The remote monad design pattern

Remote Procedure Calls are expensive. This paper demonstrates how to reduce the cost of calling remote procedures from Haskell by using the remote monad design pattern, which amortizes the cost of remote calls. This gives the Haskell community access to remote capabilities that are not directly supported, at a surprisingly inexpensive cost. We explore the remote monad design pattern through six models of remote execution patterns, using a simulated Internet of Things toaster as a running example. We consider the expressiveness and optimizations enabled by each remote execution model, and assess the feasibility of our approach. We then present a full-scale case study: a Haskell library that provides a Foreign Function Interface to the JavaScript Canvas API. Finally, we discuss existing instances of the remote monad design pattern found in Haskell libraries

New multicellular marine macroalgae from the early Tonian of northwestern Canada

Molecular phylogenetic data suggest that photosynthetic eukaryotes first evolved in freshwater environments in the early Proterozoic and diversified into marine environments by the Tonian Period, but early algal evolution is poorly reflected in the fossil record. Here, we report newly discovered, millimeter- to centimeter-scale macrofossils from outershelf marine facies of the ca. 950–900 Ma (Re-Os minimum age constraint = 898 ± 68 Ma) Dolores Creek Formation in the Wernecke Mountains, northwestern Canada. These fossils, variably preserved by iron oxides and clay minerals, represent two size classes. The larger forms feature unbranching thalli with uniform cells, differentiated cell walls, longitudinal striations, and probable holdfasts, whereas the smaller specimens display branching but no other diagnostic features. While the smaller population remains unresolved phylogenetically and may represent cyanobacteria, we interpret the larger fossils as multicellular eukaryotic macroalgae with a plausible green algal affinity based on their large size and presence of rib-like wall ornamentation. Considered as such, the latter are among the few green algae and some of the largest macroscopic eukaryotes yet recognized in the early Neoproterozoic. Together with other Tonian fossils, the Dolores Creek fossils indicate that eukaryotic algae, including green algae, colonized marine environments by the early Neoproterozoic Era

Identification and Quantification of Proteoforms by Mass Spectrometry

A proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post-translational modifications. In top-down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological developments have enabled comprehensive proteoform analyses in complex samples, and an increasing number of laboratories are adopting top-down proteomic workflows. In this review, we outline some recent advances and discuss current challenges and future directions for the field

What an Agile Leader Does: The Group Dynamics Perspective

When large industrial organizations change to (or start with) an agile approach to operations, managers and some employees are supposed to be “agile leaders” often without being given a clear definition of what that comprises when building agile teams. An inductive thematic analysis was used to investigate what 15 appointed leaders actually do and perceive as challenges regarding group dynamics working with an agile approach. Team maturity, Team design, and Culture and mindset were all categories of challenges related to group dynamics that the practitioners face and manage in their work-life that are not explicitly mentioned in the more process-focused agile transformation frameworks. The results suggest that leader mitigation of these three aspects of group dynamics is essential to the success of an agile transformation

Molecular mechanism underlying differential apoptosis between human melanoma cell lines UACC903 and UACC903(+6) revealed by mitochondria-focused cDNA microarrays

Human malignant melanoma cell line UACC903 is resistant to apoptosis while chromosome 6-mediated suppressed cell line UACC903(+6) is sensitive. Here, we describe identification of differential molecular pathways underlying this difference. Using our recently developed mitochondria-focused cDNA microarrays, we identified 154 differentially expressed genes including proapoptotic (BAK1 [6p21.3], BCAP31, BNIP1, CASP3, CASP6, FAS, FDX1, FDXR, TNFSF10 and VDAC1) and antiapoptotic (BCL2L1, CLN3 and MCL1) genes. Expression of these pro- and anti-apoptotic genes was higher in UACC903(+6) than in UACC903 before UV treatment and was altered after UV treatment. qRT-PCR and Western blots validated microarray results. Our bioinformatic analysis mapped these genes to differential molecular pathways that predict resistance and sensitivity of UACC903 and UACC903(+6) to apoptosis respectively. The pathways were functionally confirmed by the FAS ligand-induced cell death and by siRNA knockdown of BAK1 protein. These results demonstrated the differential molecular pathways underlying survival and apoptosis of UACC903 and UACC903(+6) cell lines

Enhanced protein isoform characterization through long-read proteogenomics

[Background] The detection of physiologically relevant protein isoforms encoded by the human genome is critical to biomedicine. Mass spectrometry (MS)-based proteomics is the preeminent method for protein detection, but isoform-resolved proteomic analysis relies on accurate reference databases that match the sample; neither a subset nor a superset database is ideal. Long-read RNA sequencing (e.g., PacBio or Oxford Nanopore) provides full-length transcripts which can be used to predict full-length protein isoforms.[Results] We describe here a long-read proteogenomics approach for integrating sample-matched long-read RNA-seq and MS-based proteomics data to enhance isoform characterization. We introduce a classification scheme for protein isoforms, discover novel protein isoforms, and present the first protein inference algorithm for the direct incorporation of long-read transcriptome data to enable detection of protein isoforms previously intractable to MS-based detection. We have released an open-source Nextflow pipeline that integrates long-read sequencing in a proteomic workflow for isoform-resolved analysis.[Conclusions] Our work suggests that the incorporation of long-read sequencing and proteomic data can facilitate improved characterization of human protein isoform diversity. Our first-generation pipeline provides a strong foundation for future development of long-read proteogenomics and its adoption for both basic and translational research.This work was supported by a National Institutes of Health (NIH) grant R35GM142647 (G.M.S.), NIH grant R35GM126914 (L.M.S.), and Jackson Laboratory (A.D.M.). The codeathon which initiated the project was supported by the NIH STRIDES Initiative at the NIH.Peer reviewe

Automobile Trip from San Francisco to Los Angeles

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