bluuebunny/crossref_metadata_2025 huggingface dataset:
Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of
Mycobacterium tuberculosis
MazF Toxins
Authors: Nigam Akanksha , Kumar Sathish , Engelberg-Kulka Hanna
Published: May 2018

mazEF
is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "
e
xtracellular
d
eath
f
actors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of
Escherichia coli
MazF.
Mycobacterium tuberculosis
carries several
mazEF
modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave
M. tuberculosis
rRNAs. Here we report the
in vitro
effects of EDFs on the endoribonucleolytic activities of
M. tuberculosis
MazFs.
Escherichia coli
EDF (
Ec
EDF) and the three
Pseudomonas aeruginosa
EDFs (
Pa
EDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against
M. tuberculosis
.

IMPORTANCE
Mycobacterium tuberculosis
is one of the leading causes of death from infectious disease.
M. tuberculosis
is highly drug resistant, and drug delivery to the infected site is very difficult. In previous studies, we showed that
e
xtracellular
d
eath
f
actors (EDFs) can work as quorum sensing molecules which participate in interspecies bacterial cell death. In this study, we demonstrated the role of different EDFs in the endoribonucleolytic activities of
M. tuberculosis
MazFs.
Escherichia coli
EDF (
Ec
EDF) and the three
Pseudomonas aeruginosa
EDFs (
Pa
EDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3. The current report provides a basis for the use of the EDF peptides
Ec
EDF and
Pa
EDF as novel antibiotics against
M. tuberculosis
.
Regulation of Flagellum Biosynthesis in Response to Cell Envelope Stress in
Salmonella enterica
Serovar Typhimurium
Authors: Spöring Imke , Felgner Sebastian , Preuße Matthias , Eckweiler Denitsa , Rohde Manfred , Häussler Susanne , Weiss Siegfried , Erhardt Marc
Published: May 2018

Flagellum-driven motility of
Salmonella enterica
serovar Typhimurium facilitates host colonization. However, the large extracellular flagellum is also a prime target for the immune system. As consequence, expression of flagella is bistable within a population of
Salmonella
, resulting in flagellated and nonflagellated subpopulations. This allows the bacteria to maximize fitness in hostile environments. The degenerate EAL domain protein RflP (formerly YdiV) is responsible for the bistable expression of flagella by directing the flagellar master regulatory complex FlhD
4
C
2
with respect to proteolytic degradation. Information concerning the environmental cues controlling expression of
rflP
and thus about the bistable flagellar biosynthesis remains ambiguous. Here, we demonstrated that RflP responds to cell envelope stress and alterations of outer membrane integrity. Lipopolysaccharide (LPS) truncation mutants of
Salmonella
Typhimurium exhibited increasing motility defects due to downregulation of flagellar gene expression. Transposon mutagenesis and genetic profiling revealed that σ
24
(RpoE) and Rcs phosphorelay-dependent cell envelope stress response systems sense modifications of the lipopolysaccaride, low pH, and activity of the complement system. This subsequently results in activation of RflP expression and degradation of FlhD
4
C
2
via ClpXP. We speculate that the presence of diverse hostile environments inside the host might result in cell envelope damage and would thus trigger the repression of resource-costly and immunogenic flagellum biosynthesis via activation of the cell envelope stress response.

IMPORTANCE
Pathogenic bacteria such as
Salmonella
Typhimurium sense and adapt to a multitude of changing and stressful environments during host infection. At the initial stage of gastrointestinal colonization,
Salmonella
uses flagellum-mediated motility to reach preferred sites of infection. However, the flagellum also constitutes a prime target for the host’s immune response. Accordingly, the pathogen needs to determine the spatiotemporal stage of infection and control flagellar biosynthesis in a robust manner. We found that
Salmonella
uses signals from cell envelope stress-sensing systems to turn off production of flagella. We speculate that downregulation of flagellum synthesis after cell envelope damage in hostile environments aids survival of
Salmonella
during late stages of infection and provides a means to escape recognition by the immune system.
SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin
Authors: Sun Wei-Wei , Jiao Shi , Sun Li , Zhou Zhaocai , Jin Xia , Wang Jian-Hua
Published: May 2018

The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5′-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host’s modulation of HIV-1 transcription and latency. Here we revealed that “Sad1 and UNC84 domain containing 2” (SUN2), an inner nuclear membrane protein, maintained the repressive chromatin and inhibited HIV LTR-driven transcription of proviral DNA through an association with lamin A/C. Specifically, lamin A/C tethered SUN2 to the nucleosomes 1 and 2 of the HIV-1 5′-LTR to block the initiation and elongation of HIV-1 transcription. SUN2 knockdown converted chromatin to an active form and thus enhanced the phosphorylation of RNA polymerase II and its recruitment to the 5′-LTR HIV-1 proviral DNA, leading to reactivation of HIV-1 from latency. Conversely, the exogenous factors such as tumor necrosis factor alpha (TNF-α) induced reactivation, and the replication of HIV-1 led to the disassociation between SUN2 and lamin A/C, suggesting that disruption of the association between SUN2 and lamin A/C to convert the repressive chromatin to the active form might be a prerequisite for the initiation of HIV-1 transcription and replication. Together, our findings indicate that SUN2 is a novel chromatin reassembly factor that helps to maintain chromatin in a repressive state and consequently inhibits HIV-1 transcription.

IMPORTANCE
Despite the successful use of scores of antiretroviral drugs, HIV latency poses a major impediment to virus eradication. Elucidation of the mechanism of latency facilitates the discovery of new therapeutic strategies. It has been known that the formation of repressive chromatin at the 5′-LTR of HIV-1 proviral DNA impedes viral transcription and maintains viral latency, but how the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. In this study, we performed in-depth virological and cell biological studies and discovered that an inner nuclear membrane protein, SUN2, is a novel chromatin reassembly factor that maintains repressive chromatin and thus modulates HIV-1 transcription and latency: therefore, targeting SUN2 may lead to new strategies for HIV cure.
Antibodies to the Glycoprotein GP2 Subunit Cross-React between Old and New World Arenaviruses
Authors: Amanat Fatima , Duehr James , Oestereich Lisa , Hastie Kathryn M. , Ollmann Saphire Erica , Krammer Florian
Published: May 2018

Several viruses in the
Arenaviridae
family infect humans and cause severe hemorrhagic fevers which lead to high case fatality rates. Due to their pathogenicity and geographic tropisms, these viruses remain very understudied. As a result, an effective vaccine or therapy is urgently needed. Here, we describe efforts to produce cross-reactive monoclonal antibodies that bind to both New and Old World arenaviruses. All of our MAbs seem to be nonneutralizing and nonprotective and target subunit 2 of the glycoprotein. Due to the lack of reagents such as recombinant glycoproteins and antibodies for rapid detection assays, our MAbs could be beneficial as analytic and diagnostic tools.
Invasive Methicillin-Resistant Staphylococcus aureus USA500 Strains from the U.S. Emerging Infections Program Constitute Three Geographically Distinct Lineages
Authors: Frisch M. B. , Castillo-Ramírez S. , Petit R. A. , Farley M. M. , Ray S. M. , Albrecht V. S. , Limbago B. M. , Hernandez J. , See I. , Satola S. W. , Read T. D.
Published: May 2018

In this work, we have removed some of the confusion surrounding the use of the name “USA500,” placed USA500 strains in the context of the CC8 group, and developed a strategy for assignment to subclades based on genome sequence. Our new phylogeny of USA300/USA500 will be a reference point for understanding the genetic adaptations that have allowed multiple highly virulent clonal strains to emerge from within CC8 over the past 50 years.
In Defense of an Academic Career in Microbiology
Authors: Schloss Patrick D.
Published: May 2018

The rise of Quit Lit describing the myriad reasons for leaving academia and constant complaining by mentors leave many trainees with little desire for an academic career. Although there are clearly structural and social problems in academia, I feel that they are outweighed by the benefits of working and living in an academic environment.
T-piece resuscitators: how do they compare?
Authors: Hinder Murray , McEwan Alistair , Drevhammer Thomas , Donaldson Snorri , Tracy Mark Brian
Published: May 2018

Background

The T-piece resuscitator (TPR) has seen increased use as a primary resuscitation device with newborns. Traditional TPR design uses a high resistance expiratory valve to produce positive end expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) at resuscitation. A new TPR device that uses a dual flow ratio valve (fluidic flip) to produce PEEP/CPAP is now available (rPAP). We aimed to compare the measured ventilation performance of different TPR devices in a controlled bench test study.

Design/methods

Single operator provided positive pressure ventilation to an incremental testlung compliance (Crs) model (0.5–5 mL/cmH2O) with five different brands of TPR device (Atom, Neopuff, rPAP, GE Panda warmer and Draeger Resuscitaire). At recommended peak inflation pressure (PIP) 20 cmH2O, PEEP of 5 cmH2O and rate of 60 inflations per minute.

Results

1864 inflations were analysed. Four of the five devices tested demonstrated inadvertent elevations in mean PEEP (5.5–10.3 cmH2O, p<0.001) from set value as Crs was increased, while one device (rPAP) remained at the set value. Measured PIP exceeded the set value in two infant warmer devices (GE and Draeger) with inbuilt TPR at Crs of 0.5 (24.5 and 23.5 cmH2O, p<0.001). Significant differences were seen in tidal volumes across devices particularly at higher Crs (p<0.001).

Conclusions

Results show important variation in delivered ventilation from set values due to inherent TPR device design characteristics with a range of lung compliances expected at birth. Device-generated inadvertent PEEP and overdelivery of PIP may be clinically deleterious for term and preterm newborns or infants with larger Crs during resuscitation.
All equine vets should wear helmets
Authors: Shaw Laura
Published: May 2018

Laura Shaw argues that, due to the equine profession having the highest injury rate of all civilian professions, senior veterinary surgeons should take the lead in wearing helmets as routine.
Studies on the dynamic stability of an axially moving nanobeam based on the nonlocal strain gradient theory
Authors: Wang Jing , Shen Huoming , Zhang Bo , Liu Juan
Published: May 2018

In this paper, we studied the parametric resonance issue of an axially moving viscoelastic nanobeam with varying velocity. Based on the nonlocal strain gradient theory, we established the transversal vibration equation of the axially moving nanobeam and the corresponding boundary condition. By applying the average method, we obtained a set of self-governing ordinary differential equations when the excitation frequency of the moving parameters is twice the intrinsic frequency or near the sum of certain second-order intrinsic frequencies. On the plane of parametric excitation frequency and excitation amplitude, we can obtain the instability region generated by the resonance, and through numerical simulation, we analyze the influence of the scale effect and system parameters on the instability region. The results indicate that the viscoelastic damping decreases the resonance instability region, and the average velocity and stiffness make the instability region move to the left- and right-hand sides. Meanwhile, the scale effect of the system is obvious. The nonlocal parameter exhibits not only the stiffness softening effect but also the damping weakening effect, while the material characteristic length parameter exhibits the stiffness hardening effect and damping reinforcement effect.
Stochastic resonance in an array of integrate-and-fire neurons with threshold
Authors: Zhou Bingchang , Qi Qianqian
Published: May 2018

We investigate the phenomenon of stochastic resonance (SR) in parallel integrate-and-fire neuronal arrays with threshold driven by additive noise or signal-dependent noise (SDN) and a noisy input signal. SR occurs in this system. Whether the system is subject to the additive noise or SDN, the input noise [Formula: see text] weakens the performance of SR but the array size N and signal parameter [Formula: see text] promote the performance of SR. Signal parameter [Formula: see text] promotes the performance of SR for the additive noise, but the peak values of the output signal-to-noise ratio [Formula: see text] first decrease, then increase as [Formula: see text] increases for the SDN. Moreover, when [Formula: see text] tends to infinity, for the SDN, the curve of [Formula: see text] first increases and then decreases, however, for the additive noise, the curve of [Formula: see text] increases to reach a plain. By comparing system performance with the additive noise to one with SDN, we also find that the information transmission of a periodic signal with SDN is significantly better than one with the additive noise in limited array size N.
Double Beta Decay
Authors: Shirai Junpei
Published: May 2018

Double beta decay is a key process to reveal a fundamental property of neutrinos. If neutrinos are Majorana particles, that is they are equivalent to their antiparticles, neutrinoless double beta ([Formula: see text]) decay, [Formula: see text], would occur. The process is beyond the standard model and would lead to a scenario which can explain the extremely small masses of neutrinos and provide a solution to the current matter dominance of the world. In this talk experimental efforts searching for [Formula: see text] decays are presented. Then, major [Formula: see text] experiments together with searches using [Formula: see text]Xe nuclei are described, followed by the current status of the KamLAND-Zen experiment.
Experimental Review of Hadron Spectroscopy
Authors: Shen Chengping , Li Suxian
Published: May 2018

Since the invention of the quark model in 1964 hadrons are formed from a quark-antiquark pair called mesons or three quarks called baryons. However, QCD-motivated models for hadrons predict more complex structures on the hadrons components called generically exotics. These include tetraquark, pentaquark, the six-quark H-dibaryon, hybrid, and glueball mesons. Exotic hadrons have been systematically searched for in many experiments and studied in theories. In the past decade, lots of new hadrons that cannot fit into the normal mesons or baryons were discovered, the so-called [Formula: see text] states. Even so, no unambiguous candidates for any of those exotic configurations have been identified. This review presents an overview of the remarkable progress in the field of exotic hadrons over the past few years.
Excess of J/ψ Production at Very Low Transverse Momenta in A+A Collisions from STAR
Authors: Zha Wangmei
Published: May 2018

A significant excess of [Formula: see text] yield at very low transverse momentum ([Formula: see text] GeV/c) has been observed by the ALICE Collaboration in peripheral Pb+Pb collisions, which points to evidence of coherent photoproduction of [Formula: see text] in violent hadronic interactions. The survival of photoproduced [Formula: see text] merits more experimental investigations. In this article, we report on the STAR measurements of [Formula: see text] production at very low transverse momenta ([Formula: see text]) in hadronic Au+Au collisions at [Formula: see text] = 200 GeV and U+U collisions at [Formula: see text] = 193 GeV at mid-rapidity. Centrality dependence of [Formula: see text] yields and nuclear modification factors at very low [Formula: see text] are presented.
Open Bottom Production in Au+Au Collisions at s NN = 200 GeV with the STAR Experiment
Authors: Zhang Shenghui
Published: May 2018

In these proceedings, we present measurements of open bottom hadron production through multiple decay channels in Au+Au collisions at [Formula: see text] = 200 GeV by the STAR experiment. Namely, measurements of nuclear modification factors for electrons, [Formula: see text], and [Formula: see text] from open bottom hadron decays are shown. The decay products are topologically identified utilizing the Heavy Flavor Tracker, a silicon vertex detector installed at STAR during the period of 2014 - 2016. It enables precise reconstruction of displaced decay vertices. The results show large suppression for non-prompt [Formula: see text] and non-prompt [Formula: see text] at high transverse momenta, and indicate less suppression for electrons from bottom hadron decays than for those from charm hadron decays at [Formula: see text] significance level.
Charmonium Decays at BESIII
Authors: Zhang Jielei
Published: May 2018

The BESIII Experiment at the Beijing Electron Positron Collider (BEPCII) has accumulated the largest [Formula: see text] collisions data sets in the [Formula: see text]-charm region in the world. Using the data sets of 448.1 million [Formula: see text] events and 1.3 billion [Formula: see text] events, the branching fractions and the angular distributions of [Formula: see text] and [Formula: see text] decay to [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] are measured. The branching fractions of [Formula: see text] are reported with improved precision. The higher-order multipole amplitudes in [Formula: see text] with [Formula: see text] are measured, as a byproduct the [Formula: see text] transition is searched. The Dalitz decays of [Formula: see text] and [Formula: see text] are observed and the branching fractions are measured. [Formula: see text] radiative decays [Formula: see text] are observed for the first time. Improved measurement of [Formula: see text] and search for [Formula: see text] are reported.
Heavy Flavour Spectroscopy at LHCb
Authors: Xu Ao
Published: May 2018

Recent results on heavy flavour spectroscopy with data collected by the LHCb detector are highlighted, including studies of exotic hadrons, the observation of five [Formula: see text] resonances, and the observation of the [Formula: see text] baryon.
Shedding Light on Hexaquarks
Authors: Bashkanov M. , Skorodko T. , Clement H. , Watts D. P.
Published: May 2018

Several new findings in the four, five and six quark systems reheat the interest in the field of multiquark states (beyond the trivial [Formula: see text] and [Formula: see text]). A lot of progress has recently been made in the 6q sector, on both the theoretical and experimental side. A resonance like structure observed in double-pionic fusion to the deuteron, at M = 2.38 GeV with [Formula: see text] = 70 MeV and [Formula: see text] has been consistently observed in a wealth of reaction channels, supporting the existence of a resonant dibaryon state - the [Formula: see text]. These studies include measurement of all the principle strong decay channels in pn collisions in the quasifree mode by the WASA-at-COSY and HADES collaborations. The internal structure of the [Formula: see text] is largely unknown. It can contain various ”hidden color” 6q configurations, [Formula: see text] molecular states with angular momentum L = 0,2,4,6 as well as meson-assisted dressed dibaryon structures. The large set of experimental data obtained to date gives some constraints on the internal structure of the [Formula: see text] dibaryon, but does not settle the issue. The [Formula: see text] is the only multiquark state which can be produced copiously at current facilities, offering unique access to information beyond its basic quantum numbers, particularly its physical size and internal structure.
NEXT: Searching for the ββ0νDecay at the LSC
Authors: Novella P.
Published: May 2018

The goal of the NEXT collaboration is the sensitive search of the neutrino-less double beta decay ([Formula: see text]) of [Formula: see text]Xe at the LSC. After a successful R&D phase, a first large-scale prototype of a high-pressure gas-Xenon electroluminescent TPC (NEW) is being operated at LSC since 2016. NEW is a 10-kg radiopure detector meant to understand the relevant backgrounds for the [Formula: see text]search and to perform a measurement of the two neutrino mode of the double beta decay ([Formula: see text]). The first phase of the NEW physics program comprises the commissioning of the detector and the data taking with calibration sources. This phase has allowed to understand the detector capabilities in terms of energy resolution and event topology reconstruction. The operation of NEW is setting the grounds for the construction of the NEXT-100 detector: a TPC holding 100 kg of [Formula: see text]Xe and reaching a sensitivity to the [Formula: see text]half-life of [Formula: see text] y after 3 years of data taking. The latest results of the NEW detector as well as the status of the NEXT-100 project are presented.
Tau Identification at the CMS Experiment in LHC Run-2
Authors: Choudhury Somnath
Published: May 2018

Since Run-1 of the LHC, CMS has taken the opportunity to improve further particle reconstruction. A number of improvements were made to the hadronic tau reconstruction and identification algorithms. In particular, the reconstruction of the tau decay products leaving deposits in the electromagnetic calorimeter was improved to better model signal of [Formula: see text] from [Formula: see text] decays. This modification improves energy response and removes the tau footprint from isolation area. In addition to this, improvements were made to discriminators that combine isolation and tau lifetime variables, and the rejection of electrons misidentified as hadronic taus was improved using multivariate techniques. The results of these improvements using 13 TeV data at LHC Run-2 are presented and validation of tau identification using a variety of techniques has been highlighted.
AMADEUS Experiment: Studies on Antikaon Interactions with Nucleons and Nuclei
Authors: Marton J. , Piscicchia K.
Published: May 2018

The understanding of the low-energy strong interaction involving strangeness is a challenging topic due to resonances and predicted kaonic nuclear bound states. The K- nucleon interaction is strongly attractive at low energies verified in kaonic hydrogen studied in the SIDDHARTA experiment at the DA[Formula: see text]NE electron-positron collider of LNF-INFN (Frascati/Italy). Hyperon resonances like the elusive [Formula: see text] in the s-wave impose questions about its nature. According to theoretical studies it can be described as a dynamically generated resonance with two poles or a quasi-bound [Formula: see text]N state, which could lead to kaonic nuclear bound states (e.g. K-pp). An insight in many open facets of the antikaon interactions can be provided by the AMADEUS experiment at DA[Formula: see text]NE based on the analysis of the data collected in 2004/2005 by the KLOE collaboration, and of the dedicated data set collected in 2012 by AMADEUS in collaboration with KLOE. As a first step data from antikaon-induced reactions in the drift chamber of KLOE were analyzed and yielded new results on antikaon absorption on nuclei. Recent results of the experimental studies and an outlook to the future possibilities within AMADEUS are presented.
The Upgrade of Endcap TOF in BESIII
Authors: Wu Zhi
Published: May 2018

In this paper the new endcap Time-of-Flight system (ETOF) of BESIII experiment at the IHEP is described. The new detector module is composed of multi-gap resistive plate chamber (MRPC) with the gas mixture 90% Freon+5% S[Formula: see text]+5% iso-[Formula: see text]. The whole system including the detectors, the gas system, the high voltage (HV) system, the readout electronics system is described. Finally the installation and commissioning of the whole system is introduced briefly. After the calibration with Bhabha events, the very promising time resolutions of 69 and 60 ps for one-end and two-ends of MRPCs are obtained. The average detection efficiency of two-ends is about 97.5%.
Determination of the Strong Coupling Constant αs in Multijet Production with the ATLAS Detector at the LHC
Authors: Llorente Javier
Published: May 2018

A measurement of transverse energy–energy correlations and its asymmetry in [Formula: see text] collisions recorded by the ATLAS detector at the LHC at [Formula: see text] TeV is presented. The results are used to determine the strong coupling constant [Formula: see text]. A global fit to the transverse energy–energy correlation distributions yields [Formula: see text], while a global fit to the corresponding asymmetry distributions yields a value of [Formula: see text].
Detector Performance and Physics Potential at CEPC
Authors: Liang Hao , Ruan Manqi
Published: May 2018

The Circular Electron Position Collider (CEPC) is a future [Formula: see text] and Higgs bosons factory, which targets precision electroweak and Higgs measurements. The simulation, reconstruction, analysis chain has been established at CEPC. The detector design parameters were optimized according to several performances of key physical objects. The physics potential has been studied for the detector geometry CEPC_v1.
Measuring Individual Video QoE
Authors: Zhu Yi , Guntuku Sharath Chandra , Lin Weisi , Ghinea Gheorghita , Redi Judith A.
Published: May 2018

The next generation of multimedia services have to be optimized in a personalized way, taking user factors into account for the evaluation of individual experience. Previous works have investigated the influence of user factors mostly in a controlled laboratory environment which often includes a limited number of users and fails to reflect real-life environment. Social media, especially Facebook, provide an interesting alternative for Internet-based subjective evaluation. In this article, we develop (and open-source) a Facebook application, named YouQ
1
, as an experimental platform for studying individual experience for videos. Our results show that subjective experiments based on YouQ can produce reliable results as compared to a controlled laboratory experiment. Additionally, YouQ has the ability to collect user information automatically from Facebook, which can be used for modeling individual experience.
Creating the human standard for ethical autonomous and intelligent systems (A/IS)
Authors: Havens John C.
Published: May 2018

Like most people, I first encountered Artificial Intelligence through movies - The Terminator, Blade Runner, 2001. As a rule, the future in these stories was always dystopian which I found irritating. If humanity was able to create such amazing technology, wouldn't they also have created ethical codes or standards to keep things from going awry? Granted, a film about a code of ethics isn't as sexy as killer robots, but picturing utopian futures powered or assisted by AI seemed like something not enough people were doing in my estimation.
Design and evaluation of a privacy architecture for crowdsensing applications
Authors: Perez Alfredo J. , Zeadally Sherali
Published: May 2018

By using consumer devices such as cellphones, wearables and Internet of Things devices owned by citizens, crowdsensing systems are providing solutions to the community in areas such as transportation, security, entertainment and the environment through the collection of various types of sensor data. Privacy is a major issue in these systems because the data collected can potentially reveal aspects considered private by the contributors of data. We propose the Privacy-Enabled ARchitecture (PEAR), a layered architecture aimed at protecting privacy in privacy-aware crowdsensing systems. We identify and describe the layers of the architecture. We propose and evaluate the design of MetroTrack, a crowdsensing system that is based on the proposed PEAR architecture.
SIGCSE symposium 2018 report
Authors: Barnes Tiffany , Garcia Dan
Published: May 2018

We were delighted to co-chair the 49th ACM Technical Symposium on Computer Science Education in Baltimore, Maryland from February 21-24, 2018, and we opened the conference with a CS riff of that iconic Hairspray song. This was the largest SIGCSE conference of all time, shattering many conference records: SIGCSE 2018 had 1,735 registrations and 953 submissions, with 1,119 volunteers participating in the reviewing and selection process to whittle it down to 161 papers, 35 panels and special sessions, 90 posters (growing from 3 to 4 sessions), 10 demos, 34 BOFs, 6 nifty assignments, 11 events, and 34 workshops. We needed a record number 17 parallel tracks to support all of this. We were inspired to see so many of these submissions innovating to engage a broader audience and to create equitable opportunities for access to computer science education.
ICER 2018 preview
Authors: Malmi Lauri , Korhonen Ari , McCartney Robert , Petersen Andrew
Published: May 2018

You are warmly invited to the fourteenth annual ACM International Computing Education Research (ICER) conference, which will be held in Espoo, Finland, 13-15 August 2018. ICER provides a forum for presenting and publishing high-quality research in computing education. ICER 2018 will continue to feature its traditional single-track format, which is designed to encourage the authors and audience to engage in lively discussion about each work presented.
Opportunities and Challenges of Whole-Cell and -Tissue Simulations of the Outer Retina in Health and Disease
Authors: Luthert Philip J. , Serrano Luis , Kiel Christina
Published: May 2018

Visual processing starts in the outer retina, where photoreceptor cells sense photons that trigger electrical responses. Retinal pigment epithelial cells are located external to the photoreceptor layer and have critical functions in supporting cell and tissue homeostasis and thus sustaining a healthy retina. The high level of specialization makes the retina vulnerable to alterations that promote retinal degeneration. In this review, we discuss opportunities and challenges in proposing whole-cell and -tissue simulations of the human outer retina. An implicit position taken throughout this review is that mapping diverse data sets onto integrative computational models is likely to be a pivotal approach to understanding complex disease and developing novel interventions.
Network Analysis as a Grand Unifier in Biomedical Data Science
Authors: McGillivray Patrick , Clarke Declan , Meyerson William , Zhang Jing , Lee Donghoon , Gu Mengting , Kumar Sushant , Zhou Holly , Gerstein Mark
Published: May 2018

Biomedical data scientists study many types of networks, ranging from those formed by neurons to those created by molecular interactions. People often criticize these networks as uninterpretable diagrams termed hairballs; however, here we show that molecular biological networks can be interpreted in several straightforward ways. First, we can break down a network into smaller components, focusing on individual pathways and modules. Second, we can compute global statistics describing the network as a whole. Third, we can compare networks. These comparisons can be within the same context (e.g., between two gene regulatory networks) or cross-disciplinary (e.g., between regulatory networks and governmental hierarchies). The latter comparisons can transfer a formalism, such as that for Markov chains, from one context to another or relate our intuitions in a familiar setting (e.g., social networks) to the relatively unfamiliar molecular context. Finally, key aspects of molecular networks are dynamics and evolution, i.e., how they evolve over time and how genetic variants affect them. By studying the relationships between variants in networks, we can begin to interpret many common diseases, such as cancer and heart disease.
Ancient Genomics of Modern Humans: The First Decade
Authors: Skoglund Pontus , Mathieson Iain
Published: May 2018

The first decade of ancient genomics has revolutionized the study of human prehistory and evolution. We review new insights based on prehistoric modern human genomes, including greatly increased resolution of the timing and structure of the out-of-Africa expansion, the diversification of present-day non-African populations, and the earliest expansions of those populations into Eurasia and America. Prehistoric genomes now document population transformations on every inhabited continent—in particular the effect of agricultural expansions in Africa, Europe, and Oceania—and record a history of natural selection that shapes present-day phenotypic diversity. Despite these advances, much remains unknown, in particular about the genomic histories of Asia (the most populous continent) and Africa (the continent that contains the most genetic diversity). Ancient genomes from these and other regions, integrated with a growing understanding of the genomic basis of human phenotypic diversity, will be in focus during the next decade of research in the field.
Activated NO pathway in uterine arteries during pregnancy in an IUGR rat model
Authors: Bigonnesse Emilie , Sicotte Benoit , Brochu Michèle
Published: May 2018

Insufficient development of the uteroplacental circulation may contribute to the development of intrauterine growth restriction (IUGR). We developed a rat model of IUGR by administering a low-Na+ diet. This diet reduces maternal blood volume expansion and uteroplacental perfusion. We hypothesized that an impaired endothelial function in radial arteries decreases vasorelaxation and lowers placental perfusion in this IUGR model. The objective was to assess radial uterine artery responses to vasoactive agents in the IUGR model versus controls. The vasoactive agents included phenylephrine and carbachol, use of a pressurized artery myograph, in the absence or presence of inhibitors of nitric oxide (NO) synthase [ N-nitro-l-arginine methyl ester (l-NAME)], cyclooxygenase (Ibuprofen), and endothelium-dependent hyperpolarization {apamin/1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole}, allowing better characterization of the mechanism implicated in endothelium-dependent relaxation. The results show that 1) the diameter of uterine radial arteries was significantly decreased in the IUGR group; 2) sensitivity to phenylephrine was reduced in IUGR arteries, which could be returned to control group values by inhibition of NO production; 3) the relaxation response to carbachol was increased in IUGR rats, principally mediated by endothelium-dependent hyperpolarization in both groups; 4) NO synthase inhibition by l-NAME decreased the maximum relaxation to carbachol only in the IUGR group; and 5) relaxation response to NO donors is increased in IUGR compared with control radial arteries. Contrary to the hypothesis, results in the IUGR model indicate that the NO pathway is activated in radial uterine arteries, most likely in compensation for the reduction in blood uteroplacental perfusion.

NEW & NOTEWORTHY In contrast to genetic or surgical models of intrauterine growth restriction, the diet-induced model of reduced maternal volume expansion shows the nitric oxide pathway to be activated in the uterine artery, possibly from increased shear stress and/or placental factors.
PSMD5 Inactivation Promotes 26S Proteasome Assembly during Colorectal Tumor Progression
Authors: Levin Avi , Minis Adi , Lalazar Gadi , Rodriguez Jose , Steller Hermann
Published: May 2018

Protein degradation by the ubiquitin–proteasome system (UPS) is central to protein homeostasis and cell survival. The active 26S proteasome is a large protease complex consisting of a catalytic 20S subunit and 19S regulatory particles. Cancer cells are exposed to considerable protein overload due to high metabolic rates, reprogrammed energy metabolism, and aneuploidy. Here we report a mechanism that facilitates the assembly of active 26S proteasomes in malignant cells. Upon tumorigenic transformation of the gut epithelium, 26S proteasome assembly was significantly enhanced, but levels of individual subunits were not changed. This enhanced assembly of 26S proteasomes increased further with tumor progression and was observed specifically in transformed cells, but not in other rapidly dividing cells. Moreover, expression of PSMD5, an inhibitor of proteasome assembly, was reduced in intestinal tumors and silenced with tumor progression. Reexpression of PSMD5 in tumor cells caused decreased 26S assembly and accumulation of polyubiquitinated proteins. These results suggest that inhibition of cancer-associated proteasome assembly may provide a novel therapeutic strategy to selectively kill cancer cells.

Significance: Enhanced cancer-associated proteasome assembly is a major stress response that allows tumors to adapt to and to withstand protein overload.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3458/F1.large.jpg. Cancer Res; 78(13); 3458–68. ©2018 AACR.
Dairy Consumption in Adolescence and Early Adulthood and Risk of Breast Cancer
Authors: Farvid Maryam S. , Eliassen A. Heather , Cho Eunyoung , Chen Wendy Y. , Willett Walter C.
Published: May 2018

Background: Carcinogenic exposure in early life may be critical for subsequent breast cancer risk. Dairy consumption was examined during adolescence and early adulthood in relation to incident breast cancer in the Nurses' Health Study II cohort.

Methods: For the analyses of early adulthood dairy consumption, we included 90,503 premenopausal women ages 27 to 44 years in 1991 who reported dairy consumption using a validated food-frequency questionnaire. From 1991 to 2013, 3,191 invasive breast cancer cases were identified. In 1998, 44,264 women recalled adolescent dairy consumption. This subgroup of women was followed up from 1998 to 2013; 1,318 invasive breast cancer cases were identified. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard regression.

Results: Adolescent and early adulthood total dairy consumption was not associated with overall breast cancer risk (each serving/day during adolescence, total dairy HR = 1.02, 95% CI, 0.97–1.07; for early adulthood total dairy HR = 1.01, 95% CI, 0.97–1.04), as were intakes of calcium, vitamin D, and lactose. Adolescent consumption of total and high-fat dairy was associated with higher risk of estrogen and progesterone receptor negative (each serving/day: total dairy HR = 1.11, 95% CI, 1.00–1.24; high-fat dairy HR = 1.17, 95% CI, 1.04–1.31). However, higher adolescent high-fat dairy consumption was associated with lower risk of estrogen and progesterone receptor positive tumors (each serving/day HR = 0.91, 95% CI, 0.86–0.97).

Conclusions: Our results suggest no overall association between dairy consumption during adolescence or early adulthood and breast cancer risk, but the findings may differ by hormone receptor status of tumors.

Impact: Dairy consumption in adolescence or early adulthood may not be a significant predictor of breast cancer incidence. Cancer Epidemiol Biomarkers Prev; 27(5); 575–84. ©2018 AACR.
MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease
Authors: Bhanvadia Raj R. , VanOpstall Calvin , Brechka Hannah , Barashi Nimrod S. , Gillard Marc , McAuley Erin M. , Vasquez Juan Manuel , Paner Gladell , Chan Wen-Ching , Andrade Jorge , De Marzo Angelo M. , Han Misop , Szmulewitz Russell Z. , Vander Griend Donald J.
Published: May 2018

Purpose: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS–HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored.

Experimental Design: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression.

Results: These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depletion of MEIS1 and MEIS2 resulted in increased tumor growth over time in vivo, and decreased MEIS expression in both patient-derived tumors and MEIS-depleted cell lines was associated with increased expression of the protumorigenic genes cMYC and CD142, and decreased expression of AXIN2, FN1, ROCK1, SERPINE2, SNAI2, and TGFβ2.

Conclusions: These data implicate a functional role for MEIS proteins in regulating cancer progression, and support a hypothesis whereby tumor expression of MEIS1 and MEIS2 expression confers a more indolent prostate cancer phenotype, with a decreased propensity for metastatic progression. Clin Cancer Res; 24(15); 3668–80. ©2018 AACR.
The IGF2/IR/IGF1R Pathway in Tumor Cells and Myofibroblasts Mediates Resistance to EGFR Inhibition in Cholangiocarcinoma
Authors: Vaquero Javier , Lobe Cindy , Tahraoui Sylvana , Clapéron Audrey , Mergey Martine , Merabtene Fatiha , Wendum Dominique , Coulouarn Cédric , Housset Chantal , Desbois-Mouthon Christèle , Praz Françoise , Fouassier Laura
Published: May 2018

Purpose: Cholangiocarcinoma (CCA) is a desmoplastic tumor of the biliary tree in which epidermal growth factor receptor (EGFR) is overexpressed and contributes to cancer progression. Although EGFR has been envisaged as a target for therapy, treatment with tyrosine kinase inhibitors (TKI) such as erlotinib did not provide therapeutic benefit in patients with CCA, emphasizing the need to investigate resistance mechanisms against EGFR inhibition.

Experimental Design: Resistant CCA cells to EGFR inhibition were obtained upon long-time exposure of cells with erlotinib. Cell signaling, viability, migration, and spheroid growth were determined in vitro, and tumor growth was evaluated in CCA xenograft models.

Results: Erlotinib-resistant CCA cells displayed metastasis-associated signatures that correlated with a marked change in cell plasticity associated with an epithelial–mesenchymal transition (EMT) and a cancer stem cell (CSC)–like phenotype. Resistant cells exhibited an upregulation of insulin receptor (IR) and insulin-like growth factor (IGF) 1 receptor (IGF1R), along with an increase in IGF2 expression. IR/IGF1R inhibition reduced EMT and CSC-like traits in resistant cells. In vivo, tumors developed from resistant CCA cells were larger and exhibited a more prominent stromal compartment, enriched in cancer-associated fibroblasts (CAF). Pharmacological coinhibition of EGFR and IR/IGF1R reduced tumor growth and stromal compartment in resistant tumors. Modeling of CCA-CAF crosstalk showed that IGF2 expressed by fibroblasts boosted IR/IGF1R signaling in resistant cells. Furthermore, IR/IGF1R signaling positively regulated fibroblast proliferation and activation.

Conclusions: To escape EGFR-TKI treatment, CCA tumor cells develop an adaptive mechanism by undergoing an IR/IGF1R-dependent phenotypic switch, involving a contribution of stromal cells. Clin Cancer Res; 24(17); 4282–96. ©2018 AACR.
A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure
Authors: Zeidan Amer M. , Knaus Hanna A. , Robinson Tara M. , Towlerton Andrea M.H. , Warren Edus H. , Zeidner Joshua F. , Blackford Amanda L. , Duffield Amy S. , Rizzieri David , Frattini Mark G. , Levy Yair M. , Schroeder Mark A. , Ferguson Anna , Sheldon Katherine E. , DeZern Amy E. , Gojo Ivana , Gore Steven D. , Streicher Howard , Luznik Leo , Smith B. Douglas
Published: May 2018

Purpose: After failure of hypomethylating agents (HMA), patients with myelodysplastic syndromes (MDS) have dismal survival and no approved treatment options.

Patients and Methods: We conducted a phase 1b investigator-initiated trial of ipilimumab in patients with higher risk MDS who have failed HMAs. Patients received monotherapy at two dose levels (DL; 3 and 10 mg/kg) with an induction followed by a maintenance phase. Toxicities and responses were evaluated with CTCAE.4 and IWG-2006 criteria, respectively. We also performed immunologic assays and T-cell receptor sequencing on serial samples.

Results: Twenty-nine patients from 7 centers were enrolled. In the initial DL1 (3 mg), 3 of 6 patients experienced grade 2–4 immune-related adverse events (IRAE) that were reversible with drug discontinuation and/or systemic steroids. In DL2, 4 of 5 patients experienced grade 2 or higher IRAE; thus, DL1 (3 mg/kg) was expanded with no grade 2–4 IRAEs reported in 18 additional patients. Best responses included marrow complete response (mCR) in one patient (3.4%). Prolonged stable disease (PSD) for ≥46 weeks occurred in 7 patients (24% of entire cohort and 29% of those treated with 3 mg/kg dose), including 3 patients with more than a year of SD. Five patients underwent allografting without excessive toxicity. Median survival for the group was 294 days (95% CI, 240–671+). Patients who achieved PSD or mCR had significantly higher frequency of T cells expressing ICOS (inducible T-cell co-stimulator).

Conclusions: Our findings suggest that ipilimumab dosed at 3 mg/kg in patients with MDS after HMA failure is safe but has limited efficacy as a monotherapy. Increased frequency of ICOS-expressing T cells might predict clinical benefit. Clin Cancer Res; 24(15); 3519–27. ©2018 AACR.