bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymptotic variational analysis of incompressible elastic strings
Authors: Engl Dominik , Kreisbeck Carolin
Published: September 2020

Starting from three-dimensional non-linear elasticity under the restriction of incompressibility, we derive reduced models to capture the behaviour of strings in response to external forces. Our Γ-convergence analysis of the constrained energy functionals in the limit of shrinking cross-sections gives rise to explicit one-dimensional limit energies. The latter depend on the scaling of the applied forces. The effect of local volume preservation is reflected either in their energy densities through a constrained minimization over the cross-section variables or in the class of admissible deformations. Interestingly, all scaling regimes allow for compression and/or stretching of the string. The main difficulty in the proof of the Γ-limit is to establish recovery sequences that accommodate the non-linear differential constraint imposed by the incompressibility. To this end, we modify classical constructions in the unconstrained case with the help of an inner perturbation argument tailored for 3d-1d dimension reduction problems.
Perceived stigma towards Alzheimer's disease and related dementia among Chinese older adults: do social networks matter?
Authors: Gao Xiang , Sun Fei , Prieto Lucas , Iyengar Vijeth
Published: September 2020

In mainland China, as the population ages, Alzheimer's disease and related dementia (ADRD) is estimated to increase among Chinese older adults. Chinese older adults tend to hold stigmatising beliefs about ADRD that in turn affect their help-seeking behaviour and receipt of prevention and treatment. The Framework Integrating Normative Influences on Stigma provides a rationale for Chinese older adult's stigma about ADRD. Questionnaires were administered in person to 754 older adults (42% male, mean age = 69.54 years) from two urban communities in mainland China. We examined ADRD stigma and the associations with real-life exposure, knowledge of ADRD, health conditions and social networks. This study found that Chinese older adults who had good family quality, lower depression (as measured by the Center for Epidemiological Studies Depression Scale) and better cognitive health (as measured by the Montreal Cognitive Assessment) were more likely to have lower perceived stigma. Conversely, those individuals who experienced neglect and had more ADRD knowledge exhibited higher levels of perceived stigma. Social networks moderated the associations between cognitive scores and perceived stigma. This research suggested that the quality of one's social networks is essential to reduce perceived stigma among Chinese older adults. Future research should continue to explore ADRD stigma among Chinese older adults to help guide relevant interventions, services and supports for this population.
Social network analysis of COVID-19 transmission in Karnataka, India
Authors: Saraswathi S. , Mukhopadhyay A. , Shah H. , Ranganath T. S.
Published: September 2020

We used social network analysis (SNA) to study the novel coronavirus (COVID-19) outbreak in Karnataka, India, and to assess the potential of SNA as a tool for outbreak monitoring and control. We analysed contact tracing data of 1147 COVID-19 positive cases (mean age 34.91 years, 61.99% aged 11–40, 742 males), anonymised and made public by the Karnataka government. Software tools, Cytoscape and Gephi, were used to create SNA graphics and determine network attributes of nodes (cases) and edges (directed links from source to target patients). Outdegree was 1–47 for 199 (17.35%) nodes, and betweenness, 0.5–87 for 89 (7.76%) nodes. Men had higher mean outdegree and women, higher mean betweenness. Delhi was the exogenous source of 17.44% cases. Bangalore city had the highest caseload in the state (229, 20%), but comparatively low cluster formation. Thirty-four (2.96%) ‘super-spreaders’ (outdegree ⩾ 5) caused 60% of the transmissions. Real-time social network visualisation can allow healthcare administrators to flag evolving hotspots and pinpoint key actors in transmission. Prioritising these areas and individuals for rigorous containment could help minimise resource outlay and potentially achieve a significant reduction in COVID-19 transmission.
Population growth rates in northern Cape VultureGyps coprotherescolonies between 2010 and 2019
Authors: HIRSCHAUER MARGARET T. , WOLTER KERRI , HOWARD ALEXANDRA , ROLEK BRIAN W. , MCCLURE CHRISTOPHER J. W.
Published: September 2020

The ‘Endangered’ Cape VultureGyps coprothereshas been monitored across its range for decades through disparate studies varying in geographical scope and length. Yet, no long-term, range-wide survey exists for the species. Coordinated monitoring across the range of the Cape Vulture would be logistically challenging but provide a holistic view of population dynamics in this long-lived species that forages across much of southern Africa. Here, we report breeding pair counts from seven colonies in the Cape Vulture’s north-eastern breeding region from 2010 to 2019. We used state-space models to assess population growth across time. Manutsa, Soutpansberg, and Nooitgedacht colonies increased significantly over the study period, with three other colonies having positive estimates of population growth, but 95% credible intervals overlapped zero. The smallest colony at Moletjie is declining toward extirpation; only one breeding pair remained in 2019. Our results suggest the north-eastern population has been stable or increasing since 2010 with our 2019 surveys counting 2,241 breeding pairs across all sites. Indeed, there is an 89% chance that the population across the colonies we monitored increased from 2010 to 2019. Coordinated, range-wide, full-cycle monitoring is needed to thoroughly assess conservation status and efficacy of conservation actions taken for this endangered species.
Comparison of growth and feeding method in infants with and without genetic abnormalities after neonatal cardiac surgery
Authors: Pierick Alyson R. , Pierick Trudy A. , Reinking Benjamin E.
Published: September 2020

Introduction:

Congenital heart disease (CHD) is multifactorial in origin, resulting from an interaction between environmental and genetic factors. Multifactorial growth delay is common in infants with CHD. The impact of a genetic abnormality and CHD on the growth of an infant is lacking in the literature. The aim of this study is to compare the growth and method of feeding following neonatal cardiac surgery in infants with normal versus abnormal genetic testing.

Methods:

A retrospective chart review of neonates who underwent a Risk Adjustment in Congenital Heart Surgery IV–VI procedure between 1 January, 2006 and 22 September, 2016 was performed at our institution. Weight, length, head circumference measurements, and feeding method were collected at birth, time of neonatal surgery, and monthly up to 6 months of age.

Results:

A total of 53 infants met inclusion criteria, of which 22 had abnormal genetic testing. Approximately 90% of infants were discharged following neonatal cardiac surgery with supplemental tube feeds. At each monthly follow-up visit, more infants were exclusively fed orally: 80% of infants with normal genetics at 5 months post-operative follow-up versus 60% of infants with abnormal genetic testing, although statistically insignificant. Growth was not different among the two groups.

Conclusions:

Infants with critical CHD with or without genetic abnormalities are at risk for growth delays and many need supplemental tube feeds post-operatively and throughout follow-up. Infants with genetic abnormalities are slower to achieve oral feeds and more likely to require tube feedings. It is important to have a systematic protocol for managing these high-risk infants.
A service evaluation of a group mindfulness-based intervention for distressing voices: how do findings from a randomized controlled trial compare with routine clinical practice?
Authors: Jones Anna-Marie , Strauss Clara , Hayward Mark
Published: September 2020

Background:

Person-based cognitive therapy (PBCT) was developed as a treatment for psychosis. The effectiveness of group PBCT was examined in the Mindfulness for Voices (M4V) randomized controlled trial and generated promising results. Group PBCT was implemented as a trans-diagnostic treatment for distressing voices within the Sussex Voices Clinic (SVC), a specialist secondary care mental health service.

Aim:

To conduct a service evaluation of engagement, outcomes and cost of group PBCT within SVC, and to compare engagement and outcomes from routine practice with the M4V trial. Secondary aims were to explore predictors of levels of engagement and change in group PBCT.

Method:

Service level data from 95 SVC patients were evaluated. Descriptive statistics, hypothesis tests and linear regression models were used. The primary clinical outcome was voice-related distress. Engagement levels and pre–post effect sizes were estimated; associated predictors were explored.

Results:

Fifty-nine per cent of patients completed group PBCT within SVC, compared with 72% within M4V. Completers within SVC had lower baseline depression scores compared with non-completers. There were significant improvements in voice-related distress (Cohen’s d = –0.47; p = 0.001), subjective recovery (Cohen’s d = 0.35; p = 0.001) and depression (Cohen’s d = –0.20; p = 0.044); these outcomes were comparable to M4V. Higher baseline subjective recovery and lower depression both predicted improvement in voice-related distress. Therapy within SVC cost an average of £214 per patient.

Conclusion:

PBCT groups can be delivered trans-diagnostically in routine clinical practice. Engagement was lower when compared with an RCT, but outcomes were comparable. The low level of resources involved suggests that group PBCT can offer value for money.
The Navy's Earth System Prediction Capability: A New Global Coupled Atmosphere‐Ocean‐Sea Ice Prediction System Designed for Daily to Subseasonal Forecasting
Authors: Barton Neil , Metzger E. Joseph , Reynolds Carolyn A. , Ruston Benjamin , Rowley Clark , Smedstad Ole Martin , Ridout James A. , Wallcraft Alan , Frolov Sergey , Hogan Patrick , Janiga Matthew A. , Shriver Jay F. , McLay Justin , Thoppil Prasad , Huang Andrew , Crawford William , Whitcomb Timothy , Bishop Craig H. , Zamudio Luis , Phelps Michael
Published: September 2020

This paper describes the new global Navy Earth System Prediction Capability (Navy‐ESPC) coupled atmosphere‐ocean‐sea ice prediction system developed at the Naval Research Laboratory (NRL) for operational forecasting for timescales of days to the subseasonal. Two configurations of the system are validated: (1) a low‐resolution 16‐member ensemble system and (2) a high‐resolution deterministic system. The Navy‐ESPC ensemble system became operational in August 2020, and this is the first time the NRL operational partner, Fleet Numerical Meteorology and Oceanography Center, will provide global coupled atmosphere‐ocean‐sea ice forecasts, with atmospheric forecasts extending past 16 days, and ocean and sea ice ensemble forecasts. A unique aspect of the Navy‐ESPC is that the global ocean model is eddy resolving at 1/12° in the ensemble and at 1/25° in the deterministic configurations. The component models are current Navy operational systems: NAVy Global Environmental Model (NAVGEM) for the atmosphere, HYbrid Coordinate Ocean Model (HYCOM) for the ocean, and Community Ice CodE (CICE) for the sea ice. Physics updates to improve the simulation of equatorial phenomena, particularly the Madden‐Julian Oscillation (MJO), were introduced into NAVGEM. The low‐resolution ensemble configuration and high‐resolution deterministic configuration are evaluated based on analyses and forecasts from January 2017 to January 2018. Navy‐ESPC ensemble forecast skill for large‐scale atmospheric phenomena, such as the MJO, North Atlantic Oscillation (NAO), Antarctic Oscillation (AAO), and other indices, is comparable to that of other numerical weather prediction (NWP) centers. Ensemble forecasts of ocean sea surface temperatures perform better than climatology in the tropics and midlatitudes out to 60 days. In addition, the Navy‐ESPC Pan‐Arctic and Pan‐Antarctic sea ice extent predictions perform better than climatology out to about 45 days, although the skill is dependent on season.
Critical Zone Science Comes of Age
Authors: Waldron Patricia
Published: September 2020

The developing field, which unites Earth scientists to examine the planet’s surface as a single, unified entity, is unraveling the complex, interconnected processes that support life on Earth.
Soil Signals Tell of Landscape Disturbances
Authors: Lohse Kathleen , Billings Sharon , DiBiase Roman , Kumar Praveen , Berhe Asmeret , Kaye Jason
Published: September 2020

The lasting influence humans have on Earth’s critical zone—and how geologic forces have mediated those influences—is revealed in studies of soil and carbon migration.
The miR-361-3p increases enzalutamide (Enz) sensitivity via targeting the ARv7 and MKNK2 to better suppress the Enz-resistant prostate cancer
Authors: Liu Bianjiang , Sun Yin , Tang Min , Liang Chao , Huang Chi-Ping , Niu Yuanjie , Wang Zengjun , Chang Chawnshang
Published: September 2020

The androgen receptor splicing variant 7 (ARv7) that lacks the ligand-binding domain is increasingly considered as a key player leading to enzalutamide (Enz) resistance in patients with prostate cancer (PCa). However, the detailed mechanisms of how ARv7 expression is regulated and whether it also needs other factors to induce maximal Enz resistance remain unclear. Here, we identified a microRNA, miR-361-3p, whose expression is lower in patients with recurrent PCa, could function via binding to the 3′UTR of ARv7, but not the wild type of AR, to suppress its expression to increase the Enz sensitivity. Importantly, we found that miR-361-3p could also bind to the 3′UTR of MAP kinase-interacting serine/threonine kinase 2 (MKNK2) to suppress its expression to further increase the Enz sensitivity. In turn, the increased Enz can then function via a feedback mechanism through altering the HIF-2α/VEGFA signaling to suppress the expression of miR-361-3p under hypoxia conditions. Preclinical studies using an in vivo mouse model with orthotopically xenografted CWR22Rv1 cells demonstrated that combining the Enz with the small molecule miR-361-3p would result in better suppression of the Enz-resistant PCa tumor progression. Together, these preclinical studies demonstrate that miR-361-3p can function via suppressing the expression of ARv7 and MKNK2 to maximally increase the Enz sensitivity, and targeting these newly identified Enz/miR-361-3p/ARv7 and/or Enz/miR-361-3p/MKNK2 signals with small molecules may help in the development of novel therapies to better suppress the CRPC in patients that already have developed the Enz resistance.
FZR1 as a novel biomarker for breast cancer neoadjuvant chemotherapy prediction
Authors: Liu Shuo , Wang Haobin , Li Jun , Zhang Jianhui , Wu Jian , Li Yi , Piao Yongjun , Pan Leiting , Xiang Rong , Yue Shijing
Published: September 2020

The concept of breast-conserving surgery is a remarkable achievement of breast cancer therapy. Neoadjuvant chemotherapy is being used increasingly to shrink the tumor prior to surgery. Neoadjuvant chemotherapy is reducing the tumor size to make the surgery with less damaging to surrounding tissue and downstage locally inoperable disease to operable. However, non-effective neoadjuvant chemotherapy could increase the risks of delaying surgery, develop unresectable disease and metastatic tumor spread. The biomarkers for predicting the neoadjuvant chemotherapy effect are scarce in breast cancer treatment. In this study, we identified that FZR1 can be a novel biomarker for breast cancer neoadjuvant chemotherapy according to clinical patient cohort evaluation and molecular mechanism investigation. Transcriptomic data analysis indicated that the expression of FZR1 is correlated with the effect of neoadjuvant chemotherapy. Mechanistically, we demonstrate that FZR1 is pivotal to the chemotherapy drugs induced apoptosis and cell cycle arrest. FZR1 is involved in the stability of p53 by impairing the phosphorylation at ser15 site. We demonstrate that the expression of FZR1 detected by quantification of IHC can be an effective predictor of neoadjuvant chemotherapy in animal experiment and clinical patient cohort. To obtain more benefit for breast cancer patient, we propose that the FZR1 IHC score using at the clinical to predict the effect of neoadjuvant chemotherapy.
PTPN14 aggravates inflammation through promoting proteasomal degradation of SOCS7 in acute liver failure
Authors: Fu Beibei , Yin Songna , Lin Xiaoyuan , Shi Lei , Wang Yu , Zhang Shanfu , Zhao Qingting , Li Zhifeng , Yang Yanling , Wu Haibo
Published: September 2020

Acute liver failure (ALF) is a rare but life-threatening systemic disorder. The innate immune regulation has an important role in this process; however, the specific mechanisms are not completely clear. Using the LPS + D-GalN-induced ALF mouse model, we found that the survival rate of PTPN14-deficient mice was higher than that of the control group, while the release of inflammatory factors was significantly lower. We further showed that PTPN14 interacted with SOCS7, and promoted the degradation of SOCS7 through ubiquitination at K11 and K48, thereby reducing the protein level of SOCS7 and weakening the inhibitory effects on inflammatory factors. More importantly, SOCS7 blocked the NF-κB signaling pathway by preventing the activity of the IKK complex, and then reduced the expression of downstream inflammatory factors. In this study, we firstly reported the inhibitory effect of SOCS7 on the NF-κB pathway in the ALF mouse model and elucidated the mechanism of PTPN14–SOCS7–NF-κB axis in the regulation of inflammation. These results provide new insights into the clinical treatment of ALF.
Recipe for ultrafast and persistent phase-change memory materials
Authors: Ding Keyuan , Chen Bin , Chen Yimin , Wang Junqiang , Shen Xiang , Rao Feng
Published: September 2020

The contradictory nature of increasing the crystallization speed while extending the amorphous stability for phase-change materials (PCMs) has long been the bottleneck in pursuing ultrafast yet persistent phase-change random-access memory. Scandium antimony telluride alloy (ScxSb2Te3) represents a feasible route to resolve this issue, as it allows a subnanosecond SET speed but years of reliable retention of the RESET state. To achieve the best device performances, the optimal composition and its underlying working mechanism need to be unraveled. Here, by tuning the doping dose of Sc, we demonstrate that Sc0.3Sb2Te3 has the fastest crystallization speed and fairly improved data nonvolatility. The simultaneous improvement in such ‘conflicting’ features stems from reconciling two dynamics factors. First, promoting heterogeneous nucleation at elevated temperatures requires a higher Sc dose to stabilize more precursors, which also helps suppress atomic diffusion near ambient temperatures to ensure a rather stable amorphous phase. Second, however, enlarging the kinetic contrast through a fragile-to-strong crossover in the supercooled liquid regime should require a moderate Sc content; otherwise, the atomic mobility for crystal growth at elevated temperatures will be considerably suppressed. Our work thus reveals the recipe by tailoring the crystallization kinetics to design superior PCMs for the development of high-performance phase-change working memory technology.
Arthrogryposis multiplex congenita with polymicrogyria and infantile encephalopathy caused by a novel GRIN1 variant
Authors: Nishimura Naoto , Kumaki Tatsuro , Murakami Hiroaki , Enomoto Yumi , Katsumata Kaoru , Toyoshima Katsuaki , Kurosawa Kenji
Published: September 2020

Variants of GRIN1, which encodes GluN1, are associated with developmental delay, epilepsy, and cortical malformation. Here, we report a case of arthrogryposis multiplex congenita with polymicrogyria and infantile encephalopathy caused by a heterozygous variant, c.1949A>C, p.(Asn650Thr) of GRIN1, which could result in the disruption of the third transmembrane domain (M3) of GluN1. This case expands our understanding of the known phenotypes of GRIN1-related neurodevelopmental disorders.
DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe
Authors: Liu Qi , He Qing-tao , Lyu Xiaoxuan , Yang Fan , Zhu Zhong-liang , Xiao Peng , Yang Zhao , Zhang Feng , Yang Zhao-ya , Wang Xiao-yan , Sun Peng , Wang Qian-wen , Qu Chang-xiu , Gong Zheng , Lin Jing-yu , Xu Zhen , Song Shao-le , Huang Shen-ming , Guo Sheng-chao , Han Ming-jie , Zhu Kong-kai , Chen Xin , Kahsai Alem W. , Xiao Kun-Hong , Kong Wei , Li Fa-hui , Ruan Ke , Li Zi-jian , Yu Xiao , Niu Xiao-gang , Jin Chang-wen , Wang Jiangyun , Sun Jin-peng
Published: September 2020

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group. The unique up-field 1H-NMR chemical shift and the highly efficient incorporation of TMSiPhe enabled the characterization of multiple conformational states of a phospho-β2 adrenergic receptor/β-arrestin-1(β-arr1) membrane protein signaling complex, using only 5 μM protein and 20 min of spectrum accumulation time. We further showed that extracellular ligands induced conformational changes located in the polar core or ERK interaction site of β-arr1 via direct receptor transmembrane core interactions. These observations provided direct delineation and key mechanism insights that multiple receptor ligands were able to induce distinct functionally relevant conformational changes of arrestin.
Superconductivity mediated by polar modes in ferroelectric metals
Authors: Enderlein C. , de Oliveira J. Ferreira , Tompsett D. A. , Saitovitch E. Baggio , Saxena S. S. , Lonzarich G. G. , Rowley S. E.
Published: September 2020

The occurrence of superconductivity in doped SrTiO3 at low carrier densities points to the presence of an unusually strong pairing interaction that has eluded understanding for several decades. We report experimental results showing the pressure dependence of the superconducting transition temperature, Tc, near to optimal doping that sheds light on the nature of this interaction. We find that Tc increases dramatically when the energy gap of the ferroelectric critical modes is suppressed, i.e., as the ferroelectric quantum critical point is approached in a way reminiscent to behaviour observed in magnetic counterparts. However, in contrast to the latter, the coupling of the carriers to the critical modes in ferroelectrics is predicted to be small. We present a quantitative model involving the dynamical screening of the Coulomb interaction and show that an enhancement of Tc near to a ferroelectric quantum critical point can arise due to the virtual exchange of longitudinal hybrid-polar-modes, even in the absence of a strong coupling to the transverse critical modes.
Plasmonic antenna coupling to hyperbolic phonon-polaritons for sensitive and fast mid-infrared photodetection with graphene
Authors: Castilla Sebastián , Vangelidis Ioannis , Pusapati Varun-Varma , Goldstein Jordan , Autore Marta , Slipchenko Tetiana , Rajendran Khannan , Kim Seyoon , Watanabe Kenji , Taniguchi Takashi , Martín-Moreno Luis , Englund Dirk , Tielrooij Klaas-Jan , Hillenbrand Rainer , Lidorikis Elefterios , Koppens Frank H. L.
Published: September 2020

Integrating and manipulating the nano-optoelectronic properties of Van der Waals heterostructures can enable unprecedented platforms for photodetection and sensing. The main challenge of infrared photodetectors is to funnel the light into a small nanoscale active area and efficiently convert it into an electrical signal. Here, we overcome all of those challenges in one device, by efficient coupling of a plasmonic antenna to hyperbolic phonon-polaritons in hexagonal-BN to highly concentrate mid-infrared light into a graphene pn-junction. We balance the interplay of the absorption, electrical and thermal conductivity of graphene via the device geometry. This approach yields remarkable device performance featuring room temperature high sensitivity (NEP of 82 pW$$/\sqrt{{\bf{Hz}}}$$
/

Hz

) and fast rise time of 17 nanoseconds (setup-limited), among others, hence achieving a combination currently not present in the state-of-the-art graphene and commercial mid-infrared detectors. We also develop a multiphysics model that shows very good quantitative agreement with our experimental results and reveals the different contributions to our photoresponse, thus paving the way for further improvement of these types of photodetectors even beyond mid-infrared range.
Lead halide perovskite vortex microlasers
Authors: Sun Wenzhao , Liu Yilin , Qu Geyang , Fan Yubin , Dai Wei , Wang Yuhan , Song Qinghai , Han Jiecai , Xiao Shumin
Published: September 2020

Lead halide perovskite microlasers have been very promising for versatile optoelectronic applications. However, most perovskite microlasers are linearly polarized with uniform wavefront. The structured laser beams carrying orbital angular momentum have rarely been studied and the applications of perovskites in next-generation optical communications are thus hindered. Herein, we experimentally demonstrate the perovskite vortex microlasers with highly directional outputs and well−controlled topological charges. High quality gratings have been experimentally fabricated in perovskite film and the subsequent vertical cavity surface emitting lasers (VCSELs) with divergent angles of 3o are achieved. With the control of Archimedean spiral gratings, the wavefront of the perovskite VCSELs has been switched to be helical with topological charges of q = −4 to 4. This research is able to expand the potential applications of perovskite microlasers in hybrid integrated photonic networks, as well as optical computing.
Mycobacterium tuberculosis progresses through two phases of latent infection in humans
Authors: Colangeli Roberto , Gupta Aditi , Vinhas Solange Alves , Chippada Venkata Uma Deepthi , Kim Soyeon , Grady Courtney , Jones-López Edward C. , Soteropoulos Patricia , Palaci Moisés , Marques-Rodrigues Patrícia , Salgame Padmini , Ellner Jerrold J. , Dietze Reynaldo , Alland David
Published: September 2020

Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.
Uncharted waters: the unintended impacts of residual chlorine on water quality and biofilms
Authors: Fish Katherine E. , Reeves-McLaren Nik , Husband Stewart , Boxall Joby
Published: September 2020

Disinfection residuals in drinking water protect water quality and public heath by limiting planktonic microbial regrowth during distribution. However, we do not consider the consequences and selective pressures of such residuals on the ubiquitous biofilms that persist on the vast internal surface area of drinking water distribution systems. Using a full scale experimental facility, integrated analyses were applied to determine the physical, chemical and biological impacts of different free chlorine regimes on biofilm characteristics (composition, structure and microbiome) and water quality. Unexpectedly, higher free chlorine concentrations resulted in greater water quality degredation, observable as elevated inorganic loading and greater discolouration (a major cause of water quality complaints and a mask for other failures). High-chlorine concentrations also reduced biofilm cell concentrations but selected for a distinct biofilm bacterial community and inorganic composition, presenting unique risks. The results challenge the assumption that a measurable free chlorine residual necessarily assures drinking water safety.
Clinical utility of genomic signatures in young breast cancer patients: a systematic review
Authors: Villarreal-Garza Cynthia , Ferrigno Ana S. , De la Garza-Ramos Cynthia , Barragan-Carrillo Regina , Lambertini Matteo , Azim Hatem A.
Published: September 2020

Risk stratification by genomic signatures has been shown to improve prognostication and guide treatment decisions among patients with hormone-sensitive breast cancer. However, their role in young women has not been fully elucidated. In this review, a systematic search was conducted for published articles and abstracts from major congresses that evaluated the use of genomic signatures in young breast cancer patients. A total of 71 studies were analyzed, including 561,188 patients of whom 27,748 (4.9%) were young. Women aged ≤40 years were subjected to genomic testing at a similar rate to older women but had a higher proportion of intermediate- to high-risk tumors when classified by EndoPredict (p = 0.04), MammaPrint (p < 0.01), and Oncotype DX (p < 0.01). In young women with low genomic risk, 6-year distant recurrence-free survival was 94%, while 5-year overall survival was nearly 100%. Nonetheless, young patients classified as low-risk had a higher tendency to receive chemotherapy compared to their older counterparts. In conclusion, genomic tests are useful tools for identifying young patients in whom chemotherapy omission is appropriate.
Current vortices and magnetic fields driven by moving polar twin boundaries in ferroelastic materials
Authors: Lu Guangming , Li Suzhi , Ding Xiangdong , Sun Jun , Salje Ekhard K. H.
Published: September 2020

Ferroelastic twin boundaries often have properties that do not exist in bulk, such as superconductivity, polarity etc. Designing and optimizing domain walls can hence functionalize ferroelastic materials. Using atomistic simulations, we report that moving domain walls have magnetic properties even when there is no magnetic element in the material. The origin of a robust magnetic signal lies in polar vortex structures induced by moving domain walls, e.g., near the tips of needle domains and near domain wall kinks. These vortices generate displacement currents, which are the origin of magnetic moments perpendicular to the vortex plane. This phenomenon is universal for ionic crystals and holds for all ferroelastic domain boundaries containing dipolar moments. The magnetic moment depends on the speed of the domain boundary, which can reach the speed of sound under strong mechanical forcing. We estimate that the magnetic moment can reach several tens of Bohr magnetons for a collective thin film of 1000 lattice planes and movements of the vortex by the speed of sound. The predicted magnetic fields in thin slabs are much larger than those observed experimentally in SrTiO3/LaAlO3 heterostructures, which may be due to weak (accidental) forcing and slow changes of the domain patterns during their experiments. The dynamical multiferroic properties of ferroelastic domain walls may have the potential to be used to construct localized magnetic memory devices in future.
Unfolding quantum computer readout noise
Authors: Nachman Benjamin , Urbanek Miroslav , de Jong Wibe A. , Bauer Christian W.
Published: September 2020

In the current era of noisy intermediate-scale quantum computers, noisy qubits can result in biased results for early quantum algorithm applications. This is a significant challenge for interpreting results from quantum computer simulations for quantum chemistry, nuclear physics, high energy physics (HEP), and other emerging scientific applications. An important class of qubit errors are readout errors. The most basic method to correct readout errors is matrix inversion, using a response matrix built from simple operations to probe the rate of transitions from known initial quantum states to readout outcomes. One challenge with inverting matrices with large off-diagonal components is that the results are sensitive to statistical fluctuations. This challenge is familiar to HEP, where prior-independent regularized matrix inversion techniques (“unfolding”) have been developed for years to correct for acceptance and detector effects, when performing differential cross section measurements. We study one such method, known as iterative Bayesian unfolding, as a potential tool for correcting readout errors from universal gate-based quantum computers. This method is shown to avoid pathologies from commonly used matrix inversion and least squares methods.
Causal association between mTOR-dependent EIF-4E and EIF-4A circulating protein levels and type 2 diabetes: a Mendelian randomization study
Authors: Soliman Ghada A. , Schooling C. Mary
Published: September 2020

The mammalian Target of Rapamycin complex 1 (mTORC1) nutrient-sensing pathway is a central regulator of cell growth and metabolism and is dysregulated in diabetes. The eukaryotic translation initiation factor 4E (EIF-4E) protein, a key regulator of gene translation and protein function, is controlled by mTORC1 and EIF-4E Binding Proteins (EIF4EBPs). Both EIF4EBPs and ribosomal protein S6K kinase (RP-S6K) are downstream effectors regulated by mTORC1 but converge to regulate two independent pathways. We investigated whether the risk of type 2 diabetes varied with genetically predicted EIF-4E, EIF-4A, EIF-4G, EIF4EBP, and RP-S6K circulating levels using Mendelian Randomization. We estimated the causal role of EIF-4F complex, EIF4EBP, and S6K in the circulation on type 2 diabetes, based on independent single nucleotide polymorphisms strongly associated (p = 5 × 10–6) with EIF-4E (16 SNPs), EIF-4A (11 SNPs), EIF-4G (6 SNPs), EIF4EBP2 (12 SNPs), and RP-S6K (16 SNPs). The exposure data were obtained from the INTERVAL study. We applied these SNPs for each exposure to publically available genetic associations with diabetes from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) case (n = 26,676) and control (n = 132,532) study (mean age 57.4 years). We meta-analyzed SNP-specific Wald-estimates using inverse variance weighting with multiplicative random effects and conducted sensitivity analysis. Mendelian Randomization (MR-Base) R package was used in the analysis. The PhenoScanner curated database was used to identify disease associations with SNP gene variants. EIF-4E is associated with a lowered risk of type 2 diabetes with an odds ratio (OR) 0.94, 95% confidence interval (0.88, 0.99, p = 0.03) with similar estimates from the weighted median and MR-Egger. Similarly, EIF-4A was associated with lower risk of type 2 diabetes with odds ratio (OR) 0.90, 95% confidence interval (0.85, 0.97, p = 0.0003). Sensitivity analysis using MR-Egger and weighed median analysis does not indicate that there is a pleiotropic effect. This unbiased Mendelian Randomization estimate is consistent with a protective causal association of EIF-4E and EIF-4A on type 2 diabetes. EIF-4E and EIF-4A may be targeted for intervention by repurposing existing therapeutics to reduce the risk of type 2 diabetes.
A data-driven medication score predicts 10-year mortality among aging adults
Authors: Häppölä Paavo , Havulinna Aki S. , Tasa Tõnis , Mars Nina J. , Perola Markus , Kallela Mikko , Milani Lili , Koskinen Seppo , Salomaa Veikko , Neale Benjamin M. , Palotie Aarno , Daly Mark , Ripatti Samuli
Published: September 2020

Health differences among the elderly and the role of medical treatments are topical issues in aging societies. We demonstrate the use of modern statistical learning methods to develop a data-driven health measure based on 21 years of pharmacy purchase and mortality data of 12,047 aging individuals. The resulting score was validated with 33,616 individuals from two fully independent datasets and it is strongly associated with all-cause mortality (HR 1.18 per point increase in score; 95% CI 1.14–1.22; p = 2.25e−16). When combined with Charlson comorbidity index, individuals with elevated medication score and comorbidity index had over six times higher risk (HR 6.30; 95% CI 3.84–10.3; AUC = 0.802) compared to individuals with a protective score profile. Alone, the medication score performs similarly to the Charlson comorbidity index and is associated with polygenic risk for coronary heart disease and type 2 diabetes.
Heterogeneous ozone effects on the DNA methylome of bronchial cells observed in a crossover study
Authors: Bind M.-A. C. , Rubin D. B. , Cardenas A. , Dhingra R. , Ward-Caviness C. , Liu Z. , Mirowsky J. , Schwartz J. D. , Diaz-Sanchez D. , Devlin R. B.
Published: September 2020

We used a randomized crossover experiment to estimate the effects of ozone (vs. clean air) exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours. Twenty-four hours after exposure, participants underwent bronchoscopy to collect epithelial cells whose DNA methylation was measured using the Illumina 450 K platform. We performed global and regional tests examining the ozone versus clean air effect on the DNA methylome and calculated Fisher-exactp-values for a series of univariate tests. We found little evidence of an overall effect of ozone on the DNA methylome but some suggestive changes inPLSCR1,HCAR1, andLINC00336DNA methylation after ozone exposure relative to clean air. We observed some participant-to-participant heterogeneity in ozone responses.
Dynamics of localised nitrogen supply and relevance for root growth of Vicia faba (‘Fuego’) and Hordeum vulgare (‘Marthe’) in soil
Authors: Blaser Sebastian R. G. A. , Koebernick Nicolai , Spott Oliver , Thiel Enrico , Vetterlein Doris
Published: September 2020

Root growth responds to local differences in N-form and concentration. This is known for artificial systems and assumed to be valid in soil. The purpose of this study is to challenge this assumption for soil mesocosms locally supplied with urea with and without nitrification inhibitor. Soil column experiments withVicia faba(‘Fuego’) andHordeum vulgare(‘Marthe’) were performed to investigate soil solution chemistry and root growth response of these two species with contrasting root architectures to the different N-supply simultaneously. Root growth was analysed over time and separately for the fertiliser layer and the areas above and below with X-ray CT (via region growing) and WinRHIZO. Additionally, NO3−and NH4+in soil and soil solution were analysed. InVicia faba, no pronounced differences were observed, although CT analysis indicated different root soil exploration for high NH4+. InHordeum vulgare, high NO3−inhibited lateral root growth while high NH4+stimulated the formation of first order laterals. The growth response to locally distributed N-forms in soil is species specific and less pronounced than in artificial systems. The combination of soil solution studies and non-invasive imaging of root growth can substantially improve the mechanistic understanding of root responses to different N-forms in soil.
Bioenergetic effects of hydrogen sulfide suppress soluble Flt-1 and soluble endoglin in cystathionine gamma-lyase compromised endothelial cells
Authors: Sanchez-Aranguren Lissette Carolina , Ahmad Shakil , Dias Irundika H. K. , Alzahrani Faisal A. , Rezai Homira , Wang Keqing , Ahmed Asif
Published: September 2020

Endothelial dysfunction is a hallmark of preeclampsia, a life-threatening complication of pregnancy characterised by hypertension and elevated soluble Fms-Like Tyrosine Kinase-1 (sFlt-1). Dysregulation of hydrogen sulfide (H2S) by inhibition of cystathionine γ-lyase (CSE) increases sFlt-1 and soluble endoglin (sEng) release. We explored whether compromise in CSE/H2S pathway is linked to dysregulation of the mitochondrial bioenergetics and oxidative status. We investigated whether these effects were linked to CSE-induced sFlt-1 and sEng production in endothelial cells. Here, we demonstrate that CSE/H2S pathway sustain endothelial mitochondrial bioenergetics and loss of CSE increases the production of mitochondrial-specific superoxide. As a compensatory effect, low CSE environment enhances the reliance on glycolysis. The mitochondrial-targeted H2S donor, AP39, suppressed the antiangiogenic response and restored the mitochondrial bioenergetics in endothelial cells. AP39 revealed that upregulation of sFlt-1, but not sEng, is independent of the mitochondrial H2S metabolising enzyme, SQR. These data provide new insights into the molecular mechanisms for antiangiogenic upregulation in a mitochondrial-driven environment. Targeting H2S to the mitochondria may be of therapeutic benefit in the prevention of endothelial dysfunction associated with preeclampsia.
Environmentally friendly quantum-dot color filters for ultra-high-definition liquid crystal displays
Authors: Ko Yun-Hyuk , Prabhakaran Prem , Choi Sinil , Kim Gyeong-Ju , Lee Changhee , Lee Kwang-Sup
Published: September 2020

This work reports the synthesis and application of highly tuned cadmium-free green and red InPZnSe1−xSx/ZnS quantum dots (QDs) in QD enhanced liquid crystal displays (LCD). The emissions of the quantum dots were synthetically tuned to sharp emissions at low full-width at half maximum. The QDs were incorporated in LCD devices as quantum dot enhancement film (QDEF) or as a quantum dot incorporated color filter (QDCF). Synthetic tuning of the gradient inter-shell in the QDs leads to reduced full width at half-maximum, resulting in sharp green and red emissions from both types of devices. The application of the same QDs to devices using these different integration techniques shows the superiority of QDCF devices over QDEF ones. The RGB color gamut of a QDCF-LCD was 81.4% of REC.2020 in the CIE 1931 color space compared to 71.2% obtained for a QDEF-LCD display. The improved performance of QDCF was mainly due to the optimal interactions between the green QDs and the green color filter. The superior performance of cadmium-free InPZnSe1−xSx/ZnS QDCFs in LCDs make them well-suited for ultra-high-definition TV formats.
Effects of phylogenetic uncertainty on fossil identification illustrated by a new and enigmatic Eocene iguanian
Authors: Scarpetta Simon G.
Published: September 2020

Fossil identifications made in a phylogenetic framework are beholden to specific tree hypotheses. Without phylogenetic consensus, the systematic provenance of any given fossil can be volatile. Paleobiogeographic and divergence time hypotheses are contingent on the accurate systematic placement of fossils. Thus, fossil diagnoses should consider multiple topologies when phylogenetic resolution or clear apomorphies are lacking. However, such analyses are infrequently performed. Pleurodonta (Squamata: Iguania) is an ancient and frequently-studied lizard clade for which phylogenetic resolution is notoriously elusive. I describe a skull fossil of a new pleurodontan lizard taxon from the Eocene deposits of the Willwood Formation, Wyoming, and use the new taxon as a case-study to explore the effects of phylogenetic uncertainty on fossil identification. The relationships of the new taxon differ considerably among analyses, and resulting interpretations are correspondingly disparate. These results illustrate generalizable and severe issues with fossil interpretations made without consideration of alternative phylogenetic hypotheses.
Mining data from legacy taxonomic literature and application for sampling spiders of the Teutamus group (Araneae; Liocranidae) in Southeast Asia
Authors: Rivera-Quiroz F. Andres , Petcharad Booppa , Miller Jeremy A.
Published: September 2020

Taxonomic literature contains information about virtually ever known species on Earth. In many cases, all that is known about a taxon is contained in this kind of literature, particularly for the most diverse and understudied groups. Taxonomic publications in the aggregate have documented a vast amount of specimen data. Among other things, these data constitute evidence of the existence of a particular taxon within a spatial and temporal context. When knowledge about a particular taxonomic group is rudimentary, investigators motivated to contribute new knowledge can use legacy records to guide them in their search for new specimens in the field. However, these legacy data are in the form of unstructured text, making it difficult to extract and analyze without a human interpreter. Here, we used a combination of semi-automatic tools to extract and categorize specimen data from taxonomic literature of one family of ground spiders (Liocranidae). We tested the application of these data on fieldwork optimization, using the relative abundance of adult specimens reported in literature as a proxy to find the best times and places for collecting the species (Teutamus politus) and its relatives (Teutamus group, TG) within Southeast Asia. Based on these analyses we decided to collect in three provinces in Thailand during the months of June and August. With our approach, we were able to collect more specimens of T. politus (188 specimens, 95 adults) than all the previous records in literature combined (102 specimens). Our approach was also effective for sampling other representatives of the TG, yielding at least one representative of every TG genus previously reported for Thailand. In total, our samples contributed 231 specimens (134 adults) to the 351 specimens previously reported in the literature for this country. Our results exemplify one application of mined literature data that allows investigators to more efficiently allocate effort and resources for the study of neglected, endangered, or interesting taxa and geographic areas. Furthermore, the integrative workflow demonstrated here shares specimen data with global online resources like Plazi and GBIF, meaning that others can freely reuse these data and contribute to them in the future. The contributions of the present study represent an increase of more than 35% on the taxonomic coverage of the TG in GBIF based on the number of species. Also, our extracted data represents 72% of the occurrences now available through GBIF for the TG and more than 85% of occurrences of T. politus. Taxonomic literature is a key source of undigitized biodiversity data for taxonomic groups that are underrepresented in the current biodiversity data sphere. Mobilizing these data is key to understanding and protecting some of the less well-known domains of biodiversity.
Multi-pulse laser-induced bubble formation and nanoparticle aggregation using MoS2 nanoparticles
Authors: Ko Brian , Lu Weigang , Sokolov Alexei V. , Lee Ho Wai Howard , Scully Marlan O. , Zhang Zhenrong
Published: September 2020

Understanding of how particles and light interact in a liquid environment is vital for optical and biological applications. MoS2 has been shown to enhance nonlinear optical phenomena due to the presence of a direct excitonic resonance. Its use in biological applications is predicated on knowledge of how MoS2 interacts with ultrafast (< 1 ps) pulses. In this experiment, the interaction between two femtosecond pulses and MoS2 nanoparticles suspended in liquid is studied. We found that the laser pulses induce bubble formation on the surface of a nanoparticle and a nanoparticle aggregate then forms on the surface of the trapped bubble. The processes of formation of the bubble and the nanoparticle aggregation are intertwined.