James P. Ware, Principal

The challenge for practitioners is simple to state but extremely difficult to accomplish: how to build a business and an organization that can achieve sustained competitive advantage. This objective means ensuring that IT investments are implemented solely for business purposes -- to enhance productivity, to improve product/market capabilities, or to improve managerial decision making. But it also means that line managers, from the CEO on down, must develop a much deeper understanding of what I/T is doing to organizational forms and practices, what it can do, and how to make the changes both organizationally productive and individually appealing. New forms of organization and management are emerging today, whether by design or default. IT is making possible much flatter organizations, with characteristics often more like informal, loosely coupled networks than classic bureaucracies. Organizations with rich and extensive IT support appear to operate very differently from traditional models. Horizontal communication is more extensive, more frequent, and more informal. Decisions are reached more quickly, and the organization typically tolerates a wider range of behaviors, decisions, and practices. There is often more emphasis on results, less on forms. These changes, which amount to fundamental culture shifts, are usually subtle, and are frequently unrecognized by senior executives. On rare occasions, the changes are planned and managed. But, more typically, the changes begin evolving in some niche or department within the organization and then meet substantial resistance from entrenched managers, who are unwilling to undergo the personal changes in role, influence, power, and style that must be accomplished if the optimum benefits of the new technologies and new practices are to be fully realized. We have observed how the impact of technology on organizational practices seems to develop over time through four distinct phases: technological automation, task automation, managerial transformation, and strategic transformation. While there are elements of each phase present in any organization at any one time, there is typically a dominant theme that depends on the organization\u27s level of experience with the new technology. The critical issue, however, is that progression from one level to another is neither simple nor automatic; only when organizations undergo fundamental paradigm shifts do they actually achieve the higher benefits that accompany broader and more fundamental change. In our research and consulting experience, the major benefits of I/T are achieved only when technological change is iatroduced in support of business change. While some I/T R&D is of course necessary, the only long-lasting and effective applications of technology that we have seen are those that are clearly and explicitly packaged to address defined business problems or opportunities. Most organizations are stuck in technology-driven visions that are not producing significant business benefits. The organizational world of the 2lst century will be very different from the one we know today. We face two basic challenges: defining that vision (what is possible, practical, and appropriate); and describing the pathway to get there from here

A surface mooring for air–sea interaction research in the Gulf Stream. Part I : mooring design and instrumentation

Author Posting. © American Meteorological Society, 2012. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 29 (2012): 1363–1376, doi:10.1175/JTECH-D-12-00060.1.The design of a surface mooring for deployment in the Gulf Stream in the Mid-Atlantic Bight is described. The authors' goals were to observe the surface meteorology; upper-ocean variability; and air–sea exchanges of heat, freshwater, and momentum in and near the Gulf Stream during two successive 1-yr deployments. Of particular interest was quantifying these air–sea fluxes during wintertime events that carry cold, dry air from the land over the Gulf Stream. Historical current data and information about the surface waves were used to guide the design of the surface mooring. The surface buoy provided the platform for both bulk meteorological sensors and a direct covariance flux system. Redundancy in the meteorological sensors proved to be a largely successful strategy to obtain complete time series. Oceanographic instrumentation was limited in size by considerations of drag; and two current meters, three temperature–salinity recorders, and 15 temperature recorders were deployed. Deployment from a single-screw vessel in the Gulf Stream required a controlled-drift stern first over the anchor sites. The first deployment lasted the planned full year. The second deployment ended after 3 months when the mooring was cut by unknown means at a depth of about 3000 m. The mooring was at times in the core of the Gulf Stream, and a peak surface current of over 2.7 m s−1 was observed. The 15-month records of surface meteorology and air–sea fluxes captured the seasonal variability as well as several cold-air outbreaks; the peak observed heat loss was in excess of 1400 W m−2.This work was funded by the National Science Foundation Grant OCE04-24536 as part of the CLIVAR Mode Water Dynamics Experiment (CLIMODE). The Vetlesen Foundation is also acknowledged for the early support of SB.2013-03-0

Identification of a Novel ZIC3 Isoform and Mutation Screening in Patients with Heterotaxy and Congenital Heart Disease

Patients with heterotaxy have characteristic cardiovascular malformations, abnormal arrangement of their visceral organs, and midline patterning defects that result from abnormal left-right patterning during embryogenesis. Loss of function of the transcription factor ZIC3 causes X-linked heterotaxy and isolated congenital heart malformations and represents one of the few known monogenic causes of congenital heart disease. The birth incidence of heterotaxy-spectrum malformations is significantly higher in males, but our previous work indicated that mutations within ZIC3 did not account for the male over-representation. Therefore, cross species comparative sequence alignment was used to identify a putative novel fourth exon, and the existence of a novel alternatively spliced transcript was confirmed by amplification from murine embryonic RNA and subsequent sequencing. This transcript, termed Zic3-B, encompasses exons 1, 2, and 4 whereas Zic3-A encompasses exons 1, 2, and 3. The resulting protein isoforms are 466 and 456 amino acid residues respectively, sharing the first 407 residues. Importantly, the last two amino acids in the fifth zinc finger DNA binding domain are altered in the Zic3-B isoform, indicating a potential functional difference that was further evaluated by expression, subcellular localization, and transactivation analyses. The temporo-spatial expression pattern of Zic3-B overlaps with Zic3-A in vivo, and both isoforms are localized to the nucleus in vitro. Both isoforms can transcriptionally activate a Gli binding site reporter, but only ZIC3-A synergistically activates upon co-transfection with Gli3, suggesting that the isoforms are functionally distinct. Screening 109 familial and sporadic male heterotaxy cases did not identify pathogenic mutations in the newly identified fourth exon and larger studies are necessary to establish the importance of the novel isoform in human disease

Massive Doublet Leptons

Massive vector-like electroweak doublets are generic in many extensions of the standard model. Even though one member of the doublet is necessarily electrically charged these particles are not easily detected in collider experiments. The neutral and charged states within the doublet are split by electroweak symmetry breaking. In the absence of mixing with other states, the radiatively generated splitting is in the range 200 - 350 MeV for m > mZ/2. The charged state decays to the neutral one with an O(cm) decay length, predominantly by emission of a soft charged pion. The best possibility to detect these massive charged particles is to trigger on hard initial state radiation and search for two associated soft charged pions with displaced vertices. The mass reach for this process at LEPII is limited by luminosity rather than kinematics.Comment: 4 pages, Late

Pashto Border Literature as Geopolitical Knowledge

In this article I read a selection of Pashto literatures as critical thought about geopolitics. Drawing on Michael Shapiro’s concept of aesthetic subjects, as well as on border theory, I argue that the authors, the content, and the literary networks of these works all comment on global relations of power, ranging from the local bordering effects of geopolitics, to systems of knowledge embedded in the spatiality and temporality of empire. I argue that past and current imperial processes have led to fragmenting effects in Afghan society, and literature both reflects and analyzes this. Beyond that, I argue—through the examples of authors’ lives as well as their work—that literary activity in Pashto has actively negotiated such processes throughout its history, and offers strategies for countervailing notions of global connectivity in action as well as thought. The decentralized and multiperspective images of life in these works sit in counterpoint not only to the systems-oriented views that drive military and other policy in Afghanistan during the ongoing US moment, but also to universalist perspectives upon which disciplines like world history and geopolitics traditionally rely. Additionally, though, Pashto literary networks themselves also produce alternative structures. This contributes to the aesthetic turn in IR by arguing that it is not only the aesthetic vision in works that challenges dominant knowledge; the shape of the Pashto literary formation itself, organic with its content, is an alternate form of knowledge-in-practice about the contemporary world

De novo deletions and duplications of 17q25.3 cause susceptibility to cardiovascular malformations

BACKGROUND: Genomic disorders resulting from deletion or duplication of genomic segments are known to be an important cause of cardiovascular malformations (CVMs). In our previous study, we identified a unique individual with a de novo 17q25.3 deletion from a study of 714 individuals with CVM. METHODS: To understand the contribution of this locus to cardiac malformations, we reviewed the data on 60,000 samples submitted for array comparative genomic hybridization (CGH) studies to Medical Genetics Laboratories at Baylor College of Medicine, and ascertained seven individuals with segmental aneusomy of 17q25. We validated our findings by studying another individual with a de novo submicroscopic deletion of this region from Cytogenetics Laboratory at Cincinnati Children's Hospital. Using bioinformatic analyses including protein-protein interaction network, human tissue expression patterns, haploinsufficiency scores, and other annotation systems, including a training set of 251 genes known to be linked to human cardiac disease, we constructed a pathogenicity score for cardiac phenotype for each of the 57 genes within the terminal 2.0 Mb of 17q25.3. RESULTS: We found relatively high penetrance of cardiovascular defects (~60 %) with five deletions and three duplications, observed in eight unrelated individuals. Distinct cardiac phenotypes were present in four of these subjects with non-recurrent de novo deletions (range 0.08 Mb-1.4 Mb) in the subtelomeric region of 17q25.3. These included coarctation of the aorta (CoA), total anomalous pulmonary venous return (TAPVR), ventricular septal defect (VSD) and atrial septal defect (ASD). Amongst the three individuals with variable size duplications of this region, one had patent ductus arteriosus (PDA) at 8 months of age. CONCLUSION: The distinct cardiac lesions observed in the affected patients and the bioinformatics analyses suggest that multiple genes may be plausible drivers of the cardiac phenotype within this gene-rich critical interval of 17q25.3

Comparisons of host mitochondrial, nuclear and endosymbiont bacterial genes reveal cryptic fig wasp species and the effects of Wolbachia on host mtDNA evolution and diversity

Background Figs and fig-pollinating wasp species usually display a highly specific one-to-one association. However, more and more studies have revealed that the "one-to-one" rule has been broken. Co-pollinators have been reported, but we do not yet know how they evolve. They may evolve from insect speciation induced or facilitated by Wolbachia which can manipulate host reproduction and induce reproductive isolation. In addition, Wolbachia can affect host mitochondrial DNA evolution, because of the linkage between Wolbachia and associated mitochondrial haplotypes, and thus confound host phylogeny based on mtDNA. Previous research has shown that fig wasps have the highest incidence of Wolbachia infection in all insect taxa, and Wolbachia may have great influence on fig wasp biology. Therefore, we look forward to understanding the influence of Wolbachia on mitochondrial DNA evolution and speciation in fig wasps. Results We surveyed 76 pollinator wasp specimens from nine Ficus microcarpa trees each growing at a different location in Hainan and Fujian Provinces, China. We found that all wasps were morphologically identified as Eupristina verticillata, but diverged into three clades with 4.22-5.28% mtDNA divergence and 2.29-20.72% nuclear gene divergence. We also found very strong concordance between E. verticillata clades and Wolbachia infection status, and the predicted effects of Wolbachia on both mtDNA diversity and evolution by decreasing mitochondrial haplotypes. Conclusions Our study reveals that the pollinating wasp E. verticillata on F. microcarpa has diverged into three cryptic species, and Wolbachia may have a role in this divergence. The results also indicate that Wolbachia strains infecting E. verticillata have likely resulted in selective sweeps on host mitochondrial DNA

Enhanced ultrafast X-ray diffraction by transient resonances

Diffraction-before-destruction imaging with single ultrashort X-ray pulses has the potential to visualise non-equilibrium processes, such as chemical reactions, at the nanoscale with sub-femtosecond resolution in the native environment without the need of crystallization. Here, a nanospecimen partially diffracts a single X-ray flash before sample damage occurs. The structural information of the sample can be reconstructed from the coherent X-ray interference image. State-of-art spatial resolution of such snapshots from individual heavy element nanoparticles is limited to a few nanometers. Further improvement of spatial resolution requires higher image brightness which is ultimately limited by bleaching effects of the sample. We compared snapshots from individual 100 nm Xe nanoparticles as a function of the X-ray pulse duration and incoming X-ray intensity in the vicinity of the Xe M-shell resonance. Surprisingly, images recorded with few femtosecond and sub-femtosecond pulses are up to 10 times brighter than the static linear model predicts. Our Monte-Carlo simulation and statistical analysis of the entire data set confirms these findings and attributes the effect to transient resonances. Our simulation suggests that ultrafast form factor changes during the exposure can increase the brightness of X-ray images by several orders of magnitude. Our study guides the way towards imaging with unprecedented combination of spatial and temporal resolution at the nanoscale

Genetic and environmental determinants of diastolic heart function

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between genetically-determined ventricular stiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and potential tractable targets