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Rationale: Our current understanding of tuberculosis (TB) pathophysiology is limited by a reliance on animal models, the paucity of human TB lung tissue, and traditional histopathological analysis, a destructive two-dimensional approach that provides limited spatial insight. Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more accurately inform preventive TB strategies. Objectives: To ascertain the 3D shape of the human tuberculous granuloma and its spatial relationship with airways and vasculature within large lung tissues. Methods: We characterized the 3D microanatomical environment of human tuberculous lungs by using micro computed tomography, histopathology, and immunohistochemistry. By using 3D segmentation software, we accurately reconstructed TB granulomas, vasculature, and airways in three dimensions and confirmed our findings by using histopathology and immunohistochemistry. Measurements and Main Results: We observed marked heterogeneity in the morphology, volume, and number of TB granulomas in human lung sections. Unlike depictions of granulomas as simple spherical structures, human necrotic granulomas exhibit complex, cylindrical, branched morphologies that are connected to the airways and shaped by the bronchi. The use of 3D imaging of human TB lung sections provides unanticipated insight into the spatial organization of TB granulomas in relation to the airways and vasculature. Conclusions: Our findings highlight the likelihood that a single, structurally complex lesion could be mistakenly viewed as multiple independent lesions when evaluated in two dimensions. In addition, the lack of vascularization within obstructed bronchi establishes a paradigm for antimycobacterial drug tolerance. Lastly, our results suggest that bronchogenic spread of Mycobacterium tuberculosis reseeds the lung.

The novel coronavirus (SARS-CoV-2) emerged in late 2019 and spread globally in early 2020. Initial reports suggested the associated disease, COVID-19, produced rapid epidemic growth and caused high mortality. As the virus sparked local epidemics in new communities, health systems and policy makers were forced to make decisions with limited information about the spread of the disease. We developed a compartmental model to project COVID-19 healthcare demands that combined information regarding SARS-CoV-2 transmission dynamics from international reports with local COVID-19 hospital census data to support response efforts in three Metropolitan Statistical Areas (MSAs) in Texas, USA: Austin-Round Rock, Houston-The Woodlands-Sugar Land, and Beaumont-Port Arthur. Our model projects that strict stay-home orders and other social distancing measures could suppress the spread of the pandemic. Our capacity to provide rapid decision-support in response to emerging threats depends on access to data, validated modeling approaches, careful uncertainty quantification, and adequate computational resources.

Polygenic risk score (PRS) analysis is a powerful method been used to estimate an individual's genetic risk towards targeted traits. PRS analysis could be used to obtain evidence of a genetic effect beyond Genome-Wide Association Studies (GWAS) results i.e. when there are no significant markers. PRS analysis has been widely applied to investigate the genetic basis of several traits including rare diseases. However, the accuracy of PRS analysis depends on the genomic data of the underlying population. For instance, several studies showed that obtaining higher prediction power of PRS analysis is challenging for non-Europeans. In this manuscript, we reviewed the conventional PRS methods and their application to sub-saharan Africa communities. We concluded that the limiting factor of applying PRS analysis to sub-saharan populations is the lack of sufficient GWAS data. Also, we recommended developing African-specific PRS tools

Our current understanding of the pathophysiology of human pulmonary TB is limited by the paucity of human TB lung tissue for study and reliance on 2D analytical methods. Here, to overcome the limitations of conventional 2D histopathology, we used high-resolution 3D X-ray imaging (µCT/nCT) to characterize necrotic lesions within human tuberculous lung tissues in relation to the airways and vasculature. We observed marked heterogeneity in the 3D structure and volume of lesions. Also, 3D imaging of large human TB lung sections provides unanticipated new insight into the spatial organization of TB lesions in relation to airways and the vascular system. Contrary to the current dogma depicting granulomas as simple spherical structures, we show that TB lesions exhibit complex, cylindrical, branched-type morphologies, which are connected to, and shaped by, the small airways. Our results highlight the likelihood that a single structurally complex lesion could be wrongly viewed as multiple independent lesions when evaluated in 2D. These findings have strong implications for understanding the pathophysiology and evolution of TB disease and suggest that aerosolized drug delivery strategies for TB should be reconsidered.

Life scientists are increasingly turning to high-throughput sequencing technologies in their research programs, owing to the enormous potential of these methods. In a parallel manner, the number of core facilities that provide bioinformatics support are also increasing. Notably, the generation of complex large datasets has necessitated the development of bioinformatics support core facilities that aid laboratory scientists with cost-effective and efficient data management, analysis, and interpretation. In this article, we address the challenges—related to communication, good laboratory practice, and data handling—that may be encountered in core support facilities when providing bioinformatics support, drawing on our own experiences working as support bioinformaticians on multidisciplinary research projects. Most importantly, the article proposes a list of guidelines that outline how these challenges can be preemptively avoided and effectively managed to increase the value of outputs to the end user, covering the entire research project lifecycle, including experimental design, data analysis, and management (i.e., sharing and storage). In addition, we highlight the importance of clear and transparent communication, comprehensive preparation, appropriate handling of samples and data using monitoring systems, and the employment of appropriate tools and standard operating procedures to provide effective bioinformatics support., Author summary The article we wrote draws from our experience in core support facilities and highlights 10 best practices that individuals who apply information technology approaches to biological, medical, and health research should consider when providing support to individuals who generate data for this research in the lab. As interdisciplinary approaches are increasingly being utilized within the biological and medical sciences, effective collaboration and support between the aforementioned parties is crucial to promote the quality and integrity of research. These practices highlight the importance of quality control, comprehensive reporting, effective communication, and more in the production of quality data as well as the promotion of effective collaboration.

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03286-9.

Epilepsy and intellectual disability are associated with rare variants in the GluN2A and GluN2B (encoded by GRIN2A and GRIN2B) subunits of the N-methyl-D-aspartate receptor (NMDAR), a ligand-gated ion channel with essential roles in brain development and function. By assessing genetic variation across GluN2 domains, we determined that the agonist binding domain, transmembrane domain, and the linker regions between these domains were particularly intolerant to functional variation. Notably, the agonist binding domain of GluN2B exhibited significantly more variation intolerance than that of GluN2A. To understand the ramifications of missense variation in the agonist binding domain, we investigated the mechanisms by which 25 rare variants in the GluN2A and GluN2B agonist binding domains dysregulated NMDAR activity. When introduced into recombinant human NMDARs, these rare variants identified in individuals with neurologic disease had complex, and sometimes opposing, consequences on agonist binding, channel gating, receptor biogenesis, and forward trafficking. Our approach combined quantitative assessments of these effects to estimate the overall impact on synaptic and non-synaptic NMDAR function. Interestingly, similar neurologic diseases were associated with both gain- and loss-of-function variants in the same gene. Most rare variants in GluN2A were associated with epilepsy, whereas GluN2B variants were associated with intellectual disability with or without seizures. Finally, discerning the mechanisms underlying NMDAR dysregulation by these rare variants allowed investigations of pharmacologic strategies to correct NMDAR function.

N-methyl-D-aspartate (NMDA) receptors are transmembrane glutamate-binding ion channels that mediate neurotransmission in mammals. NMDA receptor subunits are tetrameric complexes of GluN1 and GluN2A-D subunits, encoded by the GRIN gene family. Of these subunits, GluN2B is suggested to be required for normal development of the central nervous system. A mutation identified in a patient with developmental delay, E413G, resides in the GluN2B ligand-binding domain and substantially reduces glutamate potency by an unknown mechanism. GluN2B Gly413, though near the agonist, is not in van der Waals contact with glutamate. Visual analysis of the GluN2B structure with the E413G mutation modelled suggests that replacement of Glu with Gly at this position increases solvent access to the ligand-binding domain. This was confirmed by molecular modeling, which showed that the ligand is more mobile in GluN2B-E413G than WT GluN2B. Evaluation of agonist occupancy using random accelerated molecular dynamics (RAMD) simulations predicts that the glutamate exits the binding-site more rapidly for GluN2B-E413G than WT receptors. This analysis was extended to other binding-site mutations, which produced qualitative agreement between experimentally determined EC(50) values, deactivation time constants, and ligand motion within the binding-site. Furthermore, long sub-microsecond molecular dynamics simulations of the bi-lobed ligand-binding domain revealed that it adopted a cleft-open ligand-free state more often for GluN2B-E413G than wild-type GluN2B. This is consistent with the idea that L-glutamate binding is altered such that the ligand-binding domain occupies the open-cleft conformation associated with the closed channel.

The National Institutes of Health Undiagnosed Diseases Program evaluates patients for whom no diagnosis has been discovered despite a comprehensive diagnostic workup. Failure to diagnose a condition may arise from the mutation of genes previously unassociated with disease. However, we hypothesized that this could also co-occur with multiple genetic disorders. Demonstrating a complex syndrome caused by multiple disorders, we report two siblings manifesting both similar and disparate signs and symptoms. They shared a history of episodes of hypoglycemia and lactic acidosis, but had differing exam findings and developmental courses. Clinical acumen and exome sequencing combined with biochemical and functional studies identified three genetic conditions. One sibling had Smith–Magenis Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de novo mutation in GRIN2B , which resulted in markedly reduced glutamate potency of the encoded receptor. Both siblings had a protein-destabilizing homozygous mutation in PCK1 , which encodes the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). In summary, we present the first clinically-characterized mutation of PCK1 and demonstrate that complex medical disorders can represent the co-occurrence of multiple diseases.

Summary Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammatory responses and redox homeostasis; however, its role during pulmonary tuberculosis (TB) remains unclear. Using freshly resected human TB lung tissue, we examined the role of HO-1 within the cellular and pathological spectrum of TB. Flow cytometry and histopathological analysis of human TB lung tissues showed that HO-1 is expressed primarily in myeloid cells and that HO-1 levels in these cells were directly proportional to cytoprotection. HO-1 mitigates TB pathophysiology by diminishing myeloid cell-mediated oxidative damage caused by reactive oxygen and/or nitrogen intermediates, which control granulocytic karyorrhexis to generate a zonal HO-1 response. Using whole-body or myeloid-specific HO-1-deficient mice, we demonstrate that HO-1 is required to control myeloid cell infiltration and inflammation to protect against TB progression. Overall, this study reveals that zonation of HO-1 in myeloid cells modulates free-radical-mediated stress, which regulates human TB immunopathology., Graphical Abstract, Highlights • HO-1 is expressed in distinct microanatomic zones within the human TB lung • Macrophages and neutrophils are the major producers of HO-1 in human TB lungs • In diseased areas of human TB lungs, myeloid cells have low HO-1 and high ROS and RNS • Mice lacking HO-1 expression in myeloid cells are more susceptible to Mtb infection, Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammation and redox homeostasis; however, its role in tuberculosis (TB) is unclear. Using freshly resected human lung tissue and HO-1-deficient mice, Chinta et al. demonstrate that HO-1 in myeloid cells is important for controlling inflammatory and free-radical-mediated tissue damage in TB.

Three residues within the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit GluA1 C terminus (Ser818, Ser831, Thr840) can be phosphorylated by Ca(2+)/phospholipid-dependent protein kinase (PKC). Here, we show that PKC phosphorylation of GluA1 Ser818 or Thr840 enhances the weighted mean channel conductance without altering the response time course or agonist potency. These data support the idea that these residues constitute a hyper-regulatory domain for the AMPA receptor. Introduction of phosphomimetic mutations increases conductance only at these three sites within the proximal C terminus, consistent with a structural model with a flexible linker connecting the distal C-terminal domain to the more proximal domain containing a helix bracketed by Ser831 and Thr840. NMR spectra support this model and raise the possibility that phosphorylation can alter the configuration of this domain. Our findings provide insight into the structure and function of the C-terminal domain of GluA1, which controls AMPA receptor function and trafficking during synaptic plasticity in the central nervous system.

A recent study implicated a role for Plasmodium falciparum arginase in the systemic depletion of arginine levels, which in turn has been associated with human cerebral malaria pathogenesis. Arginase (EC 3.5.3.1) is a multimeric metallo-protein that catalyses the hydrolysis of arginine to ornithine and urea by means of a binuclear spin-coupled Mn2+ cluster in the active site. A previous report indicated that P. falciparum arginase has a strong dependency between trimer formation, enzyme activity and metal co-ordination. Mutations that abolished Mn2+ binding also caused dissociation of the trimer; conversely, mutations that abolished trimer formation resulted in inactive monomers. By contrast, the monomers of mammalian (and therefore host) arginase are also active. P. falciparum arginase thus appears to be an obligate trimer and interfering with trimer formation may therefore serve as an alternative route to enzyme inhibition. In the present study, the mechanism of the metal dependency was explored by means of homology modelling and molecular dynamics. When the active site metals are removed, loss of structural integrity is observed. This is reflected by a larger equilibration rmsd for the protein when the active site metal is removed and some loss of secondary structure. Furthermore, modelling revealed the existence of a novel inter-monomer salt-bridge between Glu295 and Arg404, which was shown to be associated with the metal dependency. Mutational studies not only confirmed the importance of this salt-bridge in trimer formation, but also provided evidence for the independence of P. falciparum arginase activity on trimer formation.

Discoursing, the use of language in interaction with others, plays a part in almost every human activity. Indeed, some have argued that it is discoursing that has made possible the cumulative development of culture over the course of our species' history. Whether or not that is correct, there can be no question that the ability, with the aid of linguistic discourse, to coordinate action, and to reflect together on the relationship between actions and their intended and achieved results, has been an essential contributor. The question is, How should we theorize the relationship between discoursing and the forms of joint activity in which it occurs? At the present time, not only do we not have an answer to this question but the question has hardly been addressed within activity theory. My aim in this article is to offer some suggestions that may help to advance this project. To this end, I put forward and attempt to justify the argument that discourse always functions to mediate the action in which it serve...

There is increasing agreement among those who study classrooms that learning is likely to be most effective when students are actively involved in the dialogic coconstruction of meaning about topics that are of significance to them. This article reports the results of an extended collaborative action research project in which teachers attempted to create the conditions for such dialogue by adopting an inquiry approach to the curriculum. A quantitative comparison between observations made early and late in the teachers' involvement in the project showed a number of significant changes in the characteristics of teacher–whole-class discourse, with a shift toward a more dialogic mode of interaction. Nevertheless, the initiation-response-follow-up (IRF) genre continued to be pervasive. Despite this, when the same observations were examined qualitatively, there was clear evidence of an increase over time in the teachers' adoption of a "dialogic stance." The article concludes with a consideration of the relation...

Resumen tomado de la revista Este trabajo pretende mostrar que los individuos y las sociedades se desarrollan de manera interdependiente, en y mediante la participación en actividades conjuntas mediadas por herramientas. Por esta razón, el desarrollo de las especies humanas, de los grupos culturales y de las personas individuales, depende de las herramientas de representación disponibles y de los modos de conocimiento que tales herramientas permiten. Por lo tanto, los educadores, equipando a los alumnos con las habilidades y conocimientos alcanzados por las generaciones previas y proporcionándoles guía y ayuda mientras exploran, en colaboración, temas y problemas de interés compartido; pueden preparar a los alumnos para desarrollar la disposición a buscar y ampliar la comprensión que impulsa la acción responsable y para, en el proceso, transformarse a sí mismos, transformar sus sociedades y el mundo que habitan. Cataluña ESP

The development of any robotics application relying on visual information always raises the key question of what image features would be most informative about the motion to be performed. In this paper, we address this question in the context of visual robot positioning, where a neural network is used to learn the mapping between image features and robot movements, and global image descriptors are preferred to local geometric features. Using a statistical measure of variable interdependence called Mutual Information, subsets of image features most relevant for determining pose variations along each of the six degrees of freedom (dof's) of camera motion are selected. Four families of global features are considered: geometric moments, eigenfeatures, Local Feature Analysis vectors, and a novel feature called Pose-Image Covariance vectors. The experimental results described show the quantitative and qualitative benefits of performing this feature selection prior to training the neural network: Less network inputs are needed, thus considerably shortening training times; the dof's that would yield larger errors can be determined beforehand, so that more informative features can be sought; the order of the features selected for each dof often accepts an intuitive explanation, which in turn helps to provide insights for devising features tailored to each dof.

1. Introduction Gordon Wells and Anne Edwards 2. Goal formation and identity formation in higher education Deborah Downing and Michael Cole 3. Using a cultural historical approach to understand educational change in introductory physics classrooms Chandra A. Turpen and Noah D. Finkelstein 4. Taking responsibility for learning: CHAT in a large undergraduate class Gordon Wells 5. CHAT and student writing David Russell 6. Assessment in higher education - a CHAT perspective Anton Havnes 7. The agency of the learner in the networked university: an expansive approach Russell Francis 8. Supporting access to science and engineering through scientific argumentation Tamara Ball and Lisa Hunter 9. Using CHAT to understand systems to support disabled students in higher education Jan Georgeson 10. Internship: navigating the practices of an investment bank Natalie Lundsteen and Anne Edwards 11. Identity change in the context of HE institutions Jorge Larremeamendy-Joerns 12. Developing skills for collaborative, relational research in higher education: a cultural historical analysis Ioanna Kinti and Geoff Hayward 13. Teacher education in the public university: the challenge of democratizing knowledge production Viv Ellis 14. What does 'transformation of participation' mean in a university classroom? Exploring university pedagogy with the tools of cultural historical theory Holli Tonyan and Glen Auld 15. Gentle partnerships: learning from the fifth dimension Honorine Norcon and Monica Nilsson.

Most vision-based robot positioning techniques rely on analytical formulations of the relationship between the robot pose and the projected image coordinates of several geometric features of the observed scene. This usually requires that several simple features such as points, lines or circles be visible in the image, which must either be unoccluded in multiple views or else part of a 3D model. Featurematching algorithms, camera calibration, models of the camera geometry and object feature relationships are also necessary for pose determination. These steps are often computationally intensive and error-prone, and the complexity of the resulting formulations often limits the number of controllable degrees of freedom. We provide a comparative survey of existing visual robot positioning methods, and present a new technique based on neural learning and global image descriptors which overcomes many of these limitations. A feedforward neural network is used to learn the complex implicit relationship between the pose displacements of a 6-dof robot and the observed variations in global descriptors of the image, such as geometric moments and Fourier descriptors. The trained network may then be used to move the robot from arbitrary initial positions to a desired pose with respect to the observed scene. The method is shown to be capable of positioning an industrial robot with respect to a variety of complex objects with an acceptable precision for an industrial inspection application, and could be useful in other real-world tasks such as grasping, assembly and navigation.

Drawing on Cummins' (1989) linguistic interdependence model, proponents of bilingual-bicultural models of literacy education for deaf students claim that, if ASL is well established as the L1, then literacy in English (L2) can be achieved by means of reading and writing without exposure to English through either speech or English-based sign. In our opinion, this claim is based on a false analogy: the situation of the deaf learner of English literacy does not match the conditions assumed by the linguistic interdependence model. We draw on the work of Vygotsky and Halliday to develop a conceptualization of the processes involved in becoming literate, examining the particular and unique challenges that deaf students face as they strive to become members of the linguistic community of users of written English. We argue that becoming literate involves mastering three modes of lanuage use: 'social speech,' 'inner speech,' and written text. In some respects the educational context for deaf students is analogous to that of other bilingual learners; in some crucial aspects, it is very different.

Public debate about the goals of education is often couched in terms of an opposition between, on the one hand, the need to transmit to all students the knowledge and skills that are culturally valued and, on the other, the responsibility to foster each individual student's potential and creativity. By contrast, my aim is to show that, when one adopts a social constructivist theory of learning and teaching-enacted through an inquiry-oriented curriculum-these goals, far from being in conflict, are found to be essentially complementary and interdependent. In the development and instantiation of this argument, my illustrative examples will be drawn mainly from observations of work on topics in science; however, I believe that the inquiry approach that is proposed here is of general applicability to all areas of the curriculum.

This paper describes experiments with the use of neural networks for image-based positioning of industrial robots. Firstly, an improved neural “visual-servoing” method based on geometric image characteristics is developed and analyzed. Subsequently, a more flexible and robust scheme is shown, based on global descriptors of the image.

The organization and mining of malaria genomic and post-genomic data is highly motivated by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should therefore be as reliable and versatile as possible. In this context, we examined five aspects of the organization and mining of malaria genomic and post-genomic data: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Progresses toward a grid-enabled chemogenomic knowledge space are discussed., Comment: 43 pages, 4 figures, to appear in Malaria Journal

If we interpret his commentary correctly, David Mason seems to have misunderstood our argument. We are not suggesting that ASL and written English cannot function in effective complementarity in mediating the construction of and use of educational knowledge by those who do not have access to spoken English by virtue of their hearing loss. Rather, our argument concerns their initial mastery of written English, and for this purpose we contend ASL does not provide an adequate base. In Cummins's terms, it does not meet the conditions of applicability of the theory of linguistic interdependence. Mason rightly points out that ASL functions successfully in a variety of literate settings from university lectures to political meetings, from courts of law to religious institutions, and that it can be used to discuss concepts in science and mathematics, and even to discuss aspects of English text and text structure. But what he fails to make clear is that ASL performs this role only for those who can already read the English written texts in which these concepts are encountered. Mason is also correct when he writes that "it is reasonable to infer that educational knowledge cannot be deemed bound to one language specifically since the knowledge is much deeper and broader than any one particular language can possibly represent." We make a related point by arguing that "one language is as good as any other for developing inner speech, for devel

In the malaria parasite, the two main regulatory activities of polyamine biosynthesis, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) occur in a single bifunctional protein. The AdoMetDC domain was modeled using the human and potato X-ray crystal structures as templates. Three parasite-specific inserts and the core active site region was identified using a structure-based alignment approach. The domain was modeled without the two largest inserts, to give a root mean square deviation of 1.85 A from the human template. Contact with the rest of the bifunctional complex is predicted to occur on one face of the Plasmodium falciparum AdoMetDC (PfAdoMetDC) domain. In the active site there are four substitutions compared to the human template. One of these substitutions may be responsible for the lack of inhibition by Tris, compared to mammalian AdoMetDC. The model also provides an explanation for the lack of putrescine stimulation in PfAdoMetDC compared to mammalian AdoMetDC. A network of residues that connects the putrescine-binding site with the active site in human AdoMetDC is conserved in the malarial and plant cognates. Internal basic residues are found to assume the role of putrescine, based on the model and site-directed mutagenesis: Arg11 is absolutely required for normal activity, while disrupting Lys15 and Lys215 each cause 50% inhibition of AdoMetDC activity. These novel features of malarial AdoMetDC suggest possibilities for the discovery of parasite-specific inhibitors.

Polyamine biosynthesis of the malaria parasite, Plasmodium falciparum, is regulated by a single, hinge-linked bifunctional PfAdoMetDC/ODC [ P. falciparum AdoMetDC (S-adenosylmethionine decarboxylase)/ODC (ornithine decarboxylase)] with a molecular mass of 330 kDa. The bifunctional nature of AdoMetDC/ODC is unique to Plasmodia and is shared by at least three species. The PfAdoMetDC/ODC contains four parasite-specific regions ranging in size from 39 to 274 residues. The significance of the parasite-specific inserts for activity and protein-protein interactions of the bifunctional protein was investigated by a single- and multiple-deletion strategy. Deletion of these inserts in the bifunctional protein diminished the corresponding enzyme activity and in some instances also decreased the activity of the neighbouring, non-mutated domain. Intermolecular interactions between AdoMetDC and ODC appear to be vital for optimal ODC activity. Similar results have been reported for the bifunctional P. falciparum dihydrofolate reductase-thymidylate synthase [Yuvaniyama, Chitnumsub, Kamchonwongpaisan, Vanichtanankul, Sirawaraporn, Taylor, Walkinshaw and Yuthavong (2003) Nat. Struct. Biol. 10, 357-365]. Co-incubation of the monofunctional, heterotetrameric approximately 150 kDa AdoMetDC domain with the monofunctional, homodimeric ODC domain (approximately 180 kDa) produced an active hybrid complex of 330 kDa. The hinge region is required for bifunctional complex formation and only indirectly for enzyme activities. Deletion of the smallest, most structured and conserved insert in the ODC domain had the biggest impact on the activities of both decarboxylases, homodimeric ODC arrangement and hybrid complex formation. The remaining large inserts are predicted to be non-globular regions located on the surface of these proteins. The large insert in AdoMetDC in contrast is not implicated in hybrid complex formation even though distinct interactions between this insert and the two domains are inferred from the effect of its removal on both catalytic activities. Interference with essential protein-protein interactions mediated by parasite-specific regions therefore appears to be a viable strategy to aid the design of selective inhibitors of polyamine metabolism of P. falciparum.

This paper discusses validation of the EcH2O portable ‘batch-treatment’ electron-activated reactor field unit designed to purify contaminated water to make it safe and potable. The basic EcH2O system consists of a 90-gallon plastic reactor tank (trash can), ionized nitrogen-oxygen (NI-OXTM) vapor-ion plasma generator, and 1-micron electron separation (e-SEPTM) porous cartridge water filter. While the NI-OXTM generator applies UV radiation to activate and split ambient air into aggressive water treatment agents in the form of free electrons and charged dissolved vapor ions, the e-SEPTM cartridge is designed to absorb NI-OXTM treatment agents and solvated (free) electrons to induce filtration and rapid disinfection-kill of bacteria and other pathogens. The study started by creating a water quality database from contaminated surface water, EPA/West Virginia water quality standards, and Vienna City water. The EcH2O purifier was run 14 days/month from April-September 2014 and samples analyzed for chemical and bacteriological quality. When the results were matched against published data, EcH2O compared favorably with both EPA/West Virginia water quality standards and Vienna City water (R2 = 0.99; p

We have obtained minimum age estimates for the sand units underlying the two largest meteorite deflation surfaces in Roosevelt County, New Mexico, USA, using thermoluminescence dating techniques. The dates obtained ranged from 53.5 (+/- 5.4) to 95.2 (+/- 9.5) ka, and must be considered lower limits for the terrestrial ages of the meteorites found within these specific deflation surfaces. These ages greatly exceed previous measurements from adjacent meteorite-producing deflation basins. We find that Roosevelt County meteorites are probably terrestrial contemporaries of the meteorites found at most accumulation zones in Antarctica. The apparent high meteorite accumulation rate reported for Roosevelt County by Zolensky et al. (1990) is incorrect, as it used an age of 16 ka for all Roosevelt County recovery surfaces. We conclude that the extreme variability of terrestrial ages of the Roosevelt County deflation surfaces effectively precludes their use for calculations of the meteorite accumulation rate at the Earth's surface.

IEEE International Conference on Robotics and Automation (ICRA), 1998, Lovaina (Bélgica), The authors and Venaille (1996) developed a prototype for visual robot positioning, based on global image descriptors and neural networks. Now, a procedure to automatically select subsets of image features most relevant to determine pose variations along each of the six degrees of freedom (DOFs) has been incorporated into the prototype. This procedure is based on a statistical measure of variable interdependence, called mutual information. Three families of features are considered in this paper: geometric moments, eigenfeatures and pose-image covariance vectors. The experimental results described show the quantitative and qualitative benefits of carrying out this feature selection prior to training the neural network: fewer network inputs need to be considered, thus considerably shortening training times; the DOFs that would yield larger errors can be determined beforehand, so that more informative features can be looked for; the ordering of the features selected for each DOF often admits a very natural interpretation, which in turn helps to provide insights for devising features tailored to each DOF.

Neural identification and control techniques are well-suited to the problem of controlling robot dynamics. This paper describes the use of CMAC networks for the adaptive dynamic control of an orange-harvesting robot. Among the various neural-network paradigms available, the CMAC model was chosen in this case because of its fast convergence and on-line adaptation capability. The solution of this dynamic control problem with CMAC is an encouraging demonstration of “experience-based”, as opposed to model-based, control techniques and is a good example of the use of on-line learning in adaptive neural control.