bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with newly diagnosed, metastatic hormone-naive prostate cancer: final subgroup analysis of LATITUDE, a randomized, double-blind, placebo-controlled, phase 3 study
Authors: Suzuki Hiroyoshi , Shin Toshitaka , Fukasawa Satoshi , Hashine Katsuyoshi , Kitani Sumiko , Ohtake Noriyuki , Shibayama Kazuhiro , Tran Namphuong , Mundle Suneel , Fizazi Karim , Matsubara Nobuaki 
Published: February 2020

Abstract

Background
LATITUDE was a randomized, double-blind, international and phase 3 study of abiraterone acetate plus prednisone in patients with high-risk metastatic hormone-naïve prostate cancer. In the first interim analysis of LATITUDE (clinical cutoff date: 31 October 2016), significant prolongation in overall survival and radiographic progression-free survival (co-primary endpoints) was observed when compared with placebo. The results of the Japanese subgroup analysis of LATITUDE first interim analysis were consistent with those of the overall population. In this study, overall survival and safety results from the final analysis of the Japanese subgroup of the LATITUDE study are presented (clinical cutoff date: 15 August 2018).

Methods
Abiraterone acetate (1000 mg/day) and prednisone (5 mg/day) were administered orally in the abiraterone acetate plus prednisone group, and matching placebos in the placebo group.

Results
Of the 1199 patients included in LATITUDE, 70 constituted the Japanese subgroup (abiraterone acetate plus prednisone: n = 35, placebo: n = 35). Following a median (range) follow-up of 56.6 (2.5, 64.2) months, the median overall survival was not reached in both the treatment arms of the Japanese subgroup (hazard ratio: 0.61; 95% confidence interval: 0.27–1.42; nominal P = 0.2502). A total of 23 deaths (abiraterone acetate plus prednisone: 9 [25.7%], placebo group: 14 [40.0%]) were reported in Japanese subgroup. Grade 3/4 adverse events were reported in 24 (68.6%) and 9 (25.7%) patients in the abiraterone acetate plus prednisone and placebo groups, respectively.

Conclusions
In this Japanese subgroup analysis, addition of abiraterone acetate plus prednisone to androgen-deprivation therapy demonstrated favorable efficacy and safety outcomes in patients with newly diagnosed, high-risk metastatic hormone-naïve prostate cancer. Survival benefits observed in the Japanese subgroup first interim analysis were sustained long-term and were consistent with the overall population.
Ultrastructural Dendritic Changes Underlying Diaschisis After Capsular Infarct
Authors: Lee Min-Cheol , Kim Ra Gyung , Lee Taebum , Kim Jo-Heon , Lee Kyung-Hwa , Choi Yoo-Duk , Kim Hyung-Seok , Cho Jongwook , Park Ji-Young , Kim Hyoung-Ihl 
Published: February 2020

Abstract
Diaschisis has been described as functional depression distant to the lesion. A variety of neuroscientific approaches have been used to investigate the mechanisms underlying diaschisis. However, few studies have examined the pathological changes in diaschisis at ultrastructural level. Here, we used a rat model of capsular infarct that consistently produces diaschisis in ipsilesional and contralesional motor and sensory cortices. To verify the occurrence of diaschisis and monitor time-dependent changes in diaschisis, we performed longitudinal 2-deoxy-2-[18F]-fluoro-d-glucose microPET (FDG-microPET) study. We also used light and electron microscopy to identify the microscopic and ultrastructural changes at the diaschisis site at 7, 14, and 21 days after capsular infarct modeling (CIM). FDG-microPET showed the occurrence of diaschisis after CIM. Light microscopic examinations revealed no significant histopathological changes at the diaschisis site except a mild degree of reactive astrogliosis. However, electron microscopy revealed swollen, hydropic degeneration of axial dendrites and axodendritic synapses, although the neuronal soma (including nuclear chromatin and cytoplasmic organelles) and myelinated axons were relatively well preserved up to 21 days after injury. Furthermore, number of axodendritic synapses was significantly decreased after CIM. These data indicate that a circumscribed subcortical white-matter lesion produces ultrastructural pathological changes related to the pathogenesis of diaschisis.
Stress and the Home Environment in Caregivers of Children with Sickle Cell
Authors: Varughese Taniya E , Hoyt Catherine R , L’Hotta Allison J , Ikemenogo Princess A , Howdeshell Seth G , Housten Ashley J , Abel Regina A , King Allison A 
Published: February 2020

Abstract

Objective
Caregivers of young children with chronic illnesses are at high risk for elevated levels of stress and mental health symptoms. This study examined stress and mental health symptoms as well as the socioeconomic status (SES) and home environments of a cohort of caregivers of infants and toddlers with sickle cell disease (SCD).

Methods
Forty-two caregivers of infants and toddlers (aged 1–34 months) with SCD completed the Brief Symptom Inventory (BSI) and Parent Stress Index (PSI). The Home Observation for Measurement of the Environment (HOME) was used to assess family living environments.

Results
Compared to test norms, caregivers reported high levels of situational/demographic life stress [mean difference (MD) 5.7, p = .003] and child distractibility/hyperactivity (MD 3.62, p = .001) on the PSI. However, no significant differences in psychological symptoms of distress were noted on the BSI. Caregivers scored significantly lower than norms on PSI subdomains of acceptability (MD −1.88, p = .03), competence (MD −3.11, p = .002), depression (MD −3.94, p &lt; .001), and the overall parent domain (MD −12.55, p = .005). Significant correlations were found between PSI scores and the HOME and between SES and the HOME.

Conclusion
Caregivers of infants and toddlers with SCD experience elevated levels of life stress but, in turn, endorse high acceptance of their child and self-competence in parenting. Although life stress may be high in this population, symptoms of psychological distress were not identified. Caregivers reporting elevated life and illness-specific stressors may benefit from environmental supports and interventions.
Desiccation tolerance in streptophyte algae and the algae to land plant transition: evolution of LEA and MIP protein families within the Viridiplantae
Authors: Becker Burkhard , Feng Xuehuan , Yin Yanbin , Holzinger Andreas 
Published: February 2020

Abstract
The present review summarizes the effects of desiccation in streptophyte green algae, as numerous experimental studies have been performed over the past decade particularly in the early branching streptophyte Klebsormidium sp. and the late branching Zygnema circumcarinatum. The latter genus gives its name to the Zygenmatophyceae, the sister group to land plants. For both organisms, transcriptomic investigations of desiccation stress are available, and illustrate a high variability in the stress response depending on the conditions and the strains used. However, overall, the responses of both organisms to desiccation stress are very similar to that of land plants. We highlight the evolution of two highly regulated protein families, the late embryogenesis abundant (LEA) proteins and the major intrinsic protein (MIP) family. Chlorophytes and streptophytes encode LEA4 and LEA5, while LEA2 have so far only been found in streptophyte algae, indicating an evolutionary origin in this group. Within the MIP family, a high transcriptomic regulation of a tonoplast intrinsic protein (TIP) has been found for the first time outside the embryophytes in Z. circumcarinatum. The MIP family became more complex on the way to terrestrialization but simplified afterwards. These observations suggest a key role for water transport proteins in desiccation tolerance of streptophytes.
Deciphering aquaporin regulation and roles in seed biology
Authors: Hoai Phan T T , Tyerman Stephen D , Schnell Nicholas , Tucker Matthew , McGaughey Samantha A , Qiu Jiaen , Groszmann Michael , Byrt Caitlin S 
Published: February 2020

Abstract
Seeds are the typical dispersal and propagation units of angiosperms and gymnosperms. Water movement into and out of seeds plays a crucial role from the point of fertilization through to imbibition and seed germination. A class of membrane intrinsic proteins called aquaporins (AQPs) assist with the movement of water and other solutes within seeds. These highly diverse and abundant proteins are associated with different processes in the development, longevity, imbibition, and germination of seed. However, there are many AQPs encoded in a plant’s genome and it is not yet clear how, when, or which AQPs are involved in critical stages of seed biology. Here we review the literature to examine the evidence for AQP involvement in seeds and analyse Arabidopsis seed-related transcriptomic data to assess which AQPs are likely to be important in seed water relations and explore additional roles for AQPs in seed biology.
Chemical diversity of super-Earths as a consequence of formation
Authors: Scora Jennifer , Valencia Diana , Morbidelli Alessandro , Jacobson Seth 
Published: February 2020

ABSTRACT
Recent observations of rocky super-Earths have revealed an apparent wider distribution of Fe/Mg ratios, or core to mantle ratios, than the planets in our Solar system. This study aims to understand how much of the chemical diversity in the super-Earth population can arise from giant impacts during planetary formation. Planet formation simulations have only recently begun to treat collisions more realistically in an attempt to replicate the planets in our Solar system. We investigate planet formation more generally by simulating the formation of rocky super-Earths with varying initial conditions using a version of symba, a gravitational N-body code, that incorporates realistic collisions. We track the maximum plausible change in composition after each impact. The final planets span a range of Fe/Mg ratios similar to the Solar system planets, but do not completely match the distribution in super-Earth data. We only form a few planets with minor iron-depletion, suggesting other mechanisms are at work. The most iron-rich planets have a lower Fe/Mg ratio than Mercury, and are less enriched than planets such as Kepler-100b. This indicates that further work on our understanding of planet formation and further improvement of precision of mass and radius measurements are required to explain planets at the extremes of this Fe/Mg distribution.
The Gaia DR2 parallax zero-point: hierarchical modelling of red clump stars
Authors: Chan Victor C , Bovy Jo 
Published: February 2020

ABSTRACT
The systematic offset of Gaia parallaxes has been widely reported with Gaia’s second data release, and it is expected to persist in future Gaia data. In order to use Gaia parallaxes to infer distances to high precision, we develop a hierarchical probabilistic model to determine the Gaia parallax zero-point offset along with the calibration of an empirical model for luminosity of red clump stars by combining astrometric and photometric measurements. Using a cross-matched sample of red clump stars from the Apache Point Observatory Galactic Evolution Experiment and Gaia Data Release 2 (DR2), we report the parallax zero-point offset in DR2 to be $\varpi _0 = -48 \pm 1\,\mu \text{as}$. We infer the red clump absolute magnitude to be −1.622 ± 0.004 in Ks, 0.435 ± 0.004 in G, −1.019 ± 0.004 in J, and −1.516 ± 0.004 in H. The intrinsic scatter of the red clump is ∼0.09 mag in J, H, and Ks, or ∼ 0.12 mag in G. We tailor our models to accommodate more complex analyses such as investigating the variations of the parallax zero-point with each source’s observed magnitude, observed colour, and sky position. In particular, we find fluctuations of the zero-point across the sky to be of order or less than a few 10s of $\mu \text{as}$.
Time-dependent radiation hydrodynamics on a moving mesh
Authors: Chang Philip , Davis Shane W , Jiang(姜燕飞) Yan-Fei 
Published: February 2020

ABSTRACTWe describe the structure and implementation of a radiation hydrodynamic solver for manga, the moving-mesh hydrodynamics module of the large-scale parallel code, Charm N-body GrAvity solver (changa). We solve the equations of time-dependent radiative transfer (RT) using a reduced speed of light approximation following the algorithm of Jiang et al. By writing the RT equations as a generalized conservation equation, we solve the transport part of these equations on an unstructured Voronoi mesh. We then solve the source part of the RT equations following Jiang et al. using an implicit solver, and couple this to the hydrodynamic equations. The use of an implicit solver ensures reliable convergence and preserves the conservation properties of these equations even in situations where the source terms are stiff due to the small coupling time-scales between radiation and matter. We present the results of a limited number of test cases (energy conservation, momentum conservation, dynamic diffusion, linear waves, crossing beams, and multiple shadows) to show convergence with analytic results and numerical stability. We also show that it produces qualitatively the correct results in the presence of multiple sources in the optically thin case.
The UV surface habitability of Proxima b: first experiments revealing probable life survival to stellar flares
Authors: Abrevaya X C , Leitzinger M , Oppezzo O J , Odert P , Patel M R , Luna G J M , Forte Giacobone A F , Hanslmeier A 
Published: February 2020

ABSTRACT
We use a new interdisciplinary approach to study the UV surface habitability of Proxima b under quiescent and flaring stellar conditions. We assumed planetary atmospheric compositions based on CO2 and N2 and surface pressures from 100 to 5000 mbar. Our results show that the combination of these atmospheric compositions and pressures provide enough shielding from the most damaging UV wavelengths, expanding the ‘UV-protective’ planetary atmospheric compositions beyond ozone. Additionally, we show that the UV radiation reaching the surface of Proxima b during quiescent conditions would be negligible from the biological point of view, even without an atmosphere. Given that high UV fluxes could challenge the existence of life, then, we experimentally tested the effect that flares would have on microorganisms in a ‘worst case scenario’ (no UV-shielding). Our results show the impact that a typical flare and a superflare would have on life: when microorganisms receive very high fluences of UVC, such as those expected to reach the surface of Proxima b after a typical flare or a superflare, a fraction of the population is able to survive. Our study suggests that life could cope with highly UV irradiated environments in exoplanets under conditions that cannot be found on Earth.
Sparse Epistatic Patterns in the Evolution of Terpene Synthases
Authors: Ballal Aditya , Laurendon Caroline , Salmon Melissa , Vardakou Maria , Cheema Jitender , Defernez Marianne , O’Maille Paul E , Morozov Alexandre V 
Published: February 2020

Abstract
We explore sequence determinants of enzyme activity and specificity in a major enzyme family of terpene synthases. Most enzymes in this family catalyze reactions that produce cyclic terpenes—complex hydrocarbons widely used by plants and insects in diverse biological processes such as defense, communication, and symbiosis. To analyze the molecular mechanisms of emergence of terpene cyclization, we have carried out in-depth examination of mutational space around (E)-β-farnesene synthase, an Artemisia annua enzyme which catalyzes production of a linear hydrocarbon chain. Each mutant enzyme in our synthetic libraries was characterized biochemically, and the resulting reaction rate data were used as input to the Michaelis–Menten model of enzyme kinetics, in which free energies were represented as sums of one-amino-acid contributions and two-amino-acid couplings. Our model predicts measured reaction rates with high accuracy and yields free energy landscapes characterized by relatively few coupling terms. As a result, the Michaelis–Menten free energy landscapes have simple, interpretable structure and exhibit little epistasis. We have also developed biophysical fitness models based on the assumption that highly fit enzymes have evolved to maximize the output of correct products, such as cyclic products or a specific product of interest, while minimizing the output of byproducts. This approach results in nonlinear fitness landscapes that are considerably more epistatic. Overall, our experimental and computational framework provides focused characterization of evolutionary emergence of novel enzymatic functions in the context of microevolutionary exploration of sequence space around naturally occurring enzymes.
Frank Furness
Authors: Thomas George E. 
Published: February 2020

Frank Furness (12 November 1839–27 June 1912) took an original course that accelerated the transformation of American architecture from an art rooted in the past to one that responded to the rapidly changing materials, technologies, and circumstances of the Industrial Age. After study in New York in the atelier of Richard Morris Hunt, Furness served as an officer in the Sixth Pennsylvania Cavalry, winning the Medal of Honor in the largest cavalry battle of the Civil War at Trevilian Station, Virginia, in 1864. Furness entered practice when a new generation, arising from the city’s industrial culture, had taken control of Philadelphia’s economy and institutions. Its leaders, many from the Franklin Institute of the State of Pennsylvania for the Promotion of the Mechanic Arts, proposed to hold an international exhibition in Philadelphia, ostensibly to celebrate the centennial of the Declaration of Independence, but with the larger goal of representing to the nation and the world the extraordinary innovations in modern design initiated in Philadelphia. When the Centennial Exhibition opened in May 1876, Furness had already completed half a dozen banks in the downtown area, the Pennsylvania Academy of the Fine Arts, and two religious buildings in the institutional center as well as numerous houses scattered across the elite residential district, a bank, and various pavilions at the fair. Those buildings introduced him to Centennial Exhibition visitors from both the United States and abroad. During more than forty years of practice, Furness and his various offices (Fraser, Furness & Hewitt; Furness & Hewitt, Frank Furness; Furness & Evans; Furness, Evans & Co.) produced designs for nearly 800 projects, the vast majority of which were built. Some 200 were commissioned by the nation’s largest railroads, including the Philadelphia and Reading, the Baltimore and Ohio, and the Pennsylvania Railroad. By the end of the century, Furness found himself largely excluded from the professional narrative as architects working from historical models found his ahistorical work inscrutable. Furness introduced the literature of family friends, Walt Whitman and Ralph Waldo Emerson, to the young architects working in his office, including Louis Sullivan (b. 1856–d. 1924), William L. Price (b. 1861–d. 1916), and George Howe (b. 1886–d. 1955). George Howe, who, like Sullivan and Price, shared the experience of the Furness office, laid out an American genealogy for modern architecture in his essay “What Is This Modern Architecture Trying to Express?” (1930) that included “Wright, Sullivan, and Price.” These architects and their students, from Irving Gill to Louis Kahn, carried on the discipline found in Furness’s architecture into our own time.
Henry Hobson Richardson
Authors: Ochsner Jeffrey Karl 
Published: February 2020

Henry Hobson Richardson (b. 1838–d. 1886) is considered one of the most important American architects of the nineteenth century. His achievements were celebrated during his lifetime and publications addressing his life and work have appeared almost continuously since his death. The second American architect to attend the École des Beaux Arts, his early designs show the influence of the contemporary Gothic Revival and Second Empire styles, but, about 1870, he began moving in an independent direction, creating a free interpretation of Romanesque precedents. Trinity Church, Boston, a Romanesque Revival design completed in 1877, brought Richardson national recognition and shaped his career as it led him to move from New York to Brookline, a suburb of Boston. Although most of his work is in New England and New York, as his fame grew he received commissions in Washington, Pittsburgh, Cincinnati, Chicago, St. Louis, and Wyoming. In his later projects he often reduced historical references, emphasized the qualities of materials, and moved toward simplification of form to produce masterpieces, such as the Allegheny County Courthouse and Jail in Pittsburgh and the Marshall Field Wholesale Store in Chicago. His projects also included emerging building types, such as small railroad passenger stations and free public libraries. His country houses catalyzed the development of the shingle style. Richardson was not a solitary genius. He engaged personally with a wide circle of friends and clients. In his last years, his office grew to a staff of approximately twenty. Following his early death, his leading apprentices continued the practice as Shepley, Rutan, and Coolidge. Richardson’s contemporaries understood his achievement in different ways, so his influence led in multiple directions. Unlike other leading architects, Richardson rarely wrote about his intentions, so scholars have presented his work through varying interpretive frameworks.
Bronze-Age Cycladic/Minoan Architecture
Authors: McEnroe John 
Published: February 2020

The study of Bronze Age Crete and the Cyclades is a relatively new academic discipline. The first serious archaeological investigations on Crete and on the Cycladic island of Melos began only in the years around 1900, but scholars got off to a fast start. By the time of the First World War, Greek, European, and American excavators had already uncovered vast sections of ancient cities and towns. In some of the larger ancient cities in Crete, they found distinctive monumental palaces that consisted of various specialized quarters grouped around a rectangular central court. In the outlying neighborhoods and in the smaller towns, they came across elaborate “villas” along with more modest houses, shrines, cemeteries, and other urban amenities. After only a few years of work, Arthur Evans, the excavator of the so-called Palace of Minos at Knossos, devised a system that divided the Bronze Age up into three main phases, Early, Middle, and Late. This system still provides the basis for understanding historical developments in the Bronze-Age Aegean particularly for the study of pottery and other artifacts. Increasingly a roughly parallel tripartite system is being used for the architecture of Minoan Crete, using the terms Prepalatial (ca. 3000–1900 bce), Protopalatial (ca. 1900–1700 bce), and Postpalatial (ca. 1400–1100 bce). These two chronological systems are discussed more fully later. Initially the emerging scholarship was somewhat uncomfortably grafted onto the publication outlets that already existed for the archaeology of classical Greece. Eventually new journals devoted specifically to the study of the Bronze Age began to appear. These new journals are supplemented by a number of specialized monograph series along with volumes devoted to international colloquia and workshops. From about 1970 to the present, Aegean studies has tended to shift its focus to include more scientific investigations as well as studies grounded in anthropological theory and, most recently, we have seen widespread use of digital technology. Such shifts have allowed the field to continue to thrive. The list of sites continues to grow. Indeed, the recent pace of excavations rivals the dramatic burst of activity launched by the pioneers of Aegean studies a century ago, and the number of important scholarly publications has grown even more dramatically.