bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic losses in carbon forestry due to errors in inventory data
Authors: Ruotsalainen Roope , Pukkala Timo , Kangas Annika , Myllymäki Mari , Packalen Petteri
Published: September 2020

Forestry can help to mitigate climate change by storing carbon in trees, forest soils, and wood products. Forest owners can be subsidized if forestry removes carbon from the atmosphere and taxed if forestry produces emissions. Errors in forest inventory data can lead to losses in net present value (NPV) if management prescriptions are selected based on erroneous data. This study assesses the effect of inventory errors on economic losses in forest management when the objective is to maximize the total NPV of timber production and carbon payments. Errors similar to those in airborne laser scanning based forest inventory were simulated in stand attributes with a vine copula approach and nearest neighbor method. Carbon payments were based on the total carbon balance of forestry (including trees, soil, and wood-based products) and calculations were carried out for 30 years using carbon prices of 0, 50, 75, 100, 125, and 150 €·t−1. The results revealed that increasing the carbon price and decreasing the level of errors led to decreased losses in NPV. The inclusion of carbon payments for the maximization of the NPV decreased the effect of errors on the losses, which suggests that the value of collecting more accurate forest inventory data may decrease when the carbon price increases.
Development of alien addition lines fromCucumis hystrixinCucumis sativus: cytological and molecular marker analyses
Authors: Li Mengxue , Zhao Qinzheng , Liu Yuxi , Qin Xiaodong , Hu Wei , Davoudi Marzieh , Chen Jinfeng , Lou Qunfeng
Published: September 2020

Transferring desired genes from wild species to cultivars through alien addition lines (AALs) has been shown to be an effective method for genetic improvement. Cucumis hystrix Chakr. (HH, 2n = 24) is a wild species of Cucumis that possesses many resistant genes. A synthetic allotetraploid species, C. hytivus (HHCC, 2n = 38), was obtained from the cross between cultivated cucumber, C. sativus (CC, 2n = 14), and C. hystrix followed by chromosome doubling. Cucumis sativus – C. hystrix AALs were developed by continuous backcrossing to the cultivated cucumbers. In this study, 10 different types of AALs (CC-H01, CC-H06, CC-H08, CC-H10, CC-H12, CC-H06+H09, CC-H06+H10, CC-H06+H12, CC-H08+H10, CC-H01+H06+H10) were identified based on the analysis of fluorescence in situ hybridization (FISH) and molecular markers specific to C. hystrix chromosomes. And the behavior of the alien chromosomes in three AALs (CC-H01, CC-H06+H10, CC-H01+H06+H10) at meiosis was investigated. The results showed that alien chromosomes paired with C. sativus chromosome in few pollen mother cells (PMCs). Further, disomic alien addition lines (DAALs) carrying a pair of C. hystrix chromosome H10 were screened from the selfed progenies of CC-H10. Chromosome pairing between genomes provides cytological evidence for the possible introgression of alien chromosome segments. The development of AALs could serve as a key step for exploiting and utilizing valuable genes from C. hystrix.
Dynamic Algorithms for Visibility Polygons in Simple Polygons
Authors: Inkulu R. , Sowmya K. , Thakur Nitish P.
Published: September 2020

We devise the following dynamic algorithms for both maintaining as well as querying for the visibility and weak visibility polygons amid vertex insertions and deletions to the simple polygon.

A fully-dynamic algorithm for maintaining the visibility polygon of a fixed point located interior to the simple polygon amid vertex insertions and deletions to the simple polygon. The time complexity to update the visibility polygon of a point [Formula: see text] due to the insertion (resp. deletion) of vertex [Formula: see text] to (resp. from) the current simple polygon is expressed in terms of the number of combinatorial changes needed to the visibility polygon of [Formula: see text] due to the insertion (resp. deletion) of [Formula: see text]. An output-sensitive query algorithm to answer the visibility polygon query corresponding to any point [Formula: see text] in [Formula: see text] amid vertex insertions and deletions to the simple polygon. If [Formula: see text] is not exterior to the current simple polygon, then the visibility polygon of [Formula: see text] is computed. Otherwise, our algorithm outputs the visibility polygon corresponding to the exterior visibility of [Formula: see text]. An incremental algorithm to maintain the weak visibility polygon of a fixed-line segment located interior to the simple polygon amid vertex insertions to the simple polygon. The time complexity to update the weak visibility polygon of a line segment [Formula: see text] due to the insertion of vertex [Formula: see text] to the current simple polygon is expressed in terms of the sum of the number of combinatorial updates needed to the geodesic shortest path trees rooted at [Formula: see text] and [Formula: see text] due to the insertion of [Formula: see text]. An output-sensitive algorithm to compute the weak visibility polygon corresponding to any query line segment located interior to the simple polygon amid both the vertex insertions and deletions to the simple polygon.

Each of these algorithms requires preprocessing the initial simple polygon. And, the algorithms that maintain the visibility polygon (resp. weak visibility polygon) compute the visibility polygon (resp. weak visibility polygon) with respect to the initial simple polygon during the preprocessing phase.
Analysis of Internal and External Academic Collaboration in an Institution Through Graph Theory
Authors: Guerrero-Sosa Jared D. T. , Menéndez-Domínguez Víctor H. , Castellanos-Bolaños María-Enriqueta , Curi-Quintal Luis F.
Published: September 2020

This paper presents an analysis of scientific collaboration through graph theory, based on a previous study focused on the collaborative work of researchers within an institution. This proposal also exposes the representation of inter-institutional collaboration of research groups, combining graph theory and data mining. The state of the art relates the concepts of scientific production, digital repositories, interoperability between repositories, the law of Open Science in Mexico, the theory of graphs and their use in previous studies for the analysis of scientific collaboration, and the definition of research groups in Mexico. Furthermore, the methodology uses elements of knowledge extraction for data mining, involving recovery, processing and visualization. Results present the collaboration status at the Universidad Autónoma de Yucatán, internally and externally, by the research groups. Internally, 22 groups were found and each researcher collaborates with six other professors within the institution, on average. In addition, consolidated research groups are those with the highest level of production and collaboration at national and international level, compared to the groups with less consolidation.
FaultDroid
Authors: Roy Indrani , Rebeiro Chester , Hazra Aritra , Bhunia Swarup
Published: September 2020

Fault attacks belong to a potent class of implementation-based attacks that can compromise a crypto-device within a few milliseconds. Out of the large numbers of faults that can occur in the device, only a very few are exploitable in terms of leaking the secret key. Ignorance of this fact has resulted in countermeasures that have either significant overhead or inadequate protection. This article presents a framework, referred to as FaultDroid, for automated vulnerability analysis of fault attacks. It explores the entire fault attack space, identifies the single/multiple fault scenarios that can be exploited by a differential fault attack, rank-orders them in terms of criticality, and provides design guidance to mitigate the vulnerabilities at low cost. The framework enables a designer to automatically evaluate the fault attack vulnerabilities of a block cipher implementation and then incorporate efficient countermeasures. FaultDroid uses a formal model of fault attacks on a high-level specification of a block cipher and hence is equally applicable to both software and hardware implementation of the cipher. As case studies, we employ FaultDroid to comprehensively evaluate the fault scenarios in several common ciphers—AES, CLEFIA, CAMELLIA, SMS4, SIMON, PRESENT, and GIFT—and assess their vulnerability.
Genetic Influences on Disease Subtypes
Authors: Dahl Andy , Zaitlen Noah
Published: September 2020

Disease classification, or nosology, was historically driven by careful examination of clinical features of patients. As technologies to measure and understand human phenotypes advanced, so too did classifications of disease, and the advent of genetic data has led to a surge in genetic subtyping in the past decades. Although the fundamental process of refining disease definitions and subtypes is shared across diverse fields, each field is driven by its own goals and technological expertise, leading to inconsistent and conflicting definitions of disease subtypes. Here, we review several classical and recent subtypes and subtyping approaches and provide concrete definitions to delineate subtypes. In particular, we focus on subtypes with distinct causal disease biology, which are of primary interest to scientists, and subtypes with pragmatic medical benefits, which are of primary interest to physicians. We propose genetic heterogeneity as a gold standard for establishing biologically distinct subtypes of complex polygenic disease. We focus especially on methods to find and validate genetic subtypes, emphasizing common pitfalls and how to avoid them.
Review—Futuristic Direction for R&D Challenges to Develop 2D Advanced Materials Based Supercapacitors
Authors: Raj Benjamin , Padhy Arun. K. , Basu Suddhasatwa , Mohapatra Mamata
Published: September 2020

Next-generation technologies in the development of energy storage devices are the need of current forefront research to surmount the depletion of fossils. The supercapacitor is one of the most promising energy storage devices with fast charging-discharging within second and exhibit excellent cyclic stability owing to their high power density with high mechanical compliance making them suitable electronic devices as power back-ups for stretchable electronic devices. The numerous options have been explored to increase the functionality of electrode or finding suitable and reliable electrolyte for high energy density and power density. Although it is a challenge for the scientific community and R&D sector to find the appropriate material/electrolyte for the development of supercapacitor. Under these circumstances, the two dimensional (2D) materials including quasi graphene, MXene and transition metal dichalcogenides owing high electrochemical performances attract immense interest towards the supercapacitors. These materials under the virtue of its unique physical and chemical behaviour owing to excellent electrical and mechanical properties with high surface area are well suited for supercapacitor applications. In this review, we briefly present current evolution, comparison of methods and materials in high range, a brief discussion on future directions, challenges and opportunities in the development of electrode material for supercapacitor.
Recent advances in understanding the ecology of the lung microbiota and deciphering the gut-lung axis
Authors: Willis Kent A. , Stewart Justin D. , Ambalavanan Namasivayam
Published: September 2020

A rapidly expanding new field of lung research has been produced by the emergence of culture-independent next-generation sequencing technologies. While pulmonary microbiome research lags behind the exploration of the microbiome in other organ systems, the field is maturing and has recently produced multiple exciting discoveries. In this mini-review, we will explore recent advances in our understanding of the lung microbiome and the gut-lung axis from an ecological perspective.
Influence of sympathetic activation on myocardial contractility measured with ballistocardiography and seismocardiography during sustained end-expiratory apnea
Authors: Morra Sofia , Gauthey Anais , Hossein Amin , Rabineau Jérémy , Racape Judith , Gorlier Damien , Migeotte Pierre-François , le Polain de Waroux Jean Benoit , van de Borne Philippe
Published: September 2020

Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. BCG and SCG kinetic energies (KE) and their temporal integrals ( iK) during a single heartbeat are computed in linear and rotational dimensions. Our aim was to test the hypothesis that iK from BCG and SCG are related to sympathetic activation during maximal voluntary end-expiratory apnea. Multiunit muscle sympathetic nerve traffic [burst frequency (BF), total muscular sympathetic nerve activity (tMSNA)] was measured by microneurography during normal breathing and apnea ( n = 28, healthy men). iK of BCG and SCG were simultaneously recorded in the linear and rotational dimension, along with oxygen saturation ([Formula: see text]) and systolic blood pressure (SBP). The mean duration of apneas was 25.4 ± 9.4 s. SBP, BF, and tMSNA increased during the apnea compared with baseline ( P = 0.01, P = 0.002, and P = 0.001, respectively), whereas [Formula: see text] decreased ( P = 0.02). At the end of the apnea compared with normal breathing, changes in iK computed from BCG were related to changes of tMSNA and BF only in the linear dimension ( r = 0.85, P < 0.0001; and r = 0.72, P = 0.002, respectively), whereas changes in linear iK of SCG were related only to changes of tMSNA ( r = 0.62, P = 0.01). We conclude that maximal end expiratory apnea increases cardiac kinetic energy computed from BCG and SCG, along with sympathetic activity. The novelty of the present investigation is that linear iK of BCG is directly and more strongly related to the rise in sympathetic activity than the SCG, mainly at the end of a sustained apnea, likely because the BCG is more affected by the sympathetic and hemodynamic effects of breathing cessation. BCG and SCG may prove useful to assess sympathetic nerve changes in patients with sleep disturbances.
Parasympathetic activity is the key regulator of heart rate variability between decelerations during brief repeated umbilical cord occlusions in fetal sheep
Authors: Lear Christopher A. , Westgate Jenny A. , Kasai Michi , Beacom Michael J. , Maeda Yoshiki , Magawa Shoichi , Miyagi Etsuko , Ikeda Tomoaki , Bennet Laura , Gunn Alistair J.
Published: September 2020

Fetal heart rate variability (FHRV) is a widely used index of intrapartum well being. Both arms of the autonomic system regulate FHRV under normoxic conditions in the antenatal period. However, autonomic control of FHRV during labor when the fetus is exposed to repeated, brief hypoxemia during uterine contractions is poorly understood. We have previously shown that the sympathetic nervous system (SNS) does not regulate FHRV during labor-like hypoxia. We therefore investigated the hypothesis that the parasympathetic system is the main mediator of intrapartum FHRV. Twenty-six chronically instrumented fetal sheep at 0.85 of gestation received either bilateral cervical vagotomy ( n = 7), atropine sulfate ( n = 7), or sham treatment (control, n = 12), followed by three 1-min complete umbilical cord occlusions (UCOs) separated by 4-min reperfusion periods. Parasympathetic blockade reduced three measures of FHRV before UCOs (all P < 0.01). Between UCOs, atropine and vagotomy were associated with marked tachycardia (both P < 0.005), suppressed measures of FHRV (all P < 0.01), and abolished FHRV on visual inspection compared with the control group. Tachycardia in the atropine and vagotomy groups resolved over the first 10 min after the final UCO, in association with evidence that the SNS contribution to FHRV progressively returned during this time. Our findings support that SNS control of FHRV is acutely suppressed for at least 4 min after a deep intrapartum deceleration and takes 5–10 min to recover. The parasympathetic system is therefore likely to be the key mediator of FHRV once frequent FHR decelerations are established during labor.
Multiple sclerosis-related fatigue: the role of impaired corticospinal responses and heightened exercise fatigability
Authors: Coates Kyla D. , Aboodarda Saied Jalal , Krüger Renata L. , Martin Tristan , Metz Luanne M. , Jarvis Scott E. , Millet Guillaume Y.
Published: September 2020

The etiology of fatigability from whole body exercise was examined for the first time to accurately elucidate the relationship between fatigue and fatigability in multiple sclerosis (MS). Compromised corticospinal responsiveness predicted fatigue severity, providing a novel, objective indicator of fatigue in MS. Although the impaired corticomotor transmission did not aggravate muscle activation in this group of people with multiple sclerosis (PwMS) of lower disability, heightened muscle fatigability was seen to contribute to perceptions of fatigue in PwMS.
Pentraxin 3 Levels in Young Women with and without Polycystic Ovary Syndrome (PCOS) in relation to the Nutritional Status and Systemic Inflammation
Authors: Wyskida Katarzyna , Franik Grzegorz , Choręza Piotr , Pohl Natalia , Markuszewski Leszek , Owczarek Aleksander , Madej Paweł , Chudek Jerzy , Olszanecka-Glinianowicz Magdalena
Published: September 2020

Objective. The aim of the study was to assess PTX3 levels in PCOS and non-PCOS women in relation to nutritional status and circulating markers of inflammation.Methods. The study enrolled 99 stable body mass PCOS women (17 normal weight, 21 overweight, and 61 obese) and 61 non-PCOS women (24 normal weight, 19 overweight, and 18 obese). Body composition was assessed by bioimpedance, and plasma levels of pentraxin 3 (PTX3), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) were measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was made.Results. Plasma PTX3, TNF-α, and IL-6 levels and HOMA-IR were higher in PCOS than in non-PCOS groupp<0.001. There were positive correlations between log10(PTX3) and log10(BMI), waist circumference and fat percentage, as well as log10(HOMA-IR) and free androgen index but negative between log10(estradiol) levels in PCOS. While in the non-PCOS group, the correlations between log10(PTX3) and log10(BMI), waist circumference and fat percentage, as well as log10(HOMA-IR) were negative. The positive correlations between PTX3 and MPC-1 and log10(IL-6) were shown in the PCOS group only. In multivariate regression analyses, variability in PTX3 levels in the PCOS group was proportional to log10(BMI), waist circumference, and fat percentage, but inversely proportional to log10(estradiol) levels. While in the non-PCOS group, PTX3 levels were inversely proportional to all anthropometric parameters.Conclusions. Our results show that the decrease in PTX3 levels observed in obese is distorted in PCOS by microinflammation, and possibly, dysfunction of stroma adipose tissue and liver steatosis is reflected by enhanced insulin resistance.
A New Equilibrium Strategy of Supply and Demand for the Supply Chain of Pig Cycle
Authors: Lu Changxiang , Fang Jiaqi , Fu Shaochuan
Published: September 2020

The pig market had experienced a cycle of price rise and fall, also known as the “pig cycle.” This paper analyzes the fluctuation relationship between pig price, pig supply, and pork demand, constructs a system dynamics model of the pig industry by decomposing the structure of the pig supply chain, and then discusses the causes of “pig cycle,” as well as the supply chain management strategy and industrial policy, to stabilize the pig industry market. Research shows that reducing the cost of pig breeding, countercyclical adjustment, and government macrocontrol can effectively reduce the fluctuation of pig prices. Among them, reducing the pig breeding cost is the most effective long-term strategy to stabilize the pig price.
Experimental Investigation of Damage Evolution Characteristics of C50 Concrete under Impact Load
Authors: Lei Mingfeng , Liu Linghui , Lin Yuexiang , Ma Jianjun , Shi Chenghua , Yang Weichao
Published: September 2020

Impact loads widely exist in practical engineering and often cause cumulative damage and cracks or even fracture failure of concrete structures with their repeated long-term action. This experimental research is conducted on the damage evolution characteristics of concrete under impact loads by regarding C50 nonreinforced concrete as the research object and using a self-developed drop-weight device with electromechanical impedance measurement technology. Results show the following. (1) Under low-energy impact, concrete damage has long continuous development process and remarkable cumulative effects. An apparently sudden break characteristic appears before failure. Under high-energy impact, concrete damage accumulates rapidly, and piezoceramic patch signals grow linearly. (2) The root mean square deviation (RMSD) of the concrete increases exponentially with impact times. Particularly, when the RMSD exceeds 0.075, the concrete damage process enters the rapid development stage and approaches the critical failure state. (3) Under the experimental conditions in this study, the relationship between the ultimate impact times (damage life) and impact heights of the concrete samples shows the development trend of the power function. The above results can provide reference for the research on service life prediction methods of concrete structures under impact loads.
Potential Applicability of Cocoa Pulp (Theobroma cacaoL) as an Adjunct for Beer Production
Authors: Nunes Cassiane S. O. , da Silva Marília L. C. , Camilloto Geany P. , Machado Bruna A. S. , Hodel Katharine V. S. , Koblitz Maria Gabriela B. , Carvalho Giovani B. M. , Uetanabaro Ana Paula T.
Published: September 2020

The aim of this study was to evaluate the application of cocoa pulp as an adjunct for malt in beer production. The cocoa pulp was analyzed for humidity, proteins, lipids, sugars, total soluble solids, organic acids, and minerals. A study was carried out to reduce the cocoa pulp viscosity by enzymatic depectinization, making its use viable in beer production. The cocoa pulp showed relevant quantities of compounds important in fermentation, such as sugars, acids, and minerals. In fermentation using the adjunct, the proportions of pulp used were 10, 30, and 49%. A significant difference was found between the adjunct and all-malt worts. The 30% cocoa pulp concentration as an adjunct for malt in the fermentation medium contributed the most to the fermentative performance of the yeasts at both 15 and 22°C based on the consumption of apparent extract (°Plato), ethanol production, and cellular growth.
HPLC Analysis and Antioxidant Evaluation of Acteoside-Rich Osmanthus fragrans Extracts
Authors: Lee Sung-Ho , Seo Seong-Wook , Song Seung-Yub , Oh Deuk-Sil , Shim Jung-Hyun , Yoon Goo , Choi Ye-Yong , Kim Do-Kyung , Kim Jae-Sung , Yoon In-Soo , Cho Seung-Sik
Published: September 2020

A method for the separation and quantification of acteoside by reverse-phase high-performance liquid chromatography (HPLC) was developed and validated. Hot water and ethanolic extracts of Osmanthus fragrans leaves and flowers were analyzed for acteoside content. Excellent linearity was obtained, with an r2 higher than 0.999. The precision, specificity, and accuracy of our method were excellent, suggesting that it can be conveniently used for the quantification of acteoside in the crude extract of O. fragrans. The hot water and ethanol extracts were analyzed, and their biological activities were tested. The extraction yields, marker (acteoside) contents, and antioxidant activities of the leaf and flower extracts were analyzed. The antioxidant activity was confirmed by measuring the 2,2-diphenyl-2-picrylhydrazyl radical scavenging activity, reducing power, and total phenolic content. The acteoside content tended to be higher in the 100% ethanol extract of O. fragrans compared to those with the other extraction conditions tested. Overall, almost all extracts prepared with ethanolic solvents tended to produce better antioxidant activity than those prepared with hot water. These results suggest that the ethanolic extract of O. fragrans could serve as a potential antioxidant and anti-inflammatory pharmaceutical source, and our validated method would be useful for the quality control of O. fragrans extracts.
Impact Properties of Recycled Aggregate Concrete with Nanosilica Modification
Authors: Wang Xingguo , Cheng Fei , Wang Yixin , Zhang Xianggang , Niu Haicheng
Published: September 2020

The optimal soaking time and nanosilica concentration were chosen by the physical properties of the nanosilica‐modified recycled aggregate. Recycled aggregate concrete (RAC) and nanosilica recycled aggregate concrete (SRAC) were fabricated by using ordinary recycled aggregate and nanosilica‐modified recycled aggregate. Based on the comparative experimental study of basic mechanical properties, the effects of nanosilica recycled aggregate(SRA) modification and recycled aggregate(RA) replacement percentage on the basic mechanical properties of recycled concrete were analyzed. Finally, the split‐Hopkinson pressure bar (SHPB) was used to conduct comparative experimental research on the impact resistance of recycled aggregate concrete and nanosilica‐modified recycled aggregate concrete. The effects of nanosilica recycled aggregate modification and aggregate replacement percentage on failure morphology, dynamic peak stress, dynamic increase factor (DIF), dynamic peak strain were analyzed.
Vaginal Delivery at Term in a Woman with a Spontaneous Heterotopic Pregnancy Treated with Laparoscopic Salpingectomy
Authors: Diakosavvas Michail , Blontzos Nikolaos , Daskalakis Georgios , Protopapas Athanasios , Kathopoulis Nikolaos , Antsaklis Panagiotis , Derdelis Grigorios , Angelou Kyveli , Fasoulakis Zacharias , Loutradis Dimitrios , Theodora Marianna
Published: September 2020

Background. The coexistence of an intrauterine pregnancy and an ectopic pregnancy (heterotopic pregnancy) is an extremely rare, yet major, complication during pregnancy. The early diagnosis of a heterotopic pregnancy is of great importance for fetal viability, maternal safety, and the progression of an uncomplicated intrauterine pregnancy. Case Presentation. We report a case of a naturally conceived heterotopic tubal pregnancy in a 37-year-old primigravida. The patient presented with continuous, dull, lower abdominal pain and a positive urine pregnancy test which was conducted a week prior to the start of the pain. The patient was hospitalized, and based on the clinical image and after strict monitoring, she was diagnosed with a heterotopic pregnancy. She was treated with laparoscopic salpingectomy after the rupture of the ectopic pregnancy while the desired intrauterine gestation continued without any complications. The pregnancy resulted in the birth of a healthy infant through vaginal delivery. Discussion. Strict monitoring with multiple sonographic evaluations should always be conducted in women with abnormal serum beta-hCG, adnexal abnormalities, or clinical symptoms, while heterotopic pregnancy should be in differential diagnosis and treatment should not be delayed since emerge management is important for the progression of the intrauterine pregnancy.
The Shape Effect of Gold Nanoparticles on Squeezing Nanofluid Flow and Heat Transfer between Parallel Plates
Authors: Rashid Umair , Abdeljawad Thabet , Liang Haiyi , Iqbal Azhar , Abbas Muhammad , Siddiqui Mohd. Junaid
Published: September 2020

The focus of the present paper is to analyze the shape effect of gold (Au) nanoparticles on squeezing nanofluid flow and heat transfer between parallel plates. The different shapes of nanoparticles, namely, column, sphere, hexahedron, tetrahedron, and lamina, have been examined using water as base fluid. The governing partial differential equations (PDEs) are transformed into ordinary differential equations (ODEs) by suitable transformations. As a result, nonlinear boundary value ordinary differential equations are tackled analytically using the homotopy analysis method (HAM) and convergence of the series solution is ensured. The effects of various parameters such as solid volume fraction, thermal radiation, Reynolds number, magnetic field, Eckert number, suction parameter, and shape factor on velocity and temperature profiles are plotted in graphical form. For various values of involved parameters, Nusselt number is analyzed in graphical form. The obtained results demonstrate that the rate of heat transfer is maximum for lamina shape nanoparticles and the sphere shape of nanoparticles has performed a considerable role in temperature distribution as compared to other shapes of nanoparticles.
Phase I and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer
Authors: Goyal Lipika , Sirard Cynthia , Schrag Michael , Kagey Michael H. , Eads Jennifer R. , Stein Stacey , El-Khoueiry Anthony B. , Manji Gulam A. , Abrams Thomas A. , Khorana Alok A. , Miksad Rebecca , Mahalingam Devalingam , Zhu Andrew X. , Duda Dan G.
Published: September 2020

Purpose:

Dickkopf-1 (DKK1) modulates Wnt signaling, promoting tumor growth, metastasis, and immunosuppression. High DKK1 expression has been detected in various tumor types—including biliary tract cancer (BTC)—and is associated with poor prognosis. DKN-01—a humanized mAb targeting DKK1—was evaluated in a phase I multicenter study in combination with gemcitabine and cisplatin in patients with unresectable or metastatic BTC with no prior systemic therapy for advanced disease.

Patients and Methods:

This study included a dose-escalation phase assessing DKN-01 at two dose levels (150 mg and 300 mg) combined with gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) followed by dose expansion. Primary endpoints evaluated safety and tolerability; secondary endpoints evaluated efficacy, pharmacokinetics, and circulating biomarkers.

Results:

Fifty-one patients with intrahepatic cholangiocarcinoma (63%), extrahepatic cholangiocarcinoma (8%), and gallbladder cancer (29%) were enrolled. No dose-limiting toxicities were seen, and the expansion phase proceeded with DKN-01 300 mg (N = 47). The most frequent grade 3/4 treatment-emergent adverse events included neutropenia (60%), thrombocytopenia (34%), and anemia (23%). The objective response rate was 21.3% and median progression-free survival was 8.7 months (95% confidence interval, 5.4–10.3 months). Better outcomes were associated with biomarkers of angiogenesis inhibition (increased sVEGFR1 and lower VEGF-C) and reduced inflammation (lower IL6 and decreased TNFα).

Conclusions:

DKN-01 300 mg was well tolerated in this combination but did not appear to have additional activity beyond historically reported efficacy with gemcitabine/cisplatin alone. Exploratory pharmacokinetic and biomarker data indicate potential antiangiogenic and immunomodulatory activity of DKN-01/chemotherapy and the need for increased dose/intensity. A study with DKN-01 600 mg in combination with a PD-1 inhibitor in BTC is ongoing.
LILRB4-targeting Antibody–Drug Conjugates for the Treatment of Acute Myeloid Leukemia
Authors: Anami Yasuaki , Deng Mi , Gui Xun , Yamaguchi Aiko , Yamazaki Chisato M. , Zhang Ningyan , Zhang Cheng Cheng , An Zhiqiang , Tsuchikama Kyoji
Published: September 2020

Acute myeloid leukemia (AML) is the most common and aggressive blood cancer in adults. In particular, significant unmet medical needs exist for effective treatment strategies for acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) AML subtypes. Antibody–drug conjugates (ADC) are a promising drug class for AML therapy, as demonstrated by the FDA-approved anti-CD33 ADC, gemtuzumab ozogamicin (Mylotarg). However, CD33 is expressed in normal hematopoietic stem cells, highlighting the critical need to identify AML-specific targets to minimize the risk of potential adverse effects. We have demonstrated that the leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) is expressed at significantly higher levels on monocytic M4 and M5 AML cells than on normal counterparts. Here, we test whether LILRB4 is a promising ADC target to kill monocytic AML cells while sparing healthy counterparts. To this end, we generated ADCs from a humanized anti-LILRB4 mAb and the antimitotic payload, monomethyl auristatin F. The conjugates constructed were characterized and evaluated for LILRB4-specific cell killing potency, toxicity to progenitor cells, pharmacokinetics, and therapeutic efficacy. Our ADC linker technology platform efficiently generated homogeneous anti-LILRB4 ADCs with defined drug-to-antibody ratios. The homogeneous anti-LILRB4 ADCs demonstrated the capacity for LILRB4-mediated internalization, suitable physicochemical properties, and high cell killing potency against LILRB4-positive AML cells. Importantly, our data indicate that these ADCs spare normal progenitor cells. One of our homogeneous conjugates exerted a remarkable therapeutic effect and no significant toxicity in a xenograft mouse model of disseminated human AML. Our findings highlight the clinical potential of anti-LILRB4 ADCs in monocytic AML therapy.
Initial Mechanistic Screening of Transamniotic Stem Cell Therapy in the Rodent Model of Spina Bifida: Host Bone Marrow and Paracrine Activity
Authors: Lazow Stefanie P. , Tracy Sarah A. , Chalphin Alexander V. , Kycia Ina , Zurakowski David , Fauza Dario O.
Published: September 2020

Purpose: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can induce spina bifida coverage with neoskin. We initiated a mechanistic analysis of this host response. Methods: Pregnant dams (n = 28) exposed to retinoic acid to induce fetal spina bifida were divided into an untreated group and 2 groups receiving intra-amniotic injections on gestational day 17 (E17; term = E21–22) of either amniotic fluid-derived MSCs (afMSCs; n = 105) or saline (n = 107). Gene expressions of multiple paracrine and cell clonality markers were quantified at term by RT-qPCR at the defect and fetal bone marrow. Defects were examined histologically for neoskin coverage. Comparisons were by Mann-Whitney U tests and logistic regression. Results: Defect coverage was associated with significant downregulation of both epidermal growth factor (Egf; p = 0.031) and fibroblast growth factor-2 (Fgf-2; p = 0.042) expressions at the defect and with significant downregulation of transforming growth factor-beta-1 (Tgfb-1; p = 0.021) and CD45 (p = 0.028) expressions at the fetal bone marrow. Conclusions: Coverage of experimental spina bifida is associated with local and bone marrow negative feedback of select paracrine factors, as well as increased relative mesenchymal stem cell activity in the bone marrow. Further analyses informed by these findings may lead to strategies of nonsurgical induction of prenatal coverage of spina bifida.
Phase 1 Study of Combined Chemotherapy of Nab-Paclitaxel, S-1, and Oxaliplatin for Gastric Cancer with Peritoneal Metastasis (NSOX Study)
Authors: Nakamura Masaki , Ojima Toshiyasu , Katsuda Masahiro , Hayata Keiji , Kitadani Junya , Nakamori Mikihito , Yamaue Hiroki
Published: September 2020

Objectives: A regimen of S-1 combined with oxaliplatin (SOX) has been widely used as the first-line regimen for advanced gastric cancer. To further improve the antitumor efficacy for gastric cancer patients with peritoneal metastasis, we added nab-paclitaxel to the established SOX regimen (NSOX). Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) has effective transferability to tumor tissues and strong antitumor effects for peritoneal metastasis. We performed a phase 1 study of this regimen to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in patients with gastric cancer with peritoneal metastasis. Methods: The NSOX regimen involved 21-day cycles with escalated doses of nab-paclitaxel (50 [level 1] to 80 [level 4] mg/m2 on days 1 and 8) and fixed doses of oxaliplatin (100 mg/m2 on day 1) and S-1 (80 mg/m2/day for 2 weeks). Results: Six patients with gastric cancer with peritoneal metastasis were enrolled. The MTD was determined to be dose level 2, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. No patients experienced DLTs, so the RD was determined to be dose level 1. Conclusions: The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for patients with gastric cancer with peritoneal metastasis.
Long-Term Outcome of Monochorionic Twins after Fetoscopic Laser Therapy Compared to Matched Dichorionic Twins
Authors: Rüegg Ladina , Hüsler Margaret , Krähenmann Franziska , Zimmermann Roland , Natalucci Giancarlo , Ochsenbein-Kölble Nicole
Published: September 2020

Introduction: The only causal therapy is fetoscopic laser surgery (FLS). The aims of this study were to analyze the long-term outcome of monochorionic twins treated by FLS, including their school career, need for therapy and special aid equipment, and free-time activities, and compare their outcome to matched dichorionic twins. Material and Methods: Among the 57 women treated at a single fetal treatment center between 2008 and 2017 with FLS because of twin-to-twin transfusion syndrome, 25 women with 42 children were included in the FLS group. The control group consisted of 16 dichorionic twin pairs matched for birth year, gestational age (GA), birth weight, and sex. The long-term outcome was assessed by a parental questionnaire and a standardized neurodevelopmental examination for children born before 32 gestational weeks or with a birth weight lower than 1500 g. They were also registered into the Swiss Neonatal Network database. The primary outcome was event-free survival, defined as normal neurology, behavior, vision, and hearing. The secondary outcomes were school career, need for therapy and special aid equipment, and free-time activities. Results: An event-free survival was found in 32 children (76%) in the laser and in 24 children (75%) in the control group (p = 0.91). Neurological anomalies were found in 5 children (12%) in the laser group and 3 children (9%) in the control group (p = 1.00). Multiple logistic regression analysis showed that GA at delivery was the only predictive factor for event-free survival. There were no significant differences regarding school career, therapies, or special aid equipment between the 2 groups. We found that children without FLS were involved in more free-time activities and needed fewer breaks during physical activity than children with FLS during pregnancy. Conclusion: The outcome of monochorionic twins treated with FLS is comparable to the outcome of dichorionic twins. Long-term neurodevelopment in the cohort was mainly dependent on GA at birth.
Safety and Prognostic Value of Vasodilator Stress Cardiovascular Magnetic Resonance in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Pezel Théo , Sanguineti Francesca , Kinnel Marine , Landon Valentin , Bonnet Guillaume , Garot Philippe , Hovasse Thomas , Unterseeh Thierry , Champagne Stéphane , Louvard Yves , Claude Morice Marie , Garot Jérôme
Published: September 2020

Background:

Patients with heart failure with reduced ejection fraction (HFrEF; heart failure with reduced left ventricular ejection fraction <40%) referred for stress cardiovascular magnetic resonance (CMR) may have a less optimal hemodynamic response to intravenous vasodilator. The aim was to assess the prognostic value of vasodilator stress perfusion CMR in patients with HFrEF.

Methods:

Between 2008 and 2018, consecutive patients with HFrEF defined by left ventricular ejection fraction <40% prospectively referred for vasodilator stress perfusion CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement by CMR.

Results:

Of 1053 patients with HFrEF (65±11 years, median [interquartile range] left ventricular ejection fraction 38.7% [37.2–39.0]), 1018 (97%) completed the CMR protocol and 950 (93%) completed the follow-up (median [interquartile range], 5.6 [3.6–7.3] years); 117 experienced a MACE (12.3%). Stress CMR was well tolerated without any adverse events. Patients without ischemia or late gadolinium enhancement experienced a lower annual event rate of MACE (1.8%) than those with both ischemia and late gadolinium enhancement (12.0%;
P
<0.001). Using Kaplan-Meier analysis, inducible ischemia and late gadolinium enhancement were significantly associated with the occurrence of MACE (hazard ratio, 2.46 [95% CI, 1.69–3.60]; and hazard ratio, 2.92 [95% CI, 1.77–4.83], respectively, both
P
<0.001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE (hazard ratio, 2.26 [95% CI, 1.52–3.35];
P
<0.001).

Conclusions:

Stress CMR is safe and has a good discriminative prognostic value to predict the occurrence of MACE in patients with HFrEF.
On the Event-Structural Properties of the EnglishGet-Passive
Authors: Biggs Alison , Embick David
Published: September 2020

An important discussion in theories of argument structure concerns the explanatory division of labor between thematic properties and event structure. English get-passives, analyzed in much previous work as differing thematically from be-passives, provide an interesting test case. We present an analysis of get-passives centered on the proposal that they contain additional event structure (realized as get) relative to their be counterparts. We employ by-adjuncts to identify the different event structures in passive types, and use other diagnostics to support our analysis. Further discussion considers the prominent proposal from previous studies that get-passives differ thematically from be-passives in (sometimes) assigning an Agent role to their surface subjects. We show that contrasts between get and be on this dimension are a consequence of event-structural differences between the two. The result is a unified analysis of the get-passive that has implications for the role of event structure in understanding the syntax and interpretation of arguments.
Person of Interest: Experimental Investigations into the Learnability of Person Systems
Authors: Maldonado Mora , Culbertson Jennifer
Published: September 2020

Person systems convey the roles entities play in the context of speech (e.g., speaker, addressee). As with other linguistic category systems, not all ways of partitioning the person space are equally likely crosslinguistically. Different theories have been proposed to constrain the set of possible person partitions that humans can represent, explaining their typological distribution. This article introduces an artificial language learning methodology to investigate the existence of universal constraints on person systems. We report the results of three experiments that inform these theoretical approaches by generating behavioral evidence for the impact of constraints on the learnability of different person partitions. Our findings constitute the first experimental evidence for learnability differences in this domain.
Biological attributes of Salibro™, a novel sulfonamide nematicide. Part 2: Impact on the fitness of various non-target nematodes
Authors: Thoden Tim C. , Alkader Mariam A. , Wiles John A.
Published: September 2020

Currently a renaissance in chemical nematicides is taking place with novel products like Nimitz® (a.s. fluensulfone), Velum Prime® (a.s. fluopyram) and Salibro™ (a.s. fluazaindolizine – Reklemel™ active) entering the marketplace. Although a considerable amount of published data is already available on their laboratory and field impact on plant-parasitic nematodes, little is understood of their compatibility with the beneficial or free-living nematodes that are part of the soil health network. In a range of laboratory studies, the effects of these nematicides on the vitality and reproduction of several species was tested, including both cosmopolitan free-living nematodes (Acrobeloides, Cruznema, Panagrobelus) as well as commercially applied entomopathogenic nematodes (Steinernema, Heterorhabditis). Within aqueous exposure and agar plate in vitro assays, species sensitivity to those nematicides differed significantly but their fitness (vitality and reproduction; infectivity to insect hosts) was generally not adversely impacted by concentrations of 5-50 ppm (a.s.) of Salibro. Even at 250 ppm (a.s.) of Salibro only some species of the bacterial-feeding species showed some negative impact. By contrast, both Nimitz at 50 ppm (a.s.) and Velum at 5 ppm (a.s.) consistently demonstrated stronger adverse impacts. In second level soil drenching assays, either no, or occasionally slight, adverse effects on the natural community of free-living nematodes were observed if soils were drenched with different volumes of Salibro at 5-50 ppm (a.s.), while relatively stronger reductions were measured within the plant-parasitic species (especially root-knot nematodes). Both Nimitz and Vydate (a.s. oxamyl) showed some degree of compatibility at 5 and 25 ppm (a.s.), respectively, which was generally higher than for Velum Prime at 5 ppm (a.s.). Overall, these data indicate that, when used at common field rates, Salibro will be one of the best options as part of integrated nematode management programmes where the use of chemical nematicides is required.
Molecular and morphological characterisation of Trichodorus species (Nematoda: Trichodoridae), with description of T. pseudoaequalis n. sp. from California and other states of the USA
Authors: Decraemer Wilfrida , Subbotin Sergei A.
Published: September 2020

During surveys for stubby root nematodes in the natural vegetation of California, Oregon and Washington, USA, three known species, viz., Trichodorus californicus, T. intermedius and T. obscurus were recovered together with ten unidentified Trichodorus species. The three known and one new species were studied using an integrated approach. Trichodorus pseudoaequalis n. sp. is characterised by a medium-sized body about 800 μm long on average, male with two ventromedian cervical papillae anterior to secretory-excretory pore and three precloacal supplements all located anterior to the retracted spicules; spicules 39 μm long (average), slightly ventrally curved, more so in head region and blade with slight indentation mid-way and striation more pronounced in posterior half. Females possess a rather short (average 33% of corresponding body diam.) pear-shaped vagina with small vaginal sclerotised pieces (ca 1.5 μm long), rounded triangular in shape, obliquely orientated and close together; one pair of sublateral body pores anterior (about four vulval body diam.) to vulva and one pair of post-advulvar sublateral body pores. Trichodorus pseudoaequalis n. sp. differs from the most similar species, T. aequalis, in male characters like general spicule shape and ornamentation and in the position of the dorsal pharyngeal gland nucleus in both sexes (at same level of posterior ventrosublateral pair vs clearly separated). The phylogenetic relationships of the recovered species were reconstructed using the ITS2 rRNA and the D2-D3 expansion segments of 28S rRNA gene sequences.