bluuebunny/crossref_metadata_2025_split huggingface dataset:
The C-terminus is critical for the degradation of substrates by thePseudomonas aeruginosaCtpA protease
Authors: Chung Sammi , Darwin Andrew J. 
Published: April 2020

ABSTRACTBacterial carboxyl-terminal processing proteases (CTPs) are widely conserved and have been linked to important processes including signal transduction, cell wall metabolism, and virulence. However, the features that target proteins for CTP-dependent cleavage are unclear. Studies of theEscherichia coliCTP Prc suggested that it cleaves proteins with non-polar and/or structurally unconstrained C-termini, but it is not clear if this applies broadly.Pseudomonas aeruginosahas a divergent CTP, CtpA, which is required for virulence. CtpA works in complex with the outer membrane lipoprotein LbcA to degrade cell wall hydrolases. Here, we investigated if the C-termini of two non-homologous CtpA substrates are important for their degradation. We determined that these substrates have extended C-termini, compared to their closestE. colihomologs. Removing seven amino acids from these extensions was sufficient to inhibit their degradation by CtpA bothin vivoandin vitro. Degradation of one truncated substrate was restored by adding the C-terminus from the other, but not by adding an unrelated sequence. However, modification of the C-terminus of non-substrates, by adding the C-terminal amino acids from a substrate, did not cause their degradation by CtpA. Therefore, the C-termini of CtpA substrates are required but not sufficient for degradation. Although C-terminal truncated substrates were not degraded, they still associated with the LbcA•CtpA complexin vivo. Therefore, degradation of a protein by CtpA requires a C-terminal-independent interaction with the LbcA•CtpA complex, followed by C-terminal-dependent degradation, perhaps because CtpA must initiate cleavage at a specific C-terminal site.IMPORTANCECarboxyl-terminal processing proteases (CTPs) are found in all three domains of life, but exactly how they work is poorly understood, including how they recognize substrates. Bacterial CTPs have been associated with virulence, including CtpA ofPseudomonas aeruginosa, which works in complex with the outer membrane lipoprotein LbcA to degrade potentially dangerous peptidoglycan hydrolases. We report an important advance by revealing that degradation by CtpA requires at least two separable phenomena, and that one of them depends on information encoded in the substrate C-terminus. A C-terminal-independent association with the LbcA•CtpA complex is followed by C-terminal-dependent cleavage by CtpA. Increased understanding of how CTPs target proteins is significant, due to their links to virulence, peptidoglycan remodeling, and other important processes.
Principles of mRNA control by human PUM proteins elucidated from multi-modal experiments and integrative data analysis
Authors: Wolfe Michael B. , Schagat Trista L. , Paulsen Michelle T. , Magnuson Brian , Ljungman Mats , Park Daeyoon , Zhang Chi , Campbell Zachary T. , Goldstrohm Aaron C. , Freddolino Peter L. 
Published: April 2020

AbstractThe human PUF-family proteins, PUM1 and PUM2, post-transcriptionally regulate gene expression by binding to a PUM recognition element (PRE) in the 3’ UTR of target mRNAs. Hundreds of PUM1/2 targets have been identified from changes in steady state RNA levels; however, prior studies could not differentiate between the contributions of changes in transcription and RNA decay rates. We applied metabolic labeling to measure changes in RNA turnover in response to depletion of PUM1/2, showing that human PUM proteins regulate expression almost exclusively by changing RNA stability. We also applied an in vitro selection workflow to precisely identify the binding preferences of PUM1 and PUM2. By integrating our results with prior knowledge, we developed a ‘rulebook’ of key contextual features that differentiate functional vs. non-functional PREs, allowing us to train machine learning models that accurately predict the functional regulation of RNA targets by the human PUM proteins.
The impact of the reform of PIS/COFINS on the Brazilian industry
Authors: Vasconcelos Pedro Gomes , Paes Nelson Leitão 
Published: April 2020

PurposeIn an attempt to reduce tax distortions and increase economic efficiency, in 2002 and 2003 Brazil promoted changes in the PIS/COFINS tax, the main federal tax on consumption. Thus, in addition to the old cumulative regime calculated on company revenues, the noncumulative regime was created with higher rates and the added value as a tax basis.Design/methodology/approachThis paper analyzes the effects of the PIS/COFINS reform in a context of deindustrialization in the Brazilian economy, using a neoclassical model with two sectors.FindingsThe results suggest that after a small improvement in the aggregate economy in the short term, in the long term there was a worsening of the macroeconomic indicators. From the sector perspective, the PIS/COFINS reform may have contributed to the loss of industry participation in the Brazilian economy.Originality/valueThe study of the impact of the PIS/COFINS reform on industry through a neoclassical model is unprecedented in the national literature and contributes to the investigation of changes in the tax regime that occurred in the country.
Status, stress and fit: comparing the faculty stress impact of university consolidations
Authors: Ribando Saundra J. , Slade Catherine P. , Fortner C. Kevin 
Published: April 2020

PurposeInstitutions of higher education face challenges of fiscal responsibility and their value proposition for students and other stakeholders they serve. Strategies used in business sectors, such as merger and acquisition, are being increasingly adopted by higher education governing boards, especially for public institutions and systems. The purpose of this paper is to guide policy decisions related to university mergers.Design/methodology/approachThis paper focuses on the interplay between the pre-merger status of the institution, the individual faculty member's sense of belonging, and their commitment to the organization on levels of job-related stress, which has well-established negative impacts on individual and organizational performance. Using survey data collected at the same time post-merger from two different universities within the same state system, we explore regression models to identify similarities and differences between the faculty responses in terms of the impact of the merger on faculty stress.FindingsDifferences are found between the two universities in terms of faculty stress with faculty of one low status institution pre-merger having significantly higher stress post-merger. A case is presented for differences in stress based on a part on differences in how the mergers were managed at the system and university levels.Practical implicationsThis research is instructive for higher education policy makers and university administrators as the institution of higher education continues this type of transformation.Originality/valueThis paper examines the impact of mergers on a university's single-most important asset, faculty. Comparative and timely faculty survey results from two related universities early post-merger provide valuable insights for leaders in higher education.
If you build it, will they log on? Wi–Fi usage and behavior while attending National Basketball Association games
Authors: Naraine Michael L. , O'Reilly Norm , Levallet Nadège , Wanless Liz 
Published: April 2020

PurposeAlthough sports fans have increased their use of digital media to consume sport, especially at professional sport venues, it is unknown the extent to which patrons of said venues are utilizing venue services for these activities. As such, this study asks: (1) How much data do patrons at a sports venue consume via the provided Wi–Fi? and (2) What types of online activity behaviors do Wi–Fi users at sports venues exhibit?Design/methodology/approachThis empirical study reports stadia Wi–Fi data usage and consumer behavior from three National Basketball Association venues in the United States: Amway Center in Orlando, FL, Barclays Center in Brooklyn, NY and Target Center in Minneapolis, MN, over a course of 7 games per venue.FindingsThe findings suggest that Wi–Fi usage is more limited than anticipated. Users who do utilize the venue Wi–Fi do so for very short periods, with the vast majority of user duration lasting between 1 and 10 min. Additionally, the halftime period of games experiences the peak of Wi–Fi usage.Originality/valueBy increasing our understanding of Wi–Fi usage in venues, this study informs relationship marketing theory research and contributes to the sport management literature. Practically, a better knowledge of Wi–Fi usage is critical, as it constitutes a critical antecedent to develop online marketing strategies.
Exception to the exception rule: synthetic and naturally occurring single chromosome Vibrio cholerae
Authors: Sozhamannan Shanmuga , Waldminghaus Torsten 
Published: April 2020

SummaryThe genome of Vibrio cholerae, the etiological agent of cholera, is an exception to the single chromosome rule found in the vast majority of bacteria and has its genome partitioned between two unequally sized chromosomes. This unusual two‐chromosome arrangement in V. cholerae has sparked considerable research interest since its discovery. It was demonstrated that the two chromosomes could be fused by deliberate genome engineering or forced to fuse spontaneously by blocking the replication of Chr2, the secondary chromosome. Recently, natural isolates of V. cholerae with chromosomal fusion have been found. Here, we summarize the pertinent findings on this exception to the exception rule and discuss the potential utility of single‐chromosome V. cholerae to address fundamental questions on chromosome biology in general and DNA replication in particular.
Properties of novel chitosan incorporated with hexahydro‐β‐acids edible films and its effect on shelf life of pork
Authors: Chen Fengxia , Li Shuai , Zhong Genghui , Liu Yumei 
Published: April 2020

AbstractEdible packaging films have been widely studied because of its safety, green, and effective characteristics. In this paper, chitosan (CH) edible films containing hexahydro‐β‐acids (HBA) were prepared, and its physical and mechanical properties, bioactivity, and their impact on the shelf life of pork were investigated. The infrared spectra indicated that the molecular interaction between CH and HBA was observed. Scanning electron microscopy was used to analyze the surface morphology of the film, and light transmittance analysis displayed that the addition of HBA enhanced the film's UV blocking performance. Compared to the CH film, the tensile strength of CH–HBA film increased to 29.19 ± 0.45 MPa, and the scavenging activity of 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) reached 1.40 ± 0.01 mg rutin/cm2 of the film. The antibacterial activity of the CH–HBA film on Escherichia coli (44825) and Staphylococcus aureus (26001) showed that the CH–HBA film is a feasible antibacterial package. Furthermore, compared to pork packaged in CH and polyethylene films, fresh pork packaged with CH–HBA films displayed prolongation of shelf life due to reduction in microbial proliferation, thiobarbituric values, pH, and total volatile base nitrogen contents during storage at 4 °C for 16 days. The freshness of pork was prolonged by 7−8 days when the dosage of HBA was increased to 0.3% from 0.1% (w/v). These results revealed that the CH–HBA film can effectively extend the shelf life of pork.Practical ApplicationThis study effectively prolonged the shelf life of pork. A chitosan‐edible film combined with hexahydro‐β‐acids has a potential application value in replacing traditional packaged fresh meat.
Evaluation of the introduction of a ‘traffic light protocol’ for dose‐volume histogram constraints of organs at risk in definitive radiotherapy at Liverpool and Macarthur Cancer Therapy Centres
Authors: Kasraei Farshad , Ochoa Cesar , Vial Phillip , Lee Mark T 
Published: April 2020

AbstractIntroductionProtocols have been developed in our department with recommended dose constraints for organs at risk (OAR) for each tumour site receiving definitive radiotherapy. We have developed a colour coding system to indicate when constraints are meeting objectives (green), have minor variation from planning objectives (yellow) and have major variation from planning objectives (red). We performed a quality audit to assess adherence to the protocol and to determine the rate of acute and subacute toxicities.MethodsAll definitive radiotherapy dose‐volume histogram (DVH) reports generated in the first 6 months of 2017 at Liverpool and Macarthur cancer therapy centres were collected. For each radiotherapy group, the overridden dose constraints were evaluated and categorized to red and yellow. For all patients in our data set, follow‐up documents/assessments were searched for grade 3 or higher acute or subacute radiotherapy toxicity and compared with those who had overridden dose constraints.ResultsThere were 210 (34%) plans accepted with at least one major variation and 161 (26%) plans with minor variation. Head and neck group had the most rate of major variations (77%). The best groups in adherence to protocol were lymphoma and breast groups. In general, grade 3 toxicity was observed in 1%, 4% and 9% of patients who were in green, yellow and red categories. Overall, we noted a correlation with grade 3 toxicities between acceptable plans (green) and ones with a minor or major variation (yellow or red) (1% vs. 7% P = 0.0001).ConclusionIn conclusion this study showed an increased risk of higher grade toxicities when DVHs were beyond our departmental constraints using a ‘Traffic Light System’. With this new colour coding system, we can facilitate auditing of the dose constraints in order to improve the quality of radiotherapy plans and potentially provide benchmarking for reducing toxicities in radiotherapy treatments.
Effects of simulated sample sizes on the mortality effect estimates in three randomized intensive care unit trials
Authors: Kofoed Andreas , Perner Anders , Marker Søren , Haase Nicolai , Holst Lars B. , Møller Morten Hylander 
Published: April 2020

BackgroundRandomized clinical trials (RCTs) are occasionally stopped prematurely before reaching their planned sample sizes. It has been suggested that early stopped RCTs are associated with under‐ and overestimation of the effect estimates. We simulated the effect of hypothetical premature stopping of three large RCTs done in the intensive care unit (ICU) setting.MethodsIn this post hoc study, we simulated the impact of stopping trials early by calculating mortality effect estimates continuously after the inclusion of each individual patient in three large RCTs, that is the 6S trial on hydroxyethyl starch vs Ringer's acetate in sepsis in ICU, the TRISS trial on lower vs higher haemoglobin threshold for transfusion in septic shock in ICU and the SUP‐ICU trial on pantoprazole in patients at risk for gastrointestinal bleeding in the ICU.ResultsThe three trials included a total of 5087 patients; 798 from the 6S trial, 998 from the TRISS trial and 3291 patients from the SUP‐ICU trial. The premature mortality effect estimates showed considerable fluctuations until at least 20%‐30% of the sample size was included. The premature estimates became stable after inclusion of 205 patients (26% of the final sample size) in the 6S trial, 133 patients(13%) in the TRISS trial and 1926 patients(59%) in the SUP‐ICU trial.ConclusionsIn this post hoc study of three international RCTs within intensive care, we found that the simulated interim mortality effect estimates showed considerable fluctuations until at least 20%‐30% of the sample size was included, but remained instable until the final sample sizes had been included. Thus, this study illustrates the necessity for cautious interpretations of prematurely stopped trials.
Sociomaterial movements of students' engagement in a school's makerspace
Authors: Kumpulainen Kristiina , Kajamaa Anu 
Published: April 2020

AbstractThis study investigates the sociomaterial movements of student engagement in a school's makerspace. Here, we understand sociomaterial movements as emergent and relational, comprising complex dynamics of agency across students, teachers and materials in situated, culturally framed activities. Our study draws on data comprising 85 hours of video recordings of 9–12‐year‐old students' (N = 94) engagement in a technology‐rich makerspace in a Finnish elementary school. The video data were transcribed and analyzed qualitatively using a multimodal interaction analysis. The sociomaterial movements were found to be displayed across a tension‐laden continuum between (1) procedural activity—analysis and reflection; (2) individual activity—collaboration; (3) “doing school”—empowerment; and d) alienation—identification. Together, the study offers a potential approach for investigating and understanding the often overlooked workings of sociomateriality that constitutes students' emergent engagement and learning opportunities in science, technology, engineering and mathematics (STEAM) learning contexts.
A five‐year follow‐up of untreated patients with chronic lymphocytic leukaemia treated with ofatumumab and chlorambucil: final analysis of the Complement 1 phase 3 trial
Authors: Offner Fritz , Robak Tadeusz , Janssens Ann , Govind Babu K. , Kloczko Janusz , Grosicki Sebastian , Mayer Jiri , Panagiotidis Panagiotis , Schuh Anna , Pettitt Andrew , Montillo Marco , Werner Olena , Vincent Ghislaine , Khanna Sadhvi , Hillmen Peter 
Published: April 2020

AbstractThe Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long‐term follow‐up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression‐free survival, respectively. A high rate (61%) of treatment with next‐line therapies in both the treatment arms may dilute any potential OS difference and confound the interpretation of the OS results. Addition of ofatumumab to chlorambucil demonstrated clinical benefit and tolerability as a frontline treatment option in patients unfit for fludarabine‐containing therapy, with no new safety concerns.
Making sense of complexity: A qualitative investigation into forensic learning disability nurses’ interpretation of the contribution of personal history to offending behaviour
Authors: Lovell Andrew , Skellern Joanne 
Published: April 2020

Accessible Summary

The role of an individual's personal history is important in influencing their development, especially whether they are likely to offend or engage in violent behaviour

Learning disability nurses relationships with those with a history of violence or offending will improve with a more informed knowledge of how someone's offending behaviour is related to their background

People with a learning disability can be supported best when the complexity of their lives is fully understood and properly informs the therapeutic relationship.

AbstractBackgroundThere is growing recognition that an individual's personal history can be extremely influential in shaping their future experience, though there has been a limited exploration in the context of learning disability and offending behaviour.MethodResearch questions related to participant interpretation of offending behaviour and individual and service responses. A series of focus groups comprising learning disability forensic nurses were conducted across all secure settings, high, medium and low.ResultsThree themes were produced: interpreting offending behaviour; the impact of personal history; responding therapeutically. The difficulties relating to understanding the relationship between offending behaviour and personal history significantly informed the construction of the most effective therapeutic relationships.ConclusionsAn increased focus on the impact of someone's background might inform nursing as it seeks to deliver care to individuals with increasingly complex needs in a time of service transition.
Symbiotic prodrugs (SymProDs) dual targeting of NFkappaB and CDK
Authors: Rana Sandeep , Kour Smit , Sonawane Yogesh A. , Robb Caroline M. , Contreras Jacob I. , Kizhake Smitha , Zahid Muhammad , Karpf Adam R. , Natarajan Amarnath 
Published: April 2020

AbstractThe release of an active drug from the prodrug generates a pro‐fragment that typically has no biological activity and could result in adverse effects. By combining two drugs, wherein each drug acts as a pro‐fragment of the other drug will eliminate the pro‐fragment in the prodrug. As they are prodrugs of each other and are symbiotic, we termed these as symbiotic prodrugs (SymProDs). To test this idea, we generated SymProDs using NFκB inhibitors that contain the reactive α‐methylene‐γ‐butyrolactone moiety and CDK inhibitors with solvent exposed secondary nitrogen atoms. We show that secondary amine prodrugs of α‐methylene‐γ‐butyrolactone containing NFκB inhibitors undergo slow release over a 72 hr period. Using an alkyne‐tagged secondary amine prodrug of α‐methylene‐γ‐butyrolactone containing NFκB inhibitor, we demonstrate target engagement. The NFκB‐CDK SymProDs were ~20‐ to 200‐fold less active against the corresponding CDK inhibitors in in vitro CDK kinase assays. Growth inhibition studies in a panel of ovarian cancer cell lines revealed potency trends of the SymProDs mirrored those of the single treatments suggesting their dissociation in cells. In conclusion, our results suggest that SymProDs offer a productive path forward for advancing compounds with reactive functionality and can be used as dual targeting agents.
Long‐term prognosis of Japanese Lambert–Eaton myasthenic syndrome patients with or without small‐cell lung carcinoma
Authors: Kojima Yuta , Uzawa Akiyuki , Shibuya Kazumoto , Yasuda Manato , Ozawa Yukiko , Oda Fumiko , Shiraishi Hirokazu , Motomura Masakatsu , Kuwabara Satoshi 
Published: April 2020

AbstractObjectiveLambert–Eaton myasthenic syndrome (LEMS) is a paraneoplastic neurological syndrome, most frequently associated with small‐cell lung carcinoma (SCLC). The survival of LEMS patients depends on the presence of SCLC, whereas the functional outcome in patients without SCLC has not been fully clarified. The aim of this study was to elucidate the long‐term prognosis of LEMS patients with or without SCLC.MethodsWe collected data from seven consecutive Japanese patients with LEMS without SCLC (n = 4) or LEMS with SCLC (n = 3) consulting Chiba university hospital, Chiba, Japan from 2003 to 2019. The functional disability was assessed with the modified Rankin Scale.ResultsThe median observation period was 52 months (range 18–168 months); one LEMS with SCLC patient died as a result of SCLC 18 months after diagnosis, whereas the remaining two LEMS with SCLC patients with complete remission of their tumor still showed improvement in neurological symptoms 52 and 168 months after treatment, respectively. All LEMS patients without SCLC showed a favorable response to treatment and good functional prognosis (modified Rankin Scale 1 or 2) during the follow‐up period (48–120 months).ConclusionsIn Japanese LEMS patients, the long‐term neurological outcome is generally favorable. Our results also suggest that even in LEMS with SCLC patients, successful treatment for their cancer could result in sustained improvement in neurological symptoms.