Migration to Alma/Primo: A Case Study of Central Washington University

This paper describes how Central Washington University Libraries (CWUL) interacted and collaborated with the Orbis Cascade Alliance (OCA) Shared Integrated Library System’s (SILS) Implementation Team and Ex Libris to process systems and data migration from Innovative Interfaces Inc.’s Millennium integrated library system to Alma/Primo, Ex Libris’ next-generation library management solution and discovery and delivery solution. A chronological review method was used for this case study to provide an overall picture of key migration events, tasks, and implementation efforts, including pre-migration cleanup, migration forms, integration with external systems, testing, cutover, post-migration cleanup, and reporting and fixing outstanding issues. A three-phase migration model was studied, and a questionnaire was designed to collect data from functional leads to determine staff time spent on the migration tasks. Staff time spent on each phase was analyzed and quantitated, with some top essential elements for the success of the migration identified through the case review and data analysis. An analysis of the Ex Libris’ Salesforce cases created during the migration and post-migration was conducted to be used for identifying roles of key librarians and staff functional leads during the migration

Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities

<p>Abstract</p> <p>Background</p> <p>Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element.</p> <p>Results</p> <p>This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called Gene expression and Transcription factor activity based Relevance Network (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to <it>E. coli </it>data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of <it>E. coli </it>during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by using our reconstructed network.</p> <p>Conclusions</p> <p>The GTRNetwork algorithm introduces the hidden layer TFA into classic relevance score-based gene regulatory network reconstruction processes. Integrating the TFA biological information with regulatory network reconstruction algorithms significantly improves both detection of new links and reduces that rate of false positives. The application of GTRNetwork on <it>E. coli </it>gene transcriptome data gives a set of potential regulatory links with promising biological significance for isobutanol stress and other conditions.</p

The preprophase band-associated kinesin-14 OsKCH2 is a processive minus-end-directed microtubule motor.

In animals and fungi, cytoplasmic dynein is a processive minus-end-directed motor that plays dominant roles in various intracellular processes. In contrast, land plants lack cytoplasmic dynein but contain many minus-end-directed kinesin-14s. No plant kinesin-14 is known to produce processive motility as a homodimer. OsKCH2 is a plant-specific kinesin-14 with an N-terminal actin-binding domain and a central motor domain flanked by two predicted coiled-coils (CC1 and CC2). Here, we show that OsKCH2 specifically decorates preprophase band microtubules in vivo and transports actin filaments along microtubules in vitro. Importantly, OsKCH2 exhibits processive minus-end-directed motility on single microtubules as individual homodimers. We find that CC1, but not CC2, forms the coiled-coil to enable OsKCH2 dimerization. Instead, our results reveal that removing CC2 renders OsKCH2 a nonprocessive motor. Collectively, these results show that land plants have evolved unconventional kinesin-14 homodimers with inherent minus-end-directed processivity that may function to compensate for the loss of cytoplasmic dynein

A Systematic Key Management Mechanism for Practical Body Sensor Networks

Security plays a vital role in promoting the practicality of Wireless Body Sensor Networks (BSNs), which provides a promising solution to precise human physiological status monitoring. A fundamental security issue in BSN is key management, including establishment and maintenance of the key system. However, current BSN key management solutions are either designed for specific phases of a BSN’s life-time or restricted to strong assumptions such as homogeneous BSN composition, pre-deployed key materials, and existing secure path, which limits their applications in real-world BSNs. In this paper, we develop the Systematic Key Management (SKM) for practical BSNs, where basic human interactions are conducted for non-predeployed secure BSN initialization, and authenticated key agreement is achieved using lightweight non-pairing certificateless public key cryptography. We construct a BSN prototype consisting of selfdesigned motes and Android phones to evaluate the real-world performance of SKM. Through extensive simulations and test-bed experiments, we demonstrate that our lightweight SKM scheme manages to provide high security guarantee while outperforming state-of-the-art approaches in terms of both computation and storage efficiency

Nanoscale Analysis of Frozen Water by Atom Probe Tomography Using Graphene Encapsulation and Cryo-Workflows: A Parametric Study

There has been an increasing interest in atom probe tomography (APT) to characterise hydrated and biological materials. A major benefit of APT compared to microscopy techniques more commonly used in biology is its combination of outstanding 3D spatial resolution (~0.2 nm) and mass sensitivity. APT has already been successfully used to characterise biological materials, revealing key structural information at the atomic scale, however there are many challenges inherent to the analysis of hydrated materials. New preparation protocols, often involving sample preparation and transfer at cryogenic temperature, enable APT analysis of hydrated materials and have the potential to enable 3D atomic scale characterisation of biological materials in the near-native hydrated state. In this study, APT specimens of pure water at the tips of tungsten needles were prepared at room temperature by graphene encapsulation. A parametric study was conducted where samples were transferred at either room temperature or cryo-temperature and analysed by APT by varying parameters such as the flight path and pulsing mode. The differences between the acquisition scenarios are presented along with recommendations for future studies

Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.

MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy, and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B-cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (-)-SDS-1-021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.P30 CA036727 - NCI NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHS; LB506 - Nebraska Department of Health and Human Services (Nebraska DHHS)Accepted manuscriptSupporting documentatio

Genetically Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit Heart Failure

RATIONALE: In heart failure, myofilament proteins display abnormal phosphorylation, which contributes to contractile dysfunction. The mechanisms underlying the dysregulation of protein phosphorylation on myofilaments is not clear. OBJECTIVE: This study aims to understand the mechanisms underlying altered phosphorylation of myofilament proteins in heart failure. METHODS AND RESULTS: We generate a novel genetically encoded protein kinase A (PKA) biosensor anchored onto the myofilaments in rabbit cardiac myocytes to examine PKA activity at the myofilaments in responses to adrenergic stimulation. We show that PKA activity is shifted from the sarcolemma to the myofilaments in hypertrophic failing rabbit myocytes. In particular, the increased PKA activity on the myofilaments is because of an enhanced β2 adrenergic receptor signal selectively directed to the myofilaments together with a reduced phosphodiesterase activity associated with the myofibrils. Mechanistically, the enhanced PKA activity on the myofilaments is associated with downregulation of caveolin-3 in the hypertrophic failing rabbit myocytes. Reintroduction of caveolin-3 in the failing myocytes is able to normalize the distribution of β2 adrenergic receptor signal by preventing PKA signal access to the myofilaments and to restore contractile response to adrenergic stimulation. CONCLUSIONS: In hypertrophic rabbit myocytes, selectively enhanced β2 adrenergic receptor signaling toward the myofilaments contributes to elevated PKA activity and PKA phosphorylation of myofilament proteins. Reintroduction of caveolin-3 is able to confine β2 adrenergic receptor signaling and restore myocyte contractility in response to β adrenergic stimulation

Membrane Stress Caused by Octanoic acid in Saccharomyces cerevisiae

In order to compete with petroleum-based fuel and chemicals, engineering a robust biocatalyst that can convert renewable feedstocks into biorenewable chemicals, such as carboxylic acids, is increasingly important. However, product toxicity is often problematic. In this study, the toxicity of the carboxylic acids hexanoic, octanoic, and decanoic acid on Saccharomyces cerevisiae was investigated, with a focus on octanoic acid. These compounds are completely inhibitory at concentrations of magnitude 1 mM, and the toxicity increases as chain length increases and as media pH decreases. Transciptome analysis, reconstruction of gene regulatory network, and network component analysis suggested decreased membrane integrity during challenge with octanoic acid. This was confirmed by quantification of dose-dependent and chain length-dependent induction of membrane leakage, though membrane fluidity was not affected. This induction of membrane leakage could be significantly decreased by a period of pre-adaptation, and this preadaptation was accompanied by increased oleic acid content in the membrane, significantly increased production of saturated lipids relative to unsaturated lipids, and a significant increase in the average lipid chain length in the membrane. However, during adaptation cell surface hydrophobicity was not altered. The supplementation of oleic acid to the medium not only elevated the tolerance of yeast cells to octanoic acid but also attenuated the membrane leakiness. However, while attempts to mimic the oleic acid supplementation effects through expression of the Trichoplusia ni acyl-CoA Δ9 desaturase OLE1(TniNPVE desaturase) were able to increase the oleic acid content, the magnitude of the increase was not sufficient to reproduce the supplementation effect and increase octanoic acid tolerance. Similarly, introduction of cyclopropanated fatty acids through expression of the Escherichia coli cfa gene was not helpful for tolerance. Thus, we have provided quantitative evidence that carboxylic acids damage the yeast membrane and that manipulation of the lipid content of the membrane can increase tolerance, and possibly production, of these valuable products