On Singularities and Black Holes in Combination-Driven Models of Technological Innovation Networks

It has been suggested that innovations occur mainly by combination: the more inventions accumulate, the higher the probability that new inventions are obtained from previous designs. Additionally, it has been conjectured that the combinatorial nature of innovations naturally leads to a singularity: at some finite time, the number of innovations should diverge. Although these ideas are certainly appealing, no general models have been yet developed to test the conditions under which combinatorial technology should become explosive. Here we present a generalised model of technological evolution that takes into account two major properties: the number of previous technologies needed to create a novel one and how rapidly technology ages. Two different models of combinatorial growth are considered, involving different forms of ageing. When long-range memory is used and thus old inventions are available for novel innovations, singularities can emerge under some conditions with two phases separated by a critical boundary. If the ageing has a characteristic time scale, it is shown that no singularities will be observed. Instead, a “black hole” of old innovations appears and expands in time, making the rate of invention creation slow down into a linear regime.     

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses—the so-called transfer function—and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor''s ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined.     

pH-induced co-operative effects in hysteretic enzymes. 2. pH-induced co-operative effects in a cell-wall beta-glucosyltransferase

A beta-glucosyltransferase, extracted and purified from the cell walls of isolated soybean cells, displays hysteretic behaviour. The enzyme is monomeric and has a negative co-operative between pH 5.5 and 7.5. Below and above these pH values, the enzyme follows, or approaches, classical Michaelis-Menten kinetics. The free enzyme and the enzyme-glucose complex exhibit, upon pH jumps, conformational transitions which may be followed by monitoring the fluorescence of enzyme-bound toluidinylnaphthalene sulfonate. Taken together these results are consistent with the model of pH-induced co-operativity described in the preceding paper in this journal. This special type of co-operativity relies on a change of the pK value of a strategic ionizable group located outside the active site in a region (or a domain) of the protein which undergoes the conformational transition. The result that at 'low' and 'high' pH values, the enzyme follows or approaches Michaelis-Menten kinetics is explained by assuming that the conformational changes do not affect the active site.     

Conformational change of the coronavirus peplomer glycoprotein at pH 8.0 and 37 degrees C correlates with virus aggregation and virus-induced cell fusion.

We have obtained biochemical and electron microscopic evidence of conformational changes at pH 8.0 and 37 degrees C in the coronavirus spike glycoprotein E2 (S). The importance of these changes is reflected in the loss of virus infectivity, the aggregation of virions, and increased virus-induced cell fusion at the same pH. Coronavirus (MHV-A59) infectivity is exquisitely sensitive to pH. The virus was quite stable at pH 6.0 and 37 degrees C (half-life, approximately 24 h) but was rapidly and irreversibly inactivated by brief treatment at pH 8.0 and 37 degrees C (half-life, approximately 30 min). Virions treated at pH 8.0 and 37 degrees C formed clumps and large aggregates. With virions treated at pH 8.0 and 37 degrees C, the amino-terminal peptide E2N (or S1) was released from virions and the remaining peptide, E2C (S2), was aggregated. Viral spikes isolated from detergent-treated virions also aggregated at pH 8.0 and 37 degrees C. Loss of virus infectivity and E2 (S) aggregation at pH 8.0 and 37 degrees C were markedly enhanced in the presence of dithiothreitol. On the basis of the effects of dithiothreitol on the reactions of the peplomer, we propose that release of E2N (S1) and aggregation of E2C (S2) may be triggered by rearrangement of intramolecular disulfide bonds. The aggregation of virions and the isolated E2 (S) glycoprotein at pH 8.0 and 37 degrees C or following treatment with guanidine and urea at pH 6.0 and 37 degrees C indicate that an irreversible conformational change has been induced in the peplomer glycoprotein by these conditions. It is interesting that coronavirus-induced cell fusion also occurred under mildly alkaline conditions and at 37 degrees C. Some enveloped viruses, including influenza viruses and alphaviruses, show conformational changes of spike glycoproteins at a low pH, which correlates with fusion and penetration of those viruses in acidified endocytic vesicles. For coronavirus MHV-A59, comparable conformational change of the spike glycoprotein E2 (S) and cell fusion occurred at a mildly alkaline condition, suggesting that coronavirus infection-penetration, like that of paramyxoviruses and lentiviruses, may occur at the plasma membrane, rather than within endocytic vesicles.     

Connectivity and information transfer in flow networks: Two magic numbers in ecology?

An ecosystem can be visualized as a graph of certain preassigned trophic compartments; these nodes are then mutually connected through the internal exchanges of material and energy. The mathematical theory of information can be applied to such a graph in order to define two relevant indices: a measure of connectivity (the entropy H of the connections) and a measure of the degree of the “energetic” specialization (the internal transfer of informationI). The computation of these indices in stationary real cases suggests that the observed complexity of ecosystems is conditioned by two competing effects. The first can be interpreted as a “thermodynamical” principle related to the unavoidable irreversibility taking place inside the system, whereas the second can be taken as a “biological” principle concerned with the selection of some particular interactions: those which maximize the information circulating between the compartments.     

Cloning and expression of β-galactosidase gene from Streptococcus thermophilus in Saccharomyces cerevisiae

Summary The -galactosidase gene ofStreptococcus thermophilus was cloned into plasmid vector, pVT100-U, and used to transform a strain ofEscherichia coli andSaccharomyces cerevisiae. Transformants which expressed -galactosidase activity were obtained in bothE. coli andSaccharomyces cerevisiae, the highest activity found in a yeast recombinant. The expression and thermostability of the cloned -galactosidase genes from different plasmid constructions were compared with the streptococcal -galactosidase. The recombinant protein was equivalent to the specific activity and thermostability ofS. thermophilus.     

Application of Ethical Principles to Research using Public Health Data in The Global South: Perspectives from Africa

Existing ethics guidelines, influential literature and policies on ethical research generally focus on real‐time data collection from humans. They enforce individual rights and liberties, thereby lowering need for aggregate protections. Although dependable, emerging public health research paradigms like research using public health data (RUPD) raise new challenges to their application. Unlike traditional research, RUPD is population‐based, aligned to public health activities, and often reliant on pre‐collected longitudinal data. These characteristics, when considered in relation to the generally lower protective ethico‐legal frameworks of the Global South, including Africa, highlight ethical gaps. Health and demographic surveillance systems are examples of public health programs that accommodate RUPD in these contexts. We set out to explore the perspectives of professionals with a working knowledge of these systems to determine practical ways of appropriating the foundational principles of health research to advance the ever growing opportunities in RUPD. We present their perspectives and in relation to the literature and our ethical analysis, make context relevant recommendations. We further argue for the development of a framework founded on the discussions and recommendations as a minimum base for achieving optimal ethics for optimal RUPD in the Global South.     

The Role of Sugars,Hexokinase, and Sucrose Synthase in the Determination of Hypoxically Induced Tolerance to Anoxia in Tomato Roots

Hypoxic pretreatment of tomato (Lycopersicon esculentum M.) roots induced an acclimation to anoxia. Survival in the absence of oxygen was improved from 10 h to more than 36 h if external sucrose was present. The energy charge value of anoxic tissues increased during the course of hypoxic acclimation, indicating an improvement of energy metabolism. In acclimated roots ethanol was produced immediately after transfer to anoxia and little lactic acid accumulated in the tissues. In nonacclimated roots significant ethanol synthesis occurred after a 1-h lag period, during which time large amounts of lactic acid accumulated in the tissues. Several enzyme activities, including that of alcohol dehydrogenase, lactate dehydrogenase, pyruvate decarboxylase, and sucrose synthase, increased during the hypoxic pretreatment. In contrast to maize, hexokinase activities did not increase and phosphorylation of hexoses was strongly inhibited during anoxia in both kinds of tomato roots. Sucrose, but not glucose or fructose, was able to sustain glycolytic flux via the sucrose synthase pathway and allowed anoxic tolerance of acclimated roots. These results are discussed in relation to cytosolic acidosis and the ability of tomato roots to survive anoxia.     

Rehabilitation Profiles of Older Adult Stroke Survivors Admitted to Intermediate Care Units: A Multi-Centre Study

BackgroundStroke is a major cause of disability in older adults, but the evidence around post-acute treatment is limited and heterogeneous. We aimed to identify profiles of older adult stroke survivors admitted to intermediate care geriatric rehabilitation units.MethodsWe performed a cohort study, enrolling stroke survivors aged 65 years or older, admitted to 9 intermediate care units in Catalonia-Spain. To identify potential profiles, we included age, caregiver presence, comorbidity, pre-stroke and post-stroke disability, cognitive impairment and stroke severity in a cluster analysis. We also proposed a practical decision tree for patient’s classification in clinical practice. We analyzed differences between profiles in functional improvement (Barthel index), relative functional gain (Montebello index), length of hospital stay (LOS), rehabilitation efficiency (functional improvement by LOS), and new institutionalization using multivariable regression models (for continuous and dichotomous outcomes).ResultsAmong 384 patients (79.1±7.9 years, 50.8% women), we identified 3 complexity profiles: a) Lower Complexity with Caregiver (LCC), b) Moderate Complexity without Caregiver (MCN), and c) Higher Complexity with Caregiver (HCC). The decision tree showed high agreement with cluster analysis (96.6%). Using either linear (continuous outcomes) or logistic regression, both LCC and MCN, compared to HCC, showed statistically significant higher chances of functional improvement (OR = 4.68, 95%CI = 2.54–8.63 and OR = 3.0, 95%CI = 1.52–5.87, respectively, for Barthel index improvement ≥20), relative functional gain (OR = 4.41, 95%CI = 1.81–10.75 and OR = 3.45, 95%CI = 1.31–9.04, respectively, for top Vs lower tertiles), and rehabilitation efficiency (OR = 7.88, 95%CI = 3.65–17.03 and OR = 3.87, 95%CI = 1.69–8.89, respectively, for top Vs lower tertiles). In relation to LOS, MCN cluster had lower chance of shorter LOS than LCC (OR = 0.41, 95%CI = 0.23–0.75) and HCC (OR = 0.37, 95%CI = 0.19–0.73), for LOS lower Vs higher tertiles.ConclusionOur data suggest that post-stroke rehabilitation profiles could be identified using routine assessment tools and showed differential recovery. If confirmed, these findings might help to develop tailored interventions to optimize recovery of older stroke patients.