WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring.

Neural type-specific expression of clustered Protocadherin (Pcdh) proteins is essential for the establishment of connectivity patterns during brain development. In mammals, deterministic expression of the same Pcdh isoform promotes minimal overlap of tiled projections of serotonergic neuron axons throughout the brain, while stochastic expression of Pcdh genes allows for convergence of tightly packed, overlapping olfactory sensory neuron axons into targeted structures. How can the same gene locus generate opposite transcriptional programs that orchestrate distinct spatial arrangements of axonal patterns? Here, we reveal that cell type-specific Pcdh expression and axonal behavior depend on the activity of cohesin and its unloader, WAPL (wings apart-like protein homolog). While cohesin erases genomic-distance biases in Pcdh choice, WAPL functions as a rheostat of cohesin processivity that determines Pcdh isoform diversity.

Machine Learning Generated Synthetic Faces for Use in Facial Aesthetic Research.

Importance: A centralized repository of clinically applicable facial images with unrestricted use would facilitate facial aesthetic research. Objective: Using a machine learning neural network, we aim to (1) create a repository of synthetic faces that can be used for facial aesthetic research and (2) analyze synthetic faces according to contemporary aesthetic principles. Design, Setting, and Participants: Synthetic facial images were generated using an open source generative adversarial network. Images were refined and then analyzed using computer vision technology. Interventions: Not applicable. Main Outcomes and Measures: Synthetic facial images were created for use as a facial aesthetic research data set. Results: One thousand synthetic images were generated, and 60 images underwent analysis. Image attributes, including age, gender, image principle axis, facial emotion, and facial landmark points, were attained. Images demonstrated accordance with contemporary aesthetic principles of horizontal thirds and vertical fifths. Images demonstrated excellent correspondence when compared with real human facial photographs. Conclusions and Relevance: We have generated realistic synthetic facial images that have potential as a valuable research tool and demonstrate similarity to real human photographs while adhering to contemporary aesthetic principles.

The miR-503 cluster is coordinately under-expressed in endometrial endometrioid adenocarcinoma and targets many oncogenes, cell cycle genes, DNA repair genes and chemotherapy response genes.

BACKGROUND: The miR-503 miRNA cluster, located at Xq23.1, is composed of six miRNAs; miR-424, miR-503, miR-542, miR-450a-1, miR-450a-2 and miR-450b. Numerous studies have focused on the relationship of one or two members of the cluster and various human cancers. Here, we suggest that the entire cluster as a single coordinately expressed polycistron transcribed from a single promoter in endometrial endometrioid adenocarcinoma (EEA). SUBJECTS AND METHODS: A tissue panel composed of twenty histologically confirmed endometrial endometrioid adenocarcinomas (EEA) and four benign endometrium was assembled under informed consent. Expression of each member of the miR-503 cluster was determined by quantitative PCR and differences in expression between EEA and benign tissues were assessed via the standard ΔΔCt method. In addition, the role of promoter methylation status in miRNA expression was examined in Ishikawa H cells following exposure to the cytidine analog Decitabine. RESULTS: Expression of each member of the miR-503 cluster is significantly downregulated in EEA in our tumor sample. Both in our tumor sample and in The Cancer Genome Atlas (TCGA) there is evidence of highly correlated expression further supporting the idea that the miR-503 cluster is a polycistron. Looking at each member of the miR-503 cluster we were able to identify 55 unique experimentally validated target genes which include a substantial number of genes involved in carcinogenesis, DNA damage response, cell cycle regulation and chemotherapeutic response. We also found preliminary evidence that regulation of the miR-503 cluster is governed by methylation of the promoter in EEA. CONCLUSION: The totality of the data presented here strongly suggest that the miR-503 cluster as a whole merits further investigation as an important potential therapeutic target in EEA.

Effects of vibrotactile feedback on human learning of arm motions.

Tactile cues generated from lightweight, wearable actuators can help users learn new motions by providing immediate feedback on when and how to correct their movements. We present a vibrotactile motion guidance system that measures arm motions and provides vibration feedback when the user deviates from a desired trajectory. A study was conducted to test the effects of vibrotactile guidance on a subject's ability to learn arm motions. Twenty-six subjects learned motions of varying difficulty with both visual (V), and visual and vibrotactile (VVT) feedback over the course of four days of training. After four days of rest, subjects returned to perform the motions from memory with no feedback. We found that augmenting visual feedback with vibrotactile feedback helped subjects reduce the root mean square (rms) angle error of their limb significantly while they were learning the motions, particularly for 1DOF motions. Analysis of the retention data showed no significant difference in rms angle errors between feedback conditions.

Search efficiency for tactile features rendered by surface haptic displays.

Haptic interfaces controlled by a single fingertip or hand-held probe tend to display surface features individually, requiring serial search for multiple features. Novel surface haptic devices, however, have the potential to provide displays to multiple fingertips simultaneously, affording the possibility of parallel search. Using variable-friction surface haptic devices, we investigated the ability of participants to detect a target feature among a set of distractors in parallel across the fingers. We found that searches for a material property (slipperiness) and an illusory shape (virtual hole) were significantly impaired by distractors, while search for an abrupt discontinuity (virtual edge) was not. The efficiency of search for edges rendered by surface haptics suggests that they engage primitive detectors in the haptic perceptual system.

A robotic assistant for trans-oral surgery: the robotic endo-laryngeal flexible (Robo-ELF) scope.

This paper describes the continued development of the Robotic EndoLaryngeal (Robo-ELF) Scope System, a simple clinically usable robot for manipulating flexible endoscopes, particularly in laryngeal surgery. The system includes a robot with three active and two passive degrees of freedom, a five degree of freedom passive positioning arm, a malleable scope shaft support, and a custom joystick controller. The Robo-ELF Scope allows a surgeon to control a flexible endoscope with only one hand and also to release the controls and perform bimanual surgery if desired. We have evaluated the Robo-ELF Scope system in both phantom and cadaver studies and found it superior to hand manipulation of flexible endoscopes and conventional rigid endoscopes.

Robotic endolaryngeal flexible (Robo-ELF) scope: a preclinical feasibility study.

OBJECTIVES/HYPOTHESIS: This article presents a novel robotic endolaryngeal flexible (Robo-ELF) scope driver for minimally invasive laryngeal surgery. The Robo-ELF consists of a simple, robust robotic scope driver with three active and two passive degrees of freedom, allowing it to manipulate any standard flexible endoscope. The system is controlled by a joystick-like three dimensional mouse that interfaces with the scope driver via a laptop. Because the scope is supported and controlled by the robot, motor control and therefore visualization are enhanced. Additionally, because the robot remains stationary when the mouse is not being manipulated, the surgeon can position it and operate bimanually. METHODS: The system was validated by performing visualization and biopsy procedures on two human cadavers with the Robo-ELF and comparing this with standard rigid endoscopes with three different angles. RESULTS: The Robo-ELF outperformed the rigid scopes in both image quality and range of motion, overcoming line of site constraints, and allowing visualization of otherwise hidden anatomy. The system also demonstrated a rapid learning curve and enhanced motor control over a manually operated flexible endoscope. CONCLUSIONS: The Robo-ELF is a novel robot to assist in driving a flexible endoscope for surgery of the upper aerodigestive tract.