Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations.

Neisseria meningitidis protects itself from complement-mediated killing by binding complement factor H (FH). Previous studies associated susceptibility to meningococcal disease (MD) with variation in CFH, but the causal variants and underlying mechanism remained unknown. Here we attempted to define the association more accurately by sequencing the CFH-CFHR locus and imputing missing genotypes in previously obtained GWAS datasets of MD-affected individuals of European ancestry and matched controls. We identified a CFHR3 SNP that provides protection from MD (rs75703017, p value = 1.1 × 10-16) by decreasing the concentration of FH in the blood (p value = 1.4 × 10-11). We subsequently used dual-luciferase studies and CRISPR gene editing to establish that deletion of rs75703017 increased FH expression in hepatocyte by preventing promotor inhibition. Our data suggest that reduced concentrations of FH in the blood confer protection from MD; with reduced access to FH, N. meningitidis is less able to shield itself from complement-mediated killing.

Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities.

OBJECTIVE: Gastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining multiple studies, we derived and applied a consensus Mes-GC classifier to define the Mes-GC enhancer landscape revealing disease vulnerabilities. DESIGN: Transcriptomic profiles of ~1000 primary GCs and cell lines were analysed to derive a consensus Mes-GC classifier. Clinical and genomic associations were performed across >1200 patients with GC. Genome-wide epigenomic profiles (H3K27ac, H3K4me1 and assay for transposase-accessible chromatin with sequencing (ATAC-seq)) of 49 primary GCs and GC cell lines were generated to identify Mes-GC-specific enhancer landscapes. Upstream regulators and downstream targets of Mes-GC enhancers were interrogated using chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing, CRISPR/Cas9 editing, functional assays and pharmacological inhibition. RESULTS: We identified and validated a 993-gene cancer-cell intrinsic Mes-GC classifier applicable to retrospective cohorts or prospective single samples. Multicohort analysis of Mes-GCs confirmed associations with poor patient survival, therapy resistance and few targetable genomic alterations. Analysis of enhancer profiles revealed a distinctive Mes-GC epigenomic landscape, with TEAD1 as a master regulator of Mes-GC enhancers and Mes-GCs exhibiting preferential sensitivity to TEAD1 pharmacological inhibition. Analysis of Mes-GC super-enhancers also highlighted NUAK1 kinase as a downstream target, with synergistic effects observed between NUAK1 inhibition and cisplatin treatment. CONCLUSION: Our results establish a consensus Mes-GC classifier applicable to multiple transcriptomic scenarios. Mes-GCs exhibit a distinct epigenomic landscape, and TEAD1 inhibition and combinatorial NUAK1 inhibition/cisplatin may represent potential targetable options.

Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer mortality, with ARID1A being the second most frequently mutated driver gene in GC. We sought to decipher ARID1A-specific GC regulatory networks and examine therapeutic vulnerabilities arising from ARID1A loss. DESIGN: Genomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures of ARID1A inactivation across molecular subtypes. Single-cell transcriptomic profiles of ARID1A-mutated GCs were analysed to examine tumour microenvironmental changes arising from ARID1A loss. Genome-wide ARID1A binding and chromatin profiles (H3K27ac, H3K4me3, H3K4me1, ATAC-seq) were generated to identify gastric-specific epigenetic landscapes regulated by ARID1A. Distinct cancer hallmarks of ARID1A-mutated GCs were converged at the genomic, single-cell and epigenomic level, and targeted by pharmacological inhibition. RESULTS: We observed prevalent ARID1A inactivation across GC molecular subtypes, with distinct mutational signatures and linked to a NFKB-driven proinflammatory tumour microenvironment. ARID1A-depletion caused loss of H3K27ac activation signals at ARID1A-occupied distal enhancers, but unexpectedly gain of H3K27ac at ARID1A-occupied promoters in genes such as NFKB1 and NFKB2. Promoter activation in ARID1A-mutated GCs was associated with enhanced gene expression, increased BRD4 binding, and reduced HDAC1 and CTCF occupancy. Combined targeting of promoter activation and tumour inflammation via bromodomain and NFKB inhibitors confirmed therapeutic synergy specific to ARID1A-genomic status. CONCLUSION: Our results suggest a therapeutic strategy for ARID1A-mutated GCs targeting both tumour-intrinsic (BRD4-assocatiated promoter activation) and extrinsic (NFKB immunomodulation) cancer phenotypes.

MicroLED light source for optical sectioning structured illumination microscopy.

Optical sectioning structured illumination microscopy (OS-SIM) provides optical sectioning capability in wide-field microscopy. The required illumination patterns have traditionally been generated using spatial light modulators (SLM), laser interference patterns, or digital micromirror devices (DMDs) which are too complex to implement in miniscope systems. MicroLEDs have emerged as an alternative light source for patterned illumination due to their extreme brightness capability and small emitter sizes. This paper presents a directly addressable striped microLED microdisplay with 100 rows on a flexible cable (70 cm long) for use as an OS-SIM light source in a benchtop setup. The overall design of the microdisplay is described in detail with luminance-current-voltage characterization. OS-SIM implementation with a benchtop setup shows the optical sectioning capability of the system by imaging within a 500 µm thick fixed brain slice from a transgenic mouse where oligodendrocytes are labeled with a green fluorescent protein (GFP). Results show improved contrast in reconstructed optically sectioned images of 86.92% (OS-SIM) compared with 44.31% (pseudo-widefield). MicroLED based OS-SIM therefore offers a new capability for deep tissue widefield imaging.

Multimerin 1 aids in the progression of ovarian cancer possibly via modulation of DNA damage response and repair pathways.

Ovarian cancer is one of the leading causes of deaths among women. Despite advances in the treatment regimes, a high rate of diagnosis in the advanced stage makes it almost an incurable malignancy. Thus, more research efforts are required to identify potential molecular markers for early detection of the disease and therapeutic targets to augment the survival rate of ovarian cancer patients. Previously, in this context, we identified dysregulated expression of multimerin 1 (MMRN1) in ovarian cancer. To elucidate the relationship between MMRN1 expression and ovarian cancer progression, siRNA-based MMRN1 knockdown was employed and various cell assays were performed to study its effect on ovarian cancer cells. In addition, network of dysregulated proteins was identified by quantitative proteomics and associated pathways were explored by bioinformatics analysis. MMRN1 silencing showed a significant reduction in cell viability, adhesion, migration, and invasion and a high frequency of cell apoptosis. Label-free quantitative proteomics and in-depth statistical analysis identified 448 dysregulated proteins, majority of which were overexpressed in MMRN1 knockdown cells. The pathways overrepresented in ovarian cancer were DNA replication, mismatch repair, nucleotide excision repair, and cell cycle regulation. Conclusively, the findings of this study suggest that MMRN1 aids in the progression of ovarian cancer via modulation of DNA damage response and repair pathways.

Breakdown of dipole Born approximation and the role of Rydberg's predissociation for the electron-induced ion-pair dissociation to oxygen in the presence of background gases.

We study the electron-induced ion-pair dissociation to gas-phase oxygen molecules using a state-of-the-art velocity-map ion-imaging technique. The analysis is entirely based on the conical time-gated wedge-shaped velocity slice images of O-/O2 nascent anionic fragments, and the resulting observations are in favor of Van Brunt et al.'s report [R. J. Van Brunt and L. J. Kieffer, J. Chem. Phys. 60, 3057 (1974)]. A new image reconstruction method, Jacobian over parallel slicing, is introduced to overcome the drawback of ion exaggeration in determining the kinetic energy distribution from the time-gated parallel slicing technique, which offers an alternative approach to the wedge slicing method. Most importantly, the role of the quintet-heavy Rydberg state has been drawn out to the complex ion-pair formalism. The extracted kinetic energy and angular distributions from the wedge slice images reveal a high momentum transfer during the ion-pair dissociation process, which could be the finest rationale to observe the breakdown of dipole Born approximation driven by multipole moment associated with the incident electron beam. Three distinct dissociative momentum bands have been precisely identified for O- dissociation. However, radiationless Rydberg's predissociation continuum (≥15%) has become an inherent character of electron-induced ion-pair dissociation, which could be dealt with using the beyond Born-Oppenheimer treatment. The incoherent sum of Σ and Π symmetric-associated ion-pair final states has been precisely identified by modeling the angular distribution of O-/O2 for each of the kinetic energy bands. A negligibly small amount of forward-backward asymmetry is observed in the angular distribution of O-/O2, which might be explained by the dissociative state-specific quantum coherence mechanism as reported [Krishnakumar et al., Nat. Phys. 14, 149 (2018); Kumar et al., arXiv:2206.15024 (2022)] by Prabhudesai et al.

Unveiling the Significance of FGF8 Overexpression in Orchestrating the Progression of Ovarian Cancer.

The asymptomatic nature, high rate of disease recurrence, and resistance to platinum-based chemotherapy highlight the need to identify and characterize novel target molecules for ovarian cancer. Fibroblast growth factor 8 (FGF8) aids in the development and metastasis of ovarian cancer; however, its definite role is not clear. We employed ELISA and IHC to examine the expression of FGF8 in the saliva and tissue samples of epithelial ovarian cancer (EOC) patients and controls. Furthermore, various cell assays were conducted to determine how FGF8 silencing influences ovarian cancer cell survival, adhesion, migration, and invasion to learn more about the functions of FGF8. In saliva samples, from controls through low-grade to high-grade EOC, a stepped overexpression of FGF8 was observed. Similar expression trends were seen in tissue samples, both at protein and mRNA levels. FGF8 gene silencing in SKOV3 cells adversely affected various cell properties essential for cancer cell survival and metastasis. A substantial reduction was observed in the cell survival, cell adhesion to the extracellular matrix, migration, and adhesion properties of SKOV3 cells, suggesting that FGF8 plays a crucial role in the development of EOC. Conclusively, this study suggests a pro-metastatic function of FGF8 in EOC.

Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition.

OBJECTIVES: Epigenomic alterations in cancer interact with the immune microenvironment to dictate tumour evolution and therapeutic response. We aimed to study the regulation of the tumour immune microenvironment through epigenetic alternate promoter use in gastric cancer and to expand our findings to other gastrointestinal tumours. DESIGN: Alternate promoter burden (APB) was quantified using a novel bioinformatic algorithm (proActiv) to infer promoter activity from short-read RNA sequencing and samples categorised into APBhigh, APBint and APBlow. Single-cell RNA sequencing was performed to analyse the intratumour immune microenvironment. A humanised mouse cancer in vivo model was used to explore dynamic temporal interactions between tumour kinetics, alternate promoter usage and the human immune system. Multiple cohorts of gastrointestinal tumours treated with immunotherapy were assessed for correlation between APB and treatment outcomes. RESULTS: APBhigh gastric cancer tumours expressed decreased levels of T-cell cytolytic activity and exhibited signatures of immune depletion. Single-cell RNAsequencing analysis confirmed distinct immunological populations and lower T-cell proportions in APBhigh tumours. Functional in vivo studies using 'humanised mice' harbouring an active human immune system revealed distinct temporal relationships between APB and tumour growth, with APBhigh tumours having almost no human T-cell infiltration. Analysis of immunotherapy-treated patients with GI cancer confirmed resistance of APBhigh tumours to immune checkpoint inhibition. APBhigh gastric cancer exhibited significantly poorer progression-free survival compared with APBlow (median 55 days vs 121 days, HR 0.40, 95% CI 0.18 to 0.93, p=0.032). CONCLUSION: These findings demonstrate an association between alternate promoter use and the tumour microenvironment, leading to immune evasion and immunotherapy resistance.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Analysis of Multimerin 1 (MMRN1) expression in ovarian cancer.

Ovarian cancer, the most lethal gynecological cancer, is the fifth most common cause of cancer-related deaths in women. A cost-effective and non-invasive early screening method for ovarian cancer is required to reduce the high mortality rate. Saliva is a clinically informative unique fluid, which is useful for novel approaches to prognosis, clinical diagnosis, and monitoring for non-invasive detection of disease. Multimerin1 (MMRN1) is a di-sulfide linked homo-polymeric glycoprotein from EMILIN family. Altered expression of MMRN1 has been reported in hepatocellular carcinoma, cervical cancer, and ovarian cancer. But, its role in epithelial ovarian cancer (EOC) is not clear and well documented. In this study, expression of Multimerin 1 was validated in saliva and tissues of EOC patients and age-matched controls by western blotting, ELISA, RT-PCR, and immunohistochemistry. Significant over expression of MMRN1 was observed by western blot and ELISA in saliva samples of EOC patients. The average concentration of MMRN1 in the saliva of healthy controls was 28.7 pg/ml (SE ± 1.76), 42.53 pg/ml (SE ± 4.06) in low grade and 52.91 pg/ml (SE ± 4.24) with p < 0.01 in high-grade EOC. Upregulated cytoplasmic expression of MMRN1 was observed in EOC tissue by immunohistochemistry. Our results suggest that MMRN1 expression is associated with EOC progression and MMRN1 may be potential biomarker candidates for early-stage EOC detection however further experiments are required in a large cohort to establish this proposition. Also, saliva can be explored as a novel medium for ovarian cancer diagnosis.

Structural insights of Mycobacterium GTPase-Obg and anti-sigma-F factor Usfx interaction.

An essential protein for bacterial growth, GTPase-Obg (Obg), is known to play an unknown but crucial role in stress response as its expression increases in Mycobacterium under stress conditions. It is well reported that Obg interacts with anti-sigma-F factor Usfx; however, a detailed analysis and structural characterization of their physical interaction remain undone. In view of above-mentioned points, this study was conceptualized for performing binding analysis and structural characterization of Obg-Usfx interaction. The binding studies were performed by surface plasmon resonance, while in silico docking analysis was done to identify crucial residues responsible for Obg-Usfx interaction. Surface plasmon resonance results clearly suggest that N-terminal and G domains of Obg mainly contribute to Usfx binding. Also, binding constants display strong affinity that was further evident by intermolecular hydrogen bonds and hydrophobic interactions in the predicted complex. Strong interaction between Obg and Usfx supports the view that Obg plays an important role in stress response, essentially required for Mycobacterium survival. As concluded by various studies that Obg is crucial for Mycobacterium survival under stress, this structural information may help us in designing novel and potential inhibitors against resistant Mycobacterium strains.

cnvCapSeq: detecting copy number variation in long-range targeted resequencing data.

Targeted resequencing technologies have allowed for efficient and cost-effective detection of genomic variants in specific regions of interest. Although capture sequencing has been primarily used for investigating single nucleotide variants and indels, it has the potential to elucidate a broader spectrum of genetic variation, including copy number variants (CNVs). Various methods exist for detecting CNV in whole-genome and exome sequencing datasets. However, no algorithms have been specifically designed for contiguous target sequencing, despite its increasing importance in clinical and research applications. We have developed cnvCapSeq, a novel method for accurate and sensitive CNV discovery and genotyping in long-range targeted resequencing. cnvCapSeq was benchmarked using a simulated contiguous capture sequencing dataset comprising 21 genomic loci of various lengths. cnvCapSeq was shown to outperform the best existing exome CNV method by a wide margin both in terms of sensitivity (92.0 versus 48.3%) and specificity (99.8 versus 70.5%). We also applied cnvCapSeq to a real capture sequencing cohort comprising a contiguous 358 kb region that contains the Complement Factor H gene cluster. In this dataset, cnvCapSeq identified 41 samples with CNV, including two with duplications, with a genotyping accuracy of 99%, as ascertained by quantitative real-time PCR.

Admixed origin of the Kayah (Red Karen) in Northern Thailand revealed by biparental and paternal markers.

This study analyzes the autosomal short tandem repeats (STRs) variation and the presence of Y chromosomal haplogroups from 44 individuals of the Kayah or Red Karen (KA) in Northern Thailand. The results based on autosomal STRs indicated that the KA exhibited closer genetic relatedness to populations from adjacent regions in Southeast Asia (SEA) than populations from Northeast Asia (NEA) and Tibet. Moreover, an admixed origin of the KA forming three population groups was observed: NEA, Southern China, and Northern Thailand. The NEA populations made a minor genetic contribution to the KA, while the rest came from populations speaking Sino-Tibetan (ST) languages from Southern China and Tai-Kadai (TK) speaking groups from Northern Thailand. The presence of six paternal haplogroups, composed of dual haplogroups prevalent in NEA (NO, N, and D1) and SEA (O2 and O3) as well as the intermediate genetic position of the KA between the SEA and NEA also indicated an admixed origin of male KA lineages. Our genetic results thus agree with findings in linguistics that Karenic languages are ST languages that became heavily influenced by TK during their southward spread. A result of the Mongol invasions during the 13th century A.D. is one possible explanation for genetic contribution of NEA to the KA.

Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes.

Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers.

GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)  = 0.64, P(combined)  = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted)  = 0.70, P(adjusted)  =  4 × 10(-12); rs10484561:OR(adjusted)  = 1.64, P(adjusted)  = 5 × 10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined)  = 1.36, P(combined)  =  1.4 × 10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

Target-based drug discovery: Applications of fluorescence techniques in high throughput and fragment-based screening.

Target-based discovery of first-in-class therapeutics demands an in-depth understanding of the molecular mechanisms underlying human diseases. Precise measurements of cellular and biochemical activities are critical to gain mechanistic knowledge of biomolecules and their altered function in disease conditions. Such measurements enable the development of intervention strategies for preventing or treating diseases by modulation of desired molecular processes. Fluorescence-based techniques are routinely employed for accurate and robust measurements of in-vitro activity of molecular targets and for discovering novel chemical molecules that modulate the activity of molecular targets. In the current review, the authors focus on the applications of fluorescence-based high throughput screening (HTS) and fragment-based ligand discovery (FBLD) techniques such as fluorescence polarization (FP), Förster resonance energy transfer (FRET), fluorescence thermal shift assay (FTSA) and microscale thermophoresis (MST) for the discovery of chemical probe to exploring target's role in disease biology and ultimately, serve as a foundation for drug discovery. Some recent advancements in these techniques for compound library screening against important classes of drug targets, such as G-protein-coupled receptors (GPCRs) and GTPases, as well as phosphorylation- and acetylation-mediated protein-protein interactions, are discussed. Overall, this review presents a landscape of how these techniques paved the way for the discovery of small-molecule modulators and biologics against these targets for therapeutic benefits.

Ultra-Thin Ceramic Substrates for Improved Heatsinking for microLEDs.

MicroLEDs provide unrivaled luminance and operating lifetime, which has led to significant activity using devices for display and non-display applications. The small size and high power density of microLEDs, however, causes increased adverse heating effects which can limit performance. A new generation of electrically insulating high thermal conductivity materials, such as alumina, has been proposed to mitigate these thermal effects when used as a substrate as an alternative to glass. This strategy then could be used as a method of passive heatsinking to improve the overall performance of the microLED. In this work, a newly available material, an 80 micron thick alumina ceramic substrate, is shown to yield a 30 % improvement on average in the maximum current drive over a glass substrate.

Comparative Evaluation of Shear Bond Strength of Tricalcium Silicate-based Materials to Composite Resin with Two Different Adhesive Systems: An In Vitro Study.

Background: Establishing a strong bond between the pulp capping agent and the restorative material is crucial to the success of the procedure. Without this bond, there is a risk of bacterial infiltration into the pulp, leading to treatment failure. In the past, calcium hydroxide was commonly used for such treatments, but it faced challenges, including poor adhesion to dentin, dissolution over time, and the development of multiple tunnel defects. Mineral trioxide aggregate (MTA), introduced to dentistry in 1993, offered an alternative but came with drawbacks like challenging handling and extended setting times. However, in recent times, several new calcium silicate-based materials have emerged to address MTA's limitations. Two notable examples are Biodentine and MTA Plus. Biodentine, for instance, exhibits excellent sealing ability, while MTA Plus distinguishes itself with a finer particle size compared to traditional MTA. These innovative materials offer promising solutions to enhance the efficacy of pulp capping procedures. Aim: Therefore, in this research, we conducted a comparative analysis of the shear bond strength (SBS) between composite resin and three materials-MTA, MTA Plus, and Biodentine. We examined the effects of applying two distinct adhesive systems in order to evaluate their influence on the bond strength. Materials and methods: A total of 60 acrylic blocks were evenly distributed into three groups, each containing 20 blocks-group I received Biodentine, group II was assigned MTA, and group III received MTA Plus. The respective test materials were compacted into the holes within the blocks. Following this, the samples were incubated for a period of 72 hours. Subsequently, the samples were divided into two subgroups, each consisting of 10 blocks-the self-etch and the total-etch subgroup. The SBS values were then carefully measured for analysis. Result: The SBS of the Biodentine group demonstrated a significantly higher value when compared to the other groups. It's worth noting that when the self-etch adhesive system was employed, the SBS of all the groups experienced a significant reduction. Conclusion: Biodentine cement proves to be an effective choice for pulp capping procedures, regardless of the specific adhesive system employed. Notably, the total-etch adhesive system consistently yields higher bond strength when compared to the self-etch adhesive system. How to cite this article: Kumar V, Showkat I, Manuja N, et al. Comparative Evaluation of Shear Bond Strength of Tricalcium Silicate-based Materials to Composite Resin with Two Different Adhesive Systems: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(S-3):S272-S277.

A Dense Conformal Electrode Array for High Spatial Resolution Stimulation of Electrosensory Systems.

Studies of electrosensory systems have led to insights into to a number of general issues in biology. However, investigations of these systems have been limited by the inability to precisely control spatial patterns of electrosensory input. In this paper, an electrode array and a system to selectively stimulate spatially restricted regions of an electroreceptor array is presented. The array has 96 channels consisting of chrome/gold electrodes patterned on a flexible parylene-C substrate and encapsulated with another parylene-C layer. The conformability of the electrode array allows for optimal current driving and surface interface conditions. Recordings of neural activity at the first central processing stage in weakly electric mormyrid fish support the potential of this system for high spatial resolution stimulation and mapping of electrosensory systems.

Multi-platform segmentation for joint detection of copy number variants.

MOTIVATION: With the expansion of whole-genome studies, there is rapid evolution of genotyping platforms. This leads to practical issues such as upgrading of genotyping equipment which often results in research groups having data from different platforms for the same samples. While having more data can potentially yield more accurate copy-number estimates, combining such data is not straightforward as different platforms show different degrees of attenuation of the true copy-number or different noise characteristics and marker panels. Currently, there is still a relative lack of procedures for combining information from different platforms. RESULTS: We develop a method, called MPSS, based on a correlated random-effect model for the unobserved patterns and extend the robust smooth segmentation approach to the multiple-platform scenario. We also propose an objective criterion for discrete segmentation required for downstream analyses. For each identified segment, the software reports a P-value to indicate the likelihood of the segment being a true CNV. From the analyses of real and simulated data, we show that MPSS has better operating characteristics when compared to single-platform methods, and have substantially higher sensitivity compared to an existing multiplatform method. AVAILABILITY: The methods are implemented in an R package MPSS, and the source is available from http://www.meb.ki.se/~yudpaw.