bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent Tuberculosis and HIV Infection
Authors: Bares Sara H. , Swindells Susan
Published: June 2020

Purpose of Review

Tuberculosis is the number one infectious killer of people with HIV worldwide, but it can be both prevented and treated. Prevention of tuberculosis by screening for and treating latent tuberculosis infection (LTBI), along with the initiation of antiretroviral therapy (ART), is the key component of HIV care.

Recent Findings

While access to ART has increased worldwide, uptake and completion of LTBI treatment regimens among people living with HIV (PWH) are very poor. Concomitant TB-preventive therapy and ART are complex because of drug–drug interactions, but these can be managed. Recent clinical trials of shorter preventive regimens have demonstrated safety and efficacy in PWH with higher completion rates. More research is needed to guide TB-preventive therapy in children and in pregnant women, and for drug-resistant TB (DR-TB).

Antiretroviral therapy and tuberculosis-preventive treatment regimens can be optimized to avoid drug–drug interactions, decrease pill burden and duration, and minimize side effects in order to increase adherence and treatment completion rates among PWH and LTBI.
High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms
Authors: Motylewska Ewelina , Braun Marcin , Stępień Henryk
Published: June 2020

Dysregulations of the NEK2 and PIM1-3 kinase signaling axes have been implicated in the pathogenesis of several cancers, including those with a neuroendocrine phenotype. However, their impact on bronchopulmonary neuroendocrine neoplasms (BP-NENs) has not been investigated. The aim of this pilot study was to determine mRNA and protein levels of NEK2, PIM1, and PIM3 in a group of 49 patients with BP-NENs: 11 typical carcinoids, 5 atypical carcinoids, 11 large cell neuroendocrine carcinomas, 22 small cell lung carcinomas (SCLC). The expression was measured using TaqMan-based RT-PCR and immunohistochemistry. NEK2 and PIM1 mRNA levels were higher in the SCLC patients than in the other BP-NEN groups (p < 0.001). There was an association between NEK2 mRNA and protein expression (p = 0.023) and elevated NEK2 mRNA levels were related to reduced survival in BP-NEN patients (p = 0.015). Patients with higher PIM1 protein expression had also diminished survival comparing with those with weak or no PIM1 expression (p = 0.037). Elevated NEK2 and PIM1 expression were related to aggressive tumor phenotype and indirectly affected the overall survival of BP-NEN patients. Our pilot study supports the need for future investigation of the biological function of NEK2 and PIM1 in BP-NEN transformation to verify the clinical value of our findings.
The nature, type, and origin of diagenetic fluids and their control on the evolving porosity of the Lower Cambrian Xiaoerbulak Formation dolostone, northwestern Tarim Basin, China
Authors: Liu Pei-Xian , Deng Shi-Biao , Guan Ping , Jin Yi-Qiu , Wang Kai , Chen Yong-Quan
Published: June 2020

The study on Lower Cambrian dolostones in Tarim Basin can improve our understanding of ancient and deeply buried carbonate reservoirs. In this research, diagenetic fluid characteristics and their control on porosity evolution have been revealed by studying the petrography and in situ geochemistry of different dolomites. Three types of diagenetic fluids were identified: (1) Replacive dolomites were deviated from shallow burial dolomitizing fluids, which might probably be concentrated ancient seawater at early stage. (2) Fine-to-medium crystalline, planar-e diamond pore-filling dolomites (Fd1) were likely slowly and sufficiently crystallized from deep-circulating crustal hydrothermal fluids during Devonian. (3) Coarse crystalline, non-planar-a saddle pore-filling dolomites (Fd2) might rapidly and insufficiently crystallize from magmatic hydrothermal fluids during Permian. Early dolomitizing fluids did not increase the porosity, but transformed the primary pores to dissolution pores through dolomitization. Deep-circulating crustal hydrothermal fluids significantly increased porosity in the early stages by dissolving and then slightly decreased the porosity in the late stage due to Fd1 precipitation. Magmatic hydrothermal fluids only precipitated the Fd2 dolomites and slightly decreased the porosity. In summary, Devonian deep-circulating crustal hydrothermal fluids dominated the porosity evolution of the Lower Cambrian dolostone reservoir in the Tarim Basin.
Infective endocarditis in the Netherlands: current epidemiological profile and mortality
Authors: El Kadi S. , van den Buijs D. M. F. , Meijers T. , Gilbers M. D. , Bekkers S. C. A. M. , van Melle J. P. , Riezebos R. K. , Blok W. L. , Tanis W. , Wahadat A. R. , Roos-Hesselink J. W. , van der Spoel T. I. G. , Chamuleau S. A. J. , Kamp O. ,   EURO ENDO Investigators group
Published: June 2020

Introduction

Infective endocarditis (IE) is associated with a high in-hospital and long term mortality. Although progress has been made in diagnostic approach and management of IE, morbidity and mortality of IE remain high. In the latest European guidelines, the importance of the multi-modality imaging in diagnosis and follow up of IE is emphasized.

Aim

The aim was to provide information regarding mortality and adverse events of IE, to determine IE characteristics and to assess current use of imaging in the diagnostic workup of IE.

Methods

This is a prospective observational cohort study. We used data from the EURO-ENDO registry. Seven hospitals in the Netherlands have participated and included patients with IE between April 2016 and April 2018.

Results

A total of 139 IE patients were included. Prosthetic valve endocarditis constituted 32.4% of the cases, cardiac device related IE 7.2% and aortic root prosthesis IE 3.6%. In-hospital mortality was 14.4% (20 patients) and one-year mortality was 21.6% (30 patients). The incidence of embolic events under treatment was 16.5%, while congestive heart failure or cardiogenic shock occurred in 15.1% of the patients. Transthoracic and transoesophageal echocardiography were performed most frequently (97.8%; 81.3%) and within 3 days after IE suspicion, followed by 18F‑fluorodeoxyglucose positron emission tomography/computed tomography (45.3%) within 6 days and multi-slice computed tomography (42.4%) within 7 days.

Conclusion

We observed a high percentage of prosthetic valve endocarditis, rapid and extensive use of imaging and a relatively low in-hospital and one-year mortality of IE in the Netherlands. Limitations include possible selection bias.
Detection of Leptospirosis Bacteria in Rodent Urine by Surface Plasmon Resonance Sensor Using Graphene
Authors: Raikwar Surjeet , Prajapati Y. K. , Srivastava D. K. , Maurya J. B. , Saini J. P.
Published: June 2020

In this paper, a graphene-coated surface plasmon resonance sensor is designed for the examination of Rodent urine which is responsible for Leptospirosis bacteria. Rodent urine is considered as sensing medium. Graphene surface is activated by phosphate-buffered saline solution for better attachment of Leptospirosis bacteria on its surface. Oliguria and Polyuria are the Rodent urine with high and low concentrations of Leptospirosis bacteria, respectively. The transfer matrix method is used for the formulation of reflection intensity of p-polarized light. The reflectance curves for angular interrogation are plotted and the results are obtained in terms of sensitivity, detection accuracy, and quality factor. The significantly high sensitivity and detection accuracy for Oliguria distinguishes it from Polyuria having lower sensitivity.
Preliminary 3D printing of large inclined-shaped alumina ceramic parts by direct ink writing
Authors: Yang Liangliang , Zeng Xiaojun , Ditta Allah , Feng Bo , Su Lizhong , Zhang Yue
Published: June 2020

Three dimensional (3D) printing technology by direct ink writing (DIW) is an innovative complex shaping technology, possessing advantages of flexibility in fabrication, high efficiency, low cost, and environmental-friendliness. Herein, 3D printing of complex alumina ceramic parts via DIW using thermally induced solidification with carrageenan swelling was investigated. The rheological properties of the slurry under different thermally-induced modes were systematically studied. The solidification properties of thermally-induced pastes with varying contents of carrageenan were optimized. The experimental results showed that the optimized paste consisting of 0.4 wt% carrageenan could be rapidly solidified at about 55 °C, which could print inclined-plane more than 60° in vertical without support, resulting in better homogeneity of the green body. A nearly pore-free structure was obtained after sintering at 1600 °C for 2 h.
LACE index predicts age-specific unplanned readmissions and mortality after hospital discharge
Authors: Heppleston Erica , Fry Christopher H. , Kelly Kevin , Shepherd Beth , Wright Ria , Jones Gareth , Robin Jonathan , Murray Paul , Fluck David , Han Thang S.
Published: June 2020

Background

The LACE index scoring tool (Length of stay, Acuity of admission, Co-morbidities and Emergency department visits) has been designed to predict hospital readmissions. We evaluated the ability of the LACE index to predict age-specific frequent admissions and mortality.

Methods

Analysis of prospectively collected data of alive-discharge episodes between 01/04/2017 and 31/03/2019 in an NHS hospital. Data on 14,878 men and 17,392 women of mean age 64.0 years, SD = 20.5, range 18.0–106.7 years were analysed. The association of the LACE index with frequency of all-cause readmissions within 28 days of discharge and over a 2-year period, and with all-cause mortality within 30 days or within 6 months after discharge from hospital were evaluated.

Results

Within LACE index scores of 0–4, 5–9 or ≥ 10, the proportions of readmission ≥ 2 times within 28 days of discharge were 0.1, 1.3 and 9.2% (χ2 = 3070, p < 0.001) and over a 2-year period were 1.7, 4.8 and 19.1% (χ2 = 3364, p < 0.001). Compared with a LACE index score of 0–4, a score ≥ 10 increased the risk (adjusted for age, sex and frequency of admissions) of death within 6 months of discharge by 6.8-fold (5.1–9.0, p < 0.001) among all ages, and most strongly in youngest individuals (18.0–49.9 years): adjusted odds ratio = 16.1 (5.7–45.8, p < 0.001). For those aged 50–59.9, 60–69.9, 70–79.9 and ≥ 80 years, odds ratios reduced progressively to 9.6, 7.7, 5.1 and 2.3, respectively. Similar patterns were observed for the association of LACE index with mortality within 30 days of hospital discharge.

Conclusions

The LACE index predicts short-term and long-term frequent admissions and short-term and medium-term mortality, most pronounced among younger individuals, after hospital discharge.
QSAR and molecular docking based design of some indolyl-3-ethanone-α-thioethers derivatives as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors
Authors: Ibrahim Zakari Ya’u , Uzairu Adamu , Shallangwa Gideon , Abechi Stephen
Published: June 2020

Malaria, a disease caused by one of the world’s fatal parasitesPlasmodium falciparum,is responsible for over a million death annually.P. falciparumdihydroorotate dehydrogenase (PfDHODH) is a validated target of this deadly parasite. Quantitative structure–activity relationship and molecular docking in silico methods were employed in the discovery of unique PfDHODH inhibitors from the computational design derivatives of indolyl-3-ethanone-α-thioethers through models generation via a genetic function algorithm methods. The best model indicates good power of prediction with coefficient of determination, R2 = 0.9482, adjusted coefficient of determination ($${\text{R}}_{\text{adj}}^{2}$$Radj2) = 0.9288, Leave one out cross-validation coefficient (Q2) = 0.9201 and the external validation ($${\text{R}}_{\text{pred}}^{2}$$Rpred2) = 0.6467. The contribution of every descriptor in the model was investigated through finding their mean effect to (pIC50) the activities of the compounds. With MATS5m (− 0.11725), RDF75m (− 0.12097), VE3_Dzp (0.14697), and MLFER_BH (1.08528) contributing more to the model, while AATSC8p (− 0.04833) and minHBa (0.05430) contributed the least to the model. Hence, the mean effect indicated MLFER_BH to be the most relevant descriptor, which aided the design of five derivatives of indolyl-3-ethanone-α-thioethers. All the designed antimalarial compounds were deeply docked within the binding region thereby forming several hydrogens and hydrophobic bonds leading to the generation of better binding affinity and high binding scores (− 156.181 kcal/mol) compared to the design template (− 138.201 kcal/mol) and the standard drug (− 128.467 kcal/mol). Furthermore, all the five designed antimalarial compounds were found to be better bonded to the binding pocket of PfDHODH than other compounds reported by other researchers.
Public Interest in Preventive Measures of Coronavirus Disease 2019 Associated With Timely Issuance of Statewide Stay-at-Home Orders
Authors: Greiner Benjamin , Ottwell Ryan , Vassar Matt , Hartwell Micah
Published: June 2020

Introduction:

One method of monitoring public preparedness is through measuring public interest in preventive measures. The objective of this study was to analyze public interest in the coronavirus disease 2019 (COVID-19) preventive measures and to identify variables associated with timely stay-at-home (SAH) orders issued by governors.

Methods:

State-level search volume was collected from Google Trends. Average preventive measure interest was calculated for the query terms “hand sanitizer,” “hand washing,” “social distancing,” and “COVID testing.” We then calculated the delay in statewide SAH orders from March 1, 2020, to the date of issuance and by-state presidential voting percentage. Bivariate correlations were computed to assess the relationship between interest in preventive measures and SAH order delay.

Results:

The correlation between average preventive measure interest and length of time before the SAH order was placed was −0.47. Average preventive measure interest was also inversely related to voting for a Republican presidential nominee in the 2016 election (R = −0.75), the latter of which was positively associated with longer delays in SAH orders (R = 0.48).

Conclusions:

States with greater public interest in COVID-19 preventive measures were inversely related to governor issuance of timely SAH orders. Increasing public interest in preventive measures may slow the spread of the virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by improving preparedness.
Fosamine ammonium impacts on the targeted invasive shrubRhamnus catharticaand non-target herbs
Authors: Schuster Michael J. , Bockenstedt Paul , Wragg Peter D. , Reich Peter B.
Published: June 2020

Fosamine ammonium (Krenite®) is a foliar herbicide that primarily targets woody plant species; however, formal evaluations of its efficacy and potential for non-target impacts are scarce in the literature. The few tests of fosamine ammonium that exist focus primarily on its use in open environments, and the value of fosamine ammonium in controlling invasive understory shrubs is unclear. Here, we test the impact of fosamine ammonium on invasive common buckthorn (Rhamnus catharticaL.) and co-occurring herbaceous plants across six forest sites in Minnesota, USA.Rhamnus catharticatreated with fosamine ammonium had a 95% mortality rate, indicating high efficacy of fosamine ammonium for use againstR. cathartica. Non-target impacts varied between forbs and graminoids such that forb cover was reduced by up to 85%, depending on site, whereas graminoid cover was sparse and impacts of fosamine ammonium on graminoids were unclear. These results indicate that while fosamine ammonium can provide effective control ofR. catharticaand other understory shrubs, there is potential for significant non-target impacts following its use. We therefore suggest that land managers carefully consider the timing, rate, and application method of fosamine ammonium to achieve desired target and non-target impacts.
Corruption Information and Vote Share: A Meta-Analysis and Lessons for Experimental Design
Authors: INCERTI TREVOR
Published: June 2020

Debate persists on whether voters hold politicians accountable for corruption. Numerous experiments have examined whether informing voters about corrupt acts of politicians decreases their vote share. Meta-analysis demonstrates that corrupt candidates are punished by zero percentage points across field experiments, but approximately 32 points in survey experiments. I argue this discrepancy arises due to methodological differences. Small effects in field experiments may stem partially from weak treatments and noncompliance, and large effects in survey experiments are likely from social desirability bias and the lower and hypothetical nature of costs. Conjoint experiments introduce hypothetical costly trade-offs, but it may be best to interpret results in terms of realistic sets of characteristics rather than marginal effects of particular characteristics. These results suggest that survey experiments may provide point estimates that are not representative of real-world voting behavior. However, field experimental estimates may also not recover the “true” effects due to design decisions and limitations.
The origin and effect of hemispheric helicity imbalance in solar dynamo
Authors: Yang Shangbin , Pipin V. V. , Sokoloff D. D. , Kuzanyan K. M. , Zhang Hongqi
Published: June 2020

In this paper we study the effects of the net magnetic helicity density on the hemispheric symmetry of the dynamo generated large-scale magnetic field. Our study employs the axisymmetric dynamo model which takes into account the nonlinear effect of magnetic helicity conservation. We find that, on the surface, the net magnetic helicity follows the evolution of the parity of the large-scale magnetic field. Random fluctuations of the$\unicode[STIX]{x1D6FC}$-effect and the helicity fluxes can invert the causal relationship, i.e. the net magnetic helicity or the imbalance of magnetic helicity fluxes can drive the magnetic parity breaking. We also found that evolution of the net magnetic helicity of the small-scale fields follows the evolution of the net magnetic helicity of the large-scale fields with some time lag. We interpret this as an effect of the difference of the magnetic helicity fluxes out of the Sun from the large and small scales.
Expulsion from the Synagogue: J. L. Martyn'sHistory and Theology in the Fourth GospelRevisited
Authors: De Boer Martinus C.
Published: June 2020

InHistory and Theology in the Fourth Gospel, Martyn argued that John 9.22 concerns the formal expulsion from the synagogue of Jews who were confessing Jesus as the Messiah of Jewish expectation. Johannine scholars following Martyn have often claimed that a ‘high’ Christology must have provided the catalyst for this trauma, not the ‘low’ Christology posited by Martyn. For Martyn, however, a ‘high’ Christology was a subsequent development, leading to a second trauma, that of execution for blasphemously claiming that Jesus was somehow equal to God. Accepting Martyn's argument on 9.22 with respect to this issue, and leaving aside the debate about the relevance of the Birkat ha-Minim, this article seeks to determine why local synagogue authorities, evidently represented in John's narrative by the Pharisees, would have found the acceptance of Jesus as Messiah so offensive that they formulated a decree to expel fellow Jews espousing this new messianic faith. Analysis of John 5, 7 and 9 demonstrates that the Pharisees in the Johannine setting found this confession offensive because they regarded the behaviour of Johannine disciples on the Sabbath as thoroughly inconsistent with their own understanding of the Sabbath commandment and as significantly hindering their desire to play an authoritative role in determining what counted as acceptable behaviour on the Sabbath and what did not. In short, the specific catalyst for expelling Jews confessing Jesus as Messiah from the synagogue was their Sabbath observance, which the Pharisees in the Johannine setting came to regard as an unacceptable deviation from their own developing views on the matter in the period after 70 ce.
The New Jerusalem: Wealth, Ancient Building Projects and Revelation 21–22
Authors: Moss Candida R. , Feldman Liane M.
Published: June 2020

Scholarly interpretations of the descent and description of the New Jerusalem in Revelation 21–22 have tended to evaluate the city against biblical and extra-canonical descriptions of the Jerusalem Temple, apocalyptic accounts of heaven and ancient utopian literature in general. While some have noted the ways in which the New Jerusalem parallels the description of Babylon elsewhere in the Apocalypse, no one has yet considered the ways in which the New Jerusalem mimics, mirrors and adapts the excesses of elite Roman architecture and decor. The argument of this article is that when viewed against the backdrop of literary and archaeological evidence for upper-class living space, the luxury of the New Jerusalem is domesticated and functions to democratise access to wealth in the coming epoch. The ways in which Revelation's New Jerusalem rehearses the conventions of morally problematic displays of luxury can partially explain later patristic discomfort with literalist readings of this passage.
United against precarious working conditions? Explaining the role of trade unions in improving migrants’ working conditions in the British and German meat-processing industries
Authors: Kuhlmann Johanna , Vogeler Colette S.
Published: June 2020

The literature has described trade unions’ positions towards both precarious workers and migrant workers as ambivalent. By studying an extreme case, the meat-processing industries in the United Kingdom and in Germany, we show how trade unions were decisive in both countries in bringing exploitative working conditions on the political agenda and in advancing policy change. However, the strategies through which trade unions contributed to this differed remarkably, highlighting different causal pathways in both countries. The British case can clearly be seen as an example of successful union revitalisation by relying on innovative strategies. In contrast, the German story exhibits a strong reliance on a more traditional approach to improving workers’ rights, which was only successful after employers were willing to improve working conditions in the sector as well. Our analysis shows that policy change can happen despite unfavourable conditions and weak actors, especially if these actors make strategic use of situational conditions.
Online behavioural patterns for Coronavirus disease 2019 (COVID-19) in the United Kingdom
Authors: Walker M. D. , Sulyok M.
Published: June 2020

The current coronavirus (COVID-19) pandemic offers a unique opportunity to conduct an infodemiological study examining patterns in online searching activity about a specific disease and how this relates to news media within a specific country. Google Trends quantifies volumes of online activity. The relative search volume was obtained for ‘Coronavirus’, ‘handwashing’, ‘face mask’ and symptom related keywords, for the United Kingdom, from the date of the first confirmed case until numbers peaked in April. The relationship between online search traffic and confirmed case numbers was examined. Search volumes varied over time; peaks appear related to events in the progression of the epidemic which were reported in the media. Search activity on ‘Coronavirus’ correlated well against confirmed case number as did ‘face mask’ and symptom-related keywords. User-generated online data sources such as Google Trends may aid disease surveillance, being more responsive to changes in disease occurrence than traditional disease reporting. The relationship between media coverage and online searching activity is rarely examined, but may be driving online behavioural patterns.
Anxiety reduction after pre-procedure meetings in patients with CHD
Authors: Boyer Preston J. , Yell Joshua A. , Andrews Jennifer G. , Seckeler Michael D.
Published: June 2020

Background:

Cardiac catheterisations for CHD produce anxiety for patients and families. Current strategies to mitigate anxiety and explain complex anatomy include pre-procedure meetings and educational tools (cardiac diagrams, echocardiograms, imaging, and angiography). More recently, three-dimensionally printed patient-specific models can be added to the armamentarium. The purpose of this study was to evaluate the efficacy of pre-procedure meetings and of different educational tools to reduce patient and parent anxiety before a catheterisation.

Methods:

Prospective study of patients ≥18 and parents of patients <18 scheduled for clinically indicated catheterisations. Patients completed online surveys before and after meeting with the interventional cardiologist, who was blinded to study participation. Both the pre- and post-meeting surveys measured anxiety using the State-Trait Anxiety Inventory. In addition, the post-meeting survey evaluated the subjective value (from 1 to 4) of individual educational tools: physician discussion, cardiac diagrams, echocardiograms, prior imaging, angiograms and three-dimensionally printed cardiac models. Data were compared using paired t-tests.

Results:

Twenty-three patients consented to participate, 16 had complete data for evaluation. Mean State-Trait Anxiety Inventory scores were abnormally elevated at baseline and decreased into the normal range after the pre-procedure meeting (39.8 versus 31, p = 0.008). Physician discussion, angiograms, and three-dimensional models were reported to be most effective at increasing understanding and reducing anxiety.

Conclusion:

In this pilot study, we have found that pre-catheterisation meetings produce a measurable decrease in patient and family anxiety before a procedure. Discussions of the procedure, angiograms, and three-dimensionally printed cardiac models were the most effective educational tools.
Human Sovereignty Eclipsed? Toward a Posthumanist Reading of the Traumatized Subject in J.M. Coetzee’s Disgrace
Authors: İbrişim Deniz Gündoğan
Published: June 2020

The main aim of this article is to analyse J.M. Coetzee’s Disgrace (1999) from a posthumanist perspective. By focusing on the character David Lurie, this article analyses the complex materiality of bodies and the agentic powers of nonhuman entities in coping with individual trauma, where agency is no longer considered to be the distinguishing quality unique to humans. In so doing, it highlights the interdependence of the human and the nonhuman and the idea that environment is not a mere canvas onto which characters’ traumas are being reflected. On the contrary, it is a material-affective matrix which becomes a catalyst for making sense of the world in post-apartheid South Africa. At the same time, as this article argues, it decentres the sovereignty of the human subject.
Domestic Appropriation of Chinese Literature in Europe
Authors: Cao Shunqing , Han Zhoukun
Published: June 2020

In this article, it is argued that in the process of cultural transfer, literary translation and reception, the recipient will often transform the cultural rules and literary discourse in the original texts to make them fit the rules and discourse of the recipient reader/audience to target the taste of new readers. This phenomenon, which we call literary ‘domestic appropriation’, is a kind of transformation on a deeper level. Domestic appropriation is what can we get from literary variation, and it is the core part of variation studies. In cultural and literary exchange and dialogue between Chinese and European cultures, it occurs in both literary works and literary theory. History has witnessed how Chinese literary works are translated and introduced to Europe, in the process becoming an integral part of the canon of European literature. Chinese literary theory, when interpreted by European theorists, blends with local theory and furnishes new perspectives.
Atomic-Resolution Cryo-STEM Across Continuously Variable Temperatures
Authors: Goodge Berit H. , Bianco Elisabeth , Schnitzer Noah , Zandbergen Henny W. , Kourkoutis Lena F.
Published: June 2020

Atomic-resolution cryogenic scanning transmission electron microscopy (cryo-STEM) has provided a path to probing the microscopic nature of select low-temperature phases in quantum materials. Expanding cryo-STEM techniques to broadly tunable temperatures will give access to the rich temperature-dependent phase diagrams of these materials. With existing cryo-holders, however, variations in sample temperature significantly disrupt the thermal equilibrium of the system, resulting in large-scale sample drift. The ability to tune the temperature without negative impact on the overall instrument stability is crucial, particularly for high-resolution experiments. Here, we test a new side-entry continuously variable temperature dual-tilt cryo-holder which integrates liquid nitrogen cooling with a 6-pin micro-electromechanical system (MEMS) sample heater to overcome some of these experimental challenges. We measure consistently low drift rates of 0.3–0.4 Å/s and demonstrate atomic-resolution cryo-STEM imaging across a continuously variable temperature range from ~100 K to well above room temperature. We conduct additional drift stability measurements across several commercial sample stages and discuss implications for further developments of ultra-stable, flexible cryo-stages.
Timescales and Processes of Methane Hydrate Formation and Breakdown, With Application to Geologic Systems
Authors: Ruppel C. D. , Waite W. F.
Published: June 2020

Gas hydrate is an ice‐like form of water and low molecular weight gas stable at temperatures of roughly −10°C to 25°C and pressures of ~3 to 30 MPa in geologic systems. Natural gas hydrates sequester an estimated one sixth of Earth's methane and are found primarily in deepwater marine sediments on continental margins, but also in permafrost areas and under continental ice sheets. When gas hydrate is removed from its stability field, its breakdown has implications for the global carbon cycle, ocean chemistry, marine geohazards, and interactions between the geosphere and the ocean‐atmosphere system. Gas hydrate breakdown can also be artificially driven as a component of studies assessing the resource potential of these deposits. Furthermore, geologic processes and perturbations to the ocean‐atmosphere system (e.g., warming temperatures) can cause not only dissociation, but also more widespread dissolution of hydrate or even formation of new hydrate in reservoirs. Linkages between gas hydrate and disparate aspects of Earth's near‐surface physical, chemical, and biological systems render an assessment of the rates and processes affecting the persistence of gas hydrate an appropriate Centennial Grand Challenge. This paper reviews the thermodynamic controls on methane hydrate stability and then describes the relative importance of kinetic, mass transfer, and heat transfer processes in the formation and breakdown (dissociation and dissolution) of gas hydrate. Results from numerical modeling, laboratory, and some field studies are used to summarize the rates of hydrate formation and breakdown, followed by an extensive treatment of hydrate dynamics in marine and cryospheric gas hydrate systems.
Characterization of the 2008 Phreatomagmatic Eruption of Okmok From ArcticDEM and InSAR: Deposition, Erosion, and Deformation
Authors: Dai Chunli , Howat Ian M. , Freymueller Jeffrey T. , Vijay Saurabh , Jia Yuanyuan
Published: June 2020

Okmok volcano, one of the most active volcanoes in the Aleutian Islands, erupted between 12 July and 19 August 2008 and produced a new tephra cone (Ahmanilix) up to 253 m high. A coeruptive deposit thickness map and the posteruptive elevation change rate map are generated for this phreatomagmatic eruption using the new, high‐resolution (2 m) digital elevation model (DEM) time series provided by ArcticDEM. The total dense rock equivalent (DRE) volume over the proximal deposit field classified from the elevation change map is estimated as 0.147 ± 0.001 km3 DRE (bulk volume of 0.453 ± 0.003 km3). Combined with the distal deposit volume derived from field measurements, the total DRE is 0.25 km3 (bulk volume of 0.76 km3). The estimated erosion rate is up to −15 ± 3 m/year along the flanks of Ahmanilix, and the redeposition rate is about 1 ± 0.3 m/year at the base and 6 ± 1 m/year within the center of Ahmanilix. The surface elevation change also reveals a large ground surface collapse that disrupted the old Cone D lava bench, with a total collapse area of 0.15 km2 and a volume of (7.1 ± 0.4) × 10−3 km3. We also produce a coeruptive deformation map from satellite interferometric synthetic aperture radar (InSAR) using topography from both ArcticDEM and the Shuttle Radar Topography Mission (SRTM) and compare the results. Finally, based on historical eruption volumes, the magma supply rate at Okmok is estimated as (1.77 ± 0.1) × 10−3 km3/year.
Noise Characteristics of Operational Real‐Time High‐Rate GNSS Positions in a Large Aperture Network
Authors: Melgar Diego , Crowell Brendan W. , Melbourne Timothy I. , Szeliga Walter , Santillan Marcelo , Scrivner Craig
Published: June 2020

Large earthquakes are difficult to model in real‐time with traditional inertial seismic measurements. Several algorithms that leverage high‐rate real‐time Global Navigation Satellite Systems (HR‐GNSS) positions have been proposed, and it has been shown that they can supplement the earthquake monitoring effort. However, analyses of the long‐term noise behavior of high‐rate real‐time GNSS positions, which are important to understand how the data can be used operationally by monitoring agencies, have been limited to just a few sites and to short time spans. Here, we show results from an analysis of the noise characteristics of 1 year of positions at 213 GNSS sites spanning a large geographic region from Southern California to Alaska. We characterize the behavior of noise and propose several references noise models which can be used as baselines to compare against as technological improvements allow for higher precision solutions. We also show how to use the reference noise models to generate realistic synthetic noise that can be used in simulations of HR‐GNSS waveforms. We discuss spatiotemporal variations in the noise and their potential sources and significance. We also detail how noise analysis can be used in a dynamic quality control to determine which sites should or should not contribute positions to an earthquake modeling algorithm at a particular moment in time. We posit that while there remain important improvements yet to be made, such as reducing the number of outliers in the time series, the present quality of real‐time HR‐GNSS waveforms is more than sufficient for monitoring large earthquakes.
Joint Optimization of Measurement and Modeling Strategies With Application to Radial Flow in Stratified Aquifers
Authors: Maier R. , Gonzalez‐Nicolas A. , Leven C. , Nowak W. , Cirpka O. A.
Published: June 2020

When applying environmental models, the choice of model complexity and the design of field campaigns depend on each other and on the modeling/prediction goal. We propose jointly optimizing model complexity and data collection (design) by maximizing the expected performance for the modeling goal. We use ensembles of highly resolved virtual realities and of less complex modeling variants that differ in their degrees of upscaling and simplified parameterization. For each design under consideration, we simulate hypothetical measurement data (subject to noise) with all realizations of all models. To mimic model calibration with hypothetical data, we identify pairs of best fitting realizations between virtual reality and each model variant for each design. Then, we emulate model choice by selecting (across the model variants, for each design and for each virtual reality) the pair that shows the best predictive match in the modeling goal. Finally, we identify the model/design combination that offers, on average over all virtual realities, the best predictive match. As a test application, we consider a heterogeneous, stratified aquifer, in which the stratification enhances hydraulic anisotropy on the macroscale. We define two different modeling goals: (a) estimating the hydraulic conductivity tensor upscaled to the full aquifer thickness and (b) predicting the pumping rate needed to dewater a construction pit. Our results indicate that jointly optimizing observation networks and model selection can reduce the prediction uncertainty of parameters at lower experimental costs. We also show that the involved trade‐offs between model complexity and required design depend on the target quantity.
Below the Great Pacific Garbage Patch: More Garbage
Authors: Johnson-Groh Mara
Published: June 2020

New research is finding there’s more to marine debris than just what appears near the ocean surface, including tons of microplastics extending hundreds of meters into the deep.
Everything’s Coming Up Roses for Pasadena Seismologists
Authors: Morton Mary
Published: June 2020

Using fiber-optic cables, a new seismic network charts vibrations associated with the Rose Parade’s massive floats and marching bands.
Flightless-1 inhibits ER stress-induced apoptosis in colorectal cancer cells by regulating Ca2+ homeostasis
Authors: Choi Sun Sil , Lee Sang Kwon , Kim Joong Kwan , Park Hye-Kyung , Lee Eujin , Jang Jinho , Lee Yo Han , Khim Keon Woo , Hyun Ji-Min , Eom Hye-jin , Lee Semin , Kang Byuong Heon , Chae Young Chan , Myung Kyungjae , Myung Seung-Jae , Park Chan Young , Choi Jang Hyun
Published: June 2020

The endoplasmic reticulum (ER) stress response is an adaptive mechanism that is activated upon disruption of ER homeostasis and protects the cells against certain harmful environmental stimuli. However, critical and prolonged cell stress triggers cell death. In this study, we demonstrate that Flightless-1 (FliI) regulates ER stress-induced apoptosis in colon cancer cells by modulating Ca2+homeostasis. FliI was highly expressed in both colon cell lines and colorectal cancer mouse models. In a mouse xenograft model using CT26 mouse colorectal cancer cells, tumor formation was slowed due to elevated levels of apoptosis in FliI-knockdown (FliI-KD) cells. FliI-KD cells treated with ER stress inducers, thapsigargin (TG), and tunicamycin exhibited activation of the unfolded protein response (UPR) and induction of UPR-related gene expression, which eventually triggered apoptosis. FliI-KD increased the intracellular Ca2+concentration, and this upregulation was caused by accelerated ER-to-cytosolic efflux of Ca2+. The increase in intracellular Ca2+concentration was significantly blocked by dantrolene and tetracaine, inhibitors of ryanodine receptors (RyRs). Dantrolene inhibited TG-induced ER stress and decreased the rate of apoptosis in FliI-KD CT26 cells. Finally, we found that knockdown of FliI decreased the levels of sorcin and ER Ca2+and that TG-induced ER stress was recovered by overexpression of sorcin in FliI-KD cells. Taken together, these results suggest that FliI regulates sorcin expression, which modulates Ca2+homeostasis in the ER through RyRs. Our findings reveal a novel mechanism by which FliI influences Ca2+homeostasis and cell survival during ER stress.
Regulation of natural killer cell activity by glucocorticoids, serotonin, dopamine, and epinephrine
Authors: Capellino Silvia , Claus Maren , Watzl Carsten
Published: June 2020

The immune system and the nervous system are highly complex organs composed of various different cells that must interact with each other for proper function of the system. This communication can be mediated by soluble factors. The factors released by the nervous system (neurotransmitters) differ from those released by the immune system (cytokines). Nevertheless, the nervous and immune systems can influence each other’s activity because immune cells express neurotransmitter receptors, and neurons express cytokine receptors. Moreover, immune cells can synthesize and release neurotransmitters themselves, thus using neurotransmitter-mediated pathways via autocrine and paracrine mechanisms. Natural killer (NK) cells are innate lymphocytes that are important for early and effective immune reactions against infections and cancer. Many studies have shown the strong influence of stress and the nervous system on NK cell activity. This phenomenon may be one reason why chronic stress leads to a higher incidence of infections and cancer. Here, we review the effects of neuroendocrine factors on the different activities of NK cells. Understanding the effects of neuroendocrine factors on NK cell activities during physiological and pathophysiological conditions may result in novel therapeutic strategies to enhance NK cell functions against tumors.
Multi-trait analysis of rare-variant association summary statistics using MTAR
Authors: Luo Lan , Shen Judong , Zhang Hong , Chhibber Aparna , Mehrotra Devan V. , Tang Zheng-Zheng
Published: June 2020

Integrating association evidence across multiple traits can improve the power of gene discovery and reveal pleiotropy. Most multi-trait analysis methods focus on individual common variants in genome-wide association studies. Here, we introduce multi-trait analysis of rare-variant associations (MTAR), a framework for joint analysis of association summary statistics between multiple rare variants and different traits. MTAR achieves substantial power gain by leveraging the genome-wide genetic correlation measure to inform the degree of gene-level effect heterogeneity across traits. We apply MTAR to rare-variant summary statistics for three lipid traits in the Global Lipids Genetics Consortium. 99 genome-wide significant genes were identified in the single-trait-based tests, and MTAR increases this to 139. Among the 11 novel lipid-associated genes discovered by MTAR, 7 are replicated in an independent UK Biobank GWAS analysis. Our study demonstrates that MTAR is substantially more powerful than single-trait-based tests and highlights the value of MTAR for novel gene discovery.
The effect of flow on swimming bacteria controls the initial colonization of curved surfaces
Authors: Secchi Eleonora , Vitale Alessandra , Miño Gastón L. , Kantsler Vasily , Eberl Leo , Rusconi Roberto , Stocker Roman
Published: June 2020

The colonization of surfaces by bacteria is a widespread phenomenon with consequences on environmental processes and human health. While much is known about the molecular mechanisms of surface colonization, the influence of the physical environment remains poorly understood. Here we show that the colonization of non-planar surfaces by motile bacteria is largely controlled by flow. Using microfluidic experiments with Pseudomonas aeruginosa and Escherichia coli, we demonstrate that the velocity gradients created by a curved surface drive preferential attachment to specific regions of the collecting surface, namely the leeward side of cylinders and immediately downstream of apexes on corrugated surfaces, in stark contrast to where nonmotile cells attach. Attachment location and rate depend on the local hydrodynamics and, as revealed by a mathematical model benchmarked on the observations, on cell morphology and swimming traits. These results highlight the importance of flow on the magnitude and location of bacterial colonization of surfaces.
Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing
Authors: Stangl Christina , de Blank Sam , Renkens Ivo , Westera Liset , Verbeek Tamara , Valle-Inclan Jose Espejo , González Rocio Chamorro , Henssen Anton G. , van Roosmalen Markus J. , Stam Ronald W. , Voest Emile E. , Kloosterman Wigard P. , van Haaften Gijs , Monroe Glen R.
Published: June 2020

Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection from Gene Enrichment) to accurately and impartially identify fusions. FUDGE couples target-selected and strand-specific CRISPR-Cas9 activity for fusion gene driver enrichment — without prior knowledge of fusion partner or breakpoint-location — to long read nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints within 2 days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay for diagnostic pan-cancer fusion detection.
Spitzenkörper assembly mechanisms reveal conserved features of fungal and metazoan polarity scaffolds
Authors: Zheng Peng , Nguyen Tu Anh , Wong Jie Yun , Lee Michelle , Nguyen The-Anh , Fan Jing-Song , Yang Daiwen , Jedd Gregory
Published: June 2020

The Spitzenkörper (SPK) constitutes a collection of secretory vesicles and polarity-related proteins intimately associated with polarized growth of fungal hyphae. Many SPK-localized proteins are known, but their assembly and dynamics remain poorly understood. Here, we identify protein-protein interaction cascades leading to assembly of two SPK scaffolds and recruitment of diverse effectors in Neurospora crassa. Both scaffolds are transported to the SPK by the myosin V motor (MYO-5), with the coiled-coil protein SPZ-1 acting as cargo adaptor. Neither scaffold appears to be required for accumulation of SPK secretory vesicles. One scaffold consists of Leashin-2 (LAH-2), which is required for SPK localization of the signalling kinase COT-1 and the glycolysis enzyme GPI-1. The other scaffold comprises a complex of Janus-1 (JNS-1) and the polarisome protein SPA-2. Via its Spa homology domain (SHD), SPA-2 recruits a calponin domain-containing F-actin effector (CCP-1). The SHD NMR structure reveals a conserved surface groove required for effector binding. Similarities between SPA-2/JNS-1 and the metazoan GIT/PIX complex identify foundational features of the cell polarity apparatus that predate the fungal-metazoan divergence.
Reverse engineering synthetic antiviral amyloids
Authors: Michiels Emiel , Roose Kenny , Gallardo Rodrigo , Khodaparast Ladan , Khodaparast Laleh , van der Kant Rob , Siemons Maxime , Houben Bert , Ramakers Meine , Wilkinson Hannah , Guerreiro Patricia , Louros Nikolaos , Kaptein Suzanne J. F. , Ibañez Lorena Itatí , Smet Anouk , Baatsen Pieter , Liu Shu , Vorberg Ina , Bormans Guy , Neyts Johan , Saelens Xavier , Rousseau Frederic , Schymkowitz Joost
Published: June 2020

Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants.