Miracle-dz/UniFAR-FTUs huggingface dataset:
F-SNP: computationally predicted functional SNPs for disease association studies

The Functional Single Nucleotide Polymorphism (F-SNP) database integrates information obtained from 16 bioinformatics tools and databases about the functional effects of SNPs. These effects are predicted and indicated at the splicing, transcriptional, translational and post-translational level. As such, the database helps identify and focus on SNPs with potential deleterious effect to human health. In particular, users can retrieve SNPs that disrupt genomic regions known to be functional, including splice sites and transcriptional regulatory regions. Users can also identify non-synonymous SNPs that may have deleterious effects on protein structure or function, interfere with protein translation or impede post-translational modification. A web interface enables easy navigation for obtaining information through multiple starting points and exploration routes (e.g. starting from SNP identifier, genomic region, gene or target disease). The F-SNP database is available at http://compbio.cs. queensu.ca/F-SNP/.
Distribution of Radioactivity in Plasma After Feeding Tritiated 7, 12-Dimethylbenz(a)anthracene.∗

Summary The appearance of tritiated 7, 12-dimethylbenz(a)anthracene in blood after oral administration to rats was determined and its distribution in plasma investigated. Initially the radioactivity was associated with neutral fat but after some hours the hydrocarbon migrated on electrophoresis with the albumin fraction.
Origins of Aminergic Regulation of Behavior in Complex Insect Social Systems

Neuromodulators are conserved across insect taxa, but how biogenic amines and their receptors in ancestral solitary forms have been co-opted to control behaviors in derived socially complex species is largely unknown. Here we explore patterns associated with the functions of octopamine (OA), serotonin (5-HT) and dopamine (DA) in solitary ancestral insects and their derived functions in eusocial ants, bees, wasps and termites. Synthesizing current findings that reveal potential ancestral roles of monoamines in insects, we identify physiological processes and conserved behaviors under aminergic control, consider how biogenic amines may have evolved to modulate complex social behavior, and present focal research areas that warrant further study.
Fabrication and characterisation of ultrafast direct laser written waveguides

A novel ultrafast direct laser writing (DLW) system using adaptive optics is proposed and demonstrated. This system has the potential to generate high-quality three-dimensional (3D) optical waveguides and components. The experimental setup and procedures for the DLW process are studied, after which various optical waveguides are fabricated in different transparent materials. The resulting waveguides are characterised by the measurement of the near-field laser coupling profiles in combination with optical microscopy techniques. Quantum random number generation (QRNG) and the potential application of the DLW technique in quantum information is also discussed. To completely understand the fabrication procedures for the DLW system, the experimental equipment and effects of different fabrication parameters are studied and analysed. With the use of a liquid-crystal spatial light modulator (SLM) in the DLW system, dynamic control of phase modulation can be provided to correct aberrations adaptively. An SLM can also make the cross-sectional profile of the written waveguides more circular and facilitate the fabrication of more complex 3D structures. Experiments reveal that the shape of the focal spot can be improved dramatically with adaptive optics, resulting in higher-quality optical waveguides. The refractive-index information of the written waveguides and their optical properties are measured using the propagation-mode near-field method (PMNFM). Simulation results and experimental measurements of a commercial single-mode fiber and a waveguide sample are demonstrated and compared. Quantitative phase measurement is also applied via the transport of intensity equation (TIE) to monitor the refractive-index change during fabrication. The propagation losses of the waveguides are measured and discussed. Different optical waveguides are fabricated using DLW in fused silica, potassium dihydrogen phosphate (KDP), and lithium niobate (LiNbO3) crystals. Different materials have different characteristics and properties, requiring different fabrication parameters and resulting in waveguides exhibiting different properties. Waveguides at various depths are demonstrated both with and without effects of adaptive optics. Experimental results indicate great improvements in the quality of the written waveguides after aberration correction. With an understanding of the optical properties of the straight waveguides using the characterisation methods, modelling and fabrication of bend waveguides and y-splitters are presented and studied. A high-speed QRNG system is also demonstrated in this thesis, with potential implementation using the DLW technique for a more compact and stable system. Finally, the possibility of the DLW fabrication of complex 3D optical components and their applications are discussed for future work.
Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer

A companion diagnostic assay was codeveloped by Dako for pembrolizumab non–small-cell lung cancer clinical trials to detect PD-L1 expression by immunohistochemistry (IHC). This automated IHC assay has been analytically verified and validated using Dako’s autostainer Link 48 and 22C3 mouse anti-PD-L1 monoclonal antibody to detect the PD-L1 expression in formalin-fixed paraffin-embedded human tumor tissue specimens. The PD-L1 22C3 IHC assay was optimized for high sensitivity and specificity. Repeatability and reproducibility studies were conducted at Dako and at 3 Clinical Laboratory Improvement Amendments certified laboratories during assay development. The studies included: intersite and intrasite, interobserver and intraobserver, interinstrument, interoperator, interday, and interlot, and intraday and intrarun. All precision studies performed at Dako and external laboratories achieved >85% point-estimate agreements for all 3 agreement types (negative, positive, and overall). A clinical cutoff (tumor proportion score ≥50%) of PD-L1 expression was determined and evaluated through a phase 1 clinical trial (KEYNOTE-001) for advanced non–small-cell lung cancer patients treated with pembrolizumab. The treatment effect of pembrolizumab in the 61 subjects who had a tumor PD-L1 of tumor proportion score ≥50% was substantial, with an overall response rate of 41% (95% confidence interval, 28.6-54.3) as compared with 20.6% (95% confidence interval, 15.5-26.5) observed in the 223 subjects irrespective of PD-L1 status. PD-L1 IHC 22C3 pharmDx is a sensitive, precise, and robust companion diagnostic assay, which will facilitate safe and effective use for pembrolizumab in cancer patients.
Steepened inner density profiles of group galaxies via interactions: An N-body analysis

We continue to see a range of values for the Hubble constant obtained from gravitationally lensed multiple image time-delays when assuming an isothermal lens despite a robust value from the Hubble Space Telescope (HST) key project (72 ± 8 km s -1 Mpc -1 ). One explanation is that there is a variation in Hubble constant values due to a fundamental heterogeneity in lens galaxies present in groups, that is, central galaxies with a high dark matter surface density, and satellite galaxies with a possibly stripped halo, low dark matter surface density, and a more centrally concentrated matter distribution. Our goal is to see if a variety of group interactions between the most-massive group members can result in significant changes in the galaxy density profiles over the scale probed by strong lensing ($15 kpc). While stripping of the outer parts of the halo can be expected, the impact on inner regions where the luminous component is important is less clear in the context of lensing, though still crucial, as a steepened density profile within this inner region allows these lens systems to be consistent with current HST/Wilkinson Microwave Anisotropy Probe (WMAP) estimates on H 0 . We employ the particle-mesh code SUPERBOX to carry out the group interaction simulations. An important advantage of using such a code is that it implements a fast, low-storage fast Fourier transform (FFT) algorithm allowing simulations with millions of particles on desk-top machines. We simulate interactions between group members, comparing the density profile for the satellite before and after interaction for the mass range of 1011 to 10 13 M ⊙ · Our investigations show a significant steepening of the density profile in the region of ∼5-20 kpc, i.e. that which dominates strong lensing in lens galaxies. This effect is independent of the initial mass-to-light ratio. Additionally, the steepening in the inner region is transient in nature, with consecutive interactions returning the profile to an isothermal state within a time-frame of ∼0.5-2.0 Gyr. This factor may help explain why lens galaxies that produce lower values of H 0 (i.e. those with possibly steeper profiles) are far fewer in number than those which agree with both the HST key project value for H 0 and isothermality, since one would have to observe the lens galaxy during this transient steepened phase.
Eight-Year Results of a Minimally Constrained Total Ankle Arthroplasty

Background: Few studies have reported the intermediate to long-term results of minimally constrained total ankle replacements. The purpose of this study was to investigate the efficacy and safety of a minimally constrained total ankle prosthesis in a select low-demand patient population. Methods: We reviewed a consecutive series of patients with rheumatoid arthritis who underwent a Buechel-Pappas total ankle replacement (BP TAR) between 1990 to 1997. Thirty-one ankle arthroplasties were performed in 23 patients with rheumatoid arthritis. One patient was lost to followup (deceased) and two ankles that failed resulted in fusion (overall survivorship − 93%). This left 28 ankles (21 patients) that were re-evaluated clinically and radiographically with an average followup of 8.3 (range 5.0 to 12.2) years. Preoperative and postoperative ranges of motion were measured and AOFAS hindfoot scores were calculated. Recent weightbearing radiographs were reviewed for evidence of component subsidence, radiolucent lines, and osteolysis. Results: In 25 of 28 ankles (89%), patients were completely satisfied with the result of their ankle replacement and rated their pain as only mild to none; three (11%) patients were dissatisfied. Radiographic analysis revealed stable, well-positioned implants with evidence of biologic ingrowth in 23 ankles (82%), while five implants were interpreted as being at risk for impending failure because of marked tibial or talar component subsidence (18%). Component subsidence did not correlate with the presence or absence of radiolucent lines. Only one ankle demonstrated clear evidence of osteolysis. Ten intraoperative medial malleolar fractures occurred (32% of ankles) during implantation of the prosthesis, though in only one did this adversely affect patient outcome. Nine postoperative complications (29%) occurred; four wound dehiscences, four stress fractures, and one medial malleolar nonunion. Conclusions: Improvements in prosthetic design such as cementless fixation and decreased constraint appear to make total ankle arthroplasty a more predictable procedure over this period of followup. Despite a variety of complications, we are encouraged by the intermediate-term results in a select low-demand arthritic population.
Recovering the shape of polyhedra using line-drawing analysis and complex reflectance models

Following Sugihara, we represent the geometric constraints imposed by the line-drawing of a polyhedron as a set of linear equalities and inequalities. Unlike him, we explicitly take into account the uncertainty in vertex position. This allows us to circumvent the superstrictness of the constraints without deleting any of them. For a given error bound, deciding whether a line-drawing is the correct projection of a polyhedron is reduced to linear programming, and 3D shape recovery is reduced to optimization under linear constraints. Our method can be used for recovering the shape of polyhedral objects whose reflectance can be modelled accurately. We have implemented if for the Lambertian model and the Lambertian model with interreflections. We present results obtained using real images. <<ETX>>
Laplacian surface editing

Surface editing operations commonly require geometric details of the surface to be preserved as much as possible. We argue that geometric detail is an intrinsic property of a surface and that, consequently, surface editing is best performed by operating over an intrinsic surface representation. We provide such a representation of a surface, based on the Laplacian of the mesh, by encoding each vertex relative to its neighborhood. The Laplacian of the mesh is enhanced to be invariant to locally linearized rigid transformations and scaling. Based on this Laplacian representation, we develop useful editing operations: interactive free-form deformation in a region of interest based on the transformation of a handle, transfer and mixing of geometric details between two surfaces, and transplanting of a partial surface mesh onto another surface. The main computation involved in all operations is the solution of a sparse linear system, which can be done at interactive rates. We demonstrate the effectiveness of our approach in several examples, showing that the editing operations change the shape while respecting the structural geometric detail.
Methylated nucleosides in tRNA and tRNA methyltransferases

To date, more than 90 modified nucleosides have been found in tRNA and the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s). Recent studies of the biosynthetic pathways have demonstrated that the availability of methyl group donors for the methylation in tRNA is important for correct and efficient protein synthesis. In this review, I focus on the methylated nucleosides and tRNA methyltransferases. The primary functions of tRNA methylations are linked to the different steps of protein synthesis, such as the stabilization of tRNA structure, reinforcement of the codon-anticodon interaction, regulation of wobble base pairing, and prevention of frameshift errors. However, beyond these basic functions, recent studies have demonstrated that tRNA methylations are also involved in the RNA quality control system and regulation of tRNA localization in the cell. In a thermophilic eubacterium, tRNA modifications and the modification enzymes form a network that responses to temperature changes. Furthermore, several modifications are involved in genetic diseases, infections, and the immune response. Moreover, structural, biochemical, and bioinformatics studies of tRNA methyltransferases have been clarifying the details of tRNA methyltransferases and have enabled these enzymes to be classified. In the final section, the evolution of modification enzymes is discussed.
Octahedral distortion, phase structural stability, and microwave dielectric properties in equivalently substituted LaTiNbO6 ceramics

The room-temperature phase composition, microstructural characteristic and microwave dielectric properties of equivalently substituted LaTiNbO6 ceramics were investigated by means of the Rietveld structural refinement, scanning electron microscopy and network analyzer. A special interest was focused on the influence of the variation of bond length and octahedral distortion on the phase structural stability. A monoclinic (M) aeschynite phase was obtained in B-site ions (Ta5+ and (W0.5Ti0.5)5+) substituted LaTiNbO6 ceramics while an orthorhombic (O) aeschynite structure appeared in B-site ions (Zr4+) or A-site ions (Ce3+ and Sm3+) substituted LaTiNbO6 ceramics, which owned typical polygonal and short rod-like grain morphologies, respectively. Compared with the octahedral bond length, a straightforward relation between the phase structural stability and the octahedral distortion was established, in which a reduced octahedral distortion was directly correlated with the destabilization of O or M phases or vice versa, irrespective of the substitution ionic radius. The experimentally-observed giant difference in dielectric performance of LaTiNbO6 based ceramics was believed to mainly originate from their distinct phase structure and grain morphology. This article is protected by copyright. All rights reserved.
Sex Chromosomes and Meiosis in Spiders:A Review

According to Platnick (2011), the order Araneae possesses 110 families, 3,849 genera, and 42,473 species. It is divided into two suborders: Mesothelae, consisting of only one family (Liphistiidae), and Opisthothelae. The latter suborder is divided into two infra-orders: Mygalomorphae, consisting of spiders with paraxial chelicerae, and Araneomorphae, consisting of spiders with diaxial chelicerae. The latter infra-order is divided into the basal clades (Hypochilidae and Austrochiloidea), Haplogynae, and Entelegynae, which includes the majority of extant spiders (Coddington & Levi, 1991) (Fig. 1).
False memory for idiomatic expressions in younger and older adults: evidence for indirect activation of figurative meanings

Idiomatic expressions can be interpreted literally or figuratively. These two meanings are often processed in parallel or very rapidly, as evidenced by online measures of idiomatic processing. Because in many cases the figurative meaning cannot be derived from the component lexical elements and because of the speed with which this meaning is accessed, it is assumed such meanings are stored in semantic memory. In the present study, we examined how literal equivalents and intact idiomatic expressions are stored in memory and whether episodic memory traces interact or interfere with semantic-level representations and vice versa. To examine age-invariance, younger and older adults studied lists of idioms and literal equivalents. On a recognition test, some studied items were presented in the alternative form (e.g., if the idiom was studied, its literal equivalent was tested). False alarms to these critical items suggested that studying literal equivalents activates the idiom from which they are derived, presumably due to spreading activation in lexical/semantic networks, and results in high rates of errors. Importantly, however, the converse (false alarms to literal equivalents after studying the idiom) were significantly lower, suggesting an advantage in storage for idioms. The results are consistent with idiom processing models that suggest obligatory access to figurative meanings and that this access can also occur indirectly, through literal equivalents.
PERSONALITY PROCESSES AND INDIVIDUAL DIFFERENCES Further Evidence for Mixed Emotions

Emotion theorists have long debated whether valence, which ranges from pleasant to unpleasant states, is an irreducible aspect of the experience of emotion or whether positivity and negativity are separable in experience. If valence is irreducible, it follows that people cannot feel happy and sad at the same time. Conversely, if positivity and negativity are separable, people may be able to experience such mixed emotions. The authors tested several alternative interpretations for prior evidence that happiness and sadness can co-occur in bittersweet situations (i.e., those containing both pleasant and unpleasant aspects). One possibility is that subjects who reported mixed emotions merely vacillated between happiness and sadness. The authors tested this hypothesis in Studies 1–3 by asking subjects to complete online continuous measures of happiness and sadness. Subjects reported more simultaneously mixed emotions during a bittersweet film clip than during a control clip. Another possibility is that subjects in earlier studies reported mixed emotions only because they were explicitly asked whether they felt happy and sad. The authors tested this hypothesis in Studies 4–6 with open-ended measures of emotion. Subjects were more likely to report mixed emotions after the bittersweet clip than the control clip. Both patterns occurred even when subjects were told that they were not expected to report mixed emotions (Studies 2 and 5) and among subjects who did not previously believe that people could simultaneously feel happy and sad (Studies 3 and 6). These results provide further evidence that positivity and negativity are separable in experience.
Local sensation changes and altered hip muscle function following severe ankle sprain.

BACKGROUND AND PURPOSE Changes in sensory information have been shown to influence muscle function locally. Some clinicians, however, believe that the influence may be more extensive. To investigate this clinical concept, subjects with severe ankle sprain were assessed for local sensation changes and proximal hip/back muscle function. SUBJECTS Of a total of 361 potential subjects whose medical histories were assessed, 20 men (age 18-35 years) who had previously sustained a severe unilateral ankle sprain and 11 matched "control" subjects with no previous lower-limb injury participated in the study. METHODS Using this experimental model, tests of vibration sensation in the ankle (indicating sensation changes) as well as surface electromyography of muscle recruitment patterns for hip extension (indicating muscle function proximally) of the biceps femoris, gluteus maximus, and lumbar erector spinae muscles were made on both sides of the unilaterally injured and matched control subjects. RESULTS Significant decreases in vibration perception and significant delays in gluteus maximus muscle recruitment during hip extension were found in the injured group. CONCLUSION AND DISCUSSION The author concludes that both local sensory and proximal muscle function changes are associated with unilateral severe ankle sprain.
Assessing the subglacial lake coverage of Antarctica

ABSTRACT Lakes beneath the Antarctic Ice Sheet are known to decrease traction at the ice base and therefore can have a great impact on ice dynamics. However, the total extent of Antarctic subglacial lakes is still unknown. We address this issue by combining modeling and remote-sensing strategies to predict potential lake locations using the general hydraulic potential equation. We are able to reproduce the majority of known lakes, as well as predict the existence of many new and so far undetected potential lakes. To validate our predictions, we analyzed ice-penetrating radar profiles from radio-echo sounding flights acquired over 1994–2013 in Dronning Maud Land, East Antarctica, and this led to the identification of 31 new subglacial lakes. Based on these findings, we estimate the total number of Antarctic subglacial lakes to be ~1300, a factor of three higher than the total number of lakes discovered to date. We estimate that only ~30% of all Antarctic subglacial lakes and ~65% of the total estimated lake-covered area have been discovered, and that lakes account for 0.6% of the Antarctic ice/bed interface.