bluuebunny/crossref_metadata_2025 huggingface dataset:
RcMYB84 and RcMYB123 mediate jasmonate‐induced defense responses against Botrytis cinerea in rose (Rosa chinensis)
Authors: Ren Haoran , Bai Mengjuan , Sun Jingjing , Liu Jinyi , Ren Min , Dong Yuwei , Wang Na , Ning Guogui , Wang Changquan
Published: June 2020

Jasmonates (JAs) are important for pathogen resistance in many plants, but the role of these phytohormones in fungal pathogen resistance in rose is unclear. Here, we determined that exogenous application of methyl jasmonate increased resistance to the important fungal pathogen Botrytis cinerea in Rosa chinensis ‘Old blush’, whereas silencing the JA biosynthetic pathway gene Allene Oxide Synthase (AOS) and JA co‐receptor gene CORONATINE INSENSITIVE 1 (COI1) suppressed this response. Transcriptome profiling identified various MYB transcription factor genes that responded to both JA and B. cinerea treatment. Silencing Ri‐RcMYB84/Ri‐RcMYB123 increased the susceptibility of rose plants to B. cinerea and inhibited the protective effects of JA treatment, confirming the crucial roles of these genes in JA‐induced responses to B. cinerea. JAZ1, a key repressor of JA signaling, directly interacts with RcMYB84 and RcMYB123 to deplete their free pools. The JAZ1‐RcMYB84 complex binds to the RcMYB123 promoter via the CAACTG motifs to block its transcription. Upon JA treatment, the expression of RcMYB123 is de‐repressed, and free forms of RcMYB84 and RcMYB123 are released due to JAZ1 degradation, thereby activating the defense responses of plants to B. cinerea. These findings shed light on the molecular mechanisms underlying JA‐induced pathogen resistance in roses.
PGRL1 overexpression in Phaeodactylum tricornutum inhibits growth and reduces apparent PSII activity
Authors: Zhou Lu , Gao Shan , Wu Songcui , Han Danxiang , Wang Hui , Gu Wenhui , Hu Qiang , Wang Jing , Wang Guangce
Published: June 2020

Proton gradient regulation 5‐like photosynthetic phenotype 1 (PGRL1)‐dependent cyclic electron transport around photosystem I (PSI) plays important roles in the response to different stresses, including high light. Although the function of PGRL1 in higher plants and green algae has been thoroughly investigated, little information is available on the molecular mechanism of PGRL1 in diatoms. We created PGRL1 overexpression and knockdown transformants of Phaeodactylum tricornutum, the diatom model species, and investigated the impact on growth and photosynthesis under constant and fluctuating light conditions. PGRL1 over‐accumulation resulted in significant decreases in growth rate and apparent photosystem II (PSII) activity and led to an opposing change of apparent PSII activity when turning to high light, demonstrating a similar influence on photosynthesis as a PSII inhibitor. Our results suggested that PGRL1 overexpression can reduce the apparent efficiency of PSII and inhibit growth in P. tricornutum. These findings provide physiological evidence that the accumulation of PGRL1 mainly functions around PSII instead of PSI.
Precision and accuracy of the Mindray BC‐5000Vet hematology analyzer for canine and feline blood
Authors: Thongsahuan Sorawat , Fonghoi Lalita , Kaewfai Sunita , Srinoun Kanitta
Published: June 2020

Background

The Mindray BC‐5000Vet hematology analyzer is a flow cytometry‐based automated hematology analyzer that generates a complete blood count with a five‐part white blood cell (WBC) differential count.

Objectives

We aimed to validate reliability results of the Mindray BC‐5000Vet for use in dog and cat blood.

Methods

Imprecision was performed using the manufacturer’s quality control material at low, normal, and high levels. Blood sample results of healthy and ill dogs and cats were studied for comparability between manual methods and the Mindray BC‐5000Vet analyzer. Forty dogs and 40 cats were included in the study.

Results

Precision for red blood cell (RBC) parameters was excellent, with a coefficient of variation within‐run (%CVw) and between‐run (%CVb) of <2%. WBC count and differential count showed %CVw and %CVb <8%; however, %CVw and %CVb of low‐level control material gave >9% eosinophils. The correlation between the BC‐5000 Vet and manual methods in normal and abnormal canine and feline blood samples showed excellent correlations for the RBC counts, hemoglobin concentrations, hematocrits, and WBC counts (r > .93). The differential WBC analysis of canine blood showed good correlation (r = .80‐.92). Feline blood samples showed excellent correlations for neutrophils and lymphocytes, with a good correlation for monocytes and eosinophils.

Conclusions

The Mindray BC‐5000Vet hematology analyzer proved a suitable instrument for routine analysis in dogs and cats with various hematologic abnormalities.
NAVIGATING THE FUTURE IN A SEA OF CRISPR UNCERTAINTY
Authors: Bertka Constance M.
Published: June 2020

Humanity's toolkit for altering the world we live in now includes CRISPR. Through an evolutionary process, bacteria acquired a way to protect themselves from an invading virus, making their immediate future more secure. In human hands, this powerful genome‐editing tool offers the potential to impact, at a breathtaking rate, not only our own evolutionary future, but the future of other life on this planet. Ethical concerns about altering genomes are not new, but the birth of two CRISPR gene‐edited babies last year created a renewed urgency around navigating the future and the lack of an agreed‐upon map to guide us is distressing. The goal of this article is not to provide that map but to suggest two essential questions, drawn from the context of events surrounding CRISPR to date, that should guide its drafting—“Who do we trust?” and “When is it time to act?”—and to consider what Unitarian Universalism might contribute to answering those questions.
EGO‐LESS AGENCY: DHARMA‐RESPONSIVENESS WITHOUT KANTIAN AUTONOMY
Authors: Cummiskey David
Published: June 2020

My critical focus in this article is on Rick Repetti's compatibilist conception of free will, and his apparent commitment to a Kantian conception of autonomy, which I argue is in direct conflict with the Buddhist doctrine of no‐self. As an alternative, I defend a conception of ego‐less agency that I believe better coheres with core Buddhist teachings. In the course of the argument, I discuss the competing conceptions of free agency and autonomy defended by Harry Frankfurt, John Martin Fischer, Christine Korsgaard, and David Velleman.
Glass Curtain Wall Technology and Sustainability in Commercial Buildings in Auckland, New Zealand
Authors: Wu Yi , Flemmer Claire
Published: June 2020

Glass curtain wall provides an attractive building envelope, but it is generally regarded as unsustainable because of the high energy needed to maintain thermal comfort. This research explores the advances in the technology of glass cladding and the complex issues associated with judging its sustainability. It assesses the technology and sustainability of glass curtain wall on a sample of thirty commercial buildings in Auckland, New Zealand. Field observations of the glass-clad buildings, coupled with surveys of the building occupants and of glass cladding professionals are used to investigate the cladding characteristics, operational performance, sustainability aspects and future trends. The majority of the sample buildings are low-rise office buildings. The occupants like the aesthetics and indoor environment quality of their glass-clad buildings. However, continuous heating, ventilation and air conditioning are needed in order to maintain thermal comfort within the buildings and this has high energy consumption. The increasing use of unitized systems with double glazing instead of stick-built systems with single glazing improves the sustainability of the cladding through less material wastage and better energy efficiency. Inclusion of photovoltaic modules in the curtain wall also improves energy efficiency but it is currently too expensive for use in New Zealand. Environmental sustainability is also improved when factors such as climate, the orientation of glazed façades, solar control, ventilation and the interior building layout are considered. Any assessment of glass curtain wall sustainability needs to consider the economic and social aspects as well as the environmental aspects such as energy use
Psychometric Testing of Shopping Mall Universal Design Assessment Tool (SM-UD)
Authors: Abdullah Rebaz Jalil , Jian Tang
Published: June 2020

While there are people with disability live in Kurdish parts of Iraq, a very limited number of buildings are properly designed to serve these people. Considering the challenges that people with disability face in public buildings, the United Nations has recommended the implementation of the Universal Design (UD) principles in public buildings in Iraq to ensure that all people could have access to the public buildings regardless of their abilities and backgrounds. Hence, there is a need to gather pertinent data by assessing the adherence of shopping malls in this part of Iraq to the Universal Design (UD) principles given the role of the facilities to the locals. The present study aims to develop a tool for assessing whether the shopping malls in Sulaymaniyah city adhere to Universal Design principles. An analytical tool, which was abbreviated as SM-UD, was developed using a wide range of shopping mall design elements. The tool was tested for reliability and validity through several statistical tests. Besides, the tool was tested for practicality and communicability in six different shopping malls of Sulaymaniyah. The reliability and validity test indicate that the majority of items showed good to excellent reliability and fair to excellent validity. The results of using the tool show that it is capable of identifying the drawbacks of shopping malls in terms of their universality of design. The proposed tool appears ready to be used by shopping malls’ managers and researchers.
Assessment of Career Planning as Predictor of Employee Performance: The Role of Perceived Career Opportunity
Authors: Tabiu Abubakar , Allumi Nura Abubakar
Published: June 2020

Encouraging employees to put more effort towards achieving organizational goals through good career planning practice has been the focus of many studies. Nevertheless, examining the fundamental reasons why and how career planning/development practice predict performance remains unclear. This study, examined the direct and indirect relationships between career planning/development practice with employee performance (task and contextual) through the mediation of perceived career opportunity. Using a cross sectional survey of 265 employees of 27 local governments in North Western Nigeria, the results of Partial Least Square-Structural Equation Modeling (PLS SEM) revealed that career planning practice predicts employee task and contextual performance and perceived career opportunity was found to have mediated the relationships.
Political Polarization in the Brazilian Election Campaign for the Presidency of Brazil in 2018: An Analysis of the Social Network Instagram
Authors: Fernandes Carla Montuori , Oliveira Luiz Ademir de , Campos Mariane Motta de , Gomes Vinícius Borges
Published: June 2020

The 2018 elections in Brazil were marked by major changes in the country's political and social scenario. The present work focuses on the study of the campaigns of Fernando Haddad (PT) and Jair Bolsonaro (PSL) on Instagram during the second round. Thus, through Content Analysis (Bardin, 2011) and theoretical discussion regarding political polarization and electoral communication, the work proposes to understand how the campaigns of both candidates took place and which strategies were recurrent in a scenario of political crisis and reorganization, not only in a communicational field, but also in a political field.
Quantum and transport lifetimes in optically induced GaN/AlGaN 2DEGs grown on bulk GaN
Authors: Krückeberg Luisa , Wirth Steffen , Solovyev Victor V. , Großer Andreas , Kukushkin Igor V. , Mikolajick Thomas , Schmult Stefan
Published: June 2020

A two-dimensional electron gas (2DEG) is absent in ultrapure GaN/Al0.06Ga0.94N heterostructures grown by molecular beam epitaxy on bulk GaN at 300 K and in the dark. However, such a 2DEG can be generated by UV illumination and persists at low temperature after blanking the light. Under steady UV illumination as well as under persistence conditions, pronounced quantum transport with Shubnikov–de Haas oscillations commencing below 2 T is observed. The low temperature 2DEG mobility amounts to only ∼20 000 cm2/V s, which is much lower than predicted for the dominant scattering mechanisms in GaN/AlGaN heterostructures grown on GaN with low threading dislocation density. A rather small ratio of the transport and quantum lifetimes τt/τq of ∼10 points at elastic scattering events limiting both the transport and quantum lifetimes.
Estimation of a priori signal-to-noise ratio using neurograms for speech enhancement
Authors: Jassim Wissam A. , Harte Naomi
Published: June 2020

In statistical-based speech enhancement algorithms, the a priori signal-to-noise ratio (SNR) must be estimated to calculate the required spectral gain function. This paper proposes a method to improve this estimation using features derived from the neural responses of the auditory-nerve (AN) system. The neural responses, interpreted as a neurogram (NG), are simulated for noisy speech using a computational model of the AN system with a range of characteristic frequencies (CFs). Two machine learning algorithms were explored to train the estimation model based on NG features: support vector regression and a convolutional neural network. The proposed estimator was placed in a common speech enhancement system, and three conventional spectral gain functions were employed to estimate the enhanced signal. The proposed method was tested using the NOIZEUS database at different SNR levels, and various speech quality and intelligibility measures were employed for performance evaluation. The a priori SNR estimated from NG features achieved better quality and intelligibility scores than that of recent estimators, especially for highly distorted speech and low SNR values.
Modeling of photoelastic imaging of mechanical stresses in transparent solids mimicking kidney stones
Authors: Sapozhnikov Oleg A. , Maxwell Adam D. , Bailey Michael R.
Published: June 2020

Theoretical and numerical models were developed to calculate the polariscopic integrated light intensity that forms a projection of the dynamic stress within an axisymmetric elastic object. Although the model is general, this paper addressed its application to measurements of stresses in model kidney stones from a burst wave lithotripter for stone fragmentation. The stress was calculated using linear elastic equations, and the light propagation was modeled in the instantaneous case by integrating over the volume of the stone. The numerical model was written in finite differences. The resulting images agreed well with measured images. The measured images corresponded to the maximum shear stress distribution, although other stresses were also plotted. Comparison of the modeled and observed polariscope images enabled refinement of the photoelastic constant by minimizing the error between the calculated and measured fields. These results enable quantification of the stress within the polariscope images, determination of material properties, and the modes and mechanisms of stress production within a kidney stone. Such a model may help in interpreting elastic waves in structures, such as stones, toward improving lithotripsy procedures.
Prominent Harvard anthropologist put on leave
Authors: Gibbons Ann
Published: June 2020

Three former students accuse Inca scholar Gary Urton, alleging propositions or "traumatic" affairs.
Human CNS barrier-forming organoids with cerebrospinal fluid production
Authors: Pellegrini Laura , Bonfio Claudia , Chadwick Jessica , Begum Farida , Skehel Mark , Lancaster Madeline A.
Published: June 2020

Brain barrier and support in a dish

Deep within the brain, the choroid plexus filters blood and secretes cerebrospinal fluid (CSF), a nutrient-rich liquid that bathes and supports the brain and protects it from entry of toxic compounds. Current understanding of this vital tissue in humans is limited. Pellegrini
et al.
developed choroid plexus organoids that quantitatively predict human brain permeability of small molecules and secrete an isolated CSF-like fluid (see the Perspective by Silva-Vargas and Doetsch). This CSF model reveals secretion of developmental factors and disease-related biomarkers by key cell types and provides a testing ground for drug entry into the brain.

Science
, this issue p.
eaaz5626
; see also p.
143
Plastic rain in protected areas of the United States
Authors: Brahney Janice , Hallerud Margaret , Heim Eric , Hahnenberger Maura , Sukumaran Suja
Published: June 2020

Here, there, and everywhere

No place is safe from plastic pollution. Brahney
et al.
show that even the most isolated areas in the United States—national parks and national wilderness areas—accumulate microplastic particles after they are transported there by wind and rain (see the Perspective by Rochman and Hoellein). They estimate that more than 1000 metric tons per year fall within south and central western U.S. protected areas. Most of these plastic particles are synthetic microfibers used for making clothing. These findings should underline the importance of reducing pollution from such materials.

Science
, this issue p.
1257
; see also p.
1184
Far-field excitation of single graphene plasmon cavities with ultracompressed mode volumes
Authors: Epstein Itai , Alcaraz David , Huang Zhiqin , Pusapati Varun-Varma , Hugonin Jean-Paul , Kumar Avinash , Deputy Xander M. , Khodkov Tymofiy , Rappoport Tatiana G. , Hong Jin-Yong , Peres Nuno M. R. , Kong Jing , Smith David R. , Koppens Frank H. L.
Published: June 2020

Light under compression

The ability to confine light to volumes much smaller than the wavelength produces high electromagnetic fields that can then be exploited in chemical and biological sensing and detection applications. Using silver nanocubes placed on a graphene surface, Epstein
et al.
developed a single, nanometer-scale acoustic graphene plasmon cavity device that can confine mid-infrared and terahertz radiation with mode volume confinement factors of 5 × 10
–10
. With the response being dependent on the size of the nanocube and electrically tunable, the results demonstrate a powerful platform with which to develop sensors in what has been a challenging wavelength regime where molecular fingerprints reside.

Science
, this issue p.
1219
A precise polyrotaxane synthesizer
Authors: Qiu Yunyan , Song Bo , Pezzato Cristian , Shen Dengke , Liu Wenqi , Zhang Long , Feng Yuanning , Guo Qing-Hui , Cai Kang , Li Weixingyue , Chen Hongliang , Nguyen Minh T. , Shi Yi , Cheng Chuyang , Astumian R. Dean , Li Xiaopeng , Stoddart J. Fraser
Published: June 2020

Ten rings on one axle

Rotaxanes consist of molecular rings threaded on a central axle. Most approaches to their synthesis have focused on introducing a single ring per axle. Qiu
et al.
now report a systematic approach to threading up to 10 adjacent rings consecutively. The axle's end groups were constructed to attract free-floating rings when reduced and then to push those rings toward the center upon oxidation. Products of each successive reduction-oxidation cycle were characterized by nuclear magnetic resonance spectroscopy and mass spectrometry.

Science
, this issue p.
1247
A gene for color differences between sexes
Authors: Chen Nancy
Published: June 2020

Sex differences in plumage color in hybrid canaries are controlled by a single enzyme
Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats
Authors: van der Weide Hessel , Cossío Unai , Gracia Raquel , te Welscher Yvonne M. , ten Kate Marian T. , van der Meijden Aart , Marradi Marco , Ritsema Jeffrey A. S. , Vermeulen-de Jongh Denise M. C. , Storm Gert , Goessens Wil H. F. , Loinaz Iraida , van Nostrum Cornelus F. , Llop Jordi , Hays John P. , Bakker-Woudenberg Irma A. J. M.
Published: June 2020

Antimicrobial peptides (AMPs) have seen limited clinical use as antimicrobial agents, largely due to issues relating to toxicity, short biological half-life, and lack of efficacy against Gram-negative bacteria. However, the development of novel AMP-nanomedicines, i.e., AMPs entrapped in nanoparticles, has the potential to ameliorate these clinical problems. The authors investigated two novel nanomedicines based on AA139, an AMP currently in development for the treatment of multidrug-resistant Gram-negative infections.
Radial Expansion Facilitates the Maintenance of Double Antibiotic Resistances
Authors: Durão Paulo , Ramiro Ricardo S. , Pereira Cátia , Jurič Jernej , Pereira Delfina , Gordo Isabel
Published: June 2020

Most microbes live in spatially confined subpopulations. Under spatial structure conditions, the efficacy of natural selection is often reduced (relative to homogeneous conditions) due to the increased importance of genetic drift and local competition. Additionally, under spatial structure conditions, the fittest genotype may not always be the one with better access to the heterogeneous distribution of nutrients. The effect of radial expansion may be particularly relevant for the elimination of antibiotic resistance mutations, as their dynamics within bacterial populations are strongly dependent on their growth rate.
Evidence for Expanding the Role of Streptomycin in the Management of Drug-Resistant Mycobacterium tuberculosis
Authors: Cohen Keira A. , Stott Katharine E. , Munsamy Vanisha , Manson Abigail L. , Earl Ashlee M. , Pym Alexander S.
Published: June 2020

In 2019, the WHO tuberculosis (TB) treatment guidelines were updated to recommend only limited use of streptomycin, in favor of newer agents or amikacin as the preferred aminoglycoside for drug-resistant
Mycobacterium tuberculosis
. However, the emergence of resistance to newer drugs, such as bedaquiline, has prompted a reanalysis of antitubercular drugs in search of untapped potential. Using 211 clinical isolates of
M. tuberculosis
from South Africa, we performed phenotypic drug susceptibility testing (DST) to aminoglycosides by both critical concentration and MIC determination in parallel with whole-genome sequencing to identify known genotypic resistance elements.
Removing hospital-based triage from suspected colorectal cancer pathways: the impact and learning from a primary care-led electronic straight-to-test pathway
Authors: Orchard Philippa , Arvind Nitin , Wint Alison , Kynaston James , Lyons Ann , Loveday Eric , Pullyblank Anne
Published: June 2020

Background

The 2-week wait referral pathway for suspected colorectal cancer was introduced in England to improve time from referral from a general practitioner (GP) to diagnosis and treatment. Patients are required to be seen by a hospital clinician within 2 weeks if their symptoms meet the criteria set by the National Institute for Health and Care Excellence (NICE) and to start cancer treatment within 62 days. To achieve this, many hospitals have introduced a straight-to-test (STT) strategy requiring hospital-based triage of referrals. We describe the impact and learning from a new pathway which has removed triage and moved the process of requesting tests from hospital to GPs in primary care.

Method

An electronic STT pathway was introduced allowing GPs to book tests supported by a decision aid based on NICE guidance eliminating the need for a standard referral form or triage process. The hospital identified referrals as being on a cancer pathway and dealt with all ongoing management. Routinely collected cancer data were used to identify time to cancer diagnosis compared with national data

Results

11357 patients were referred via the new pathway over 3 years. Time from referral to diagnosis reduced from 39 to 21 days and led to a dramatic improvement in patients starting treatment within 62 days. Challenges included adapting to a change in referral criteria and developing a robust hospital system to monitor the pathway.

Conclusion

We have changed the way patients with suspected colorectal cancer are managed within the National Health Service by giving GPs the ability to order tests electronically within a monitored cancer pathway halving time from referral to diagnosis
Dexmedetomidine for dyspnoea
Authors: Mano Akiko , Murata Tomohiro , Date Kazuma , Kawata Mitsuhiro , Sato Miyuki , Yamashita Norie , Iino Kimie , Kyo Shunei , Saito Eiichi
Published: June 2020

Dexmedetomidine is a selective α2-adrenoreceptor agonist with a broad range of effects, including easily controllable sedation, analgesia and anxiolysis. Because of these favorable features, it has replaced traditional sedatives, such as benzodiazepines, and is becoming the first-line sedative for the patients in intensive care units. Terminally ill patients often need sedatives for symptom management, especially for dyspnoea. However, the use of dexmedetomidine in a palliative care setting has rarely been recognised to date. We experienced a patient nearing the end of life due to uncontrollable pulmonary haemorrhage on ventilator, whose dyspnoea was successfully managed by dexmedetomidine in addition to continuous intravenous infusion of oxycodone.
CD103+ tumor-resident CD8+ T cell numbers underlie improved patient survival in oropharyngeal squamous cell carcinoma
Authors: Hewavisenti Rehana , Ferguson Angela , Wang Kevin , Jones Deanna , Gebhardt Thomas , Edwards Jarem , Zhang Mei , Britton Warwick , Yang Jean , Hong Angela , Palendira Umaimainthan
Published: June 2020

Background

Human Papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing cancers in the Western world. When compared to OPSCCs induced by smoking or alcohol, patients with HPV+ OPSCC, have better survival and the mechanisms remain unclear.

Methods

The Cancer Genome Atlas (TCGA) database was examined for genes associated with tissue-resident CD8+ T cells. Multiplex immunohistochemistry (IHC) staining was performed on tumor specimen taken from 35 HPV+ and 27 HPV- OPSCC patients.

Results

TCGA database revealed that the expression of genes encoding CD103 and CD69 were significantly higher in HPV+ head and neck SCCs (HNSCC) than in HPV- HNSCC. Higher expression levels of these two genes were also associated with better overall survival. IHC staining showed that the proportion of CD103+ tumor-resident CD8+ T cells were significantly higher in HPV+ OPSCCs when compared to HPV- OPSCC. This higher level was also associated with both lower risk of loco-regional failure, and better overall survival. Importantly, patients with HPV- OPSCC who had comparable levels of CD103+ tumor-resident CD8+ T cells to those with HPV+ OPSCC demonstrated similar survival as those with HPV+OPSCC.

Conclusion

Our results show that CD103+ tumor-resident CD8+ T cells are critical for protective immunity in both types of OPSCCs. Our data further suggest that the enhanced local protective immunity provided by tumor-resident T cell responses is the underlying factor driving favorable clinical outcomes in HPV+ OPSCCs over HPV- OPSCCs.
41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo
Authors: Baroni Matteo Libero , Sanchez Martinez Diego , Gutierrez Aguera Francisco , Roca Ho Heleia , Castella Maria , Zanetti Samanta Romina , Velasco Hernandez Talia , Diaz de la Guardia Rafael , Castaño Julio , Anguita Eduardo , Vives Susana , Nomdedeu Josep , Lapillone Helene , Bras Anne E , van der Velden Vincent H J , Junca Jordi , Marin Pedro , Bataller Alex , Esteve Jordi , Vick Binje , Jeremias Irmela , Lopez Angel , Sorigue Marc , Bueno Clara , Menendez Pablo
Published: June 2020

Background

Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative.

Methods

We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs.

Results

Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs.

Conclusions

This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.
Feasibility and safety of thrombectomy for isolated occlusions of the posterior cerebral artery: a multicenter experience and systematic literature review
Authors: Meyer Lukas , Papanagiotou Panagiotis , Politi Maria , Kastrup Andreas , Kraemer Christoffer , Hanning Uta , Kniep Helge , Broocks Gabriel , Pilgram-Pastor Sara Magdalena , Wallocha Marta , Chapot René , Fiehler Jens , Stracke Christian Paul , Leischner Hannes
Published: June 2020

Background

Substantial clinical evidence supporting the benefit of mechanical thrombectomy (MT) for distal occlusions within the posterior circulation is still missing. This study aims to investigate the procedural feasibility and safety of MT for isolated occlusions of the posterior cerebral artery.

Methods

We retrospectively reviewed patients from three stroke centers with acute ischemic stroke attributed to isolated posterior cerebral artery occlusion (IPCAOs) who underwent MT between January 2014 and December 2019. Procedural and safety assessment included successful recanalization rates (defined as Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b), number of MT attempts and first-pass effect (TICI 3), intracranial hemorrhage (ICH), mortality, and intervention-related serious adverse events. Treatment effects were evaluated by the rate of early neurological improvement (ENI) and early functional outcome was assessed with the modified Rankin Scale (mRS) at discharge. A systematic literature review was conducted to identify and summarize previous reports on MT for IPCAOs.

Results

Forty-three patients with IPCAOs located in the P1 (55.8%, 24/43), P2 (37.2%, 16/43), and P3 segment (7%, 3/43) were analyzed. The overall rate of successful recanalization (TICI ≥2b) was 86% (37/43), including a first pass-effect of 48.8% (21/43) leading to TICI 3. sICH occurred in 7% (3/43) and there were two cases with iatrogenic vessel dissection and one perforation. ENI was observed in 59% (23/39) and excellent functional outcome (mRS ≤1) in 46.2% (18/39) of patients who were discharged. The in-hospital mortality rate was 9.3% (4/43).

Conclusion

Our study suggests the technical feasibility and safety of thrombectomy for IPCAOs. Further studies are needed to investigate safety and long-term functional outcomes with posterior circulation stroke-adjusted outcome assessment.
Data analysis on Coronavirus spreading by macroscopic growth laws
Authors: Castorina P. , Iorio A. , Lanteri D.
Published: June 2020

To evaluate the effectiveness of the containment on the epidemic spreading of the new Coronavirus disease 2019, we carry on an analysis of the time evolution of the infection in a selected number of different Countries, by considering well-known macroscopic growth laws, the Gompertz law, and the logistic law. We also propose here a generalization of Gompertz law. Our data analysis permits an evaluation of the maximum number of infected individuals. The daily data must be compared with the obtained fits, to verify if the spreading is under control. From our analysis, it appears that the spreading reached saturation in China, due to the strong containment policy of the national government. In Singapore a large growth rate, recently observed, suggests the start of a new strong spreading. For South Korea and Italy, instead, the next data on new infections will be crucial to understand if the saturation will be reached for lower or higher numbers of infected individuals.
Global bounded solution of the higher-dimensional forager–exploiter model with/without growth sources
Authors: Wang Jianping , Wang Mingxin
Published: June 2020

This paper concerns with the global existence and boundedness of classical solution of the higher-dimensional forager–exploiter model with homogeneous Neumann boundary condition and nonnegative initial data. For cases where there are no forager and exploiter growth sources, it will be shown that if either the initial data and the production rate of nutrient are small or the taxis effects are small, then the classical solution exists globally and is bounded. For the case that only the forager has growth source, when [Formula: see text], it will be shown that if the taxis effect of exploiter is small then the classical solution exists globally and is bounded. For the case that both the forager and exploiter have growth restrictions, when [Formula: see text], we find a condition for the logistic degradation rates that ensures the global existence and boundedness of the classical solution.
Brownian fluctuations of flame fronts with small random advection
Authors: Henderson Christopher , Souganidis Panagiotis E.
Published: June 2020

We study the effect of small random advection in two models in turbulent combustion. Assuming that the velocity field decorrelates sufficiently fast, we (i) identify the order of the fluctuations of the front with respect to the size of the advection; and (ii) characterize them by the solution of a Hamilton–Jacobi equation forced by white noise. In the simplest case, the result yields, for both models, a front with Brownian fluctuations of the same scale as the size of the advection. That the fluctuations are the same for both models is somewhat surprising, in view of known differences between the two models.
From particles to firms: on the kinetic theory of climbing up evolutionary landscapes
Authors: Bellomo Nicola , Dosi Giovanni , Knopoff Damián A. , Virgillito Maria Enrica
Published: June 2020

This paper constitutes the first attempt to bridge the evolutionary theory in economics and the theory of active particles in mathematics. It seeks to present a kinetic model for an evolutionary formalization of economic dynamics. The new derived mathematical representation intends to formalize the processes of learning and selection as the two fundamental drivers of evolutionary environments [G. Dosi, M.-C. Pereira and M.-E. Virgillito, The footprint of evolutionary processes of learning and selection upon the statistical properties of industrial dynamics, Ind. Corp. Change, 26 (2017) 187–210]. To coherently represent the aforementioned properties, the kinetic theory of active particles [N. Bellomo, A. Bellouquid, L. Gibelli and N. Outada, A Quest Towards a Mathematical Theory of Living Systems (Birkhäuser-Springer, 2017)] is here further developed, including the complex interaction of two hierarchical functional subsystems. Modeling and simulations enlighten the predictive ability of the approach. Finally, we outline the potential avenues for future research.
Synthesis, microstructure, mechanical properties and luminescence of a ceramics Gd(NbxTa1−x)O4
Authors: Shcherbina O. B. , Masloboeva S. M. , Steblevskaya N. I. , Belobeletskaya M. V. , Efremov V. V. , Smirnov M. V. , Palatnikov M. N.
Published: June 2020

Ceramic solid solutions GdNbx[Formula: see text]O4 ([Formula: see text]–1) were synthesized by sol–gel. Morphological particularities of microstructure were studied, strength characteristics (Young’s modulus) and stress intensity factor for mode I [Formula: see text] were evaluated. The latter is a criterion of crack resistance of the material. Luminescent properties of solid solutions GdNbx[Formula: see text]O4 were researched under UV exciting radiation. A comparatively small addition of Ta ([Formula: see text]) was shown to increase luminescence intensities of centers [Formula: see text]–O−. An addition of Ta to GdNbO4 leads to creation of solid solution [Formula: see text][Formula: see text]O4. Intensity of these centers is 3–6.5 times larger than that of GdNbO4 and GdTaO4.
Graphite Particle-Size Induced Morphological and Performance Changes of Graphite–Silicon Electrodes
Authors: Jeschull Fabian , Surace Yuri , Zürcher Simone , Lari Giacomo , Spahr Michael E. , Novák Petr , Trabesinger Sigita
Published: June 2020

Silicon is a long-standing candidate for replacing graphite as the active material in negative electrodes for Li-ion batteries, due to its significantly higher specific capacity. However, Si suffers from rapid capacity fading, as a result of the large volume expansion upon lithiation. As an alternative to pure Si electrodes, Si could be used, instead, as a capacity-enhancing additive in graphite electrodes. Such graphite–Si blended electrodes exhibit lower irreversible-charge losses during the formation of the passivation layer and maintain a better electronic contact than pure Si electrodes. While previous works have mostly focused on the Si properties and Si content, this study investigates how the choice of graphite matrix can alter the electrode properties. By varying the type of graphite and the Si content (5 or 20 wt%), different electrode morphologies were obtained and their capacity retention upon long-term cycling was studied. Despite unfavorable electrode morphologies, such as large void spaces and poor active-material distribution, certain types of graphites with large particle sizes were found to be competitive with graphite–Si blends, containing smaller graphite particles. In an attempt to mitigate excess void-space and inhomogeneous material distribution, two approaches were examined: densification (calendering) and blending in a fraction of smaller graphite particles. While the former approach led in general to poorer capacity retention, the latter yielded an improved Coulombic efficiency without compromising the cycling performance.
Arterial structure and function during and after long-duration spaceflight
Authors: Lee Stuart M. C. , Ribeiro L. Christine , Martin David S. , Zwart Sara R. , Feiveson Alan H. , Laurie Steven S. , Macias Brandon R. , Crucian Brian E. , Krieger Stephanie , Weber Daniela , Grune Tilman , Platts Steven H. , Smith Scott M. , Stenger Michael B.
Published: June 2020

Carotid artery structure and stiffness did not change on average in astronauts during long-duration spaceflight (<12 mo), despite increased oxidative stress and inflammation. Most oxidative stress and inflammation biomarkers returned to preflight levels soon after landing. Brachial artery structure and function also were unchanged by spaceflight. In this group of healthy middle-aged male and female astronauts, spaceflight in low Earth orbit does not appear to increase long-term cardiovascular health risk.
Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain
Authors: Kuner Rohini , Kuner Thomas
Published: June 2020

Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating, or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics, and imaging technological tools in rodent models with a view towards decoding sensory, affective, and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward, and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic, and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.
Evaluation of the Operational Simplified Surface Energy Balance Model for Pastureland Evapotranspiration Mapping and Drought Monitoring in North Central Kentucky
Authors: Gebremedhin Maheteme , Ries Ian , Senay Gabriel B. , Matisoff Martin , Amusan Ibukun , Sandifer Jeremy , Gyawali Buddhi
Published: June 2020

The use of remotely sensed evapotranspiration (ET) for field applications in drought monitoring and assessment is gaining momentum, but meeting this need has been hampered by the absence of extensive ground-based measurement stations for ground validation across agricultural zones and natural landscapes. This is particularly crucial for regions more prone to recurring droughts with limited ground monitoring stations. A three-year (2016–2018) flux ET dataset from a pastureland in north central Kentucky was used to validate the Operational Simplified Surface Energy Balance (SSEBop) model at monthly and annual scales. Flux and SSEBop ET track each other in a consistent manner in response to seasonal changes. The mean bias error (MBE), root mean squared error (RMSE), mean absolute percentage error (MAPE), and coefficient of determination (R2) were 5.47, 21.49 mm mon−1, 30.94%, and 0.87, respectively. The model consistently underestimated ET values during winter months and overestimated them during summer months. SSEBop’s monthly ET anomaly maps show spatial ET distribution and its accurate representation. This is particularly important in areas where detailed surface meteorological and hydrological data are limited. Overall, the model estimated monthly ET magnitude satisfactorily and captured it seasonally. The SSEBop’s functionality for remote ET estimation and anomaly detection, if properly coupled with ground measurements, can significantly enhance SSEBop’s ability to monitor drought occurrence and prevalence quickly and accurately.
Study on the Anticancer Effect of an Astragaloside‐ and Chlorogenic Acid‐Containing Herbal Medicine (RLT‐03) in Breast Cancer
Authors: Li Yanchu , Li Xianyong , Cuiping Chen , Pu Rong , Weihua Yin
Published: June 2020

Background. Although surgery, chemotherapy, radiotherapy, and endocrine therapy are widely used in clinical practice for breast cancer treatment, herbal medicines (HMs) are considered as an alternative to palliative treatments because of their coordinated intervention effects and relatively low side effects. Astragaloside (AS) and chlorogenic acid (CGA) are major active ingredients of Radix Astragali and Lonicera japonica, which have shown antitumorigenic properties in certain cancers, but the role of HMs containing both AS and CGA remains unclear in breast cancer. In this study, we explored an AS‐ and CGA‐containing HM (RLT‐03) extracted from Radix Astragali, Lonicerae Japonicae Flos, Trichosanthin, and Rhizoma imperatae. Methods. RLT‐03 was extracted using water and n‐butanol, and the AS and CGA ingredients in RLT‐03 were identified by high‐performance liquid chromatography (HPLC) and evaporative light‐scattering detector (ELSD). 4T1, EMT6, BT‐549, and MDA‐MB‐231 breast cancer cell lines were used, and an EMT6 xenograft model was established. Cell proliferation, migration, and apoptosis were measured in vitro, and tumor volume and weight were observed in vivo. The expression of VEGF, EGF, IL‐10, TGF‐β, and CD34 and cell apoptosis in tumors were examined. Results. RLT‐03 inhibited cell viability and induced apoptosis in a dose‐ and time‐dependent manner. In vivo, tumor volume and weight were reduced, and the expression of VEGF, EGF, IL‐10, TGF‐β, and CD34 was suppressed in the tumor microenvironment, while cell apoptosis was induced. Conclusion. RLT‐03 exhibited therapeutic effects against breast cancer by regulating the expression of ligands of receptor tyrosine kinases (RTKs) and inflammatory factors. Thus, RLT‐03 represents a potential supplementary HM that can be used in breast cancer therapy.
Pirfenidone Inhibits Hypoxic Pulmonary Hypertension through the NADPH/ROS/p38 Pathway in Adventitial Fibroblasts in the Pulmonary Artery
Authors: Zhang Song , Yin ZongXiu , Qin WeiDong , Ma XiaoLi , Zhang Yao , Liu EnXiu , Chu YanBiao
Published: June 2020

Hypoxic pulmonary hypertension (HPH) is a devastating disease characterized by progressive vasoconstriction and vascular remodeling. Pirfenidone (PFD) inhibits the progression of HPH, though the molecular mechanisms remain unknown. This study is aimed at determining the role and mechanism of PFD in HPH in human pulmonary artery adventitial fibroblasts (HPAAFs), which were cultured under normal or hypoxic conditions. NOX4 and Rac1 were inhibited or overexpressed by shRNA or pcDNA3.1, respectively. Proliferation of HPAAFs was quantified by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assays to assess cellular metabolic activity, cell counts, and ethynyldeoxyuridine (EdU) assays to detect DNA synthesis. Migration of HPAAFs was assessed by a wound healing assay. The expression levels of smooth muscle alpha-actin (a-SMA) and procollagen I (COL1A1) were assessed by RT-PCR and western blot analysis. PFD suppressed hypoxia-induced proliferation and migration of HPAAFs. Compared with the hypoxic control group, PFD reduced the expression of a-SMA and procollagen I (COL1A1). PFD reduced hypoxia-induced phosphorylation of p38 through the NOX4/reactive oxygen species (ROS) signaling pathway. Moreover, Rac1 also decreased hypoxia-induced phosphorylation of p38, without any cross-interaction with NOX4. These findings demonstrate that PFD is a novel therapeutic agent to prevent cell proliferation, migration, and fibrosis, which might be useful in inhibiting vascular remodeling in patients with HPH.
A Triband Patch Antenna with Monopole-like and Patch-like Radiation Patterns for Multifunctional Wireless Systems
Authors: Song Hai-Na , Chen Zhao-Hui , Li Jian-Feng
Published: June 2020

A triband patch antenna with monopole-like and patch-like radiation patterns for multifunctional wireless systems is proposed. The antenna consists of a single square radiation patch with an annular slot, a ground plane, and a top-loaded metal sheet. The top-loaded metal sheet is shorted to the ground plane for producing a zeroth-order resonant (ZOR) mode, which has an omnidirectional radiation pattern at the lowest operation band, and its performance is robust to the location of the probe feed. With the annular slot and the off-center probe feed, a dual-resonant TM01 mode is excited, yielding unidirectional radiation patterns for the two upper operation bands. The ZOR and the dual-resonant TM01 modes can be independently controlled, and a triband antenna prototype with a square patch of 24 mm is fabricated and tested. The first bandwidth is 2.5–2.7 GHz with omnidirectional radiation pattern, the second and the third bandwidths with unidirectional radiation are 3.3–3.9 GHz and 4.8–6.1 GHz, and the realized gains over the three bands are about 2.6, 6.5, and 7.5 dBi, respectively.