Search

Students in statistics, data science, analytics, and related fields study the theory and methodology of data-related topics. Some, but not all, are exposed to experiential learning courses that cover essential parts of the life cycle of practical problem-solving. Experiential learning enables students to convert real-world issues into solvable technical questions and effectively communicate their findings to clients. We describe several experiential learning course designs in statistics, data science, and analytics curricula. We present findings from interviews with faculty from the U.S., Europe, and the Middle East and surveys of former students. We observe that courses featuring live projects and coaching by experienced faculty have a high career impact, as reported by former participants. However, such courses are labor-intensive for both instructors and students. We give estimates of the required effort to deliver courses with live projects and the perceived benefits and tradeoffs of such courses. Overall, we conclude that courses offering live-project experiences, despite being more time-consuming than traditional courses, offer significant benefits for students regarding career impact and skill development, making them worthwhile investments. Supplementary materials for this article are available online.

Abstract Driven by digital technologies, manufacturers aim to tap into data-driven business models, in which value is generated from data as a complement to physical products. However, this transformation can be complex, as different archetypes of data-driven business models require substantially different business and technical capabilities. While there are manifold contributions to research on technical capability development, an integrated and aligned perspective on both business and technology capabilities for distinct data-driven business model archetypes is needed. This perspective promises to enhance research’s understanding of this transformation and offers guidance for practitioners. As maturity models have proven to be valuable tools in capability development, we follow a design science approach to develop a maturity model for the transformation toward archetypal data-driven business models. To provide an integrated perspective on business and technology capabilities, the maturity model leverages a layered enterprise architecture model. By applying and evaluating in use at two manufacturers, we find two different transformation approaches, namely ‘data first’ and ‘business first’. The resulting insights highlight the model’s integrative perspective’s value for research to improve the understanding of this transformation. For practitioners, the maturity model allows a status quo assessment and derives fields of action to develop the capabilities required for the aspired data-driven business model.

Chromatin has been shown to undergo diffusional motion, which is affected during gene transcription by RNA polymerase activity. However, the relationship between chromatin mobility and other genomic processes remains unclear. Hence, we set out to label the DNA directly in a sequence unbiased manner and followed labeled chromatin dynamics in interphase human cells expressing GFP-tagged proliferating cell nuclear antigen (PCNA), a cell cycle marker and core component of the DNA replication machinery. We detected decreased chromatin mobility during the S-phase compared to G1 and G2 phases in tumor as well as normal diploid cells using automated particle tracking. To gain insight into the dynamical organization of the genome during DNA replication, we determined labeled chromatin domain sizes and analyzed their motion in replicating cells. By correlating chromatin mobility proximal to the active sites of DNA synthesis, we showed that chromatin motion was locally constrained at the sites of DNA replication. Furthermore, inhibiting DNA synthesis led to increased loading of DNA polymerases. This was accompanied by accumulation of the single-stranded DNA binding protein on the chromatin and activation of DNA helicases further restricting local chromatin motion. We, therefore, propose that it is the loading of replisomes but not their catalytic activity that reduces the dynamics of replicating chromatin segments in the S-phase as well as their accessibility and probability of interactions with other genomic regions.

Automatic analysis of colocalizing biological structures in multi-channel fluorescence microscopy images is an important task to quantify and understand biological processes at high spatial-temporal resolution. Here, we introduce a software suite for colocalization analysis of spot-like objects in multi-channel fluorescence microscopy images. The software suite consists of ColocQuant and ColocJ, and is easy to use for biologists. ColocQuant is a Python-based software with graphical user interface to quantify colocalization of particles in two or three channels. Object-based colocalization is performed by an efficient multi-dimensional graph-based $k$ -d-tree approach, which determines nearest neighbors involved in double or triple colocalization. ColocJ enables efficient and intuitive visualization of the color composition of colocalizations by a Maxwell color triangle and a color ribbon. Colocalization information can be visualized for an entire image or a selected region-of-interest. In addition, global statistics of the particle intensity, particle size, and the number of colocalizations over time are provided. The colocalization analysis results can be exported and used in other software. We illustrate the application of our software suite for multi-channel live cell fluorescence microscopy image sequences of viral proteins in hepatitis C virus infected cells. We performed two-channel and three-channel colocalization analysis.

Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions.

Introduction: The high burden of left ventricular (LV) abnormalities in patients with advanced chronic kidney disease (CKD) is well established. However, less is known about the prevalence, patterns, and determinants of LV abnormalities in patients with early CKD. Methods: We examined LV structure in 290 patients with a median estimated glomerular filtration rate (eGFR) of 51 ml/min per 1.73 m2 by magnetic resonance imaging (MRI). We explored associations with clinical and hemodynamic parameters, hydration (bioimpedance), endothelial function, inflammation (including C-reactive protein and tumor necrosis factor−α and its soluble receptors) and mineral bone disease (MBD) markers (including vitamin D, parathyroid hormone, α-klotho and fibroblast growth factor−23). Results: Normal geometry was found in 56% of patients, dilation in 4%, concentric remodeling in 10%, and LV hypertrophy in 29%. Linear regression analysis revealed that greater LV mass was independently associated with male sex, greater body mass index (BMI), and higher 24-hour systolic blood pressure (24-hour SBP). Concentric remodeling was independently associated with age, male sex, higher 24-hour SBP, and greater hemoglobin levels. Surprisingly, neither hydration status, nor endothelial function, nor any of the inflammatory or MBD parameters added significantly to these models. Conclusion: Abnormal LV structure was found in almost one-half of the patients. Reducing BMI and 24-hour SBP and avoiding high hemoglobin concentrations appear to be the key factors to prevent abnormal LV remodeling in patients with mild-to-moderate CKD. Key words: chronic kidney disease, hypertension, kidney diseases, left ventricular hypertrophy, mineral metabolism

Background: Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG). Methods: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133+ bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0). Subsequently, the findings have been validated in an independent patient cohort (n=14) as well as in two preclinical mouse models investigating SH2B3/LNK antisense or knockout deficient conditions. Findings: 1. Clinical: R differed from NR in a total of 161 genes in differential expression (n=23, q

Abstract Background Severe hypoperfusion can cause lung damage. We studied the effects of regional perfusion block in normal lungs and in the lungs that had been conditioned by lavage with 500 ml saline and high V T (20 ml kg−1) ventilation. Methods Nineteen pigs (61.2 ± 2.5 kg) were randomized to five groups: controls (n = 3), the right lower lobe block alone (n = 3), lavage and high V T (n = 4), lung lavage, and high V T plus perfusion block of the right (n = 5) or left (n = 4) lower lobe. Gas exchange, respiratory mechanics, and hemodynamics were measured hourly. After an 8-h observation period, CT scans were obtained at 0 and 15 cmH2O airway pressure. Results Perfusion block did not damage healthy lungs. In conditioned lungs, the left perfusion block caused more edema in the contralateral lung (777 ± 62 g right lung vs 484 ± 204 g left; p

Summary: The hepatitis C virus (HCV) is a major cause of chronic liver disease, affecting around 71 million people worldwide. Viral RNA replication occurs in a membranous compartment composed of double-membrane vesicles (DMVs), whereas virus particles are thought to form by budding into the endoplasmic reticulum (ER). It is unknown how these steps are orchestrated in space and time. Here, we established an imaging system to visualize HCV structural and replicase proteins in live cells and with high resolution. We determined the conditions for the recruitment of viral proteins to putative assembly sites and studied the dynamics of this event and the underlying ultrastructure. Most notable was the selective recruitment of ER membranes around lipid droplets where structural proteins and the viral replicase colocalize. Moreover, ER membranes wrapping lipid droplets were decorated with double membrane vesicles, providing a topological map of how HCV might coordinate the steps of viral replication and virion assembly. : Lee et al. visualized likely HCV assembly in live cells and with high resolution. During assembly, HCV structural proteins relocalize to the viral replicase and together induce the wrapping of lipid droplets by ER membranes. These membranes are linked to the viral replication organelle, allowing spatial coordination of replication and assembly. Keywords: replication organelle, double-membrane vesicles, correlative light and electron microscopy, CLEM, HCV, lipid metabolism, virus–host interaction, assembly, lipid droplet, plus-strand RNA virus

Paclitaxel is an integral component of solid tumor treatment. This chemotherapeutic agent provokes an often irreversible peripheral sensory neuropathy with pathological features of distal axonal degeneration. Current pathological concepts assume that polymerization of axonal microtubules and mitochondrial dysfunction contributes to the development of paclitaxel-induced peripheral neuropathy. The relationship, however, between microtubule stabilization, mitotoxicity and axonal degeneration is still not completely understood. To explore the function of axonal mitochondria we treated transgenic mice that harbor cyan fluorescent protein (CFP)-labeled neuronal mitochondria with repeated doses of paclitaxel and assessed neuropathic changes by nerve conduction and histological studies. In addition, mitochondrial content and morphology was determined by ex vivo imaging of axons containing CFP-labeled mitochondria. Using quantitative RT-PCR and fluorescence-labeled mRNA we determined axonal mRNA transport of nuclear encoded mitochondrial proteins. Prolonged treatment with high doses of paclitaxel-induced a predominant sensory neuropathy in mice. Although mitochondrial velocity in axons per se was not altered, we observed significant changes in mitochondrial morphology, suggesting that paclitaxel treatment impairs the dynamics of axonal mitochondria. These changes were caused by decreased levels of nuclear encoded mRNA, including the mitochondrial fusion/fission machinery. Moreover, impaired axonal mRNA transport in vitro resulted in mitochondrial dysfunction and subsequent axonal degeneration. Taken together, our experiments provide evidence that disrupted axonal transport of nuclear derived mRNA plays a crucial role in the pathogenesis of paclitaxel-induced sensory neuropathy.

HPLC-DAD systems generate time intensity (absorbance) matrices called spectrochromatograms. Under good experimental conditions, spectro-chromatograms of elution peaks of pure analytes are bilinear products of a time peak and an absorbance spectrum. Co-eluting impurities create deviations from this pure bilinear structure. Unfortunately, other imperfections, such as scan averaging, large optical windows, imperfect lamp alignment, mobile phase fluctuations, etc. also create departures from the pure bilinear structure. This makes it hard to distinguish low concentration impurities from artifacts and hampers safe detection of contaminants. There are two main ways to deal with such artifacts: removal and simulation, and ImpuR provides R functions to do both and to integrate both approaches. More specifically, ImpuR provides a set of tools to explore time-intensity matrices with respect to their bilinear structure and departures from it. It includes exploratory graphs for bilinear matrices (bilinear residual graphs and singular value decompositions), spectral dissimilarity curves via window-evolving factor analysis with heteroscedasticity correction and the sine method, methods for removal of artifacts, and a comprehensive simulation tool to assess the impact of potential artifacts and to allow for the construction of guide curves for use with the sine method.

Most students in engineering programmes start their first university physics course with a system of beliefs and intuitions which are often inconsistent with the standard Newtonian framework. This paper presents an experiment in collaborative learning with small teams aiming at helping students to relinquish their naïve intuitions about dynamics. An important aspect of this experiment is that students were asked to both critically analyze the contents of video clips illustrating mechanical dynamics and design and realize their own video clip. The efficacy of the activity was assessed. The success of the experiment is attributed to the choice of video clips clearly belonging to student culture, to the students working in teams, and to the quality of the tutoring.