Using Background Knowledge from Preceding Studies for Building a Random Forest Prediction Model: A Plasmode Simulation Study

There is an increasing interest in machine learning (ML) algorithms for predicting patient outcomes, as these methods are designed to automatically discover complex data patterns. For example, the random forest (RF) algorithm is designed to identify relevant predictor variables out of a large set of candidates. In addition, researchers may also use external information for variable selection to improve model interpretability and variable selection accuracy, thereby prediction quality. However, it is unclear to which extent, if at all, RF and ML methods may benefit from external information. In this paper, we examine the usefulness of external information from prior variable selection studies that used traditional statistical modeling approaches such as the Lasso, or suboptimal methods such as univariate selection. We conducted a plasmode simulation study based on subsampling a data set from a pharmacoepidemiologic study with nearly 200,000 individuals, two binary outcomes and 1152 candidate predictor (mainly sparse binary) variables. When the scope of candidate predictors was reduced based on external knowledge RF models achieved better calibration, that is, better agreement of predictions and observed outcome rates. However, prediction quality measured by cross-entropy, AUROC or the Brier score did not improve. We recommend appraising the methodological quality of studies that serve as an external information source for future prediction model development.     

Triplet-Triplet Energy Transfer: A Simple Strategy for an Efficient Visible Light-Induced Photoclick Reaction

Photoclick reactions combine the advantages offered by light-driven processes and classical click chemistry and have found applications ranging from surface functionalization, polymer conjugation, photo-crosslinking, and protein labeling. Despite these advances, the dependency of most of the photoclick reactions on UV light poses a severe obstacle for their general implementation, as this light can be absorbed by other molecules in the system resulting in their degradation or unwanted reactivity. However, the development of a simple and efficient system to achieve bathochromically shifted photoclick transformations remains challenging. Here, we introduce triplet-triplet energy transfer as a fast and selective way to enable visible light-induced photoclick reactions. Specifically, we show that 9,10-phenanthrenequinones ( PQ s) can efficiently react with electron-rich alkenes ( ERA s) in the presence of a catalytic amount (as little as 5 mol %) of photosensitizers. The photocycloaddition reaction can be achieved under green (530 nm) or orange (590 nm) light irradiation, representing a bathochromic shift of over 100 nm as compared to the classical PQ-ERA s system. Furthermore, by combining appropriate reactants, we establish an orthogonal, blue and green light-induced photoclick reaction system in which the product distribution can be precisely controlled by the choice of the color of light.     

Peptide Conjugated Dihydroazulene/Vinylheptafulvene Photoswitches in Aqueous Environment

Light-responsive molecules have seen a major advance in modulating biological functions in recent years. Especially photoswitches are highly attractive building blocks due to the reversible nature of their light-mediated reactivity. They are frequently used to affect both the properties of small bioactive compounds and biomacromolecules if incorporated suitably. Despite their success in a plethora of applications, only a limited set of photochromic core structures is routinely employed and a large number of photochromic couples are under-investigated in biological context. Broadening the toolbox of photoswitches available to modulate biological activity would open new avenues and unlock the full potential of photoswitchable molecules for biological studies. In this work, we explore the photochemical and thermal properties of the dihydroazulene/vinylheptafulvene photochromic couple as peptide conjugates in aqueous environment.     

New In Situ Trapping Metalations of Functionalized Arenes and Heteroarenes with TMPLi in the Presence of ZnCl2 and Other Metal Salts

The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate with a metal salt such as MgCl₂, ZnCl₂, or CuCN at ?78 °C first leads to lithiation of the arene followed by transmetalation with the metal salt to afford functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping method allows an expedited metalation (?78 °C, 5 min) of a range of sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles not otherwise available by standard metalating agents, such as TMPMgCl?LiCl or TMPZnCl?LiCl.     

Continuous glucose monitoring in interstitial fluid using glucose oxidase-based sensor compared to established blood glucose measurement in rats

Glucose monitoring is of importance for success of complex therapeutic interventions in diabetic patients. Its impact on treatment and glycemic control is demonstrated in large clinical trials. Up to eight blood glucose measurements per day are recommended. Notwithstanding, a substantial number of diabetic patients cannot or will not monitor their blood glucose appropriately. Considerable progress in control of disturbed metabolism in diabetic patients can be expected by continuous glucose monitoring. The aim of the study was to evaluate the performance of a new amperometric glucose oxidase-based glucose sensor in vitro and in vivo after subcutaneous implantation into rats.For in vitro testing current output of sensors was measured by exposure to increasing and decreasing glucose concentrations up to 472 mg dL⁻¹ over a time period of 7 days. After subcutaneous implantation of sensors into interscapular region of male rats glucose in interstitial fluid was evaluated and compared to glucose in arterial blood up to 7 days. Hyper- and hypoglycaemia were induced by intravenous application of glucose and insulin, respectively. Current of each implanted sensor was converted into glucose concentration using the first blood glucose measurement only.A change of current with glucose of 0.35 nA mg⁻¹ dL⁻¹ indicates high sensitivity of the sensor in vitro. The response time (90% of steady state) was calculated by approximately 60 s. Test strips for blood glucose measurement as reference for sensor readings was found as an appropriate and rapidly available method in rats by comparison with established hexokinase method in an automated lab analyzer with limits of agreement of +32.8 and −25.7 mg dL⁻¹ in Bland-Altman analysis. In normo- and hypoglycaemic range sensor readings in interstitial fluid correlated well with blood glucose measurements whereas hyperglycaemia was not reflected by the sensor completely when blood glucose was changing rapidly.The data given characterize a sensor with high sensitivity, long term stability and short response time. A single calibration of the sensor is required only in measurement periods up to 7 days. The findings demonstrate that the sensor is a highly promising candidate for assessment in humans.     

Photochemical Z-->E isomerization of a hemithioindigo/hemistilbene omega-amino acid.

The molecule HTI, which combines hemithioindigo and hemistilbene molecular parts, allows reversible switching between two isomeric states. Photochromic behaviour of the HTI molecule is observed by irradiation with UV/Vis light. The photochemical reaction, a Z/E isomerization around the central double bond connecting the two molecular parts, is investigated by transient absorption and emission spectroscopy. For a special HTI molecule, namely, an omega-amino acid, the Z-->E isomerization process occurs on a timescale of 30 ps. In the course of the reaction fast processes on the 1-10 ps timescale are observed which point to motions of the molecule on the potential-energy surface of the excited state. The combination of transient absorption experiments in the visible spectral range with time-resolved fluorescence and infrared measurements reveal a photochemical pathway with three intermediate states. Together with a theoretical modelling procedure the experiments point to a sequential reaction scheme and give indications of the nature of the involved intermediates.     

Tree decompositions of graphs: Saving memory in dynamic programming

We propose a simple and effective heuristic to save memory in dynamic programming on tree decompositions when solving graph optimization problems. The introduced “anchor technique” is based on a tree-like set covering problem. We substantiate our findings by experimental results. Our strategy has negligible computational overhead concerning running time but achieves memory savings for nice tree decompositions and path decompositions between 60% and 98%.     

A mathematical insight in the epithelial-mesenchymal-like transition in cancer cells and its effect in the invasion of the extracellular matrix

Current biological knowledge supports the existence of a secondary group of cancer cells within the body of the tumour that exhibits stem cell-like properties. These cells are termed cancer stem cells, and as opposed to themore usual differentiated cancer cells, they exhibit highermotility, they are more resilient to therapy, and are able to metastasize to secondary locations within the organism and produce new tumours. The origin of the cancer stem cells is not completely clear; they seem to stem from the differentiated cancer cells via a transition process related to the epithelial-mesenchymal transition that can also be found in normal tissue. In the current work we model and numerically study the transition between these two types of cancer cells, and the resulting “ensemble” invasion of the extracellular matrix. This leads to the derivation and numerical simulation of two systems: an algebraic-elliptic system for the transition and an advection-reaction-diffusion system of Keller-Segel taxis type for the invasion.     

Barium isotope fractionation during experimental formation of the double carbonate BaMn[CO3]2 at ambient temperature

In this study, we present the first experimental results for stable barium (Ba) isotope (¹³⁷Ba/¹³⁴Ba) fractionation during low-temperature formation of the anhydrous double carbonate BaMn[CO₃]₂. This investigation is part of an ongoing work on Ba fractionation in the natural barium cycle. Precipitation at a temperature of 21±1°C leads to an enrichment of the lighter Ba isotope described by an enrichment factor of?0.11±0.06‰ in the double carbonate than in an aqueous barium-manganese(II) chloride/sodium bicarbonate solution, which is within the range of previous reports for synthetic pure BaCO ₃ (witherite) formation.     

Supercritical CO2-Brine Relative Permeability Experiments in Reservoir Rocks��Literature Review and Recommendations

The relative permeability of carbon dioxide (CO₂) to brine influences the injectivity and plume migration when CO₂ is injected in a reservoir for CO₂ storage or enhanced oil recovery (EOR) purposes. It is common practice to determine the relative permeability of a fluid by means of laboratory measurements. Two principal approaches are used to obtain a relative permeability data: steady state and unsteady state. Although CO₂ has been employed in enhanced oil recovery, not much data can be found in the open literature. The few studies available report wide ranges for CO₂ relative permeability in typical sedimentary rocks such as Berea sandstone, dolomite, and others. The experimental setups vary for each study, employing steady and unsteady state approaches, different experimental parameters such as temperature, pressure, rock type, etc. and various interpretation methods. Hence, it is inherently difficult to compare the data and determine the origin of differences. It is evident that more experiments are needed to close this knowledge gap on relative permeability. This article concludes that standards for lab measurements need to be defined a. to establish a reliable CO₂-brine relative permeability measurement method that can be repeated under the same conditions in any lab and b. to enable comparison of the data to accurately predict the well injection and fluid migration behavior in the reservoir.