bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Packaging in Murine Coronavirus Promotes Virulence by Limiting Type I Interferon Responses
Authors: Athmer Jeremiah , Fehr Anthony R. , Grunewald Matthew E. , Qu Wen , Wheeler D. Lori , Graepel Kevin W. , Channappanavar Rudragouda , Sekine Aimee , Aldabeeb Dana Saud , Gale Michael , Denison Mark R. , Perlman Stanley
Published: May 2018

Selective packaging is a mechanism used by multiple virus families to specifically incorporate genomic RNA (gRNA) into virions and exclude other types of RNA. Lineage A betacoronaviruses incorporate a 95-bp stem-loop structure, the packaging signal (PS), into the nsp15 locus of ORF1b that is both necessary and sufficient for the packaging of RNAs. However, unlike other viral PSs, where mutations generally resulted in viral replication defects, mutation of the coronavirus (CoV) PS results in large increases in subgenomic RNA packaging with minimal effects on gRNA packaging
in vitro
and on viral titers. Here, we show that selective packaging is also required for viral evasion of the innate immune response and optimal pathogenicity. We engineered two distinct PS mutants in two different strains of murine hepatitis virus (MHV) that packaged increased levels of subgenomic RNAs, negative-sense genomic RNA, and even cellular RNAs. All PS mutant viruses replicated normally
in vitro
but caused dramatically reduced lethality and weight loss
in vivo
. PS mutant virus infection of bone marrow-derived macrophages resulted in increased interferon (IFN) production, indicating that the innate immune system limited the replication and/or pathogenesis of PS mutant viruses
in vivo
. PS mutant viruses remained attenuated in MAVS
−/−
and Toll-like receptor 7-knockout (TLR7
−/−
) mice, two well-known RNA sensors for CoVs, but virulence was restored in interferon alpha/beta receptor-knockout (IFNAR
−/−
) mice or in MAVS
−/−
mice treated with IFNAR-blocking antibodies. Together, these data indicate that coronaviruses promote virulence by utilizing selective packaging to avoid innate immune detection.

IMPORTANCE
Coronaviruses (CoVs) produce many types of RNA molecules during their replication cycle, including both positive- and negative-sense genomic and subgenomic RNAs. Despite this, coronaviruses selectively package only positive-sense genomic RNA into their virions. Why CoVs selectively package their genomic RNA is not clear, as disruption of the packaging signal in MHV, which leads to loss of selective packaging, does not affect genomic RNA packaging or virus replication in cultured cells. This contrasts with other viruses, where disruption of selective packaging generally leads to altered replication. Here, we demonstrate that in the absence of selective packaging, the virulence of MHV was significantly reduced. Importantly, virulence was restored in the absence of interferon signaling, indicating that selective packaging is a mechanism used by CoVs to escape innate immune detection.
Signature Arsenic Detoxification Pathways in
Halomonas
sp. Strain GFAJ-1
Authors: Wu Shuangju , Wang Lianrong , Gan Rui , Tong Tong , Bian Hao , Li Zhiqiang , Du Shiming , Deng Zixin , Chen Shi
Published: May 2018

Since the original report that
Halomonas
sp. strain GFAJ-1 was capable of using arsenic instead of phosphorus to sustain growth, additional studies have been conducted, and GFAJ-1 is now considered a highly arsenic-resistant but phosphorus-dependent bacterium. However, the mechanisms supporting the extreme arsenic resistance of the GFAJ-1 strain remain unknown. In this study, we show that GFAJ-1 has multiple distinct arsenic resistance mechanisms. It lacks the genes to reduce arsenate, which is the essential step in the well-characterized resistance mechanism of arsenate reduction coupled to arsenite extrusion. Instead, GFAJ-1 has two arsenic resistance operons,
arsH1
-
acr3
-
2
-
arsH2
and
mfs1
-
mfs2
-
gapdh
, enabling tolerance to high levels of arsenate.
mfs2
and
gapdh
encode proteins homologous to
Pseudomonas aeruginosa
ArsJ and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively, which constitute the equivalent of an As(V) efflux system to catalyze the transformation of inorganic arsenate to pentavalent organoarsenical 1-arseno-3-phosphoglycerate and its subsequent extrusion. Surprisingly, the
arsH1
-
acr3
-
2
-
arsH2
operon seems to consist of typical arsenite resistance genes, but this operon is sufficient to confer both arsenite and arsenate resistance on
Escherichia coli
AW3110 even in the absence of arsenate reductase, suggesting a novel pathway of arsenic detoxification. The simultaneous occurrence of these two unusual detoxification mechanisms enables the adaptation of strain GFAJ-1 to the particularly arsenic-rich environment of Mono Lake.

IMPORTANCE
Halomonas
sp. strain GFAJ-1 was previously reported to use arsenic as a substitute for phosphorus to sustain life under phosphate-limited conditions. Although this claim was later undermined by several groups, how GFAJ-1 can thrive in environments with high arsenic concentrations remains unclear. Here, we determined that this ability can be attributed to the possession of two arsenic detoxification operons,
arsH1
-
acr3
-
2
-
arsH2
and
mfs1
-
mfs2
-
gapdh
.
mfs2
and
gapdh
encode proteins homologous to ArsJ and GAPDH in
Pseudomonas aeruginosa
; these proteins create an arsenate efflux pathway to reduce cellular arsenate accumulation. Interestingly, the combination of
acr3
-
2
with either
arsH
gene was sufficient to confer resistance to both arsenite and arsenate in
E. coli
AW3110, even in the absence of arsenate reductase, suggesting a new strategy for bacterial arsenic detoxification. This study concludes that the survival of GFAJ-1 in high arsenic concentrations is attributable to the cooccurrence of these two unusual arsenic detoxification mechanisms.
Pseudomonas aeruginosa
Protease IV Exacerbates Pneumococcal Pneumonia and Systemic Disease
Authors: Bradshaw Jessica L. , Caballero Armando R. , Bierdeman Michael A. , Adams Kristen V. , Pipkins Haley R. , Tang Aihua , O’Callaghan Richard J. , McDaniel Larry S.
Published: May 2018

S. pneumoniae
remains the leading cause of bacterial pneumonia despite widespread use of pneumococcal vaccines, forcing the necessity for appropriate treatment to control pneumococcal infections. Coinfections involving
S. pneumoniae
with other bacterial pathogens threaten antibiotic treatment strategies and disease outcomes. Currently, there is not an effective treatment for alveolar-capillary barrier dysfunction that precedes bacteremia. An understanding of the dynamics of host-pathogen interactions during single and mixed pulmonary infections could elucidate proper treatment strategies needed to prevent or reduce invasive disease. Antibiotic treatment decreases bacterial burden in the lung but also increases acute pathology due to cytotoxins released via antibiotic-induced bacterial lysis. Therefore, targeted therapeutics that inhibit or counteract the effects of bacterial proteases and toxins are needed in order to limit pathology and disease progression. This study identifies the cooperative effect of PIV and Ply, products of separate lung pathogens that additively alter the lung environment and facilitate invasive disease.
Improved Subtyping of Staphylococcus aureus Clonal Complex 8 Strains Based on Whole-Genome Phylogenetic Analysis
Authors: Bowers Jolene R. , Driebe Elizabeth M. , Albrecht Valerie , McDougal Linda K. , Granade Mitchell , Roe Chandler C. , Lemmer Darrin , Rasheed J. Kamile , Engelthaler David M. , Keim Paul , Limbago Brandi M.
Published: May 2018

Staphylococcus aureus
is a major human pathogen worldwide in both community and health care settings. Surveillance for
S. aureus
strains is important to our understanding of their spread and to informing infection prevention and control. Confusion surrounding the strain nomenclature of one of the most prevalent lineages of
S. aureus
, clonal complex 8 (CC8), and the imprecision of current tools for typing
S. aureus
make surveillance and source tracing difficult and sometimes misleading. In this study, we clarify the CC8 strain designations and propose a new typing scheme for CC8 isolates that is rapid and easy to use. This typing scheme is based on relatively stable genomic markers, and we demonstrate its superiority over traditional typing techniques. This scheme has the potential to greatly improve epidemiological investigations of
S. aureus
.
Neutrino Physics with Nuclear Reactors: An Overview
Authors: Ochoa-Ricoux J. P.
Published: May 2018

Nuclear reactors provide an excellent environment for studying neutrinos and continue to play a critical role in unveiling the secrets of these elusive particles. A rich experimental program with reactor antineutrinos is currently ongoing, and leads the way in precision measurements of several oscillation parameters and in searching for new physics, such as the existence of light sterile neutrinos. Ongoing experiments have also been able to measure the flux and spectral shape of reactor antineutrinos with unprecedented statistics and as a function of core fuel evolution, uncovering anomalies that will lead to new physics and/or to an improved understanding of antineutrino emission from nuclear reactors. The future looks bright, with an aggressive program of next generation reactor neutrino experiments that will go after some of the biggest open questions in the field. This includes the JUNO experiment, the largest liquid scintillator detector ever constructed which will push the limits of this detection technology.
Theory Concepts for Heavy Exotic Mesons
Authors: Hanhart C.
Published: May 2018

Some of the currently most popular conjectures for the structure of the recently discovered heavy mesons that do not find a place in the quark model quarkonium spectrum are sketched. Furthermore, some observables are identified that should allow one to identify the most prominent components of individual states.
Searches for Supersymmetry
Authors: Ventura Andrea
Published: May 2018

New and recent results on Supersymmetry searches are shown for the ATLAS and the CMS experiments. Analyses with about 36 fb[Formula: see text] are considered for searches concerning light squarks and gluinos, direct pair production of 3[Formula: see text] generation squarks, electroweak production of charginos, neutralinos, sleptons, R-parity violating scenarios and long-lived particles.
e+e− Pair Production at Very Low Transverse Mometum in Au+Au Collisions at s NN = 200 GeV and U+U Collisions at sNN = 193 GeV at STAR
Authors: Yang Shuai
Published: May 2018

We present the first measurements of [Formula: see text] pair production at very low transverse momentum ([Formula: see text] 0.15 GeV/[Formula: see text]) in Au + Au collisions at [Formula: see text] = 200 GeV and U + U collisions at [Formula: see text] = 193 GeV using the STAR detector at the Relativistic Heavy Ion Collider. A significant excess, with respect to known hadronic contributions, is observed in 60-80% central heavy-ion collisions over the whole [Formula: see text] range. Remarkably, the excess almost entirely happens below [Formula: see text] 0.15 GeV/[Formula: see text], and can not be explained by a theoretical model calculation incorporating in-medium broadened [Formula: see text] spectral function. Moreover, the observed excess yield has no significant centrality dependence. In addition, the steepness of [Formula: see text] distribution exhibits mild invariant mass and collision species dependence.
Measurement of the D-meson Nuclear Modification Factor and Elliptic Flow in Pb–Pb Collisions at sNN = 5.02 TeV with ALICE at the LHC
Authors: Jaelani Syaefudin
Published: May 2018

Heavy-flavour hadrons are effective probes to study the Quark-Gluon Plasma (QGP) formed in ultra-relativistic heavy-ion collisions. The ALICE Collaboration measured the D-mesons (D0, D[Formula: see text], D*[Formula: see text] and D[Formula: see text]) production in Pb–Pb collisions at [Formula: see text] = 5.02 TeV. The in-medium energy loss can be studied by means of the nuclear modification factor ([Formula: see text]). The comparison between the D[Formula: see text] and the non-strange D-meson [Formula: see text] can help to study the hadronisation mechanism of the charm quark in the QGP. In semi-central collisions the measurement of the D-meson elliptic flow, [Formula: see text], at low [Formula: see text] allows to investigate the participation of the heavy quarks in the collective expansion of the system while at high [Formula: see text] it constrains the path-length dependence of the energy loss. Furthermore the Event-Shape Engineering (ESE) technique is used to measure D-meson elliptic flow in order to study the coupling of the charm quarks to the light quarks of the underlying medium.
The High-Energy Photoproduction of Light-Quark Pseudoscalar and Scalar Meson at GlueX
Authors: Zhang Zhenyu
Published: May 2018

The high-energy photoproduction of light-quark pseudoscalar and scalar mesons is an effective tool for understanding the properties of strong interaction in the nonperturbative regime. It has been investigated theoretically using Regge-cut phenomenology with massive quasi-particle exchange in the high-energy regime, and the linearly polarized photon beam asymmetry [Formula: see text] can provide insight into the dominant production mechanism. In the low-energy region, it can provide constraints on ”background” to baryon resonance extraction. With an almost 50-year history, intensive experiments on meson photoproduction are growing vigorously at several international laboratories, such as JLab, ELSA, and MAMI. Recently the beam asymmetry [Formula: see text] in high-energy [Formula: see text] photoproduction has been measured at GlueX, which is the first measurement both from the GlueX experiment and the 12 GeV upgraded JLab. The highest precision measurement of the [Formula: see text] asymmetry and the first measurement of [Formula: see text] beam asymmetry at a beam energy above 3 GeV are presented. A broad meson photoproduction project, including scalar meson [Formula: see text], is under way at GlueX. In the proceedings, we report the beam asymmetry results for [Formula: see text] photoproduction at GlueX, as well as preliminary results for scalar meson photoproduction in the [Formula: see text] and [Formula: see text] channels.
Hidden-Charm Decays: An Elegant Probe for Internal Structure
Authors: Anwar Muhammad Naeem , Zou Bing-Song
Published: May 2018

Hadronic transitions are important decay modes of heavy quarkonia and serve as an elegant probe for the internal structure. Several remarkable discoveries have been made to identify the conventional heavy quarkonia and to extract useful information about the so called “XYZ” exotic states. We studied the hadronic transitions of higher charmonia in the framework of our recently proposed effective model to create light meson(s) in heavy quarkonium transitions. In this contribution, we discuss our results for the charmonium-[Formula: see text] decays of higher [Formula: see text] and [Formula: see text] wave vector charmonia. We also discuss quantum number [Formula: see text] assignments for few experimentally observed charmoniumlike states.
Dark Photon Search with PADME at LNF
Authors: Piperno Gabriele
Published: May 2018

Dark Matter elusiveness could be explained by speculating that it lives in a separate sector with respect to the Standard Model and that interacts with it only by means of messengers. The simplest model foresees just one messenger: a, possibly massive, vector boson given by a new U(1) symmetry. This mediator can faintly mix with the photon and, hence, interact with SM charged particles, seeing an effective charge equal to [Formula: see text], with [Formula: see text] SM charge. The PADME experiment, hosted at Laboratori Nazionali di Frascati, is designed to search for such kind of particle, looking for its production in [Formula: see text] annihilations. Exploiting the DA[Formula: see text]NE linac, the collaboration aims to collect [Formula: see text] positrons on target by the end of 2018, reaching a sensitivity of [Formula: see text] for masses up to [Formula: see text][Formula: see text]Mev.
Charm Physics Prospects at the Belle II Experiment
Authors: Li Long-Ke
Published: May 2018

With a total integrated luminosity of 50 ab[Formula: see text] of data and improved performances at the Belle II detector, especially vertex resolution and particle identification, sensitivity estimations for [Formula: see text]-[Formula: see text] mixing, [Formula: see text] violation and time integrated [Formula: see text] asymmetries measurements are presented. Prospects on charm rare decays and (semi-)leptonic decays are discussed. Besides, a new [Formula: see text] flavor-tagging technique, ROE method, is introduced.
Charm Meson Physics at BESIII
Authors: Li Lei
Published: May 2018

Based on 2.93 fb[Formula: see text] data taken at the center-of-mass energy of [Formula: see text] GeV with the BESIII detector at the BEPCII collider, we report the precise measurements of the decay constant [Formula: see text], the form factors of [Formula: see text] semileptonic decays [Formula: see text] and [Formula: see text], the Dalitz plot analysis of [Formula: see text], the strong phase measurement in [Formula: see text] and the [Formula: see text] mixing parameter [Formula: see text].
COMET, an Experiment to Search for mu-e Conversion in a Nuclear Field
Authors: Natori Hiroaki
Published: May 2018

Charged lepton flavor violating (CLFV) process is predicted to be out of experimental reach by the Standard Model of elementary particle physics (SM). However, many models of the new physics beyond the SM predicts that it is just below the current experimental limit. COMET searches for one of the CLFV process, mu-e conversion in a nuclear field, improving the sensitivity by a factor of approximately [Formula: see text] for Phase-I and [Formula: see text] for Phase-II experiment from a past experiment.
The CMS High Granularity Calorimeter for HL-LHC
Authors: Mastrolorenzo L.
Published: May 2018

The High Luminosity LHC (HL-LHC) will integrate 10 times more luminosity than the LHC, posing significant challenges for radiation tolerance and event pileup on detectors, especially for forward calorimetry, and hallmarks the issue for future colliders. As part of its HL-LHC upgrade program, the CMS Collaboration is designing a High Granularity Calorimeter (HGCAL) to replace the existing endcap calorimeters. It features unprecedented transverse and longitudinal segmentation for both electromagnetic (CE-E) and hadronic (CE-H) compartments. This will facilitate particle-flow (PF) calorimetry, where the fine structure of showers can be measured and used to enhance pileup rejection and particle identification, whilst still achieving good energy resolution. The CE-E and a large fraction of CE-H will be based on hexagonal silicon sensors of [Formula: see text] cell size, with the remainder of the CE-H based on highly-segmented scintillators with SiPM readout. The intrinsic high-precision timing capabilities of the silicon sensors will add an extra dimension to event reconstruction, especially in terms of pileup rejection. An overview of the HGCAL project is presented in this paper.
Current and Future Trends in Mobile Device Forensics
Authors: Barmpatsalou Konstantia , Cruz Tiago , Monteiro Edmundo , Simoes Paulo
Published: May 2018

Contemporary mobile devices are the result of an evolution process, during which computational and networking capabilities have been continuously pushed to keep pace with the constantly growing workload requirements. This has allowed devices such as smartphones, tablets, and personal digital assistants to perform increasingly complex tasks, up to the point of efficiently replacing traditional options such as desktop computers and notebooks. However, due to their portability and size, these devices are more prone to theft, to become compromised, or to be exploited for attacks and other malicious activity. The need for investigation of the aforementioned incidents resulted in the creation of the Mobile Forensics (MF) discipline. MF, a sub-domain of digital forensics, is specialized in extracting and processing evidence from mobile devices in such a way that attacking entities and actions are identified and traced. Beyond its primary research interest on evidence acquisition from mobile devices, MF has recently expanded its scope to encompass the organized and advanced evidence representation and analysis of future malicious entity behavior. Nonetheless, data acquisition still remains its main focus. While the field is under continuous research activity, new concepts such as the involvement of cloud computing in the MF ecosystem and the evolution of enterprise mobile solutions—particularly mobile device management and bring your own device—bring new opportunities and issues to the discipline. The current article presents the research conducted within the MF ecosystem during the last 7 years, identifies the gaps, and highlights the differences from past research directions, and addresses challenges and open issues in the field.
ReveNAND
Authors: Shihab Mustafa M. , Zhang Jie , Jung Myoungsoo , Kandemir Mahmut
Published: May 2018

The paradigm shift from planar (two dimensional (2D)) to vertical (three-dimensional (3D)) models has placed the NAND flash technology on the verge of a design evolution that can handle the demands of next-generation storage applications. However, it also introduces challenges that may obstruct the realization of such 3D NAND flash. Specifically, we observed that the fast threshold drift (fast-drift) in a charge-trap flash-based 3D NAND cell can make it lose a critical fraction of the stored charge relatively soon after programming and generate errors.

In this work, we first present an elastic read reference (

V
Ref

) scheme (ERR) for reducing such errors in ReveNAND—our fast-drift aware 3D NAND design. To address the inherent limitation of the adaptive

V
Ref

, we introduce a new intra-block page organization (hitch-hike) that can enable stronger error correction for the error-prone pages. In addition, we propose a novel reinforcement-learning-based smart data refill scheme (iRefill) to counter the impact of fast-drift with minimum performance and hardware overhead. Finally, we present the first analytic model to characterize fast-drift and evaluate its system-level impact. Our results show that, compared to conventional 3D NAND design, our ReveNAND can reduce fast-drift errors by 87%, on average, and can lower the ECC latency and energy overheads by 13× and 10×, respectively.
ThreadScan
Authors: Alistarh Dan , Leiserson William , Matveev Alexander , Shavit Nir
Published: May 2018

The concurrent memory reclamation problem is that of devising a way for a deallocating thread to verify that no other concurrent threads hold references to a memory block being deallocated. To date, in the absence of automatic garbage collection, there is no satisfactory solution to this problem; existing tracking methods like hazard pointers, reference counters, or epoch-based techniques like RCU are either prohibitively expensive or require significant programming expertise to the extent that implementing them efficiently can be worthy of a publication. None of the existing techniques are automatic or even semi-automated.

In this article, we take a new approach to concurrent memory reclamation. Instead of manually tracking access to memory locations as done in techniques like hazard pointers, or restricting shared accesses to specific epoch boundaries as in RCU, our algorithm, called ThreadScan, leverages operating system signaling to automatically detect which memory locations are being accessed by concurrent threads.

Initial empirical evidence shows that ThreadScan scales surprisingly well and requires negligible programming effort beyond the standard use of Malloc and Free.
Welcome to AI matters 4(1)
Authors: McGovern Amy , Eaton Eric
Published: May 2018

Welcome to the first issue in our fourth year of
AI Matters.
This issue has lots of great new ways for you to catch up on the latest in AI News, beginning with reports on conferences and events. The first is a report on the first AAAI/ACM Conference on Artificial Intelligence, Ethics, and Society, which SIGAI helped to start. We also have a discussion on the 2018 AAAI job fair. We also have a forward looking vision of what AI could be like in 2017, from the perspective of four prominent AI researchers who discussed this issue at IJCAI 2017.
AI education matters
Authors: Neller Todd W.
Published: May 2018

In this column, we share resources for learning about and teaching Hidden Markov Models (HMMs). HMMs find many important applications in temporal pattern recognition tasks such as speech/handwriting/gesture recognition and robot localization. In such domains, we may have a finite state machine model with known state transition probabilities, state output probabilities, and state outputs, but lack knowledge of the states generating such outputs. HMMs are useful in framing problems where external sequential evidence is used to derive underlying state information (e.g. intended words and gestures).
AI amusements
Authors: Genesereth Michael
Published: May 2018

California today became the first state in the Union to elect a computer as governor. The independent candidate,
Corpus Legis
, handily defeated its human opponents in a special election following the retirement of former governor
Jerry (Moonbeam) Brown.
Applying software-defined networking to minimize the end-to-end delay of network services
Authors: Chin Tommy , Rahouti Mohamed , Xiong Kaiqi
Published: May 2018

There is a grand challenge to transfer the gigantic volume of data generated from a variety of smart cities applications. It is an urgent need to efficiently and effectively transmit such time-sensitive data in a wide-area communication. In this paper, we propose an approach by leveraging Software-Defined Networking (SDN) to develop a communication solution for data transfers in smart city applications. Our approach is Quality of Service (QoS)-aware that minimizes the end-to-end delay for data transmission in an SDN infrastructure by using a Timestamp Recording method to compare the arrival and departure of flows and packets over a period. Finally, we evaluate our solution on the Global Environment for Network Innovations (GENI), a real-world federated testbed. We first compare the Timestamp Recording to other common delay measurement techniques. Our analysis demonstrates its effectiveness at scale. Additionally, we carefully examine the accuracy and efficiency in minimizing end-to-end delay delivered by our SDN solution with contrast to a non-optimized SDN environment. Our experiments demonstrate the proposed solution effective and efficient in delivering data with an optimal delay. Particularly, our solution reduces about 22% in end-to-end-delay compared to a non-optimized SDN environment.
NMF based sparse Cholesky decomposition technique for dimensionality scale back in large data sets
Authors: Alostad Jasem M.
Published: May 2018

This paper aims at resolving the issues related to increased dimensionality of data in data mining. In this paper, Sparse Cholesky decomposition (SCD) is combined with Non-integer Matrix Factorization (NMF) to remove the problems arising due to increased data dimensionality. The increased data dimensionality in datasets is probably due to non-orthogonality of datasets. The complex conjugate values is used to remove the sparse matrix and a complex gradient algorithm reduces the sparse matrix by the extraction of conjugate values. The SCD-MNF extracts the feature vector and upper triangular matrix linearly maps the feature vector obtained from the SCD. Hence, NMF is employed with SCD for structuring the datasets and this helps to form a well-defined data geometry. The proposed system is evaluated against normalized mutual information and accuracy against different text datasets. The results prove that SCD-NMF attains better results than conventional methods in finding the instances related to the given query.
SIGCSE 2019 paper length change
Authors: Heckman Sarah , Zhang Jian , Peérez-Quiñones Manuel A. , Hawthorne Elizabeth K.
Published: May 2018

We are pleased to announce that the SIGCSE Board has approved a change to the length of SIGCSE papers. Submissions of CS Education Research papers; Experience Report and Tool papers; and New Curriculum, Program, and Degree Initiative papers can use up to six full pages for content, with references extending to a seventh page!
Koli Calling 2017 conference report
Authors: Montero Calkin Suero , Joy Mike
Published: May 2018

The Koli Calling International Conference on Computing Education Research is a single-track conference dedicated to publishing high quality work in all areas of teaching and learning in the computing disciplines. The 17th Koli Calling was held in November 2017, as per tradition, in the Koli National Park in Finland, organized by the University of Eastern Finland and the University of Warwick, UK. At the time of the conference every year, the national park is filled with white beautiful snow adding a mystical character to the iconic panoramic view from top of the Ukko-Koli hill. The quietly cold temperatures of the season are perfectly balanced by the lively and warm atmosphere of the conference.
Fixed Effects Estimation of Large-TPanel Data Models
Authors: Fernández-Val Iván , Weidner Martin
Published: May 2018

This article reviews recent advances in fixed effects estimation of panel data models for long panels, where the number of time periods is relatively large. We focus on semiparametric models with unobserved individual and time effects, where the distribution of the outcome variable, conditional on covariates and unobserved effects, is specified parametrically while the distribution of the unobserved effects is left unrestricted. In contrast to existing reviews on long panels, we discuss models with both individual and time effects, split-panel jackknife bias corrections, unbalanced panels, distribution and quantile effects, and other extensions. Understanding and correcting the incidental parameter bias caused by the estimation of many fixed effects are our main focuses, and the unifying theme is that the order of this bias is given by the simple formula p/ n for all models discussed, with p being the number of estimated parameters and n the total sample size.
A Guide to Emerging Technologies for Large-Scale and Whole-Brain Optical Imaging of Neuronal Activity
Authors: Weisenburger Siegfried , Vaziri Alipasha
Published: May 2018

The mammalian brain is a densely interconnected network that consists of millions to billions of neurons. Decoding how information is represented and processed by this neural circuitry requires the ability to capture and manipulate the dynamics of large populations at high speed and high resolution over a large area of the brain. Although the use of optical approaches by the neuroscience community has rapidly increased over the past two decades, most microscopy approaches are unable to record the activity of all neurons comprising a functional network across the mammalian brain at relevant temporal and spatial resolutions. In this review, we survey the recent development in optical technologies for Ca2+ imaging in this regard and provide an overview of the strengths and limitations of each modality and its potential for scalability. We provide guidance from the perspective of a biological user driven by the typical biological applications and sample conditions. We also discuss the potential for future advances and synergies that could be obtained through hybrid approaches or other modalities.
Anxiety, Depression, and Decision Making: A Computational Perspective
Authors: Bishop Sonia J. , Gagne Christopher
Published: May 2018

In everyday life, the outcomes of our actions are rarely certain. Further, we often lack the information needed to precisely estimate the probability and value of potential outcomes as well as how much effort will be required by the courses of action under consideration. Under such conditions of uncertainty, individual differences in the estimation and weighting of these variables, and in reliance on model-free versus model-based decision making, have the potential to strongly influence our behavior. Both anxiety and depression are associated with difficulties in decision making. Further, anxiety is linked to increased engagement in threat-avoidance behaviors and depression is linked to reduced engagement in reward-seeking behaviors. The precise deficits, or biases, in decision making associated with these common forms of psychopathology remain to be fully specified. In this article, we review evidence for which of the computations supporting decision making are altered in anxiety and depression and consider the potential consequences for action selection. In addition, we provide a schematic framework that integrates the findings reviewed and will hopefully be of value to future studies.
Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease
Authors: Monday Hannah R. , Younts Thomas J. , Castillo Pablo E.
Published: May 2018

Long-lasting changes of brain function in response to experience rely on diverse forms of activity-dependent synaptic plasticity. Chief among them are long-term potentiation and long-term depression of neurotransmitter release, which are widely expressed by excitatory and inhibitory synapses throughout the central nervous system and can dynamically regulate information flow in neural circuits. This review article explores recent advances in presynaptic long-term plasticity mechanisms and contributions to circuit function. Growing evidence indicates that presynaptic plasticity may involve structural changes, presynaptic protein synthesis, and transsynaptic signaling. Presynaptic long-term plasticity can alter the short-term dynamics of neurotransmitter release, thereby contributing to circuit computations such as novelty detection, modifications of the excitatory/inhibitory balance, and sensory adaptation. In addition, presynaptic long-term plasticity underlies forms of learning and its dysregulation participates in several neuropsychiatric conditions, including schizophrenia, autism, intellectual disabilities, neurodegenerative diseases, and drug abuse.
Closing the Loop: From Motor Neuroscience to Neurorehabilitation
Authors: Roemmich Ryan T. , Bastian Amy J.
Published: May 2018

The fields of human motor control, motor learning, and neurorehabilitation have long been linked by the intuition that understanding how we move (and learn to move) leads to better rehabilitation. In reality, these fields have remained largely separate. Our knowledge of the neural control of movement has expanded, but principles that can directly impact rehabilitation efficacy remain somewhat sparse. This raises two important questions: What can basic studies of motor learning really tell us about rehabilitation, and are we asking the right questions to improve the lives of patients? This review aims to contextualize recent advances in computational and behavioral studies of human motor learning within the framework of neurorehabilitation. We also discuss our views of the current challenges facing rehabilitation and outline potential clinical applications from recent theoretical and basic studies of motor learning and control.
The Impact of Gender Inequality on Economic Performance in Developing Countries
Authors: Klasen Stephan
Published: May 2018

Despite substantial progress, gender gaps persist in many developing countries. Since the 1990s, a literature has emerged arguing that these gaps not only are inequitable but also reduce economic performance. This review finds that, first, it is methodologically difficult to determine reliable effects of gender gaps on economic performance. Second, accounting studies that calculate how much larger GDP would be if gender gaps in employment disappeared vastly overestimate likely effects. Third, the theoretical literature has generated important insights on mechanisms linking gender gaps to economic performance. Fourth, systematic reviews of the cross-country evidence robustly show that lowering gender gaps in education leads to higher economic performance, while the literature on the impact of other gaps is much more limited. Fifth, there is accumulating micro evidence on how reducing particular gender gaps at the level of households, farms, or firms can improve economic performance in particular contexts, with robust results in some areas, and less clear evidence in others.
A Cohort Study of Metformin and Colorectal Cancer Risk among Patients with Diabetes Mellitus
Authors: Bradley Marie C. , Ferrara Assiamira , Achacoso Ninah , Ehrlich Samantha F. , Quesenberry Charles P. , Habel Laurel A.
Published: May 2018

Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these biases.

Methods: A cohort study was conducted among 47,351 members of Kaiser Permanente Northern California with diabetes and no history of cancer or metformin use. Follow-up for incident colorectal cancer occurred from January 1, 1997, until June 30, 2012. Cox regression was used to calculate HRs and 95% confidence intervals (CIs) for colorectal cancer risk associated with metformin use (ever use, total duration, recency of use, and cumulative dose).

Results: No association was observed between ever use of metformin and colorectal cancer risk (HR, 0.90; 95% CI, 0.76–1.07) and there was no consistent pattern of decreasing risk with increasing total duration, dose, or recency of use. However, long-term use (≥5.0 years) appeared to be associated with reduced risk of colorectal cancer in the full population (HR, 0.78; 95% CI, 0.60–1.02), among current users (HR, 0.78; 95% CI, 0.59–1.04), and in men (HR, 0.65; 95% CI, 0.45–0.94) but not in women. Higher cumulative doses of metformin were associated with reduced risk. In initial users of sulfonylureas, switching to or adding metformin was also associated with decreased colorectal cancer risk.

Conclusions: Our findings showed an inverse association between long-term use of metformin and colorectal cancer risk. Findings, especially the risk reduction among men, need to be confirmed in large, well-conducted studies.

Impact: If our findings are confirmed, metformin may have a role in the chemoprevention of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 525–30. ©2018 AACR.

See related commentary by Jackson and García-Albéniz, p. 520
Dual MAPK/CDK Targeting in Melanoma: New Approaches, New Challenges
Authors: Sullivan Ryan J.
Published: May 2018

Summary: Dual MAPK and CDK4/6 targeting is an emerging strategy in melanoma, but toxicity and acquired resistance are limitations. In this issue, two groups (Teh and colleagues and Romano and colleagues) show that therapeutic resistance mechanisms converge on the PI3K pathway, and inhibition of this pathway's mediators can overcome this resistance. Cancer Discov; 8(5); 532–3. ©2018 AACR.

See related article by Romano et al., p. 556.

See related article by Teh et al., p. 568.
Hallmarks of T-cell Exit from Quiescence
Authors: Chapman Nicole M. , Chi Hongbo
Published: May 2018

The appropriate activation of the adaptive immune system relies upon the reprogramming of naïve T cells into specialized effector T cells that can combat pathogens and tumors. Naïve T cells are actively maintained in a state of hyporesponsiveness termed quiescence, which is characterized by small cell size, low proliferative rate, and low basal metabolism. Engagement of antigen and costimulatory receptors drives T cells to exit quiescence to promote subsequent clonal expansion and functional differentiation. The exit from quiescence, which precedes activation-induced proliferation, is associated with extensive remodeling of cellular morphology and metabolism. Here, we define and discuss the implications of the six key features of the exit of naïve T cells from quiescence: (i) cell-cycle entry, (ii) cell growth, (iii) autocrine or paracrine interleukin-2 signaling, (iv) anabolic metabolism, (v) nutrient uptake, and (vi) remodeling of mitochondrial function. Ultimately, understanding how naïve T cells meet each of these requirements for quiescence exit will allow for the tuning of T-cell responses to treat infectious diseases, autoimmunity, and cancer. Cancer Immunol Res; 6(5); 502–8. ©2018 AACR.
Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure
Authors: Weinheimer Carla J. , Kovacs Attila , Evans Sarah , Matkovich Scot J. , Barger Philip M. , Mann Douglas L.
Published: May 2018

Background:

To better understand reverse left ventricular (LV) remodeling, we developed a murine model wherein mice develop LV remodeling after transverse aortic constriction (TAC) and a small apical myocardial infarct (MI) and undergo reverse LV remodeling after removal of the aortic band.

Methods and Results:

Mice studied were subjected to sham (n=6) surgery or TAC+MI (n=12). Two weeks post-TAC+MI, 1 group underwent debanding (referred to as heart failure debanding [HF-DB] mice; n=6), whereas the aortic band remained in a second group (heart failure [HF] group; n=6). LV remodeling was evaluated by 2D echocardiography at 1 day, 2 weeks and 6 weeks post-TAC+MI. The hearts were analyzed by transcriptional profiling at 4 and 6 weeks and histologically at 6 weeks. Debanding normalized LV volumes, LV mass, and cardiac myocyte hypertrophy at 6 weeks in HF-DB mice, with no difference in myofibrillar collagen in the HF and HF-DB mice. LV ejection fraction and radial strain improved after debanding; however, both remained decreased in the HF-DB mice relative to sham and were not different from HF mice at 6 weeks. Hemodynamic unloading in the HF-DB mice was accompanied by a 35% normalization of the HF genes at 2 weeks and 80% of the HF genes at 4 weeks.

Conclusions:

Hemodynamic unloading of a pathophysiologically relevant mouse model of HF results in normalization of LV structure, incomplete recovery of LV function, and incomplete reversal of the HF transcriptional program. The HF-DB mouse model may provide novel insights into mechanisms of reverse LV remodeling.
Taking the Reins on Systems of Care for ST-Segment–Elevation Myocardial Infarction Patients
Authors: Green Jacqueline L. , Jacobs Alice K. , Holmes DaJuanicia , Chiswell Karen , Blanco Rosalia , Bates Eric R. , French William , Kupas Douglas F. , Mears Greg , Roe Matthew , Nallamothu Brahmajee K.
Published: May 2018

Background—

Early success with regionalization of ST-segment–elevation myocardial infarction (STEMI) care has led many states to adopt statewide prehospital STEMI hospital destination policies, allowing emergency medical services to bypass non–percutaneous coronary intervention–capable hospitals. The association between adoption of these policies and patterns of care among STEMI patients is unknown.

Methods and Results—

Using data from January 1, 2013, to December 31, 2014, from the National Cardiovascular Data Registry and Acute Coronary Treatment and Intervention Outcomes Network Registry, 6 states with bypass policies (cases included Delaware, Iowa, Maryland, North Carolina, Pennsylvania, and Massachusetts) were matched to 6 states without bypass policies (controls included South Carolina, Minnesota, Virginia, Texas, New York, and Connecticut) a priori on region, hospital density, and percent state participation in the registry. Using the matched sample, logistic regression models were adjusted for patient- and state-level characteristics. Outcomes were receipt of reperfusion and receipt of timely percutaneous coronary intervention. Our study cohort included 19 287 patients at 379 sites across 12 states. Patients from states with hospital destination policies were similar in age, sex, and comorbidities to patients from states without such policies. After adjustment for patient- and state-level characteristics, 57.9% (95% confidence intervals, 53.2%–62.5%) of patients living in states with hospital destination policies when compared with 47.5% (95% confidence intervals, 43.4%–51.7%) living in states without hospital destination policies received primary percutaneous coronary intervention within their relevant guideline-recommended time from first medical contact.

Conclusions—

Statewide adoption of STEMI hospital destination policies allowing emergency medical services to bypass non–percutaneous coronary intervention–capable facilities is associated with significantly faster treatment times for patients with STEMI.
Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5)
Authors: Xiang Rong , Fan Liang-liang , Huang Hao , Chen Ya-qin , He Wanxia , Guo Shuai , Li Jing-Jing , Jin Jie-yuan , Du Ran , Yan Riqiang , Xia Kun
Published: May 2018

Background:

Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has previously been shown to play a role in neurodegenerative diseases, but little is known about its role in lipid metabolism.

Methods:

Obese patients (n=149), hypertriglyceridemic patients (n=343), and healthy control subjects (n=84) were enrolled to assess their levels of RTN3. To explore the pathophysiological roles of RTN3 in the control of lipid metabolism, we used transgenic mice overexpressing the wild-type human RTN3 gene, the RTN3-null transgenic mouse model, and multiple
Caenorhabditis legans
strains for molecular characterization. The underlying mechanisms were studied with 3T3L1 cell cultures in vitro.

Results:

We report that overexpressed RTN3 in mice induces obesity and higher accumulation of triglycerides. Increased RTN3 expression is also found in patients with obesity and hypertriglyceridemia. We reveal that RTN3 plays critical roles in regulating the biosynthesis and storage of triglycerides and in controlling lipid droplet expansion. Mechanistically, RTN3 regulates these events through its interactions with heat shock protein family A (Hsp70) member 5, and this enhanced interaction increases sterol regulatory element-binding protein 1c and AMP-activated kinase activity.

Conclusions:

This study provides evidence for a role of RTN3 in inducing obesity and triglyceride accumulation and suggests that inhibiting the expression of RTN3 in fat tissue may be a novel therapeutic approach to treat obesity and hypertriglyceridemia.