_tot and C₈/F_tot. Considering that control rods in an SCWR assembly are foreseen to be inserted into the central moderator regions, these results may be considered as generic validation of Monte Carlo simulations for the two different types of lattice perturbations which inserted control rods imply, viz. moderator displacement and strong neutron absorption.In a second step, calculated C₈, F_tot and C₈/F_tot distributions for the two perturbed lattices (as well as for the unperturbed lattice) have been compared, at assembly level, between MCNPX and the deterministic LWR lattice code CASMO-4E. In the case of the unperturbed lattice, as well as for the lattice with steel rods, the agreement between the codes is found to be within ～1% for all pins and each reaction rate. However, for the lattice with aluminum rods, i.e. the case with mainly just moderator displacement involved, CASMO overestimates the reaction rates in the vicinity of the perturbations by up to 2–3%, when employing the standard input options. The reason for this discrepancy has been found to be the leakage treatment, which uses the fundamental-mode buckling applied in a homogenized sense across the lattice. In this way, global leakage gradients get averaged out over the entire assembly. The optional input card BZ2 for CASMO resolves this problem, and the codes then agree within 1% even for the aluminum case.     

As you like it: Understanding the relationship between packing design and accessibility

Accessible packaging is continually receiving greater attention as an ageing population becomes a primary driver behind inclusive design. As we age, our strength dexterity and some cognitive functions decline. For this reason, the ease of interaction with simple tasks in daily living becomes an ever increasing concern. ISO 17480 “Packaging Guidelines” consider capability issues relating to packaging and ageing to broadly come under three areas, namely, strength, dexterity, and cognition. Significant previous work has been undertaken looking at the issue of strength on packaging accessibility, with fewer studies looking at the relationship between the physical demands of dexterity and the understanding of how to open the pack. In this previous work, there has been little attempt to quantify the effect of the affordances, perceptual information and symbology, and the physical demands of the pack and how this relates to accessibility. Hence, this exploratory study seeks to use motion capture and a dexterity test, along with a cognitive demand test to study this relationship and any changes with age. This research indicates that the dexterous demands of a task are linked to the cognitive demands; and thus in reaching a level of comprehension of the pack and how to access the product a subject may interact with a pack effectively.     

Medical Image Encryption Based on Hybrid Chaotic DNA Diffusion

Wireless Personal Communications - We explore the use of two chaotic systems (Bernoulli shift map and Zizag map) coupled with deoxyribonucleic acid coding in an encryption scheme for medical images...     

Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed‐loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S‐MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed‐loop guidance or guide tubes. S‐MINIs reduce glial scarring 3.5‐fold compared to prior implants. Bevel steered needles are utilized for open‐loop targeting of deep‐brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel‐tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed‐loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed‐loop feedback and complex imaging.     

Quantum Sensing in a Physiological‐Like Cell Niche Using Fluorescent Nanodiamonds Embedded in Electrospun Polymer Nanofibers

Fluorescent nanodiamonds (fNDs) containing nitrogen vacancy (NV) centers are promising candidates for quantum sensing in biological environments. This work describes the fabrication and implementation of electrospun poly lactic‐co‐glycolic acid (PLGA) nanofibers embedded with fNDs for optical quantum sensing in an environment, which recapitulates the nanoscale architecture and topography of the cell niche. A protocol that produces uniformly dispersed fNDs within electrospun nanofibers is demonstrated and the resulting fibers are characterized using fluorescent microscopy and scanning electron microscopy (SEM). Optically detected magnetic resonance (ODMR) and longitudinal spin relaxometry results for fNDs and embedded fNDs are compared. A new approach for fast detection of time varying magnetic fields external to the fND embedded nanofibers is demonstrated. ODMR spectra are successfully acquired from a culture of live differentiated neural stem cells functioning as a connected neural network grown on fND embedded nanofibers. This work advances the current state of the art in quantum sensing by providing a versatile sensing platform that can be tailored to produce physiological‐like cell niches to replicate biologically relevant growth environments and fast measurement protocols for the detection of co‐ordinated endogenous signals from clinically relevant populations of electrically active neuronal circuits.     

Smoothness maximization along a predefined path accurately predicts the speed profiles of complex arm movements

The speed profiles of arm movements display a number of regularities, including bell-shaped speed profiles in straight reaching movements and an inverse relationship between speed and curvature in extemporaneous drawing movements (described as a 2/3 power law). Here we propose a new model that simultaneously accounts for both regularities by replacing the 2/3 power law with a smoothness constraint. For a given path of the hand in space, our model assumes that the speed profile will be the one that minimizes the third derivative of position (or "jerk"). Analysis of the mathematical relationship between this smoothness constraint and the 2/3 power law revealed that in both two and three dimensions, the power law is equivalent to setting the jerk along the normal to the path to zero; it generates speed predictions that are similar, but clearly distinguishable from the predictions of our model. We have assessed the accuracy of the model on a number of motor tasks in two and three dimensions, involving discrete movements along arbitrary paths, traced with different limb segments. The new model provides a very close fit to the observed speed profiles in all cases. Its performance is uniformly better compared with all existing versions of the 2/3 power law, suggesting that the correlation between speed and curvature may be a consequence of an underlying motor strategy to produce smooth movements. Our results indicate that the relationship between the path and the speed profile of a complex arm movement is stronger than previously thought, especially within a single trial. The accuracy of the model was quite uniform over movements of different shape, size, and average speed. We did not find evidence for segmentation, yet prediction error increased with movement duration, suggesting a continuous fluctuation of the "tempo" of discrete movements. The implications of these findings for motor planning and on-line control are discussed.     

Investigating different factor structures of the Psychopathy Checklist: Youth version: Confirmatory factor analytic findings.

There has been a recent push to extend the construct of psychopathy into adolescence, primarily as a result of the impressive reliability, validity, and utility of this construct in samples of adults. The value of this work rests, however, on creating an equally reliable and valid assessment tool for adolescents. One promising measure is the Psychopathy Checklist: Youth Version (A. E. Forth, D. S. Kosson, & R. D. Hare, 2003). The current study uses a large, diverse sample of serious adolescent offenders to assess the overall fit of various underlying factor structures of this measure and to test the equivalence of these models across sex and race/ethnicity. The results suggest that either a 3- or 4-factor model provides the best overall fit and that these models are invariant across sex and race/ethnicity. The decision to use the 3- or 4-factor model will likely hinge on researchers' underlying conceptualization of psychopathy, specifically whether antisocial behavior is viewed as a core feature of this construct. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A cost comparison of balloon angioplasty and stenting versus endarterectomy for the treatment of carotid artery stenosis

PURPOSE: Percutaneous transluminal angioplasty with stenting (PTAS) of the carotid artery has been advocated as an alternative treatment for high-grade stenosis. Rationale for this approach includes less morbidity, shorter recovery, and lower cost when compared with carotid endarterectomy (CEA). METHODS: The clinical results and hospital charges of patients who underwent elective treatment for carotid stenosis were reviewed. During a concurrent 14-month period, 218 patients were admitted 229 times for 234 procedures for the treatment of 239 carotid bifurcation stenoses, 109 by PTAS and 130 by CEA. Hospital charges were reviewed for each hospitalization and were categorized according to radiology, operating room, cardiac catheterization laboratory, and all other hospital charges. RESULTS: The combined incidence of postprocedure strokes and deaths were: PTAS, eight strokes (7.7%) and one death (0.9%); CEA, two strokes (1.5%) and two deaths (1.5%). Total hospital charges per admission for the two groups were $30,140 for PTAS and $21,670 for CEA. The average postprocedure length of stay for PTAS was 2.9 days (median, 2 days) and for CEA was 3.1 days (median, 3 days). Cardiac catheterization laboratory charges for the PTAS group were $12,968, whereas the operating room charges for the CEA group were $4263. When hospitalizations that were extended by complications were excluded, the average total charges for the PTAS group (n = 84) dropped to $24,848 (mean length of stay, 1.9 days) and for the CEA group (n = 111) to $19,247 (mean length of stay, 2.6 days). CONCLUSIONS: After evaluating hospital charges, PTAS for the treatment of carotid stenosis cannot currently be justified on the basis of reduced costs alone. With future cost-containing measures, total hospital charges can be reduced in both groups.