bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing soil water holding capacity and provision of a potassium source via optimization of the pyrolysis of bamboo biochar
Authors: Hien Tran Thi Thu , Tsubota Toshiki , Taniguchi Tomoyuki , Shinogi Yoshiyuki
Published: October 2020

Rapid expansion of cultivated bamboo negatively impacts on biodiversity and soil microbial community. As such, it is important to properly manage and use bamboo to prevent and control such issues. This study focuses on optimizing pyrolysis conditions to produce bamboo biochar for agricultural soil amendment, particularly soil potassium (K) and water holding capacity. Bamboo chips were pyrolyzed under nitrogen gas at 400, 600, and 800 °C for 1 and 2 h of retention. A total of six biochar products were created: 400-1 (i.e., 400 °C in 1 h), 400-2, 600-1, 600-2, 800-1, and 800-2. The 600 °C bamboo biochar products were observed to have the greatest potential in increasing soil K and water holding capacity. The 600-1 product had the highest potassium content (4.87%), with a water holding capacity of 3.73 g g−1, while the 600-2 product had the second-highest potassium content (4.13%) and the highest water holding capacity (4.21 g g−1) and cation exchange capacity. The K release in 600 °C products was larger and slower than that of the 400 °C and 800 °C products, respectively. The results also indicated that the physicochemical characteristics of bamboo biochar, such as yield, pH, surface area, water holding capacity, and K content, were significantly impacted by temperature, retention time, or a combination of these parameters. The outcomes from this study are a valuable reference for bamboo biochar production targeting agricultural soil amendment, particularly when it is directed at increasing soil K and water holding capacity.
When is asthma not guilty?
Authors: Al Shamrani Abdullah , AlShammari Ayshah , AlAlkami Halima , AlShanwani Jawaher , Alharbi Adel S.
Published: October 2020

Asthma is a common childhood condition. Its prevalence in Saudi Arabia is high, increasing, and could exceed 20% at the current trajectory. Asthma is a syndrome with different clinical presentations and phenotypes. Many conditions are often misdiagnosed as asthma because they share the same symptoms, particularly coughing and shortness of breath; physical findings, such as wheezing; radiological findings, such as hyperinflation on chest X-ray; or even responses to asthma therapies, as in some patients with bronchiolitis. When treating the younger age group (>5 years old), there should be a high degree of suspicion of alternative causes when evaluating patients presenting with clinical features suggestive of asthma or patients who do not respond well to asthma therapies. This study will highlight common conditions that may mimic asthma and, as a result of incorrect treatment, unnecessarily expose patients to steroids and other therapies for extended periods. Furthermore, we seek to alert healthcare providers to common symptoms and signs that suggest a cause other than asthma and suggest when to refer the patient to subspecialists.
How threat actors abuse ICS-specific file types
Authors: Erez Nadav
Published: October 2020

Project files are integral to industrial control system (ICS) solutions, providing all the necessary data and instructions each machine on the operational technology (OT) network needs to operate. While engineers will use them to ensure the smooth running of operations, security teams can use them to gather an accurate picture of what machines are running on the system along with other critical data, such as where they are and what they are supposed to be doing.

Project files are integral to industrial control system (ICS) solutions, providing the data and instructions each machine on the operational technology (OT) network needs to operate.

While engineers will use them to ensure the smooth running of operations, security teams can use these files to gather an accurate picture of what machines are running, along with other critical data, such as where they are and what they are supposed to be doing. However, extracting information from ICS engineering project files is not always straightforward, and a lack of full visibility into what is running on the network and how it normally functions presents a significant security risk, explains Nadav Erez at Claroty.
Music Transforming Conflict
Authors: Phillips-Hutton Ariana
Published: October 2020

Teach the world to sing, and all will be in perfect harmony - or so the songs tell us. Music is widely believed to unify and bring peace, but the focus on music as a vehicle for fostering empathy and reconciliation between opposing groups threatens to overly simplify our narratives of how interpersonal conflict might be transformed. This Element offers a critique of empathy's ethical imperative of radical openness and positions the acknowledgement of moral responsibility as a fundamental component of music's capacity to transform conflict. Through case studies of music and conflict transformation in Australia and Canada, Music Transforming Conflict assesses the complementary roles of musically mediated empathy and guilt in post-conflict societies and argues that a consideration of musical and moral implication as part of studies on music and conflict offers a powerful tool for understanding music's potential to contribute to societal change.
Pandemics as Rights-Generators
Authors: Jain Neha
Published: October 2020

While the global pandemic has exposed the fragility of human rights protections, it has also resulted in rights victories for some of the most vulnerable members of society. This Essay examines epistemic, consequentialist, and normative rights reframing efforts that have been mobilized to advocate for and secure human rights during the pandemic through the lens of prisoners’ rights. It argues that these rights seeking strategies hold promise for advancing rights claims of prisoners and other marginalized groups beyond the pandemic.
The Once and Future Law of State Responsibility
Authors: Paparinskis Martins
Published: October 2020

The current (once) international law of state responsibility is shaped by the International Law Commission's Articles on responsibility of States for internationally wrongful acts, generally endorsed in state and judicial practice as consonant with custom. This Essay makes the case that the global pandemic and associated practice may affect foundational elements of the (future) law of state responsibility. It outlines the contours of systemic grain of possible developments by reference to the tension between bilateralism and community interests in international law.
A Global Leviathan Emerges: The Federal Reserve, COVID-19, and International Law
Authors: Bradlow Daniel D. , Park Stephen Kim
Published: October 2020

The COVID-19 pandemic highlights the importance of the Federal Reserve as a leading actor in global economic governance. As a creature of U.S. domestic law with an international presence and operational independence, the Fed wields authority without a well-defined international legal status, international legal standards to guide its conduct, or accountability to those around the world affected by its decisions. This Essay explores three conceptual approaches that could be used to develop norms, standards, and principles to address this gap.
Joined Cases C-585/18, C-624/18, C-625/18
Authors: Uhma Piotr
Published: October 2020

The judgment of the Grand Chamber of the Court of Justice of the European Union (CJEU) announced on November 19, 2019 in response to a preliminary reference from the Polish Supreme Court is of fundamental importance for the independence of courts and judges in EU countries, establishing a pillar on which subsequent CJEU decisions have been based. The CJEU concluded that a national court is not an independent and impartial tribunal within the meaning of the European Union (EU) law where the objective circumstances in which that court was formed, its characteristics, and the means by which its members have been appointed are capable of giving rise to legitimate doubts, in the minds of subjects of the law, as to the imperviousness of that court to external interference. In particular, a court may cease to be seen as independent or impartial when it appears to be under the direct or indirect influence of the legislature and/or the executive, or where doubts emerge about their neutrality with respect to the interests before them. Such circumstances threaten the trust that justice in a democratic society must inspire in subjects of the law.
Targeted gown and glove use to prevent Staphylococcus aureus acquisition in community-based nursing homes: A pilot study
Authors: Lydecker Alison D. , Osei Patience A. , Pineles Lisa , Johnson J. Kristie , Meisel Jacquelyn , Stine O. Colin , Magder Laurence , Gurses Ayse P. , Hebden Joan , Oruc Cagla , Mody Lona , Jacobs Slifka Kara , Stone Nimalie D. , Roghmann Mary-Claire
Published: October 2020

Objective:

To test the feasibility of targeted gown and glove use by healthcare personnel caring for high-risk nursing-home residents to prevent Staphylococcus aureus acquisition in short-stay residents.

Design:

Uncontrolled clinical trial.

Setting:

This study was conducted in 2 community-based nursing homes in Maryland.

Participants:

The study included 322 residents on mixed short- and long-stay units.

Methods:

During a 2-month baseline period, all residents had nose and inguinal fold swabs taken to estimate S. aureus acquisition. The intervention was iteratively developed using a participatory human factors engineering approach. During a 2-month intervention period, healthcare personnel wore gowns and gloves for high-risk care activities while caring for residents with wounds or medical devices, and S. aureus acquisition was measured again. Whole-genome sequencing was used to assess whether the acquisition represented resident-to-resident transmission.

Results:

Among short-stay residents, the methicillin-resistant S. aureus acquisition rate decreased from 11.9% during the baseline period to 3.6% during the intervention period (odds ratio [OR], 0.28; 95% CI, 0.08–0.92; P = .026). The methicillin-susceptible S. aureus acquisition rate went from 9.1% during the baseline period to 4.0% during the intervention period (OR, 0.41; 95% CI, 0.12–1.42; P = .15). The S. aureus resident-to-resident transmission rate decreased from 5.9% during the baseline period to 0.8% during the intervention period.

Conclusions:

Targeted gown and glove use by healthcare personnel for high-risk care activities while caring for residents with wounds or medical devices, regardless of their S. aureus colonization status, is feasible and potentially decreases S. aureus acquisition and transmission in short-stay community-based nursing-home residents.
Aprovechamiento de animales en la puna transicional de Chaschuil (Catamarca, Argentina): Análisis zooarqueológico de dos ocupaciones del sitio San Francisco Inca (ca. siglos diez a quince dC)
Authors: Miyano Juan Pablo
Published: October 2020

Este trabajo discute las estrategias vinculadas al aprovechamiento de animales durante dos ocupaciones del sitio San Francisco Inca (puna transicional de Chaschuil, Catamarca, Argentina): una incaica (ca. siglos catorce y quince dC) y otra preincaica (ca. siglos diez a trece dC). Los grupos agropastoriles preincaicos que ocuparon estacionalmente el sitio desarrollaron una estrategia de diversificación, intensificación y almacenamiento de los recursos de origen animal para hacer frente a la impredecibilidad puneña y al contexto regional de restricción ambiental. Esta incluyó la caza de vicuñas, la tendencia a evitar el sacrificio de llamas durante dicha ocupación, el procesamiento relativamente intensivo de partes de bajo retorno de los camélidos, el secado de elementos del esqueleto axial y, posiblemente, el consumo diferido de la médula ósea de los metapodios. Durante la ocupación incaica, el Estado organizó festines para legitimar su presencia en la región y sirvió comidas basadas fundamentalmente en los recursos brindados por animales silvestres capturados localmente (vicuñas y, en menor proporción, roedores, aves y guanacos). Además, se plantea la posibilidad de que en dichos eventos festivos se hayan realizado sacrificios de llamas y producido carne seca para su consumo diferido en otros pisos altitudinales o para el intercambio.
Keeping the “Recovered Territories”: Evolving Administrative Approaches Toward Indigenous Silesians
Authors: Woodard Stefanie M.
Published: October 2020

This article traces changes in Polish administrative approaches toward indigenous Upper Silesians in the 1960s and 1970s. By commissioning reports from voivodeship leaders in 1967, the Ministry of Internal Affairs recognized that native Silesians held reservations toward Poland and, moreover, that postwar “Polonization” efforts may have backfired. These officials further understood the need to act quickly against “disintegration” trends. Although administrators in Katowice and Opole noted that relatively few Silesians engaged in clearly anti-Polish activities, these leaders still believed that West German influence threatened their authority in Silesia. Increasing West German involvement in the area, particularly through care packages and tourism, seemed to support this conclusion. In response to fears of West German infiltration and the rise in emigration applications, local authorities sought to bolster a distinctly Silesian identity. Opole officials in particular argued that strengthening a regional identity, rather than a Polish one, could combat the “tendency toward disintegration” in Silesia. This policy shift underscored an even greater change in attitude toward the borderland population: instead of treating native Silesians as an innate threat to Polish sovereignty, as had been the case immediately after the war, the administration now viewed them as essential for maintaining authority in western Poland.
Subversive Celebrations: Holidays as Sites of Minority Identity Contestation in Repressive Regimes
Authors: Hintz Lisel , Quatrini Allison L.
Published: October 2020

What role do nationally celebrated holidays play for groups that are not considered—or do not consider themselves—to be part of the majority nation of a state? What function do holidays specific to minority group cultures serve under regimes that discriminate against those groups? This article explores holidays as a forum for contestation for the national identity proposals promulgated by the state in repressive regimes. We argue that national holidays are meaningful sites of identity contestation for four reasons: the role of holidays in heightening identity salience, the malleability of identity narratives, the relative lack of institutional barriers to acts of celebration, and the significance of refusing to participate in celebrations. We collected the data through interviews and participant observation of the Hui in China and the Kurds in Turkey. We employ ethnographic observation and intertextual analysis to compare these identity narratives. We find that the Hui legitimize their group’s existence by co-opting the traditional Spring Festival, or by outwardly insisting they are not celebrating while still engaging in festivities. In contrast, Turkey’s Kurds resist the government’s co-optation of the spring celebration of Newroz as a Turkish national holiday.
Safe-Asset Shortages: Evidence from the European Government Bond Lending Market
Authors: Aggarwal Reena , Bai Jennie , Laeven Luc
Published: October 2020

We identify the unique role of the government bond lending market in collateral transformation during periods of market stress. Using a novel database, we provide evidence that safe assets in the lending market have higher demand, higher borrowing cost, and higher usage of noncash collateral relative to nonsafe assets during stressed market conditions. Moreover, we find that market participants are able to obtain safe assets using relatively low-quality noncash collateral, allowing for collateral transformation. We show that policy interventions by central banks can help reduce safe-asset shortages by returning sought-after safe assets to the market.
Toward measuring effective treatment coverage: critical bottlenecks in quality- and user-adjusted coverage for major depressive disorder
Authors: Vigo Daniel , Haro Josep Maria , Hwang Irving , Aguilar-Gaxiola Sergio , Alonso Jordi , Borges Guilherme , Bruffaerts Ronny , Caldas-de-Almeida Jose Miguel , de Girolamo Giovanni , Florescu Silvia , Gureje Oye , Karam Elie , Karam Georges , Kovess-Masfety Viviane , Lee Sing , Navarro-Mateu Fernando , Ojagbemi Akin , Posada-Villa Jose , Sampson Nancy A. , Scott Kate , Stagnaro Juan Carlos , ten Have Margreet , Viana Maria Carmen , Wu Chi-Shin , Chatterji Somnath , Cuijpers Pim , Thornicroft Graham , Kessler Ronald C.
Published: October 2020

Background

Major depressive disorder (MDD) is a leading cause of morbidity and mortality. Shortfalls in treatment quantity and quality are well-established, but the specific gaps in pharmacotherapy and psychotherapy are poorly understood. This paper analyzes the gap in treatment coverage for MDD and identifies critical bottlenecks.

Methods

Seventeen surveys were conducted across 15 countries by the World Health Organization-World Mental Health Surveys Initiative. Of 35 012 respondents, 3341 met DSM-IV criteria for 12-month MDD. The following components of effective treatment coverage were analyzed: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) adequate severity-specific combination of both.

Results

MDD prevalence was 4.8% (s.e., 0.2). A total of 41.8% (s.e., 1.1) received any mental health services, 23.2% (s.e., 1.5) of which was deemed effective. This 90% gap in effective treatment is due to lack of utilization (58%) and inadequate quality or adherence (32%). Critical bottlenecks are underutilization of psychotherapy (26 percentage-points reduction in coverage), underutilization of psychopharmacology (13-point reduction), inadequate physician monitoring (13-point reduction), and inadequate drug-type (10-point reduction). High-income countries double low-income countries in any mental health service utilization, adequate pharmacotherapy, adequate psychotherapy, and adequate combination of both. Severe cases are more likely than mild-moderate cases to receive either adequate pharmacotherapy or psychotherapy, but less likely to receive an adequate combination.

Conclusions

Decision-makers need to increase the utilization and quality of pharmacotherapy and psychotherapy. Innovations such as telehealth for training and supervision plus non-specialist or community resources to deliver pharmacotherapy and psychotherapy could address these bottlenecks.
A Parameter Dimension Reduction-Based Estimation Approach to Enhance the Kinematic Accuracy of a Parallel Hardware-in-the-Loop Docking Simulator
Authors: Hu Yan , Gao Feng , Zhao Xianchao , Yang Tianhao , Shen Haoran , Qi Chenkun , Cao Rui
Published: October 2020

The docking simulators are significant ground test equipment for aerospace projects. The fidelity of docking simulation highly depends on the accuracy performance. This paper investigates the kinematic accuracy for the developed docking simulator. A novel kinematic calibration method which can reduce the number of parameters for error modeling is presented. The principle of parameters separation is studied. A simplified error model is derived based on Taylor series. This method can contribute to the simplification of the error model, fewer measurements, and easier convergence during the parameters identification. The calibration experiment validates this method for further accuracy enhancement.
Dynamic Strategy Planning of Humanoid Robots Using Glowworm-Based Optimization
Authors: Kumar Priyadarshi Biplab , Parhi Dayal R. , Muni Manoj Kumar , Pandey Krishna Kant , Chhotray Animesh , Pradhan Diana
Published: October 2020

In this paper, a novel dynamic navigational planning strategy is proposed for single as well as multiple humanoids in intricate environments on a glowworm-based optimization method. The sensory information regarding the obstacle distances and target information are supplied as inputs to the navigational model. The essential turning angle is generated as the output of the controller to avoid obstacles present in the environment and reach the target location with ease. The proposed model is certified in a V-REP simulation software, and the simulation results are authenticated in a real-time setup arranged under testing conditions.
Three Models of Democratic Expertise
Authors: Moore Alfred
Published: October 2020

How can expertise best be integrated within democratic systems? And how can such systems best enable lay judgment of expert claims? These questions are obscured by the common framing of democratic politics against an imagined system of pure and unmixed expert rule or “epistocracy.” Drawing on emerging research that attempts to think critically and institutionally about expertise, I distinguish three ways of democratically organizing relations between experts and non-experts: representative expertise, in which experts are taken to exercise limited and delegated power under the supervision of political representatives; participatory expertise, in which expertise is integrated with publics by means of directly participatory processes; and associative expertise, in which civil society groups, advocacy organizations, and social movements organize expert knowledge around the objectives of a self-organized association. Comparing these models according to the cognitive demands they make on lay citizens, the epistemic value of citizen contributions, and the ways in which they enable public scrutiny and contestation, I go on to explore how they can support and undermine one another, and how they can open up new questions about democracy, trust, and expertise in political science and political theory.
Parity and the risk of incident dementia: a COSMIC study
Authors: Bae J. B. , Lipnicki D. M. , Han J. W. , Sachdev P. S. , Kim T. H. , Kwak K. P. , Kim B. J. , Kim S. G. , Kim J. L. , Moon S. W. , Park J. H. , Ryu S.-H. , Youn J. C. , Lee D. Y. , Lee D. W. , Lee S. B. , Lee J. J. , Jhoo J. H. , Skoog I. , Najar J. , Sterner T. R. , Scarmeas N. , Yannakoulia M. , Dardiotis E. , Riedel-Heller S. , Roehr S. , Pabst A. , Ding D. , Zhao Q. , Liang X. , Lobo A. , De-la-Cámara C. , Lobo E. , Kim K. W. ,   for Cohort Studies of Memory in an International Consortium (COSMIC)
Published: October 2020

Aims

To investigate the association between parity and the risk of incident dementia in women.

Methods

We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).

Results

Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.

Conclusions

Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Unraveling the Formation Mechanism for the Bursts of Electron Butterfly Distributions: Test Particle and Quasilinear Simulations
Authors: Gan L. , Li W. , Ma Q. , Artemyev A. V. , Albert J. M.
Published: October 2020

Energetic electron dynamics is highly affected by plasma waves through quasilinear and/or nonlinear interactions in the Earth's inner magnetosphere. In this letter, we provide physical explanations for a previously reported intriguing event from the Van Allen Probes observations, where bursts of electron butterfly distributions at tens of keV exhibit remarkable correlations with chorus waves. Both test particle and quasilinear simulations are used to reveal the formation mechanism for the bursts of electron butterfly distribution. The test particle simulation results indicate that nonlinear phase trapping due to chorus waves is the key process to accelerate electrons to form the electron butterfly distribution within ~30 s, and reproduces the observed features. Quasilinear simulation results show that although the diffusion process alone also contributes to form the electron butterfly distribution, the timescale is slower. Our study demonstrates the importance of nonlinear interaction in rapid electron acceleration at tens of keV by chorus waves.
Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants
Authors: Singh Abanish , Babyak Michael A. , Sims Mario , Musani Solomon K. , Brummett Beverly H. , Jiang Rong , Kraus William E. , Shah Svati H. , Siegler Ilene C. , Hauser Elizabeth R. , Williams Redford B.
Published: October 2020

In prior work, we identified a novel gene-by-stress association of EBF1’s common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to “racism/discrimination” (P = 0.036) and “not meeting basic needs” (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e−03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.
Emerging role of the Hippo pathway in autophagy
Authors: Wang Dongying , He Jiaxing , Huang Bingyu , Liu Shanshan , Zhu Hongming , Xu Tianmin
Published: October 2020

Autophagy is a dynamic circulatory system that occurs in all eukaryotic cells. Cytoplasmic material is transported to lysosomes for degradation and recovery through autophagy. This provides energy and macromolecular precursors for cell renewal and homeostasis. The Hippo-YAP pathway has significant biological properties in controlling organ size, tissue homeostasis, and regeneration. Recently, the Hippo-YAP axis has been extensively referred to as the pathophysiological processes regulating autophagy. Understanding the cellular and molecular basis of these processes is crucial for identifying disease pathogenesis and novel therapeutic targets. Here we review recent findings from Drosophila models to organisms. We particularly emphasize the regulation between Hippo core components and autophagy, which is involved in normal cellular regulation and the pathogenesis of human diseases, and its application to disease treatment.
Immunomodulatory activity of IR700-labelled affibody targeting HER2
Authors: Mączyńska Justyna , Da Pieve Chiara , Burley Thomas A. , Raes Florian , Shah Anant , Saczko Jolanta , Harrington Kevin J. , Kramer-Marek Gabriela
Published: October 2020

There is an urgent need to develop therapeutic approaches that can increase the response rate to immuno-oncology agents. Photoimmunotherapy has recently been shown to generate anti-tumour immunological responses by releasing tumour-associated antigens from ablated tumour cell residues, thereby enhancing antigenicity and adjuvanticity. Here, we investigate the feasibility of a novel HER2-targeted affibody-based conjugate (ZHER2:2395-IR700) selectively to induce cancer cell death in vitro and in vivo. The studies in vitro confirmed the specificity of ZHER2:2395-IR700 binding to HER2-positive cells and its ability to produce reactive oxygen species upon light irradiation. A conjugate concentration- and light irradiation-dependent decrease in cell viability was also demonstrated. Furthermore, light-activated ZHER2:2395-IR700 triggered all hallmarks of immunogenic cell death, as defined by the translocation of calreticulin to the cell surface, and the secretion of ATP, HSP70/90 and HMGB1 from dying cancer cells into the medium. Irradiating a co-culture of immature dendritic cells (DCs) and cancer cells exposed to light-activated ZHER2:2395-IR700 enhanced DC maturation, as indicated by augmented expression of CD86 and HLA-DR. In SKOV-3 xenografts, the ZHER2:2395-IR700-based phototherapy delayed tumour growth and increased median overall survival. Collectively, our results strongly suggest that ZHER2:2395-IR700 is a promising new therapeutic conjugate that has great potential to be applicable for photoimmunotherapy-based regimens.
Selective knockdown of hexokinase 2 in rods leads to age-related photoreceptor degeneration and retinal metabolic remodeling
Authors: Zhang Rui , Shen Weiyong , Du Jianhai , Gillies Mark C.
Published: October 2020

Photoreceptors, the primary site of phototransduction in the retina, require energy and metabolites to constantly renew their outer segments. They preferentially consume most glucose through aerobic glycolysis despite possessing abundant mitochondria and enzymes for oxidative phosphorylation (OXPHOS). Exactly how photoreceptors balance aerobic glycolysis and mitochondrial OXPHOS to regulate their survival is still unclear. We crossed rhodopsin-Cre mice with hexokinase 2 (HK2)-floxed mice to study the effect of knocking down HK2, the first rate-limiting enzyme in glycolysis, on retinal health and metabolic remodeling. Immunohistochemistry and Western blots were performed to study changes in photoreceptor-specific proteins and key enzymes in glycolysis and the tricarboxylic acid (TCA) cycle. Changes in retinal structure and function were studied by optical coherence tomography and electroretinography. Mass spectrometry was performed to profile changes in 13C-glucose-derived metabolites in glycolysis and the TCA cycle. We found that knocking down HK2 in rods led to age-related photoreceptor degeneration, evidenced by reduced expression of photoreceptor-specific proteins, age-related reductions of the outer nuclear layer, photoreceptor inner and outer segments and impaired electroretinographic responses. Loss of HK2 in rods led to upregulation of HK1, phosphorylation of pyruvate kinase muscle isozyme 2, mitochondrial stress proteins and enzymes in the TCA cycle. Mass spectrometry found that the deletion of HK2 in rods resulted in accumulation of 13C-glucose along with decreased pyruvate and increased metabolites in the TCA cycle. Our data suggest that HK2-mediated aerobic glycolysis is indispensable for the maintenance of photoreceptor structure and function and that long-term inhibition of glycolysis leads to photoreceptor degeneration.
setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals
Authors: Liu Dian-Jia , Zhang Fan , Chen Yi , Jin Yi , Zhang Yuan-Liang , Chen Shu-Bei , Xie Yin-Yin , Huang Qiu-Hua , Zhao Wei-Li , Wang Lan , Xu Peng-Fei , Chen Zhu , Chen Sai-Juan , Li Bing , Zhang Aijun , Sun Xiao-Jian
Published: October 2020

Setd2 is the only enzyme that catalyzes histone H3 lysine 36 trimethylation (H3K36me3) on virtually all actively transcribed protein-coding genes, and this mechanism is evolutionarily conserved from yeast to human. Despite this widespread and conserved activity, Setd2 and H3K36me3 are dispensable for normal growth of yeast but are absolutely required for mammalian embryogenesis, such as oocyte maturation and embryonic vasculogenesis in mice, raising a question of how the functional requirements of Setd2 in specific developmental stages have emerged through evolution. Here, we explored this issue by studying the essentiality and function of Setd2 in zebrafish. Surprisingly, the setd2-null zebrafish are viable and fertile. They show Mendelian birth ratio and normal embryogenesis without vascular defect as seen in mice; however, they have a small body size phenotype attributed to insufficient energy metabolism and protein synthesis, which is reversable in a nutrition-dependent manner. Unlike the sterile Setd2-null mice, the setd2-null zebrafish can produce functional sperms and oocytes. Nonetheless, related to the requirement of maternal Setd2 for oocyte maturation in mice, the second generation of setd2-null zebrafish that carry no maternal setd2 show decreased survival rate and a developmental delay at maternal-to-zygotic transition. Taken together, these results indicate that, while the phenotypes of the setd2-null zebrafish and mice are apparently different, they are matched in parallel as the underlying mechanisms are evolutionarily conserved. Thus, the differential requirements of Setd2 may reflect distinct viability thresholds that associate with intrinsic and/or extrinsic stresses experienced by the organism through development, and these epigenetic regulatory mechanisms may serve as a reserved source supporting the evolution of life from simplicity to complexity.
Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals
Authors: Xu Ke , Li Boyang , McGinnis Kathleen A. , Vickers-Smith Rachel , Dao Cecilia , Sun Ning , Kember Rachel L. , Zhou Hang , Becker William C. , Gelernter Joel , Kranzler Henry R. , Zhao Hongyu , Justice Amy C. ,   VA Million Veteran Program
Published: October 2020

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.
AKAP5 complex facilitates purinergic modulation of vascular L-type Ca2+ channel CaV1.2
Authors: Prada Maria Paz , Syed Arsalan U. , Reddy Gopireddy R. , Martín-Aragón Baudel Miguel , Flores-Tamez Víctor A. , Sasse Kent C. , Ward Sean M. , Sirish Padmini , Chiamvimonvat Nipavan , Bartels Peter , Dickson Eamonn J. , Hell Johannes W. , Scott John D. , Santana Luis F. , Xiang Yang K. , Navedo Manuel F. , Nieves-Cintrón Madeline
Published: October 2020

The L-type Ca2+ channel CaV1.2 is essential for arterial myocyte excitability, gene expression and contraction. Elevations in extracellular glucose (hyperglycemia) potentiate vascular L-type Ca2+ channel via PKA, but the underlying mechanisms are unclear. Here, we find that cAMP synthesis in response to elevated glucose and the selective P2Y11 agonist NF546 is blocked by disruption of A-kinase anchoring protein 5 (AKAP5) function in arterial myocytes. Glucose and NF546-induced potentiation of L-type Ca2+ channels, vasoconstriction and decreased blood flow are prevented in AKAP5 null arterial myocytes/arteries. These responses are nucleated via the AKAP5-dependent clustering of P2Y11/ P2Y11-like receptors, AC5, PKA and CaV1.2 into nanocomplexes at the plasma membrane of human and mouse arterial myocytes. Hence, data reveal an AKAP5 signaling module that regulates L-type Ca2+ channel activity and vascular reactivity upon elevated glucose. This AKAP5-anchored nanocomplex may contribute to vascular complications during diabetic hyperglycemia.
Prevalent and sex-biased breathing patterns modify functional connectivity MRI in young adults
Authors: Lynch Charles J. , Silver Benjamin M. , Dubin Marc J. , Martin Alex , Voss Henning U. , Jones Rebecca M. , Power Jonathan D.
Published: October 2020

Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex. Deep breaths are not sex-biased. Bursts, which are serial taperings of respiratory depth typically spanning minutes at a time, are more common in males. Bursts share features of chemoreflex-driven clinical breathing patterns that also occur primarily in males, with notable neurological, psychiatric, medical, and lifespan associations. These results identify common breathing patterns in healthy young adults with distinct influences on functional connectivity and an ability to differentially influence resting state fMRI studies.
Lithium systematics in global arc magmas and the importance of crustal thickening for lithium enrichment
Authors: Chen Chen , Lee Cin-Ty A. , Tang Ming , Biddle Kevin , Sun Weidong
Published: October 2020

Much of the world’s Li deposits occurs as basinal brines in magmatic orogens, particularly in continental volcanic arcs. However, the exact origin of Li enrichment in arc magmatic systems is not clear. Here, we show that, globally, primitive arc magmas have Li contents and Li/Y ratios similar to mid-ocean ridge basalts, indicating that the subducting slab has limited contribution to Li enrichment in arc magmas. Instead, we find that Li enrichment is enhanced by lower degrees of sub-arc mantle melting and higher extents of intracrustal differentiation. These enrichment effects are favored in arcs with thick crust, which explains why magmatism and differentiation in continental arcs, like the Andes, reach greater Li contents than their island arc counterparts. Weathering of these enriched source rocks mobilizes and transports such Li into the hydrologic system, ultimately developing Li brines with the combination of arid climate and the presence of landlocked extensional basins in thickened orogenic settings.
Twisted-Planar-Twisted expanded porphyrinoid dimer as a rudimentary reaction-based methanol indicator
Authors: Li Qizhao , Li Chengjie , Baryshnikov Glib , Ding Yubin , Zhao Chengxi , Gu Tingting , Sha Feng , Liang Xu , Zhu Weihua , Wu Xinyan , Ågren Hans , Sessler Jonathan L. , Xie Yongshu
Published: October 2020

Directly linked porphyrin dimers have attracted considerable attention because of their intriguing electronic features. Most emphasis has been placed on either dimers with large dihedral angles between the constituent planar monomeric subunits or those with overall planarity, referred to as “Planar-Twisted-Planar” and “Planar-Planar-Planar”, respectively. Herein, we report a “Twisted-Planar-Twisted” framework, the hexaphyrin dimer D that exists in a trans configuration. Treatment of D with MeOH affords two isomeric dimers, MD1 and MD2, both of which incorporate a methoxy moiety and exist in cis orientations with respect to the tethering linkage. The methanol-promoted conversion is accompanied by a readily discernible color change from green to brown and is not induced to an appreciable level by other alcohols. Dimer D thus acts as a rudimentary, albeit highly selective, reaction-based methanol indicator. This work provides a promising approach for constructing reaction-based chemosensors using porphyrinoid dimers of nonplanar subunits with biased reactivity.
Telomere damage induces internal loops that generate telomeric circles
Authors: Mazzucco Giulia , Huda Armela , Galli Martina , Piccini Daniele , Giannattasio Michele , Pessina Fabio , Doksani Ylli
Published: October 2020

Extrachromosomal telomeric circles are commonly invoked as important players in telomere maintenance, but their origin has remained elusive. Using electron microscopy analysis on purified telomeres we show that, apart from known structures, telomeric repeats accumulate internal loops (i-loops) that occur in the proximity of nicks and single-stranded DNA gaps. I-loops are induced by single-stranded damage at normal telomeres and represent the majority of telomeric structures detected in ALT (Alternative Lengthening of Telomeres) tumor cells. Our data indicate that i-loops form as a consequence of the exposure of single-stranded DNA at telomeric repeats. Finally, we show that these damage-induced i-loops can be excised to generate extrachromosomal telomeric circles resulting in loss of telomeric repeats. Our results identify damage-induced i-loops as a new intermediate in telomere metabolism and reveal a simple mechanism that links telomere damage to the accumulation of extrachromosomal telomeric circles and to telomere erosion.
Subtle metastability of the layered magnetic topological insulator MnBi2Te4 from weak interactions
Authors: Ning Jinliang , Zhu Yanglin , Kidd Jamin , Guan Yingdong , Wang Yu , Mao Zhiqiang , Sun Jianwei
Published: October 2020

Layered quantum materials can host interesting properties, including magnetic and topological, for which enormous computational predictions have been done. Their thermodynamic stability is much less visited computationally, which however determines the existence of materials and can be used to guide experimental synthesis. MnBi2Te4 is one of such layered quantum materials that was predicted to be an intrinsic antiferromagnetic topological insulator, and later experimentally realized but in a thermodynamically metastable state. Here, using a combined first-principles-based approach that considers lattice, charge, and spin degrees of freedom, we investigate the metastability of MnBi2Te4 by calculating the Helmholtz free energy for the reaction Bi2Te3 + MnTe → MnBi2Te4. We identify a temperature range (~500–873 K) in which the compound is stable with respect to the competing binary phases, consistent with experimental observation. We validate the predictions by comparing the calculated specific heats contributed from different degrees of freedom with experimental results. Our findings indicate that the degrees of freedom responsible for the van der Waals interaction, lattice vibration, magnetic coupling, and nontrivial band topology in MnBi2Te4 not only enable emergent phenomena but also play a crucial role in determining its thermodynamic stability. This conclusion lays the foundation for the future computational material synthesis of novel layered systems.
Towards a passive limitation of particle surface contamination in the Columbus module (ISS) during the MATISS experiment of the Proxima Mission
Authors: Lemelle Laurence , Campagnolo Lucie , Mottin Eléonore , Le Tourneau Denis , Garre Emmanuel , Marcoux Pierre , Thévenot Cécile , Maillet Alain , Barde Sébastien , Teisseire Jérémie , Nonglaton Guillaume , Place Christophe
Published: October 2020

Future long-duration human spaceflight calls for developments to limit biocontamination of the surface habitats. The MATISS experiment tests surface treatments in the ISS’s atmosphere. Four sample holders were mounted with glass lamella with hydrophobic coatings, and exposed in the Columbus module for ~6 months. About 7800 particles were detected by tile scanning optical microscopy (×3 and ×30 magnification) indicating a relatively clean environment (a few particles per mm2), but leading to a significant coverage-rate (>2% in 20 years). Varied shapes were displayed in the coarse (50–1500 µm2) and fine (0.5–50 µm2) area fractions, consistent with scale dices (tissue or skin) and microbial cells, respectively. The 200–900 µm2 fraction of the coarse particles was systematically higher on FDTS and SiOCH than on Parylene, while the opposite was observed for the <10 µm2 fraction of the fine particles. This trend suggests two biocontamination sources and a surface deposition impacted by hydrophobic coatings.
3D convolutional neural networks-based segmentation to acquire quantitative criteria of the nucleus during mouse embryogenesis
Authors: Tokuoka Yuta , Yamada Takahiro G. , Mashiko Daisuke , Ikeda Zenki , Hiroi Noriko F. , Kobayashi Tetsuya J. , Yamagata Kazuo , Funahashi Akira
Published: October 2020

During embryogenesis, cells repeatedly divide and dynamically change their positions in three-dimensional (3D) space. A robust and accurate algorithm to acquire the 3D positions of the cells would help to reveal the mechanisms of embryogenesis. To acquire quantitative criteria of embryogenesis from time-series 3D microscopic images, image processing algorithms such as segmentation have been applied. Because the cells in embryos are considerably crowded, an algorithm to segment individual cells in detail and accurately is needed. To quantify the nuclear region of every cell from a time-series 3D fluorescence microscopic image of living cells, we developed QCANet, a convolutional neural network-based segmentation algorithm for 3D fluorescence bioimages. We demonstrated that QCANet outperformed 3D Mask R-CNN, which is currently considered as the best algorithm of instance segmentation. We showed that QCANet can be applied not only to developing mouse embryos but also to developing embryos of two other model species. Using QCANet, we were able to extract several quantitative criteria of embryogenesis from 11 early mouse embryos. We showed that the extracted criteria could be used to evaluate the differences between individual embryos. This study contributes to the development of fundamental approaches for assessing embryogenesis on the basis of extracted quantitative criteria.