Miracle-dz/UniFAR-FTUs huggingface dataset:
Translational Pharmacology of the Metabotropic Glutamate 2 Receptor–Preferring Agonist LY2812223 in the Animal and Human Brain

LY2812223 [(1R,2S,4R,5R,6R)-2-amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1. 0]hexane-2,6-dicarboxylic acid] was identified via structure-activity studies arising from the potent metabotropic glutamate mGlu2/3 receptor agonist LY354740 [(+)-2-aminobicyclo[3.1. 0] hexane-2,6-dicarboxylic acid] as an mGlu2-preferring agonist. This pharmacology was determined using stably transfected cells containing either the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human postmortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies. A guanosine 5′-O-(3-[35S]thio)triphosphate (GTPγS) functional binding assay, a method for measuring Gi-coupled signaling that is inherent to the group 2 mGlu receptors, was used to evaluate LY2812223 pharmacology of native mGlu receptors in mouse, rat, nonhuman primate, and human cortical brain tissue samples. In native tissue membranes, LY2812223 unexpectedly acted as a partial agonist across all species tested. Activity of LY2812223 was lost in cortical membranes collected from mGlu2 knockout mice, but not those from mGlu3 knockout mice, providing additional support for mGlu2-preferring activity. Other signal transduction assays were used for comparison with the GTP binding assay (cAMP, calcium mobilization, and dynamic mass redistribution). In ectopic cell line–based assays, LY2812223 displayed near maximal agonist responses at the mGlu2 receptor across all assay formats, while it showed no functional agonist activity at the mGlu3 receptor except in the cAMP assay. In native brain slices or membranes that express both mGlu2 and mGlu3 receptors, LY2812223 displayed unexpected partial agonist activity, which may suggest a functional interplay between these receptor subtypes in the brain.
Second harmonic nanoparticles in imaging applications

Nanocrystals with second harmonic response is a new class of nonlinear optical nanoprobes with dramatically different properties from fluorescent agents. Compared with two-photon fluorescence, second harmonic generation is an ultrafast, lossless, and coherent process. In particular, the absence of photobleaching and emission intermittency in the optical response of the second harmonic nanoparticles is likely to complement the fluorescent agents widely used today in many imaging applications. Furthermore, the coherent emission from the second harmonic generation process provides unique opportunities for the application of coherence domain techniques that are not available with fluorescent agents. We review the application of the second harmonic nanocrystals in imaging applications, especially those pertaining to biomedicine.
The study of palliative therapy for intranasal tumors in dogs ( 犬の鼻腔腫瘍における緩和療法に関する研究)

An ideal head-immobilization method provides a high level of accuracy and reproducibility in the immobilization. Various head-immobilization methods for radiotherapy have been published and are excellent in terms of accuracy; however, these methods are complicated to use and labor intensive. This study describes 2 new bite-block-type head-immobilization devices designed for greater stability and decreased vertical variation. The device designed in our previous study (“the bite-block-type head-immobilization device”; Device A) was modified by creating a groove on the upper surface of the horizontal plate (Device B) for a stable ventral–dorsal position or on the underside of the horizontal plate (Device C) for a stable dorsal–ventral position. These 3 devices were objectively compared with respect to setup time and accuracy of computed tomography (CT) images by 2 independent authors. Five healthy male beagles were used in this study. For each device, the setup time and variation in the coordinates were measured 5 times for each dog. The median setup time for Devices A, B, and C was 3.1, 1.6, and 2.3 min, respectively, showing that the groove modifications enabled reduced setup time (in Device B, by at least 50%). Moreover, three-dimensional analysis of the CT images revealed that the measurement variability of Device A (median, 1.3 mm) was significantly higher than that of Device C (median, 0.6 mm; p < 0.001). Collectively, our results show that use of a bite-block-type head-immobilization device
Compliance with established guidelines for the radiological reporting of atypical femoral fractures.

OBJECTIVE Atypical femoral fractures (AFFs) are important to diagnose early to avoid progression to complete fracture. We set out to determine the reporting accuracy of AFFs. METHODS We conducted a retrospective analysis of imaging performed between November 2010 and June 2013 to analyse the X-ray reporting of AFFs and to describe the key clinical considerations. Radiological reports were reviewed from the 3805 separate femoral images for search terms thought likely to identify AFFs. This identified 1558 patients. The identified radiographs were reviewed by radiologists with reference to the 2010 American Society of Bone and Mineral Research (ASBMR) criteria. RESULTS Within these 1558 patients, 16 patients met the radiological criteria for AFF according to the 2010 ASBMR task force statement of which, although all were identified as fractures, 15 were not reported as "atypical" by the original reporting author and none was formally classified as AFF by the original reporting author. Within the 1558 patients, there were an additional 17 patients labelled as having "atypical" fracture features originally, although only 1 patient met the 2010 ASBMR task force criteria for AFF. Only 13 of 16 patients had imaging of the contralateral femur, and there was a significant delay for those who were imaged (111 ± 44 days). Furthermore, two of the patients with an AFF had previous radiographs demonstrating cortical changes indicative of AFFs prior to formal diagnosis. CONCLUSION Whilst AFFs are rare diagnoses, the compliance with published guidelines for their radiological classification is low. ADVANCES IN KNOWLEDGE We have raised awareness of the importance of recognizing AFFs to guide management.
Effect of crosslinking on the elasticity of polyelectrolyte multilayer films measured by colloidal probe AFM

A homemade colloidal probe atomic force microscope was used to perform nanoindentation with a spherical probe of 5 μm in diameter, at different approach velocities in order to extract the Young's modulus, E0, of poly(L‐lysine)/hyaluronan (PLL/HA) films. This parameter is of prime importance to control cellular adhesion. The films were either kept in their native form or cross‐linked with a mixture of 1‐ethyl‐3‐(3‐dimethyl aminopropyl)carbodiimide (EDC) and N‐hydrosulfosuccinimide (sulfo‐NHS), where the EDC concentration was varied from 1 up to 100 mg mL−1 (approximately from 5 to 500 mM). A model based on Hertz mechanics was used to account for the interactions between film and probe. It is shown that the Young's modulus varies with the approach velocity for the native (PLL/HA) films, whereas for cross‐linked ones, E0 is independent from the velocity over the whole range investigated. It is found that for native films, E0 takes a value of 3 kPa at low approach velocities, a velocity domain that should be relevant in cellular adhesion processes. The Young's modulus increases with the EDC concentration used to cross‐link the films and levels off at a value of about 400 kPa for EDC concentrations exceeding 40 mg mL−1. Thus, it is possible by crosslinking PLL/HA films to control their elastic properties with the aim to alter their behavior as to the cellular adhesion. Microsc. Res. Tech. 69:84–92, 2006. © 2006 Wiley‐Liss, Inc.
Tobamovirus 3′-Terminal Gene Overlap May be a Mechanism for within-Host Fitness Improvement

Overlapping genes (OGs) are a universal phenomenon in all kingdoms, and viruses display a high content of OGs combined with a high rate of evolution. It is believed that the mechanism of gene overlap is based on overprinting of an existing gene. OGs help virus genes compress a maximum amount of information into short sequences, conferring viral proteins with novel features and thereby increasing their within-host fitness. Analysis of tobamovirus 3′-terminal genes reveals at least two modes of OG organization and mechanisms of interaction with the host. Originally isolated from Solanaceae species, viruses (referred to as Solanaceae-infecting) such as tobacco mosaic virus do not show 3′-terminal overlap between movement protein (MP) and coat protein (CP) genes but do contain open reading frame 6 (ORF6), which overlaps with both genes. Conversely, tobamoviruses, originally isolated from Brassicaceae species (referred to as Brassicaceae-infecting) and also able to infect Solanaceae plants, have no ORF6 but are characterized by overlapping MP and CP genes. Our analysis showed that the MP/CP overlap of Brassicaceae-infecting tobamoviruses results in the following: (i) genome compression and strengthening of subgenomic promoters; (ii) CP gene early expression directly from genomic and dicistronic MP subgenomic mRNA using an internal ribosome entry site (IRES) and a stable hairpin structure in the overlapping region; (iii) loss of ORF6, which influences the symptomatology of Solanaceae-infecting tobamoviruses; and (iv) acquisition of an IRES polypurine-rich region encoding an MP nuclear localization signal. We believe that MP/CP gene overlap may constitute a mechanism for host range expansion and virus adjustment to Brassicaceae plants.
Quantitative analysis of variable‐angle total internal reflection fluorescence microscopy (VA‐TIRFM) of cell/substrate contacts

Variable‐angle total internal reflection fluorescence microscopy (VA‐TIRFM) allows controlled variation of the illumination depth with the potential of measuring both membrane/substrate separation distances and sizes of focal contacts. VA‐TIRFM images are collected from well‐spread bovine aortic endothelial cells (BAEC) stained with a membrane‐bound carbocyanine dye. Quantitative determination of absolute membrane/substrate separation distances and individual focal contact area are attempted using a simplified model of TIRFM optics. For angles slightly greater than the critical angle of 64°, both the dorsal and ventral membranes were illuminated, while images excited above 66° illuminated only focal contacts. Above 74° the fluorescence of focal contacts was dominated by background noise. Direct application of the simplified optical model without accounting for background intensity was unsatisfactory. However, correction for background fluorescence and nonlinear regression of the untransformed data over the working range yielded focal contact separation distances of 24 ± 13 nm. Focal contact areas estimated by TIRFM (1·3 ± 0·7 μm2) agreed closely with areas observed by immunofluorescence staining of vinculin (1·5 ± 0·3 μm2).
Cystoid Macular Edema Associated With Topical Latanoprost in Glaucomatous Eyes With a Normally Functioning Blood–Ocular Barrier

PurposeTo study prospectively using optical coherence tomography (OCT) whether topical latanoprost induces retinal disorders, such as cystoid macular edema, in patients with glaucoma and a normally functioning blood–ocular barrier. MethodsSixty-eight eyes of 38 patients with glaucoma and no history of intraocular surgery, uveitis, or laser trabeculoplasty were studied. Before initiation of latanoprost treatment and after 1, 3, and 6 months of treatment, OCT images were taken, and the following tests were performed: visual acuity examination, fundus ophthalmoscopy, intraocular pressure measurement, and fundus color photography. To evaluate retinal thickness in the fovea accurately, OCT scanning was repeated six times, and the smallest value was used as the retinal thickness in the fovea. ResultsLatanoprost ophthalmic solution did not influence retinal thickness in the fovea at any investigated time points compared with the time before instillation, and no changes were observed in visual acuity, ophthalmoscopic findings, and fundus photographs. The intraocular pressure was reduced significantly at all investigated time points compared with the time before instillation. ConclusionsIt is unlikely that topical latanoprost induces retinal disorders, such as cystoid macular edema, in glaucomatous eyes with a normally functioning blood–ocular barrier.
Quantifying the Influence of Network Conditions on the Service Quality Experienced by a Thin Client User

Quality of Experience (QoE) is a measure for the satisfaction of a user with a given service. Despite the popularity of the term, there is a lack of understanding of how to capture or quantify QoE. In this paper we therefore take a step forward in this direction using the example of thin client architectures, where the client is only used as a dumb terminal while the applications run on a central server. The satisfaction of a thin client user is thus heavily influenced by the quality of the network connection between the client and the server. We study this influence by varying different network parameters like packet loss, jitter, and delay in a controlled testbed environment. The service quality is assessed using objective measurements on application level (oQoE) and verified by means of a survey among test persons capturing subjective user satisfactions (sQoE).
Slew/Translation Positioning and Swing Suppression for 4-DOF Tower Cranes With Parametric Uncertainties: Design and Hardware Experimentation

As a powerful large-scale construction tool, a tower crane is a strongly nonlinear underactuated system presenting complicated dynamical characteristics. Existing control methods for tower cranes are developed on the basis of simplified (i.e., linearized/approximated) crane dynamics, and most of them require exact model knowledge. However, practical tower cranes usually suffer from uncertainties (e.g., unknown rope length and payload mass); moreover, when the state variables are not close enough to the equilibrium point due to unexpected disturbances, simplified models might not reflect the actual dynamics any longer, which usually badly degrades the control performance. To tackle these problems, this paper proposes an adaptive control scheme for underactuated tower cranes to achieve simultaneous slew/translation positioning and swing suppression, which can reduce unexpected overshoots for the jib/trolley movements. The closed-loop stability is backed up with the rigorous mathematical analysis. To the best of our knowledge, the proposed controller is the first method for tower cranes with parametric uncertainties, which is developed without linearizing/approximating their nonlinear dynamics. Finally, we introduce our self-built multifunctional hardware crane experiment testbed and present experimental studies for the proposed method. Experimental results show that the new control approach is effective and admits satisfactory robustness.
Improved BP Neural Network for Intrusion Detection Based on AFSA

Establishing a complete information security policy is the most important step to solve the problem of information security and the basis for the entire information security system. Using intrusion detection technology to identify the source of threats and adjusting security policy is an effective operation of network protection. Trained BP neural network model is usually adopted as detector, but because of defects of weights training algorithm of BPNN, the weights always fall into local minima area. In order to address this problem, we propose a detection model based on BP neural network training by AFSA (Artificial Fish Swarming Algorithm). The algorithm optimizes the weights of BP neural network by AFSA. It shortens the sample training time and improves BP neural network classification accuracy. Experimental results demonstrated that it has a shorter training time and can achieve a superior detection rate than BPNN.
Joint Signal Alignment and Power Allocation for a Diagonalized AF MIMO Two-Way Relay Channel

This paper uses generalized singular value decomposition (GSVD) to reduce decoding complexity in an amplify-andforward, multiple-input multiple-output, two-way relay channel (TWRC). The key is diagonalization of the effective channels at the source nodes; this formulation also simplifies the optimization problem of designing linear transceivers at each node to maximize the achievable sum rate (ASR). For the given diagonalized structure, we first align the entries of the diagonalized channels using a permutation followed by power allocation, provided in closed form. Simulation results demonstrate that the proposed GSVD-based relaying scheme, with the signal alignment and power allocation, significantly improves the ASR while retaining the diagonalized channel structure.
Interrelationships and evolution of the tapeworms (Platyhelminthes: Cestoda).

Interrelationships of the tapeworms (Platyhelminthes: Cestoda) were examined by use of small (SSU) and large (LSU) subunit ribosomal DNA sequences and morphological characters. Fifty new complete SSU sequences were added to 21 sequences previously determined, and 71 new LSU (D1-D3) sequences were determined for the complementary set of taxa representing each of the major lineages of cestodes as currently understood. New sequences were determined for three amphilinidean taxa, but were removed from both alignments due to their excessively high degree of divergence from other cestode sequences. A morphological character matrix coded for supraspecific taxa was constructed by the modification of matrices from recently published studies. Maximum-parsimony (MP) analyses were performed on the LSU, SSU, LSU+SSU, and morphological data partitions, and minimum-evolution (ME) analyses utilizing a general time reversible model of nucleotide substitution including estimates of among-site rate heterogeneity were performed on the molecular data partitions. Resulting topologies were rooted at the node separating the Gyrocotylidea from the Eucestoda. The LSU data were found to be more informative than the SSU data and were more consistent with inferences from morphology, although nodal support was generally weak for most basal nodes. One class of transitions was found to be saturated for comparisons between the most distantly related taxa (gyrocotylideans vs cyclophyllideans and tetrabothriideans). Differences in the topologies resulting from MP and ME analyses were not statistically significant. Nonstrobilate orders formed the basal lineages of trees resulting from analysis of LSU data and morphology. Difossate orders were basal to tetrafossate orders, the latter of which formed a strongly supported clade. A clade including the orders Cyclophyllidea, Nippotaeniidea, and Tetrabothriidea was supported by all data partitions and methods of analysis. Paraphyly of the orders Pseudophyllidea, Tetraphyllidea, and Trypanorhyncha was consistent among the molecular data partitions. Inferences are made regarding a monozoic (nonsegmented) origin of the Eucestoda as represented by the Caryophyllidea and for the evolution of the strobilate and acetabulate/tetrafossate conditions having evolved in a stepwise pattern.
Grandfathers, Google, and Dreams: Medical Pluralism, Globalization, and New Healing Encounters in Ghana

Across contemporary Africa, pluralistic medical fields are becoming increasingly complex, giving rise to newly emerging constellations of healing practices and a vast array of therapeutic possibilities. We present portraits of four ‘traditional’ healers in southern Ghana who selectively adapt, adopt, and modify elements of biomedical, ‘local,’ and ‘exotic’ healing practices in eclectic and creative ways, positioning themselves strategically in a highly pluralistic, contested, and globalized medical arena. Their practices are informed by ‘traditional’ knowledge, passed down through families and acquired through spiritually directed dreams, but also from medical textbooks, Google searches, ‘scientific’ experimentation, and interactions with the biomedical sector. The healers make use of modern information and communication technologies to increase their geographical reach, and respond to the opportunities and risks of an increasingly global but strongly differentiated therapeutic market. However, while apparently transgressing therapeutic boundaries, they are simultaneously drawing on a discourse of stabilizing and straddling those boundaries to legitimize their practices.
Mechanism of biosynthesis of unsaturated fatty acids in Pseudomonas sp. strain E-3, a psychrotrophic bacterium

Biosynthesis of palmitic, palmitoleic, and cis-vaccenic acids in Pseudomonas sp. strain E-3 was investigated with in vitro and in vivo systems. [1-14C]palmitic acid was aerobically converted to palmitoleate and cis-vaccenate, and the radioactivities on their carboxyl carbons were 100 and 43%, respectively, of the total radioactivity in the fatty acids. Palmitoyl coenzyme A desaturase activity was found in the membrane fraction. [1-14C]stearic acid was converted to octadecenoate and C16 fatty acids. The octadecenoate contained oleate and cis-vaccenate, but only oleate was produced in the presence of cerulenin. [1-14C]lauric acid was aerobically converted to palmitate, palmitoleate, and cis-vaccenate. Under anaerobic conditions, palmitate (62%), palmitoleate (4%), and cis-vaccenate (34%) were produced from [1-14C]acetic acid, while they amounted to 48, 39, and 14%, respectively, under aerobic conditions. In these incorporation experiments, 3 to 19% of the added radioactivity was detected in released 14CO2, indicating that part of the added fatty acids were oxidatively decomposed. Partially purified fatty acid synthetase produced saturated and unsaturated fatty acids with chain lengths of C10 to C18. These results indicated that both aerobic and anaerobic mechanisms for the synthesis of unsaturated fatty acid are operating in this bacterium.
Hybrid Active Filter with Variable Conductance for Harmonic Suppression

The tuned passive filter and the line inductance, causes unintentional series and/or parallel resonances, may result in severe harmonic distortion in the industrial power system. Here we present a paper in which hybrid active filter is used to suppress harmonic resonance and to reduce harmonic distortion. The proposed hybrid filter is operated as variable harmonic conductance according to the voltage total harmonic distortion; therefore, harmonic distortion can be reduced to an acceptable level in response to load change or parameter variation of the power system. Since the hybrid filter is composed of a seventh-tuned passive filter and an active filter in series connection, both DC voltage and kVA rating of the active filter are dramatically decreased compared with the pure shunt active filter. In real application, this feature is very attractive since the active power filter with fully power electronics is very expensive. A reasonable trade off between filtering performances and cost is to use the hybrid active filter. Design consideration is presented, and experimental results are provided to validate effectiveness of the proposed method. Furthermore, this paper discusses filtering performances on line impedance, line resistance, voltage unbalance, and capacitive filters. Keywords— Harmonic resonance, hybrid active filter, industrial power system.