bluuebunny/crossref_metadata_2025 huggingface dataset:
Gaia 8: Discovery of a star cluster containing β Lyrae
Authors: Bastian U.
Published: September 2019

Aims. The aim here is to try and clarify whether there are stars in the neighbourhood of β Lyrae which are physically connected to the famous prototype eclipsing binary.

Methods. We scrutinised the astrometric and photometric data (from HIPPARCOS and Gaia DR2) of stars in a limited sky field around β Lyrae.

Results. A star cluster of about 100 members was discovered, nicely centred on β Lyrae in five dimensions. There are clear indications that the newly discovered cluster belongs to a larger old (extinct) star formation complex, including two known star clusters and an extended, strewn field of stars at practically the same distance and space velocity.

Conclusions. This discovery opens up the possibility of determining a precise distance and precise age for β Lyrae using the combined properties of the cluster members. This in turn may form an important basis for an improved astrophysical interpretation of the model binary β Lyrae and its kin. The larger old star formation complex is of scientific interest in its own right.
A new compact hydraulic propeller turbine for low heads
Authors: Barsi Dario , Ubaldi Marina , Zunino Pietro , Fink Robert
Published: September 2019

In this paper, a design procedure for a compact hydraulic propeller turbine for low heads is proposed and developed. The design is based upon classical criteria and on the employment of statistical correlations, which relates the main geometrical parameters to the fundamental design parameters of turbomachinery. The procedure for obtaining the meridional flow path and the stator vanes and rotor blades geometries is explained step by step. The obtained 3D model is employed to carry out a CFD calculation in order to obtain the turbine overall performance and main working parameters.
Analysis of annual energy consumption by a warehouse building
Authors: Besler Maciej , Cepiński Wojciech , Kęskiewicz Piotr , Skrzycki Maciej
Published: September 2019

This analysis was carried out to present the distribution of energy demand for air heating, air cooling and technology equipment for a warehouse through the year. The supplied energy is used to maintain the assumed temperatures in the rooms and for the needs of technology. During the work, the calculation model of the building was prepared and imported into the calculation program. The simulation was based on the planned building parameters (partitions structure, dimensions, technology) taken from the architectural executive design. Several versions of the structure of the construction and technical equipment have been analyzed. The obtained results show differences in the formation of energy demand and indoor room conditions.
Systematic approach for improving energy efficiency in industrial facilities, from energy audit to practical implementation – case study production of autoclaved aerated concrete
Authors: Sucic Boris , Peckaj Marko , Tomsic Zeljko , Uranic Jani
Published: September 2019

In today’s globalized world, need for competitiveness on one side and constant pressure on the reduction of negative environmental impacts on the other side, are forcing industrial companies to systematically analyse all possibilities for the optimization of their production processes. This paper presents a systematic approach for improving energy efficiency in industrial facilities. Special attention was given to activities that were necessary for the proper identification of energy saving potential and implementation of selected energy efficiency measures in the complex industrial environment. The proposed approach includes four main activities: (1) energy auditing, identification and valorisation of opportunities for improving energy efficiency, (2) identification of key personnel who needs to be trained and motivated to become involved and to make energy efficient decisions in practice, (3) implementation of selected energy efficiency measures and (4) continuous monitoring and verification of achieved results. The proposed approach has been tested in the real industrial environment and the results are confirming that significant energy savings and overall improvement of competitiveness can be reached. Additionally, special emphasis was placed on soft elements like cooperation between energy experts, process operators and maintenance staff that are crucial for the overall success.
Grand, A Giant Radio Array For Neutrino Detection: Objectives, Design And Current Status
Authors: Tueros Matias
Published: September 2019

The Giant Radio Array for Neutrino Detection (GRAND) aims to answer one of the most pressing open questions in astrophysics: what is the origin of ultra-highenergy cosmic rays (UHECRs)?. It will do so indirectly: UHECRs make secondary UHE neutrinos which encode information about the properties of UHECRs and their sources. GRAND is designed to discover UHE neutrinos even under pessimistic predictions of their flux, reaching a sensitivity of 6x10−9GeV.cm−2.s−1.sr−1 around 109GeV. It will do so by using 20 sub-arrays of 10 000 radio antennas forming a total detector area of 200 000 km2, making it the largest air-shower detector ever built. With this sensitivity, GRAND will discover cosmogenic neutrinos in 3 years of operation, even in disfavorable scenarios. Because of its subdegree angular resolution, GRAND will also search for point sources of UHE neutrinos, both steady and transient. Moreover, GRAND will be a valuable instrument for astronomy and cosmology, allowing for the discovery and followup of large numbers of radio transients - fast radio bursts, giant radio pulses - and studies of the epoch of reionization. In this contribution we will present briefly some of the science goals, detection strategy, construction plans and current status of the GRAND project.
ARIANNA: Measurement of cosmic rays with a radio neutrino detector in Antarctica
Authors: Glaser Christian
Published: September 2019

The ARIANNA detector aims to detect neutrinos with energies above 1016 eV by instrumenting 0.5 Teratons of ice with a surface array of a thousand independent radio detector stations in Antarctica. The Antarctic ice is transparent to the radio signals caused by the Askaryan effect which allows for a cost-effective instrumentation of large volumes. Several pilot stations are currently operating successfully at the Moore’s Bay site (Ross Ice Shelf) and at the South Pole. As the ARIANNA detector stations are positioned at the surface, the more abundant cosmic-ray air showers are also measured and serve as a direct way to prove the capabilities of the detector. We will present measured cosmic rays and will show how the incoming direction, polarization and electric field of the cosmicray pulse can be reconstructed from single detector stations comprising 4 upward and 4 downward facing LPDA antennas.
Observation of radio emissions from electron beams using an ice target
Authors: Mase Keiichi , Ikeda Daisuke , Ishihara Aya , Sagawa Hiroyuki , Shibata Tatsunobu , Fukushima Masaki , Yamamoto Tokonatsu , Yoshida Shigeru , Gaïor Romain , Hanson Kael , Matthews John N. , Meures Thomas , Shin Bokkyun , Thomson Gordon , de Vries Krijn
Published: September 2019

To observe high energy cosmogenic neutrinos above 50 PeV, the large neutrino telescope ARA is being built at the South Pole. The ARA telescope detects neutrinos by observing radio signals by the Askaryan effect. We performed an experiment using 40 MeV electron beams of the Telescope Array Electron Light Source to verify the understanding of the Askaryan emission as well as the detector responses used in the ARA experiment. Clear coherent polarized radio signals were observed with and without an ice target. We found that the observed radio signals are consistent with simulation, showing that our understanding of the radio emissions and the detector responses are within the systematic uncertainties of the ARAcalTA experiment which is at the level of 30%.
Virtual reality – level of immersion within the crime investigation
Authors: Mach Václav , Valouch Jan , Adámek Milan , Ševčík Jiří
Published: September 2019

The 3D reconstruction and visualization of crime scenarios, such as criminal assaults, traffic accidents or homicides are defining a new approach with potential for increasing effectiveness within the criminal investigation process. Modern 3D capturing and processing methods are utilized to create an authentic and immersive virtual environment. Nonetheless, an immersion to virtual environment enables different levels of view. Virtual reality immersion views which are proposed and described. These views are specific by reasons of its role within the criminal investigation as well as its technical severity. Moreover, the possible methods for the design of proposed virtual views are analyzed and the next research steps are exposed.
Networking solutions for connecting bluetooth low energy devices - a comparison
Authors: Labib Mostafa , Ghalwash Atef , Abdulkader Sarah , Elgazzar Mohamed
Published: September 2019

The Bluetooth Low Energy (BLE) is an attractive solution for implementing low-cost, low power consumption, short-range wireless transmission technology and high flexibility wireless products, which working on standard coin-cell batteries for years. The original design of BLE is restricted to star topology networking, which limits network coverage and scalability. In contrast, other competing technologies like Wi-Fi and ZigBee overcome those constraints by supporting different topologies such as the tree and mesh network topologies. This paper presents a part of the researchers’ efforts in designing solutions to enable BLE mesh networks and implements a tree network topology which is not supported in the standard BLE specifications. In addition, it discusses the advantages and drawbacks of the existing BLE network solutions. During analyzing the existing solutions, we highlight currently open issues such as flooding-based and routing-based solutions to allow end-to-end data transmission in a BLE mesh network and connecting BLE devices to the internet to support the Internet of Things (IoT). The approach proposed in this paper combines the default BLE star topology with the flooding based mesh topology to create a new hybrid network topology. The proposed approach can extend the network coverage without using any routing protocol.
Enhanced public transport management employing AI and anonymous data collection
Authors: Minea Marius , Dumitescu Cătălin
Published: September 2019

The paper proposes a simple, economic and expandable solution for enhancing the data collection process used in public transport and transport demand management. A non-intrusive and anonymous method is employed to collect an estimative number of passengers in vehicles and public transport stops, along with other, relevant data. Machine learning and specific algorithms are used to improve the data collection process. No specific infrastructure equipment is required.
Deep Generative Model with Supervised Latent Space for Text Classification
Authors: Jankowski Maciej
Published: September 2019

Recent advances in applying deep neural networks to Bayesian Modelling, sparked resurgence of in- terest in Variational Methods. Notably, the main contribution in this area is Reparametrization Trick introduced in [1] and [2]. VAE model [1], is unsupervised and therefore its application to classification is not optimal. In this work, we research the possibility to extend the model to supervised case. We first start with the model known as Supervised Variational Autoencoder that is researched in the literature in various forms [3] and [4]. We then modify objective function in such a way, that latent space can be better fitted to multiclass problem. Finally, we introduce a new method that uses information about classes to modify latent space, so it even better reflects differences between classes. All of this, will use only two dimensions. We will show, that mainstream classifiers applied to such a space, achieve significantly better performance than if applied to original datasets and VAE generated data. We also show, how our novel approach can be used to calculate better classification score, and how it can be used to generate data for a given class.
Effectiveness of Surgical Treatments for Basal Ganglia Hemorrhage and Imaging Factors Affecting Hematoma Evacuation Rate by Neuroendoscopic Surgery
Authors: Guo Ai-Shun , Lin Guo-Shi , Xie Da-Hua , Huang Yan , Zhou Chang-Fu , Chen Yan-Feng , Sun Mei-Zhen , Shi Gui-Mei , Lin Rui-Sheng
Published: September 2019

Background Basal ganglia hemorrhage (BGH) is a devastating neurologic disease with high morbidity and mortality, and its management is still controversial. We evaluated the effectiveness of surgical treatments for BGH and investigated computed tomography (CT) imaging features affecting the hematoma evacuation rate (ER) in patients treated with neuroendoscopic surgery.

Materials and Methods A total of 104 BGH patients who underwent craniotomy, burr-hole drainage, or neuroendoscopic surgery were analyzed retrospectively. Clinical characteristics, imaging features, and postoperative complications were compared. Univariate and multivariate regression analyses were applied to identify imaging factors associated with ER.

Results A significant difference in ER was observed: 78.4% in patients treated with neuroendoscopic surgery, 33.6% in patients treated with burr-hole drainage, and 82.5% in patients treated with craniotomy (p < 0.001). Similar results were observed for operative time (p < 0.001). Five cases (12.5%) of rebleeding were found in patients treated with burr-hole drainage (p = 0.020). No significant difference was found for pneumonia, intracranial infection, gastrointestinal bleeding, hospital mortality, hospital stay, expenses, 3-day Glasgow Coma Scale (GCS) scores after surgery, or GCS at discharge. The CT imaging feature, the island sign (p = 0.004), was observed as an independent factor correlated with lower ER for neuroendoscopic surgery.

Conclusions The benefits and drawbacks of surgical treatments confirmed they have their own indications, and neuroendoscopic surgery may be relatively beneficial for BGH treatment. The island sign was an independent factor affecting ER for neuroendoscopic surgery. Therefore, comprehensive assessment of clinical data, especially the island sign, should be performed preoperatively in BGH patients.
Cyber espionage through Botnets
Authors: Bederna Zsolt , Szadeczky Tamas
Published: September 2019

Botnets, the groups of illegally controlled infected devices on the Internet have had a history of two decades already. This history shows an evolution of the infection techniques, the scope of the target devices, and their usage. Thus, the new direction is the usage of sophisticated data leakage techniques by state-sponsored hacker groups. Our article analyses this evolution while focusing on Botnet usage for cyber espionage. We present the Botnet architecture in the context of network science research, lifecycle, applied network protocols, and capabilities. Next, we analyze two examples, the APT28 group activities and the VPNFilter Botnet, which demonstrate the real-life cyber espionage capability of this technique.
The Trinity Lancaster Corpus
Authors: Gablasova Dana , Brezina Vaclav , McEnery Tony
Published: September 2019

This paper introduces a new corpus resource for language learning research, the Trinity Lancaster Corpus (TLC), which contains 4.2 million words of interaction between L1 and L2 speakers of English. The corpus includes spoken production from over 2,000 L2 speakers from different linguistic and cultural backgrounds at different levels of proficiency engaged in two to four tasks. The paper provides a description of the TLC and places it in the context of current learner corpus development and research. The discussion of practical decisions taken in the construction of the TLC also enables a critical reflection on current methodological issues in corpus construction.
State of the art measurements with TexAT
Authors: Bishop J , Rogachev G V , Aboud E , Ahn S , Assunção M , Barbui M , Bosh A , Guimarães V , Hooker J , Hunt C , Jayatissa D , Koshchiy E , Lukyanov S , O’Dwyer R , Penionzhkevich Y , Pollacco E , Pruitt C , Roeder B T , Saastamoinen A , Sobotka L , Uberseder E , Upadhyayula S , Zamora J
Published: September 2019

In the past several years, there has been a large interest of Time Projection Chambers (TPCs) for use in experimental nuclear physics. This has continued in tandem with the requirement for high efficiency detectors with low intensity radioactive ion beams. TexAT is a Active Target TPC (AT-TPC) built at Texas A&M University utilizing MICRO MEsh GASeous (MicroMegas) pads and GET electronics developed specifically for TPCs. This design combines good TPC pixelation with a surrounding shell of Si/CsI telescopes to make an extremely versatile detector capable of a wide range of different experimental techniques with only minor modifications to the electronics setup. Two recent experiments performed at the Cyclotron Institute, Texas A&M University, are detailed here demonstrating versatility beyond the usual Thick Target Inverse Kinematics (TTIK) or transfer reactions that these TPCs are more typically used for. The first, a measurement of the 12N → 12C* → 3α decay demonstrates the capabilities of TexAT as a low-energy detector operating at low pressure (20 Torr) to measure β-delayed particle decay. The second, a direct measurement of the 8B+40Ar fusion cross section shows the advantages of operating in active target mode where the target also functions as the detector gas.
Significantly Increased Patient Satisfaction Following Liquid Formulation AbobotulinumtoxinA Treatment in Glabellar Lines: FACE-Q Outcomes From a Phase 3 Clinical Trial
Authors: Ascher Benjamin , Rzany Berthold , Kestemont Philippe , Hilton Said , Heckmann Marc , Bodokh Isaac , Noah Ernst Magnus , Boineau Dominique , Kerscher Martina , Volteau Magali , Le Berre Philippe , Picaut Philippe
Published: September 2019

Background

The FACE-Q patient-reported outcome assesses patient experiences/outcomes with aesthetic facial procedure. A recent trial of abobotulinumtoxinA (ASI, liquid formulation) was the first to our knowledge to assess satisfaction with FACE-Q after glabellar line (GL) injection.

Objectives

The authors sought to evaluate patient satisfaction with ASI for GL treatment employing 3 FACE-Q scales: facial appearance, psychological well-being, and aging appearance.

Methods

This was a Phase 3, randomized, double-blind, placebo-controlled trial (NCT02353871) of ASI 50 units in adults with moderate-to-severe GL with 6-month follow-up.

Results

Significantly greater least squares mean changes from baseline were associated with ASI treatment (N = 125) vs placebo (N = 59) for satisfaction with facial appearance at all visits until day 148 (5 months; P < 0.0001-0.0037), psychological well-being at all visits (P < 0.0001-0.0279), and aging appearance at all visits except day 148 (P < 0.0001-0.0409). Significant differences (ASI vs placebo) were observed at all visits for individual items: “how rested your face looks” (P < 0.0001-0.0415), “I feel okay about myself” (P = 0.0011-0.0399), and “I feel attractive” (P < 0.0001-0.0102). Maximal least squares mean (standard error) changes in aging appearance score were −1.4 (0.3; ASI) and −0.3 (0.4; placebo). Investigators’ live assessment of GL at maximum frown significantly correlated with improvements in FACE-Q facial appearance and psychological scales (all patients: r = −0.41 and r = −0.36 [both P < 0.0001], respectively).

Conclusions

Significant improvements in patient satisfaction with aging, facial appearance, and, importantly, psychological well-being were demonstrated with ASI employing FACE-Q scales up to 5 to 6 months post-injection. Results support a long duration of efficacy with ASI and use of FACE-Q in future trials and clinical practice.

Level of Evidence: 1
ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND RISK OF TRACTION RETINAL DETACHMENT IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY
Authors: Bressler Neil M. , Beaulieu Wesley T. , Bressler Susan B. , Glassman Adam R. , Melia B. Michele , Jampol Lee M. , Jhaveri Chirag D. , Salehi-Had Hani , Velez Gisela , Sun Jennifer K. ,   for the DRCR Retina Network
Published: September 2019

Purpose:

To investigate whether anti–vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR.

Methods:

Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization.

Results:

The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%–9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%–7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54–1.66,P= 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P= 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity.

Conclusion:

These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.
Considering Propulsion Pattern in Therapeutic Outcomes for Children Who Use Manual Wheelchairs
Authors: Rammer Jacob R. , Krzak Joseph J. , Slavens Brooke A. , Winters Jack M. , Riedel Susan A. , Harris Gerald F.
Published: September 2019

Purpose:

Children who use manual wheelchairs encounter pain and injury risks to the upper body. Current literature does not describe how propulsion pattern and physiotherapeutic training methodologies impact response to treatment.

Methods:

This study assesses the effect of community-based intensive physical and occupational therapy on functional outcomes over a 7-week period in pediatric manual wheelchair users.

Results:

Key results include significant joint and musculotendon kinematic differences at the shoulder, improved speed and propulsion effectiveness, and changed propulsion pattern.

Conclusions:

Statistics also revealed that propulsion pattern was a predictor of response to therapy, as was weekly therapeutic duration, wheelchair-specific focus by the therapists, and stretching.
Blood Pressure and Memory
Authors: Liu Anran , Sun Zhaowen , McDade Eric M. , Hughes Tiffany F. , Ganguli Mary , Chang Chung-Chou H.
Published: September 2019

Background:

Linear models cannot capture nonlinear associations when the relationships between cognition and risk factors vary across risk levels. We demonstrate a method of modelling nonlinear associations using the example of blood pressure (BP) and memory.

Methods:

We measured memory and BP (in mm Hg) annually for 10 years in a population-based cohort (N=1982) aged 65+. We evaluated the relationship between BP and memory at the same time points using both linear mixed models and generalized additive mixed models with smoothing splines, adjusting for relevant covariates.

Results:

Linear mixed models found no significant associations. Generalized additive mixed models detected different associations between BP and memory across baseline BP categories (normotensive, hypertensive, hypotensive). Among normotensives, systolic blood pressure (SBP)/diastolic blood pressure (DBP) around 140/80 was associated with the highest, while SBP/DBP around 110/60 was associated with the lowest, predicted memory scores. Among hypertensives, SBP/DBP around 130/85 was associated with the highest, while SBP/DBP around 150/65 was associated with the lowest, predicted memory scores. Among hypotensives, no significant association was found. Among both normotensives and hypertensives, a DBP >75 was associated with better memory.

Conclusions:

By modelling nonlinear associations, we showed that the relationship between BP and memory performance varied by baseline BP among normotensives and hypertensives.
Virtual Support Groups for Informal Caregivers of Individuals With Dementia
Authors: Armstrong Melissa J. , Alliance Slande
Published: September 2019

Objective:

The purpose of this scoping systematic review was to inform virtual support group development for informal caregivers of dementia by identifying published approaches, outcomes, barriers, and facilitators.

Methods:

A scoping systematic review was performed using 5 search engines. Studies were included if they utilized virtual support groups for informal caregivers of persons with dementia. Study details, support group characteristics, outcomes, barriers, facilitators, and recommended approaches were extracted and summarized.

Results:

Of 1052 identified articles, 87 were retrieved; 62 were excluded largely because they described other virtual interventions. Groups typically used teleconferences or internet-based videoconferences, included 4 to 6 participants, lasted 60 minutes, and occurred weekly or monthly. Moderators were professionals; moderator training was common. Content focused on support, education, or both. Covered topics included dementia knowledge, caregiving skills, coping, and resources. Costs related to technology, programming, and staffing. Although most studies identified no statistical differences, caregivers described many participation benefits. Common barriers were technology and access. Facilitators included training, technology support, small groups, and skilled leaders.

Conclusions:

Clinics desiring to start virtual support groups should consider videoconferencing or telephone approaches with pretraining, technology support, and professional moderators. Clinics need adequate resources, particularly for technology, and identification of locally relevant goals and approach.
EomesandBrachyurycontrol pluripotency exit and germ layer segregation by changes of chromatin state
Authors: Tosic Jelena , Kim Gwang-Jin , Pavlovic Mihael , Schröder Chiara M. , Mersiowsky Sophie-Luise , Barg Margareta , Hofherr Alexis , Probst Simone , Köttgen Michael , Hein Lutz , Arnold Sebastian J.
Published: September 2019

The first lineage specification of pluripotent mouse epiblast segregates neuroectoderm (NE) from mesoderm and endoderm (ME) by currently poorly understood mechanisms. Here we demonstrate that the induction of any ME-gene programs critically relies on the T-box (Tbx) transcription factorsEomesandBrachyurythat concomitantly repress pluripotency and NE gene programs. Tbx-deficient cells retain pluripotency and differentiate to NE lineages despite the presence of ME-inducing signals TGFβ/Nodal and WNT. Pluripotency and NE gene networks are additionally repressed by Tbx-induced ME factors, demonstrating a remarkable redundancy in program regulation to safeguard mutually exclusive lineage specification. Chromatin analyses revealed that accessibility of ME-gene enhancers depends on Tbx-binding, while NE-gene enhancers are accessible and activation-primed already at pluripotency state. This asymmetry of chromatin landscape thus explains the default differentiation of pluripotent cells to NE in the absence of ME-induction mediated through the activating and repressive functions of early Tbx factorsEomes andBrachyury.
The Mosquito Electrocuting Trap As An Exposure-Free Method For Measuring Human Biting Rates ByAedesMosquito Vectors
Authors: Ortega-López Leonardo D. , Pondeville Emilie , Kohl Alain , León Renato , Betancourth Mauro Pazmiño , Almire Floriane , Torres-Valencia Sergio , Saldarriaga Segundo , Mirzai Nozrat , Ferguson Heather M.
Published: September 2019

Background

Entomological monitoring ofAedesvectors has largely relied on surveillance of larvae, pupae and non-host-seeking adults, which have been poorly correlated with human disease incidence. Exposure to mosquito-borne diseases can be more directly estimated using Human Landing Catches (HLC), although this method is not recommended forAedes-borne arboviruses. We evaluated a new method previously tested with malaria vectors, the Mosquito Electrocuting Trap (MET) as an exposure-free alternative for measuring landing rates ofAedesmosquitoes on people. Aims were to 1) compare the MET to the BG-sentinel (BGS) trap gold standard approach for sampling host-seekingAedesvectors; 2) characterize the diel activity ofAedesvectors and their association with microclimatic conditions.

Methods

The study was conducted over 12 days in Quinindé – Ecuador in May 2017. Mosquito sampling stations were set up in the peridomestic area of four houses. On each day of sampling, each house was allocated either a MET or a BGS trap, which were rotated amongst the four houses daily in a Latin square design. Mosquito abundance and microclimatic conditions were recorded hourly at each sampling station between 07:00-19:00 hours to assess variation between vector abundance, trapping methods, and environmental conditions. AllAedes aegyptifemales were tested for the presence of Zika (ZIKV), dengue (DENV) and chikungunya (CHIKV) viruses.

Results

A higher number ofAe. aegyptifemales were found in MET than in BGS collections, although no statistically significant differences in meanAe. aegyptiabundance between trapping methods were found. Both trapping methods indicated femaleAe. aegyptihad bimodal patterns of host seeking, being highest during early morning and late afternoon hours. MeanAe. aegyptidaily abundance was negatively associated with daily temperature. No infection by ZIKV, DENV or CHIKV was detected in anyAedesmosquitoes caught by either trapping method.

Conclusion

We conclude the MET performs at least as well as the BGS standard, and offers the additional advantage of direct measurement ofper capitahuman biting rates. If detection of arboviruses can be confirmed in MET-collectedAedesin future studies, this surveillance method could provide a valuable tool for surveillance and prediction on human arboviral exposure risk.
Internalizing Symptoms Associate with the Pace of Epigenetic Aging in Childhood
Authors: Tollenaar Marieke S. , Beijers Roseriet , Garg Elika , Nguyen T.T. Thao , Lin David T.S. , MacIsaac Julia L. , Shalev Idan , Kobor Michael S. , Meaney Michael J. , O’Donnell Kieran J. , de Weerth Carolina
Published: September 2019

Childhood psychiatric symptoms may be associated with advanced biological aging. This study examined whether epigenetic age acceleration (EAA) associates with internalizing and externalizing symptoms across childhood in a longitudinal cohort study. At age 6 buccal epithelial cells from 148 children (69 girls) were collected to survey genome-wide DNA methylation. EAA was estimated using the Horvath clock. Internalizing symptoms at ages 2.5 and 4 years significantly predicted higher EAA at age 6, which in turn was significantly associated with internalizing symptoms from ages 6 to 10 years. Similar trends for externalizing symptoms did not reach significance. These findings indicate advanced biological aging in relation to child mental health and may help better identify those at risk for lasting impairments associated with internalizing disorders.
Diversity and function of maternal HIV-1-specific antibodies at the time of vertical transmission
Authors: Doepker Laura E. , Simonich Cassandra A. , Ralph Duncan , Gobillot Theodore , Garrett Meghan , Vigdorovich Vladimir , Sather D. Noah , Nduati Ruth , Matsen Frederick A. , Overbaugh Julie M.
Published: September 2019

Infants of HIV positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies may provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically-infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer. Here, we isolated and characterized 39 HIV-specific neutralizing monoclonal antibodies (nAbs) from MG505, the mother of BG505, at a time point just prior to vertical transmission. These nAbs belonged to 21 clonal families, employed a variety of VH genes, many were specific for the HIV-1 Env V3 loop, and this V3 specificity correlated with measurable antibody-dependent cellular cytotoxicity (ADCC) activity. The isolated nAbs did not recapitulate the full breadth of heterologous nor autologous virus neutralization by contemporaneous plasma. Notably, we found that the V3-targeting nAb families neutralized one particular maternal Env variant even though all tested variants had low V3 sequence diversity and were measurably bound by these nAbs. None of the nAbs neutralized the BG505 transmitted virus. Furthermore, the MG505 nAb families were found at relatively low frequencies within the maternal B cell repertoire: all less than 0.25% of total IgG sequences. Our findings demonstrate the diversity of HIV-1 nAbs that exist within a single mother, resulting in a collection of antibody specificities that can shape the transmission bottleneck.

Importance

Mother-to-child-transmission of HIV-1 offers a unique setting in which maternal antibodies both within the mother and passively-transferred to the infant are present at the time of viral exposure. Untreated HIV-exposed human infants are infected at a rate of 30-40%, meaning that some infants do not get infected despite continued exposure to virus. Since the potential of HIV-specific immune responses to provide protection against HIV is a central goal of HIV vaccine design, understanding the nature of maternal antibodies may provide insights into immune mechanisms of protection. In this study, we isolated and characterized HIV-specific antibodies from the mother of an infant whose transmitted virus has been well studied.
The 5’-NAD cap of RNAIII modulates toxin production in Staphylococcus aureus isolates
Authors: Morales-Filloy Hector Gabriel , Zhang Yaqing , Nübel Gabriele , George Shilpa Elizabeth , Korn Natalya , Wolz Christiane , Jäschke Andres
Published: September 2019

1

Nicotinamide adenosine dinucleotide (NAD) has been found to be covalently attached to the 5’-ends of specific RNAs in many different organisms, but the physiological consequences of this modification are largely unknown. Here we report the occurrence of several NAD-RNAs in the opportunistic human pathogen Staphylococcus aureus. Most prominently, RNAIII, a central quorum-sensing regulator of this bacterium’s physiology, was found to be 5’-NAD-capped to a significant extent. NAD incorporation efficiency into RNAIII was found to depend in vivo on the −1 position of the P3 promoter. Reduction of RNAIII’s NAD content led to a decreased expression of alpha- and delta-toxins, resulting in reduced cytotoxicity of the modified strains. These effects to not seem to be due to changes in RNAIII’s secondary structure upon NAD attachment, as indicated by largely unaltered patterns in in vitro chemical probing experiments. Our study represents a large step towards establishing a biological function of the 5’-NAD cap, which for RNAIII in S. aureus is to modulate the expression of virulence factors.

2

Importance

Numerous organisms, including bacteria, are endowed with a 5’-NAD cap in specific RNAs. While the presence of the 5’-NAD cap modulates the stability of the modified RNA species, a significant biological function and phenotype have not been assigned so far. Here, we show the presence of a 5’-NAD cap in RNAIII from S. aureus, a dual-function regulatory RNA involved in quorum-sensing processes and regulation of virulence factor expression. We also demonstrate that altering the natural NAD modification ratio of RNAIII leads to a decrease in exotoxin production, thereby modulating bacterium’s virulence. Our work unveils a new layer of regulation of RNAIII and the agr system that might be linked to the redox state of the NAD molecule in the cell.
Selection and drift determine phenotypic stasis despite genetic divergence
Authors: Mallard François , Noble Luke , Guzella Thiago , Afonso Bruno , Baer Charles F. , Teotónio Henrique
Published: September 2019

1

Evolutionary theory suggests that phenotypic stasis is explained by natural selection and genetic drift, or by constraints imposed by mutation and recombination of standing genetic variation. We performed experimental evolution from standing genetic variation with the nematodeCaenorhabditis elegans, measuring individual locomotion in outcrossing populations for 240 generations. We find that, in our constant environment, locomotion bias shows no directional divergence, due to both stabilizing and disruptive selection on specific combinations of component traits. Despite phenotypic stasis, the genetic variance-covariance structure between component traits shows clear divergence from the ancestral state and extensive differentiation among replicated populations facing the same environment. Analysis of mutation accumulation experiments and genome-sequenced recombinant inbred lines from the experimental populations indicates that the evolution of the genetic variance-covariance structure is independent ofde novomutation or major effect QTL; being instead explained by the joint action of selection and drift in generating subtle linkage disequilibrium differences between small effect QTL among replicate populations. These findings indicate that phenotypic evolution is repeatable because of selection, even if the genetic structuring of component traits within lineages is mostly contingent upon drift history.
Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity
Authors: Shani Ophir , Raz Yael , Monteran Lea , Megides Or , Shacham Hila , Cohen Noam , Silverbush Dana , Levi-Galibov Oshrat , Avivi Camilla , Sharan Roded , Madi Asaf , Scherz-Shouval Ruth , Barshack Iris , Tsarfaty Ilan , Erez Neta
Published: September 2019

Mortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with worse survival in human breast cancer.
Thrombospondin module 1 domain (TSP1) of the matricellular protein CCN3 shows an atypical disulfide pattern and incomplete CWR layers
Authors: Xu Emma-Ruoqi , Lafita Aleix , Bateman Alex , Hyvönen Marko
Published: September 2019

Members of the CCN (Cyr61/CTGF/Nov) family are a group of matricellular regulatory proteins, essential to a wide range of functional pathways in cell signalling. Through interacting with extracellular matrix components and growth factors via one of its four domains, the CCN proteins are involved in critical biological processes such as angiogenesis, cell proliferation, bone development, fibrogenesis, and tumorigenesis. We present here the crystal structure of the thrombospondin module 1 (TSP1) domain of CCN3 (previously known as Nov), which shares a similar three-stranded fold with the thrombospondin type 1 repeats of thrombospondin-1 and Spondin-1, but with variations in the disulfide connectivity. Moreover, the CCN3 TSP1 lacks the typical pi-stacked ladder of charged and aromatic residues on one side of the domain, as seen in other TSP1 domains. Using conservation analysis among orthologous domains, we show that a charged cluster in the centre of the domain is the most conserved site and predict it to be a potential functional epitope for heparan sulphate binding. This variant TSP1 domain has also been used to revise the sequence determinants of TSP1 domains and derive improved Pfam sequence profiles for identification of novel TSP1 domains in more than 10,000 proteins across diverse phyla.

Synopsis

The first structure of a thrombospondin module 1 domain (TSP1) from a CCN family matricellular protein has been determined by X-ray crystallography. The structure shows a typical three-stranded fold, but with an incomplete pi-stacked structure that is usually found in these domains. The structure reveals highest conservation in the positively charged central segment, which we predict to be a binding site for heparan sulphates. The atypical features of this domain have been used to revise the definition of the TSP1 domains and identify a number of new domains in sequence databases.
A reverse chemical ecology approach to explore wood natural durability
Authors: Thomas Perrot , Guillaume Salzet , Nadine Amusant , Jacques Beauchene , Philippe Gérardin , Stéphane Dumarçay , Rodnay Sormani , Mélanie Morel-Rouhier , Eric Gelhaye
Published: September 2019

The natural durability of wood species, defined as their inherent resistance to wood-destroying agents is a complex phenomenon depending of many biotic and abiotic factors. Besides the presence of recalcitrant polymers, the presence of compounds with antimicrobial properties is known to be important to explain wood durability. Based on the advancement in our understanding of fungal detoxification systems, a reverse chemical ecology approach was proposed to explore wood natural durability. A set of six glutathione transferases from the white-rot Trametes versicolor was used as targets to test wood extracts from seventeen French Guiana neotropical species. Fluorescent thermal shift assays allowed to quantify interactions between fungal glutathione transferases and these extracts. From these data, a model combining this approach and wood density predicts significantly wood natural durability of the tested species previously estimated by long-term soil bed tests. Overall, our findings confirm that detoxification systems could be used to explore the chemical environment encountered by wood decaying fungi and then wood natural durability.
MicroRNA and Gene Expression Analysis on Placenta Tissue: An Approach to Understanding Obstetric Antiphospholipid Syndrome at the Molecular Level
Authors: Mohamad Muhammad Aliff , Manzor Nur Fariha Mohd , Suhiman Muhammad Shazwan , Sathar Jameela , Rahman Hayati Abdul , Masri Maiza , Rahim Nur Syahrina Abdul , Hamid Nazefah Abdul , Mohamad Nor Nadeeya , Asnawi Asral Wirda Ahmad
Published: September 2019

Obstetric antiphospholipid syndrome is initiated by the action of antiphospholipid antibodies on placenta. The characteristics of APS in pregnancy include vascular thrombosis, inflammation and impairment of trophoblast implantation. MicroRNA (miRNA) expression has been suggested as one of the genetic factors that contribute to the development of this syndrome. miRNAs regulate gene expressions in a vast assortment of cellular biological mechanisms include the development of placental tissue. Hence, further investigation on the regulation of placental miRNA in APS is required. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesized signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation from the qPCR data while retinoblastoma gene (RET), dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.
Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy
Authors: Su Xuelian , Wang Jizeng , Bao Guangjie , Zhou Haijing , Liu Lin , Zheng Qian , Guo Manli , Zhang Jinting
Published: September 2019

Stem cell apoptosis exists widely in embryonic development, tissue regeneration, repair, aging and pathophysiology of disease. The molecular mechanism of stem cell apoptosis has been extensively investigated. However, alterations in biomechanics and nanomorphology have rarely been studied. Therefore, an apoptosis model was established for bone marrow mesenchymal stem cells (BMSCs) and the reconstruction of the mechanical properties and nanomorphology of the cells were investigated in detail. Atomic force microscopy (AFM), scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), flow cytometry and Cell Counting Kit-8 analysis were applied to assess the cellular elasticity modulus, geometry, nanomorphology, cell surface ultrastructure, biological viability and early apoptotic signal (phosphatidylserine, PS). The results indicated that the cellular elastic modulus and volume significantly decreased, whereas the cell surface roughness obviously increased during the first 3 h of cytochalasin B (CB) treatment. Moreover, these alterations preceded the exposure of biological apoptotic signal PS. These findings suggested that cellular mechanical damage is connected with the apoptosis of BMSCs, and the alterations in mechanics and nanomorphology may be a sensitive index to detect alterations in cell viability during apoptosis. The results contribute to a further understanding of the apoptosis from the perspective of cell mechanics.
Crystal structure of the N-terminal domain of the fibronectin-binding protein PavA fromStreptococcus pneumoniae
Authors: Manne Kartik , Narayana Sthanam V. L. , Chattopadhyay Debasish
Published: September 2019

The Gram-positive bacteriumStreptococcus pneumoniae, a major human pathogen, is a regular colonizer of the upper and lower respiratory tracts. Pneumococcal adherence and virulence factor A (PavA), a fibronectin-binding bacterial protein, fromS. pneumoniaeis an important facilitator of its colonization of host cells. In this study, the crystal structure of the N-terminal domain of PavA (SpPavA-N) determined at a resolution of 2.39 Å is reported. Each monomer of the dimeric protein consists of two domains (domains I and II) and a short α-helix (α6) at the C-terminus that are connected by elongated loops. Comparison of the SpPavA-N structure with that of its homolog fromStreptococcus suis(FBPS-N) revealed differences in α5, α6 and the domain II/α6 inter-loop region within domain II. The α5 helix of FBPS-N folds back toward domain I, whereas in SpPavA-N it adopts an elongated rod shape.