Popper or Kuhn: Truth and the progress of science

The questions of whether science pursues truth as correspondence to reality and whether science in fact progresses towards attaining a truthful understanding of physical reality are fundamental and contested in the philosophy of science. On one side of the debate stands Popper, who argues that science is objective, necessarily assumes a correspondence theory of truth, and inevitably progresses toward truth as physical theories develop, gaining a more truthful understanding of reality through progressively more sophisticated empirical analysis. Conversely Kuhn, influenced by postmodern philosophy, argues that ultimate truth cannot be attained since no objective metaphysical reality exists and it cannot be known, and consequently the notion of scientific objectivity and "progress" is a myth, marred by philosophical and ideological value judgments. Ultimately, Kuhn reduces so-called scientific progress through the adoption of successive paradigms to leaps of "faith". This paper seeks a reconciliation of the two extremes, arguing that Popper is correct in the sense that science assumes a correspondence theory of truth and may progress toward truth as physical theories develop, while simultaneously acknowledging with Kuhn that science is not purely objective and free of value judgments. The notion of faith is also critical, for it was the acknowledgement of God's existence as the creator and instituter of observable natural laws which allowed the development of science and the scientific method in the first place. Therefore, accepting and synthesising the contentions that science is to some extent founded on faith, assumes and progresses toward truth, and is subject to value judgments is necessary for the progress of science.

Ambient air pollution exposure estimation for the global burden of disease 2013

Exposure to ambient air pollution is a major risk factor for global disease. Assessment of the impacts of air pollution on population health and the evaluation of trends relative to other major risk factors requires regularly updated, accurate, spatially resolved exposure estimates. We combined satellite-based estimates, chemical transport model (CTM) simulations and ground measurements from 79 different countries to produce new global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0.1° spatial resolution for five-year intervals from 1990-2010 and the year 2013. These estimates were then applied to assess population-weighted mean concentrations for 1990 – 2013 for each of 188 countries. In 2013, 87% of the world’s population lived in areas exceeding the World Health Organization (WHO) Air Quality Guideline of 10 μg/m3 PM2.5 (annual average). Between 1990 and 2013, decreases in population-weighted mean concentrations of PM2.5 were evident in most high income countries, in contrast to increases estimated in South Asia, throughout much of Southeast Asia, and in China. Population-weighted mean concentrations of ozone increased in most countries from 1990 - 2013, with modest decreases in North America, parts of Europe, and several countries in Southeast Asia.

Using enterprise social networks as innovation platforms

Do enterprise social network platforms in an organization make the company more innovative? In theory, through communication, collaboration, and knowledge exchange, innovation ideas can easily be expressed, shared, and discussed with many partners in the organization. Yet, whether this guarantees innovation success remains to be seen. The authors studied how innovation ideas moved--or not--from an enterprise social network platform to regular innovation processes at a large Australian retailer. They found that the success of innovation ideas depends on how easily understandable the idea is on the platform, how long it has been discussed, and how powerful the social network participants are in the organization. These findings inform management strategies for the governance of enterprise social network use and the organizational innovation process.

Solution NMR studies of acetohydroxy acid synthase I: Identification of the sites of inter-subunit interactions using multidimensional NMR methods

The novel multidomain organization in the multimeric Escherichia coli AHAS I (ilvBN) enzyme has been dissected to generate polypeptide fragments. These fragments when cloned, expressed and purified reassemble in the presence of cofactors to yield a catalytically competent enzyme. Structural characterization of AHAS has been impeded due to the fact that the holoenzyme is prone to dissociation leading to heterogeneity in samples. Our approach has enabled the structural characterization using high-resolution nuclear magnetic resonance methods. Near complete sequence specific NMR assignments for backbone H-N, N-15, C-13 alpha and C-13(beta) atoms of the FAD binding domain of ilvB have been obtained on samples isotopically enriched in H-2, C-13 and N-15. The secondary structure determined on the basis of observed C-13(alpha) secondary chemical shifts and sequential NOEs indicates that the secondary structure of the FAD binding domain of E. coli AHAS large Subunit (ilvB) is similar to the structure of this domain in the catalytic subunit of yeast AHAS. Protein-protein interactions involving the regulatory subunit (ilvN) and the domains of the catalytic subunit (ilvB) were studied using circular dichroic and isotope edited solution nuclear magnetic resonance spectroscopic methods. Observed changes in circular dichroic spectra indicate that the regulatory subunit (ilvN) interacts with ilvB alpha and ilvB beta domains of the catalytic subunit and not with the ilvB gamma domain. NMR chemical shift mapping methods show that ilvN binds close to the FAD binding site in ilvB beta and proximal to the intrasubunit ilvB alpha/ilvB beta domain interface. The implication of this interaction on the role of the regulatory subunit oil the activity of the holoenzyme is discussed. NMR studies of the regulatory domains show that these domains are structured in solution. Preliminary evidence for the interaction of ilvN with the metabolic end product of the pathway, viz., valine is also presented.

Knowledge management research in the construction industry: a review

Purpose: Knowledge management (KM) is important to the knowledge-intensive construction industry. The diversified and changing nature of works in this field warrants us to stocktake, identify changes and map out KM research framework for future exploration. Design/methodology/approach: The study involves three aspects. First, three stages of KM research in construction were distinguished in terms of the time distribution of 217 target publications. Major topics in the stages were extracted for understanding the changes of research emphasis from evolutionary perspective. Second, the past works were summed up in a three-dimensional research framework in terms of management organization, managerial methodology and approach, and managerial objective. Finally, potential research orientations in the future were predicted to expand the existing research framework. Findings: It was found that (1) KM research has significantly blossomed in the last two decades with a great potential; (2) major topics of KM were changing in terms of technology, technique, organization, attribute of knowledge and research objectives; (3) past KM studies centred around management organization, managerial methodology and approach, and managerial objective thus a three-dimensional research framework was proposed; (4) within the research framework, team-level, project-level and firm-level KM were studied to achieve project, organizational and competitive objectives by integrated methodologies of information technology, social technique and KM process tool; and (5) nine potential research orientations were predicted corresponding to the three dimensions. Finally, an expanded research framework was proposed to encourage and guide future research works in this field. Research limitations/implications: The paper only focused on the construction industry. The findings need further exploration in order to discover any possible missing important research works which were not published in English or not included in the time period. Originality/value: The paper formed a systematic framework of KM research in construction and predicted the potential research orientations. It provides much value for the researchers who want to understand the past and the future of global KM research in the construction industry.

An algorithm to find similar internal sequence repeats

In recent years, identification of sequence patterns has been given immense importance to understand better their significance with respect to genomic organization and evolutionary processes. To this end, an algorithm has been derived to identify all similar sequence repeats present in a protein sequence. The proposed algorithm is useful to correlate the three-dimensional structure of various similar sequence repeats available in the Protein Data Bank against the same sequence repeats present in other databases like SWISS-PROT, PIR and Genome databases.

Analysis of the fusA2 locus encoding EFG2 in Mycobacterium smegmatis

The translation elongation factor G (EFG) is encoded by the fusA gene.Several bacteria possess a second fusA-like locus,fusA2 which encodes EFG2. A comparison of EFG and EFG2 from various bacteria reveals that EFG2 preserves domain organization and maintains significant sequence homology with EFG, suggesting that EFG2 may function as an elongation factor. However, with the single exception of a recent study on Thermus thermophilus EFG2, this class of EFG-like factors has not been investigated. Here, we have characterized EFG2 (MSMEG_6535) from Mycobacterium smegmatis. Expression of EFG2 was detected in stationary phase cultures of M.smegmatis (Msm). Our in vitro studies show that while MsmEFG2 binds guanine nucleotides, it lacks the ribosome-dependent GTPase activity characteristic of EFGs. Furthermore,unlike MsmEFG (MSMEG_1400), MsmEFG2 failed to rescue an E. coli strain harboring a temperature-sensitive allele of EFG, for its growth at thenon-permissive temperature. Subsequent experiments showed that the fusA2 gene could be disrupted in M. smegmatis mc(2)155 with Kan(R)marker. The M. smegmatis fusA2::kan strain was viable and showed growth kinetics similar to that of the parent strain (wild-type for fusA2).However, in the growth competition assays, the disruption of fusA2 was found to confer a fitness disadvantage to M. smegmatis, raising the possibility that EFG2 is of some physiological relevance to mycobacteria.

Posters versus lurkers. Improving participation in enterprise social networks through management interventions

This thesis investigated the phenomenon of underutilised Enterprise social networks (ESNs). Guided by established theories, we identified key reasons that drive ESN members to either post (i.e., create content) or lurk (i.e., read others' content) and examined the influence of three management interventions - aim to boost participation - on lurkers' and posters' beliefs and participation. We test our model with data collected from 366 members in Google⁺ communities in a large Australian retail organization. We find that posters and lurkers are motivated and hindered by different factors. Moreover, management interventions do not – always – yield the hoped-for results among lurkers.

Processing of SeMV polyproteins revisited

Processing of Sesbania mosaic virus (SeMV) polyprotein 2a and 2ab was reanalyzed in the view of the new genome organization of sobemoviruses. Polyprotein 2a when expressed in E coli, from the new cDNA clone, got cleaved at the earlier identified sites E325-T326, E402-T403 and E498-S499 to release protease, VPg, P10 and P8, respectively. Additionally, a novel cleavage was identified within the protease domain at position E132-S133, which was found to be essential for efficient polyprotein processing. Products, corresponding to cleavages identified in E. coli, were also detected in infected Sesbania leaves. Interestingly, though the sites are exactly the same in polyprotein 2ab, it got cleaved between Protease-VPg but not between VPg-RdRp. This indicates to a differential cleavage preference, governed probably by the conformation of 2ab. Also, the studies revealed that, in SeMV, processing is regulated by mode of cleavage and context of the cleavage site.

The Role of UPF0157 in the Folding of M-tuberculosis Dephosphocoenzyme A Kinase and the Regulation of the Latter by CTP

Background: Targeting the biosynthetic pathway of Coenzyme A (CoA) for drug development will compromise multiple cellular functions of the tubercular pathogen simultaneously. Structural divergence in the organization of the penultimate and final enzymes of CoA biosynthesis in the host and pathogen and the differences in their regulation mark out the final enzyme, dephosphocoenzyme A kinase (CoaE) as a potential drug target. Methodology/Principal Findings: We report here a complete biochemical and biophysical characterization of the M. tuberculosis CoaE, an enzyme essential for the pathogen's survival, elucidating for the first time the interactions of a dephosphocoenzyme A kinase with its substrates, dephosphocoenzyme A and ATP; its product, CoA and an intrinsic yet novel inhibitor, CTP, which helps modulate the enzyme's kinetic capabilities providing interesting insights into the regulation of CoaE activity. We show that the mycobacterial enzyme is almost 21 times more catalytically proficient than its counterparts in other prokaryotes. ITC measurements illustrate that the enzyme follows an ordered mechanism of substrate addition with DCoA as the leading substrate and ATP following in tow. Kinetic and ITC experiments demonstrate that though CTP binds strongly to the enzyme, it is unable to participate in DCoA phosphorylation. We report that CTP actually inhibits the enzyme by decreasing its Vmax. Not surprisingly, a structural homology search for the modeled mycobacterial CoaE picks up cytidylmonophosphate kinases, deoxycytidine kinases, and cytidylate kinases as close homologs. Docking of DCoA and CTP to CoaE shows that both ligands bind at the same site, their interactions being stabilized by 26 and 28 hydrogen bonds respectively. We have also assigned a role for the universal Unknown Protein Family 0157 (UPF0157) domain in the mycobacterial CoaE in the proper folding of the full length enzyme. Conclusions/Significance: In view of the evidence presented, it is imperative to assign a greater role to the last enzyme of Coenzyme A biosynthesis in metabolite flow regulation through this critical biosynthetic pathway.

Recognition of Interaction Interface Residues in Low-Resolution Structures of Protein Assemblies Solely from the Positions of C alpha Atoms

Background: The number of available structures of large multi-protein assemblies is quite small. Such structures provide phenomenal insights on the organization, mechanism of formation and functional properties of the assembly. Hence detailed analysis of such structures is highly rewarding. However, the common problem in such analyses is the low resolution of these structures. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the C alpha atoms which are modeled with modest accuracy. Methodology/Principal Findings: In this paper first we present an objective approach to identify potentially solvent exposed and buried residues solely from the position of C alpha atoms and amino acid sequence using residue type-dependent thresholds for accessible surface areas of C alpha. We extend the method further to recognize potential protein-protein interface residues. Conclusion/Significance: Our approach to identify buried and exposed residues solely from the positions of C alpha atoms resulted in an accuracy of 84%, sensitivity of 83-89% and specificity of 67-94% while recognition of interfacial residues corresponded to an accuracy of 94%, sensitivity of 70-96% and specificity of 58-94%. Interestingly, detailed analysis of cases of mismatch between recognition of interface residues from C alpha positions and all-atom models suggested that, recognition of interfacial residues using C alpha atoms only correspond better with intuitive notion of what is an interfacial residue. Our method should be useful in the objective analysis of structures of protein assemblies when positions of only C alpha positions are available as, for example, in the cases of integration of cryo-EM data and high resolution structures of the components of the assembly.

Structure-Based Phylogeny as a Diagnostic for Functional Characterization of Proteins with a Cupin Fold

Background: The members of cupin superfamily exhibit large variations in their sequences, functions, organization of domains, quaternary associations and the nature of bound metal ion, despite having a conserved beta-barrel structural scaffold. Here, an attempt has been made to understand structure-function relationships among the members of this diverse superfamily and identify the principles governing functional diversity. The cupin superfamily also contains proteins for which the structures are available through world-wide structural genomics initiatives but characterized as ``hypothetical''. We have explored the feasibility of obtaining clues to functions of such proteins by means of comparative analysis with cupins of known structure and function. Methodology/Principal Findings: A 3-D structure-based phylogenetic approach was undertaken. Interestingly, a dendrogram generated solely on the basis of structural dissimilarity measure at the level of domain folds was found to cluster functionally similar members. This clustering also reflects an independent evolution of the two domains in bicupins. Close examination of structural superposition of members across various functional clusters reveals structural variations in regions that not only form the active site pocket but are also involved in interaction with another domain in the same polypeptide or in the oligomer. Conclusions/Significance: Structure-based phylogeny of cupins can influence identification of functions of proteins of yet unknown function with cupin fold. This approach can be extended to other proteins with a common fold that show high evolutionary divergence. This approach is expected to have an influence on the function annotation in structural genomics initiatives.

Practising Western Science Outside the West: Personal Observations on the Indian Scene

Modern science, which was an indigenous product of Western culture, is now being practised in many non-Western countries. This paper discusses the peculiar social, cultural and intellectual problems which scientists of these non-Western countries face in adopting Western science in their situations, with special reference to India. It is pointed out that, in addition to money and communication, it is necessary to have a proper psychological gestalt to practise science satisfactorily. The author analyzes his experience as a physics student in India and in the United States to clarify the nature of this psychological gestalt, and to explain what makes it difficult for non-Western scientists to acquire it.

Amorphization by dislocation accumulation in shear bands

Microcrystalline γ-Y2Si2O7 was indented at room temperature and the deformation microstructure was investigated by transmission electron microscopy in the vicinity of the indent. The volume directly beneath the indent comprises nanometer-sized grains delimited by an amorphous phase while dislocations dominate in the periphery either as dense slip bands in the border of the indent or, further away, as individual dislocations. The amorphous layers and the slip bands are a few nanometers thick. They lie along well-defined crystallographic planes. The microstructural organization is consistent with a stress-induced amorphization process whereby, under severe mechanical conditions, the crystal to amorphous transformation is mediated by slip bands containing a high density of dislocations. It is suggested that the damage tolerance of γ-Y2Si2O7, which is exceptional for a ceramic material, benefits from this transformation.