Perfect match – Understanding personality based compatibility in dog-owner dyads

SAT0064 Therapy Adherence, Prescribed Medications, Disease Activity and Psychosocial Consequences in Patients with Rheumatoid Arthritis

In 1978, Rahimtoola published a successful series of surgical aortic valve replacements (SAVR) on patients with severe aortic stenosis (AS) with congestive heart failure (CHF). He described the perfect prosthesis-patient match as a "prosthetic valve with a functioning opening area that matches the patient's normal functioning valve." This manuscript revisits the forty-six-year journey in pursuit of that perfect match. We address the essential components for the perfect match, such as the usefulness of the current valve sizing techniques using the manufacturer's labeled valve size (MLVS) and sizer, the accuracy of an objective parameter to define the perfect match, and the need and safety to enlarge the patient's annulus and root to accommodate the proper size valve. A thorough literature search was performed using the University of Michigan Medical Library search engine. The population included patients who underwent SAVR. Three individual searches were conducted: (I) valve size and sizing techniques; (II) hemodynamic performance (HP) and prosthesis-patient mismatch (PPM); and (III) aortic root enlargement (ARE) procedures. Excluded were articles not in English, articles that involved animal research, duplicate articles, articles involving valve repair, allograft or autograft replacement, and articles specific to aortic sizing and congenital heart surgery. The emphasis was placed on randomized prospective trials, large registry trials with and without propensity matching, and meta-analysis articles. We discovered that the manufacturer-labeled valve size and sizing technique does not accurately represent the functional opening area of the valve. A pre-operative multidetector computed tomography (CT) scan is an accurate and reproducible method for measuring patient root and annulus dimensions and should be used for pre-operative valve sizing for SAVR. Matching the CT area derived aortic diameter with the true functional diameter of the opening of the prosthetic valve will yield the best prosthesis-patient match. ARE is safe and should be used to attain the best match.

For Affymetrix microarray platforms, gene expression is determined by computing the difference in signal intensities between perfect match (PM) and mismatch (MM) probesets. Although the use of PM is not controversial, MM probesets have been associated with variance and ultimately inaccurate gene expression calls. A principal focus of this study was to investigate the nature of the MM signal intensities and demonstrate its contribution to the experimental results. While most MM intensities were likely associated with random noise, a subset of approximately 20% (99,485) of the MM probes displayed relatively high signal intensities to the corresponding PM probes (MM > PM) in a non-random fashion; 13,440 of these probes demonstrated exceptionally high 'outlier' intensities. About 15,938 PM probes also demonstrated exceptionally high outlier intensities consistently across all hybridizations. About 92% of the MM > PM probes had either a dThymidine (dT) or a dCytidine (dC) at the 13th position of the probe sequence. MM and PM probes displaying extremely high outlier intensities contained high dC rich nucleotides, and low dA contents at other nucleotides positions along the 25mer probe sequence. Differentially expressed genes generated using Genechip Operating System (GCOS) or modified PM-only methods were also examined. Of those candidate genes identified in the PM-only method, 157 of them were designated by GCOS as absent across all datasets and many others contained probes with MM > PM signal intensities. Our data suggests that MM intensity from PM signal can be a major source of error analysis, leading to fewer potentially biologically important candidate genes. Supplementary data are available at Bioinformatics online.

Background: DNA microarrays are routinely used to monitor the transcript levels of thousands of genes simultaneously. However, the array design, hybridization conditions, and oligodeoxyribonucleotide probe sequence influence the performance of the DNA microarray platform and must be considered by data analysis. Results: We analyzed the signal intensities of GeneChip microarrays in terms of a microscopic binding model. It considers specific and non-specific transcripts, which both compete for duplex formation with perfect match (PM) and mismatch (MM) oligonucleotide probes. Intensity simulations enable us to judge the accuracy and precision of gene expression measures. The accuracy of the estimated fold changes ranks according to PM − MM > PM > MM, whereas the precision decreases with PM ≥ MM > PM − MM, where PM − MM denotes the respective intensity difference. Conclusions: MM probes possess the potency to correct the intensity of the respective PM probe for the non-specific background. The middle base related bias of the MM intensity must, however, be considered by improved algorithms of data analysis. Moreover, the knowledge of base pair interactions suggests substituting the complementary mismatches on GeneChips by alternative rules of MM design.Key wordsDNA/RNA duplex stabilityperfect match and mismatch probesgene expression

Microarrays provide a means of studying expression level of tens of thousands of genes by providing one or more oligonucleotide probe(s) for each transcript studied. Affymetrix® GeneChip™ platforms historically pair each 25-base perfect match (PM) probe with a mismatch probe (MM) differing by a complementary base located in the 13th position to quantify and deflate effects of cross-hybridization. Analytical routines for analyzing these arrays take into account difference in expression levels of MM and PM probes to determine which ones are useful for further study. If a single nucleotide polymorphism (SNP) occurs at the 13th base, a probe with a higher MM expression level may be incorrectly omitted. In order to examine SNP affects on PM and MM expression levels, known human SNPs from dbSNP were mapped to probe sets within the Affymetrix® HG-U133A platform. Probe sets containing one or more probe pairs with a single SNP at the 13th position were extracted. A set of twelve microarray experiments were analyzed for the PM and MM expression levels for these probe sets. Over 6,000,000 human SNPs and their flanking regions were extracted from dbSNP. These sequences were aligned against each of the 247,965 probe pair sequences from the Affymetrix® HG-U133A platform. A total of 915 probe sets containing a single probe sequence with a SNP mapped to the 13th base were extracted. A subset containing 166 probe sets result in complementary base SNPs. Comparison of gene expression levels for the SNP to non-SNP PM and MM probes does not yield a significant difference using χ2 analysis. Thus, omission of probes with MM expression levels higher than PM expression levels does not appear to result in a loss of information concerning SNPs for these regions.

The microarray technology enables the expression degree of thousands of genes to be estimated at once by the measurement of the abundance of the respective messenger RNA. This method is based on the sequence specific binding of RNA to DNA probes and its detection using fluorescent labels. The raw intensity data are affected by the sequence-specific affinity of probe and RNA for duplex formation, by the background intensity due to nonspecific hybridization at small transcript concentrations and by the saturation of the probes at high transcript concentration owing to surface adsorption. We address these issues using a binding model which describes specific and nonspecific hybridization in terms of a competitive two-species Langmuir isotherm and DNA/RNA duplex formation in terms of sequence-specific, single-base related interactions. The GeneChip microarrays technology uses pairs of so-called perfect match (PM) and mismatch (MM) oligonucleotide probes to estimate the amount of nonspecific hybridization. The mean affinity of the probes decrease according to PM(specific) > MM(specific) >> PM(nonspecific) approximately MM(nonspecific). The stability of specific and nonspecific DNA/RNA duplexes is mainly determined by Watson Crick (WC) pairings. Mismatched self-complementary pairings in the middle of the MM sequence only weakly contribute to the duplex stability. The asymmetry of base pair interaction in the DNA/RNA hybrid duplexes gives rise to a duplet-like symmetry of the PM - MM intensity difference at dominating nonspecific hybridization and a triplet-like symmetry at specific hybridization. The signal intensities of the PM and MM probes and their difference are assessed in terms of sensitivity and specificity. The presented results imply the refinement of existing algorithms of probe level analysis to correct microarray data for nonspecific background intensities and saturation on the basis of the probe sequence.

Affymetrix® GeneChip® micro array design defines probe sets consisting of 11, 16, or 20 distinct 25 base pair (BP) probes for determining mRNA expression for a specific gene, which may be covered by one or more probe sets. Each probe has a corresponding perfect match (PM) and mismatch (MM) set. Traditional analytical techniques have either used the MM probes to determine the level of cross-hybridization or reliability of the PM probe, or have been completely ignored. Given the availability of reference genome sequences, we have reanalyzed the mapping of both PM and MM probes to reference genomes in transcript regions. Our results suggest that depending of the species of interest, 66%-93% of the PM probes can be used reliably in terms of single unique matches to the genome, while a small number of the MM probes (typically less than 1%) could be incorporated into the analysis. In addition, we have examined the mapping of PM and MM probes to five different human genome projects, resulting in approximately a 70% overlap of uniquely mapping PM probes, and a subset of 51 uniquely mapping MM probes commonly found in all five projects, 24 of which are found within annotated exonic regions. These results suggest that individual variation in transcriptome regions provides an additional complexity to micro array data analysis. Given these results, we conclude that the development of custom chip definition files (CDFs) should include MM probe sequences to provide the most effective means of transcriptome analysis of Affymetrix® GeneChip® arrays.

In normal acoustic hearing the mapping of acoustic frequency information onto the appropriate cochlear place is a natural biological function, but in cochlear implants it is controlled by the speech processor. The cochlear tonotopic range of the implant is determined by the length and insertion depth of the electrode array. Conventional cochlear implant electrode arrays are designed for an insertion of 25 mm inside the round window and the active electrodes occupy 16 mm, which would place the electrodes in a cochlear region corresponding to an acoustic frequency range of 500-6000 Hz. However, some implant speech processors map an acoustic frequency range from 150 to 10000 Hz onto these electrodes. While this mapping preserves the entire range of acoustic frequency information, it also results in a compression of the tonotopic pattern of speech information delivered to the brain. The present study measured the effects of such a compression of frequency-to-place mapping on speech recognition using acoustic simulations. Also measured were the effects of an expansion of the frequency-to-place mapping, which produces an expanded representation of speech in the cochlea. Such an expanded representation might improve speech recognition by improving the relative spatial (tonotopic) resolution, like an "acoustic fovea." Phoneme and sentence recognition was measured as a function of linear (in terms of cochlear distance) frequency-place compression and expansion. These conditions were presented to normal-hearing listeners using a noise-band vocoder, simulating cochlear implant electrodes with different insertion depths and different number of electrode channels. The cochlear tonotopic range was held constant by employing the same noise carrier bands for each condition, while the analysis frequency range was either compressed or expanded relative to the carrier frequency range. For each condition, the result was compared to that of the perfect frequency-place match, where the carrier and the analysis bands were perfectly matched. Speech recognition in the matched conditions was generally better than any condition of frequency-place expansion and compression, even when the matched condition eliminated a considerable amount of acoustic information. This result suggests that speech recognition, at least without training, is dependent on the mapping of acoustic frequency information onto the appropriate cochlear place.

By performing a swarm-intelligent global structure search combined with first-principles calculations, a stable two-dimensional (2D) AlB3 heterostructure with directed, covalent Al–B bonds forms due to a nearly perfect lattice match between 2D borophene and the Al(111) surface. The AlB3 heterosheet with the P6mm space group is composed of a planar Al(111) layer and a corrugated borophene layer, where the in-plane coordinates of Al covalently link with the corrugated B atoms. The resulting structure shows a similar interlayer interaction energy to that of the Al(111) surface layer to the bulk and high mechanical and thermal stability, possesses multiple Dirac points in the Brillouin zone with a remarkably high Fermi velocity of 1.09 × 106 m s−1, which is comparable to that of graphene. Detailed analysis of the electronic structure employing the electron localisation function and topological analysis of the electron density confirm the covalent Al–B bond with high electron localisation between the Al and B centres and with only little interatomic charge transfer. The combination of borophene with metal monolayers in 2D heterostructures opens the door to a rich chemistry with potentially unprecedented properties.

When employing conditionally stable transistors in microwave amplifier design, it is impossible to have both parts perfectly matched. One can easily design for a perfect match at one of the parts, but the resulting mismatch at the remaining part may be unacceptable. Through trial and error using graphical methods, the designer may trade-off the perfect part match for improved match at the other part. In this paper, we propose a systematic approach whereby the maximisation of an objective function results in maximum gain and part match, for given stability safety margins.

A virtual matching technique for three-field breast irradiation using 3-D planning

BackgroundSchizophrenia is a complex disorder in which infection and immune mechanisms are thought to play a role. Epidemiological and ecological studies have implicated influenza infection in particular and it is possible that cross-reactivity, or molecular mimicry, between the influenza virus and brain proteins underlies this association. Proteins might share amino acid sequences, which could thus provide the basis for an autoimmune response that targets endogenous proteins. This study is the first to characterise sequence alignment between schizophrenia-related brain proteins and the proteome of the influenza A virus, and comparing it with sequence alignment in proteins not implicated in schizophrenia.MethodsThe software Peptide Match Service (https://research.bioinformatics.udel.edu/peptidematch/index.jsp; Protein Information Resource, University of Delaware and Georgetown University Medical Center) was used to obtain sequence alignments between protein sequences. A case-control study design was used to compare schizophrenia-related proteins to proteins not involved in schizophrenia. Schizophrenia-related proteins were operationalised as proteins found significant in the Psychiatric Genomics Consortium schizophrenia genome-wide association studies (GWAS). The control group consisted of null proteins (p-value > .75) in the GWAS. Null proteins were also selected to represent genes expressed in tissues other than central nervous system tissues. Both groups were equalised for the total amino acid count. Perfect pentapeptide matches (i.e. 5 amino acids) in proteins and the influenza proteome were explored.ResultsThere was a link between schizophrenia-related (GWAS-significant) proteins and presence of perfect matches between proteins and the influenza proteins polymerase acidic protein (χ2 (1) = 5.284, p = .022, two-sided) and RNA-directed RNA polymerase catalytic subunit (χ2 (1) = 6.132, p = .013, two-sided). Pentapeptide-sharing was found to be highly significant between schizophrenia-related proteins and the hemagglutinin precursor (χ2 (1) = 17.723, p = .000026, two-sided). There was no significant difference (p > .05) between schizophrenia-related proteins and proteins not implicated in schizophrenia (GWAS-null proteins) in the frequency of proteins having perfect matches with the influenza A proteins PB2-S1, polymerase basic protein 2, matrix protein 1 and 2, and neuraminidase. However, the result for matrix protein 1 approached statistical significance (χ2 (1) = 3.319, p = .068, two-sided).DiscussionWe find evidence to suggest there is significant overlap between the linear structures of proteins involved in schizophrenia and those integral to the influenza virus. Future research should establish the biological relevance of this finding, particularly regarding the antigenicity of the peptide sequences which we have identified. Extra studies should also go beyond sequences and address structural homologies. Future research could assess whether an immune reaction against particular schizophrenia-related proteins is a plausible mechanism contributing to psychotic disorders. Also, exploring peptide sharing in different influenza strains could offer insights into links between influenza pandemics, maternal infection, and psychosis. Elucidating peptide sharing might have implications for schizophrenia risk management and safe influenza prevention.

The mapping of frequency information onto the correct cochlear place is critical for speech recognition. In cochlear implants, the cochlear tonotopic range represented by the electrode array is smaller than the acoustic frequency range used in the speech processor. While this condition utilizes a wide range of speech frequency information, it results in a compression of the tonotopic pattern of speech information delivered to the brain. An alternative approach is to take the core frequency range necessary for speech and expand its representation in the cochlea, like an ‘‘acoustic fovea.’’ This study examined the effect of linear frequency-place compression and expansion on speech intelligibility for various cochlear locations and number of spectral channels. These conditions were presented to normal-hearing listeners using a noise band vocoder. The cochlear tonotopic range was held constant by employing the same carrier bands for each condition, while the frequency range of the analysis bands was changed. For each condition, the result was compared to that of the perfect tonotopic match, where the carrier and the analysis bands were perfectly matched. Speech recognition in frequency-place expansion and compression was always equal to or poorer than the matched condition. [Work supported by NIDCD.]

99mTc-Methoxy-Isobuty-Isonitrile (MIBI) imaging is used for risk stratifications of hypofunctioning thyroid nodules (TNs). MIBI uptake in the nodular tissue is compared to the uptake in the paranodular thyroid tissue. MIBI imaging may be interpreted visually and/or semi-quantitatively. This study aimed to evaluate the interobserver agreement (IOA) of different methods of interpreting MIBI imaging (visual and semi-quantitative approaches). MIBI imaging data from 2018 to 2020 were collected. Four readers with varying work experience prospectively evaluated MIBI images (planar, SPECT/CT) visually and semi-quantitatively (Wash-Out Index (WOI)). After identifying the nodules on 99mTc-pertechnetate scintigram, the readers evaluated MIBI imaging data by using early, late, early-to-late, and SPECT late acquisitions. Region of interests (ROIs) were defined for semi-quantitative analysis and average counts were calculated using the WOI formula (by Campenni et al.) 1 2. IOA was assessed using Fleiss Kappa, Pearson correlation and Analysis of Variance (ANOVA). 23 patients with hypofunctioning nodules were included. Kappa analysis revealed an IOA of 0.57 for all readers for early imaging (moderate agreement); perfect matches were found in 57%. For late imaging, the IOA was 0.48 (moderate) for all, with perfect matches in 48%. The visual pattern (early-to-late) exhibited an IOA of 0.45 for all, with perfect matches in 57%. SPECT/CT evaluation showed an overall IOA of 0.44, with perfect matches in 48%. The semi-quantitative approach WOI yielded an overall result of 0.64 (good agreement) and perfect matches in 91%. The IOA for WOI was higher than for visual methods. The WOI is independent of the reader's experience level. Visual analysis requires a certain level of experience from the reader.

BackgroundHigh-density oligonucleotide arrays are widely used for analysis of genome-wide expression and genetic variation. Affymetrix GeneChips – common high-density oligonucleotide arrays – contain perfect match (PM) and mismatch (MM) probes generated by changing a single nucleotide of the PMs, to estimate cross-hybridization. However, a fraction of MM probes exhibit larger signal intensities than PMs, when the difference in the amount of target specific hybridization between PM and MM probes is smaller than the variance in the amount of cross-hybridization. Thus, pairs of PM and MM probes with greater specificity for single nucleotide mismatches are desirable for accurate analysis.ResultsTo investigate the specificity for single nucleotide mismatches, we designed a custom array with probes of different length (14- to 25-mer) tethered to the surface of the array and all possible single nucleotide mismatches, and hybridized artificially synthesized 25-mer oligodeoxyribonucleotides as targets in bulk solution to avoid the effects of cross-hybridization. The results indicated the finite availability of target molecules as the probe length increases. Due to this effect, the sequence specificity of the longer probes decreases, and this was also confirmed even under the usual background conditions for transcriptome analysis.ConclusionOur study suggests that the optimal probe length for specificity is 19–21-mer. This conclusion will assist in improvement of microarray design for both transcriptome analysis and mutation screening.