bluuebunny/crossref_metadata_2025 huggingface dataset:
Small tropical forest trees have a greater capacity to adjust carbon metabolism to long‐term drought than large canopy trees
Authors: Bartholomew David C. , Bittencourt Paulo R. L. , da Costa Antonio C. L. , Banin Lindsay F. , de Britto Costa Patrícia , Coughlin Sarah I. , Domingues Tomas F. , Ferreira Leandro V. , Giles André , Mencuccini Maurizio , Mercado Lina , Miatto Raquel C. , Oliveira Alex , Oliveira Rafael , Meir Patrick , Rowland Lucy
Published: July 2020

The response of small understory trees to long‐term drought is vital in determining the future composition, carbon stocks and dynamics of tropical forests. Long‐term drought is, however, also likely to expose understory trees to increased light availability driven by drought‐induced mortality. Relatively little is known about the potential for understory trees to adjust their physiology to both decreasing water and increasing light availability. We analysed data on maximum photosynthetic capacity (Jmax, Vcmax), leaf respiration (Rleaf), leaf mass per area (LMA), leaf thickness and leaf nitrogen and phosphorus concentrations from 66 small trees across 12 common genera at the world's longest running tropical rainfall exclusion experiment and compared responses to those from 61 surviving canopy trees. Small trees increased Jmax, Vcmax, Rleaf and LMA (71, 29, 32, 15% respectively) in response to the drought treatment, but leaf thickness and leaf nutrient concentrations did not change. Small trees were significantly more responsive than large canopy trees to the drought treatment, suggesting greater phenotypic plasticity and resilience to prolonged drought, although differences among taxa were observed. Our results highlight that small tropical trees have greater capacity to respond to ecosystem level changes and have the potential to regenerate resilient forests following future droughts.
Single residues in the LRR domain of the wheat PM3A immune receptor can control the strength and the spectrum of the immune response
Authors: Lindner Stefan , Keller Bettina , Singh Simrat P. , Hasenkamp Zsuzsanna , Jung Esther , Müller Marion C. , Bourras Salim , Keller Beat
Published: July 2020

The development of improved plant nucleotide‐binding, leucine‐rich repeat (LRR) immune receptors (NLRs) has mostly been based on random mutagenesis or on structural information available for specific receptors complexed with the recognized pathogen effector. Here, we use a targeted mutagenesis approach based on the natural diversity of the Pm3 powdery mildew resistance alleles present in different wheat (Triticum aestivum) genotypes. In order to understand the functional importance of the amino acid polymorphisms between the active immune receptor PM3A and the inactive ancestral variant PM3CS, we exchanged polymorphic regions and residues in the LRR domain of PM3A with the corresponding segments of PM3CS. These novel variants were functionally tested for recognition of the corresponding AVRPM3A2/F2 avirulence protein in Nicotiana benthamiana. We identified polymorphic residues in four regions of PM3A that enhance the immune response, but also residues that reduce it or result in complete loss of function. We found that the identified critical residues in PM3A modify its activation threshold towards different protein variants of AVRPM3A2/F2. PM3A variants with a lowered threshold gave a stronger overall response and gained an extended recognition spectrum. One of these variant proteins with a single amino acid change was stably transformed into wheat, where it conferred race‐specific resistance to mildew. This is a proof of concept that improved PM3A variants with an enlarged recognition spectrum can be engineered based on natural diversity by exchanging single or multiple residues that modulate resistance function.
Retrospective evaluation of fresh frozen plasma use in 121 cats: 2009–2016
Authors: Lane William G. , Sinnott‐Stutzman Virginia B.
Published: July 2020

Objectives

To document indications for fresh frozen plasma (FFP) use in cats, doses administered, and frequency of adverse transfusion reactions (ATR).

Design

Retrospective observational study from January 2009 to November 2016.

Setting

Large urban referral and emergency facility.

Animals

One hundred twenty‐one client‐owned cats that received FFP.

Interventions

None.

Measurements and Main Results

Signalment, indication(s), dose, pre‐ and posttransfusion total plasma protein, prothrombin time, activated partial thromboplastin time, as well as possible ATR, primary disease process, and outcome were recorded. Doppler blood pressure was increased posttransfusion (mean pre 99.5 ± 30.8 mm Hg; post 108.5 ± 32.5 mm Hg, P = .027). Cats were significantly less likely to be coagulopathic posttransfusion (P < 0.001). Most common indications were suspected coagulopathy (n = 105, 83%), hemorrhage (n = 45, 35%), and hypotension (n = 32, 25%). Median dose was 6 mL/kg (interquartile range = 3 mL/kg) and was negatively correlated with body weight (r = –.598, P < 0.001). Possible ATR occurred in 17 of 108 (16%, 95% confidence interval [CI], 10–24%) of transfusions. Increased body temperature was most common in 11 of 108 (10%, 95% CI, 5–18%), followed by tachypnea/dyspnea in 8 of 108 (7%, 95% CI, 3–13%). Common primary disease processes included liver disease (n = 41, 34%), neoplasia (n = 19, 16%), and sepsis (n = 15, 12%). Overall mortality was 54%. Improvement of clotting times was associated with increased odds of survival (odds ratio = 2.4; 95% CI, 1.1–5.3; P = 0.023).

Conclusions

Clinician justifications for FFP transfusions are comparable to that reported in dogs; however, the mL/kg dose is lower. Coagulopathy and blood pressure significantly improve posttransfusion. Possible ATR were as frequent as that reported with feline packed RBCs transfusions and classified as mild.
Observation and control of maximal Chern numbers in a chiral topological semimetal
Authors: Schröter Niels B. M. , Stolz Samuel , Manna Kaustuv , de Juan Fernando , Vergniory Maia G. , Krieger Jonas A. , Pei Ding , Schmitt Thorsten , Dudin Pavel , Kim Timur K. , Cacho Cephise , Bradlyn Barry , Borrmann Horst , Schmidt Marcus , Widmer Roland , Strocov Vladimir N. , Felser Claudia
Published: July 2020

A very high Chern number

Topologically nontrivial electronic structure can often be characterized by the Chern number, the value of which is related to the magnitude of some of the exotic effects predicted to occur in such systems. Many topological phases discovered so far have a Chern number of 1 or 2, but higher values are also theoretically possible. Schröter
et al.
predicted that the chiral material palladium gallium (PdGa) would have a Chern number of 4, and they confirmed that prediction using photoemission experiments. Interestingly, the sign of the Chern number was opposite for the two enantiomers of PdGa.

Science
, this issue p.
179
Mycoavidus
sp. Strain B2-EB: Comparative Genomics Reveals Minimal Genomic Features Required by a Cultivable
Burkholderiaceae
-Related Endofungal Bacterium
Authors: Guo Yong , Takashima Yusuke , Sato Yoshinori , Narisawa Kazuhiko , Ohta Hiroyuki , Nishizawa Tomoyasu
Published: July 2020

This study attempted the isolation of a novel endobacterium,
Mycoavidus
sp. B2-EB (JCM 33615), harbored in the fungal host
Mortierella parvispora
E1425 (JCM 39028). We report the complete genome sequence of this strain, which possesses a reduced genome size with relatively high genome completeness and a streamlined genome structure. The information indicates the minimal genomic features required by both the endofungal lifestyle and artificial cultivation, which furthers our understanding of genome reduction in fungal endosymbionts and extends the culture resources for biotechnological development on engineering synthetic microbiomes.
Late-onset ‘sloughing esophagitis’ (esophagitis dissecans superficialis) associated with bullous pemphigoid
Authors: Morel-Cerda Eliana Carolina , Priego-Parra Bryan Adrian , Grube-Pagola Peter , Remes-Troche Jose Maria
Published: July 2020

Pemphigus is a rare autoimmune disease that causes blistering of the skin and oral mucosa. In bullous pemphigoid (BP), skin involvement is predominant, whereas oesophageal involvement is rare, compared with other blistering diseases. We present, herein, the case of a 67-year-old man with a history of successfully treated BP that 2 years later developed progressive dysphagia, unintentional weight loss and iron deficiency anaemia. An endoscopy with biopsies was performed, and its findings were consistent with ‘sloughing esophagitis’ (esophagitis dissecans superficialis) associated with BP. Oesophageal involvement was present during the first weeks, making our case unusual due to the isolated oesophageal symptoms that developed 24 months later.
Mental capacity assessment: a descriptive, cross-sectional study of what doctors think, know and do
Authors: Penn Dexter , Lanceley Anne , Petrie Aviva , Nicholls Jacqueline
Published: July 2020

Background

The Mental Capacity Act (MCA) (2005) was enacted in 2007 in England and Wales, but the assessment of mental capacity still remains an area of professional concern. Doctors’ compliance with legal and professional standards is inconsistent, but the reasons for poor compliance are not well understood. This preliminary study investigates doctors’ experiences of and attitudes toward mental capacity assessment (MCAx).

Methods

This is a descriptive, cross-sectional study where a two-domain, study-specific structured questionnaire was developed, piloted and digitally disseminated to doctors at differing career stages employed in a large, multi-site National Health Service Trust in London over 4 months in 2018. Descriptive statistics and frequency tables adjusted for missing data were generated and secondary analysis was conducted.

Results

Participants (n=92) were predominantly UK trained (82%), female (58%) and between the ages of 30 and 44 years (45%). Less than half (45%) of the participants reported receiving formal MCAx training. Only one-third (32%) of the participants self-rated themselves as very competent (29%) or extremely competent (4%). Self-reported MCA confidence was significantly affected by career stage with Consultants with over 10 years of experience reporting lowest confidence (p=0.001).

Conclusions

This study describes significant variation in practice by doctors and low self-confidence in the practice of MCAx. These results raise concerns that MCAx continues to be inconsistently performed by doctors despite appropriate awareness of the law and professional guidance on best practice.
Tree regeneration on industrial linear disturbances in treed peatlands is hastened by wildfire and delayed by loss of microtopography
Authors: Filicetti Angelo T. , Nielsen Scott E.
Published: July 2020

The world’s forests are highly fragmented by linear disturbances, and many forests have failed to recover decades after abandonment. Lack of recovery is common in unproductive forests, such as treed peatlands, because of conditions that limit tree growth, including simplification of microtopography (loss of microsites). The persistence of these features affects biodiversity, but of particular concern in Canada is the detrimental effects on threatened woodland caribou. Although natural regeneration of trees in peatlands occurs in some places, it is not an effective recovery strategy for restoring the habitat of woodland caribou. This has led to restoration activities with costs exceeding CAD$12 500/km. However, current restoration does not consider wildfires, which can destroy planted trees but also initiate early seral conditions that favor natural regeneration. Here we compared tree regeneration on seismic lines and adjacent forest controls for burnt (75 sites) and unburnt (68 sites) treed peatlands in northeast Alberta, Canada. Tree regeneration (stems with a DBH < 1 cm/ha) varied from 28 500 in burnt lines, 11 440 in unburnt lines, and 18 210 in burnt forest, to 9520 in unburnt forest. Wildfires promoted denser regeneration in sites with a greater proportion of serotinous species and water table depth. Microtopography and terrain wetness explained regeneration on burnt lines, but not unburnt lines. In burnt and unburnt lines, sunlight, microtopography, and depth of water table most affected tree regeneration patterns.
Ecological research should consider Indigenous peoples and stewardship
Authors: Schang Kyle A. , Trant Andrew J. , Bohnert Sara A. , Closs Alana M. , Humchitt Megan , McIntosh Kelsea P. , Way Robert G. , Wickham Sara B.
Published: July 2020

The relationship between Indigenous peoples and the functioning of terrestrial ecosystems has received increased attention in recent years. As a result, it is becoming more critical for researchers focusing on terrestrial ecosystems to work with Indigenous groups to gain a better understanding of how past and current stewardship of these lands may influence results. As a case study to explore these ideas, we systematically reviewed articles from 2008 to 2018 where research was conducted in North America, South America, and Oceania. Of the 159 articles included, 11 included acknowledgement of Indigenous stewardship, acknowledged the Indigenous Territories or lands, or named the Indigenous group on whose Territory the research was conducted. Within the scope of this case study, our results demonstrate an overall lack of Indigenous acknowledgement or consideration within the scope of our review. Given the recent advancements in our understanding of how Indigenous groups have shaped their lands, we implore researchers to consider collaboration among local Indigenous groups as to better cultivate relationships and foster a greater understanding of their ecosystems.
Strong coupling constants of the doubly heavy $$ \Xi _{QQ} $$ Baryons with $$ \pi $$ Meson
Authors: Olamaei A. R. , Azizi K. , Rostami S.
Published: July 2020

The doubly charmed $$\Xi _{cc}^{++} (ccu)$$Ξcc++(ccu) state is the only listed baryon in PDG, which was discovered in the experiment. The LHCb collaboration gets closer to discovering the second doubly charmed baryon $$\Xi _{cc}^{+} (ccd)$$Ξcc+(ccd), hence the investigation of the doubly charmed/bottom baryons from many aspects is of great importance that may help us not only get valuable knowledge on the nature of the newly discovered states, but also in the search for other members of the doubly heavy baryons predicted by the quark model. In this context, we investigate the strong coupling constants among the $$\Xi _{cc}^{+(+)}$$Ξcc+(+) baryons and $$\pi ^{0(\pm )}$$π0(±) mesons by means of light cone QCD sum rule. Using the general forms of the interpolating currents of the $$\Xi _{cc}^{+(+)}$$Ξcc+(+) baryons and the distribution amplitudes (DAs) of the $$\pi $$π meson, we extract the values of the coupling constants $$g_{\Xi _{cc} \Xi _{cc} \pi }$$gΞccΞccπ. We extend our analyses to calculate the strong coupling constants among the partner baryons with $$\pi $$π mesons, as well, and extract the values of the strong couplings $$g_{\Xi _{bb} \Xi _{bb} \pi }$$gΞbbΞbbπ and $$g_{\Xi _{bc} \Xi _{bc} \pi }$$gΞbcΞbcπ. The results of this study may help experimental groups in the analyses of the data related to the strong coupling constants among the hadronic multiplets.
Fluctuation-driven superconductivity in Sr2RuO4 from weak repulsive interactions
Authors: Rømer A. T. , Andersen B. M.
Published: July 2020

We provide results for the leading superconducting instabilities for a model pertaining to [Formula: see text] obtained within spin-fluctuation mediated superconductivity in the very weak-coupling limit. The theory incorporates spin–orbit coupling (SOC) effects both in the band structure and in the pairing kernel in the form of associated magnetic anisotropies. The leading superconducting phase is found to be [Formula: see text] and a nodal [Formula: see text]-wave state. However, the odd-parity helical solution can become leading either for small SOC and Hund’s coupling [Formula: see text] in the weak [Formula: see text]-limit, or in the opposite limit with large SOC and [Formula: see text] at larger values of the Hubbard-[Formula: see text]. The odd-parity chiral solution is never found to be leading. Finally we discuss the form of the resulting superconducting spectral gaps in the different explored parameter regimes.
A Method of Improving Time Integration Algorithm Accuracy for Long-Term Dynamic Simulation
Authors: Li Shi , Qin Leibo , Guo Hongchao , Yang Dixiong
Published: July 2020

This paper aims to improve the accuracy of time integration algorithms (TIAs) for long-term simulation of structural dynamics. To this end, a new method of reducing the period elongation (numerical dispersion) was proposed by utilizing the mass scaling matrix. Firstly, the period elongation of explicit Gui-[Formula: see text] algorithm as a representative was analyzed, and the strategy of enhancing the algorithm accuracy was investigated. Subsequently, the period elongation was reduced by introducing a parameter to change the mass matrix, which is weighted by the original mass matrix and stiffness matrix. The bisection method is utilized to determine the parameter according to the formulation of period elongation. Since just the mass matrix of original algorithm is changed slightly, the convergence rate of original TIA remains unchanged and the proposed mass scaling method imposes little influence on the stability condition of original algorithm. Moreover, this method has few modifications to the computer program of TIA and is easy to implement. Finally, both linear and nonlinear long-term dynamic response analyses for multiple-degree-of-freedom systems indicated that the proposed mass scaling method is effective and convenient to reduce the period elongation for several typical TIAs.
Quantum Computing
Authors: Piattini Mario , Peterssen Guido , Pérez-Castillo Ricardo
Published: July 2020

Quantum computing, and to an even greater extent quantum technology, is changing the world. Quantum computing is not an evolution of classical computer science; it is actually a revolution that completely changes the computing paradigm. Quantum computers are based on the principles of quantum mechanics, such as superposition and entanglement, and they seek to boost computational power exponentially. Many problems that have until now been impossible to solve, in practical terms, might very well be able to be addressed by means of quantum computing. The fact is that at the present time quantum computing is influencing most business sectors and research fields, due to its various promising applications. To make such applications become reality, quantum algorithms must be specially coded for these extremely different computers. Although some well-known quantum algorithms already exist, the need for quantum software will increase dramatically in the next years. In that context, quantum software has to be produced in a more industrial and controlled way, i.e., aspects such as quality, delivery, project management, or evolution of quantum software must be addressed. We are sure that quantum computing will be the main driver for a new software engineering golden age during the present decade of the 2020s.
Software Engineering Worldwide
Authors: Kuhrmann Marco , Pfahl Dietmar , Soldani Jacopo
Published: July 2020

Software engineering is a key discipline in computer science. Its purpose is to develop software products and services of high quality within economic constraints that meet customer requirements and create value. Considerable shares of the societal and industrial infrastructure depend on software, and software has become a key driver for innovation. So far, so good, but who shapes software engineering, who defines what the problems to be solved look like, and who decides about the importance of certain streams in software engineering research and practice? Furthermore, is software engineering in the USA or in Europe the same as, e.g., software engineering in Oceania or Africa? In this new column Software Engineering Worldwide, we aim to provide an overview of software engineering, its importance and its manifestation, in different regions worldwide. We wish to take a look behind the scenes to learn about the different environments and the respective key problems to be addressed in "local" software engineering research, practice, and education. We also aim to open the minds of the community regarding the involvement of new locations not yet on the software engineering map, and to stimulate constructive discussion on how to better involve such locations.
Non-Asymptotic Analysis of Monte Carlo Tree Search
Authors: Shah Devavrat , Xie Qiaomin , Xu Zhi
Published: July 2020

In this work, we consider the popular tree-based search strategy within the framework of reinforcement learning, the Monte Carlo Tree Search (MCTS), in the context of infinite-horizon discounted cost Markov Decision Process (MDP) with deterministic transitions. While MCTS is believed to provide an approximate value function for a given state with enough simulations, cf. [5, 6], the claimed proof of this property is incomplete. This is due to the fact that the variant of MCTS, the Upper Confidence Bound for Trees (UCT), analyzed in prior works utilizes "logarithmic" bonus term for balancing exploration and exploitation within the tree-based search, following the insights from stochastic multi-arm bandit (MAB) literature, cf. [1, 3]. In effect, such an approach assumes that the regret of the underlying recursively dependent non-stationary MABs concentrates around their mean exponentially in the number of steps, which is unlikely to hold as pointed out in [2], even for stationary MABs.
Heavy-traffic Analysis of the Generalized Switch under Multidimensional State Space Collapse
Authors: Hurtado-Lange Daniela , Theja Maguluri Siva
Published: July 2020

Stochastic Processing Networks that model wired and wireless networks, and other queueing systems, have been studied in heavytraffic limit under the so-called Complete Resource Pooling (CRP) condition. When the CRP condition is not satisfied, heavy-traffic results are known only in the special case of an input-queued switch and bandwidth-sharing network.

In this paper, we consider a very general queueing system called the 'generalized switch' that includes wireless networks under fading, data center networks, input-queued switch, etc. The primary contribution of this paper is to present the exact value of the steadystate mean of certain linear combinations of queue lengths in the heavy-traffic limit under MaxWeight scheduling algorithm. We use the Drift method, and we also present a negative result that it is not possible to obtain the remaining linear combinations (and consequently all the individual mean queue lengths) using this method. We do this by presenting an alternate view of the Drift method in terms of an (under-determined) system of linear equations. Finally, we use this system of equations to obtain upper and lower bounds on all linear combinations of queue lengths.
Fundamental Limits of Volume-based Network DoS Attacks
Authors: Fu Xinzhe , Modiano Eytan
Published: July 2020

Volume-based network denial-of-service (DoS) attacks refer to a class of cyber attacks where an adversary seeks to block user traffic from service by sending adversarial traffic that reduces the available user capacity. In this paper, we explore the fundamental limits of volume-based network DoS attacks by studying the minimum required rate of adversarial traffic and investigating optimal attack strategies. We start our analysis with single-hop networks where user traffic is routed to servers following the Join-the-Shortest- Queue (JSQ) rule. Given the service rates of servers and arrival rates of user traffic, we first characterize the feasibility region of the attack and show that the attack is feasible if and only if the rate of the adversarial traffic lies in the region.We then design an attack strategy that is (i). optimal: it guarantees the success of the attack whenever the adversarial traffic rate lies in the feasibility region and (ii). oblivious: it does not rely on knowledge of service rates or user traffic rates. Finally, we extend our results on the feasibility region of the attack and the optimal attack strategy to multi-hop networks that employ Back-pressure (Max-Weight) routing. At a higher level, this paper addresses a class of dual problems of stochastic network stability, i.e., how to optimally de-stabilize a network.
Measuring Membership Privacy on Aggregate Location Time-Series
Authors: Pyrgelis Apostolos , Troncoso Carmela , De Cristofaro Emiliano
Published: July 2020

While location data is extremely valuable for various applications, disclosing it prompts serious threats to individuals' privacy. To limit such concerns, organizations often provide analysts with aggregate time-series that indicate, e.g., how many people are in a location at a time interval, rather than raw individual traces. In this paper, we perform a measurement study to understand Membership Inference Attacks (MIAs) on aggregate location time-series, where an adversary tries to infer whether a specific user contributed to the aggregates. We find that the volume of contributed data, as well as the regularity and particularity of users' mobility patterns, play a crucial role in the attack's success. We experiment with a wide range of defenses based on generalization, hiding, and perturbation, and evaluate their ability to thwart the attack vis-à-vis the utility loss they introduce for various mobility analytics tasks. Our results show that some defenses fail across the board, while others work for specific tasks on aggregate location time-series. For instance, suppressing small counts can be used for ranking hotspots, data generalization for forecasting traffic, hotspot discovery, and map inference, while sampling is effective for location labeling and anomaly detection when the dataset is sparse. Differentially private techniques provide reasonable accuracy only in very specific settings, e.g., discovering hotspots and forecasting their traffic, and more so when using weaker privacy notions like crowd-blending privacy. Overall, our measurements show that there does not exist a unique generic defense that can preserve the utility of the analytics for arbitrary applications, and provide useful insights regarding the disclosure of sanitized aggregate location time-series.
Set the Configuration for the Heart of the OS
Authors: Kuo Hsuan-Chi , Chen Jianyan , Mohan Sibin , Xu Tianyin
Published: July 2020

This paper presents a study on the practicality of operating system (OS) kernel debloating-reducing kernel code that is not needed by the target applications-in real-world systems. Despite their significant benefits regarding security (attack surface reduction) and performance (fast boot times and reduced memory footprints), the state-of-the-art OS kernel debloating techniques are seldom adopted in practice, especially in production systems. We identify the limitations of existing kernel debloating techniques that hinder their practical adoption, including both accidental and essential limitations. To understand these limitations, we build an advanced debloating framework named Cozart which enables us to conduct a number of experiments on different types of OS kernels (including Linux and the L4 microkernel) with a wide variety of applications (including HTTPD, Memcached, MySQL, NGINX, PHP and Redis). Our experimental results reveal the challenges and opportunities towards making kernel debloating techniques practical for realworld systems. The main goal of this paper is to share these insights and our experiences to shed light on addressing the limitations of kernel debloating in future research and development efforts.
Dynamic Pricing and Matching for Two-Sided Queues
Authors: Mahavir Varma Sushil , Bumpensanti Pornpawee , Theja Maguluri Siva , Wang He
Published: July 2020

Motivated by diverse applications in sharing economy and online marketplaces, we consider optimal pricing and matching control in a two-sided queueing system. We assume that heterogeneous customers and servers arrive to the system with price-dependent arrival rates. The compatibility between servers and customers is specified by a bipartite graph. Once a pair of customer and server are matched, they depart from the system instantaneously. The objective is to maximize the long-run average profits of the system while minimizing average waiting time. We first propose a static pricing and max-weight matching policy, which achieves O(√ n) optimality rate when all of the arrival rates are scaled by n. We further show that a dynamic pricing and modified max-weight matching policy achieves an improved O(n1/3) optimality rate. In addition, we propose a constraint generation algorithm that solves value function approximation of the MDP and demonstrate strong numerical performance of this algorithm.
3D Brain Organoids: Studying Brain Development and Disease Outside the Embryo
Authors: Velasco Silvia , Paulsen Bruna , Arlotta Paola
Published: July 2020

Scientists have been fascinated by the human brain for centuries, yet knowledge of the cellular and molecular events that build the human brain during embryogenesis and of how abnormalities in this process lead to neurological disease remains very superficial. In particular, the lack of experimental models for a process that largely occurs during human in utero development, and is therefore poorly accessible for study, has hindered progress in mechanistic understanding. Advances in stem cell–derived models of human organogenesis, in the form of three-dimensional organoid cultures, and transformative new analytic technologies have opened new experimental pathways for investigation of aspects of development, evolution, and pathology of the human brain. Here, we consider the biology of brain organoids, compared and contrasted with the endogenous human brain, and highlight experimental strategies to use organoids to pioneer new understanding of human brain pathology.
Critical importance of dietary methionine and choline in the maintenance of lung homeostasis during normal and cigarette smoke exposure conditions
Authors: Jubinville Éric , Milad Nadia , Maranda-Robitaille Michaël , Lafrance Marc-Alexandre , Pineault Marie , Lamothe Jennifer , Routhier Joanie , Beaulieu Marie-Josée , Aubin Sophie , Laplante Mathieu , Morissette Mathieu C.
Published: July 2020

Genetic predispositions and environmental exposures are regarded as the main predictors of respiratory disease development. Although the impact of dietary essential nutrient deficiencies on cardiovascular disease, obesity, and type II diabetes has been widely studied, it remains poorly explored in chronic respiratory diseases. Dietary choline and methionine deficiencies are common in the population, and their impact on pulmonary homeostasis is currently unknown. Mice were fed choline- and/or methionine-deficient diets while being exposed to room-air or cigarette smoke for up to 4 wk. Lung functions were assessed using the FlexiVent. Pulmonary transcriptional activity was assessed using gene expression microarrays and quantitative PCR. Immune cells, cytokines, and phosphatidylcholine were quantified in the bronchoalveolar lavage. In this study, we found that short-term dietary choline and/or methionine deficiencies significantly affect lung function in mice in a reversible manner. It also reduced transcriptional levels of collagens and elastin as well as pulmonary surfactant phosphatidylcholine levels. We also found that dietary choline and/or methionine deficiencies markedly interfered with the pulmonary response to cigarette smoke exposure, modulating lung function and dampening inflammation. These findings clearly show that dietary choline and/or methionine deficiencies can have dramatic pathophysiological effects on the lungs and can also affect the pathobiology of cigarette smoke-induced pulmonary alterations. Expanding our knowledge in the field of “nutri-respiratory research” may reveal a crucial role for essential nutrients in pulmonary health and disease, which may prove to be as relevant as genetic predispositions and environmental exposures.
Mapping the relationships between joint stiffness, modeled muscle stiffness, and shear wave velocity
Authors: Vigotsky Andrew D. , Rouse Elliott J. , Lee Sabrina S. M.
Published: July 2020

Shear wave velocity is commonly assessed to infer the muscular origins of changes in joint stiffness, but the exact relationship between shear wave velocity changes in muscle and joint stiffness changes remains unknown. Here, we systematically evaluated and quantified this relationship in the plantar flexors. Our results provide evidence for the ability of shear wave velocity to elucidate the muscular origins of joint stiffness changes.
Combining cooling or heating applications with exercise training to enhance performance and muscle adaptations
Authors: Hyldahl Robert D. , Peake Jonathan M.
Published: July 2020

Athletes use cold water immersion, cryotherapy chambers, or icing in the belief that these strategies improve postexercise recovery and promote greater adaptations to training. A number of studies have systematically investigated how regular cold water immersion influences long-term performance and muscle adaptations. The effects of regular cold water immersion after endurance or high-intensity interval training on aerobic capacity, lactate threshold, power output, and time trial performance are equivocal. Evidence for changes in angiogenesis and mitochondrial biogenesis in muscle in response to regular cold water immersion is also mixed. More consistent evidence is available that regular cold water immersion after strength training attenuates gains in muscle mass and strength. These effects are attributable to reduced activation of satellite cells, ribosomal biogenesis, anabolic signaling, and muscle protein synthesis. Athletes use passive heating to warm up before competition or improve postexercise recovery. Emerging evidence indicates that regular exposure to ambient heat, wearing garments perfused with hot water, or microwave diathermy can mimic the effects of endurance training by stimulating angiogenesis and mitochondrial biogenesis in muscle. Some passive heating applications may also mitigate muscle atrophy through their effects on mitochondrial biogenesis and muscle fiber hypertrophy. More research is needed to consolidate these findings, however. Future research in this field should focus on 1) the optimal modality, temperature, duration, and frequency of cooling and heating to enhance long-term performance and muscle adaptations and 2) whether molecular and morphological changes in muscle in response to cooling and heating applications translate to improvements in exercise performance.
Analyzing EEG Signals Using Decision Trees: A Study of Modulation of Amplitude
Authors: Bastos Narusci S. , Marques Bianca P. , Adamatti Diana F. , Billa Cleo Z.
Published: July 2020

An electroencephalogram (EEG) is a test that records electrical activity of the brain using electrodes attached to the scalp, and it has recently been used in conjunction with BMI (Brain-Machine Interface). Currently, the analysis of the EEG is visual, using graphic tools such as topographic maps. However, this analysis can be very difficult, so in this work, we apply a methodology of EEG analysis through data mining to analyze two different band frequencies of the brain signals (full band and Beta band) during an experiment where visually impaired and sighted individuals recognize spatial objects through the sense of touch. In this paper, we present details of the proposed methodology and a case study using decision trees to analyze EEG signals from visually impaired and sighted individuals during the execution of a spatial ability activity. In our experiment, the hypothesis was that sighted individuals, even if they are blindfolded, use vision to identify objects and that visually impaired people use the sense of touch to identify the same objects.
Impervious Surface Expansion: A Key Indicator for Environment and Urban Agglomeration—A Case Study of Guangdong-Hong Kong-Macao Greater Bay Area by Using Landsat Data
Authors: Liu Fan , Zhao Yaolong , Muhammad Rizwan , Liu Xiaoding , Chen Mingqiang
Published: July 2020

Impervious surface (IS) is a key indicator to measure the urbanization process and ecological environment. Many studies have observed an urbanization process based on IS at the city scale. Understanding the changes in the IS over a period at a regional level offers an alternative and effective approach to characterize and quantify the spatial process of urban agglomeration. This study focuses on the urban agglomeration of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) by utilizing the sensor-based Landsat data during 1987-2017 and investigates the spatiotemporal distribution of IS expansion at both regional and city scales. The modified linear spectral mixture analysis (MLSMA) method is used to extract the IS of the GBA. Then, the IS mapping accuracies were assessed after comparison with high-resolution historical data. The spatiotemporal and directional changes of IS surfaces for GBA are analyzed by using Gravity Center (GC) and Standard Deviational Ellipse (SDE). Finally, Shannon’s Diversity Index (SHDI) is used to analyze the overall characteristics of landscape level, and the Patch Density (PD) and Landscape Shape Index (LSI) are used to describe the characteristics of different classes of the IS. The results show that the IS of the whole region experienced rapid and massive expansion during the past 30 years and exhibited a distinct characteristic along the Pearl River Delta (PRD) and the coastline. Furthermore, the IS area increased rapidly in the PRD, while it is relatively stable in Hong Kong and Macao. We believe that the findings of this study can help policy makers to better understand and maintain the sustainable development of the GBA.
Wear Behavior of the Multiheterostructured AZ91 Mg Alloy Prepared by ECAP and Aging
Authors: Xu Bingqian , Sun Jiapeng , Yang Zhenquan , Han Jing , Song Dan , Jiang Jinghua , Ma Aibin
Published: July 2020

The microstructure design based on the development of heterostructure provides a new way for high strength and ductility Mg alloys. However, the wear property, as an important service performance, of Mg alloys with heterostructure is scarcely investigated. In this work, a high strength and ductility AZ91 Mg alloy with multiheterostructure was prepared via a processing route combined industrial-scale equal channel angular pressing (ECAP) and aging. The multiheterostructure consists of the heterogeneous grain structure and heterogeneous precipitates. The dry sliding wear behavior of this multiheterostructured (MH) alloy is investigated compared to the as-cast alloy. The impacts of the applied load and duration time on the wear volume and coefficient of friction (COF) are analyzed, and the wear mechanism is further discussed. The result indicates that although the MH alloy exhibits high-desirable strength-ductility synergy, it shows a poorer wear resistance but a relatively lower COF compared to the as-cast alloy at the present condition. The wear mechanism of both alloys mainly involves abrasive wear, as well as mild adhesion, delamination, and oxidation. In comparison, the MH alloy shows relatively severe adhesion, delamination, and oxidation. The poor wear resistance of the MH alloy at the present dry sliding wear condition is linked to the abundant grain boundaries and fine precipitates. Therefore, one should reasonably use the MH Mg alloy considering the service conditions to seek advantages and avoid disadvantages.
Hepatoprotective Effect of Pericarpium zanthoxyli Extract Is Mediated via Antagonism of Oxidative Stress
Authors: Park Sang Mi , Kim Jae Kwang , Kim Eun Ok , Jegal Kyung Hwan , Jung Dae Hwa , Lee Sang Gon , Cho Il Je , Kim SeungMo , Byun Sung Hui , Ku Sae-kwang , Park Chung A. , Lee Chul Won , An Won G. , Kim Sang Chan , Zhao Rongjie
Published: July 2020

Pericarpium zanthoxyli has been extensively used in traditional Oriental medicine to treat gastric disorders and has anti‐inflammatory and antioxidative activities. Therefore, the present study examined a possible hepatoprotective effect of a P. zanthoxyli extract (PZE) and investigated the underlying molecular mechanisms. We employed an in vitro model of arachidonic acid (AA) + iron‐induced hepatocyte damage and an in vivo model of CCl4‐induced liver injury to assess the effects of PZE and evaluated the relevant molecular targets using biochemical assays, flow cytometry analysis, Western blot, and histopathological analysis. The PZE inhibited AA + iron‐induced hepatotoxicity in HepG2 cells, improved mitochondrial dysfunction, and reversed an increase in the cellular H2O2 production and a decrease in the reduced GSH levels induced by AA + iron. Treatment with either 30 or 100 μg/ml PZE significantly increased the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) protein, and the latter dose also increased the antioxidant response element‐ (ARE‐) driven luciferase activity and enhanced the protein expressions of glutamate‐cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. In addition, treatment with 100 μg/ml PZE for 3 or 6 h increased the phosphorylation rates of Nrf2 and the extracellular signal‐regulated kinase. In the in vivo experiment, oral treatment with both 100 and 300 mg/kg PZE inhibited the plasma aspartate aminotransferase activity, and the latter also inhibited the plasma alanine aminotransferase activity. In addition, both doses of PZE ameliorated the parenchymal degeneration and necrosis in the liver induced by CCl4 administration, which was associated with reduced expressions of cleaved caspase‐3, cleaved poly (ADP‐ribose) polymerase, nitrotyrosine, and 4‐hydroxynonenal by PZE. These findings suggest that PZE has protective effects against hepatotoxicity both in vitro and in vivo, which are mainly mediated via its antioxidant activity.
The Impact of Antidiabetic Agents on Sarcopenia in Type 2 Diabetes: A Literature Review
Authors: Wu Chen-Ning , Tien Kai-Jen
Published: July 2020

Sarcopenia is a geriatric syndrome characterized by decline of skeletal muscle mass and function. Contributing factors include nutritional, genetic, inflammatory, and endocrinal factors. The reported prevalence of sarcopenia in type 2 diabetes mellitus is high, especially in patients with poor glycemic control. Additionally, antidiabetic agents may alter the balance between protein synthesis and degradation through various mechanisms of skeletal muscle mass regulation. This study reviewed the literature on the pathogenesis of sarcopenia in diabetes mellitus and the current understanding of whether antidiabetic agents contribute positively or negatively to sarcopenia and muscle wasting.
The YAP-Interacting Phosphatase SHP2 Can Regulate Transcriptional Coactivity and Modulate Sensitivity to Chemotherapy in Cholangiocarcinoma
Authors: Buckarma EeeLN H. , Werneburg Nathan W. , Conboy Caitlin B. , Kabashima Ayano , O'Brien Daniel R. , Wang Chen , Ilyas Sumera I. , Smoot Rory L.
Published: July 2020

The Hippo pathway effector Yes-associated protein (YAP) is localized to the nucleus and transcriptionally active in a number of tumor types, including a majority of human cholangiocarcinomas. YAP activity has been linked to chemotherapy resistance and has been shown to rescue KRAS and BRAF inhibition in RAS/RAF-driven cancers; however, the underlying mechanisms of YAP-mediated chemoresistance have yet to be elucidated. Herein, we report that the tyrosine phosphatase SHP2 directly regulates the activity of YAP by dephosphorylating pYAPY357 even in the setting of RAS/RAF mutations, and that diminished SHP2 phosphatase activity is associated with chemoresistance in cholangiocarcinomas. A screen for YAP-interacting tyrosine phosphatases identified SHP2, and characterization of cholangiocarcinomas cell lines demonstrated an inverse relationship between SHP2 levels and pYAPY357. Human sequencing data demonstrated lower SHP2 levels in cholangiocarcinomas tumors as compared with normal liver. Cell lines with low SHP2 expression and higher levels of pYAPY357 were resistant to gemcitabine and cisplatin. In cholangiocarcinomas cells with high levels of SHP2, pharmacologic inhibition or genetic deletion of SHP2 increased YAPY357 phosphorylation and expression of YAP target genes, including the antiapoptotic regulator MCL1, imparting resistance to gemcitabine and cisplatin. In vivo evaluation of chemotherapy sensitivity demonstrated significant resistance in xenografts with genetic deletion of SHP2, which could be overcome by utilizing an MCL1 inhibitor.

Implications:

These findings demonstrate a role for SHP2 in regulating YAP activity and chemosensitivity, and suggest that decreased phosphatase activity may be a mechanism of chemoresistance in cholangiocarcinoma via a MCL1-mediated mechanism.
Maternal Motivation: Exploring the Roles of Prolactin and Pup Stimuli
Authors: Salais-López Hugo , Abellán-Álvaro María , Bellés María , Lanuza Enrique , Agustin-Pavon Carmen , Martínez-García Fernando
Published: July 2020

Motherhood entails increased motivation for pups, which become strong reinforcers and guide maternal behaviours. This depends on steroids and lactogens acting on the brain of females during pregnancy and postpartum. Since virgin female mice exposed to pups are nearly spontaneously maternal, the specific roles of endocrine and pup-derived signals in the induction of maternal motivation remain unclear. This work investigates maternal motivation in dams and virgin female mice, using a novel variant of the pup retrieval paradigm, the motivated pup retrieval test. We also analyse the role of prolactin (PRL) and of stimuli derived from a litter of pups and its mother, in the acquisition of maternal motivation. Experimental design included female mice in 3 conditions: lactating dams, comothers (virgins housed and sharing pup care with dams) and pup-naïve virgins. Females underwent 3 motivated-pup-retrieval trials, with pups displaced behind a 10-cm-high wire-mesh barrier. Dams retrieved with significantly lower latencies than comothers or virgins, indicating that full maternal motivation appears only after pregnancy. Although initially comothers and virgins showed no retrieval, comothers significantly improved throughout the experiment, suggesting an induced sensitization process. Lengthening exposure of comothers to the dyad pups-dam (from 2 to 5 days at the beginning of testing) had no strong effects on maternal sensitization. PRL responsiveness was analysed in these animals using immunohistochemical detection of phosphorylated signal transducer and activator of transcription 5 (pSTAT5, PRL-derived signalling marker). As expected, dams showed significantly higher pSTAT5 expression in most of the analysed nuclei. Moreover, comothers displayed significantly higher PRL responsiveness than pup-naïve virgins in the medial preoptic nucleus, even if they display similar circulating PRL levels, which are significantly lower than those of dams. Given the instrumental role of this nucleus in the relay and integration of pup-derived stimuli to facilitate proactive maternal responses, this increase in PRL responsiveness likely reflects the mechanism underlying the maternal sensitization process reported in this work. Since the analyses of maternal motivation and PRL signalling in the brain were performed in the same animals, we were able to explore correlation between both set of data. The results shed light on the neuroendocrine mechanisms underlying maternal motivation and other aspects of maternal behaviour.