Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Alterations in Dog Pheochromocytomas and Paragangliomas

Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways.
The influence of IMF By on the nature of the nightside high-latitude ionospheric flow during intervals of positive IMF Bz

This paper further addresses the issue of nightside flow bursts which occur during intervals of northward but strongly BY-influenced IMF. Recent discussions of such bursts concerned intervals during which the IMF BY component was negative. The present study concerns an interval of BY-positive IMF which occurred on 20 March 2002 (01:00-12:00UT). During the interval BY increased steadily from ~2 to 12nT, whilst the BZ component decreased steadily from ~10 to 0nT. There was thus a ~6-h sub-interval during which the IMF clock angle remained between 30° and 60°, such that moderate dayside reconnection and open flux production was maintained. It is found that flow bursts of a similar size and speed to those observed under BY negative (~1000m s-1, spanning 2-3h of MLT in the midnight sector) also occur when BY is positive. However, the direction of east-west flow is reversed, indicating that they are driven by processes in the magnetosphere which are directly related to the orientation of the IMF. It is suggested that they are caused by a reconfiguration of an asymmetric tail resulting from prolonged dayside reconnection with a BY-dominated IMF. This is consistent with previous suggestions that they are associated with convective transport following reconnection in the more distant tail. Analysis of ground magnetic data, auroral images and geosynchronous particle data also show associated features, but indicate that the flow bursts are not directly associated with substorms.
Biochemical reconstitution of UV-induced mutational processes

Abstract We reconstituted two biochemical processes that may contribute to UV-induced mutagenesis in vitro and analysed the mutational profiles in the products. One process is translesion synthesis (TLS) by DNA polymerases (Pol) δ, η and ζ, which creates C>T transitions at pyrimidine dimers by incorporating two dAMPs opposite of the dimers. The other process involves spontaneous deamination of cytosine, producing uracil in pyrimidine dimers, followed by monomerization of the dimers by secondary UV irradiation, and DNA synthesis by Pol δ. The mutational spectrum resulting from deamination without translesion synthesis is similar to a mutational signature found in melanomas, suggesting that cytosine deamination encountered by the replicative polymerase has a prominent role in melanoma development. However, CC>TT dinucleotide substitution, which is also commonly observed in melanomas, was produced almost exclusively by TLS. We propose that both TLS-dependent and deamination-dependent mutational processes are likely involved in UV-induced melanoma development.
On the Choice of Regions for Generalized Belief Propagation

Generalized belief propagation (GBP) has proven to be a promising technique for approximate inference tasks in AI and machine learning. However, the choice of a good set of clusters to be used in GBP has remained more of an art then a science until this day. This paper proposes a sequential approach to adding new clusters of nodes and their interactions (i.e. "regions") to the approximation. We first review and analyze the recently introduced region graphs and find that three kinds of operations ("split", "merge" and "death") leave the free energy and (under some conditions) the fixed points of GBP invariant. This leads to the notion of "weakly irreducible" regions as the natural candidates to be added to the approximation. Computational complexity of the GBP algorithm is controlled by restricting attention to regions with small "region-width". Combining the above with an efficient (i.e. local in the graph) measure to predict the improved accuracy of GBP leads to the sequential "region pursuit" algorithm for adding new regions bottom-up to the region graph. Experiments show that this algorithm can indeed perform close to optimally.
Susceptibility Testing with the Manual Mycobacteria Growth Indicator Tube (MGIT) and the MGIT 960 System Provides Rapid and Reliable Verification of Multidrug-Resistant Tuberculosis

ABSTRACT The objective of the study was to compare the manual Mycobacteria Growth Indicator Tube (MGIT) method and the BACTEC MGIT 960 system to the BACTEC 460 method for susceptibility testing of Mycobacterium tuberculosis. The evaluation was based on testing of 36 M. tuberculosis strains with various susceptibilities to isoniazid (INH), rifampin (RMP), ethambutol (EMB), and streptomycin (SM). In addition, five of the strains generating discrepant results in testing for EMB were analyzed for heteroresistance. For INH, the susceptibility test results obtained by the MGIT 960 and the manual MGIT systems agreed with the BACTEC 460 results in 94 and 97% of the cases, respectively. The results of susceptibility to RMP were all in agreement. For SM, 78 and 72% of the results obtained by the MGIT 960 and the manual MGIT systems, respectively, agreed with the BACTEC 460 results. In contrast, less than 80% of the results for susceptibility to EMB obtained by the two MGIT methods agreed with the BACTEC 460 results. All five strains analyzed for EMB heteroresistance were found to consist of resistant and susceptible subpopulations. The average turnaround times were 6.4 days for the MGIT 960 system, 6.5 for the manual MGIT system, and 8.7 days for the BACTEC 460 method. Both MGIT methods can be regarded as accurate and rapid alternatives to the BACTEC 460 method for detection of strains resistant to INH and RMP. However, more studies are needed for solving the problems associated with susceptibility testing to EMB and SM.
Unveiling optical in-plane anisotropy of 2D materials from oblique incidence of light

In this work, we present a theoretical study of the dispersion of linearly polarized light between two dielectric media separated by an anisotropic two-dimensional (2D) material under oblique incidence. Assuming that the 2D material is a conducting sheet of negligible thickness, generalized Fresnel coefficients are derived as a function of usual quantities (e.g. refraction indexes and scattering angles) and the anisotropic in-plane optical conductivity of the interstitial 2D material. In particular, we analyzed the modifications due to the 2D material of two classical optical phenomena: the Brewster effect and the total internal reflection. As a application, our general findings are particularized for uniaxially strained graphene. Effects of a uniaxial strain on the Brewster angle and the reflectance (under total internal reflection) are evaluated as a function of the magnitude and direction of strain.
Biomechanical properties of marsh vegetation in space and time: effects of salinity, inundation and seasonality.

BACKGROUND AND AIMS Over the last decade, the importance of plant biomechanical properties in shaping wave dissipation efficiency of marsh vegetation has gained growing attention. Here we provide the first analyses of how biomechanical stem properties vary with seasons and along environmental gradients in coastal and estuarine marshes, which is essential to enable accurate assessments of flood defence value of marsh vegetation. METHODS We quantified both spatial and seasonal variation in stem flexibility and breakability for a variety of common marsh vegetation (Spartina anglica, Scirpus maritimus, Phragmites australis, Elymus athericus, Suaeda maritima, Aster tripolium, Saliconia procumbens) distributed along both salinity and inundation gradients. KEY RESULTS Increasing salinity tends to induce a shift from species with tall shoots, high flexural stiffness (stem resistance to bending; N mm2) towards species with shorter and more flexible stems. The same trend was found with increasing inundation stress (i.e. decreasing elevation) from the higher part of the low marsh towards the pioneer zone. Stem breakability (the force required to break or fold a stem, N) followed the same pattern of stem stiffness due to the positive relationship between flexural strength (material resistance to flexure, N mm-2) and Young's bending modulus (material resistance to bending; N mm-2). Shifts in stem stiffness and breakability at the community level were found to relate positively to the variation in canopy height between species, highlighting the concurrence of changes in morphological and biomechanical traits under environmental changes. Compared to the differences between species, within-species variability between sampling locations and between seasons is generally minor. CONCLUSIONS Our findings imply that environmental changes may significantly modify wave attenuation capacity of coastal vegetation by inducing species shifts. This emphasizes the need to understand the response of community composition to climate change and human disturbances, when using nature-based flood protection by coastal vegetation as an adaptive response to global change.
Touch-Typing Detection Using Eyewear: Toward Realizing a New Interaction for Typing Applications †

Typing skills are important in the digital information society of this generation. As a method to improve typing speed, in this study, we focused on the training of touch typing that enables typing a key without looking at the keyboard. For support of touch-typing training, it is efficient to apply a penalty if a learner looks at the keyboard; however, to realize the penalty method, the computer needs to be able to recognize whether the learner looked at the keyboard. We, therefore, proposed a method to detect a learner’s eye gaze, namely, using eyewear to detect whether the learner looked at the keyboard, and then evaluating the detection accuracy of our proposed method. We examined the necessity for our system by analyzing the relationship between a learner’s eye gaze and touch-typing skills.
Carbon Dioxide Permeability of Aquaporin-1 Measured in Erythrocytes and Lung of Aquaporin-1 Null Mice and in Reconstituted Proteoliposomes*

Measurements of CO2permeability in oocytes and liposomes containing water channel aquaporin-1 (AQP1) have suggested that AQP1 is able to transport both water and CO2. We studied the physiological consequences of CO2 transport by AQP1 by comparing CO2permeabilities in erythrocytes and intact lung of wild-type and AQP1 null mice. Erythrocytes from wild-type mice strongly expressed AQP1 protein and had 7-fold greater osmotic water permeability than did erythrocytes from null mice. CO2 permeability was measured from the rate of intracellular acidification in response to addition of CO2/HCO3 − in a stopped-flow fluorometer using 2′,7′-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein (BCECF) as a cytoplasmic pH indicator. In erythrocytes from wild-type mice, acidification was rapid (t 1 2 , 7.3 ± 0.4 ms, S.E., n = 11 mice) and blocked by acetazolamide and increasing external pH (to decrease CO2/HCO3 − ratio). Apparent CO2permeability (PCO2 ) was not different in erythrocytes from wild-type (0.012 ± 0.0008 cm/s)versus null (0.011 ± 0.001 cm/s) mice. Lung CO2 transport was measured in anesthetized, ventilated mice subjected to a decrease in inspired CO2 content from 5% to 0%, producing an average decrease in arterial bloodpCO2 from 77 ± 4 to 39 ± 3 mm Hg (14 mice) with a t 1 2 of 1.4 min. ThepCO2 values and kinetics of decreasing pCO2 were not different in wild-type versusnull mice. Because AQP1 deletion did not affect CO2transport in erythrocytes and lung, we re-examined CO2permeability in AQP1-reconstituted liposomes containing carbonic anhydrase (CA) and a fluorescent pH indicator. Whereas osmotic water permeability in AQP1-reconstituted liposomes was >100-fold greater than that in control liposomes, apparent PCO2 (∼10−3 cm/s) did not differ. Measurements using different CA concentrations and HgCl2 indicated that liposome PCO2 is unstirred layer-limited and that HgCl2 slows acidification because of inhibition of CA rather than AQP1. These results provide direct evidence against physiologically significant AQP1-mediated CO2 transport and establish an upper limit to the CO2 permeability through single AQP1 water channels.
An information-theoretic approach to autonomous navigation and guidance of an uninhabited aerial vehicle in unknown environments

This paper presents an intelligent, on-line guidance scheme for maximising vehicle navigation and snap information for an uninhabited aerial vehicle while operating over unknown terrain. The tasks of localisation and mapping are performed concurrently using the well known extended Kalman filter implementation of the simultaneous localisation and mapping (SLAM) algorithm. A guidance scheme is formulated using vehicle actions in order to maximise the quality of the resulting vehicle pose estimates and environment map by maximising the entropic information in vehicle and map estimates. Results are presented using a high-fidelity six-degree of freedom simulation of an aerial vehicle using inertial navigation and a range/hearing sensor.
Surface Characteristics of Esthetic Nickel–Titanium and Beta-Titanium Orthodontic Archwires Produced by Plasma Electrolytic Oxidation (PEO)—Primary Results

Background/Aim: There is continuing interest in engineering esthetic labial archwires. The aim of this study was to coat nickel–titanium (NiTi) and beta-titanium (β-Ti), also known as titanium molybdenum (TMA), archwires by plasma electrolytic oxidation (PEO) and to analyze the characteristics of the PEO-surfaces. Materials and Methods: PEO-coatings were generated on 0.014-inch NiTi and 0.19 × 0.25-inch β-Ti archwires. The surfaces were analyzed by scanning electron microscopy and stereomicroscopy. Cytocompatibility testing was performed with ceramized and untreated samples according to EN ISO 10993-5 in XTT-, BrdU- and LDH-assays. The direct cell impact was analyzed using LIVE-/DEAD-staining. In addition, the archwires were inserted in an orthodontic model and photographs were taken before and after insertion. Results: The PEO coatings were 15 to 20 µm thick with a whitish appearance. The cytocompatibility analysis revealed good cytocompatibility results for both ceramized NiTi and β-Ti archwires. In the direct cell tests, the ceramized samples showed improved compatibility as compared to those of uncoated samples. However, bending of the archwires resulted in loss of the PEO-surfaces. Nevertheless, it was possible to insert the β-Ti PEO-coated archwire in an orthodontic model without loss of the PEO-ceramic. Conclusion: PEO is a promising technique for the generation of esthetic orthodontic archwires. Since the PEO-coating does not resist bending, its clinical use seems to be limited so far to orthodontic techniques using straight or pre-bent archwires.
Deficiency of Small Gtpase Rac2 Affects T Cell Activation

Rac2 is a hematopoietic-specific GTPase acting as a molecular switch to mediate both transcriptional activation and cell morphological changes. We have examined the effect of Rac2 deficiency during T cell activation. In Rac2−/− T cells, proliferation was reduced upon stimulation with either plate-bound anti-CD3 or T cell receptor–specific antigen. This defect is accompanied with decreased activation of mitogen activated protein kinase extracellular signal–regulated kinase (ERK)1/2 and p38, and reduced Ca2+ mobilization. TCR stimulation–induced actin polymerization is also reduced. In addition, anti-CD3 cross-linking–induced T cell capping is reduced compared with wild-type T cells. These results indicate that Rac2 is important in mediating both transcriptional and cytoskeletal changes during T cell activation. The phenotypic similarity of Rac2−/− to Vav−/− cells implicates Rac2 as a downstream mediator of Vav signaling.
Plasmonics with Metallic Nanowires

The purpose of this review is to introduce and present the concept of metallic nanowires as building-blocks of plasmonically active structures. In addition to concise description of both the basic physical properties associated with the electron oscillations as well as energy propagation in metallic nanostructures, and methods of fabrication of metallic nanowires, we will demonstrate several key ideas that involve interactions between plasmon excitations and electronic states in surrounding molecules or other emitters. Particular emphasis will be placed on the effects that involve not only plasmonic enhancement or quenching of fluorescence, but also propagation of energy on lengths that exceed the wavelength of light.
Toward stable gene expression in CHO cells

Maintaining high gene expression level during long-term culture is critical when producing therapeutic recombinant proteins using mammalian cells. Transcriptional silencing of promoters, most likely due to epigenetic events such as DNA methylation and histone modifications, is one of the major mechanisms causing production instability. Previous studies demonstrated that the core CpG island element (IE) from the hamster adenine phosphoribosyltransferase gene is effective to prevent DNA methylation. We generated one set of modified human cytomegalovirus (hCMV) promoters by insertion of one or two copies of IE in either forward or reverse orientations into different locations of the hCMV promoter. The modified hCMV with one copy of IE inserted between the hCMV enhancer and core promoter in reverse orientation (MR1) was most effective at enhancing expression stability in CHO cells without comprising expression level when compared with the wild type hCMV. We also found that insertion of IE into a chimeric murine CMV (mCMV) enhancer and human elongation factor-1α core (hEF) promoter in reverse orientation did not enhance expression stability, indicating that the effect of IE on expression stability is possibly promoter specific.
Waveforms for the Massive MIMO Downlink: Amplifier Efficiency, Distortion, and Performance

In massive multiple-input multiple-output (MIMO), most precoders result in downlink signals that suffer from high peak-to-average ratio (PAR), independently of modulation order and whether single-carrier or orthogonal frequency-division multiplexing (OFDM) transmission is used. The high PAR lowers the power efficiency of the base-station amplifiers. To increase the power efficiency, low-PAR precoders have been proposed. In this paper, we compare different transmission methods for massive MIMO in terms of the power consumed by the amplifiers. It is found that: 1) OFDM and single-carrier transmission have the same performance over a hardened massive MIMO channel and 2) when the higher amplifier power efficiency of low-PAR precoding is taken into account, conventional and low-PAR precoders lead to approximately the same power consumption. Since downlink signals with low PAR allow for simpler and cheaper hardware, than signals with high PAR, therefore, the results suggest that low-PAR precoding with either single-carrier or OFDM transmission should be used in a massive MIMO base station.
Crystallization Tendency of Pharmaceutical Glasses: Relevance to Compound Properties, Impact of Formulation Process, and Implications for Design of Amorphous Solid Dispersions

Amorphous solid dispersions (ASDs) are important formulation strategies for improving the dissolution process and oral bioavailability of poorly soluble drugs. Physical stability of a candidate drug must be clearly understood to design ASDs with superior properties. The crystallization tendency of small organics is frequently estimated by applying rapid cooling or a cooling/reheating cycle to their melt using differential scanning calorimetry. The crystallization tendency determined in this way does not directly correlate with the physical stability during isothermal storage, which is of great interest to pharmaceutical researchers. Nevertheless, it provides important insights into strategy for the formulation design and the crystallization mechanism of the drug molecules. The initiation time for isothermal crystallization can be explained using the ratio of the glass transition and storage temperatures (Tg/T). Although some formulation processes such as milling and compaction can enhance nucleation, the Tg/T ratio still works for roughly predicting the crystallization behavior. Thus, design of accelerated physical stability test may be possible for ASDs. The crystallization tendency during the formulation process and the supersaturation ability of ASDs may also be related to the crystallization tendency determined by thermal analysis. In this review, the assessment of the crystallization tendency of pharmaceutical glasses and its relevance to developmental studies of ASDs are discussed.
Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro

High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile for HPV-related cancers, this study aims to explore the effects of length of ligand spacers of folate-targeted liposomes on the efficiency of ATO delivery to HPV-infected cells. Fluorescent ATO encapsulated liposomes with folic acid (FA) conjugated to two different PEG lengths (2000 Da and 5000 Da) were synthesised, and their cellular uptake was examined for HPV-positive HeLa and KB and HPV-negative HT-3 cells using confocal microscopy, flow cytometry, and spectrophotometer readings. Cellular arsenic quantification and anti-tumour efficacy was evaluated through inductively coupled plasma-mass spectrometry (ICP-MS) and cytotoxicity studies, respectively. Results showed that liposomes with a longer folic acid-polyethylene glycol (FA-PEG) spacer (5000 Da) displayed a higher efficiency in targeting folate receptor (FR) + HPV-infected cells without increasing any inherent cytotoxicity. Targeted liposomally delivered ATO also displayed superior selectivity and efficiency in inducing higher cell apoptosis in HPV-positive cells per unit of arsenic taken up than free ATO, in contrast to HT-3. These findings may hold promise in improving the management of HPV-associated cancers.