Comparing and linking machine learning and semi-mechanistic models for the predictability of endemic measles dynamics

Measles is one the best-documented and most-mechanistically-studied non-linear infectious disease dynamical systems. However, systematic investigation into the comparative performance of traditional mechanistic models and machine learning approaches in forecasting the transmission dynamics of this pathogen are still rare. Here, we compare one of the most widely used semi-mechanistic models for measles (TSIR) with a commonly used machine learning approach (LASSO), comparing performance and limits in predicting short to long term outbreak trajectories and seasonality for both regular and less regular measles outbreaks in England and Wales (E&W) and the United States. First, our results indicate that the proposed LASSO model can efficiently use data from multiple major cities and achieve similar short-to-medium term forecasting performance to semi-mechanistic models for E&W epidemics. Second, interestingly, the LASSO model also captures annual to biennial bifurcation of measles epidemics in E&W caused by susceptible response to the late 1940s baby boom. LASSO may also outperform TSIR for predicting less-regular dynamics such as those observed in major cities in US between 1932–45. Although both approaches capture short-term forecasts, accuracy suffers for both methods as we attempt longer-term predictions in highly irregular, post-vaccination outbreaks in E&W. Finally, we illustrate that the LASSO model can both qualitatively and quantitatively reconstruct mechanistic assumptions, notably susceptible dynamics, in the TSIR model. Our results characterize the limits of predictability of infectious disease dynamics for strongly immunizing pathogens with both mechanistic and machine learning models, and identify connections between these two approaches.     

Immobilization of Escherichia coli containing ω-transaminase activity in LentiKats®

Whole Escherichia coli cells overexpressing ω‐transaminase (ω‐TA) and immobilized cells entrapped in LentiKats® were used as biocatalysts in the asymmetric synthesis of the aromatic chiral amines 1‐phenylethylamine (PEA) and 3‐amino‐1‐phenylbutane (APB). Whole cells were permeabilized with different concentrations of cetrimonium bromide (CTAB) and ethanol; the best results were obtained with CTAB 0.1% which resulted in an increase in reaction rate by 40% compared to the whole cells. The synthesis of PEA was carried out using isopropyl amine (IPA) and L ‐alanine (Ala) as amino donors. Using whole cell biocatalysis, the reaction with IPA was one order of magnitude faster than with Ala. No reaction was detected when permeabilized E. coli cells containing ω‐TA were employed using Ala as the amino donor. Additionally, the synthesis of APB from 4‐phenyl‐2‐butanone and IPA was studied. Whole and permeabilized cells containing ω‐TA and their immobilized LentiKats® counterparts showed similar initial reactions rates and yields in the reaction systems, indicating 100% of immobilization efficiency (observed activity/activity immobilized) and absence of diffusional limitations (due to the immobilization). Immobilization of whole and permeabilized cells containing ω‐TA in LentiKats® allowed improved stability as the biocatalyst was shown to be efficiently reused for five reaction cycles, retaining around 80% of original activity. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012     

Hexon Modification to Improve the Activity of Oncolytic Adenovirus Vectors against Neoplastic and Stromal Cells in Pancreatic Cancer

Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety.     

Reductive Dehalogenation of Brominated Phenolic Compounds by Microorganisms Associated with the Marine Sponge Aplysina aerophoba

Marine sponges are natural sources of brominated organic compounds, including bromoindoles, bromophenols, and bromopyrroles, that may comprise up to 12% of the sponge dry weight. Aplysina aerophoba sponges harbor large numbers of bacteria that can amount to 40% of the biomass of the animal. We postulated that there might be mechanisms for microbially mediated degradation of these halogenated chemicals within the sponges. The capability of anaerobic microorganisms associated with the marine sponge to transform haloaromatic compounds was tested under different electron-accepting conditions (i.e., denitrifying, sulfidogenic, and methanogenic). We observed dehalogenation activity of sponge-associated microorganisms with various haloaromatics. 2-Bromo-, 3-bromo-, 4-bromo-, 2,6-dibromo-, and 2,4,6-tribromophenol, and 3,5-dibromo-4-hydroxybenzoate were reductively debrominated under methanogenic and sulfidogenic conditions with no activity observed in the presence of nitrate. Monochlorinated phenols were not transformed over a period of 1 year. Debromination of 2,4,6-tribromophenol, and 2,6-dibromophenol to 2-bromophenol was more rapid than the debromination of the monobrominated phenols. Ampicillin and chloramphenicol inhibited activity, suggesting that dehalogenation was mediated by bacteria. Characterization of the debrominating methanogenic consortia by using terminal restriction fragment length polymorphism (TRFLP) and denaturing gradient gel electrophoresis analysis indicated that different 16S ribosomal DNA (rDNA) phylotypes were enriched on the different halogenated substrates. Sponge-associated microorganisms enriched on organobromine compounds had distinct 16S rDNA TRFLP patterns and were most closely related to the δ subgroup of the proteobacteria. The presence of homologous reductive dehalogenase gene motifs in the sponge-associated microorganisms suggested that reductive dehalogenation might be coupled to dehalorespiration.     

Observations on Bostrychia radicosa comb. nov. (Rhodomelaceae, Rhodophyta)

Only two genera in the Rhodomelaceae share the morphological character of transverse division of periaxial cells into two or more tier cells in which the pit connection is retained between the lower cell and the axial cell: Bostrychia and Rhodolachne. One species, Rhodolachne radicosa Itono, has been reported from mangroves, a common habitat for Bostrychia. Many collections of an entity similar to Rhodolachne radicosa have been made from localities around the Indo‐Pacific. Culture observations show a Polysiphonia‐type sexual life history in Malaysia and New Caledonia isolates that produce self‐compatible bisexual gametophytes. The New Caledonia isolate also has unisexual gametophytes. An isolate from New South Wales (Australia) reproduces asexually through successive generations of tetrasporophytes. The Thailand isolate has successive generations of mixed‐phase tetrasporophytes. The tetrasporangial stichidia also bear male spermatangial sectors, but female structures are lacking. Western Australia and Madagascar isolates do not reproduce in culture. Molecular evidence, based on sequencing of the rbcL and the large subunit ribosomal RNA genes, shows that these isolates belong to the genus Bostrychia. Low molecular weight carbohydrate analysis reveals high levels of digeneaside in all isolates. The sugar hexitol sorbitol, an osmolyte characteristic of Bostrychia, occurs in all isolates, whereas the Madagascar and New Caledonia isolates have very low levels of dulcitol. Molecular, low molecular weight carbohydrate and morphological evidence show that Rhodolachne radicosa belongs within the genus Bostrychia. We transfer Rhodolachne radicosa to Bostrychia radicosa (Itono) West, Zuccarello and Hommersand.     

Caenorhabditis nematodes colonize ephemeral resource patches in neotropical forests

Factors shaping the distribution and abundance of species include life‐history traits, population structure, and stochastic colonization–extinction dynamics. Field studies of model species groups help reveal the roles of these factors. Species of Caenorhabditis nematodes are highly divergent at the sequence level but exhibit highly conserved morphology, and many of these species live in sympatry on microbe‐rich patches of rotten material. Here, we use field experiments and large‐scale opportunistic collections to investigate species composition, abundance, and colonization efficiency of Caenorhabditis species in two of the world''s best‐studied lowland tropical field sites: Barro Colorado Island in Panamá and La Selva in Sarapiquí, Costa Rica. We observed seven species of Caenorhabditis, four of them known only from these collections. We formally describe two species and place them within the Caenorhabditis phylogeny. While these localities contain species from many parts of the phylogeny, both localities were dominated by globally distributed androdiecious species. We found that Caenorhabditis individuals were able to colonize baits accessible only through phoresy and preferentially colonized baits that were in direct contact with the ground. We estimate the number of colonization events per patch to be low.