System identification and validation for output prediction of a dynamic hydrologic process

The paper presents an identification procedure for a dynamic model of am hydrologic process. The process involves solute transport in streams subject to aquifer interaction and unsteady flows and the intended use of the model is prediction. Detailed assumptions and results are provided to illustrate the level of comprehensive analysis required to assess model adequacy. The assessment procedure easily generalizes to any dynamic model which is linear-in-the-parameters. As a fundamental tool, instrumental variable algorithms can be adopted which have a number of attractive features. These algorithms make both model-order identification and specification among alternatives a straightforward task. They are known to be consistent estimators in the presence of a wide class of errors. It is seen that they can be made stable and robust in the presence of data outliers. Instrumental variable algorithms can also be used which are asymptotically efficient and provide a covariance matrix of parameter estimates. The paper shows how they aid the quantification of predictive uncertainty and investigates the validity of the underlying assumptions. Further, it illustrates that, when instrumental variable algorithms are used in recursive mode, they can be used not only as an additional tool to access model inadequacy but also as an aid to model improvements.     

Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin.

Post-translational modifications of histone amino termini are an important regulatory mechanism that induce transitions in chromatin structure, thereby contributing to epigenetic gene control and the assembly of specialized chromosomal subdomains. Methylation of histone H3 at lysine 9 (H3-Lys9) by site-specific histone methyltransferases (Suv39h HMTases) marks constitutive heterochromatin. Here, we show that H3-Lys9 methylation also occurs in facultative heterochromatin of the inactive X chromosome (Xi) in female mammals. H3-Lys9 methylation is retained through mitosis, indicating that it might provide an epigenetic imprint for the maintenance of the inactive state. Disruption of the two mouse Suv39h HMTases abolishes H3-Lys9 methylation of constitutive heterochromatin but not that of the Xi. In addition, HP1 proteins, which normally associate with heterochromatin, do not accumulate with the Xi. These observations suggest the existence of an Suv39h-HP1-independent pathway regulating H3-Lys9 methylation of facultative heterochromatin.     

A comparison of pyridoxal 5′-phosphate dependent decarboxylase and transaminase enzymes at a molecular level

Pyridoxal 5′-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C^α of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-α-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.     

A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level.

Pyridoxal 5'-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C alpha of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-alpha-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.     

Single cell biology beyond the era of antibodies: relevance,challenges, and promises in biomedical research

Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems. Even though microfluidics and microraft array are newer techniques exploited for single cell biology, fluorescence-activated cell sorting (FACS) remains the gold standard technique for isolation of cells for many biomedical applications, like stem cell therapy. Here, we present a comprehensive and comparative account of some of the probes that are useful in FACS. Further, we illustrate how these techniques could be applied in biomedical research. It is postulated that intracellular molecular markers like nucleostemin (GNL3), alkaline phosphatase (ALPL) and HIRA can be used for improving the outcome of cardiac as well as bone regeneration. Another field that could utilize intracellular markers is diagnostics, and we propose the use of specific peptide nucleic acid probes (PNPs) against certain miRNAs for cancer surgical margin prediction. The newer techniques for single cell biology, based on intracellular molecules, will immensely enhance the repertoire of possible markers for the isolation of cell types useful in biomedical research.     

Why history matters to philosophy of physics

Naturalized metaphysics remains the default presupposition of much contemporary philosophy of physics. As metaphysics is supposed to concern the general structure of reality, so scientific naturalism draws upon our best physical theories to attempt to answer the foundational question “par excellence ” viz., “how could the world possibly be the way this theory says it is?” A particular case study, Hilbert's attempt to analyze and explain a seeming “pre-established harmony” between mind and nature, is offered as a salutary reminder that naturalism's ready inference from physical theory to ontology may be too quick.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.     

Dam-forming cacti and nitrogen enrichment in a pi?on-juniper woodland in northwestern Arizona

In a pi?on-juniper woodland in northwestern Arizona, connected basal cladodes of a prickly pear cactus ( Opuntia littoralis var. martiniana ) form check dams that cause deposition of N-rich detritus interspaces otherwise lacking litter. Seventy-eight percent of connected basal cladodes measured in transects grew at an angle (with respect to the slope contour) ≤ 45° -an orientation facilitating deposition of flood-borne debris. Soil total N was significantly greater ( P P = 0.0001) compared to adjacent interspaces. Soil total N and organic C above cactus dams were equal to areas beneath canopies (tree and shrub combined). Net NO 3 - (0-5 cm depth) above cactus dams was significantly greater ( P = 0.0001) than below cactus dams, at interspaces, and beneath canopies. Net NH 4 + (0-5 cm soil depth) above cactus dams was significantly greater ( P s ￣x = 0.625, P = 0.0001).