Identifying Robust Plans through Plan Diagram Reduction

Estimates of predicate selectivities by database query optimizers often differ significantly from those actually encountered during query execution, leading to poor plan choices and inflated response times. In this paper, we investigate mitigating this problem by replacing selectivity error-sensitive plan choices with alternative plans that provide robust performance. Our approach is based on the recent observation that even the complex and dense "plan diagrams" associated with industrial-strength optimizers can be efficiently reduced to "anorexic" equivalents featuring only a few plans, without materially impacting query processing quality. Extensive experimentation with a rich set of TPC-H and TPC-DS-based query templates in a variety of database environments indicate that plan diagram reduction typically retains plans that are substantially resistant to selectivity errors on the base relations. However, it can sometimes also be severely counter-productive, with the replacements performing much worse. We address this problem through a generalized mathematical characterization of plan cost behavior over the parameter space, which lends itself to efficient criteria of when it is safe to reduce. Our strategies are fully non-invasive and have been implemented in the Picasso optimizer visualization tool.

Novel Pentameric Structure of the Diarrhea-Inducing Region of the Rotavirus Enterotoxigenic Protein NSP4

A novel pentameric structure which differs from the previously reported tetrameric form of the diarrhea-inducing region of the rotavirus enterotoxin NSP4 is reported here. A significant feature of this pentameric form is the absence of the calcium ion located in the core region of the tetrameric structures. The lysis of cells, the crystallization of the region spanning residues 95 to 146 of NSP4 (NSP4(95-146)) of strain ST3 (ST3: NSP4(95-146)) at acidic pH, and comparative studies of the recombinant purified peptide under different conditions by size-exclusion chromatography (SEC) and of the crystal structures suggested pH-, Ca(2+)-, and protein concentration-dependent oligomeric transitions in the peptide. Since the NSP4(95-146) mutant lacks the N-terminal amphipathic domain (AD) and most of the C-terminal flexible region (FR), to demonstrate that the pentameric transition is not a consequence of the lack of the N- and C-terminal regions, glutaraldehyde cross-linking of the Delta N72 and Delta N94 mutant proteins, which contain or lack the AD, respectively, but possess the complete C-terminal FR, was carried out. The results indicate the presence of pentamers in preparations of these longer mutants. Detailed SEC analyses of Delta N94 prepared under different conditions, however, revealed protein concentration-dependent but metal ion-and pH-independent pentamer accumulation at high concentrations which dissociated into tetramers and lower oligomers at low protein concentrations. While calcium appeared to stabilize the tetramer, magnesium in particular stabilized the dimer. Delta N72 existed primarily in the multimeric form under all conditions. These findings of a calcium-free NSP4 pentamer and its concentration-dependent and largely calcium-independent oligomeric transitions open up a new dimension in an understanding of the structural basis of its multitude of functions.

Determination of alpha(s)(M-tau(2)) from improved fixed order perturbation theory

We revisit the extraction of alpha(s)(M-tau(2)) from the QCD perturbative corrections to the hadronic tau branching ratio, using an improved fixed-order perturbation theory based on the explicit summation of all renormalization-group accessible logarithms, proposed some time ago in the literature. In this approach, the powers of the coupling in the expansion of the QCD Adler function are multiplied by a set of functions D-n, which depend themselves on the coupling and can be written in a closed form by iteratively solving a sequence of differential equations. We find that the new expansion has an improved behavior in the complex energy plane compared to that of the standard fixed-order perturbation theory (FOPT), and is similar but not identical to the contour-improved perturbation theory (CIPT). With five terms in the perturbative expansion we obtain in the (MS) over bar scheme alpha(s)(M-tau(2)) = 0.338 +/- 0.010, using as input a precise value for the perturbative contribution to the hadronic width of the tau lepton reported recently in the literature.

Cyclic AMP-induced Conformational Changes in Mycobacterial Protein Acetyltransferases

The activities of a number of proteins are regulated by the binding of cAMP and cGMP to cyclic nucleotide binding (CNB) domains that are found associated with one or more effector domains with diverse functions. Although the conserved architecture of CNB domains has been extensively studied by x-ray crystallography, the key to unraveling the mechanisms of cAMP action has been protein dynamics analyses. Recently, we have identified a novel cAMP-binding protein from mycobacteria, where cAMP regulates the activity of an associated protein acetyltransferase domain. In the current study, we have monitored the conformational changes that occur upon cAMP binding to the CNB domain in these proteins, using a combination of bioluminescence resonance energy transfer and amide hydrogen/deuterium exchange mass spectrometry. Coupled with mutational analyses, our studies reveal the critical role of the linker region (positioned between the CNB domain and the acetyltransferase domain) in allosteric coupling of cAMP binding to activation of acetyltransferase catalysis. Importantly, major differences in conformational change upon cAMP binding were accompanied by stabilization of the CNB and linker domain alone. This is in contrast to other cAMP-binding proteins, where cyclic nucleotide binding has been shown to involve intricate and parallel allosteric relays. Finally, this powerful convergence of results from bioluminescence resonance energy transfer and hydrogen/deuterium exchange mass spectrometry reaffirms the power of solution biophysical tools in unraveling mechanistic bases of regulation of proteins in the absence of high resolution structural information.

Some questions on integral geometry on noncompact symmetric spaces of higher rank

Let be a noncompact symmetric space of higher rank. We consider two types of averages of functions: one, over level sets of the heat kernel on and the other, over geodesic spheres. We prove injectivity results for functions in which extend the results in Pati and Sitaram (Sankya Ser A 62:419-424, 2000).

Case for multiple views of function in design based on a common definition

Functions are important in designing. However, several issues hinder progress with the understanding and usage of functions: lack of a clear and overarching definition of function, lack of overall justifications for the inevitability of the multiple views of function, and scarcity of systematic attempts to relate these views with one another. To help resolve these, the objectives of this research are to propose a common definition of function that underlies the multiple views in literature and to identify and validate the views of function that are logically justified to be present in designing. Function is defined as a change intended by designers between two scenarios: before and after the introduction of the design. A framework is proposed that comprises the above definition of function and an empirically validated model of designing, extended generate, evaluate, modify, and select of state-change, and an action, part, phenomenon, input, organ, and effect model of causality (Known as GEMS of SAPPhIRE), comprising the views of activity, outcome, requirement-solution-information, and system-environment. The framework is used to identify the logically possible views of function in the context of designing and is validated by comparing these with the views of function in the literature. Describing the different views of function using the proposed framework should enable comparisons and determine relationships among the various views, leading to better understanding and usage of functions in designing.

Role of the loop L-4,L-5 in allosteric regulation in mtHsp70s: in vivo significance of domain communication and its implications in protein translocation

Mitochondrial Hsp70 (mtHsp70) is essential for a vast repertoire of functions, including protein import, and requires effective interdomain communication for efficient partner-protein interactions. However, the in vivo functional significance of allosteric regulation in eukaryotes is poorly defined. Using integrated biochemical and yeast genetic approaches, we provide compelling evidence that a conserved substrate-binding domain (SBD) loop, L-4,L-5, plays a critical role in allosteric communication governing mtHsp70 chaperone functions across species. In yeast, a temperature-sensitive L-4,L-5 mutation (E467A) disrupts bidirectional domain communication, leading to compromised protein import and mitochondrial function. Loop L-4,L-5 functions synergistically with the linker in modulating the allosteric interface and conformational transitions between SBD and the nucleotide-binding domain (NBD), thus regulating interdomain communication. Second-site intragenic suppressors of E467A isolated within the SBD suppress domain communication defects by conformationally altering the allosteric interface, thereby restoring import and growth phenotypes. Strikingly, the suppressor mutations highlight that restoration of communication from NBD to SBD alone is the minimum essential requirement for effective in vivo function when primed at higher basal ATPase activity, mimicking the J-protein-bound state. Together these findings provide the first mechanistic insights into critical regions within the SBD of mtHsp70s regulating interdomain communication, thus highlighting its importance in protein translocation and mitochondrial biogenesis.

Density control of ZnO nanowires grown using Au-PMMA nanoparticles and their growth behavior.

Au nanoparticles stabilized by poly(methyl methacrylate) (PMMA) were used as a catalyst to grow vertically aligned ZnO nanowires (NWs). The density of ZnO NWs with very uniform diameter was controlled by changing the concentration of Au-PMMA nanoparticles (NPs). The density was in direct proportion to the concentration of Au-PMMA NPs. Furthermore, the growth process of ZnO NWs using Au-PMMA NPs was systematically investigated through comparison with that using Au thin film as a catalyst. Au-PMMA NPs induced polyhedral-shaped bases of ZnO NWs separated from each other, while Au thin film formed a continuous network of bases of ZnO NWs. This approach provides a facile and cost-effective catalyst density control method, allowing us to grow high-quality vertically aligned ZnO NWs suitable for many viable applications.

Fixed Points of Closed and Compact Composite Sequences of Operators and Projectors in a Class of Banach Spaces

Some results on fixed points related to the contractive compositions of bounded operators in a class of complete metric spaces which can be also considered as Banach's spaces are discussed through the paper. The class of composite operators under study can include, in particular, sequences of projection operators under, in general, oblique projective operators. In this paper we are concerned with composite operators which include sequences of pairs of contractive operators involving, in general, oblique projection operators. The results are generalized to sequences of, in general, nonconstant bounded closed operators which can have bounded, closed, and compact limit operators, such that the relevant composite sequences are also compact operators. It is proven that in both cases, Banach contraction principle guarantees the existence of unique fixed points under contractive conditions.

The application of metallointercalators in recognition of and charge transport in nucleic acids

Metal complexes that utilize the 9,10-phenanthrene quinone diimine (phi) moiety bind to DNA through the major groove. These metallointercalators can recognize DNA sites and perform reactions on DNA as a substrate. The site-specific metallointercalator Λ-1-Rh(MGP)_2phi^(5+) competitively disrupts the major groove binding of a transcription factor, yAP-1, from an oligonucleotide that contains a common binding site. The demonstration that metal complexes can prevent transcription factor binding to DNA site-specifically is an important step in using metallointercalators as therapeutics.

The distinctive photochemistry of metallointercalators can also be applied to promote long range charge transport in DNA. Experiments using duplexes with regions 4 to 10 nucleotides long containing strictly adenine and thymine sequences of varying order showed that radical migration is more dependent on the sequence of bases, and less dependent on the distance between the guanine doublets. This result suggests that mechanistic proposals of long range charge transport must involve all the bases.

RNA/DNA hybrids show charge migration to guanines from a remote site, thus demonstrating that nucleic acid stacking other than B-form can serve as a radical bridge. Double crossover DNA assemblies also provide a medium for charge transport at distances up to 100 Å from the site of radical introduction by a tethered metal complex. This radical migration was found to be robust to mismatches, and limited to individual, electronically distinct base stacks. In single DNA crossover assemblies, which have considerably greater flexibility, charge migration proceeds to both base stacks due to conformational isomers not present in the rigid and tightly annealed double crossovers.

Finally, a rapid, efficient, gel-based technique was developed to investigate thymine dimer repair. Two oligonucleotides, one radioactively labeled, are photoligated via the bases of a thymine-thymine interface; reversal of this ligation is easily visualized by gel electrophoresis. This assay was used to show that the repair of thymine dimers from a distance through DNA charge transport can be accomplished with different photooxidants.

Thus, nucleic acids that support long range charge transport have been shown to include A-track DNA, RNA/DNA hybrids, and single and double crossovers, and a method for thymine dimer repair detection using charge transport was developed. These observations underscore and extend the remarkable finding that DNA can serve a medium for charge transport via the heteroaromatic base stack.

Lq estimates for rearrangements of Fourier series

This work is concerned with estimating the upper envelopes S* of the absolute values of the partial sums of rearranged trigonometric sums. A.M. Garsia [Annals of Math. 79 (1964), 634-9] gave an estimate for the L₂ norms of the S*, averaged over all rearrangements of the original (finite) sum. This estimate enabled him to prove that the Fourier series of any function in L₂ can be rearranged so that it converges a.e. The main result of this thesis is a similar estimate of the L_q norms of the S*, for all even integers q. This holds for finite linear combinations of functions which satisfy a condition which is a generalization of orthonormality in the L₂ case. This estimate for finite sums is extended to Fourier series of L_q functions; it is shown that there are functions to which the Men’shov-Paley Theorem does not apply, but whose Fourier series can nevertheless be rearranged so that the S* of the rearranged series is in L_q.

Studies of dinucleoside monophosphates and monomer-polynucleotide interactions by proton magnetic resonance

The nature of the intra- and intermolecular base-stacking interactions involving several dinucleoside monophosphates in aqueous solution have been investigated by proton magnetic resonance spectrosocopy, and this method has been applied to a study of the interaction of polyuridylic acid with purine and adenosine monomers.

The pmr spectra of adenylyl (3' → 5') cytidine (ApC) and cytidylyl (3' → 5') adenosine (CpA) have been studied as a function of concentration and temperature. The results of these studies indicate that the intramolecular base-stacking interactions between the adenine and cytosine bases of these dinucleoside monophosphates are rather strong, and that the stacking tendencies are comparable for the two sequence isomers. The chemical shifts of the cytosine H₅ and adenine H₂ protons, and their variations with temperature, were shown to be consistent with stacked conformations in which both bases of the dinucleoside monophosphates are preferentially oriented in the anti conformation as in similar dApdC, and dCpdA (dA = deoxyadenosine; dC = deoxycytidine) segments in double helical DNA. The intramolecular stacking interaction was found to have a pronounced effect on the conformations of the ribose moieties, and these conformational changes are discussed. The concentration studies indicate extensive self-association of these dinucleoside monophosphates, and analysis of the concentration data facilitated determination of the dimerization constant for the association process as well as the nature of the intermolecular complexes.

The dependence of the ribose conformation upon the extent of intramolecular base-stacking was used to demonstrate that the base-base interaction in cytidylyl (3' → 5') cytidine (CpC) is rather strong, while there appears to be little interaction between the two uracil bases of uridylyl (3' → 5') uridine (UpU).

Studies of the binding of purine to several ribose and deoxyribose dinucleoside monophosphates show that the mode of interaction is base-stacking, and evidence for the formation of a purine-dinucleoside monophosphate intercalated complex is presented. The purine proton resonances are markedly broadened in this complex, and estimates of the purine linewidths in the complex and the equilibrium constant for purine intercalation are obtained.

A study of the interaction of unsubstitued purine with polyuridylic acid at 29°C by pmr indicated that purine binds to the uracil bases of the polymer by base-stacking. The severe broadening of the purine proton resonances observed provides strong evidence for the intercalation of purine between adjacent uracil bases of poly U. This interaction does not result in a more rigid or ordered structure for the polymer.

Investigation of the interaction between adenosine and polyuridylic acid revealed two modes of interaction between the monomer and the polymer, depending on the temperature. At temperatures above 26°C or so, monomeric adenosine binds to poly U by noncooperative A-U base stacking. Below this temperature, a rigid triple-stranded 1A:2U complex is formed, presumably via cooperative hydrogen-bonding as has previously been reported.

These results clearly illustrate the importance of base-stacking in non-specific interactions between bases, nucleosides and nucleotides, and also reveal the important role of the base-stacking interactions in cooperatively for med structures involving specific base-pairing where both types of interaction are possible.

1. Ultrasonic studies of binary liquid structure in the critical region. Theory and experiment for the 2,6-lutidine/water system. 2. Hartree-Fock calculations of electric polarizabilities of some simple atoms and molecules, and their practicality. 3. Calculation of vibrational transition probabilities in collinear atom-diatom and diatom-diatom collisions with Lennard-Jones interaction

Part 1. Many interesting visual and mechanical phenomena occur in the critical region of fluids, both for the gas-liquid and liquid-liquid transitions. The precise thermodynamic and transport behavior here has some broad consequences for the molecular theory of liquids. Previous studies in this laboratory on a liquid-liquid critical mixture via ultrasonics supported a basically classical analysis of fluid behavior by M. Fixman (e. g., the free energy is assumed analytic in intensive variables in the thermodynamics)--at least when the fluid is not too close to critical. A breakdown in classical concepts is evidenced close to critical, in some well-defined ways. We have studied herein a liquid-liquid critical system of complementary nature (possessing a lower critical mixing or consolute temperature) to all previous mixtures, to look for new qualitative critical behavior. We did not find such new behavior in the ultrasonic absorption ascribable to the critical fluctuations, but we did find extra absorption due to chemical processes (yet these are related to the mixing behavior generating the lower consolute point). We rederived, corrected, and extended Fixman's analysis to interpret our experimental results in these more complex circumstances. The entire account of theory and experiment is prefaced by an extensive introduction recounting the general status of liquid state theory. The introduction provides a context for our present work, and also points out problems deserving attention. Interest in these problems was stimulated by this work but also by work in Part 3.

Part 2. Among variational theories of electronic structure, the Hartree-Fock theory has proved particularly valuable for a practical understanding of such properties as chemical binding, electric multipole moments, and X-ray scattering intensity. It also provides the most tractable method of calculating first-order properties under external or internal one-electron perturbations, either developed explicitly in orders of perturbation theory or in the fully self-consistent method. The accuracy and consistency of first-order properties are poorer than those of zero-order properties, but this is most often due to the use of explicit approximations in solving the perturbed equations, or to inadequacy of the variational basis in size or composition. We have calculated the electric polarizabilities of H₂, He, Li, Be, LiH, and N₂ by Hartree-Fock theory, using exact perturbation theory or the fully self-consistent method, as dictated by convenience. By careful studies on total basis set composition, we obtained good approximations to limiting Hartree-Fock values of polarizabilities with bases of reasonable size. The values for all species, and for each direction in the molecular cases, are within 8% of experiment, or of best theoretical values in the absence of the former. Our results support the use of unadorned Hartree-Pock theory for static polarizabilities needed in interpreting electron-molecule scattering data, collision-induced light scattering experiments, and other phenomena involving experimentally inaccessible polarizabilities.

Part 3. Numerical integration of the close-coupled scattering equations has been carried out to obtain vibrational transition probabilities for some models of the electronically adiabatic H₂-H₂ collision. All the models use a Lennard-Jones interaction potential between nearest atoms in the collision partners. We have analyzed the results for some insight into the vibrational excitation process in its dependence on the energy of collision, the nature of the vibrational binding potential, and other factors. We conclude also that replacement of earlier, simpler models of the interaction potential by the Lennard-Jones form adds very little realism for all the complication it introduces. A brief introduction precedes the presentation of our work and places it in the context of attempts to understand the collisional activation process in chemical reactions as well as some other chemical dynamics.

Social structure and underwater behavior of harbor seals in southern Monterey Bay, California

To understand harbor seal social and mating strategies, I examined site fidelity, seasonal abundance and distribution, herd integrity, and underwater behavior of individual harbor seals in southern Monterey Bay. Individual harbor seals (n = 444) were identified by natural markings and represented greater than 80% of an estimated 520 seals within this community. Year to year fidelity of individual harbor seals to southern Monterey Bay coastline was 84% (n = 388), and long-term associations (>2 yrs) among individuals were common (>40%). Consistent with these long-term associations, harbor seals were highly social underwater throughout the year. Underwater social behavior included three primary types: (1) visual and acoustic displays, such as vocalizing, surface splashing, and bubble-blowing; (2) playful or agonistic social behavior such as rolling, mounting, attending, and biting; and (3) signal gestures such as head-thrusting, fore-flipper scratch~ng, and growling. Frequency of these types of behavior was related to seal age, gender, season, and resource availability. Underwater behavior had a variety of functions, including promotion of learning and social development, reduction of aggression and preservation of social bonds by maintaining social hierarchy, and facilitation of mate selection during breeding season. Social behavior among adult males was significantly correlated with vocalization characteristics (r = 0.99, X2 = 37.7, p = 0.00087), indicating that seals may assess their competition based on underwater vocalization displays and adopt individual strategies for attracting females during breeding season based on social status. Individual mating strategies may include defending underwater territories, using scramble tactics, and developing social alliances. (PDF contains 105 pages)

The activity view of inner speech

We distinguish two general approaches to inner speech (IS) the "format" and the "activity" views and defend the activity view. The format view grounds the utility of IS on features of the representational format of language, and is related to the thesis that the proper function of IS is to make conscious thinking possible. IS appears typically as a product constituted by representations of phonological features. The view also has implications for the idea that passivity phenomena in cognition may be misat-tributed IS. The activity view sees IS as a speaking activity that does not have a proper function in cognition. It simply inherits the array of functions of outer speech. We argue that it is methodologically advisable to start from this variety of uses, which suggests commonalities between internal and external activities. The format view has several problems; it has to deny "unsymbolized thinking"; it cannot easily explain how IS makes thoughts available to consciousness, and it cannot explain those uses of IS where its format features apparently play no role. The activity view not only lacks these problems but also has explanatory advantages: construing IS as an activity allows it to be integrally constituted by its content; the view is able to construe unsymbolized thinking as part of a continuum of phenomena that exploit the same mechanisms, and it offers a simple explanation for the variety of uses of IS