3,149 research outputs found
Determinants of Long-Term Growth: A Bayesian Averaging of Classical Estimates (BACE) Approach
This paper examines the robustness of explanatory variables in cross-country economic growth regressions. It employs a novel approach, Bayesian Averaging of Classical Estimates (BACE), which constructs estimates as a weighted average of OLS estimates for every possible combination of included variables. The weights applied to individual regressions are justified on Bayesian grounds in a way similar to the well-known Schwarz criterion. Of 32 explanatory variables we find 11 to be robustly partially correlated with long-term growth and another five variables to be marginally related. Of all the variables considered, the strongest evidence is for the initial level of real GDP per capita.
The dynamics of games of innovation
Many executives see innovation as an unmanageable process, riddled with risks. The\ud
research we conducted with the Industrial Research Institute, interviewing over 200 vicepresidents\ud
of research and development and chief technical officers in many sectors around\ud
the world, yields a more nuanced view. Innovation becomes manageable once managers\ud
move away from normative prescriptions that view the process as uniform and recognise\ud
that different rules and practices apply to different circumstances.\ud
Our argument is that clusters of interdependent firms contributing to the building of a set of\ud
interacting products and services tend to self-organise themselves into distinct and relatively\ud
persistent âgames of innovatio
Sinorhizobium Meliloti, A Bacterium Lacking The Autoinducer-2 (AI-2) Synthase, Responds To AI-2 Supplied By Other Bacteria
Many bacterial species respond to the quorum-sensing signal autoinducer-2 (AI-2) by regulating different niche-specific genes. Here, we show that Sinorhizobium meliloti, a plant symbiont lacking the gene for the AI-2 synthase, while not capable of producing AI-2 can nonetheless respond to AI-2 produced by other species. We demonstrate that S. meliloti has a periplasmic binding protein that binds AI-2. The crystal structure of this protein (here named SmlsrB) with its ligand reveals that it binds (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF), the identical AI-2 isomer recognized by LsrB of Salmonella typhimurium. The gene encoding SmlsrB is in an operon with orthologues of the lsr genes required for AI-2 internalization in enteric bacteria. Accordingly, S. meliloti internalizes exogenous AI-2, and mutants in this operon are defective in AI-2 internalization. S. meliloti does not gain a metabolic benefit from internalizing AI-2, suggesting that AI-2 functions as a signal in S. meliloti. Furthermore, S. meliloti can completely eliminate the AI-2 secreted by Erwinia carotovora, a plant pathogen shown to use AI-2 to regulate virulence. Our findings suggest that S. meliloti is capable of \u27eavesdropping\u27 on the AI-2 signalling of other species and interfering with AI-2-regulated behaviours such as virulence
Have we been measuring their effectiveness all wrong?
Evaluating whether sustainability indicator schemes contribute to better sustainable destination management has proven challenging. We adopt a systems thinking approach to shed light on the elusive impacts of sustainable tourism indicator schemes. We conduct online participatory workshops with 19 experts in sustainable tourism monitoring, to produce a causal loop diagram that illustrates how destination systems behave when indicator schemes are implemented. The results show that until now, these schemes have been expected to follow utopian, evidence-based, policy pathways to change, but we now understand that this linear-thinking approach fails to recognize the complex interplay of factors that occur during implementation. We find that indicator schemes can spark a rich, yet unappreciated, series of conceptual, instrumental, and structural dynamics. We conclude that the hidden power of these schemes lies in their ability to foster dialog, stimulate learning, incentivize network development, challenge takeholder worldviews, and steer systems change toward sustainable destination management.authorsversioninpres
Dice: Blessed or Cursed?
Every year, hundreds of millions of dice are manufactured and sold. Because of the impossibility of precise dimensional control and nonuniform density, none of these dice are fair. Polyhedral dice manufactured for role-playing games like Dungeons and Dragons typically contain 4-sided, 6-sided, 8-sided, 10-sided, 12-sided, and 20-sided dice (D4, D6, D8, D10, D12, and D20). D20s are especially problematic. In 3000-roll tests of several D20s, only about one-quarter tested fair. In light of the inherent unfairness of most dice, we explored the possibility of using dice mechanics involving multiple dice to obtain fairer results. For D20s, summing three dice gave promising results. Even using dice that tested highly unfair individually, sums of three dice tested fair. We also considered Fate or Fudge dice mechanics which effectively use the sum of 4 D3s. With one exception, these dice tested fair. In our tests, three D20s tested fairer than four Fate dice
Innovation Games: A new approach to the competitive challenge
Firms need to be innovative to stay ahead of the competition. But what form does innovation take in today's fast-moving world? The conventional view is that innovation is confined to the R&D departments of large firms, where boffins labour to perfect new products that meet presently unmet customer needs, and patents and copyrights protect market supremacy. In this âclosed systemâ scenario, all managers are striving to follow universal best practices, and as a consequence can find themselves trapped in competition that ultimately gets no one very far. The authors argue that in reality, 21st century innovation is a much more fluid affair. For example, rather than being released as a finished product, the first generation of a new product may be a prototype with corners still to be rubbed off when it enters the market: adventurous early customers themselves help to hone performance over time. Similarly, rather than R&D being an internal business, an entire ecosystem of smaller firms may collaborate and interact, under the direction of the lead company, in the innovation process. Analysing data collected from a large number of firms across different industry sectors, the authors set out to create a more holistic, multi-dimensional approach to understanding innovation. To this end, they draw up a typology of seven âgames of innovationâ with different characteristics; games cut across industries and sectors, and different firms may play one or more. Their empirical findings highlight the fact that âdesign rulesâ are not always drawn up in R&D laboratories but in many cases emerge as a result of negotiations and competition between many players. Rather than imitating competitors, managers should focus on identifying the games their own firm is playing and the strategic issues that shape those games
A satellite perspective on interactions between convective storms and the upper atmosphere
Ponencia presentada en: 10th European Conference on Severe Storms celebrada en Cracovia (Polonia) del 4 al 8 de noviembre de 2019
Processing The Interspecies Quorum-Sensing Signal Autoinducer-2 (AI-2) Characterization Of Phospho-(S)-4,5-Dihydroxy-2,3-Pentanedione Isomerization By LsrG Protein
The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior
First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
Ablation; Hepatocellular carcinoma; HistotripsyAblaciĂłn; Carcinoma hepatocelular; HistotriciaAblaciĂł; Carcinoma hepatocel·lular; HistotrĂciaRationale Current hepatic locoregional therapies are limited in terms of effectiveness and toxicities. Given promising pre-clinical results, a first in-human trial was designed to assess the technical effectiveness and safety profile of histotripsy, a noninvasive, non-thermal, non-ionizing focused ultrasound therapy that creates precise, predictable tissue destruction, in patients with primary and secondary liver tumors.
Methods A multicenter phase I trial (Theresa Study) was performed in a single country with 8âweeks of planned follow-up. Eight of fourteen recruited patients were deemed eligible and enrolled in the study. Hepatic histotripsy, was performed with a prototype system (HistoSonics, Inc., Ann Arbor, MI). Eleven tumors were targeted in the 8 patients who all had unresectable end-stage multifocal liver tumors: colorectal liver metastases (CRLM) in 5 patients (7 tumors), breast cancer metastases in 1 (1 tumor), cholangiocarcinoma metastases in 1 (2 tumors), and hepatocellular carcinoma (HCC) in 1 (1 tumor). The primary endpoint was acute technical success, defined as creating a zone of tissue destruction per planned volume assessed by MRI 1-day post-procedure. Safety (device-related adverse events) through 2âmonths was a secondary endpoint.
Results The 8 patients had a median age of 60.4âyears with an average targeted tumor diameter of 1.4âcm. The primary endpoint was achieved in all procedures. The secondary safety profile endpoint identified no device-related adverse events. Two patients experienced a continuous decline in tumor markers during the eight weeks following the procedure.
Conclusions This first-in-human trial demonstrates that hepatic histotripsy effectively destroys liver tissue in a predictable manner, correlating very well with the planned histotripsy volume, and has a high safety profile without any device-related adverse events. Based on these results, the need for more definitive clinical trials is warranted. Trial Registration: Study to Evaluate VORTX Rx (Theresa). NCT03741088. https://clinicaltrials.gov/ct2/show/NCT03741088This study was supported by the funding from Histosonics, Inc
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