bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells
Authors: Bian Guohui , Gu Yanzheng , Xu Changlu , Yang Wenyu , Pan Xu , Chen Yijin , Lai Mowen , Zhou Ya , Dong Yong , Mao Bin , Zhou Qiongxiu , Chen Bo , Nakathata Tatsutoshi , Shi Lihong , Wu Min , Zhang Yonggang , Ma Feng 
Published: October 2020

AbstractMast cells (MCs) play a pivotal role in the hypersensitivity reaction by regulating the innate and adaptive immune responses. Humans have two types of MCs. The first type, termed MCTC, is found in the skin and other connective tissues and expresses both tryptase and chymase, while the second, termed MCT, which only expresses tryptase, is found primarily in the mucosa. MCs induced from human adult-type CD34+ cells are reported to be of the MCT type, but the development of MCs during embryonic/fetal stages is largely unknown. Using an efficient coculture system, we identified that a CD34+c-kit+ cell population, which appeared prior to the emergence of CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), stimulated robust production of pure Tryptase+Chymase+ MCs (MCTCs). Single-cell analysis revealed dual development directions of CD34+c-kit+ progenitors, with one lineage developing into erythro-myeloid progenitors (EMP) and the other lineage developing into HSPC. Interestingly, MCTCs derived from early CD34+c-kit+ cells exhibited strong histamine release and immune response functions. Particularly, robust release of IL-17 suggested that these early developing tissue-type MCTCs could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MCTCs and have significant therapeutic implications.
Wave field reconstruction and phase imaging by electron diffractive imaging
Authors: Yamasaki Jun 
Published: October 2020

Abstract
In electron diffractive imaging, the phase image of a sample is reconstructed from its diffraction intensity through iterative calculations. The principle of this method is based on the Fourier transform relation between the real-space wave field transmitted by the sample and its Fraunhofer diffraction wave field. Since Gerchberg’s experimental work in 1972, various advancements have been achieved, which have substantially improved the quality of the reconstructed phase images and extended the applicable range of the method. In this review article, the principle of diffractive imaging, various experimental processes using electron beams and application to specific samples are explained in detail.
Climate change, human mobility, and development
Authors: Martin Susan F , Bergmann Jonas , Rigaud Kanta Kumari , Yameogo Nadege Desiree 
Published: October 2020

Absftract
Elizabeth Ferris’ review of research on environmental change and human mobility in this colloquium points to the important role that development actors play in identifying potential solutions for affected persons. She mentions in particular the work of the World Bank’s Climate Change Group and the Global Knowledge Partnership on Migration and Development (KNOMAD). Such mobility is indeed a critical issue from a development perspective, as reflected in the Sustainable Development Goals. Goals 10.7. and 13 encourage states to ‘facilitate orderly, safe, regular and responsible migration and mobility of people’ and demand ‘urgent action to combat climate change and its impacts’, with a focus on enhancing mitigation, adaptation, and disaster risk reduction practices. The World Bank’s development goals of eradicating extreme poverty and boosting shared prosperity further recognize the need to build capacity in these areas.
Detection of urethane-induced genotoxicity in vitro using metabolically competent human 2D and 3D spheroid culture models
Authors: Shah Ume-Kulsoom , Verma Jatin R , Chapman Katherine E , Wilde Eleanor C , Tonkin James A , Brown Martyn R , Johnson George E , Doak Shareen H , Jenkins Gareth J 
Published: October 2020

Abstract
In vitro genotoxicity studies are a quick and high throughput approach to assess the genotoxic potential of chemicals; however, the reliability of these tests and their relevance to in vivo effects depends on the choice of representative cell line and optimisation of assay conditions. For chemicals like urethane that require specific metabolic activation to cause genotoxicity, it is important that in vitro tests are conducted using cell lines exhibiting the activity and induction of CYP450 enzymes, including CYP2E1 enzyme that is important in the metabolism of urethane, at a concentration representing actual or perceived chemical exposure. We compared 2D MCL-5 cells and HepG2 cells with 3D HepG2 hanging drop spheroids to determine the genotoxicity of urethane using the micronucleus assay. Our 2D studies with MCL-5 did not show any statistically significant genotoxicity [99% relative population doubling (RPD)] compared to controls for concentrations and time point tested in vitro. HepG2 cells grown as 2D indicated that exposure to urethane of up to 30 mM for 23 h did not cause any genotoxic effect (102% RPD) but, at higher concentrations, genotoxicity was produced with only 89–85% RPD. Furthermore, an exposure of 20–50 mM for 23 h using 3D hanging drop spheroid assays revealed a higher MN frequency, thus exhibiting in vitro genotoxicity of urethane in metabolically active cell models. In comparison with previous studies, this study indicated that urethane genotoxicity is dose, sensitivity of cell model (2D vs. 3D) and exposure dependent.
Datanator: an integrated database of molecular data for quantitatively modeling cellular behavior
Authors: Roth Yosef D , Lian Zhouyang , Pochiraju Saahith , Shaikh Bilal , Karr Jonathan R 
Published: October 2020

Abstract
Integrative research about multiple biochemical subsystems has significant potential to help advance biology, bioengineering and medicine. However, it is difficult to obtain the diverse data needed for integrative research. To facilitate biochemical research, we developed Datanator (https://datanator.info), an integrated database and set of tools for finding clouds of multiple types of molecular data about specific molecules and reactions in specific organisms and environments, as well as data about chemically-similar molecules and reactions in phylogenetically-similar organisms in similar environments. Currently, Datanator includes metabolite concentrations, RNA modifications and half-lives, protein abundances and modifications, and reaction rate constants about a broad range of organisms. Going forward, we aim to launch a community initiative to curate additional data. Datanator also provides tools for filtering, visualizing and exporting these data clouds. We believe that Datanator can facilitate a wide range of research from integrative mechanistic models, such as whole-cell models, to comparative data-driven analyses of multiple organisms.
Structural and dynamical insights into the PH domain of p62 in human TFIIH
Authors: Okuda Masahiko , Ekimoto Toru , Kurita Jun-ichi , Ikeguchi Mitsunori , Nishimura Yoshifumi 
Published: October 2020

AbstractTFIIH is a crucial transcription and DNA repair factor consisting of the seven-subunit core. The core subunit p62 contains a pleckstrin homology domain (PH-D), which is essential for locating TFIIH at transcription initiation and DNA damage sites, and two BSD (BTF2-like transcription factors, synapse-associated proteins and DOS2-like proteins) domains. A recent cryo-electron microscopy (cryo-EM) structure of human TFIIH visualized most parts of core, except for the PH-D. Here, by nuclear magnetic resonance spectroscopy we have established the solution structure of human p62 PH-D connected to the BSD1 domain by a highly flexible linker, suggesting the flexibility of PH-D in TFIIH. Based on this dynamic character, the PH-D was modeled in the cryo-EM structure to obtain the whole human TFIIH core structure, which indicates that the PH-D moves around the surface of core with a specific but limited spatial distribution; these dynamic structures were refined by molecular dynamics (MD) simulations. Furthermore, we built models, also refined by MD simulations, of TFIIH in complex with five p62-binding partners, including transcription factors TFIIEα, p53 and DP1, and nucleotide excision repair factors XPC and UVSSA. The models explain why the PH-D is crucially targeted by these factors, which use their intrinsically disordered acidic regions for TFIIH recruitment.
Exchange of endogenous and heterogeneous yeast terminators in Pichia pastoris to tune mRNA stability and gene expression
Authors: Ito Yoichiro , Terai Goro , Ishigami Misa , Hashiba Noriko , Nakamura Yasuyuki , Bamba Takahiro , Kumokita Ryota , Hasunuma Tomohisa , Asai Kiyoshi , Ishii Jun , Kondo Akihiko 
Published: October 2020

Abstract
In the yeast Saccharomyces cerevisiae, terminator sequences not only terminate transcription but also affect expression levels of the protein-encoded upstream of the terminator. The non-conventional yeast Pichia pastoris (syn. Komagataella phaffii) has frequently been used as a platform for metabolic engineering but knowledge regarding P. pastoris terminators is limited. To explore terminator sequences available to tune protein expression levels in P. pastoris, we created a ‘terminator catalog’ by testing 72 sequences, including terminators from S. cerevisiae or P. pastoris and synthetic terminators. Altogether, we found that the terminators have a tunable range of 17-fold. We also found that S. cerevisiae terminator sequences maintain function when transferred to P. pastoris. Successful tuning of protein expression levels was shown not only for the reporter gene used to define the catalog but also using betaxanthin production as an example application in pathway flux regulation. Moreover, we found experimental evidence that protein expression levels result from mRNA abundance and in silico evidence that levels reflect the stability of mRNA 3′-UTR secondary structure. In combination with promoter selection, the novel terminator catalog constitutes a basic toolbox for tuning protein expression levels in metabolic engineering and synthetic biology in P. pastoris.
Prophages are associated with extensive CRISPR–Cas auto-immunity
Authors: Nobrega Franklin L , Walinga Hielke , Dutilh Bas E , Brouns Stan J J 
Published: October 2020

Abstract
CRISPR–Cas systems require discriminating self from non-self DNA during adaptation and interference. Yet, multiple cases have been reported of bacteria containing self-targeting spacers (STS), i.e. CRISPR spacers targeting protospacers on the same genome. STS has been suggested to reflect potential auto-immunity as an unwanted side effect of CRISPR–Cas defense, or a regulatory mechanism for gene expression. Here we investigated the incidence, distribution, and evasion of STS in over 100 000 bacterial genomes. We found STS in all CRISPR–Cas types and in one fifth of all CRISPR-carrying bacteria. Notably, up to 40% of I-B and I-F CRISPR–Cas systems contained STS. We observed that STS-containing genomes almost always carry a prophage and that STS map to prophage regions in more than half of the cases. Despite carrying STS, genetic deterioration of CRISPR–Cas systems appears to be rare, suggesting a level of escape from the potentially deleterious effects of STS by other mechanisms such as anti-CRISPR proteins and CRISPR target mutations. We propose a scenario where it is common to acquire an STS against a prophage, and this may trigger more extensive STS buildup by primed spacer acquisition in type I systems, without detrimental autoimmunity effects as mechanisms of auto-immunity evasion create tolerance to STS-targeted prophages.
Synchronization within synchronization: transients and intermittency in ecological networks
Authors: Fan Huawei , Kong Ling-Wei , Wang Xingang , Hastings Alan , Lai Ying-Cheng 
Published: October 2020

Abstract
Transients are fundamental to ecological systems with significant implications to management, conservation and biological control. We uncover a type of transient synchronization behavior in spatial ecological networks whose local dynamics are of the chaotic, predator–prey type. In the parameter regime where there is phase synchronization among all the patches, complete synchronization (i.e. synchronization in both phase and amplitude) can arise in certain pairs of patches as determined by the network symmetry—henceforth the phenomenon of  ‘synchronization within synchronization.’ Distinct patterns of complete synchronization coexist but, due to intrinsic instability or noise, each pattern is a transient and there is random, intermittent switching among the patterns in the course of time evolution. The probability distribution of the transient time is found to follow an algebraic scaling law with a divergent average transient lifetime. Based on symmetry considerations, we develop a stability analysis to understand these phenomena. The general principle of symmetry can also be exploited to explain previously discovered, counterintuitive synchronization behaviors in ecological networks.
Parenteral Antibiotic Use Among Ambulatory Children in United States Children’s Hospital Emergency Departments
Authors: Howard Leigh M , Thurm Cary , Dantuluri Keerti , Griffith Hannah G , Katz Sophie E , Ward Michael J , Banerjee Ritu , Grijalva Carlos G 
Published: October 2020

Abstract

Background
Despite increasing recognition of the importance of optimal antibiotic selection and expansion of antimicrobial stewardship activities to ambulatory settings, few studies have examined the frequency of parenteral antibiotic use among ambulatory children. We assessed the prevalence and patterns of parenteral antibiotic administration among ambulatory children in pediatric emergency departments (EDs).

Methods
We conducted a cross-sectional assessment of parenteral antibiotic use among ambulatory children aged 0–18 years in 49 US children’s hospital EDs in 2018. We assessed the prevalence rates of parenteral antibiotic use and stratified these by patient-, clinic-, and hospital-level characteristics. We also assessed the prevalence of use of specific antibiotics by age and diagnosis category. Among encounters associated with an infection diagnosis, we identified factors associated with parenteral antibiotic use using multivariable logistic regression.

Results
Among 3 452 011 ambulatory ED encounters in 2018, parenteral antibiotics were administered in 62 648 (1.8%). The highest proportion of parenteral antibiotic use occurred in the 15–18-year age group (3.3%) and among encounters in children with complex chronic conditions (8.9%) and with primary diagnoses of neoplasms (36%). Ceftriaxone was the most commonly administered parenteral antibiotic (61%). In multivariable analysis, several factors including age ≤2 months, White race, private insurance, complex chronic conditions, digestive and genitourinary system diseases, and encounters attributed to emergency medicine providers were significantly associated with higher odds of parenteral antibiotic use.

Conclusions
This study demonstrates substantial variability in the frequency of parenteral antibiotic administration by age and diagnosis in the ambulatory ED setting and highlights potential opportunities to target stewardship activities.
Cary Grant, the Making of a Hollywood Legend
Authors: Glancy Mark 
Published: October 2020

Abstract
Archie Leach was a poorly educated, working-class boy from a troubled family living in the backstreets of Bristol. Cary Grant was Hollywood’s most debonair film star—the embodiment of worldly sophistication. Cary Grant: The Making of a Hollywood Legend tells the incredible story of how the sad, neglected boy became the suave, glamorous star. The first biography to be based on Grant’s own personal papers, the book takes the reader on a fascinating journey from his difficult childhood through years of struggle in music hall and vaudeville, a hit-and-miss career in Broadway musicals, and three decades of film stardom during Hollywood’s golden age. For the first time, the bitter realities of Grant’s impoverished childhood are revealed, including his mother’s mental illness and his expulsion from school at the age of fourteen. New light is shed on his trailblazing path as a film star who defied the studio system and took control of his own career. His genius as an actor and a filmmaker is highlighted through identifying the crucial contributions he made to classic films such as Bringing Up Baby (1938), The Philadelphia Story (1940), Notorious (1946), An Affair to Remember (1957), North by Northwest (1959), Charade (1963) and Father Goose (1964). His own search for happiness and fulfilment, which led him to having his first child at the age of sixty-two and embarking on his fifth marriage at the age of seventy-seven—is explored with new candor and insight. Cary Grant: The Making of a Hollywood Legend is the definitive account of the professional and personal life of an unforgettable star.
Introduction
Authors: Glancy Mark 
Published: October 2020

Abstract
Cary Grant had good reason to dislike biographies. Many of his own biographers (including those writing before and after his death) insisted that he was defined by a “dark side’ that lay hidden beneath his charm and good looks. The starting point of this book is the aim to offer a fair, sympathetic, documented account of Grant’s life, and one based on extensive archival research, including the star’s own personal papers and home movies. The Introduction also addresses what in recent times has become one of the key issues in accounts of his life, his sexuality, stating that there are few signs that he had gay relationships but many signs that he had genuinely romantic and sexual relationships with women.
Chapter 15
Authors: Glancy Mark 
Published: October 2020

Abstract
In 1938 and 1939, Cary Grant enjoyed a close, romantic relationship with the actress Phyllis Brooks. They travelled together through Europe in the summer of 1939 and they very nearly married on their return to the USA. Brooks’ mother, however, disliked Grant, and this proved fatal to their relationship. Professionally, Grant continued to branch out as an actor, making the tough aviation drama Only Angels Have Wings (1939). Howard Hawks directed Grant alongside co-stars Jean Arthur and Rita Hayworth, both of whom found the director difficult to work with. Grant branched out further by making the melodramatic “woman’s film” In Name Only (1939) with co-star Carole Lombard. These films were well received by critics and the public, but his next film, His Girl Friday (1940), was a much more significant hit. In this quintessential screwball comedy, director Howard Hawks encouraged Grant and co-star Rosalind Russell to adlib lines, speaking over one another to build a frenzied comic atmosphere. Although critical reviews were mixed in 1940, the film’s reputation has grown over the years, and His Girl Friday now stands among his very best films.
Chapter 17
Authors: Glancy Mark 
Published: October 2020

Abstract
By 1941, Cary Grant had his pick of films. Almost everything was offered to him and everyone wanted to work with him. Wary of being typecast, he resisted making more screwball comedies. Instead, he made the gentle “weepie” Penny Serenade (1941) with George Stevens directing and Irene Dunne co-starring. His performance, including a tearful moment when he must plead with a judge to maintain custody of an adopted child, brought his first nomination for an Academy Award. He made an even more dramatic departure from his established image playing the wayward, possibly murderous Johnny Aysgarth in Alfred Hitchcock’s Suspicion (1941). The making of this film was rocky, not least because of on-the-set friction between Grant and co-star Joan Fontaine, but Grant’s relationship with Hitchcock was strong both personally and professionally. His relationship with director Frank Capra, with whom he made Arsenic and Old Lace (1944), was not as strong. Grant hated his own manic performance in this slapstick comedy. Although the film was a big success at the time and still has many admirers, he always cited it as the least favorite of his films.
Chapter 18
Authors: Glancy Mark 
Published: October 2020

Abstract
When the Japanese attack on Pearl Harbor brought the United States into the Second World War, Cary Grant finally felt able to apply for US citizenship and then to serve in the US military. He also married Barbara Hutton, and they were dubbed “Cash and Cary” in the press. While he waited for his citizenship papers, he continued making films. In George Stevens’ The Talk of the Town (1942) he vies with co-star Ronald Colman for the affections of Jean Arthur. Anxious that Stevens was favouring Arthur, Grant was unhappy making this film. Afterward, he embarked on the Hollywood Victory Caravan, a fundraising tour of American cities, and he was touched to see the public’s affection for him. With director Leo McCarey and co-star Ginger Rogers, he made Once Upon A Honeymoon (1942). The original story, co-written by McCarey, appears in some respects to be an apologia for Barbara’s Hutton’s previous marriage to a Prussian-born aristocrat who served in the German army during the First World War. Still eager to serve in the military, Grant made one more film at the behest of RKO. Mr Lucky (1943) is a “conversion narrative” in which he plays an initially cynical gangster who ultimately volunteers to serve his country. While making it, the military ruled that no one over the age of 38 could enter the services. Grant, who turned 39 as Mr Lucky was completed, would not be able to serve his adopted country.
Chapter 21
Authors: Glancy Mark 
Published: October 2020

Abstract
In 1946, Howard Hughes nearly killed himself testing a new aircraft over Beverly Hills, and he spent weeks in the hospital before convalescing at Grant’s home. In 1947, when Hughes had recovered, he and Grant went on a cross country flight and their plane fell out of radio contact, leading the press to report that they were missing and presumed dead. On his return to Hollywood, Grant was unhappy making The Bishop’s Wife (1947), and he wanted to trade roles with his co-star David Niven, but producer Samuel Goldwyn refused his requests. While Grant hoped to make films in Britain with Alexander Korda, the plans eventually fizzled out. Nevertheless, he enjoyed a trip to London and Bristol, where he visited his mother again. On the voyage home, he met his future wife, the young actress Betsy Drake. The comedy Mr Blandings Builds His Dream House (1948), was made at a time when the House Un-American Activities Committee (HUAC) was investigating communist subversion in Hollywood. Grant’s co-stars, Myrna Loy and Melvyn Douglas, were committed to resisting the investigation and promoting First Amendment rights. Grant, however, was reluctant to take a stand, believing that actors had no place making political pronouncements. It was only when Charlie Chaplin was attacked a few years later that Grant finally spoke out against the investigations.
Chapter 22
Authors: Glancy Mark 
Published: October 2020

Abstract
When Cary Grant coaxed Betsy Drake to join him in Hollywood in 1948, he did everything he could to kickstart her career as a film star. He used his own leverage with the powerful gossip columnists Hedda Hopper and Louella Parsons to win favourable coverage for Drake, and he agreed to co-star with Drake in her first film, Every Girl Should Be Married (1948). He turned down several other promising films, including Alfred Hitchcock’s Rope (1948), to make this feeble comedy. His next film was Howard Hawks’ screwball comedy I Was a Male War Bride (1949). Filming began on location in Europe, but Grant developed hepatitis and nearly died. It was several months before he could complete filming in Hollywood. The film turned out to be a huge box-office success, but the grim political drama Crisis (1950), was a box-office disaster that marked the beginning of a downturn in his career fortunes. By this time, however, he had married Betsy Drake, in a ceremony arranged by Howard Hughes, and he was looking forward to his new life with her.