bluuebunny/crossref_metadata_2025_split huggingface dataset:
A “New Deal” for the profession
Authors: Detzen Dominic 
Published: March 2018

Purpose
The purpose of this paper is to analyze how “New Deal” regulatory initiatives, primarily the Securities Acts and the Securities and Exchange Commission (SEC), changed US auditors’ professional knowledge conception, culminating in the 1938 expansion of the Committee on Accounting Procedure (CAP), the first US body to set accounting principles.

Design/methodology/approach
The paper combines Halliday’s (1985) knowledge mandates with Hancher and Moran’s (1989) regulatory space to attain a theory-based understanding of auditors’ changing knowledge conceptions amid regulatory pressure. It draws on a range of primary and secondary sources to examine the period from 1929 to 1938.

Findings
Following the stock market crash, the newly created SEC aimed to engage auditors as a means to regulate companies’ accounting practices based on a set of codified principles. While entailing increased status, this new role conflicted with the auditors’ knowledge conception, which was based on professional judgment and personal integrity. Pressure from the SEC and academics eventually made auditors agree to a codification of their professional knowledge and create the CAP as a cooperative regulatory solution.

Originality/value
The paper explores the role of auditors’ knowledge conceptions in the emergence of today’s standard setting. It is suggested that auditors’ incomplete control of their professional knowledge made standard setting a form of co-regulation, located between the actors occupying the regulatory space of accounting.
What do teachers share within Socialized Knowledge Communities: a case of Pinterest
Authors: Hu Sihua , Torphy Kaitlin T. , Opperman Amanda , Jansen Kimberly , Lo Yun-Jia 
Published: March 2018

PurposeThe purpose of this paper is to examine early career teachers’ Socialized Knowledge Communities (SKCs) as they relate to the pursuit of mathematics knowledge and teaching. The authors investigate Pinterest, a living data archive, as an opportunity to view teachers’ sense-making and construction of instructional resources. Through this lens, the authors examine how teachers form and share mathematical meaning individually and collectively through professional collaboration.Design/methodology/approachThis work characterizes teachers’ curation of mathematical resources both in the kinds of mathematics teachers are choosing and the quality therein. Finally, the authors examine through epistemic network analysis how teachers are sense-making through a statistical approach to identifying their organization of mathematics curation by typology and cognitive process demand.FindingsResults show that sampled teachers predominantly curate instructional resources that require students to perform standard algorithm and represent mathematics relationships in visualization within Pinterest. Additionally, the authors find the resources curated by teachers have lower cognitive demand. Finally, epistemic networks show teachers make connections among instructional resources with particular types as well as with different levels of cognitive demand as they sense-make their curated curriculum. In particular, difference in teachers’ internal consideration of the quality of tasks is associated with their years of experience.Originality/valueTwenty-first century classrooms and teachers engage frequently in curation of instructional resources online. The work contributes to an emergent understanding of teachers’ professional engagement in virtual spaces by characterizing the instructional resources being accessed, shared, and diffused. Understanding the nature of the content permeating teachers’ SKCs is essential to increase teachers’ professional capital in the digital age.
Depletion of Glucose Activates Catabolite Repression during Pneumonic Plague
Authors: Ritzert Jeremy T. , Lathem Wyndham W. 
Published: March 2018

ABSTRACT

Bacterial pathogenesis depends on changes in metabolic and virulence gene expression in response to changes within a pathogen's environment. The plague-causing pathogen,
Yersinia pestis
, requires expression of the gene encoding the Pla protease for progression of pneumonic plague. The catabolite repressor protein Crp, a global transcriptional regulator, may serve as the activator of
pla
in response to changes within the lungs as disease progresses. By using gene reporter fusions, the spatial and temporal activation of the
crp
and
pla
promoters was measured in a mouse model of pneumonic plague. In the lungs,
crp
was highly expressed in bacteria found within large aggregates resembling biofilms, while
pla
expression increased over time independent of the aggregated state. Increased expression of
crp
and
pla
correlated with a reduction in lung glucose levels. Deletion of the glucose-specific phosphotransferase system EIIBC (PtsG) of
Y. pestis
rescued glucose levels in the lungs, resulting in reduced expression of both
crp
and
pla
. We propose that activation of
pla
expression during pneumonic plague is driven by an increase of both Crp and cAMP levels following consumption of available glucose in the lungs by
Y. pestis
. Thus, Crp operates as a sensor linking the nutritional environment of the host to regulation of virulence gene expression.

IMPORTANCE
Using
Yersinia pestis
as a model for pneumonia, we discovered that glucose is rapidly consumed, leading to a catabolite-repressive environment in the lungs. As a result, expression of the gene encoding the plasminogen activator protease, a target of the catabolite repressor protein required for
Y. pestis
pathogenesis, is activated. Interestingly, expression of the catabolite repressor protein itself was also increased in the absence of glucose but only in biofilms. The data presented here demonstrate how a bacterial pathogen senses changes within its environment to coordinate metabolism and virulence gene expression.
Nonstructural Protein 5A Impairs DNA Damage Repair: Implications for Hepatitis C Virus-Mediated Hepatocarcinogenesis
Authors: Nguyen Tram T. T. , Park Eun-Mee , Lim Yun-Sook , Hwang Soon B. 
Published: March 2018

ABSTRACT
RAD51-associated protein 1 (RAD51AP1) is a member of the multiprotein complexes postulated to carry out RAD51-mediated homologous recombination and DNA repair in mammalian cells. In the present study, we showed that hepatitis C virus (HCV) NS5A directly bound RAD51AP1 and increased the protein level of RAD51AP1 through modulation of the ubiquitin-proteasome pathway. We also demonstrated that RAD51AP1 protein levels were increased in the liver tissues of HCV-infected patients and NS5A-transgenic mice. Importantly, NS5A impaired DNA repair by disrupting the RAD51/RAD51AP1/UAF1 complex and rendered HCV-infected cells more sensitive to DNA damage. Silencing of RAD51AP1 expression resulted in a decrease of viral propagation. We further demonstrated that RAD51AP1 was involved in the assembly step of the HCV life cycle by protecting viral RNA. These data suggest that HCV exploits RAD51AP1 to promote viral propagation and thus that host DNA repair is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the pathogenesis of HCV infection.

IMPORTANCE
Chronic infection with HCV is the leading cause of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCV-induced HCC are not fully understood. Here we demonstrate that the HCV NS5A protein physically interacts with RAD51AP1 and increases the RAD51AP1 protein level through modulation of the ubiquitin-proteasome pathway. HCV coopts host RAD51AP1 to protect viral RNA at an assembly step of the HCV life cycle. Note that the RAD51 protein accumulates in the cytoplasm of HCV-infected cells, and thus the RAD51/RAD51AP1/UAF1-mediated DNA damage repair system in the nucleus is compromised in HCV-infected cells. Our data may provide new insight into the molecular mechanisms of HCV-induced pathogenesis.
Atomic Structure of the Murine Norovirus Protruding Domain and Soluble CD300lf Receptor Complex
Authors: Kilic Turgay , Koromyslova Anna , Malak Virginie , Hansman Grant S. 
Published: March 2018

ABSTRACT
Human noroviruses are the leading cause of acute gastroenteritis in humans. Noroviruses also infect animals, such as cows, mice, cats, and dogs. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and the murine norovirus capsid protruding domain complex at a 2.05-Å resolution. We found that the sCD300lf-binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf-interacting residues were partially conserved in CD300ld but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms.

IMPORTANCE
Noroviruses exhibit exquisite host range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host range restriction, it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrate that noroviruses can interact with carbohydrates, recent work has shown that expression of the protein CD300lf is both necessary and sufficient for murine norovirus infection of mice and binding of the virus to permissive cells. Importantly, the expression of this murine protein by human cells renders them fully permissive for murine norovirus infection, indicating that at least in this case, host range restriction is determined by molecular events that control receptor binding and entry. Defining the atomic-resolution interactions between the norovirus capsid protein and its cognate receptor is essential for a molecular understanding of host-range restriction and norovirus tropism.
Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses
Authors: Aarreberg Lauren D. , Wilkins Courtney , Ramos Hilario J. , Green Richard , Davis Michael A. , Chow Kwan , Gale Michael 
Published: March 2018

ABSTRACT

Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV)
in vivo
. Here we utilized
ex vivo
global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response. Dendritic cells that were deficient in IL-1 receptor signaling showed dysregulation of cell-intrinsic defense genes and loss of viral control during WNV infection. Surprisingly, we found that in wild-type cells, IL-1β treatment, in the absence of infection, drove the transcription of IFN-β and ISGs at late times following treatment. Expression of these antiviral innate immune genes was dependent on the transcription factor IFN regulatory factor 3 (IRF3) and appears to reflect a general shift in IL-1β signaling from an early inflammatory response to a late IFN-mediated response. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection in myeloid cells through a process of IL-1β-to-IRF3 signaling crosstalk. Strategies to exploit these cytokines in the activation of host defense programs should be investigated as novel therapeutic approaches against individual pathogens.

IMPORTANCE
West Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses.
Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study
Authors: Ho Chau Le Bao , Breslin Monique , Doust Jenny , Reid Christopher M , Nelson Mark R 
Published: March 2018

ObjectivesIn many current guidelines, blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease (CVD) is based on absolute risk. However, in clinical practice, therapeutic decisions are often based on BP levels alone. We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure (ANBP) cohort, a seminal study establishing the efficacy of BP lowering in ‘mild hypertensive’ persons.DesignA post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile.Setting and participants3244 participants aged 35–69 years in a community-based randomised placebo controlled trial of blood pressure-lowering medication.InterventionsChlorothiazide500 mg versus placebo.Primary outcome measuresAll-cause mortality and non-fatal events (non-fatal CVD, congestive cardiac failure, renal failure, hypertensive retinopathy or encephalopathy).ResultsTreatment effects were assessed by HR, absolute risk reduction and number needed to treat. Participants had an average 5-year CVD risk in the intermediate range (10.5±6.5) with moderately elevated BP (mean 159/103 mmHg) and were middle aged (52±8 years). In a subgroup analysis, the relative effects (HR) and absolute effects (absolute risk reduction and number needed to treat) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality (p for heterogeneity=0.04). With respect to absolute benefit, drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 (10 to 64), death from any cause with 45 (25 to 196) and major CVD events with 23 (12 to 193).ConclusionOur analysis confirms that the benefit of treatment was substantial only in the high-risk tertile, reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation.
Extra-small dual-lumen micro-balloon catheters can improve endovascular embolization: an experimental in vivo and in vitro study
Authors: Vollherbst Dominik F , Otto Ruth , Do Thuy D , von Deimling Andreas , Kauczor Hans U , Bendszus Martin , Sommer Christof M , Möhlenbruch Markus A 
Published: March 2018

BackgroundThe embolization technique can have significant impact on the success of endovascular embolization.ObjectiveTo evaluate the feasibility, embolization characteristics, and embolization extent with a newly developed extra-small micro-balloon catheter in an in vivo and in an in vitro embolization model in comparison with standard microcatheter embolizations.Materials and methodsTwenty-eight embolization procedures were performed in the porcine rete mirabile (RM) and in an in vitro embolization model, using either an extra-small (distal outer diameter 1.6 F) dual-lumen micro-balloon catheter or a standard microcatheter. Precipitating hydrophobic injectable liquid (PHIL) was used as embolic agent. Procedure times, number of injections, required volume of embolic agent, and embolization extent (percentage of embolized RM in postinterventional X-ray scans or number of filled sections of the in vitro model) were assessed. Histopathological analyses were performed.ResultsTotal procedure time was significantly shorter (in vivo: 123 s vs 615 s (medians), P=0.001; in vitro: 180 s vs 496 s (medians), P=0.001), number of reflux events was significantly lower (in vivo: 0 vs 9 (medians), P=0.001; in vitro: 0 vs 3 (medians), P=0.001), and embolization extent was significantly higher (in vivo: 96.9% vs 65.6% (medians), P=0.011; in vitro: 26 vs 18 filled sections (medians); P=0.041) for the micro-balloon catheter groups. There was antegrade movement of the PHIL cast after balloon deflation in one in vitro embolization procedure and spontaneous balloon deflation with subsequent reflux in one in vivo embolization procedure.ConclusionExtra-small dual-lumen micro-balloon catheters can improve endovascular embolization in comparison with standard microcatheter embolization.
A low temperature drift coefficient crystal-less frequency reference clock compensated by temperature sensor for microsystem
Authors: Gao Zhiqiang , Wu Ruixuan , Wang Yuteng , Gao Yuan , Liu Xiaowei , Zhu Jiaqi 
Published: March 2018

Quartz oscillator has been widely used as reference clock source in the microsystems due to its good performance. But a good crystal oscillator costs too much and its bulky size is not desired. This paper aims at designing an alternative integrated oscillator to replace the external quartz oscillator. The proposed circuit used maneatis delay cell to construct a ring oscillator for its superior linear I–V characteristic. As for a frequency reference clock, its frequency stability over temperature is required at first. After detailed mathematical deducing and careful analysis, a formula is proposed to describe the relationship between desired control voltage and temperature by assuming the frequency as constant. This paper utilized bipolar transistor as the temperature sensor, combining it with CTAT current source and resistor to create a first-order temperature compensation control voltage. The chip with typical frequency of 10 MHz was fabricated in a 0.35 [Formula: see text]m CMOS technology and occupied 0.45 mm2. The measured results show that the frequency variation is ±0.2% for supply changes from 4.8 V to 5 V, and frequency variation is 48 ppm when the temperature change is from −40[Formula: see text]C to 85[Formula: see text]C, while the average current of the tested chip consumes 50 [Formula: see text]A from 5 V.
The influence of geological conditions on erosion of unlined spillways in rock
Authors: Douglas Kurt , Pells Steven , Fell Robin , Peirson William 
Published: March 2018

Erosion in 33 unlined spillways in rock has been studied for dams in Australia, South Africa and the USA. Geological factors which influence the amount of erosion have been identified using published and project data and spillway site inspections by the authors. These are the orientation, persistence, spacing and nature of rock defects including bedding partings, joints, foliation and shears. The presence of kinematically viable blocks which can be detached and the persistence of the basal defect for these blocks are the most important factors.
Where spillways discharge on to a natural slope the presence of valley stress relief features, such as sheet joints parallel to the slope, or kinematically viable blocks, often with open sub-vertical defects, can lead to significant erosion even with small spillway discharges. The mechanism can be one of slope instability rather than erosion as water pressure destabilizes the slope.
A rock mass characterization index, the ‘Rock Mass Erodibility Index’ (RMEI), which considers spillway flow conditions and erosion mechanisms, has been developed. It can be used as a guide to spillway erosion and, when coupled with stream power for spillway flows, provides a method for preliminary assessments of likely amounts of spillway erosion.
Reactivation of Mutant-EGFR Degradation through Clathrin Inhibition Overcomes Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Ménard Ludovic , Floc'h Nicolas , Martin Matthew J. , Cross Darren A.E. 
Published: March 2018

Abstract
Tyrosine kinase inhibitors (TKI) targeting mutant EGFR in non–small cell lung cancer (NSCLC) have been successful to control cancer growth, but acquired resistance inevitably occurs, including mutations directly on EGFR, for example, T790M and C797S. Strategies to prevent such acquired mutations by reducing mutant-EGFR expression have met limited success. Here, we propose a new model of mutant-EGFR trafficking and demonstrate that clathrin inhibition induces rapid degradation across a large panel of endogenous mutant-EGFR (Ex19del, L858R, and Ex20Ins). This panel included mutant-EGFR (T790M) resistant to the first- and second-generation EGFR inhibitors and to the third-generation TKI osimertinib and occurs through both mutational (C797S) and nonmutational EGFR mechanisms. Clathrin-mediated endocytosis inhibition of mutant EGFR induced a macropinocytosis-dependent lysosomal pathway associated with a loss of mutant-EGFR–dependent signaling (pAKT, pERK). Moreover, induction of this macropinocytic pathway led to robust apoptosis-dependent death across all mutant-EGFR cell lines tested, including those resistant to TKIs. We, therefore, propose a novel strategy to target mutant-EGFR refractory to approved existing TKI treatments in NSCLC and where new treatment strategies remain a key area of unmet need.
Significance:These findings extend our mechanistic understanding of NSCLC mutant EGFR trafficking biology, the role that trafficking may play in resistance of mutant EGFR to tyrosine kinase inhibitors, and provide new therapeutic and biological insights to tackle this fundamental issue and improve benefit to patients. Cancer Res; 78(12); 3267–79. ©2018 AACR.