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Summary: Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored. Here, we have evaluated the combined effects from five SCN5A enhancers and their regulatory variants that are known to collectively correlate with SCN5A cardiac expression and underlie QT interval association in the general population. Using small deletions centered at the regulatory variants in episomal reporter assays in a mouse cardiomyocyte cell line, we demonstrate that the variants and their flanking sequences play critical role in individual enhancer activities, likely being a transcription factor (TF) binding site. By oligonucleotide-based pulldown assays on predicted TFs, we identify the TFs likely driving allele-specific enhancer activities. Using all 32 possible allelic synthetic constructs in reporter assays, representing the five bi-allelic enhancers, we demonstrate combined additive effects on overall enhancer activities. Using transient enhancer assays in zebrafish embryos we demonstrate that four elements act as enhancers in vivo. Together, these studies uncover the TFs driving the enhancer activities of QT interval associated SCN5A regulatory variants, reveal the additive effects from allelic combinations of these regulatory variants, and prove their potential to act as enhancers in vivo.

This paper presents an experimental study regarding the use of OpenAI’s ChatGPT for robotics applications. We outline a strategy that combines design principles for prompt engineering and the creation of a high-level function library which allows ChatGPT to adapt to different robotics tasks, simulators, and form factors. We focus our evaluations on the effectiveness of different prompt engineering techniques and dialog strategies towards the execution of various types of robotics tasks. We explore ChatGPT’s ability to use free-form dialog, parse XML tags, and to synthesize code, in addition to the use of task-specific prompting functions and closed-loop reasoning through dialogues. Our study encompasses a range of tasks within the robotics domain, from basic logical, geometrical, and mathematical reasoning all the way to complex domains such as aerial navigation, manipulation, and embodied agents. We show that ChatGPT can be effective at solving several of such tasks, while allowing users to interact with it primarily via natural language instructions. In addition to these studies, we introduce an open-sourced research tool called PromptCraft, which contains a platform where researchers can collaboratively upload and vote on examples of good prompting schemes for robotics applications, as well as a sample robotics simulator with ChatGPT integration, making it easier for users to get started with using ChatGPT for robotics. Videos and blog: aka.ms/ChatGPT-Robotics PromptCraft, AirSim-ChatGPT code: https://github.com/microsoft/PromptCraft-Robotics

Rapid and effective methods for the detection of analytes such as water contaminants, food adulterants and biomolecules are essential for the protection of public health and environmental protection. Most of the currently established analytical techniques need sophisticated equipment, centralized testing facilities, costly operations, and trained personnel. Such limitations make them inaccessible to the general populace, particularly in regions with limited resources. The emergence of microfluidic devices offers a promising alternative to overcome several such constraints. This work describes a protocol for fabricating a low-cost, open-source paper-based microfluidic device using easily available tools and materials for colorimetric detection of analytes. The ease and simplicity of fabrication allow users to design customized devices. The device is coupled with an imaging box assembled from 3D printed parts to maintain uniform lighting conditions during analytical testing. The platform allows digital imaging using smartphones or cameras to instantaneously capture images of reaction zones on the device for quantitative analysis. The system is demonstrated for detecting hexavalent chromium, a toxic water contaminant. The image analysis is performed using open-source ImageJ for quantification of results. The approach demonstrated in this work can be readily adopted for a wide range of sensing applications.

Background: Dermatoglyphics can be utilised in clinical settings to identify those who are more likely to have impacted teeth. Additionally, dermatoglyphics looks to have potential as a non-invasive diagnostic method for predicting the presence or absence of an impacted tooth. The goal of this study was to look at the most common dermatoglyphic pattern in people who had or didn't have an impacted mandibular third molar teeth and see if there was a dermatoglyphic signature. Methods: A cross-sectional study with 180 participants was conducted (90 cases and 90 controls). The rolling impression technique was used to apply blue duplicating ink to participants' fingertips, which was then recorded. There was an increase in the frequency of the whorl-plain pattern in the right-hand ring finger (60%; p=0.028) and left-hand little finger (33.3%; p=0.009), as well as the loop-ulnar pattern in the right-hand middle finger (74.4%; p=0.024) in individuals with a predisposition to the presence of impacted teeth. Results: The left-hand little finger was found to be the most predictive for impaction in a forward stepwise binary logistic regression analysis. Conclusions: Dermatoglyphics could be used as a non-invasive sign to predict whether or not a tooth is affected. Its value comes in early detection, which helps to avoid the surgical problems that come with symptomatic extraction of an impacted tooth.

Abstract Background The purpose of this parametric design of experiments was to identify and summarize how the influence of knit structure (single jersey vs. terry), fiber composition (polyester vs. cotton), fiber linear density (30/1 Ne vs. 18/1 Ne & 1/150/34 vs. 2/150/34), and yarn type (filament vs. spun) affected the frictional profile across the sock‐skin interface. Methods Friction testing trials were completed against both a polypropylene probe and a synthetic skin material (Lorica soft®) to determine if there was a difference in friction based on interface interaction. Friction testing was completed by sliding a probe across the inside bottom surface of the sock (the part that is usually in‐contact with the bottom of the foot) while instantaneously measuring the frictional force every tenth of a second. Results For both trials (plastic probe and synthetic skin), in the dry condition, knit structure was found to be the most prominent fabric parameter affecting the frictional force experienced at the sock‐skin interface. It was also determined that fiber linear density, and yarn type are tertiary factors affecting the frictional force measured at the sock‐skin interface. Finally, in the dry state, it was determined that fiber composition had seemingly no effect on the frictional force experienced at the sock‐skin interface. Conclusion This parametric design of experiments has further enhanced the understanding of the tribology at the sock‐skin interface. Through strategic design, four different textile parameters have been investigated, measured, and justified as to how each influence the friction measured between the two interfaces. This knowledge can be used to develop socks that mitigate the risk of friction blisters formation.

Polymers have gained an extensive application due to their versatility of properties and benefits. Hence, the polymer blends and composites reinforced with different infusions at different scales, macro to nanofillers, can be fabricated, leading to specific tailormade applications. The main objective of this investigation is to overview the various studies carried out to reuse the waste materials like electroplating sludge, fly ash, etc. For the development of construction materials. This paper summarizes the use of polymers in composite material formulations for the development of building materials such as lightweight concrete, protective coatings, paver blocks, bricks, and structural components. Different tests, namely viscosity, density, flash point, amine value, and epoxy equivalent weight, were performed on polymers to find their suitability as binder materials. Various laboratory tests such as compressive strength, water absorption, tear resistance, flexural strength, and split tensile tests were carried out to determine the mechanical properties of the developed materials. By using polymers with the addition of sustainable filler and waste materials, the replacement of costly raw material can be achieved by more than 50% in the case of paver blocks, up to 60% in bitumen-polymer composite, 80% in case of lightweight concrete and polymer-based panels. This insight gives the framework for the selection of different materials, optimization of combining ratio of materials, and their testing for the development of polymer-based materials.

Background/objective Nummular headache (NH) is a primary headache disorder characterised by intermittent or continuous scalp pain, affecting a small circumscribed area of the scalp. As there are limited data in the literature on NH, we conducted this review to evaluate demographic characteristics and factors associated with complete resolution of the headache, and effectiveness of treatment options.Methods We performed a systematic review of cases reported through PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and ‘nummular headache’, ‘coin-shaped headache’ and ‘coin-shaped cephalalgia’ keywords. Analysis was performed by using χ2 test and Wilcoxon rank-sum test. For individual interventions, the response rate (RR%) of the treatment was calculated.Results We analysed a total of 110 NH cases, with median age 47 years and age of pain onset 42 years. Median duration to make correct diagnosis was 18 months after first attack. The median intensity of each attack was 5/10 on verbal rating scale over 4 cm diameter with duration of attack

Neutrophils constitute the largest class of white blood cells and are the first responders in the innate immune response. They are able to sense and migrate up concentration gradients of chemoattractants in search of primary sites of infection and inflammation through a process known as chemotaxis. These chemoattractants include formylated peptides and various chemokines. While much is known about chemotaxis to individual chemoattractants, far less is known about chemotaxis towards many. Previous studies have shown that in opposing gradients of intermediate chemoattractants (interleukin-8 and leukotriene B4), neutrophils preferentially migrate toward the more distant source. In this work, we investigated neutrophil chemotaxis in opposing gradients of chemoattractants using a microfluidic platform. We found that primary neutrophils exhibit oscillatory motion in opposing gradients of intermediate chemoattractants. To understand this behavior, we constructed a mathematical model of neutrophil chemotaxis. Our results suggest that sensory adaptation alone cannot explain the observed oscillatory motion. Rather, our model suggests that neutrophils employ a winner-take-all mechanism that enables them to transiently lock onto sensed targets and continuously switch between the intermediate attractant sources as they are encountered. These findings uncover a previously unseen behavior of neutrophils in opposing gradients of chemoattractants that will further aid in our understanding of neutrophil chemotaxis and the innate immune response. In addition, we propose a winner-take-all mechanism allows the cells to avoid stagnation near local chemical maxima when migrating through a network of chemoattractant sources.

Background: The human protein atlas (HPA) is a powerful proteomic tool for visualizing the distribution of protein expression across most human tissues and many common malignancies. The HPA includes immunohistochemically-stained images from tissue microarrays (TMAs) that cover 48 tissue types and 20 common malignancies. The TMA data are used to provide expression information at the tissue, cellular, and occasionally, subcellular level. The HPA also provides subcellular data from confocal immunofluorescence data on three cell lines. Despite the availability of localization data, many unique patterns of cellular and subcellular expression are not documented. Materials and Methods: To get at this more granular data, we have developed a suite of Python scripts, HPASubC, to aid in subcellular, and cell-type specific classification of HPA images. This method allows the user to download and optimize specific HPA TMA images for review. Then, using a playstation-style video game controller, a trained observer can rapidly step through 10′s of 1000′s of images to identify patterns of interest. Results: We have successfully used this method to identify 703 endothelial cell (EC) and/or smooth muscle cell (SMCs) specific proteins discovered within 49,200 heart TMA images. This list will assist us in subdividing cardiac gene or protein array data into expression by one of the predominant cell types of the myocardium: Myocytes, SMCs or ECs. Conclusions: The opportunity to further characterize unique staining patterns across a range of human tissues and malignancies will accelerate our understanding of disease processes and point to novel markers for tissue evaluation in surgical pathology.

Background: Dermatoglyphics can be utilised in clinical settings to identify those who are more likely to have impacted teeth. Additionally, dermatoglyphics looks to have potential as a non-invasive diagnostic method for predicting the presence or absence of an impacted tooth. The goal of this study was to look at the most common dermatoglyphic pattern in people who had or didn't have an impacted mandibular third molar teeth and see if there was a dermatoglyphic signature. Methods: A cross-sectional study with 180 participants was conducted (90 cases and 90 controls). The rolling impression technique was used to apply blue duplicating ink to participants' fingertips, which was then recorded. There was an increase in the frequency of the whorl-plain pattern in the right-hand ring finger (60%; p=0.028) and left-hand little finger (33.3%; p=0.009), as well as the loop-ulnar pattern in the right-hand middle finger (74.4%; p=0.024) in individuals with a predisposition to the presence of impacted teeth. Results: The left-hand little finger was found to be the most predictive for impaction in a forward stepwise binary logistic regression analysis. Conclusions: Dermatoglyphics could be used as a non-invasive sign to predict whether or not a tooth is affected. Its value comes in early detection, which helps to avoid the surgical problems that come with symptomatic extraction of an impacted tooth.