A hybrid-qudit representation of digital RGB images.

Quantum image processing is an emerging topic in the field of quantum information and technology. In this paper, we propose a new quantum image representation of RGB images with deterministic image retrieval, which is an improvement over all the similar existing representations in terms of using minimum resource. We use two entangled quantum registers constituting of total 7 qutrits to encode the color channels and their intensities. Additionally, we generalize the existing encoding methods by using both qubits and qutrits to encode the pixel positions of a rectangular image. This hybrid-qudit approach aligns well with the current progress of NISQ devices in incorporating higher dimensional quantum systems than qubits. We then describe the image encoding method using higher-order qubit-qutrit gates, and demonstrate the decomposition of these gates in terms of simpler elementary gates. We use the Google Cirq's quantum simulator to verify the image preparation in both the ideal noise-free scenario and in presence of realistic noise modelling. We show that the complexity of the image encoding process is linear in the number of pixels. Lastly, we discuss the image compression and some basic RGB image processing protocols using our representation.

Children with severe acute malnutrition have high rates of bone resorption: A cross-sectional comparative study.

Malnutrition in under-5 children (i.e., children younger than age 5 years) remains a major public health problem. Because of the reductive adaptation in children with severe acute malnutrition (SAM), changes in bone health are often subtle. We hypothesized that children with SAM have higher rates of bone resorption than bone formation, which can be assessed using bone turnover markers. In this cross-sectional comparative study, we evaluated the status of bone turnover markers, serum osteocalcin and serum tartrate-resistant acid phosphatase-5b (TRAP-5b) in under-5 children with SAM. Thirty children (6-59 months) with SAM (defined as per World Health Organization criteria) were enrolled as cases and another 30 children (age and sex matched) with normal nutritional status (weight for height -1 standard deviation [SD] to +1 SD) were enrolled for comparison of bone turnover markers. Serum TRAP-5b concentrations were significantly higher in children with SAM compared with children with normal nutritional status (mean [SD] 22.6 [15.3] vs. 11.3 [9.6], P = .009), whereas serum osteocalcin concentrations were comparable between the 2 groups (mean [SD] 40.6 [17.9] vs. 36.0 [12.5], P = .344). Frequency of hypocalcemia and vitamin D deficiency were also significantly high in children with SAM (P < .05). An inverse correlation was found between serum calcium and serum osteocalcin (r = -0.383, P < .05). Our results indicate that children with SAM have a higher bone resorption rate than children with normal nutrition status indicating compromised bone health.

Concept of Orbital Entanglement and Correlation in Quantum Chemistry.

A recent development in quantum chemistry has established the quantum mutual information between orbitals as a major descriptor of electronic structure. This has already facilitated remarkable improvements in numerical methods and may lead to a more comprehensive foundation for chemical bonding theory. Building on this promising development, our work provides a refined discussion of quantum information theoretical concepts by introducing the physical correlation and its separation into classical and quantum parts as distinctive quantifiers of electronic structure. In particular, we succeed in quantifying the entanglement. Intriguingly, our results for different molecules reveal that the total correlation between orbitals is mainly classical, raising questions about the general significance of entanglement in chemical bonding. Our work also shows that implementing the fundamental particle number superselection rule, so far not accounted for in quantum chemistry, removes a major part of correlation and entanglement seen previously. In that respect, realizing quantum information processing tasks with molecular systems might be more challenging than anticipated.

Interrogation of 3D-swapped structure and functional attributes of quintessential Sortase A from Streptococcus pneumoniae.

The anchoring of the surface proteins to the cell wall in gram-positive bacteria involves a peptide ligation reaction catalyzed by transpeptidase sortase. Most bacterial genomes encode multiple sortases with dedicated functions. Streptococcus pneumoniae (Sp) carries four sortases; a housekeeping sortase (SrtA), and three pilin specific sortases (SrtC1, C2, C3) dedicated to the biosynthesis of covalent pilus. Interestingly, SrtA, meant for performing housekeeping roles, is also implicated in pilus assembly of Sp. The allegiance of SpSrtA to the pathogenic pilus assembly makes it an ideal target for clinical inhibitor development. In this paper, we describe biochemical characterization, crystal structure and peptide substrate preference of SpSrtA. Transpeptidation reaction with a variety of substrates revealed that the enzyme preferred elongated LPXTG sequences and transferred them equally well to both Ala- and Gly-terminated peptides. Curiously, crystal structure of both wild type and an active site (Cys to Ala) mutant of SpSrtA displayed inter-twined 3D-swapped dimers in which each protomer generated a classic eight stranded beta-barrel "sortase fold". Size-exclusion chromatography and sedimentation equilibrium measurements revealed predominant presence of a dimer in equilibrium with its monomer. The crystal structure-based Cys-Cys distance mapping with defined chemical cross-linkers established the existence of 3D-swapped structure in solution. The swapping in SpSrtA, unprecedented for sortase family, may be physiologically relevant and meant to perform regulatory functions.

Non-Invasive Estimation of Hemoglobin Using a Multi-Model Stacking Regressor.

OBJECTIVE: We describe a novel machine-learning based method to estimate total Hemoglobin (Hb) using photoplethysmograms (PPGs) acquired non-invasively. METHODS: In a study conducted in Karnataka, India, 1583 women (pregnant and non-pregnant) of childbearing age, with Hb values ranging between 1.6 to 14.8 g/dL, had their Hb values estimated using intravenous blood samples and concurrently by a finger sensor custom designed and prototyped for this study. The finger sensor collected PPG signals at four wavelengths: 590 nm, 660 nm, 810 nm, and 940 nm. A novel feature vector was derived from these PPGs. A machine learning model comprising of a two-layer stack of regressors including Least Absolute Shrinkage and Selection Operator (LASSO), Ridge, Elastic Net, Adaptive (Ada) Boost and Support Vector Regressors (SVR) was designed and tested. RESULTS: We report a statistically significant Pearson's correlation coefficient (PCC) of 0.81 (p < 0.01) between the Hb value estimated by the proposed methodology and gold standard values of Hb, with a Root Mean Square Error (RMSE) of 1.353 ± 0.042 g/dL. The performance of the stacked regressor model was significantly better than the performance of individual regressors (low RMSE, and better CC; p < 0.05). Post-hoc analysis showed that including pregnant women in the training data set significantly improved the performance of the algorithm. CONCLUSION: This article demonstrates the feasibility of a machine learning based non-invasive hemoglobin measurement system, especially for maternal anemia detection. SIGNIFICANCE: By developing and demonstrating a machine learning approach on a large data set, we have demonstrated that such an approach could become the basis for a public health screening tool to detect and treat maternal anemia and could supplement global health intervention strategies.

Molecular Dynamics Information Improves cis-Peptide-Based Function Annotation of Proteins.

cis-Peptide bonds, whose occurrence in proteins is rare but evolutionarily conserved, are implicated to play an important role in protein function. This has led to their previous use in a homology-independent, fragment-match-based protein function annotation method. However, proteins are not static molecules; dynamics is integral to their activity. This is nicely epitomized by the geometric isomerization of cis-peptide to trans form for molecular activity. Hence we have incorporated both static (cis-peptide) and dynamics information to improve the prediction of protein molecular function. Our results show that cis-peptide information alone cannot detect functional matches in cases where cis-trans isomerization exists but 3D coordinates have been obtained for only the trans isomer or when the cis-peptide bond is incorrectly assigned as trans. On the contrary, use of dynamics information alone includes false-positive matches for cases where fragments with similar secondary structure show similar dynamics, but the proteins do not share a common function. Combining the two methods reduces errors while detecting the true matches, thereby enhancing the utility of our method in function annotation. A combined approach, therefore, opens up new avenues of improving existing automated function annotation methodologies.

Structure and specificity of a new class of Ca2+-independent housekeeping sortase from Streptomyces avermitilis provide insights into its non-canonical substrate preference.

Surface proteins in Gram-positive bacteria are incorporated into the cell wall through a peptide ligation reaction catalyzed by transpeptidase sortase. Six main classes (A-F) of sortase have been identified of which class A sortase is meant for housekeeping functions. The prototypic housekeeping sortase A (SaSrtA) from Staphylococcus aureus cleaves LPXTG-containing proteins at the scissile T-G peptide bond and ligates protein-LPXT to the terminal Gly residue of the nascent cross-bridge of peptidoglycan lipid II precursor. Sortase-mediated ligation ("sortagging") of LPXTG-containing substrates and Gly-terminated nucleophiles occurs in vitro as well as in cellulo in the presence of Ca2+ and has been applied extensively for protein conjugations. Although the majority of applications emanate from SaSrtA, low catalytic efficiency, LPXTG specificity restriction, and Ca2+ requirement (particularly for in cellulo applications) remain a drawback. Given that Gram-positive bacteria genomes encode a variety of sortases, natural sortase mining can be a viable complementary approach akin to engineering of wild-type SaSrtA. Here, we describe the structure and specificity of a new class E sortase (SavSrtE) annotated to perform housekeeping roles in Streptomyces avermitilis Biochemical experiments define the attributes of an optimum peptide substrate, demonstrate Ca2+-independent activity, and provide insights about contrasting functional characteristics of SavSrtE and SaSrtA. Crystal structure, substrate docking, and mutagenesis experiments have identified a critical residue that dictates the preference for a non-canonical LAXTG recognition motif over LPXTG. These results have implications for rational tailoring of substrate tolerance in sortases. Besides, Ca2+-independent orthogonal specificity of SavSrtE is likely to expand the sortagging toolkit.

Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation.

Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve > 0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

Crystallization and preliminary X-ray diffraction studies of sortase A from Streptococcus pneumoniae.

Sortases are cell-membrane-anchored cysteine transpeptidases that are essential for the assembly and anchoring of cell-surface adhesins in Gram-positive bacteria. Thus, they play critical roles in virulence, infection and colonization by pathogens. Sortases have been classified into four types based on their primary sequence and the target-protein motifs that they recognize. All Gram-positive bacteria express a class A housekeeping sortase (SrtA). Sortase A from Streptococcus pneumoniae (NP_358691) has been crystallized in two crystal forms. Diamond-shaped crystals of ΔN(59)SrtA diffracted to 4.0 Å resolution and belonged to a tetragonal system with unit-cell parameters a = b = 122.8, c = 86.5 Å, α = ß = γ = 90°, while rod-shaped crystals of ΔN(81)SrtA diffracted to 2.91 Å resolution and belonged to the monoclinic space group P2(1) with unit-cell parameters a = 66.8, b = 103.47, c = 74.79 Å, α = γ = 90, ß = 115.65°. The Matthews coefficient (V(M) = 2.77 Å(3) Da(-1)) with ~56% solvent content suggested the presence of four molecules in the asymmetric unit for ΔN(81)SrtA. Also, a multi-copy search using a monomer as a probe in the molecular-replacement method resulted in the successful location of four sortase molecules in the asymmetric unit, with statistics R = 41.61, R(free) = 46.44, correlation coefficient (CC) = 64.31, CC(free) = 57.67.