bluuebunny/crossref_metadata_2025 huggingface dataset:
Physicochemical Characterization and Oral Dosage Form Design and Selection
Authors: Dening Tahnee J. , Amidon Gregory E. , He Xiaorong , Hageman Michael J.
Published: April 2021

In order to initiate formulation development activities – that is the identification of a “marketable” product – important physical and chemical properties (physicochemical properties) as well as permeability properties need to be determined. Evaluation of these properties early in the discovery process can help discovery teams select which templates to pursue as well as identify the most promising leads. This information is also valuable “downstream” as decisions regarding dosage form design are being made. The focus of this article will be on the physicochemical properties that are most important in the evaluation of discovery leads and that provide the information needed as dosage form development is initiated and progresses. It will become apparent that the most appropriate dosage forms that make sense to consider are dictated by both the physicochemical and biopharmaceutical properties of the drug molecule. Throughout this article, there will be an emphasis on the tools and principles that will help the medicinal chemist during the drug discovery process, with particular emphasis on oral dosage forms.
The FDA and Drug Regulatory Issues
Authors: Randad Ramnarayan S.
Published: April 2021

The U.S. Food and Drug Administration (FDA) is a part of the U.S. Department of Health and Human Services (HHS). It is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, tobacco products, cosmetics, products that emit radiation, and our nation's food supply. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science‐based information they need to use medicines and foods to improve their health. FDA also plays a significant role in the Nation's counterterrorism capability (
https://www.fda.gov/AboutFDA/WhatWeDo/default.htm
).
New and Emerging Antiepileptic Drugs
Authors: Witkin Jeffrey M. , Golani Lalit K. , Smith Jodi L.
Published: April 2021

This article provides the biologist, chemist, and clinician with an overview into currently existing epilepsy medicines, an appreciation of those currently in development, and a glimpse at future possibilities. The discovery and development of antiepileptic drugs with improved efficacy and side‐effect dimensions are urgently needed. We discuss various strategies for discovering new antiepileptic drugs. We then provide summary data on the mechanisms of action, efficacy, and tolerability of some of the newer third‐generation antiepileptic drugs – eslicarbazepine, brivaracetam, retigabine, lacosamide, and perampanel. Additional compounds that are currently in development for epilepsy are also reviewed. These include the novel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonists CERC‐611 and JNJ‐55511118 that are first‐in‐class drugs blocking only those AMPA receptors associated with the auxiliary protein TAPP γ‐8. The GABA
A
(α2/3)‐selective compounds, KRM‐II‐81, MP‐III‐080, and PF‐06372865 hold additional promise and potential advantage over nonselective GABA
A
receptor modulators. The developmental status of another positive allosteric modulator of GABA
A
receptors, the neuroactive steroid ganaxolone, is also summarized. In addition, two mGlu2 receptor modulators, JNJ‐40411813 and LY2812223 are discussed. Finally, initial data on cannabidiol, anakinra, and padsevonil are reviewed. Literature data derived from studies on both human epileptic tissue and rodent seizure modeling were utilized to glean several compelling novel drug targets for consideration in future antiepileptic drug discovery programs. Thus, in the past decade, key advances have been made that are benefiting the epileptic patient community. The current compounds in development and new drug targets give additional promise of improved antiepileptic drugs.
Advances in Multiobjective Optimization for Drug Discovery and Development
Authors: Honeycutt J. Dana , Zorn Kimberley M. , Clark Alex M. , Ekins Sean
Published: April 2021

Drug discovery requires the simultaneous optimization of many properties such as bioactivity, absorption, distribution, metabolism, excretion, toxicity, and the underlying physicochemical properties. The ability to satisfy many requirements at once is termed multiobjective optimization, and we will discuss the importance of research in this area for drug discovery and development. In particular, we provide examples of Pareto and other optimization methods and how they can be used in drug discovery to make trade‐offs between different predicted or real molecular properties, and we describe advances in software that applies these approaches.
Prodrugs: Strategic Deployment, Metabolic Considerations, and Chemical Design Principles
Authors: Erhardt Paul W. , Khupse Rahul , Sarver Jeffrey G. , Kress Brian J.
Published: April 2021

This article begins by providing a brief history about prodrugs, and then delineates their specific definition while contrasting them to “regular” drugs and to soft drugs. It continues by discussing their strategic deployment during today's drug discovery and development paradigm, including their union with biological molecules to produce antibody–drug conjugates (ADCs) which are becoming extremely popular as new molecular entities (NMEs). Metabolic considerations focus upon hydrolytic processes while emphasizing, in particular, the important roles that are often played by the carboxylesterases. Design aspects include both a listing of commonly deployed functional groups and a discussion of how to impact upon their reaction rates by manipulating steric features of the chemical constructs. While replete with chemical structures and metabolic reactions throughout, the next section highlights all prodrug entries within the NMEs entering the US marketplace for the periods 2004–2008 and 2009–2017. Cataloged information relevant to this section is provided in two comprehensive appendices. The article concludes by conveying three case studies, which further serve to highlight the practical applications of prodrug design principles.
Effects of Deformation Processing Parameters on the Microstructure Evolution and Microhardness of GH4169 Superalloy during Annealing Treatment
Authors: Wang Guan-Qiang , Chen Ming-Song , Lin Yong‐Cheng , Li Hong-Bin , Ma Yan-Yong , Zou Zong-Huai , Chen Quan
Published: April 2021

Effects of deformation processing parameters on the microstructural evolution and microhardness of deformed samples during annealing treatment were analyzed. The results show that the initial aging time has the greatest influence on the refinement of annealed grain compared with other processing parameters. This attributes to more δ phases precipitating with the improving initial aging time. The high content of δ phase hinders the quick dynamic recrystallization (DRX) grain growth during annealing. Thus, the high strain rate helps to refine deformed grain by annealing treatment due to a high content of δ phase retained after deformation. Additionally, the massive appearance of recrystallized nuclei/grains also hinders adjacent grain growth. The appearance of many DRX nuclei at high deformation temperature or true strain will cause the fine annealed grain, although the dissolution of δ phase is enhanced. Thus, the grain deformed at 950–1010 °C can be refined to 11–14 μm during annealing. Furthermore, the high true strain is beneficial to obtain fine and homogeneous microstructure during annealing because the high deformation energy promotes static recrystallization (SRX) nucleation. Besides, the microhardness of GH4169 superalloy depends on the grain size and retained content of δ phase due to the fine‐grain and γ″ phase strengthening.
Phase Engineering of Nickel Sulfides to Boost Sodium‐ and Potassium‐Ion Storage Performance
Authors: Wu Jingxing , Liu Sailin , Rehman Yaser , Huang Taizhong , Zhao Jiachang , Gu Qinfen , Mao Jianfeng , Guo Zaiping
Published: April 2021

Sulfides are promising anode candidates because of their relatively large theoretical discharge/charge specific capacity and pretty small volume changes, but suffers from sluggish kinetics and structural instability upon cycling. Phase engineering can be designed to overcome the weakness of the electrochemical performance of sulfide anodes. By choosing nickel sulfides (α‐NiS, β‐NiS, and NiS2) supported by reduced graphene oxide (rGO) as model systems, it is demonstrated that the nickel sulfides with different crystal structures show different performances in both sodium‐ion and potassium‐ion batteries. In particular, the α‐NiS/rGO display superior stable capacity (≈426 mAh g−1 for 500 cycles at 500 mA g−1) and exceptional rate capability (315 mAh g−1 at 2000 mA g−1). The combined density functional theory calculations and experimental studies reveal that the hexagonal structure is more conducive to ion absorption and conduction, a higher pseudocapacitive contribution, and higher mechanical ability to relieve the stress caused by the volume changes. Correspondingly, the phase engineered nickel sulfide coupled with the conducting rGO network synergistically boosts the electrochemical performance of batteries. This work sheds light on the use of phase engineering as an essential strategy for exploring materials with satisfactory electrochemical performance for sodium‐ion and potassium‐ion batteries.
Multivalent Nanosheet Antibody Mimics for Selective Microbial Recognition and Inactivation
Authors: Kang Tae Woog , Hwang In‐Jun , Lee Sin , Jeon Su‐Ji , Choi Chanhee , Han Juhee , So Yoonhee , Son Wooic , Kim Hyunsung , Yang Chul‐Su , Park Jae‐Hyoung , Lee Hwankyu , Kim Jong‐Ho
Published: April 2021

Antibodies are widely used as recognition elements in sensing and therapy, but they suffer from poor stability, long discovery time, and high cost. Herein, a facile approach to create antibody mimics with flexible recognition phases and luminescent rigid scaffolds for the selective recognition, detection, and inactivation of pathogenic bacteria is reported. Tripeptides with a nitriloacetate‐Cu group are spontaneously assembled on transition metal dichalcogenide (TMD) nanosheets via coordination bonding, providing a diversity of TMD‐tripeptide assembly (TPA) antibody mimics. TMD‐TPA antibody mimics can selectively recognize various pathogenic bacteria with nanomolar affinities. The bacterial binding sites for TMD‐TPA are identified by experiments and molecular dynamics simulations, revealing that the dynamic and multivalent interactions of artificial antibodies play a crucial role for their recognition selectivity and affinity. The artificial antibodies allow the rapid and selective detection of pathogenic bacteria at single copy in human serum and urine, and their effective inactivation for therapy of infected mice. This work demonstrates the potential of TMD‐TPA antibody mimics as an alternative to natural antibodies for sensing and therapy.
Controlled Structural Transformation in Sb‐Doped Indium Halides A3InCl6 and A2InCl5∙H2O Yields Reversible Green‐to‐Yellow Emission Switch
Authors: Huang Jialuo , Chang Tong , Zeng Ruosheng , Yan Jun , Wei Qilin , Zhou Weichang , Cao Sheng , Zou Bingsuo
Published: April 2021

Lead halide perovskites have demonstrated promising emission tunability achieved by composition engineering, which makes them viable in several potential applications. Determining how to effectively control the crystalline structural transformation and composition in lead‐free halide perovskites is of great importance. Herein, a controllable synthetic method is reported to obtain the 0D metal halide perovskite derivatives (Cs1−xRbx)2InCl5∙H2O and (Cs1−xRbx)3InCl6, through synergistic regulation of the Cs/Rb feed ratios and the reaction solvent. When hydrochloric acid (HCl) is used as the reaction solvent, (Cs1−xRbx)2InCl5∙H2O is obtained at a high Cs/Rb feed ratio greater than 2:1, while (Cs1−xRbx)3InCl6 is obtained at a low Cs/Rb feed ratio of less than 2:5. However, when anhydrous methanol (MeOH) is used as the reaction solvent, only the (Cs1−xRbx)3InCl6 structure is obtained at all Cs/Rb feed ratios. In addition, a reversible crystalline structural transformation is demonstrated between (Cs0.67Rb0.33)2InCl5∙H2O and (Cs0.67Rb0.33)3InCl6 by immersing the as‐prepared products into MeOH and HCl sequentially, which generates a novel green/yellow reversible emission switch. The Sb3+ ion self‐trapped exciton emission and stability of the synthesized (Cs1−xRbx)2InCl5∙H2O and (Cs1−xRbx)3InCl6 are systematically investigated. The results are helpful for promoting the diverse photonics and optoelectronics applications of these environmentally stable perovskite derivatives.
Assessment of soybean test weight among genotypes, environments, agronomic and seed compositional traits
Authors: McNeece Brant T. , Gillenwater Jay H. , Li Zenglu , Mian M.A. Rouf
Published: April 2021

The value of soybean [Glycine max (L.) Merr.] depends on quantity (yield) and quality, such as seed composition and test weight (TW). Test weight is a bulk density measurement for grain quality evaluation, and higher TW grains are preferred for storage, transport, and export. Thus, soybean breeding should focus on improvement of TW. The objectives of this study were to determine genotypic and environmental effects on TW of soybean and explore relationships of TW with yield, maturity, 100 seed weight (SDWT), seed quality (SQ), seed oil concentration (SOC), and seed protein concentration (SPC). Three sets of breeding populations (BPs), two mapping populations (MPs), and five different high vs. low seed protein near‐isogenic lines populations (NILPs) were used. The BPs and MPs had an average range of 3.5 kg hectoliter (hL)–1 in TW among genotypes. The average ranges of TW in the NILPs were equal for both low protein (LP) and high protein (HP) lines (2.7 kg hL–1). Broad‐sense heritability estimates for TW ranged from .62 to .95. The genotypic and G × E effects on TW were significant in all trials. The SDWT, SQ, SOC, and SPC had strong significant relationships with TW in multiple trials, but were inconsistent overall. Test weight of NILPs differing by presence of ‘Danbaekkong’ high protein allele on chromosome 20 had mostly significant positive and negative relationships with SPC and SOC,  respectively.
Low dose venetoclax as a single agent treatment of plasma cell malignancies harboring t(11;14)
Authors: Nahi Hareth , Kashif Muhammad , Klimkowska Monika , Karvouni Maria , Wallblom Ann , Gran Charlotte , Hauenstein Julia , Frengen Nicolai , Gustafsson Charlotte , Afram Gabriel , Uttervall Katarina , Lund Johan , Månsson Robert , Wagner Arnika K. , Alici Evren
Published: April 2021

Approximately 20% of newly diagnosed multiple myeloma (NDMM) patients harbor t(11;14), a marker of inferior prognosis, resulting in up‐regulation of CCND1. These patients respond to BCL2 inhibitor experimental drug venetoclax. Furthermore, t(11;14) is reported to be associated with increased BCL2/MCL1 ratio. We investigated the use of venetoclax (400 mg daily) in a cohort of 25 multiple myeloma (MM) and AL‐amyloidosis patients harboring t(11;14) and assessed safety and efficacy. Efficacy was assessed by response rate (RR) and time on treatment. Furthermore, immunohistochemistry (IHC), for BCL2 family member expression was assessed at diagnosis and relapse in the venetoclax‐treated group and analyzed for correlation with clinical RR. Additionally, patient material from venetoclax non‐treated group including non‐t(11;14) diagnosis (n = 27), t(11;14) diagnosis (n = 17), t(11;14) relapse (n = 7), hyperdiploidy (n = 6) and hyperdiploidy + t(11;14) (n = 6) was used for RNA sequencing (RNASeq) and validation by qPCR. Venetoclax treatment in t(11;14) patients demonstrated manageable safety and promising efficacy. Partial responses or better were observed in eleven patients (44%). Responding patients had significantly higher BCL2/MCL1 (p = 0.031) as well as BCL2/BCL‐XL (p = 0.021) ratio, regardless of time of measurement before venetoclax treatment. Furthermore, an IRF5 motif was enriched (p < .001) in the downregulated genes in t(11;14) relapses vs diagnoses. The RR with single agent venetoclax was 71% in AL‐amyloidosis and 33% in MM, and IHC proved useful in prediction of treatment outcome. We could also demonstrate possible resistance mechanisms of t(11;14), downregulation of IRF5 targeted genes, which can be exploited for therapeutic advantages.
Factors influencing the survival of wild cotton‐top tamarin (Saguinus oedipus) infants
Authors: Savage Anne , Snowdon Charles T. , Soto Luis , Medina Felix , Emeris German , Guillen Rosamira
Published: April 2021

Studies of cooperative breeding species have suggested that helpers are needed for infant survival and that helpers gain skills to successfully raise their own offspring. Studies of callitrichids in managed care and early field studies suggested that group size correlated with infant survival and that helpers needed to learn parental skills to be successful breeders. We present infant survival data from a 20‐year field study of cotton‐top tamarins (Saguinus oedipus) in Colombia involving 126 litters born to 41 females. There was no difference in the survival of male and female offspring to 6 months of age. However, litter size impacted survival, with triplet litters having lower survival and male triplets having lower survival than females. Loss of infants was highest in the first week of life and, of the animals remaining in the group at 6 months of age, 90% of them survived to 1 year. The mean length of time in the natal group was 2.3 years but some young migrated to other groups after 4 months of age. Group size and number of male helpers (>1 year) was not related to infant survival. However, groups with only one male had fewer surviving infants. Primiparous females had lower infant survival, but previous infant care experience by mothers as helpers had no effect on survival. A major cause of infant loss was group disruption due to deaths/evictions/loss of the reproductively active animals, or immigration of pregnant females. Thus, factors that cause a change in the stability of the reproductively active animals can disrupt group cohesion. Capture of individuals for the illegal pet trade, as well as habitat fragmentation, may increase competition between groups for access to territories and breeding opportunities. This may have long‐term impacts to infant survival in this critically endangered species.
Stress behaviors in captive robust capuchins: Effects of humidity, visitors, management and sex
Authors: de la Barrera Cardozo Marina , Chiba de Castro Wagner A. , Aguiar Lucas M.
Published: April 2021

Wild robust capuchins (Sapajus spp.) are omnivorous neotropical primates that live in relatively large groups in extensive home and daily ranges with activity budgets dominated by traveling, foraging, and object manipulation, meaning that enclosed spaces can result in significant deprivation. Space restriction, manipulation by caretakers, and the chronic presence of visitors, can disrupt the animals' welfare, altering their normal activities and inducing stress behaviors. We aimed to study the behavioral repertoire, activity budget, and frequency of stress behaviors (stereotypes and self‐directed behaviors) between two captive groups of robust capuchins in a public zoo in Foz do Iguaçu, Brazil, to understand how much their behavioral homeostasis has been affected. More specifically, we assessed the effect of environmental variables (temperature, relative air humidity, number of visitors, and food management) and sex on the frequency of stress behaviors. Capuchins showed a high frequency of stress behaviors, which represented around 10% of their activity budget (though the frequencies were unevenly distributed among the individuals), and traveling was positively correlated with stereotypes. We found that high relative air humidity appears to induce more stereotypes, high numbers of visitors appear to increase self‐directed and vigilance behaviors and reduce stereotypes, food management can increase both kinds of stress behaviors, and females demonstrated more frequent stress behaviors than males, but individual variation may play a role. Capuchins in the group with a greater space restriction showed more stereotypes, while those in the group with more individuals showed more self‐directed behaviors. Our study shows that the stress behaviors performed by the capuchins are complex and it is difficult to determine a single cause, because many traits could be involved. Despite that, this study enlightens us to direct some approaches to help these animals to meet their ecological and social needs, mitigating their stress.
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease
Authors: Blauwendraat Cornelis , Iwaki Hirotaka , Makarious Mary B. , Bandres‐Ciga Sara , Leonard Hampton L. , Grenn Francis P. , Lake Julie , Krohn Lynne , Tan Manuela , Kim Jonggeol J. , Gibbs Jesse R. , Hernandez Dena G. , Ruskey Jennifer A. , Pihlstrøm Lasse , Toft Mathias , van Hilten Jacobus J. , Marinus Johan , Schulte Claudia , Brockmann Kathrin , Sharma Manu , Siitonen Ari , Majamaa Kari , Eerola‐Rautio Johanna , Tienari Pentti J. , Grosset Donald G. , Lesage Suzanne , Corvol Jean‐Christophe , Brice Alexis , Wood Nick , Hardy John , Gan‐Or Ziv , Heutink Peter , Gasser Thomas , Morris Huw R. , Noyce Alastair J. , Nalls Mike A. , Singleton Andrew B. ,   and the International Parkinson's Disease Genomics Consortium (IPDGC)
Published: April 2021

Objective

Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average ~ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex‐specific manner.

Methods

In an effort to study sex‐specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson's Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWAS meta‐analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases.

Results

In total, 19 genomewide significant regions were identified and no sex‐specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%).

Interpretation

We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. ANN NEUROL 2021;90:41–48
Middle Bronze Age cemeteries, ‘double barrows’ and mortuary houses in the Upper Dniester Basin, Western Ukraine: Geophysical prospection and archaeological verification
Authors: Romaniszyn Jan , Niebieszczański Jakub , Cwaliński Mateusz , Rud Vitaliy , Hildebrandt‐Radke Iwona , Spychalski Waldemar , Kochkin Ihor , Jarosz Paweł , Bahyrycz Cezary , Staniuk Robert , Panakhyd Halyna , Makarowicz Przemysław
Published: April 2021

This article discusses two cases of so‐called double barrows from the Middle Bronze Age Komarów culture cemetery in Bukivna, in the Upper Dniester Basin (Ukraine), in order to demonstrate the potential of incorporating geophysical image analysis, excavations and sedimentological studies towards identifying subterranean funerary architecture. The magnetometer prospection of the Bukivna necropolis revealed the presence of a specific dipolar anomaly within the extent of a double barrow. The excavations uncovered burnt wooden‐clay constructions related to mortuary houses. The sedimentological samples collected from the features below the mound provided data for the increased ferrous content. Another double barrow located in the Pidhoroddia cemetery was prospected by means of magnetometry, which did not reveal any similar anomaly within the magnetometry plan, thus providing evidence for a possible lack of discussed mortuary structure.
Optimization of the Forward‐Osmosis Performance with a Low‐Concentration Draw Solution Using Response Surface Modeling
Authors: Karunakaran Aghilesh , Mungray Alka A. , Agarwal Smriti , Garg Manoj Chandra
Published: April 2021

Forward osmosis (FO) has recently gained interest in wastewater treatment and seawater and brackish groundwater desalination. Response surface methodology (RSM) was used for the prediction and optimization of the FO process using a low‐concentration draw solution (DS). The process variables were the feed solution (FS) temperature, the DS concentration, and the FS concentration. These variables were subjected to regression models and had R2 values > 0.9. The FS temperature had a negative impact on the weight transfer from the DS, while the FS and DS concentrations had a direct correlation with the performance. At an FS temperature of 29 °C, the DS at 13 986 mg L−1 and the FS at 1702 mg L−1 produced the best results, thereby lowering the DS regeneration costs. Under this condition, the models were experimentally validated, confirming the predictive ability of the models.
Tailoring Valence Tautomerism by Using Redox Potentials: Studies on Ferrocene‐Based Triarylmethylium Dyes with Electron‐Poor Fluorenylium and Thioxanthylium Acceptors
Authors: Casper Larissa A. , Linseis Michael , Demeshko Serhiy , Azarkh Mykhailo , Drescher Malte , Winter Rainer F.
Published: April 2021

Three new electrochromic ferrocenyl triarylmethylium dyes with fluorenylium (1 a+,1 b+) or thioxanthylium (1 c+) residues were selected in order to keep the intrinsic differences of redox potentials for ferrocene oxidation and triarylmethylium reduction small and to trigger valence tautomerism (VT). UV/Vis/NIR and quantitative EPR spectroscopy identified paramagnetic diradical isomers1 a..+–1 c..+alongside diamagnetic forms1 a+–1 c+, which renders these complexes magnetochemical switches. The diradical forms1 a..+–1 c..+as well as the one‐electron‐reduced triarylmethyl forms of the complexes were found to dimerize in solution. For radical1 a., dimerization occurs on the timescale of cyclic voltammetry; this allowed us to determine the kinetics and equilibrium constant for this process by digital simulation. Mößbauer spectroscopy indicated that1 a+and1 b+retain VT even in the solid state. UV/Vis/NIR spectro‐electrochemistry revealed the poly‐electrochromic behaviour of these complexes by establishing the distinctly different electronic absorption profiles of the corresponding oxidized and reduced forms.
Functionalized 1,8‐Diazaiptycenes as Monomers for Aromatic Oligoamide Foldamers
Authors: Kerff Francois , Liu Cui‐Lian , Mu Xiao , Gilbert Ugo , Smal Louis , Meinertzhagen Loic , Kauffmann Brice , Robeyns Koen , Singleton Michael L.
Published: April 2021

Diversification of the structures and the applications possible for foldamers rely on expansion of the building block library available for their synthesis. In this work, we describe the synthesis of a range of three dimensional heteroaromatic monomers, based on iptycene scaffolds, that are suitable for the synthesis of aromatic oligoamide foldamers. These units can be obtained in gram quantities in up to 80 % yield through [4+2] cycloaddition between diester, diamine, and amino acid derivatives of 1,8‐diazaanthracenes and a variety of dienophiles. X‐ray structural studies of the monomers and an oligomer show that the new motif orients the two heterocyclic rings and attached groups at an angle of approximately 120° to each other, opening new geometric considerations for the design of this class of foldamer.
The Missing Piece: Concentration Dependence of Donor‐Acceptor Stenhouse Adduct (DASA) Reactivity
Authors: Alves Jessica , Wiedbrauk Sandra , Barner‐Kowollik Christopher , Blinco James P.
Published: April 2021

Donor‐Acceptor Stenhouse Adducts (DASAs) are molecular photoswitches that reversibly isomerize from a linear to a cyclized form upon visible light irradiation. In the cyclized form, these molecules selectively react with a thiol in a thiol‐Michael addition. Driven by the complexity of the switching mechanism and chemical properties of DASAs, the effect of concentration (ranging from 1 to 5 mM DASA) on the thiol‐Michael addition was investigated. We find that the rate limiting step in the reaction is the photochemically induced DASA isomerization, as higher concentrations of thiol do not alter the rate at which the thiol‐Michael adduct (TMA) is formed. Moreover, the kinetics of the product formation were found to be more significantly affected by irradiation at higher concentrations. In two distinct scenarios, where either the concentration or the molar equivalence of the reaction partner was kept constant, the TMA was found to be more efficiently formed under irradiation at higher concentrations. These findings indicate that the DASA reactivity towards thiol‐Michael reactions appear to be equilibrium‐driven at lower concentrations and light‐driven at higher concentrations.
Fallow replacement cover crops in a semi‐arid High Plains cropping system
Authors: Holman Johnathon D. , Obour Augustine K. , Assefa Yared
Published: April 2021

Replacing portions of fallow between sorghum [Sorghum bicolor (L.) Moench] harvest and wheat (Triticum aestivum) planting with cover crops provides opportunity to increase productivity and profitability in dryland winter wheat–sorghum–fallow (WSF) cropping systems. The objective of this study was to identify potential spring fallow replacement cover crops and management to optimize productivity and resource use efficiency of a WSF system. The study was conducted 2013–2018 at Garden City, KS. Three crop rotation phases (WSF, SFW, and FWS) were the main plot, and fallow replacement cover crops were the sub plot. Cover crop treatments were further split into hayed and cover crop left standing groups to estimate forage potential. Results showed precipitation utilization and storage efficiency (PUtSE) increased by 146% for grain cover crop, 50% for cover crop hayed, and 38% for cover crop left standing compared with fallow. Available soil water at wheat planting (ASWPww) was not different between cover crop left standing and fallow. Spring triticale [×Triticosecale Wittm. ex A. Camus (Secale × Triticum)] had up to 182% more forage accumulation over other forage cover crops and a 108% grain yield advantage over other grain cover crops. Our findings showed fallow replacement, forage‐hayed, and grain cover crops have a greater PUtSE than fallow which may increase economic returns if subsequent crop yields are not reduced. Cover crops left standing had a moderate PUtSE advantage and similar ASWPww compared to fallow, and cover crop left standing, or fallow would be the best choice if the production goal is to maximize ASWPww and subsequent crop yields.
Phenotypic diversity for phenological and agronomic traits in the UC‐Riverside cowpea (Vigna unguiculata L. Walp) mini‐core collection
Authors: Dareus Rocheteau , Acharya Janam P. , Paudel Dev R. , Lopes De Souza Cleber Henrique , Tome Gouveia Beatriz , Chase Carlene A. , DiGennaro Peter , Mulvaney Michael J. , Koenig Rosalie , Rios Esteban F.
Published: April 2021

Cowpea (Vigna unguiculata L. Walp) is a multipurpose crop widely cultivated in tropical and subtropical regions around the world. Characterizing cowpea phenotypes in germplasm collections is a crucial step to ensure future breeding efforts in the species. In this study, we estimated variance components and calculated genetic parameters for eight traits in 292 accessions from the University of California Riverside cowpea mini‐core collection, along with three lines released by the USDA, and seven cultivars. Broad‐sense heritability (H2) ranged from .21 to .83 for all accessions evaluated in Year 1, and from .16 to .83 for traits evaluated in 100 accessions during Year 2. Genotype × year correlations ranged from .45 to .99, illustrating consistency in phenotypic performance for some traits. Positive trait correlations were estimated for plant height and days to flowering, biomass at flowering (R1), and biomass at pod maturity (R6). Biomass at R1 and R6 were highly positively correlated. The USDA line US‐1137 showed high biomass production and can be used as forage and cover crop, whereas US‐1136, US 1138, and the cultivar Iron Clay showed superior traits as dual‐purpose (grain and/or fodder). Several accessions from the mini‐core outperformed cultivars and represent valuable genetic resources that can contribute to cowpea improvement. Moreover, these results showed that multiyear and/or multienvironment studies are needed to reliable select improved germplasm for agronomic traits. This study will provide cowpea breeders and geneticists with valuable phenotypic data to start new breeding efforts, and/or opportunities for gene discovery for key phenological and agronomic traits.
Survey shows mental health concerns rising due to COVID‐19
Authors: Sutton Halley
Published: April 2021

Student mental health crises have increasingly been a point of concern for campus safety officials (as well as other administrators on campus). The COVID‐19 pandemic has only increased reports of mental health concerns, according to a survey by the Center for Collegiate Mental Health at Penn State University.
Sagebrush recovery patterns after fuel treatments mediated by disturbance type and plant functional group interactions
Authors: Chambers Jeanne C. , Urza Alexandra K. , Board David I. , Miller Richard F. , Pyke David A. , Roundy Bruce A. , Schupp Eugene W. , Tausch Robin J.
Published: April 2021

Fire and fuel management is a high priority in North American sagebrush ecosystems where the expansion of piñon and juniper trees and the invasion of nonnative annual grasses are altering fire regimes and resulting in loss of sagebrush species and habitat. We evaluated 10‐yr effects of woody fuel treatments on sagebrush recruitment and plant functional group interactions using Sagebrush Steppe Treatment Evaluation Project data. We used mixed‐effects ANOVAs to examine treatment effects on sagebrush density and cover and perennial and annual grass cover in expansion woodlands (prescribed fire and cut‐and‐leave) and annual grass invasion areas (prescribed fire, mowing, tebuthiuron herbicide application). We used piecewise structural equation models to evaluate interactions among sagebrush seedling density, juvenile and adult density, and cover and perennial and annual grass cover. Fuel treatments were equated to pulse or press disturbances varying in resource release and subsequent intra‐ and interspecific interactions. Prescribed fire, a high magnitude pulse disturbance with more severe effects in warm and dry sites, reduced sagebrush cover and decoupled associations among sagebrush seedlings, juvenile and adult density, and cover indicating changed population structure. Cutting and leaving trees, a low magnitude pulse disturbance in cooler and moister woodlands, increased sagebrush density and cover and generally had lesser effects on sagebrush intraspecific associations. Mowing, a moderate magnitude pulse disturbance, and tebuthiuron herbicide application, a multiyear press disturbance, reduced sagebrush cover and disrupted intraspecific relationships. Competitive release increased cover of perennial grass in all treatments but tebuthiuron. Annual grass increased in all treatments, especially prescribed fire and tebuthiuron. Annual and perennial grass interactions with sagebrush were generally rare, but in woodland treatments perennial grass suppressed annual grass through year 6. Treatments in cooler and moister woodland sites had more positive effects on sagebrush recruitment and perennial grass cover, less negative effects on sagebrush intraspecific interactions, and smaller increases in annual grass cover indicating potential increases in resilience to fire. In warmer and drier invasion sites, reductions in woody fuels resulted in lack of sagebrush recruitment, disruption of sagebrush intraspecific interactions, and progressive increases in annual grass indicating reduced resilience to fire and resistance to invaders.
Hierarchical Microspheres Constructed by Te@N‐Doped Carbon for Efficient Potassium Storage
Authors: Wang Xin , Qian Kun , Zhou Minfei , Li Muhan , Guo Cong , Li Jingfa
Published: April 2021

Tellurium (Te) has attracted intensive attention for its potential as stationary energy storage system due to its high volumetric capacity and the intrinsic electronic conductivity. Nevertheless, this battery suffers from the low utilization of active Te and the vast volume variations during cycling. Hierarchical N‐doped carbon (N−C) porous microspheres etched from MnCO3 microsphere template are designed as a host for Te. The hierarchical microspheres, with abundant pores and voids, shortens the ions diffusion/electrons transport distances and buffers the volume expansion of the active materials. When constructed the K−Te battery, the Te@N−C electrode delivers a remarkable reversible capacity of 390 mA h g−1 (corresponding to 2437.5 mA h cm−3) at 0.1 A g−1 after 100 cycles and 170 mA h g−1 (corresponding to 1062.5 mA h cm−3) after 2000 cycles at 0.5 A g−1. This novel design in this work may open up new opportunities for the development of the new energy storage systems with high volumetric energy density.
The relational nature of Evaluation Capacity Building: Lessons from facilitated evaluation partnerships
Authors: Buckley Jane , Hargraves Monica , Moorman Leslie
Published: April 2021

This paper explores the nature and importance of the relationship between Evaluation Capacity Builders (ECBers) and their program partner(s) in the context of the Partnerships for Advancing Character program Evaluation (PACE) Project. PACE, a 3‐year initiative supported by the John Templeton Foundation, offered a unique opportunity to initiate, structure, support, and observe evaluation partnerships between an evaluation professional and a program team over 15 months. In this paper, after reviewing pertinent Evaluation Capacity Building (ECB) and adult education literature, we report on our qualitative inquiry into the PACE Evaluation Partnerships, in response to the following three research questions: (1) What did PACE participants consider to be positive characteristics of or contributing factors to the Evaluation Partnerships? (2) What did PACE participants identify as negative characteristics of or challenging factors to the partnerships? And (3) Are the patterns of positive/negative characteristics and contributing/challenging factors consistent with the hypothesis that relational qualities are important in Evaluation Capacity Building? The results of this analysis indicate that partnerships that were characterized by relational qualities (e.g., responsiveness, trust, mutual respect) tended to be more successful—in the eyes of the people in those relationships—than those that did not. Both the variety of the relationships described by the participants, as well as the emerging patterns, offer fertile ground for future questions about the relational nature of positive ECB relationships.
Applying the Systems Evaluation Protocol in the real world: Six case studies
Authors: Urban Jennifer Brown , Linver Miriam R. , Chauveron Lisa M. , Archibald Thomas , Hargraves Monica , Buckley Jane
Published: April 2021

In this paper, we present six case studies that illustrate the application of the Systems Evaluation Protocol (SEP) in different real‐world implementation conditions. The SEP is a step‐by‐step guide for how to implement Relational Systems Evaluation (RSE), accounting for the complex factors inherent in the larger systems within which a given program is embedded. We discuss the specific SEP steps used and products developed in each case study project, including an emphasis on how decisions were made to include particular SEP elements in different contexts. The six cases differ in terms of the scale of the programs involved, the nature of the SEP delivery or facilitation process, and the balance among multiple desired outcomes reflecting differential emphases on evaluation capacity building. As such, the cases reported here demonstrate that RSE, as implemented using the SEP, is a widely applicable approach to evaluation and ECB.
A view from the outside: Reflections on Relational Systems Evaluation
Authors: Bollinger Richard
Published: April 2021

This paper provides a review of the current volume and RSE. The author is a senior program officer at the John Templeton Foundation, which has funded some of the work described in this volume. He brings a unique perspective as he has both observed RSE in practice and experienced it first hand as a participant in strategic planning processes that use RSE. In addition, several of the grantees in his portfolio have implemented RSE as part of their projects. This paper offers reflections on these experiences as well as on the information presented in the volume and provides a critical review of RSE, including its strengths and weaknesses.
Functional Characterization of Organoids Derived From Irreversibly Damaged Liver of Patients With NASH
Authors: McCarron Sarah , Bathon Brooke , Conlon Donna M. , Abbey Deepti , Rader Daniel J. , Gawronski Katerina , Brown Christopher D. , Olthoff Kim M. , Shaked Abraham , Raabe Tobias D.
Published: April 2021

Background and Aims

NASH will soon become the leading cause of liver transplantation in the United States and is also associated with increased COVID‐19 mortality. Currently, there are no Food and Drug Administration–approved drugs available that slow NASH progression or address NASH liver involvement in COVID‐19. Because animal models cannot fully recapitulate human NASH, we hypothesized that stem cells isolated directly from end‐stage liver from patients with NASH may address current knowledge gaps in human NASH pathology.

Approach and Results

We devised methods that allow the derivation, proliferation, hepatic differentiation, and extensive characterization of bipotent ductal organoids from irreversibly damaged liver from patients with NASH. The transcriptomes of organoids derived from NASH liver, but not healthy liver, show significant up‐regulation of proinflammatory and cytochrome p450–related pathways, as well as of known liver fibrosis and tumor markers, with the degree of up‐regulation being patient‐specific. Functionally, NASH liver organoids exhibit reduced passaging/growth capacity and hallmarks of NASH liver, including decreased albumin production, increased free fatty acid–induced lipid accumulation, increased sensitivity to apoptotic stimuli, and increased cytochrome P450 metabolism. After hepatic differentiation, NASH liver organoids exhibit reduced ability to dedifferentiate back to the biliary state, consistent with the known reduced regenerative ability of NASH livers. Intriguingly, NASH liver organoids also show strongly increased permissiveness to severe acute respiratory syndrome–coronavirus 2 (SARS‐CoV‐2) vesicular stomatitis pseudovirus as well as up‐regulation of ubiquitin D, a known inhibitor of the antiviral interferon host response.

Conclusion

Expansion of primary liver stem cells/organoids derived directly from irreversibly damaged liver from patients with NASH opens up experimental avenues for personalized disease modeling and drug development that has the potential to slow human NASH progression and to counteract NASH‐related SARS‐CoV‐2 effects.
Cancer survivors’ perspectives of dietary information provision after cancer treatment: A scoping review of the Australian context
Authors: Barlow Katherine H. , van der Pols Jolieke C. , Ekberg Stuart , Johnston Elizabeth A.
Published: April 2021

Issue addressed

To support survivor‐centred care in Australia, this review maps current knowledge regarding adult cancer survivors’ perspectives of dietary information provision post‐treatment.

Methods

A scoping review of research conducted in Australia within the past decade reported using PRISMA‐ScR guidelines. Seven databases were searched (01/01/2009‐05/06/2020) and records were independently screened by two researchers using eligibility criteria. Papers in the peer‐reviewed literature with dietary information post‐treatment as a primary and secondary outcome were eligible for inclusion. Data charting included participant characteristics, study methodology and cancer survivors’ reports of dietary information provision post‐treatment.

Results

Of 531 records identified, 12 met eligibility criteria. Most studies included breast (58%) and colorectal (42%) cancer survivors within 5 years post‐diagnosis (84%). Three studies were conducted amongst specific ethnic groups (Indigenous Australians, Chinese‐Australians, Greek‐Australians). Participants in the included studies commonly reported limited or ineffective dietary information from healthcare providers post‐treatment. Cancer survivors identified a need for individualised information regarding dietary strategies to manage ongoing symptoms, professional support for weight management, and practical skills for healthy eating. Amongst ethnic groups, there was a need for dietary information that considers traditional foods and cultural beliefs, and is available in their native language. Cancer survivors valued ongoing dietary follow‐up and support post‐treatment, and suggested a variety of face‐to‐face and online delivery modes. Those residing in rural and remote areas reported barriers to accessing dietary information post‐treatment including time, cost, and availability of local services.

Conclusions

There is scope to improve dietary information provision after cancer treatment in Australia.

So what?

Dietary guidance post‐treatment should consider individual needs, cultural background, and opportunity for ongoing follow‐up and support.