Pachyonychia Congenita Project

The Reclassifying Epidermal Differentiation Disorders Initiative (REDDI) taskforce has introduced a pathogenesis-based classification for epidermal differentiation disorders (EDDs), to address limitations with the previous terminology. Replacing older terms, the updated classification groups EDDs by protein function and promotes genotyping, offering potential for targeted treatments. EDDs are now categorized as nonsyndromic (nEDD), syndromic (sEDD) or palmoplantar-focused (pEDD). This system supports healthcare providers, patients and caregivers in diagnosis and treatment, with the goal of improving clinical outcomes through periodic updates as new genetic insights emerge.

More than 50 palmoplantar epidermal differentiation disorders (pEDDs) have been reported in the literature. Various descriptors have been used to name these conditions, including clinical features often designated as acronyms or evocative terms, and names of clinicians and of geographical locations. Not only has this nomenclature been criticized for its lack of methodological consistency, but it has also progressively lost its clinical relevance. Indeed, the advent of a wide range of pathogenesis-targeting therapeutic solutions for these disorders has raised the need for a novel classification of pEDDs, based on their causative genetic defects, to provide clinicians with genuine therapeutic guidance. Here, we present a novel classification scheme for pEDDs and its application in the form of a practical algorithm for the rapid diagnosis of pEDDs.

The Pro-Am Collaborative Astronomy (PACA) Project 1.0, evolved from the successful NASA observational campaign CIOC to characterize Oort-cloud comet C/2012 S1(ISON) in 2013 on its initial passage through the inner solar system. With no spacecraft en route to comet ISON, many of NASA assets were utilised to characterize the comet. With the inclusion of amateur astronomers, educators, students, outreach coordinators and astronomy journalists; adaptation of various social media platforms and components of emerging field of citizen science, four phases for a successful pro-am collaboration were identified: (1) identification of a scientific knowledge gap; (2) integration of the pro-am communities; (3) adopt emerging technology and (4) stay in the limelight with results of the campaign. Several important results that emerged from the successful campaigns are: (i) establishment of a global network of astronomers that can be galvanized into action on short notice; (ii) provide an alert mechanism to all observers; (iii) immediate outreach and dissemination of results via our media/blogger members; (iv) provide a forum for discussions between the communities to help strategize the observing campaign for maximum benefit and (v) identify potential challenges on the data archival and its crowdsourcing. We will illustrate these concepts in detail for the first comet campaign, PACA_CIOC. We will also share some strategies for building successful pro-am campaigns, with examples from various PACA- and non-PACA campaigns, including NASA/CIOC campaigns; ESA/Rosetta mission to comet 67P; 2017 and 2019 Total Solar Eclipses (TSE) polarization experiments with citizen scientists; planetary oppositions of Jupiter, Saturn and Mars in 2018 and other observing modes of polarization and spectroscopy now available to the amateur community. The evolution of Citizen Science in astronomy is intimately tied to professional-amateur collaboration (pro-am) observing campaigns. We will provide a framework from the set-up of the pro-am observing campaign to identifying challenges (such as data archival and its crowdsourcing) unique to each campaign. We will identify future opportunities for small aperture pro-am campaigns to include elements of citizen science (i) for engaging various audiences; and (ii) to include scientists and educators to provide guidance for the project and post-activity analysis of the data collected. The inclusion of educators from the start in defining such activities is vital for their success. Yet many scientists do not include educators till later in campaign. While some of this is mitigated by preparing a parallel outreach/citizen science program, the lack of scientists is highlighted by the lack of useable research results. Citizen science has evolved from a simple sort of data by engaging the public to iteratively cycling through the dimensions of a pro-am campaign (listed above). The PACA Observer comprises of a global network consisting of professional observers, individual amateur observers (solar, planetary, cometary), remote telescope networks and portable, mobile telescope networks.  We will share the various products delivered via the PACA Project and highlight several new PACA campaigns that will be instituted soon, including the return of comet 67P/C-G (target of the ESA/NASA Rosetta mission). The deliverables of the observational campaigns include long data sets of various planetary atmospheres (Jupiter, Saturn and Mars); upcoming total and annular solar eclipses; involvement of students and data scientists in all phases of data acquisition and analysis. All amateur observers are invited to join the new campaigns and participate in the upcoming PACA campaigns and the evolution of the next generation of citizen science projects with new tools like correlative analysis and virtual/augmented reality.  

Abstract

The phenotypic spectrum of genodermatoses is continuously expanding. Three siblings were referred because of a highly unusual phenotype comprising alopecia, dystrophic nails, palmoplantar keratoderma and trauma-induced skin blistering. Whole-exome sequencing analysis identified a heterozygous large genomic alteration of around 116 0000 bp resulting in the deletion of the KRT9, KRT14, KRT15, KRT16 and KRT19 genes, as well as part of KRT17. This genomic change leads to the generation of a truncated keratin 17 (KRT17) protein encoded by the first three exons of the gene and part of intron 3. The three patients were found to carry the heterozygous genomic deletion while their healthy parents did not, indicative of germline mosaicism. The genomic alteration was found to result in reduced KRT17 expression in patient skin. More importantly, the abnormal truncated KRT17 was found to exert a deleterious effect on keratinocyte cytoskeleton formation, leading to keratin aggregation. Coexpression of wildtype and truncated KRT17 proteins also caused keratin aggregation, demonstrating that the deletion exerts a dominant negative effect. In conclusion, we are reporting on a novel clinical phenotype that was found to result from germline mosaicism for a large genomic deletion spanning six keratin genes, thus expanding the spectrum of clinical manifestations associated with keratin disorders. What is already known about this topic? Various conditions known as keratinopathies have been shown over recent years to be associated with dominant or recessive variants in several individual keratin genes. What does this study add? We report three patients presenting with a unique clinical phenotype that was found to result from germline mosaicism for a large genomic deletion spanning six keratin genes. The genomic variant is predicted to result in a truncated form of keratin 17, which was found in an in vitro assay to disrupt keratinocyte cell cytoskeleton formation.

The building demand for environmentally friendly materials has led to develop new systems such as "Pablok", a panel made up of a wood platform frame, insulated with compressed straw and covered with a gypsum fiber board, applied to the wall or the deck.Straw is the inedible stalks, especially of certain species of grain, chiefly wheat, rye, oats, and barley.Unlike hay, which is used as a forage, straw does not attract mice or insects and does not rot unless wetted.The sound reduction index in laboratory was measured for a wall 39.25 cm thick with a wall lining with CW profile-single layer cladding for a total thickness of 46.5 cm.The study shows the airborne sound insulation measured in laboratory and in situ and compares the results with a software prediction.

Abstract Stream drying, especially in the western United States, is becoming more common as the climate warms and precipitation patterns become less predictable; consequently, fisheries managers need to prioritize conservation efforts where water (and fish) will persist in the future. Yellow Creek in the upper Bear River watershed (Utah and Wyoming) contains one of the largest remaining populations of Northern Leatherside Chub Lepidomeda copei, an imperiled fish. Lower reaches are drying during summer months, partly due to water withdrawals, thus reducing Northern Leatherside Chub populations and relegating the remaining fish to isolated pools until the water returns. This study used an unmanned aerial vehicle to capture high-resolution and spatially explicit imagery over 19 km of Yellow Creek in a few weeks during late August when the water is the most limiting to the fish. Through imagery and subsequent GIS analysis, we identified 405 previously unknown potential refuge-pool habitats for Northern Leatherside Chub and determined their location, size, and spatial distribution, thereby helping managers prioritize stream reaches for native fish conservation and restoration. While the cost of unmanned aerial vehicle flights was estimated to be 2.5 times that of on-the-ground surveys in 2016, unmanned aerial vehicle technology continues to become more cost effective and, unlike traditional surveys, provides high-resolution and spatially referenced data.

The use of artificial groundwater storage and recovery is rapidly becoming an essential component of water resources management systems. It improves their efficiency and cost-effectiveness by providing broad operational flexibility. The demand for new sites, the growing regulatory controls and the need to reduce the unit cost of underground storage could benefit from the use of new techniques that could improve site selection, monitoring and operation of groundwater recharge facilities. The use of surface geophysical methods can supplement and enhance the more traditional hydrogeological assessment methods such as geological mapping, subsurface drilling and pumping tests. For site selection the use of ground and aero-magnetic surveys, reflection and refraction seismic surveys, gravity and magnetotelluric surveys are good methods for hydrogeologic assessment. For monitoring and operational control vertical electric sounding, transient electromagnetic and temporal gravity surveys are applicable, particularly for groundwater mound tracking.

This paper presents the modeling and simulation of power loads due to plug-in electric vehicles’ (EVs) charging events at a dc fast charging station. Two algorithms for modeling the loads are introduced and compared, one based on sampling and one based on statistical distribution built from the sample database. Simulation of load versus time was performed using a horizon of 7 days using both techniques. The cause for the difference in the result of these two approaches is explored. Regardless of the method used, the results show that a dc fast charging station with 6 fast chargers potentially serving 700 plugin EVs generally gets 105 charging events per day with a peak load of 375 kW.