'Genome order index' should not be used for defining compositional constraints in nucleotide sequences - a case study of the Z-curve

Background: The Z-curve is a three dimensional representation of DNA sequences proposed over a decade ago and has been extensively applied to sequence segmentation, horizontal gene transfer detection, and sequence analysis. Based on the Z-curve, a “genome order index,” was proposed, which is defined as S = a2 + c 2 +t 2 +g2 , where a, c, t, and g are the nucleotide frequencies of A, C, T, and G, respectively. This index was found to be smaller than 1/3 for almost all tested genomes, which was taken as support for the existence of a constraint on genome composition. A geometric explanation for this constraint has been suggested. Each genome was represented by a point P whose distance from the four faces of a regular tetrahedron was given by the frequencies a, c, t, and g. They claimed that an inscribed sphere of radius r = 1/ 3 contains almost all points corresponding to various genomes, implying that S < r 2 . The distribution of the points P obtained by S was studied using the Z-curve. Results: In this work, we studied the basic properties of the Z-curve using the “genome order index” as a case study. We show that (1) the calculation of the radius of the inscribed sphere of a regular tetrahedron is incorrect, (2) the S index is narrowly distributed, (3) based on the second parity rule, the S index can be derived directly from the Shannon entropy and is, therefore, redundant, and (4) the Z-curve suffers from over dimensionality, and the dimension stands for GC content alone suffices to represent any given genome. Conclusion: The “genome order index” S does not represent a constraint on nucleotide composition. Moreover, S can be easily computed from the Gini-Simpson index and be directly derived from entropy and is redundant. Overall, the Z-curve and S are over-complicated measures to GC content and Shannon H index, respectively. Reviewers: This article was reviewed by Claus Wilke, Joel Bader, Marek Kimmel and Uladzislau Hryshkevich (nominated by Itai Yanai)

Ultra-short pulses in linear and nonlinear media

We consider the evolution of ultra-short optical pulses in linear and nonlinear media. For the linear case, we first show that the initial-boundary value problem for Maxwell's equations in which a pulse is injected into a quiescent medium at the left endpoint can be approximated by a linear wave equation which can then be further reduced to the linear short-pulse equation. A rigorous proof is given that the solution of the short pulse equation stays close to the solutions of the original wave equation over the time scales expected from the multiple scales derivation of the short pulse equation. For the nonlinear case we compare the predictions of the traditional nonlinear Schr\"odinger equation (NLSE) approximation which those of the short pulse equation (SPE). We show that both equations can be derived from Maxwell's equations using the renormalization group method, thus bringing out the contrasting scales. The numerical comparison of both equations to Maxwell's equations shows clearly that as the pulse length shortens, the NLSE approximation becomes steadily less accurate while the short pulse equation provides a better and better approximation

Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

Effect of Orthophosphoric Acid and Er:YAG Laser Etching on Micro-shear Bond Strength to Enamel: An In Vitro Pilot Study

Background: Dental conditioning is one of the most important phases during enamel bonding procedures to obtain clean surfaces, smear layer removal with collagen active sites and hydroxyapatite exposure. Objective: The aim of this study was to compare the micro-shear bond strength (μSBS) of different adhesive systems after two different etching techniques: 37% orthophosphoric acid (H3PO4) and Er:YAG laser. Methods: Ninety permanent extracted molars were embedded into epoxy resin blocks and sectioned longitudinally. Specimens were randomly assigned to one of the following groups (n=30), depending on the etching protocol: 37% H3PO4 for 30 s (Group 1), Er:YAG laser 100mJ-10Hz (Group 2), and Er:YAG laser 100mJ-10Hz followed by 37% H3PO4 for 30 s (Group 3). Each group was further divided into two subgroups depending on the bonding agent used on enamel (n=15): A) EE-Bond (Tokuyama) and B) Peak universal (Ultradent). A two-way analysis of variance (two-way ANOVA) was conducted and the level of significance was set to p=0.05. Results: The etching procedure was a significant factor influencing the results (p=0.006), while no differences were observed for the two adhesive systems tested (p&gt;0.05). Group 3 recorded the highest bond strength values, according to the following sequel: Group 3 &lt; Group 2 &lt; Group 1 &lt; 0.05. Conclusion: The combination of phosphoric acid etching with Er:YAG laser provided the most favourable bond strength to enamel. Further morphological studies are currently ongoing

Comparisons of ammonia- and water-based silver-containing solutions on dentin bonding and enzymatic activity: 1-yr evaluation

Objective: To evaluate the effects of an ammonia-based and a water-based silver-containing solutions on bonding performance and matrix-metalloproteinases (MMPs) activity of a universal adhesive to dentin after 1 year of artificial aging. Methods: Mid-coronal dentin surfaces of 60 sound human molars were exposed and the following groups were formed according to the surface pre-treatment and etching mode of the universal adhesive (Zipbond Universal, SDI) (n&nbsp;=&nbsp;10): G1) Zipbond in the self-etch mode (ZSE); G2) Riva Star (SDI) applied before ZSE; G3) Riva Star Aqua (SDI) applied before ZSE; G4) Zipbond in the etch-and-rinse mode (ZER); G5) Riva Star applied before ZER; G6) Riva Star Aqua applied before ZER. The specimens were sectioned and subjected to microtensile bond strength (μTBS) test at baseline (T0) and after 12 months (T12) of artificial storage. Scanning electron microscope (SEM) and energy dispersive spectroscopy analysis (EDS) were also conducted. Three additional molars per group were processed for the in situ zymography analysis at T0 and T12. Data were statistically analyzed (p&nbsp;&lt;&nbsp;0.05). Results: Dentin pre-treatments and aging decreased bonding values, regardless of the etching mode (p&nbsp;&lt;&nbsp;0.05). No differences in μTBS were observed between the two silver-containing solutions, both at T0 and T12. Riva Star Aqua and etching significantly increased the MMPs activity, independent of the storage period (p&nbsp;&lt;&nbsp;0.05). Significance: Dentin surface pre-treatment with silver-containing solutions negatively affects the bonding performances of resin composite restorations placed with a universal adhesive. However, the ammonia-based product Riva Star might show better stability in the long term, due to lower activation of MMPs

Glutaraldehyde-based desensitizers’ influence on bonding performances and dentin enzymatic activity of universal adhesives

Objectives: To evaluate the influence of two glutaraldehyde-based desensitizers (L: GLUMA Desensitizer, Heraeus Kulzer and G: GLUMA Desensitizer PowerGel) prior to the adhesive procedures on microtensile bond strength (μTBS) to dentin and endogenous enzymatic activity. Methods: Noncarious human third molars (N = 48) were cut to expose middle coronal dentin. Six experimental groups were formed according to the dentin pre-treatment (L or G) and the universal adhesives (IBU - iBond universal, Kulzer or AU - Adhese Universal, Ivoclar Vivadent) used in the self-etch mode (n = 8): 1) L/IBU; 2) G/IBU; 3) IBU; 4) L/AU; 5) G/AU; 6) AU. Specimens were cut into sticks and stressed until failure after 24 h (T0) or 1 yr of aging (T12). Additional 4 teeth were used for in situ zymography evaluation and data were statistically analyzed (α = 0.05). Results: Dentin pre-treatment, adhesive and aging statistically influenced bond strength and enzymatic activity (P&lt;0.001). AU demonstrated higher bond strength values than IBU (P&lt;0.001). The L resulted in higher bond strength compared to the G and control groups (P&lt;0.001). aging statistically influenced bonding performance, especially when no dentin pre-treatment was performed (P&lt;0.001). In situ zymography revealed that at baseline the control groups exhibited lower interfacial fluorescence compared to the experimental groups, irrespective of the adhesive used (P&lt;0,001). However, after 1 yr of artificial storage, no differences were found among the groups (P&gt;0.05). Conclusions: : Glutharldeadeyde-based products increased bond strength and determined a stabilization of the adhesive interface over time apparently not related to the MMPs inhibition. Clinical Significance: The results of this in vitro study suggest that the application of glutaraldehyde-based desensitizers prior to the adhesive procedures when associated with universal adhesives could result in increased bond strength and stabilization of the adhesive interface over time

Comparisons of ammonia- and water-based silver-containing solutions on dentin bonding and enzymatic activity: 1-yr evaluation

Objective: To evaluate the effects of an ammonia-based and a water-based silver-containing solutions on bonding performance and matrix-metalloproteinases (MMPs) activity of a universal adhesive to dentin after 1 year of artificial aging. Methods: Mid-coronal dentin surfaces of 60 sound human molars were exposed and the following groups were formed according to the surface pre-treatment and etching mode of the universal adhesive (Zipbond Universal, SDI) (n = 10): G1) Zipbond in the self-etch mode (ZSE); G2) Riva Star (SDI) applied before ZSE; G3) Riva Star Aqua (SDI) applied before ZSE; G4) Zipbond in the etch-and-rinse mode (ZER); G5) Riva Star applied before ZER; G6) Riva Star Aqua applied before ZER. The specimens were sectioned and subjected to microtensile bond strength (μTBS) test at baseline (T0) and after 12 months (T12) of artificial storage. Scanning electron microscope (SEM) and energy dispersive spectroscopy analysis (EDS) were also conducted. Three additional molars per group were processed for the in situ zymography analysis at T0 and T12. Data were statistically analyzed (p &lt; 0.05). Results: Dentin pre-treatments and aging decreased bonding values, regardless of the etching mode (p &lt; 0.05). No differences in μTBS were observed between the two silver-containing solutions, both at T0 and T12. Riva Star Aqua and etching significantly increased the MMPs activity, independent of the storage period (p &lt; 0.05). Significance: Dentin surface pre-treatment with silver-containing solutions negatively affects the bonding performances of resin composite restorations placed with a universal adhesive. However, the ammonia-based product Riva Star might show better stability in the long term, due to lower activation of MMPs

Finite element and in vitro study on biomechanics behavior of endodontically treated premolars restored with direct or indirect composite restorations

Objectives of the study were to investigate biomechanical properties of severely compromised premolars restored with composite restorations using finite element analysis (FEA), and in vitro fracture resistance test. A 3-D model of an endodontically treated premolar was created in Solidworks. Different composite restorations were modelled (direct restoration-DR; endo-crown-EC; post, core, and crown-C) with two different supporting tissues: periodontal ligament/alveolar bone (B), and polymethyl methacrylate (PMMA). Models were two-point axially loaded occlusally (850 N). Von Mises stresses and strains were calculated. The same groups were further tested for static fracture resistance in vitro (n = 5, 6.0 mm-diameter ball indenter, vertical load). Fracture resistance data were statistically analyzed (p &lt; 0.050). The highest stresses and strains in all FEA models were observed on occlusal and vestibular cervical surfaces, corresponding to fracture propagation demonstrated in vitro. C showed the lowest stress in dentin, while EC showed lower stresses and strains in crown cement. B models demonstrated larger high stress areas in the root than PMMA models. No significant differences in fracture resistance (N) were observed between groups (DR: 747.7 ± 164.0, EC: 867.3 ± 108.1, C: 866.9 ± 126.3; p = 0.307). More conservative restorations seem a feasible alternative for endodontically treated premolars to conventional post-core-crown